RSUs

~~Restricted Share Units (RSUs)~~

The following table summarizes the ~~RSUs~~RSU activity for the ~~nine~~three months ended ~~September 30, 2017:~~March 31, 2024:

RSU

Weighted average

grant-date fair

Number of shares

value
Non-vested at December 31, 2016

307,063

$
9.11
Granted

428,350

$
6.00
Vested

(25,000)

$
18.21
Forfeited

(38,550)

$
7.15
Non-vested at September 30, 2017

671,863

$
6.90

Total weighted average grant date fair value of RSUs issued during the period (in $ million)

$
2.6
Grants during the period to directors and officers

255,000

$
5.95


	RSUs
		Weighted average
	Number of	grant-date fair
	ordinary shares	value
Non-vested at December 31, 2023	2,264,369	$	18.07
Granted	1,160,800	$	5.59
Vested	(659,240)	$	20.30
Forfeited	(58,401)	$	17.39
Non-vested at March 31, 2024	2,707,528	$	12.19

Total weighted average grant date fair value of RSUs granted during the period (in $ millions)		$	6.5

RSUs generally vest over one to three years. RSUs granted ~~in March 2017 to the Company’s Chief Executive Officer will vest equally over two years from the date of grant and RSUs granted~~ to non-executive directors ~~will~~ vest one year from the date of grant. ~~RSUs granted during the period include 255,000 RSUs granted to directors and officers~~

~~Performance Share Units (PSUs)~~PSUs

The following table summarizes the ~~PSUs~~PSU activity for the ~~nine~~three months ended ~~September 30, 2017:~~

PSU

Weighted average

grant-date fair

Number of shares

value
Non-vested at December 31, 2016

111,564

$
5.76
Granted

13,000

$
4.99
Retired

(12,000)

$
5.76
Vested

(58,500)

$
5.76
Non-vested at September 30, 2017

54,064

$
5.57
PSUs awarded but not yet earned

437,060

Total non-vested and discretionary PSUs

491,124

Total weighted average grant date fair value of PSUs awarded during the period (in $ million)

$
2.0

March 31, 2024:


	PSUs
		Weighted average
	Number of	grant-date fair
	ordinary shares	value
Non-vested at December 31, 2023	222,550	$	28.09
Forfeited	(17,030)	$	27.12
Non-vested at March 31, 2024	205,520	$	27.99

The Company granted ordinary shares to certain employees in December 2021 and at various dates during the year ended December 31, 2022 that will be earned upon achievement of defined milestones. Earned ordinary shares will vest upon the later of a minimum service period of one year or three years, or the achievement of defined milestones, subject to the grantee’s continued employment. In ~~January 2017,~~addition, portions of the ~~Company awarded PSUs~~ordinary shares granted in December 2021 to ~~its~~ executives and other members of senior ~~management. These PSUs~~management are ~~earned based on~~subject to achieving a minimum total shareholder return relative to the ~~Board’s assessment~~NASDAQ Biotechnology Index. The Company recognizes the compensation cost related to these grants to the extent it considers achievement of the ~~level~~milestones to be probable. As of ~~achievement~~March 31, 2024, two milestones had been achieved and vested in either 2022 or 2023. Additionally, another two milestones are considered probable as of ~~agreed performance targets through~~ December 31, ~~2017.~~2023 and March 31, 2024.

~~In September 2016,~~The ESPP

During the Company awarded PSUs to its Chief Executive Officer, subject to the successful implementation of the strategic plan. The earning of these PSUs is based on the Board’s assessment of the Chief Executive Officer’s performance through December 31, 2017.

~~Table of Contents~~

~~Other Plans~~

Under Rule 5653(c)(4) of the NASDAQ Global Select Market, the Company grants share options and RSUs to officers as a material inducement to enter into employment with the Company. In 2017, the Company granted 175,000 inducement RSUs with a grant date fair value of $1.0 million.

~~The following table summarizes option activity under Other Plans for the nine~~three months ended ~~September 30, 2017:~~

Other plans

Weighted average

Options

exercise price

Outstanding at December 31, 2016

187,500

$
17.93
Granted

300,000

$
6.90
Expired

(62,500)

$
27.82
Outstanding at September 30, 2017

425,000

$
8.69
Fully vested and exercisable

39,062

$
12.98
Outstanding and expected to vest

385,938

$
8.25

Total weighted average grant date fair value of options issued during the period (in $ million)

$
1.2

~~The fair value of the inducement grant options was estimated at the date of grant using the Hull & White option pricing model with the same assumptions as used in determining the fair value of options~~March 31, 2024, nil ordinary shares were issued under the ~~2014 Plan.~~ESPP compared to 2,495 during the same period in 2023. As of March 31, 2024, 96,862 ordinary shares remain available for issuance under the ESPP compared to a total of 113,565 as of March 31, 2023.

11	Income taxes

~~2012 Plan~~

The ~~following table summarizes option activity under~~Company recorded $0.7 million deferred tax expense in relation to its operations in the ~~Company’s 2012 Plan for~~U.S. during the ~~nine~~three months ended ~~September 30, 2017:~~

2012 plan

Weighted average

Options

exercise price

Outstanding at December 31, 2016

483,006

€
5.13
Exercised

(286,804)

€
3.07
Forfeited

(5,000)

€
3.07
Expired

(9,000)

€
3.07
Outstanding, fully vested and exercisable at September 30, 2017

182,202

€
8.52

~~Options exercised under~~March 31, 2024. The Company recorded $1.2 million deferred tax benefit in relation to its operations in the ~~2012 plan~~U.S. and France during the ~~nine~~three months ended ~~September 30, 2017, resulted~~March 31, 2023.

The effective income tax rate of 1.0% during the three ended March 31, 2024 is substantially lower than the enacted rate of 25.8% in ~~total proceeds to~~the Netherlands as the Company ~~of $1.0 million.~~

~~11 Income taxes~~

Deferred tax assets and deferred tax liabilities are recognized based on the expected future tax consequences temporary differences between the financial statement carrying amounts and the income tax basis of assets and liabilities, using current statutory rates. Arecords a valuation allowance ~~is recorded~~ against its net deferred tax assets ~~if it is more likely than not that some or all~~in the Netherlands and a partial a valuation allowance against its net deferred tax assets ~~will not be realized. Due to~~in France. The effective income tax rate during the ~~uncertainty surrounding the realization of the favorable tax attributes in future tax returns,~~three months ended March 31, 2023 was (1.5%), as the Company ~~has~~had recorded a ~~full~~ valuation allowance against ~~the Company’s otherwise recognizable~~its net deferred tax ~~assets.~~

assets in the Netherlands.

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14Basic and diluted earnings per share

Diluted earnings per share isare calculated by adjusting the weighted average number of ordinary shares outstanding, assuming conversion of all potentially dilutive ordinary shares. As the Company has incurred a loss in the three months ended March 31, 2024, all potentially dilutive ordinary shares would have an antidilutive effect, if converted, and thus have been excluded from the computation of loss per ~~share.~~share for the three months ended March 31, 2024. The ordinary shares are presented without giving effect to the application of the treasury method or exercise prices that would be above the share price as of March 31, 2024 and March 31, 2023, respectively.

The potentially dilutive ordinary shares are summarized below:

September 30,

September 30,

2017

2016

ordinary shares
BMS warrants

5,286,254

3,442,655
Warrants

37,175

37,175
Stock options under 2012 Plan

182,202

681,057
Stock options under 2014 Plan

2,241,188

2,036,372
Stock options (other)

425,000

325,000
Non-vested and earned RSUs and PSUs

900,927

297,198
Total potential dilutive ordinary shares

9,072,746

6,819,457


	Three months ended March 31,
	2024		2023
Anti-dilutive ordinary share equivalents
Stock options under 2014 Plans and previous plan		5,821,909		5,150,690
Non-vested RSUs and PSUs		2,913,048		2,772,146
ESPP		3,140		801
Total anti-dilutive ordinary share equivalents		8,738,097		7,923,637

13 ~~Leases~~Subsequent events

~~The Company leases various office space and laboratory space under the following operating lease agreements:~~None.

~~Lexington, Massachusetts / United States~~

In July 2013, uniQure entered into a lease for a facility in Lexington, Massachusetts, United States. The term of the lease commenced in November 2013 and was set for 10 years and is non-cancellable. The lease for this facility terminates in 2024, and subject to the provisions of the lease, may be renewed for two subsequent five-year terms. The lease provides for annual minimum increases in rent, based on a consumer price index.

~~Amsterdam / The Netherlands~~

In March 2016, the Company entered into a 16-year lease for a facility in Amsterdam, the Netherlands, and amended this agreement in June 2016. The Company consolidated its three Amsterdam sites into the new site at the end of May 2017. The lease for this facility terminates in 2032, with an option to extend in increments of five year periods. The lease contract provides for annual minimum increases in rent, based on a consumer price index.

~~As of September 30, 2017, aggregate minimum lease payments for the calendar years and lease incentives received were as follows:~~

Lexington

Amsterdam

Total

in thousands
2017 (three months remaining)
$
453

$
—

$
453
2018

1,849

1,963

3,812
2019

1,903

1,963

3,866
2020

1,956

1,963

3,919
2021 and beyond

6,899

21,595

28,494
Total minimum lease payments
$
13,060

$
27,484

$
40,544

Deferred rent related to lease incentives
$
5,739

$
3,814

$
9,553
Current portion

724

—

724

2215

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~~Rent expense is calculated on a straight-line basis over the term of the leases and considers the lease incentives received. Aggregate rent expense was as follows:~~

Three months ended September 30,

Nine months ended September 30,

2017

2016

2017

2016

in thousands
Rent expense-Lexington
$
276

$
276

$
828

$
828
Rent expense-Amsterdam

555

782

2,080

2,089
Total rent expense
$
831

$
1,058

$
2,908

$
2,917

~~14 Other commitments~~

The Company’s predecessor entity received a technical development loan from the Dutch government in relation to the development of Glybera. The Company is required to repay the grant through a percentage of revenue derived from product sales of Glybera up to December 31, 2019. Any grant balance remaining at this date will be forgiven. The Company decided not to renew its marketing authorization for Glybera in the European Union, which expires in October 2017. The Company does not expect to derive any revenue from Glybera.

~~15 Related party transaction~~

On August 7, 2017, the Company appointed Dr. Sander van Deventer as its Chief Scientific Officer and General Manager of its Amsterdam site. Dr. van Deventer served on the Company’s Board until September 14, 2017. Dr. van Deventer currently is Managing Director at the Company’s largest shareholder Forbion Capital Partners. Dr. van Deventer has agreed to resign as Managing Partner of Forbion Capital Partners by June 30, 2018, it being understood that he will thereafter continue as a venture partner or similar function with Forbion Capital Partners or its affiliated funds for up to 50% of his time. Dr. van Deventer is entitled to EUR 200,000 gross annual salary (“Base Salary”), including an 8% holiday allowance to be paid annually in May based upon the previous year’s gross annual salary. Dr. van Deventer will also be eligible for a bonus amounting to a maximum of 40% of his annual gross salary, such amount to be determined by the Board. On September 20, 2017, Dr. van Deventer was granted an option to purchase 150,000 shares at a price of $8.49, in accordance with the Company’s Amended and Restated 2014 Share Incentive Plan.

On October 26, 2017, the Company and our Chief Executive Officer and Executive Director, Matthew Kapusta, entered into an amendment (the “Amendment”) to Mr. Kapusta’s employment agreement dated December 9, 2014, as previously amended (the “Agreement”). The Amendment changes Mr. Kapusta’s severance entitlement in the event of a termination of his employment that occurs within the period that starts ninety days preceding a Change of Control (as defined in the Agreement) and ends one year following a Change of Control. Mr. Kapusta will be entitled in such circumstances to a lump sum payment equal to two times Mr. Kapusta’s then-current base salary (as defined in the Agreement) to be paid no later than sixty days after the termination date, his bonus (as defined in the Agreement) for the year of termination pro-rated based upon Mr. Kapusta’s termination date, and a lump sum representing and additional two times Mr. Kapusta’s bonus , to be paid no later than sixty days following the termination date. Mr. Kapusta’s employment agreement previously provided for severance payments of one times his then- current base salary, his pro-rated bonus for the year of termination and a lump-sum payment representing one times his bonus. Mr. Kapusta’s other severance entitlements with respect to a termination connected with a Change of Control have not changed.

~~16 Subsequent event~~

On October 27, 2017, the Company completed its public offering which was announced on October 23, 2017. The Company issued and sold 5,000,000 ordinary shares at $18.25 per ordinary share, resulting in gross proceeds to the Company of approximately $91.3 million. The net proceeds to the Company from this offering were approximately $85.4 million, after deducting underwriting discounts and commissions and other estimated offering expenses payable by the Company. The Company has granted the underwriters an option to purchase up to 750,000 ordinary shares at the public offering price of $18.25 for within thirty days of the date of the underwriting agreement.

~~Table of Contents~~

The Company intends to use the net proceeds from this offering to fund the continued clinical development of AMT-061 in hemophilia B and other programs, including AMT-130 in Huntington’s disease and other preclinical product candidates focused on rare and orphan diseases and to fund general corporate and working capital purposes.

The above equity financing entitles the Company to extend the interest interest-only payment period of its 2016 Amended Facility by 12 months from November 2017 to November 2018 as described in footnote 8.

~~Table of Contents~~

Item 2.Management’s Discussion and Analysis of Financial Condition and Results of Operations

The following Management’s Discussion and Analysis of Financial Condition and Results of Operations (“MD&A”) is intended to help the reader understand our results of operations and financial condition. This MD&A is provided as a supplement to, and should be read in conjunction with, our unaudited ~~condensed~~ consolidated financial statements and the accompanying notes thereto and other disclosures included in this Quarterly Report on Form 10-Q, including the disclosures under Part II, Item 1A “Risk ~~Factors”,~~Factors,” and our audited financial information and the notes thereto included in our Annual Report on Form 10-K ~~for the year ended December 31, 2016, which was filed with the Securities and Exchange Commission ( the “SEC”~~ (the “Annual Report”)~~, on March 15, 2017.~~. Our unaudited ~~condensed~~ consolidated financial statements have been prepared in accordance with generally accepted accounting principles in the USU.S. (“U.S. GAAP”) and unless otherwise indicated are presented in U.S. dollars.

Overview

We are a leader in the field of gene therapy, seeking to ~~develop~~deliver to patients suffering from rare and other devastating diseases single treatments with potentially curative ~~results for patients suffering from genetic and other devastating diseases.~~ results. We are advancing a focused pipeline of innovative gene therapies, ~~that have been~~including our clinical candidates for the treatment of Huntington’s disease, amyotrophic lateral sclerosis (“ALS”), refractory mesial temporal lobe epilepsy (“MTLE”) and Fabry disease. Our internally developed ~~both internally and through partnerships, such as our collaboration with Bristol Myers-Squibb focused on cardiovascular diseases. We have established clinical proof-of-concept in our lead indication,~~HEMGENIX®, a gene therapy for the treatment of hemophilia B, has been approved for commercialization by the United States Food and ~~achieved preclinical proof-of-concept~~Drug Administration (the “FDA”) in ~~Huntington’s disease.~~ November 2022 and the European Medicines Agency (“EMA”) in February 2023. The approval of HEMGENIX® follows more than a decade of research and clinical development, represents a major milestone in the field of gene therapy and ushers in a new treatment approach for patients living with hemophilia B. We license HEMGENIX® to CSL Behring LLC (“CSL Behring”), which is responsible for its commercialization. We are manufacturing HEMGENIX® for CSL Behring and are entitled to specific milestone payments and royalties on net sales of the product, a portion of which we sold to a royalty acquisition company in 2023 in exchange for up-front cash.

We believe our validated technology platform and manufacturing capabilities provide us with distinct competitive advantages, including the potential to reduce development risk, cost, and time to market. We produce our ~~AAV-based~~adeno-associated virus-based gene therapies in our own facilities with a proprietary, ~~commercial-scale, GMP-compliant,~~current good manufacturing practices (“GMP”) -compliant manufacturing process. We believe our Lexington, Massachusetts-based facility is one of the ~~world's~~world’s leading, most versatile, gene therapy manufacturing facilities.

~~Business~~

Recent Product Candidate Developments

~~Below~~Huntington’s disease program (AMT-130)

AMT-130 is our novel gene therapy candidate for the treatment of Huntington’s disease, which utilizes our proprietary, gene-silencing miQURE platform and incorporates an AAV vector carrying a ~~summary of our recent significant business developments:~~

~~Hemophilia B program~~

~~On October 19, 2017, we announced that following multi-disciplinary meetings with~~miRNA specifically designed to silence the ~~U.S. Food and Drug Administration (FDA)~~huntingtin gene and the ~~European Medicines Agency (EMA), we plan to expeditiously advance AMT-061, which combines an AAV5 vector with the FIX-Padua mutant, into~~potentially highly toxic exon 1 protein fragment.

We are currently conducting a ~~pivotal study in 2018 for patients with severe~~multi-center randomized, controlled, and ~~moderately severe hemophilia B.~~

~~AMT-061 and AMT-060, the latter of which has been tested in 10 patients in an ongoing~~blinded Phase I/II clinical trial ~~are identical in structure apart from two nucleotide substitutions~~for AMT-130 in the ~~coding sequence~~U.S. (“US study”) as well as an open-label Phase Ib/II study in Europe with the same early-manifest criteria for ~~FIX. The gene variant, referred~~Huntington’s disease as the U.S. study (“European study”). We completed the enrollment of all 26 patients in the first two cohorts of our US study in March 2022 and the enrollment of 13 patients in the two cohorts of our European study in June 2023.

In November 2023, we initiated patient dosing in a third cohort of up to ~~as FIX-Padua, expresses a protein~~12 patients to further investigate both doses of AMT-130 in combination with perioperative immunosuppression. Patient enrollment is ongoing in this cohort with a ~~single amino acid substitution that has been reported~~focus on evaluating near-term safety and tolerability.

In June 2023, we announced interim data, including up to 24-month follow-up, from 26 patients enrolled in ~~multiple preclinical and nonclinical studies~~the ongoing U.S. Phase I/II clinical trial of AMT-130. In December 2023, we announced updated interim data, including up to ~~provide an approximate 8~~30-month follow-up from the 26 patients enrolled in the ongoing US study as well as the 13 patients enrolled in the European study.

Table of ~~hemophilia B with Chiesi.~~ Contents

Cost of contract manufacturing

We ~~recognized $1.9~~incurred $9.1 million ~~collaboration revenue during~~of cost of contract manufacturing related to the ~~same period~~manufacture of HEMGENIX® in ~~2016~~. the three months ended March 31, 2024, compared to $2.4 million cost of contract manufacturing in the three months ended March 31, 2023. The increase in cost of $6.7 million in 2024 is primarily related to expensing costs previously capitalized as work in progress, including a write-down to lower net realizable value.

~~Research and development~~R&D expenses

~~Research and development~~R&D expenses for the three months ended ~~September 30, 2017,~~March 31, 2024 were ~~$20.1~~$40.7 million, compared to ~~$16.6~~$60.8 million for the same period in ~~2016~~. 2023. Other research and development expenses are separately classified in the table below. These other expenses are not allocated as they are deployed across multiple projects under development.


	Three months ended March 31,
	2024		2023		2024 vs 2023
	(in thousands)
Huntington's disease (AMT-130)	$	2,426	$	3,733	$	(1,307)
Temporal lobe epilepsy (AMT-260)		2,254		4,320		(2,066)
Amyotrophic lateral sclerosis (AMT-162)		1,977		10,041		(8,064)
Fabry disease (AMT-191)		1,370		1,088		282
Programs in preclinical development and platform related expenses		449		1,885		(1,436)
Etranacogene dezaparvovec (AMT-060/061)		—		667		(667)
Total direct research and development expenses	$	8,476	$	21,734	$	(13,258)

Employee and contractor-related expenses		16,923		18,703		(1,780)
Facility expenses		7,095		6,786		309
Share-based compensation expense		3,425		4,305		(880)
Other expenses		2,687		4,400		(1,713)
Disposables		1,921		3,906		(1,985)
Fair value changes related to contingent consideration		165		975		(810)
Total other research and development expenses	$	32,216	$	39,075	$	(6,859)

Total research and development expenses	$	40,692	$	60,809	$	(20,117)

Direct research and development expenses

Huntington’s disease (AMT-130)

In the three months ended March 31, 2024 and March 31, 2023, we incurred costs of $2.4 million and $3.7 million respectively. Our external costs for the development of AMT-130 were primarily related to the execution of our Phase I/II clinical trials in the U.S. and in Europe. In the prior year, we had enrollment for the European clinical trial.

Temporal lobe epilepsy (AMT-260)

In the three months ended March 31, 2024 and March 31, 2023, we incurred costs of $2.3 million and $4.3 million respectively, for the development of AMT-260. In August 2023, the FDA cleared our IND application, and we started incurring costs for the preparation of a Phase I clinical trial.

Amyotrophic Lateral Sclerosis caused by mutations in SOD1 (AMT-162)

On January 31, 2023, we entered into a global licensing agreement with Apic Bio for AMT-162. In the three months ended March 31, 2024, we incurred $2.0 million of costs to initiate a Phase I/II clinical trial in 2024. In the three months ended March 31, 2023 we incurred $10.0 million of expenses related to the transaction.

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Table of Contents

Fabry disease (AMT-191)

In the three months ended March 31, 2024 and March 31, 2023, we incurred costs of $1.3 million and $1.1 million, respectively, related to our development of AMT-191. In November 2023, the FDA cleared the IND application, and we started incurring additional costs for the Phase I/II clinical trial preparation.

Preclinical programs & platform development

In the three months ended March 31, 2024 and March 31, 2023, we incurred $0.4 million and $1.9 million of costs, respectively, primarily related to our preclinical activities associated with product candidates for various other research programs and technology innovation projects.

Etranacogene dezaparvovec (AMT-060/061)

We transitioned activities related to the clinical trial and long-term follow-up of patients to CSL Behring in December 2022. Direct research and development expenses related to clinical development and other regulatory activities and commercialization expenses incurred in the three months ended March 31, 2024 and March 31, 2023 are presented net of reimbursements due from CSL Behring and include settlement amounts from the transition.

Other research & development expenses

●

We incurred ~~$9.5~~$16.9 million in personnel ~~share-based compensation~~and contractor-related expenses ~~and consulting cost~~ in the three months ended ~~September 30,~~ ~~2017,~~March 31, 2024, compared to ~~$10.1million during the three months ended~~ ~~September 30,~~ ~~2016. The decrease was a combination of $0.8million one-off expenses related to termination benefits and cost reductions resulting from our restructuring initiated in November 2016;~~

~~We incurred $4.8million in external services and cost related to the development of our product candidates in the three months ended~~ ~~September 30,~~ ~~2017, compared to $4.8million~~ ~~for the same period in 2016~~;

~~We recorded~~ ~~$2.3 million in expenses related to an increase in the fair value of the contingent consideration owed to the sellers of InoCard business~~ ~~in the three months ended~~ ~~September 30,~~ ~~2017,~~ ~~compared to a decrease of $1.8~~$18.7 million for the same period in ~~2016.~~2023. The ~~increase~~decrease was primarily related to the reduction in ~~2017 is partially driven by the amendment~~personnel and contractors as a result of the ~~sale and purchase~~restructuring that occurred in ~~August 2017; and~~

October 2023;

●

We incurred ~~$3.6~~$7.1 million in operating expenses and depreciation expenses related to our rented facilities in Amsterdam and Lexington, Massachusetts in the three months ended ~~September 30,~~ ~~2017,~~March 31, 2024, compared to ~~$3.5~~$6.8 million in the same period in 2023;

●	We incurred $3.4 million in share-based compensation expenses in the three months ended March 31, 2024, compared to $4.3 million for the same period in ~~2016~~.2023. The decrease was primarily a result of the reduction in expense from the restructuring that occurred in October 2023;

●	We incurred $2.7 million of other expenses for the three months ended March 31, 2024, compared to $4.4 million for the same period in 2023;

●	We incurred $1.9 million in disposable costs in the three months ended March 31, 2024, compared to $3.9 million for the same period in 2023. The decrease was primarily a result of the reduction in expense from the restructuring that occurred in October 2023; and

●

We incurred $0.2 million of expenses in the three months ended March 31, 2024 related to an increase in ~~2017 is driven primarily by~~ the ~~additional costs~~fair value of contingent consideration associated with the ~~refurbishment~~acquisition of ~~our new Amsterdam facility, which commenced~~uniQure France SAS, compared to $1.0 million increase in ~~March 2016.~~

fair value for the same period in 2023.

Selling, general and administrative expenses

Selling, general and administrative expenses for the three months ended ~~September 30, 2017,~~March 31, 2024 were $~~5.6~~$13.9 million, compared to $~~5.1~~$17.8 million for the same period in ~~2016~~. 2023.

●

~~Our~~We incurred $6.2 million in personnel and contractor-related expenses ~~related to employees, contractors and consultants~~ in the three months ended ~~September 30,~~ ~~2017, were $1.9million~~March 31, 2024, compared to ~~$2.0~~$5.9 million ~~for~~in the same period in ~~2016~~;

2023;

●

We incurred $~~1.3~~ $3.4 million ofin share-based compensation expenses in the three months ended ~~September 30,~~ ~~2017,~~March 31, 2024, compared to $~~0.0~~ $3.7 million ~~for~~in the same period in ~~2016. The increase was related to equity instruments offered to employees during the last twelve months as well as a one-time reversal of share-based compensation expenses of $0.7~~2023;

●	We incurred $2.0 million in ~~the three months ended September 30, 2016, because of forfeitures of options to acquire 800,000 ordinary shares by our former CEO;~~

~~We incurred~~ ~~$0.9million of~~ professional fees in the three months ended ~~September 30,~~ ~~2017,~~March 31, 2024, compared to ~~$1.4~~$3.2 million ~~for~~in the same period in ~~2016.~~2023. We regularly incur accounting, audit and legal fees associated with operating as a public company. In the prior period, we incurred professional fees related to our global licensing agreement with Apic Bio; and

●

We incurred $2.0 million in other expenses in the three months ended March 31, 2024, compared to $4.0 million in the same period in 2023. The $2.0 million decrease was primarily related to ~~costs incurred~~a decrease in ~~2016 associated with our conversion from IFRS to U.S. GAAP; and~~

intellectual property fees as well as a reduction of expenses for information technology.

~~We incurred~~ $~~0.0~~ ~~million of costs associated with the Glybera~~ ~~global registry and Phase IV study~~ ~~during~~ ~~the three months ended~~ ~~September 30,~~ ~~2017, compared to $0.5million~~ ~~during the same period in 2016. These costs were presented as selling, general and administrative costs prior to May 2017, after which time they are presented as other~~ ~~expense.~~

Table of Contents

Other items, net

We recognized ~~$13.8~~$1.3 million ~~of income~~ in ~~the three months ended September 30, 2017, following the termination of our collaboration with Chiesi in July 2017. The income related to the full amortization~~ ~~of the outstanding deferred revenue. We recognized no such income in the same period in 2016.~~

~~We recognized~~ $~~0.3 million of~~other income from payments received from European authorities to subsidize our research and development efforts in the Netherlands in the three months ended ~~September 30, 2017,~~March 31, 2024, compared to ~~$0.3~~$1.3 million for the same period in ~~2016.~~2023.

~~We recognized other~~

Other items, net ~~expenses of $0.3 million~~for the periods presented primarily related to ~~various exit activities~~ income from the subleasing of our Amsterdam facility and expenses we incur in relation to the subleasing facility.

Other non-operating items, net

Our other non-operating items, net, for the three months ended ~~September 30, 2017. We did not recognize any such expenses in the same period in 2016.~~March 31, 2024 and 2023 were as follows:


	Three months ended March 31,
	2024		2023		2024 vs 2023

	(in thousands)
Interest income	$	6,508	$	1,669	$	4,839
Interest expense		(16,097)		(3,562)		(12,535)
Foreign currency losses, net		(1,145)		(2,369)		1,224
Total non-operating expense, net	$	(10,734)	$	(4,262)	$	(6,472)

~~Other non-operating items, net~~

We recognize interest income associated with our cash and cash ~~equivalents.~~equivalents and investment securities. We recognized $6.5 million in interest income in the three months ended March 31, 2024, compared to $1.7 million in the same period in the prior year. Our interest income increased by $4.8 million due to the interest income earned on investment securities as well as cash on hand during the three months ended March 31, 2024.

~~Table~~We recognized $16.1 million in interest expense for the three months ended March 31, 2024 and $3.6 million for the three months ended March 31, 2023. Our interest expense in 2024 increased due to an increase in market interest rates related to the Hercules debt as well as the recognition of ~~Contents~~

$12.4 million of interest expense related to the Royalty Financing Agreement that we entered into in May 2023.

We hold monetary items and enter into transactions in foreign currencies, predominantly in euros and U.S. dollars. We recognize foreign exchange results related to changes in these foreign currencies.

We ~~issued warrants to Hercules in 2013 and to BMS in 2015. We recognize changes in the fair value of these warrants within other non-operating income / (expense).~~

~~Our other non-operating items, net, for the three months ended September 30, 2017, and 2016 were as follows:~~

Three months ended September 30,


2017

2016

2017 vs 2016

in thousands
Interest income

$
10

$
14

$
(4)
Interest expense Hercules long-term debt

(577)

(507)

(70)
Foreign currency losses

(681)

(496)

(185)
Other non-operating income

—

54

(54)
Total other non-operating income / (expense), net

$
(1,248)

$
(935)

$
(313)

We recognized a net foreign currency loss, related to our borrowings from Hercules, the Royalty Financing Agreement and our cash and cash equivalents and investment securities as well as loans between entities within the uniQure group, of ~~$0.7~~$1.1 million during the three months ended ~~September 30, 2017,~~March 31, 2024, compared to a net loss of ~~$0.5~~$2.4 million during the same period in ~~2016.~~2023.

InIncome tax benefit

We recognized $0.7 million of deferred tax expense in the three months ended ~~September 30, 2017, we did not recognize any gain or loss related to fair value changes~~March 31, 2024, and $1.2 million of ~~warrants compared to a gain of $0.1 million~~deferred tax benefit for the same period in ~~2016.~~2023.

~~Comparison of the nine months ended September 30, 2017, and 2016~~

~~The following table presents a comparison of the nine months ended September 30, 2017, and 2016.~~

Nine months ended September 30,

2017

2016

2017 vs 2016

in thousands
Total revenues

$
10,523

$
15,967

$
(5,444)
Operating expenses:

Research and development expenses

(53,963)

(52,531)

(1,432)
Selling, general and administrative expenses

(17,352)

(20,245)

2,893
Total operating expenses

(71,315)

(72,776)

1,461
Other income

14,995

1,256

13,739
Other expense

(2,901)

—

(2,901)
Loss from operations

(48,698)

(55,553)

6,855
Other non-operating items, net

(3,366)

(2,697)

(669)
Loss before income tax benefit / (expense)

(52,064)

(58,250)

6,186
Income tax benefit / (expense)

278

(401)

679
Net loss

$
(51,786)

$
(58,651)

$
6,865

~~Table of Contents~~

~~Revenue~~

~~Our revenue for the nine months ended September 30, 2017, and 2016 was as follows:~~

Nine months ended September 30,

2017

2016

2017 vs 2016

in thousands
License revenue
$
3,068

$
3,713

$
(645)
Collaboration revenue Chiesi

4,638

4,835

(197)
Collaboration revenue BMS

2,817

7,419

(4,602)
Total revenues
$
10,523

$
15,967

$
(5,444)

In association with the upfront payments and target designation fees received from BMS in the second and third quarters of 2015, we recognized $3.1 million in license revenue during the nine months ended September 30, 2017, compared to $3.0 million during the same period in 2016. Following the termination of our collaboration with Chiesi in July 2017, we no longer recognize license revenue in association with the upfront fees received in 2013. We recognized $0.0 million license revenue during the nine months ended September 30, 2017, compared to $0.7 million during the same period in 2016. We recognized our license revenue for the nine months ended September 30, 2017, net of a $0.5 million reduction for amounts previously amortized in relation to the $2.3 million up-front payments that we were required to repay in accordance with the termination of the Glybera Termination Agreement.

Collaboration revenue generated during the nine months ended September 30, 2017, from research activities associated with AMT-126, our BMS-partnered S100A1 heart failure program, was $2.8 million compared to $7.4 million ~~for the same period in 2016. The reduction in the current year period was driven by the timing of various preclinical activities as well as the production of preclinical material during the same period in 2016.~~

~~Research and development expenses~~

~~Research and development expenses for the nine months ended September 30, 2017, were $54.0 million compared to $52.5 million~~ ~~for the same period in 2016~~.

~~We incurred $27.9million in personnel, share-based compensation expenses and consulting cost in the nine months ended~~ ~~September 30,~~ ~~2017, compared to $29.5million during the nine months ended~~ ~~September 30,~~ ~~2016. The decrease was a combination of $1.7million one-off expenses related to termination benefits and cost reductions resulting from our restructuring initiated in November 2016;~~

~~We incurred $11.9million in external services and costs related to the development of our product candidates in the nine months ended~~ ~~September 30,~~ ~~2017, compared to $14.2million~~ ~~for the same period in 2016. The reduction was primarily driven by lower costs of manufacturing drug substance to supply our studies;~~

~~We incurred $10.8million operating expenses and depreciation expenses related to our rented facilities in the nine months ended~~ ~~September 30,~~ ~~2017, compared to $10.3million~~ ~~for the same period in 2016. The~~ ~~increase was driven primarily by additional costs incurred during the first months of 2017 associated with the refurbishment of our new Amsterdam facility;~~

~~We recorded~~ ~~$2.7 million in expenses related to an increase in the fair value of the contingent consideration owed to the sellers of InoCard business~~ ~~in the nine months ended~~ ~~September 30,~~ ~~2017,~~ ~~compared to a decrease of $1.6 million for the same period in 2016. The increase in 2017 is partially driven by the amendment of the sale and purchase in August 2017;and~~

~~We incurred no share-based compensation expenses related to our collaboration with 4D Molecular Therapeutics in the nine months ended~~ ~~September 30,~~ ~~2017, compared to $0.7 million~~ ~~for the same period in 2016~~.

~~Table of Contents~~

~~Selling, general and administrative expenses~~

~~Selling, general and administrative expenses for the nine months ended September 30, 2017, were~~ $~~17.4 million compared to~~ $~~20.2million~~ ~~for the same period in 2016~~.

~~Our expenses related to employees, contractors and consultants in the nine months ended~~ ~~September 30,~~ ~~2017, were $6.1million compared to $6.6million~~ ~~for the same period in 2016. The decrease was primarily driven by $0.8million in one-time costs related to the CEO-transition that took place during~~ ~~the first half of 2016~~;

~~We incurred $3.4million of share-based compensation expenses in the nine months ended~~ ~~September 30,~~ ~~2017, compared to $1.7million~~ ~~for the same period in 2016~~. The increase was related to equity instruments offered to employees during the last twelve months as well as a one-time reversal of share-based compensation expenses of $0.7 million in the three months ended September 30, 2016, because of forfeitures of options to acquire 800,000 ordinary shares by our former CEO;

~~We incurred $3.8million of professional fees in the nine months ended~~ ~~September 30,~~ ~~2017, compared to $4.4million~~ ~~for the same period in 2016~~. ~~The decrease was primarily due to the cost of our conversion from IFRS to U.S. GAAP which we incurred in 2016~~;

~~We incurred legal and settlement costs of $1.9million in connection with our arbitration proceeding with Extera during the nine months ended September 30, 2016. No such costs were incurred during the nine months ended September 30, 2017; and~~

~~We incurred $0.3million of costs associated with the Glybera global registry and Phase IV study during~~ ~~the nine months ended~~ ~~September 30,~~ ~~2017~~, ~~compared to $2.3million~~ ~~during the same period in 2016. These costs were presented as selling, general and administrative costs prior to May 2017, after which time they are presented as other expense.~~

~~Other items, net~~

Following the termination of our collaboration with Chiesi in July 2017, we recognized $13.8 million income in the nine months ended September 30, 2017, related to the full amortization of the outstanding deferred revenue. We recognized no such income in the same period 2016.

We recognized $0.9 million in income during the nine months ended September 30, 2017, from payments received from European authorities to subsidize our research and development efforts in the Netherlands compared to $1.3 million for the same period in 2016.

We recognized other expense in the nine months ended September 30, 2017, of $1.8 million related to contractual commitments in relation to terminating the marketing our Glybera program, as well as our collaborations with Chiesi. We did not recognize any such expenses in the same period in 2016.

We accrued $0.6 million of contract termination costs in the nine months ended September 30, 2017, related to vacated facilities at our Amsterdam site. We did not recognize any such expenses in the same period in 2016.

~~In addition, we accrued $0.5 million related to~~ ~~various exit activities~~ ~~during the nine months ended September 30, 2017. We did not recognize any such expenses in the same period in 2016.~~

~~Other non-operating items, net~~

~~We recognize interest income associated with cash and cash equivalents.~~

~~We hold monetary items and enter into transactions in foreign currencies, predominantly in euros and U.S. dollars. We recognize foreign exchange results related to changes in these foreign currencies.~~

~~Table of Contents~~

~~We issued warrants to Hercules in 2013 and to BMS in 2015. We recognize changes in the fair value of these warrants within other non-operating income / (expense).~~

~~Our other non-operating items, net, for the nine months ended September 30, 2017, and 2016 were as follows:~~

Nine months ended September 30,

2017

2016

2017 vs 2016

in thousands
Interest income

$
33

$
51

$
(18)
Interest expense Hercules borrowing

(1,583)

(1,685)

102
Foreign currency losses

(1,845)

(1,764)

(81)
Other non-operating income

29

701

(672)
Total other non-operating income / (expense), net

$
(3,366)

$
(2,697)

$
(669)

We recognized a net foreign currency loss related to our borrowings from Hercules and our cash and cash equivalents of $1.8 million during the nine months ended September 30, 2017, compared to a net loss of $1.8 million during the same period in 2016.

~~In the nine months ended September 30, 2017, we recognized no gain or loss related to fair value changes of warrants compared to a gain of $0.7 million for the same period in 2016.~~

Financial Position, Liquidity and Capital Resources

As of ~~September 30, 2017,~~March 31, 2024, we had cash and cash equivalents, ~~of $88.9 million. We currently expect that our~~restricted cash and ~~cash equivalents will be sufficient to fund operations into early 2020. The table below summarizes our consolidated cash flow data for the nine months ended September 30, 2017, and 2016.~~

Nine months ended September 30,

2017

2016

in thousands
Cash and cash equivalents at the beginning of the period

$
132,496

$
221,626
Net cash used in operating activities

(46,223)

(56,515)
Net cash used in investing activities

(4,935)

(13,548)
Net cash generated from financing activities

1,036

2,069
Foreign exchange impact

6,560

3,919
Cash and cash equivalents at the end of the period

$
88,934

$
157,551

~~We have incurred losses and cumulative negative cash flows from operations since our business was founded by our predecessor entity AMT Therapeutics (“AMT”) Holding N.V. in 1998. We had a net loss~~investment securities of $10.2 million and $51.8 million during the three and nine months ended September 30, 2017, respectively, compared to a loss of $15.3 million and $58.7 million during the same periods in 2016. As of September 30, 2017, we had an accumulated deficit of $447.8$558.9 million.

~~Sources of liquidity~~

From our first institutional venture capital financing in 2006 through September 30, 2017, we funded our operations primarily through private and public placements of equity securities and convertible and other debt securities and to a much lesser extend upfront, target designation or similar payments from our collaboration partners as well as collaboration revenues.

~~We expect to continue to incur losses and to generate negative cash flows. We have no firm sources of additional financing other than our collaboration agreement~~s ~~with BMS.~~ Until such time, if ever, as we can generate substantial cash flows from successfully commercializing our proprietary product candidates, we expect to finance our cash needs through a combination of equity offerings, debt financings, collaborations, strategic alliances and marketing, distribution, and licensing arrangements.

Based on our current operating plan, research and development plans and our timing expectations related to the progress of our programs and following the Reorganization, we believe that our cash and cash equivalents and investment securities will fund our operations into second quarter of 2027. We have based this estimate on assumptions that may prove to be wrong, and we could exhaust our available capital resources sooner than we expect. We expect that we will require additional funding if we decide to advance AMT-130 for our Huntington’s disease gene therapy program or any of our other product candidates into late-stage clinical development. Our material cash requirements include the following contractual and other obligations:

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Debt

As of March 31, 2024, we had an outstanding loan amount owed to Hercules Capital, Inc. (“Hercules”) for an aggregate principal amount of $100.0 million. Future interest payments and financing fees associated with the loan total $44.2 million, with $13.4 million payable within 12 months. We are contractually required to repay the $100.0 million in full in January 2027.

Leases

We entered into lease arrangements for facilities, including corporate, manufacturing and office space. As of March 31, 2024, we had fixed lease payment obligations of $50.7 million, with $8.4 million payable within 12 months.

Commitments related to uniQure France SAS acquisition (nominal amounts)

In relation to our acquisition of uniQure France SAS in 2021, we entered into commitments to make payments to the former shareholders upon the achievement of certain contractual milestones. The commitments include payments related to post-acquisition services that we agreed to as part of the transaction. In September 2023, we made a payment of EUR 10.0 million ($10.6 million) to the former shareholders of uniQure France SAS following the FDA’s clearance of the IND application for AMT-260. As of March 31, 2024, our remaining commitment amounts include a EUR 30.0 million ($32.4 million) milestone payment due upon treating the first patient in a Phase I/II clinical trial for AMT-260 and EUR 160.0 million ($172.7 million) in potential milestone payments associated with Phase III development and the approvals of AMT-260 in the U.S. and European Union. The timing of achieving these milestones and consequently the timing of payments, as well as whether the milestone will be achieved at all, is generally uncertain. These payments are owed in euro and have been translated at the foreign exchange rate as of March 31, 2024, of $1.08/€1.00. As of March 31, 2024, we expect these obligations will become payable between 2024 and 2031. If and when due, up to 25% of the milestone payments can be settled with our ordinary shares.

Commitments related to licensors and financial advisors

We have obligations to make future payments to third parties that become due and payable on the achievement of certain development, regulatory and commercial milestones (such as the start of a clinical trial, filing of a BLA, approval by the FDA or product launch) or as a result of collecting payments related to our sale of the exclusive global rights of HEMGENIX® to CSL Behring. We also owe payments to a financial advisor related to certain payments we will collect under the CSL Behring Agreement.

The table below summarizes our consolidated cash flow data for the three months ended:


	Three months ended March 31,
	2024		2023
	(in thousands)
Cash, cash equivalents and restricted cash at the beginning of the period	$	244,544	$	231,173
Net cash used in operating activities		(60,575)		(78,302)
Net cash generated from investing activities		63,985		2,988
Net cash generated from financing activities		—		131
Foreign exchange impact		(1,725)		1,034
Cash, cash equivalents and restricted cash at the end of period	$	246,229	$	157,024

We had previously incurred losses and cumulative negative cash flows from operations since our business was founded by our predecessor entity AMT Therapeutics Holding N.V. (“AMT”) in 1998, with the exception of generating income in 2021 after receiving the upfront payment upon closing of the CSL Behring Agreement. We continue to incur losses in the current period. We recorded a net loss of $65.6 million in the three months ended March 31, 2024, compared to a net loss of $77.2 million during the same period in 2023. As of March 31, 2024, we had an accumulated deficit of $956.0 million.

Sources of liquidity

From our first institutional venture capital financing in 2006 through the current period, we funded our operations primarily through private and public placements of equity securities, debt securities, payments from our collaboration partners as well as from selling a portion of royalties due from our collaboration partner CSL Behring. We have collected $100.0 million in July 2023 related to the first sale milestone of HEMGENIX® in the U.S., and are eligible to receive additional milestone payments, as well as royalties (to the extent not owed to settle the liability from royalty financing) on net sales of HEMGENIX®.

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~~In September 2017, we established an “at the market” equity offering program pursuant to which we can sell up to 5 million ordinary shares at prevailing market prices from time to time.~~

On ~~October 27, 2017,~~May 12, 2023 we ~~completed our public offering announced on October 23, 2017. We issued~~ and ~~sold 5,000,000 ordinary shares at $18.25 per ordinary share, resulting in gross proceeds of approximately $91.3 million.~~Hercules amended the 2021 Restated Facility. The ~~net proceeds~~2023 Amended Facility extends the maturity date and interest-only period from December 1, 2025 to us from this offering were approximately $85.4 million, after deducting underwriting discounts and commissions and other estimated offering expenses payable by us. We granted the underwriters an option to purchase up to 750,000 ordinary shares at the public offering price of $18.25.January 5, 2027.

We ~~intend~~are required to ~~use~~repay the ~~net proceeds from this offering to fund~~entire principal balance of $100.0 million on the ~~continued clinical development~~maturity date. The interest rate is adjustable and is the greater of ~~AMT-061 in hemophilia B~~(i) 7.95% and ~~other programs, including AMT-130 in Huntington’s disease and other preclinical product candidates focused on rare and orphan diseases and to fund general corporate and working capital purposes.~~

~~The above equity financing entitles us to extend~~(ii) 7.95% plus the ~~interest interest-only payment period of its 2016~~prime rate less 3.25% per annum. Under the 2023 Amended Facility, ~~by 12 months from November 2017 to November 2018.~~we owe a back-end fee of $4.9 million on December 1, 2025 and a back-end fee of $1.3 million on the maturity date.

We are subject to certain covenants under ~~our Loan Agreement with Hercules,~~the 2023 Amended Facility and may become subject to covenants under any future indebtedness that could limit our ability to take specific actions, such as incurring additional debt, making capital expenditures, or declaring dividends, which could adversely impact our ability to conduct our business. In addition, our pledge of assets as collateral to secure our obligations under the ~~Hercules loan agreement~~2023 Amended Facility may limit our ability to obtain debt financing. The 2023 Amended Facility permits us to issue up to $500.0 million of convertible debt.

To the extent we need to finance our cash needs through equity offerings or debt financings, such financing may be subject to unfavorable terms including without limitation, the negotiation and execution of definitive documentation, as well as credit and debt market conditions, and we may not be able to obtain such financing on terms acceptable to us or at all. If financing is not available when needed, including through debt or equity ~~financings,~~financing, or is available only on unfavorable terms, we may be unable to meet our cash needs. If we raise additional funds through collaborations, strategic alliances or marketing, distribution, or licensing arrangements with third parties, we may have to relinquish valuable rights to our technologies, future revenue streams or product candidates or grant licenses on terms that may not be favorable to us. If we are unable to raise additional funds through equity or debt financings when needed, we may be required to delay, limit, reduce or terminate our product development or future commercialization efforts or grant rights to develop and market product candidates that we would otherwise prefer to develop and market ourselves, which could have a material adverse effect on our business, financial conditions, results of operations and cash flows.

Net ~~Cash~~cash used in operating activities

Net cash used in operating activities was ~~$46.2~~$60.6 million for the ~~nine~~three months ended ~~September 30, 2017,~~March 31, 2024 and consisted of net loss of $65.6 million adjusted for non-cash items, including depreciation and amortization expense of $2.6 million, amortization of the discount on investment securities of $3.7 million, share-based compensation expense of $7.2 million, changes in the fair value of contingent consideration of $0.2 million, unrealized foreign exchange losses of $1.4 million, $12.4 million of interest expense related to the royalty financing and a ~~reduction~~change in deferred taxes of $0.7 million. Net cash used in operating activities also included unfavorable changes in operating assets and liabilities of $18.4 million. There was a net increase in accounts receivable, prepaid expenses, and other current assets and receivables of $10.4 million. There was a decrease in inventory balances of $2.2 million. There was a net decrease in accounts payable, accrued expenses, other liabilities, and operating leases of $10.3 million, ~~compared to the $56.5 million of cash used in~~ ~~the same period in 2016~~.

~~The reduction is~~ primarily ~~due~~related to a decrease of $6.7 million favorable change in our net working capital during the nine months ended September 30, 2017, compared to a $2.2 million unfavorable change in our net working capital during the same period in 2016. In addition, we collected $1.1 million in lease incentive paymentsfrom personnel related ~~to our new Amsterdam facility and reduced our operating expenses during the nine months ended September 30, 2017 by $0.3 million compared to the same period in 2016.~~accruals.

~~Table of Contents~~

Net cash used in operating activities was $78.3 million for the three months ended March 31, 2023 and consisted of net loss of $77.2 million adjusted for non-cash items, including depreciation and amortization expense of $2.5 million, amortization of the discount on investment securities of $0.9 million, share-based compensation expense of $8.1 million, changes in the fair value of contingent consideration of $1.0 million, unrealized foreign exchange losses of $1.2 million and a change in deferred taxes of $1.2 million. Net cash generated from operating activities also included unfavorable changes in operating assets and liabilities of $12.2 million. There was a net increase in accounts receivable, prepaid expenses, and other current assets and receivables of $0.9 million. These changes also relate to a net decrease in accounts payable, accrued expenses, other liabilities, and operating leases of $10.7 million, primarily related to a decrease of $7.9 million from personnel related accruals.

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Net cash generated from investing activities

In the ~~nine~~three months ended ~~September 30, 2017~~,March 31, 2024, we ~~used~~ ~~$4.9~~ generated $64.4 million in our investing activities compared to ~~$13.5~~generating $3.0 million for the same period in ~~2016~~.2023.

Nine months ended September 30,

2017

2016

in thousands
Build out of Lexington site

$
(638)

$
(1,483)
Build out of Amsterdam sites

(2,606)

(9,551)
Acquisition of licenses and patents

(1,124)

(1,897)
Restricted cash

(567)

(617)
Total investments

$
(4,935)

$
(13,548)


	Three months ended March 31,
	2024		2023
	(in thousands)
Proceeds from maturity of investment securities	$	150,107	$	5,330
Investment in investment securities		(83,778)		—
Build out of Amsterdam site		(1,051)		(686)
Build out of Lexington site		(1,293)		(1,656)
Net cash generated from investing activities	$	63,985	$	2,988

During the ~~nine~~three months ended ~~September 30, 2017~~, March 31, 2024, we received $150.1 million from the repayment of previous investments into euro and U.S. dollar denominated government bonds ($5.3 million for three months ended March 31, 2023).

During the three months ended March 31, 2024, we invested ~~$2.~~6 $83.8 million inof our ~~new facility in~~cash on hand into euro denominated government bonds (nil for the three months ended March 31, 2023).

We invested $1.1 million and $1.3 million, respectively, into our Amsterdam, Netherlands and ~~$9.6~~Lexington, Massachusetts sites during the three months ended March 31, 2024, compared to $0.7 million inand $1.7 million for the same period ~~2016.~~in 2023.

Net cash generated from financing activities

In the three months ended March 31, 2024, we generated nil from financing activities compared to $0.1 million for the same period in 2023.


	Three months ended March 31,
	2024		2023

	(in thousands)
Cash flows from financing activities
Proceeds from issuance of ordinary shares related to employee stock option and purchase plans		-		131
Net cash generated from financing activities	$	-	$	131

During the ~~nine~~three months ended ~~September 30, 2017,~~March 31, 2024, we received ~~$1.0 million~~nil from the exercise of options to purchase ordinary shares in relation to our ~~share incentive plans~~2014 Plans, compared to ~~$2.2~~$0.1 million infor the same period ~~2016.~~in 2023.

Funding requirements

~~We believe our cash and cash equivalents as of~~ ~~September 30,~~ ~~2017, will enable us to fund our operating~~ ~~expenses including our debt repayment obligations as they become due and capital expenditure requirements, for at least the next twelve months.~~ Our future capital requirements will depend on many factors, including but not limited to:

●

contractual milestone payments and royalties we might be owed in accordance with the ~~potential to receive future consideration pursuant to our collaboration with BMS, which is largely contingent on achieving certain research, development, regulatory and sales milestones;~~

CSL Behring Agreement;

●

~~our ability~~earnout payments we might owe the former shareholders of uniQure France SAS, which are subject to ~~enter into collaboration arrangements in~~ the ~~future;~~

achievement of specific development and regulatory milestones;

●

the scope, timing, results, and costs of our current and planned clinical trials, including those for ~~AMT-061 in hemophilia B and~~ AMT-130 in Huntington’s disease;

●

the scope, obligations and restrictions on our business related to our existing equity, debt or royalty monetization financings and underlying agreements;

●

the extent to which we acquire or in-license other businesses, products, product candidates or technologies;

●

the amount and timing of revenue, if any, we receive from manufacturing products for CSL Behring;

Table of Contents

●

the scope, timing, results and costs of preclinical development and laboratory testing of our additional product ~~candidates, including~~candidates;

●

the need for additional resources and related recruitment costs to support the preclinical and clinical development of our ~~S100A1 gene therapy candidate for the treatment of heart failure;~~

product candidates;

●

the need for any additional tests, studies, or trials beyond those originally anticipated to confirm the safety or efficacy of our product candidates and technologies;

●

the cost, timing and outcome of regulatory reviews associated with our product candidates;

●

~~the cost and timing of future commercialization activities, including product manufacturing, marketing, sales and distribution of any of~~ our ~~product candidates for which we receive marketing approval~~ability to enter into collaboration arrangements in the future;

●

~~the amount and timing of revenue, if any, we receive from commercial sales of any product candidates for which we, or our collaboration partner, receives marketing approval in the future;~~

the costs and timing of preparing, filing, expanding, acquiring, licensing, maintaining, enforcing, and prosecuting patents and patent applications, as well as defending any intellectual property-related claims;

and

●

~~the repayments of the principal amount of our venture debt loan with Hercules, which will contractually start in December 2018 and will run through May 2020;~~

~~the extent to which we acquire or in-license other businesses, products, product candidates or technologies;~~

the costs associated with maintaining quality compliance and optimizing our manufacturing processes, including the operating costs associated with our Lexington, Massachusetts manufacturing ~~facility;~~

facility.

~~the costs associated with recent and future hiring of senior management and other personnel,~~

~~the timing, costs, savings and operational implications of the corporate restructuring we are implementing following the completion of our strategic review last year.~~

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~~Contractual obligations and commitments~~

~~The table below sets forth our contractual obligations and commercial commitments as of September 30, 2017, that are expected to have an impact on liquidity and cash flows in future periods.~~

Less than 1

Between 1

Between 2


Undefined

year

and 2 years

and 5 years

Over 5 years

Total

in thousands
Debt obligations (including $3.6 million interest payments)

$
—

$
7,888

$
8,848

$
6,869

$
—

$
23,605
Operating lease obligations

—

3,308

3,852

11,877

21,507

40,544
Contingent consideration (nominal amount)

15,949

—

—

—

—

15,949
Total

$
15,949

$
11,196

$
12,700

$
18,746

$
21,507

$
80,098

Due to uncertainty of the timing of achieving certain contractual milestones, the contingent consideration of $15.9 million related to our acquisition of InoCard (later renamed uniQure GmbH) is considered to have an undefined contractual maturity. As of September 30, 2017, we expect the milestone obligations will become payable between 2018 and 2021. When due, 50% of the obligations can be settled either in cash or in a variable number of our shares. As of September 30, 2017, we recorded this obligation at its fair value of $3.6 million. In addition, we recorded ~~$1.2 million owed to the former shareholders of Inocard (presented as other current liabilities).~~

We also have obligations to make future payments to third parties that become due and payable on the achievement of certain development, regulatory and commercial milestones (such as the start of a clinical trial, filing of a Biologics License Application, approval by the FDA or product launch). We have not included these commitments on our balance sheet or in the table above because the achievement and timing of these milestones is not fixed and determinable.

We enter into contracts in the normal course of business with clinical research organizations (“CROs”) for preclinical research studies and clinical trials, research supplies and other services and products for operating purposes. These contracts generally provide for termination on notice, and therefore are cancelable contracts and not included in the table of contractual obligations and commitments.

The Company’s predecessor entity received a technical development loan from the Dutch government in relation to the development of Glybera. The Company needs to repay the grant through a percentage of revenue derived from product sales of Glybera up to December 31, 2019. Any grant balance remaining at this date will be forgiven. We have decided not to renew our marketing authorization for Glybera in the European Union, which expires in October 2017. We do not expect to derive any revenue from Glybera or to be required to make any repayments under this loan.

~~Off-Balance Sheet Arrangements~~

~~As of~~ ~~September~~ ~~30, 2017, we did not have any off-balance sheet arrangements as defined in Item 303(a) (4) of Regulation S-K.~~

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Item 3.Quantitative and Qualitative Disclosures about Market Risk

We are exposed to a variety of financial risks in the normal course of our business, including market risk (including currency, price, and interest rate risk), credit risk and liquidity risk. Our overall risk management program focuses on the preservation of capital and the unpredictability of financial markets and has sought to minimize potential adverse effects on our financial performance and position.

Our market risks and exposures to such market risks during the ~~nine~~three months ended ~~September 30,~~ ~~2017, has~~March 31, 2024, have not materially changed from our market risks and our exposure to market risk discussed in Part II, Item 7A of our Annual Report ~~on Form 10-K for the year ended December 31, 2016, which was filed with the SEC on March 15, 2017.~~.

Item 4.Controls and Procedures

Evaluation of Disclosure Controls and Procedures

Our management, with the participation of our chief executive officer (“CEO”) and chief ~~finance~~financial officer (“~~CEO”~~CFO”), evaluated the effectiveness of our disclosure controls and procedures (as defined in Rules 13a-15(e) and 15d-15(e) under the Securities Exchange Act of 1934, as amended (the “Exchange Act”)) as of ~~September 30,~~ ~~2017.~~March 31, 2024. Based on such evaluation, our CEO ~~has~~and CFO concluded that as of ~~September 30,~~ ~~2017,~~March 31, 2024, our disclosure controls and procedures were effective to ensure that information required to be disclosed by it in reports the Company files or submits under the Exchange Act is recorded, processed, summarized and reported within the time periods specified in the rules and forms of the SEC, and that such material information is accumulated and communicated to the Company’s management, including its Principal Executive Officer and Principal Financial Officer, to allow timely decisions regarding required disclosure. Because of the inherent limitations in all control systems, any controls and procedures, no matter how well designed and operated, can provide only reasonable assurance of achieving the desired control objectives, and management necessarily is required to apply its judgment in evaluating the cost-benefit relationship of possible controls and procedures. Furthermore, the Company’s controls and procedures can be circumvented by the individual acts of some persons, by collusion of two or more people or by management override of such control, and misstatements due to error or fraud may occur and not be detected on a timely basis.

Changes in Internal Control over Financial Reporting

During the ~~nine months ended September 30, 2017,~~period covered by this Quarterly Report on Form 10-Q, there were no changes in our internal control over financial reporting (as defined in Rule 13a-15(f) under the Exchange Act) that materially affected, or are reasonably likely to materially affect, our internal control over financial reporting.

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Part II – OTHER INFORMATION

Item 1.Legal Proceedings

None.

Item 1A.Risk Factors

An investment in our ordinary shares involves a high degree of risk. You should carefully consider the following information about these risks, together with the other information appearing elsewhere in this Quarterly Report on Form 10-Q, including our financial statements and related notes thereto, and the risk factors discussed in Part I, Item 1A “Risk Factors” in our Annual Report ~~on Form 10-K for the year ended December 13, 2016, field with the SEC on March 15, 2017,~~, before deciding to invest in our ordinary shares. We operate in a dynamic and rapidly changing industry that involves numerous risks and uncertainties. The risks and uncertainties described below are not the only ones we face. Other risks and uncertainties, including those that we do not currently consider material, may impair our business. If any of the risks discussed below actually occur, our business, financial condition, operating results, or cash flows could be materially adversely affected. This could cause the value of our securities to decline, and you may lose all or part of your investment.

~~Those risk factors below denoted~~

Summary Risk Factors

The following is a summary of the principal risks associated with ~~a “*” are newly added or have been materially updated from~~an investment in our ~~Annual Report on 10-K filed with the SEC on March 15, 2017.~~ordinary shares:

●

We are dependent on the success of our lead product candidate in clinical development, AMT-130 for the treatment of Huntington’s disease. A failure of AMT-130 in clinical development, challenges associated with its regulatory pathway, or its inability to demonstrate sufficient efficacy to warrant further clinical development could adversely affect our business.

●

We have encountered and may encounter future delays in and impediments to the progress of our clinical trials or fail to demonstrate the safety and efficacy of our product candidates.

●

Our progress in early-stage clinical trials may not be predictive of long-term efficacy in late-stage clinical trials, and our progress in trials for one product candidate may not be predictive of progress in trials for other product candidates.

●

We may not be successful in our efforts to use our gene therapy technology platform to build a pipeline of additional product candidates or otherwise leverage our research and technology to remain competitive.

●

Our future success depends on our ability to retain key executives, technical staff, and other employees and to attract, retain and motivate qualified personnel.

●

Actions that we have taken to restructure our business in alignment with our strategic priorities may not be as effective as anticipated, may not result in cost savings to us and could disrupt our business.

●

Gene therapies are complex, expensive and difficult to manufacture. We could experience capacity, production or technology transfer challenges that could result in delays in our development or commercialization schedules or otherwise adversely affect our business.

●

We will need to raise additional funding in order to advance the development of our product candidates, which may not be available on acceptable terms, or at all. Failure to obtain capital when needed may force us to delay, limit or terminate our product development efforts or other operations which could have a material adverse effect on our business, financial condition, results of operations and cash flows.

●

We had net losses in the years ended December 31, 2023 and 2022, have incurred significant losses in previous years and expect to incur losses during the current and over the next several years and may never achieve or maintain profitability.

●

The price of our ordinary shares has been and may in the future be volatile and fluctuate substantially.

●

If we do not achieve our projected development goals in the timeframes we announce and expect, the commercialization of our product candidates may be delayed and, as a result, our stock price may decline.

●

If we are unable to obtain and maintain patent protection for our technology and products, or if the scope of the patent protection is not sufficiently broad, our ability to successfully commercialize our products may be impaired.

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●

We may become involved in lawsuits to protect or enforce our patents or other intellectual property, or third parties may assert their intellectual property rights against us, which could be expensive, time consuming and unsuccessful.

●

We rely, and expect to continue to rely, on third parties to conduct, supervise, and monitor our preclinical studies and clinical trials, and those third parties may not perform satisfactorily, including failing to meet deadlines in the conduct or completion of such trials or failing to comply with regulatory requirements.

●

We rely on third parties for important aspects of our development programs. If these parties do not perform successfully or if we are unable to enter into or maintain key collaborations or other contractual arrangements, our business could be adversely affected.

●

We face substantial competition, and others may discover, develop, or commercialize competing products before or more successfully than we do.

●

Our business development strategy depends on our ability to obtain rights to key technologies through in-licenses and support the development of our product pipeline through out-licenses, and those efforts may not be successful.

●

Our business development strategy may not produce the cash flows expected or could result in additional costs and challenges.

●

We may be adversely affected by unstable market and economic conditions, such as inflation, which may negatively impact our business, financial condition and stock price.

Risks Related to the Development of Our Product Candidates

We have invested a significant portion of our development efforts and financial resources in the development of our lead clinical product candidate, AMT-130. In December 2023, we announced updated interim data from our ongoing Phase I/II clinical trials of AMT-130, including 30 months of follow-up data from the 39 patients then enrolled in our trials in the U.S. and in Europe. We also announced our plans to continue enrollment in a third cohort to investigate AMT-130 in combination with perioperative immune suppression to evaluate near-term safety, along with our plans to initiate regulatory interactions with the FDA and EMA to discuss the interim data and strategies for ongoing development of AMT-130.

There are numerous factors that could impede or otherwise negatively impact our further development of AMT-130, including, but not limited to, patient safety issues, our failure to demonstrate sufficient clinical efficacy or durability of response data to warrant further development, delays in our ability to enroll patients or challenges with regulatory authorities. Any one or combination of these factors could force us to halt or discontinue the ongoing clinical trials of AMT-130. Certain of these risk factors are heightened in the context of drug development for rare diseases like Huntington’s disease in which non-traditional study designs are utilized to demonstrate efficacy and safety, including open-label studies, single arm studies, studies utilizing active comparators or natural history data, biomarkers or other forms of surrogate endpoints, which may be utilized due to the challenges inherent in designing and conducting clinical trials for severe diseases that progress slowly and that affect small patient populations. For example, in the course of our interactions with the FDA and EMA, the regulatory authorities may disagree with our interpretation of the interim safety and efficacy data we have received to date. Since AMT-130 is based on our novel gene therapy technology, we are unable predict how regulatory authorities will interpret our data or whether they will agree with our interim conclusions or trial design or whether those data may be utilized in later-stage or registrational trials. We may be required by such regulatory authorities to conduct additional randomized studies of AMT-130 beyond our existing clinical trials, which would be costly and would significantly delay the potential approval of AMT-130. We may not be able to commit sufficient capital to support additional clinical studies of AMT-130, in which case we may need to secure a development partner for AMT-130. Such partnerships may not be available, in which case we may not be able to fully fund the AMT-130 program.

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If AMT-130 fails in development as a result of any underlying problem with our technology, then we may be required to discontinue development of other product candidates that are based on the same novel therapeutic approach. We cannot be certain that AMT-130, or any of our product candidates, will be successful in clinical trials or receive regulatory approval. If we were required to, or if we chose to, discontinue development of AMT-130 or any other future product candidates, or if any of them were to fail to receive regulatory approval or achieve sufficient market acceptance, we could be prevented from or significantly delayed in achieving profitability and our business would be adversely affected.

We have encountered and may encounter ~~substantial~~future delays in and impediments to the progress of our clinical trials or fail to demonstrate the safety and efficacy of our product candidates.

~~Clinical and non-clinical~~Drug development is expensive, time-consuming, and uncertain as to the outcome. Our product candidates are in ~~early~~different stages of clinical or preclinical development, and there is a significant risk of failure or delay in each of these programs. We ~~cannot guarantee that any preclinical tests or~~are currently conducting Phase I/II clinical trials ~~will be completed as planned or completed~~in the U.S. and Europe for AMT-130, our investigational gene therapy for the treatment of Huntington’s disease. We are also advancing three other product candidates into clinical development – AMT-260 for the treatment of refractory mesial temporal lobe epilepsy, AMT-162 for the treatment of SOD1-ALS and AMT-191 for the treatment of Fabry disease.

We have experienced clinical setbacks in the past and may experience setbacks in the future. For example, we experienced an immaterial but unexpected delay when our clinical trials of HEMGENIX® were placed on ~~schedule, if at all.~~ clinical hold by the FDA from December 2020 to April 2021 following a preliminary diagnosis of hepatocellular carcinoma in one patient. Similarly, we experienced an unexpected delay in the enrollment of our Phase Ib/II clinical trial of AMT-130 for the treatment of Huntington’s disease between July and October 2022 due to our voluntary postponement and comprehensive safety investigation into suspected unexpected serious adverse reactions in three patients.

A failure of one or more ~~preclinical tests or~~ clinical trials can occur at any stage and for a variety of ~~testing.~~reasons that we cannot predict with accuracy and that are out of our control. Events that may prevent successful or timely completion of clinical development, as well as product candidate approval, include, but are not limited to:

●

occurrence of serious adverse events associated with a product candidate that are viewed to outweigh its potential benefits;

●

insufficient number of patients treated with the product candidate or study period for assessing the effectiveness of the product candidate insufficient in length to assess potential clinical development;

●

failures or delays in reaching ~~a consensus~~agreement with regulatory agencies on study ~~design;~~

design, particularly with respect to our novel gene therapies for which regulatory pathways remain untested;

●

failures or delays in hiring sufficient personnel with the requisite expertise to execute multiple clinical programs simultaneously;

●

failures or delays in reaching agreement on acceptable terms with ~~prospective CROs~~clinical research organizations (“CROs”) and clinical trial sites;

●

failures or delays in patient recruiting into clinical trials or in the addition of new investigators;

●

delays in receiving regulatory ~~authority~~authorization to conduct ~~the~~our clinical trials or a regulatory authority decision that the clinical trial should not proceed;

●

failures or delays in obtaining or failure to obtain required ~~Institutional Review Board (“IRB”)~~IRB and IBC approval at each clinical trial site;

●

requirements of regulatory authorities, IRBs, or IBCs to modify a study in such a way that it makes the study impracticable to conduct;

●

regulatory authority requirements to perform additional or unanticipated clinical trials or testing;

●

changes in standards of care which may necessitate the modification of our clinical trials or the conduct of new trials;

●

regulatory authority refusal to accept data from foreign clinical study sites;

●

disagreements with regulatory authorities regarding our study design, including endpoints, our chosen indication, our chosen bases for comparison as it relates to clinical efficacy, our interpretation of data from preclinical studies and clinical trials or a finding that a product candidate’s benefits do not outweigh its safety risks;

●

recommendations from DSMBs to discontinue, pause, or modify the trial;

●

imposition of a clinical hold by regulatory agencies after an inspection of our clinical trial operations or trial sites;

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●

suspension or termination of clinical research for various reasons, including noncompliance with regulatory requirements or a finding that the participants are being exposed to unacceptable health risks, undesirable side effects, or other unexpected characteristics (alone or in combination with other products) of the product candidate, or due to findings of undesirable effects caused by a chemically or mechanistically similar therapeutic or therapeutic candidate;

●

failure by CROs, other third parties or us to adhere to clinical trial requirements or otherwise properly manage the clinical trial process, including meeting applicable timelines, properly documenting case files, including the retention of proper case files, and properly monitoring and auditing clinical sites;

●

failure of sites or clinical investigators to perform in accordance with ~~good clinical practices (“GCP”)~~Good Clinical Practice or applicable regulatory guidelines in other countries;

●

~~difficulty or delays in patient recruiting into~~failure of patients to abide by clinical ~~trials;~~

trial requirements;

●

delays or deviations in the testing, validation, manufacturing, and delivery of our product candidates to the clinical sites;

●

delays in having patients complete participation in a study or return for post-treatment follow-up;

●

clinical trial sites or patients dropping out of a study;

●

~~occurrence~~the number of ~~serious adverse events associated with a~~patients required for clinical trials of our product ~~candidate that are viewed to outweigh its potential benefits; or~~

candidates being larger than we anticipate;

●

clinical trials producing negative or inconclusive results, or our studies failing to reach the necessary level of statistical significance, requiring that we conduct additional clinical trials or abandon product development programs;

●

interruptions in manufacturing clinical supply of our product candidates or issues with manufacturing product candidates that meet the necessary quality requirements;

●

unanticipated clinical trial costs or insufficient funding, including paying substantial application user fees;

●

emergence of new information about or impacting our product candidates or the field of gene therapy;

●

with respect to the product candidates for which we manufacture drug product in-house, determinations that there are issues with our manufacturing facility or process; or

●

changes in regulatory requirements and guidance, as well as new, revised, postponed, or frozen regulatory requirements (such as the EU Clinical Trials Regulation), that require amending or submitting new clinical protocols, undertaking additional new tests or analyses, or submitting new types or amounts of clinical data.

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Before obtaining marketing approval from regulatory authorities for the sale of our product candidates, we must conduct extensive clinical trials to demonstrate the safety and efficacy of the product candidates in humans. Such trials and regulatory review and approval take many years. It is impossible to predict when or if any of our clinical trials will demonstrate that product candidates are effective or safe in humans.

If the results of our clinical trials are inconclusive, or fail to meet the level of statistical significance required for regulatory approval or if there are safety concerns, concerns around durability of response or other adverse events associated with our product candidates, we may:

●

be delayed in or altogether prevented from obtaining marketing approval for our product candidates;

●

obtain approval for indications or patient populations that are not as broad as intended or desired;

●

obtain approval with labeling that includes significant use or distribution restrictions, safety warnings, labeling statements or ~~safety warnings;~~

contraindications;

●

be subject to changes ~~with~~in the way ~~the product is~~our products are administered;

●

be required to perform additional clinical trials to support approval or be subject to additional post-marketing testing requirements;

●

have regulatory authorities withdraw their approval of the product or impose restrictions on its distribution in the form of a modified risk evaluation and mitigation strategy;

●

be subject to ~~the addition of labeling statements, such as warnings~~legal action or ~~contraindications;~~

other challenges; or

●

~~be sued; or~~

experience damage to our reputation.

Because of the nature of the gene therapies we are developing, regulators may also require us to demonstrate long-term gene expression, or clinical efficacy, and safety, which may require additional or longer clinical trials ~~and~~for which we may not be able to ~~be demonstrated to~~meet the regulatory authorities’ standards.

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Our ability to recruit patients for our clinical trials is ~~often~~heavily reliant on third parties, such as ~~the pharmacies at our~~ clinical trial sites. ~~These third parties~~Clinical trial sites may not have the adequate infrastructure established to handle the administration of our gene therapy products, related surgeries or ~~to support certain gene therapy~~other means of product ~~formulations,~~administration, or may ~~not agree~~have difficulty finding eligible patients to ~~recruit patients on~~enroll into a clinical trial, which may delay or impede our ~~behalf.~~

planned trials. In addition, we or any of our ~~collaborator~~collaborators may not be able to locate and enroll enough eligible patients to participate in these trials as required by the FDA, the ~~European Medicines Agency (“EMA”)~~EMA or similar regulatory authorities outside the ~~United States~~U.S. and the European Union. This may result in our failure to initiate or continue clinical trials for our product candidates or may cause us to abandon one or more clinical trials altogether. Because our programs are focused on the treatment of patients with rare or orphan or ultra-orphan diseases, our ability to enroll eligible patients in these trials may be limited or slower than we anticipate considering the small patient populations involved and the specific age range required for treatment eligibility in some indications. In addition, our potential competitors, including major pharmaceutical, specialty pharmaceutical and biotechnology companies, academic institutions and governmental agencies and public and private research institutions, may seek to develop competing therapies, which would further limit the small patient pool available for our studies. Also, patients may be reluctant to enroll in gene therapy trials where there are other therapeutic alternatives available or that may become available for various reasons, including, but not limited to, uncertainty about the safety or effectiveness of a new therapeutic such as a gene therapy and the possibility that treatment with a gene therapy therapeutic could preclude future gene therapy treatments due to the formation of antibodies following and in response to the treatment.

Any inability to successfully initiate or complete preclinical and clinical development could result in additional costs to us or impair our ability to receive marketing approval, to generate revenues from product sales or obtain regulatory and commercialization milestones and royalties. In addition, if we make manufacturing or formulation changes to our product candidates, including changes in the vector or manufacturing process used, we may need to conduct additional studies to bridge our modified product candidates to earlier versions. It is also possible that any such manufacturing or formulation changes may have an adverse impact on the performance of the product candidate. Clinical trial delays could also shorten any periods during which we may have the exclusive right to commercialize our product candidates or allow our competitors to bring products to market before we do, which could impair our ability to successfully commercialize our product candidates and may materially harm our business, financial condition, and results of operations.

Our progress in early-stage clinical trials may not be ~~indicative~~predictive of long-term efficacy in late-stage clinical trials, and our progress in trials for one product candidate may not be ~~indicative~~predictive of progress in trials for other product candidates.

The product candidates in our pipeline are at early-stages of development. Study designs and results from previous studies are not necessarily predictive of our future clinical study designs or results, and initial results may not be confirmed upon full analysis of the complete study data. Our product candidates may fail to show the required level of safety and efficacy in later stages of clinical development despite having successfully advanced through initial clinical studies.

~~Table~~ For example, the results from early clinical trials of ~~Contents~~

AMT-130, our product candidate targeting Huntington’s disease, may not be predictive of the results of later-stage trials. In some instances, there can be significant variability in safety or efficacy results between different clinical trials of the same product candidate due to numerous factors, including changes in trial procedures set forth in protocols, differences in the size and type of the patient populations, changes in and adherence to the clinical trial protocols and the rate of dropout among clinical trial participants. Moreover, should there be an issue with the design of any of our clinical trials, our results may be impacted. We may not discover such a flaw until the clinical trial is at an advanced stage. Changes to product candidates, whether as a result of regulatory feedback or changes in clinical trial procedures and protocols, may also impact their performance in subsequent studies.

A number of companies in the pharmaceutical and biotechnology industries have suffered significant setbacks in ~~late-stage~~later-stage clinical trials even after achieving promising results in early-stage clinical trials. If a larger population of patients does not experience positive results during our clinical trials, if ~~these~~the results are not reproducible or if our products show diminishing activity over time, our ~~products~~product candidates may not receive approval from the FDA, EMA or ~~EMA.~~comparable regulatory authorities. Data obtained from preclinical and clinical activities are subject to varying interpretations, which may delay, limit, or prevent regulatory approval. In addition, we may encounter regulatory delays or rejections because of many factors, including changes in regulatory policy during the period of product development. Failure to confirm favorable results from earlier trials by demonstrating the safety and effectiveness of our products in ~~late-stage~~later-stage clinical trials with larger patient populations could have a material adverse effect on our business, financial condition, and results of operations.

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Interim or preliminary data from studies or trials announced or published from time to time may change as more data become available and are subject to audit and verification procedures that ~~would cause~~could result in material changes in the final data.

From time to time, we publicly disclose interim or preliminary data from preclinical studies and clinical trials, which are based on a preliminary analysis of then-available data, and the results and related findings and conclusions are subject to change following a more comprehensive review of the data, the particular study, or trial. We also make assumptions, estimations, calculations, and conclusions as part of our ~~share price~~preliminary or interim analyses of data, and we may not have received or had the opportunity to ~~decline.~~evaluate all data at that time. As a result, the interim or preliminary data that we report may differ from future results of the same studies, or different conclusions or considerations may qualify such results once additional data have been received and fully evaluated. Interim or preliminary data also remain subject to audit and verification procedures that may result in the final data being materially different from the preliminary data we previously published. As a result, preliminary or interim data should be viewed with caution until the final data are available.

~~Fast track product, breakthrough therapy, priority review, or Regenerative Medicine Advanced Therapy (“RMAT”) designation by~~From time to time, we also disclose interim data from our preclinical studies and clinical trials. For example, in December 2023, we announced updated interim data from our ongoing Phase I/II clinical trial of AMT-130, along with our expectation that we will present additional clinical updates with respect to AMT-130 in the ~~FDA, or access~~future. Interim data from clinical trials that we may complete are subject to the ~~PRIME scheme~~risk that one or more of the clinical outcomes may materially change as patient enrollment continues and more patient data become available. Significant differences between interim data and final data could seriously harm our business.

Third parties, including regulatory agencies, may not accept or agree with our assumptions, estimates, calculations, conclusions, or analyses or may interpret or weigh the importance of data differently, which could impact the value of the particular program, the approvability or commercialization of the particular product candidate or product and our company in general. For example, we plan to initiate regulatory interactions in the first half of 2024 to discuss the U.S. and European data from our ongoing Phase I/II clinical trial of AMT-130 and potential strategies for ongoing development of AMT-130. These regulatory authorities may not agree with the assumptions, estimates, calculations, conclusions or analyses underlying the interim data from our ongoing clinical trial of AMT-130 or any of our future proposals regarding the ongoing development of AMT-130. Even if the data supporting such regulatory interactions are suggestive of clinical responses, the durability of response may not be sustained over time or may not be sufficient to support regulatory approval.

In addition, the information we choose to publicly disclose regarding a particular study or clinical trial is based on what is typically extensive information, and you or others may not agree with what we determine is the material or otherwise appropriate information to include in our disclosure. Any information we determine not to disclose may ultimately be deemed significant by you or others with respect to future decisions, conclusions, views, activities or otherwise regarding a particular product candidate or our business. If the ~~EMA,~~preliminary or interim data that we report differ from final results, or if others, including regulatory authorities, disagree with the conclusions reached, our ability to obtain approval for, and commercialize, product candidates may be harmed, which could seriously harm our business.

We are making use of exploratory biomarkers and other data that are not scientifically validated, and our reliance on these data may lead us to direct our resources inefficiently.

We are making use of experimental biological markers, or biomarkers, in an effort to facilitate our drug development and to optimize our clinical trials. Biomarkers are proteins or other substances which can serve as an indicator of specific cell processes or as evidence of a patient’s biological response to drug product administration. For example, with respect to our ongoing clinical trials of AMT-130, we are measuring NfL in cerebrospinal fluid (“CSF”) as a potential indicator of neurodegeneration, as well as the pharmacodynamics of mHTT in CSF and changes in total brain volume of patients treated with AMT-130.

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While we believe that these biomarkers and data may serve useful purposes for us, including in the evaluation of whether our product candidates ~~may~~are having their intended effects through their assumed mechanisms of action, improving patient selection and monitoring patient compliance with trial protocols, these biomarkers and data have not ~~lead to faster development~~been scientifically validated and are considered experimental as used in our trials. If our understanding and use of biomarkers is inaccurate or ~~regulatory review~~flawed, or ~~approval process, and it does not increase the likelihood that~~if our ~~product candidates will receive marketing approval.~~

We may seek fast track, a breakthrough therapy designation, RMAT designation, and priority review designation and PRIME scheme access for our product candidates if supported by the results of clinical trials. A fast track product designation is designed to facilitate the clinical development and expedite the review of drugs intended to treat a serious or life-threatening condition which demonstrate the potential to address an unmet medical need. A breakthrough therapy is defined as a drug that is intended, alone or in combination with one or more other drugs, to treat a serious or life-threatening disease or condition, and preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over existing therapiesreliance on ~~one or more clinically significant endpoints,~~specific biomarkers such as ~~substantial treatment effects observed early in clinical development. A RMAT designation~~NfL and mHTT is ~~designed~~otherwise misplaced, then we may fail to ~~accelerate approval for regenerative advanced therapies. Priority review designation is intended to speed the FDA marketing application review timeframe for drugs that treat a serious condition~~realize any benefits from using these data and if approved, would provide a significant improvement in safety or effectiveness. PRIME is a scheme provided by the EMA to enhance support for the development of medicines that target an unmet medical need.

For drugs and biologics that have been designated as fast track products or breakthrough therapies, or granted access to the PRIME schema, interaction and communication between the regulatory agency and the sponsor of the trial can help to identify the most efficient path for clinical development. Sponsors of drugs with fast track products or breakthrough therapies may also be ~~able~~led to ~~submit marketing applications on a rolling basis, meaning that the FDA may review portions of a marketing application before the sponsor submits the complete application~~invest time and financial resources inefficiently in attempting to the FDA, if the sponsor pays the user fee upon submission of the first portion of the marketing application. For products that receive a priority review designation, the FDA's marketing application review goal is shortened to six months, as opposed to ten months under standard review. This review goal is based on the date the FDA accepts the marketing application for review, this application validation period typically adds approximately two months to the timeline for review and decision from the date of submission. RAT designations will accelerate approval but the exact mechanisms have not yet been announced by FDA.develop inappropriate drug candidates.

Designation as a fast track product, breakthrough therapy, RMAT, PRIME, or priority review product is within the discretion of the regulatory agency. Accordingly, even if we believe one of our product candidates meets the criteria for designation as a fast track product, breakthrough therapy, RMAT, PRIME, or priority review product, the agency may disagree and instead determine not to make such designation. In any event, the receipt of such a designation for a product candidate may not result in a faster development process, review or approval compared to drugs considered for approval under conventional regulatory procedures and does not assure ultimate marketing approval by the agency. In addition, regarding fast track products and breakthrough therapies, the FDA may later decide that the products no longer meet the conditions for qualification as either a fast track product, RMAT, or a breakthrough therapy or, for priority review products, decide that period for FDA review or approval will not be shortened.

We may not be successful in our efforts to use our gene therapy technology platform to build a pipeline of additional product ~~candidates.~~candidates or otherwise leverage our research and technology to remain competitive.

An element of our strategy is to use our gene therapy technology platform to expand our product pipeline and to progress ~~these~~our product candidates through preclinical and clinical development ourselves or together with collaborators. To date, we have only been successful in obtaining regulatory approval for one product, HEMGENIX®, our ~~collaborator.~~gene therapy for the treatment of hemophilia B, which was approved for commercialization by the FDA and the EMA in November 2022 and February 2023, respectively. AMT-130 is our investigational gene therapy candidate for the treatment of Huntington’s disease that utilizes our proprietary, gene-silencing miQURE platform and incorporates an AAV vector carrying a miRNA specifically designed to silence the huntingtin gene and the potentially highly toxic exon 1 protein fragment, which is currently in ongoing Phase I/II studies in the U.S. and Europe. In addition to AMT-130, we are also developing other investigational gene therapies, including AMT-260 for the treatment of MTLE, AMT-162 for the treatment of SOD1 ALS and AMT-191 for the treatment of Fabry’s disease. Although we currently have a pipeline of programs at various stages of development, including an approved product, we may not be able to identify or develop product candidates that are safe and effective. Even if we are successful in continuing to build our pipeline, the potential product candidates that we identify may not be suitable for clinical development.

Research programs to identify new product candidates

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require substantial technical, financial, and human resources. Due to the significant resources required for the development of our product candidates, we must decide which product candidates to pursue and advance and the resources to allocate to each. For example, as a result of the Reorganization, we discontinued investments in certain of our prior research and development programs, including AMT-210 for the treatment of Parkinson’s disease, and certain other technology projects, prioritizing instead our early clinical-stage programs, including AMT-130, AMT-260, AMT-162 and AMT-191.

Our decisions concerning the allocation of research, development, collaboration, management, and financial resources toward particular product candidates, including the decisions stemming from our Reorganization, may not lead to the development of any viable commercial product and may divert resources away from better opportunities. We or ~~our collaborator~~any collaborators may focus our efforts and resources on potential programs or product candidates that ultimately prove to be unsuccessful. If we do not continue to successfully develop and commercialize product candidates based upon our technology, we may face difficulty in obtaining product revenues in future periods, which could result in significant harm to our business, results of operations and financial position and materially adversely affect our share price.

Our business development strategy ~~of obtaining~~depends on our ability to obtain rights to key technologies through in-licenses and support the development of our product pipeline through out-licenses, and those efforts may not be successful.

We ~~seek to~~may expand our product pipeline ~~in part by~~from time to time through strategic transactions that involve in-licensing the rights to key technologies, including those related to gene delivery, genes, and gene cassettes. For example, in July 2021, we acquired uniQure France (formerly Corlieve Therapeutics SAS) and its lead program, now known as AMT-260, to treat refractory MTLE. AMT-260 is being developed based on exclusive licenses to certain patents uniQure France obtained from two French research institutions that continue to collaborate with us. uniQure France also obtained an exclusive license from Regenxbio, Inc. to use AAV9 in connection with the delivery of any sequence that affects the expression of the GRIK2 gene in humans. Notwithstanding efforts to expand our product pipeline, the cost of drug development is high as is the rate of failure in the drug development process. In order to fund the development of some of our existing product candidates, we may seek to out-license some of our product candidates or technologies to other pharmaceutical or biotechnology companies or other third parties. The aim of such out-licensing would be generate non-dilutive funds in the form of up-front or milestone payments or royalties. Such decisions will be taken on a case-by-case basis, as the opportunity arises or is required.

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The future ~~growth~~success of our business will depend in significant part on our business development efforts with respect to existing and future product candidates, including our ability to in-license or otherwise acquire the rights to additional product candidates or technologies, particularly through our collaborations with academic research ~~institutions.~~institutions, and our ability to out-license product candidates and technologies for which collaboration with external parties forms a part of our business strategy. However, we may be unable to in-license or acquire the rights to any such product candidates or technologies from third parties on acceptable terms or at all. The in-licensing and acquisition of ~~these~~gene therapy technologies is a competitive area, and many more established companies are also pursuing strategies to license or acquire product candidates or technologies that we may consider attractive. These established companies may have a competitive advantage over us due to their size, cash resources and greater clinical development and commercialization capabilities. In addition, companies that perceive us to be competitors may be unwilling to license rights to us. Furthermore, we may be unable to identify suitable product candidates or technologies within our areas of focus. If we are unable to successfully obtain rights to suitable product candidates or technologies, our business, financial condition, and prospects could suffer.

Similarly, there is no guarantee that we will generate product candidates that are suitable for out licensing or attractive to potential collaborators, and even if we do, there is no guarantee that we will be successful in identifying potential licensees and successfully negotiating such collaborations on agreeable terms if and when required. Any failure with respect to our business development efforts may materially affect our ability to finance our business and support the development of our product pipeline.

Negative public opinion and increased regulatory scrutiny of gene therapy and genetic research may damage public perception of our product candidates or adversely affect our ability to conduct our business or obtain marketing approvals for our product candidates.

Gene therapy remains a novel technology. Our technology utilizes vectors derived from viruses, which may be perceived as unsafe or may result in unforeseen adverse events.Public perception may be influenced by claims that gene ~~therapy is~~therapies are unsafe, and gene ~~therapy~~therapies may not ultimately gain the acceptance of the public or the medical community. The risk of cancer remains a concern for gene therapy, and we cannot ~~assure~~guarantee that ~~it will not occur~~patients treated in any of our planned or future clinical ~~studies.~~studies will not develop cancer as a result of being treated with our product candidates. In addition, there is the potential risk of delayed adverse events following exposure to gene therapy products due to persistent biological activity of the genetic material or other components of products used to carry the genetic material.

AsPublic and medical community adoption of ~~September 30, 2017,~~any of our gene therapies will depend on other factors, including the ease of administration in comparison to other therapeutics and the extent to which our therapies are successful in slowing disease progression if not acting as a ~~total~~cure for the disease. For example, the need for lengthy and complex surgeries for the administration of ~~three~~a product candidate may impact the acceptance of a product. In particular, our success will depend upon physicians who specialize in the treatment of genetic diseases targeted by our products prescribing treatments that involve the use of our products in lieu of, or in addition to, existing treatments with which they are familiar and for which greater clinical data may be available.

More restrictive government regulation of gene therapies or negative public opinion may have an adverse effect on our business, financial condition, results of operations and prospects and may delay or impair the development and commercialization of our product candidates or demand for any products we may develop. For example, earlier gene therapy trials led to several well-publicized adverse events, including cases of leukemia and death seen in other trials using other vectors.

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Serious adverse events in our clinical trials, or other clinical trials involving gene therapy products or our competitors’ products, even if not ultimately attributable to the relevant product candidates, and the resulting publicity, could result in increased government regulation, unfavorable public perception, potential regulatory delays in the testing or approval of our product candidates, stricter labeling requirements for those product candidates that are approved and a decrease in demand for any products for which we obtain marketing approval. A small number of patients ~~reported~~have experienced serious adverse events ~~related to the treatment~~during our clinical trials of AMT-060 ~~in our Phase I/II hemophilia B trial, including one patient with a short, self-limiting fever in the first 24 hours after treatment~~(HEMGENIX®), etranacogene dezaparvovec (AMT-061), and ~~two patients with mild, asymptomatic elevations in liver transaminases.~~

~~Adverse~~AMT-130. However, adverse events in our clinical trials or those conducted by ~~other~~third parties (even if not ultimately attributable to our product candidates), and the resulting publicity, could result in delay, a hold or termination of our clinical trials, increased governmental regulation, unfavorable public perception, failure of the medical community to accept and prescribe gene therapy treatments, potential regulatory delays in the testing or approval of our product candidates, stricter labeling requirements for those product candidates that are approved and a decrease in demand for any such product candidates. If any of these events should occur, it may have a material adverse effect on our business, financial condition, and results of operations.

Certain of our product candidates may require medical devices for product administration and/or diagnostics, resulting in our product candidates being deemed combination products or otherwise being dependent upon additional regulatory approvals. This may result in the need to comply with additional regulatory requirements. If we are unable to meet these regulatory requirements, we may be delayed or not be able to obtain product approval.

Certain of our product candidates require medical devices for administration, such as AMT-130 and AMT-260, each of which requires a stereotactic, magnetic resonance imaging guided catheter. Other of our product candidates may also require the use of a companion diagnostic device to confirm the presence of specific genetic or other biomarkers. In addition, certain of our product candidates, including AMT-130 and AMT-260, may require the use of immunosuppressive agents to reduce the inflammatory responses associated with administration.

It is possible that our product candidates would be deemed to be combination products, potentially necessitating compliance with the FDA’s investigational device regulations, separate marketing application submissions for the medical device component, a demonstration that our product candidates are safe and effective when used in combination with the medical devices, cross-labeling with the medical device, and compliance with certain of the FDA’s device regulations. If we are not able to comply with the FDA’s device regulations, if we are not able to effectively partner with the applicable medical device manufacturers, if we or any partners are not able to obtain any required FDA clearances or approvals of the applicable medical devices, or if we are not able to demonstrate that our product candidates are safe and efficacious when used with the applicable medical devices, we may be delayed in or may never obtain FDA approval for our product candidates, which would materially harm our business.

Moreover, certain of our delivery modalities, such as direct delivery of product candidates to the brain, may require significant time and physician ability and skill. If physicians are not able to effectively deliver our product candidates to the applicable site of action or if delivery modalities are too difficult, or if there is reluctance to administer immunosuppressive agents that are outside of the standard of care to treat immune responses from the administration of our therapies, we may never be able to obtain approval for our product candidates, may be delayed in obtaining approval, or, following approval, physicians may not adopt our product candidates, any of which may materially harm our business.

Risks Related to Our Manufacturing

Our manufacturing ~~facility is~~facilities are subject to significant government regulations and approvals. If we fail to comply with these regulations or maintain these approvals, our business ~~will~~could be materially harmed. *

With the exception of AMT-260 and AMT-162, we produce our gene therapies at our Lexington Facility using a proprietary baculovirus expression vector system. Our ~~manufacturing facility in~~ Lexington ~~will be~~Facility, where we manufacture HEMGENIX®, is subject to ongoing regulation and periodic inspection by the ~~EMA,~~ FDA, EU member state, and other regulatory bodies to ensure compliance with ~~current Good Manufacturing Practices (“cGMP”).~~cGMP and other requirements. Any failure to follow and document our adherence to such cGMP regulations or other regulatory requirements may lead to significant delays in the availability of products for commercial sale or clinical study, may result in the termination of or a hold on a clinical study, or may delay or prevent filing or approval of marketing applications for our products.

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Failure to comply with applicable regulations could also result in the ~~EMA,~~ FDA, EU member state, or other applicable authorities taking various actions, ~~including~~ including:

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levying fines and other civil penalties;

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imposing consent decrees or injunctions;

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requiring us to suspend or put on hold one or more of our clinical trials;

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suspending or withdrawing regulatory approvals;

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delaying or refusing to approve pending applications or supplements to approved applications;

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requiring us to suspend manufacturing activities or product sales, imports or exports;

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requiring us to communicate with physicians and other customers about concerns related to actual or potential safety, efficacy, and other issues involving our products;

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mandating or recommending product recalls or seizing products;

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imposing operating restrictions; or

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seeking criminal prosecutions, among other outcomes.

Poor control of production processes can also lead to the introduction of adventitious agents or other contaminants, or to inadvertent changes in the properties or stability of a product candidate that may not be detectable in final product testing and ~~other civil penalties; imposing consent decrees~~that could have an adverse effect on clinical studies, or ~~injunctions; requiring us~~patient safety or efficacy. Moreover, if our manufacturing facility is not able to ~~suspend or put on hold one or more of our clinical trials; suspending or withdrawing~~meet regulatory ~~approvals; delaying or refusing~~requirements, we may need to ~~approve pending applications or supplements to approved applications; requiring us to suspend manufacturing activities or product sales, imports or exports; requiring us to communicate with physicians~~implement costly and ~~other customers about concerns related to actual or potential safety, efficacy, and other issues involving our products; mandating~~

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~~product recalls or seizing products; imposing operating restrictions; and seeking criminal prosecutions.~~time-consuming remedial actions. Any of the foregoing could materially harm our ~~business.~~business, financial condition, and results of operations.

Moreover, if we are not able to manufacture a sufficient amount of our product candidates for clinical studies or eventual commercialization, or if we are unable to manufacture sufficient supply of HEMGENIX® consistent with our manufacturing and supply obligations to CSL Behring, our development programs and commercial prospects will be harmed. If we cannot produce an adequate amount of our drug substance and product in compliance with the applicable regulatory requirements, we may need to contract with a third party to do so, in which case third party manufacturers may not be available to us on favorable terms or at all. The addition of a new manufacturer may also require FDA, EMA, EU, and other regulatory authority approvals, which we may not be able to obtain.

Gene therapies are complex, expensive and difficult to manufacture. We could experience capacity, production or technology transfer ~~problems~~challenges that could result in delays in our development or commercialization schedules or otherwise adversely affect our business. *

~~The insect-cell based~~Our proprietary manufacturing process ~~we use~~leveraging insect cells and baculoviruses to produce ~~our products and product candidates~~to AAV-based gene therapies is highly complex and ~~in the normal course~~ is regularly subject to variation or production difficulties. Issues with ~~the~~any of our manufacturing ~~process,~~processes, even minor deviations from ~~the normal process,~~our standard processes, could result in insufficient yield, product deficiencies or manufacturing failures that result in adverse patient reactions, lot failures, insufficient inventory, product recalls and product liability claims. Additionally, we may not be able to scale up some or all our manufacturing processes as necessary and on our desired timelines to meet the demands of our clinical product pipeline, which may result in delays in regulatory approvals, inability to produce sufficient amounts of clinical or commercial product, or otherwise adversely affect our business.

~~Many factors~~Factors common to the manufacturing ofprocess associated with most biologics and drugs could also cause production interruptions for us, including, without limitation, raw materials shortages and other supply chain challenges, raw material failures, limited control over pricing of raw materials, growth media failures, equipment malfunctions, costs associated with servicing real property lease and other contractual obligations, facility contamination, labor problems, natural disasters, disruption in utility services, public health crises, terrorist activities, war or cases of force majeure and acts of ~~god~~God that are beyond our control. We also may encounter problems in hiring and retaining the experienced and specialized personnel needed to operate our manufacturing ~~process, particularly as we transition manufacturing to Lexington,~~facilities, processes and testing, which could result in delays in our production or difficulties in maintaining compliance with applicable regulatory requirements.

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We manufacture HEMGENIX® at our Lexington Facility which is optimized to meet our commercial manufacturing and supply obligations pursuant to the CSL Behring collaboration. This optimization and dedicated capacity for HEMGENIX® could limit our ability to manufacture other product candidates or components thereof to support our development programs or those of third parties. The manufacturing of HEMGENIX® pursuant to our obligations under the CSL Behring Agreement is expensive and requires the dedication of significant company resources. In September 2022, CSL Behring notified us of its intent to transfer manufacturing technology in the coming years related to HEMGENIX® to a third-party contract manufacturer to be designated by CSL Behring in the future. Until CSL Behring identifies and designates a new manufacturer capable of supporting the commercial requirements of HEMGENIX®, we will continue to incur significant costs associated with our manufacturing and supply obligations. Following such transfer, we may experience challenges in adapting our Lexington Facility to meet the manufacturing and supply needs for products other than HEMGENIX® as a result of excess capacity or our ability to adapt to new processes, among other challenges. Any problems inor limitations with respect to our manufacturing processes or facilities, including our existing commercial supply and manufacturing obligations to CSL Behring, could make us a less attractive collaborator for academic research institutions and other parties, which could limit our access to additional attractive development programs or sources of capital, result in delays in our clinical development or marketing schedules and materially harm our business.

We currently rely and expect to continue to rely on third parties to conduct product manufacturing for certain of our product candidates, and these third parties may not perform satisfactorily.

We currently rely, and expect to continue to rely, on third parties for the production of some of our preclinical study and planned clinical trial materials and, therefore, we can control only certain aspects of their activities. The facilities used by us and our contract manufacturers to manufacture certain of our product candidates must be reviewed by the FDA pursuant to inspections that will be conducted after we submit a BLA to the FDA. We do not control the manufacturing process of, and are completely dependent on, our contract manufacturing partners for compliance with the cGMP for the manufacture of our products and product candidates that are not manufactured in house. If we or our contract manufacturers cannot successfully manufacture material that conforms to our specifications and the strict regulatory requirements of the FDA or other regulatory bodies, we will not be able to obtain and/or maintain regulatory approval for our products manufactured by third parties. In addition, we have no control over the ability of our contract manufacturers to maintain adequate quality control, quality assurance and qualified personnel. If the FDA or a comparable foreign regulatory authority does not approve these facilities for the manufacture of our product candidates or if it withdraws any such approval in the future, we may need to find alternative third-party manufacturers, which may not be available and which would significantly impact our ability to develop, obtain regulatory approval for or market our product candidates, if approved.

Our use of viruses, chemicals and other potentially hazardous materials requires us to comply with regulatory requirements and exposes us to significant potential liabilities.

Our development and manufacturing processes involve the use of viruses, chemicals, other ~~(potentially)~~potentially hazardous materials and produce waste products. Accordingly, we are subject to national, federal, state, and local laws and regulations in the ~~United States~~U.S. and the Netherlands governing the use, manufacture, distribution, storage, handling, treatment, and disposal of these materials. In addition to ensuring the safe handling of these materials, ~~applicable requirements require~~we are subject to increased safeguards and security measures for many of these agents, including controlling access and screening of entities and personnel who have access to them, and establishing a comprehensive national database of registered entities. In the event of an accident or failure to comply with environmental, occupational health and safety and export control laws and regulations, we could be held liable for damages that result, and any such liability could exceed our assets and ~~resources.~~resources, and could result in material harm to our business, financial condition, and results of operations.

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Our resources might be adversely affected if we are unable to validate our manufacturing processes and methods or develop new processes and methods to meet our product supply needs and obligations.

The manufacture of our AAV gene therapies is complex and requires significant expertise. Even with the relevant experience and expertise, manufacturers of gene therapy products often encounter difficulties in production, particularly in scaling out and validating initial production and ensuring that the product meets required specifications. These problems include difficulties with production costs and yields, quality control, including stability and potency of the product, quality assurance testing, operator error, shortages of qualified personnel, as well as compliance with strictly enforced federal, state, and foreign regulations. In the past, we have manufactured certain batches of product candidates intended for nonclinical, clinical and process validation purposes that have not met all our pre-specified quality parameters. To meet our expected future production needs and our regulatory filing timelines for gene therapy product candidates, we will need to complete the validation of our manufacturing processes and methods for each program, and we may need to develop and validate new or larger scale manufacturing processes and methods. If we are unable to consistently manufacture our gene therapy product candidates or any approved products in accordance with our pre-specified quality parameters and applicable regulatory standards, it could adversely impact our ability to validate our manufacturing processes and methods, to meet our production needs, to file a BLA or other regulatory submissions, to develop our other proprietary programs, to conserve our cash, or to receive financial payments pursuant to our agreements with third parties.

Risks Related to Regulatory Approval of Our Products

We are implementing changes in our lead product candidate for hemophilia B, which may require additional pre-clinical, non-clinical, or clinical studies, or additional chemistry, manufacturing and control development *

We have recently changed our lead product candidate for hemophilia B from AMT-060 (an AAV-5 based vector encoding the wild-type factor IX gene) to a hemophilia B product candidate designated AMT-061 (an AAV5 based vector encoding the FIX-Padua mutant). Both are identical in structure apart from two nucleotide substitutions in the coding sequence for FIX. We believe the FIX-Padua mutant to result in enhanced FIX activity. We have conducted a GLP non-human primate pre-clinical study using AMT-061, which demonstrated a substantial increase in FIX activity over AMT-060. The results of our pre-clinical study using AMT-061 may not be predictive of any future clinical trial results for AMT-061. Our pivotal trial, which will be conducted with AMT-061 may not ultimately provide the desired efficacy results or may reveal adverse events or other safety concerns.

Because of changing our product candidate, we will be required to conduct a clinical study confirming the dosing with AMT-061 and the resulting fold increase in FIX activity. If we are unable to confirm the dose, we might be required to modify the design or extend the study, resulting in a delay of the treatment phase of our pivotal trial.

We have conducted our pre-clinical studies with both AMT-060 and AMT-061 as well our Phase I/II clinical study with AMT-060 with drug product manufactured at our Amsterdam facility. We intend to manufacture AMT-061 for our future clinical studies at our Lexington facility using a scaled-up and modified process. We will need to demonstrate comparability between AMT-061, manufactured at our Lexington facility and AMS-060, manufactured at our Amsterdam, facility to support regulatory approval to commence our Phase III clinical trial.

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It is also possible that the applicable regulatory authorities may ultimately not agree with the design or conduct of our comparability, clinical, pre-clinical or non-clinical studies, or with our chemistry, manufacturing, and control development work. The applicable regulatory authorities may also find that the outcome of the foregoing does not support the submission or approval of a marketing application. We are planning to have additional interactions with FDA and the EMA, during which we may receive additional comments, guidance, and recommendations. The approach required by the applicable regulatory authorities, may, however, change in the future due to a variety of reasons, including changes in regulatory policy, the outcome of our studies and continuing development, and how our studies and continuing development efforts are ultimately conducted.

Any of the above could delay the submission of a marketing application, or regulatory authorities may not approve or may require material restrictions on any approvals that are received. Any of the foregoing would materially harm our commercial prospects.

We cannot predict when or if we will obtain marketing approval to commercialize aour product candidate *candidates.

The development and commercialization of our product candidates, including their design, testing, manufacture, safety, efficacy, purity, recordkeeping, labeling, storage, approval, advertising, promotion, sale, and distribution, are subject to comprehensive regulation by the FDA and other regulatory agencies in the ~~United States,~~U.S., the EMA, and other regulatory agencies of the member states of the European Union, and similar regulatory authorities in other jurisdictions. Failure to obtain marketing approval for a product candidate in a specific jurisdiction will prevent us from commercializing the product candidate in that ~~jurisdiction.~~jurisdiction and our ability to generate revenue will be materially impaired.

The process of obtaining marketing approval for our product candidates in the U.S., the European Union, ~~the United States~~ and other countries is expensive and may take many years, if approval is obtained at all. Changes in marketing approval policies during the development period, changes in or the enactment of additional statutes or regulations, or changes in regulatory review for each submitted product application, may cause delays in the approval or rejection of an application. Regulatory authorities may also be delayed in completing their review of any marketing applications submitted by us or our partners. Regulatory authorities have substantial discretion in the approval process and may refuse to accept any application, may decide that our data are insufficient for approval, may require additional preclinical, clinical, or other studies and may not complete their review in a timely manner. Further, any marketing approval we ultimately obtain may be for only limited indications or be subject to stringent labeling or other restrictions or post-approval commitments that render the approved product not commercially viable.

If we experience delays in obtaining marketing approval of any of our product candidates in the United States or other countries, the commercial prospects of our other product candidates may be harmed and our ability to generate revenues will be materially impaired.

The risks associated with the marketing approval process are heightened by the status of our products as gene therapies.

We believe that all our current product candidates will be viewed as gene therapy products by the applicable regulatory authorities. ~~Gene therapies~~While there are ~~relatively new treatments for which~~several gene therapy product candidates under development in the U.S., the FDA has only approved a limited number of gene therapy products, to date. Accordingly, regulators ~~do not~~like the FDA may have ~~extensive~~limited experience ~~or standard~~with the review and approval ~~processes. The FDA unlike~~of marketing applications for gene therapy products, which may adversely affect the ~~EMA, does not have an exceptional circumstances~~ approval ~~pathway.~~prospects for our product candidates.

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Both the FDA and the EMA have demonstrated caution in their regulation of gene therapy treatments, and ethical and legal concerns about gene therapy and genetic testing may result in additional regulations or restrictions on the development and commercialization of our product candidates that are difficult to predict. The FDA and the EMA have issued various guidance documents pertaining to gene therapy products, ~~with~~ which wewill likely ~~must comply~~be applicable to ~~gain regulatory approval of any of~~ our product candidates prior to our obtaining regulatory approval in the ~~United States~~U.S. or ~~European Union, respectively.~~the EU. The close regulatory scrutiny of gene therapy products may result in delays and increased costs and may ultimately lead to the failure to obtain approval for any gene therapy product. Experiences with existing gene therapies, including any emergent adverse effects, could also impact how the FDA and the EMA view our products and product candidates, making it harder to obtain or maintain regulatory approvals.

Regulatory requirements affecting gene therapy have changed frequently and ~~may~~ continue to ~~change,~~evolve, and agencies at both the U.S. federal and state level, as well as congressional committees and foreign governments, have sometimes expressed interest in further regulating biotechnology. ~~For~~In the U.S., there have been a number of changes relating to gene therapy development. By example, FDA issued a number of guidance documents, and continues to issue guidance documents, on human gene therapy development, one of which was specific to human gene therapy for hemophilia, one that was specific to neurodegenerative diseases, and another of which was specific to rare diseases. Moreover, the European Commission conducted a public consultation in early 2013 on the application of EU legislation that governs advanced therapy medicinal products, including gene therapy products, which could result in changes in the data we need to submit to the EMA for our product candidates to gain regulatory approval or change the requirements for tracking, handling and distribution of the products which may be associated with increased costs. In addition, divergent scientific opinions among the various bodies involved

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in the review process may result in delays, require additional resources, and ultimately result in rejection.

The FDA, EMA, and other regulatory authorities will likely continue to revise and further update their approaches to gene therapies in the coming years. These regulatory agencies, committees and advisory groups and the new regulations and guidelines they promulgate may lengthen the regulatory review process, require us to perform additional studies, increase our development costs, lead to changes in regulatory positions and interpretations, delay or prevent approval and commercialization of our product candidates or lead to significant post-approval limitations or restrictions. Delay or failure to obtain, or unexpected costs in obtaining, the regulatory approval necessary to bring a potential product to market could decrease our ability to generate sufficient product revenues to maintain our business.

We may use certain specialized pathways to develop our product candidates or to seek regulatory approval. We may not qualify for these pathways, or such pathways may not ultimately speed the time to approval or result in product candidate approval.

We have obtained and may in the future seek one or more fast-track designations, breakthrough therapy designation, RMAT designation, PRIME scheme access or priority review designation for our product candidates. A fast-track product designation is designed to facilitate the clinical development and expedite the review of drugs intended to treat a serious or life-threatening condition and which demonstrate the potential to address an unmet medical need. A breakthrough therapy is defined as a drug that is intended, alone or in combination with one or more other drugs, to treat a serious or life-threatening disease or condition, where preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints, such as substantial treatment effects observed early in clinical development. An RMAT designation is designed to accelerate approval for regenerative advanced therapies. Priority review designation is intended to accelerate the FDA marketing application review timeframe for drug products that treat a serious condition and that, if approved, would provide a significant improvement in safety or effectiveness. PRIME is a scheme provided by the EMA, similar to the FDA’s breakthrough therapy designation, to enhance support for the development of medicines that target an unmet medical need.

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For drugs and biologics that have been designated as fast track products, RMAT, or breakthrough therapies, or granted access to the PRIME scheme, interaction and communication between the regulatory agency and the sponsor of the trial can help to identify the most efficient path for clinical development. Sponsors of fast-track products, RMAT products, or breakthrough therapies may also be able to submit marketing applications on a rolling basis, meaning that the FDA may review portions of a marketing application before the sponsor submits the complete application to the FDA, if the sponsor pays the user fee upon submission of the first portion of the marketing application and the FDA approves a schedule for the submission of the remaining sections. For products that receive a priority review designation, the FDA’s marketing application review goal is shortened to six months, as opposed to ten months under standard review.

Designation as a fast-track product, breakthrough therapy, RMAT, PRIME, or priority review product is within the discretion of the regulatory agency. Accordingly, even if we believe one of our product candidates meets the relevant criteria, the agency may disagree and instead determine not to make such a designation. In any event, the receipt of such a designation for a product candidate may not result in a faster development process, review or approval compared to drugs considered for approval under conventional regulatory procedures and does not assure ultimate marketing approval by the agency. In addition, the FDA may later decide that the products no longer meet the applicable conditions for qualification as either a fast-track product, RMAT, or a breakthrough therapy or, for priority review products, decide that the period for FDA review or approval will not be shortened. Moreover, in the U.S., the FDA expects that sponsors with products under these programs will be prepared for a more rapid pace of development, including with respect to manufacturing or any combination medical devices, such as companion diagnostics. If we are unable to meet these expectations, we may not be able to fully avail ourselves of certain advantages of these programs.

Biologics studied for their safety and effectiveness in treating serious or life-threatening illnesses and that provide meaningful therapeutic benefit over existing treatments may receive accelerated approval by the FDA, meaning the agency may approve the product candidate based upon a surrogate endpoint that is reasonably likely to predict clinical benefit, or on a clinical endpoint that is reasonably likely to predict an effect on irreversible morbidity or mortality or other clinical benefit. Even if we do qualify for accelerated approval, we may be unsuccessful in meeting post-marketing compliance requirements, or fail to conduct required post-approval studies, or to confirm a clinical benefit during post-marketing studies, which could result in the FDA withdrawing our product from the market. In recent years, the accelerated approval pathway has come under significant FDA and public scrutiny. Accordingly, it is uncertain whether the FDA may be more conservative in granting accelerated approval or, if granted, more apt to withdraw approval if clinical benefit is not confirmed. There is no guarantee that regulatory interactions with FDA or comparable foreign authorities will result in our ability to avail ourselves of any specialized approval pathways for our product candidates.

Our failure to obtain or maintain orphan product exclusivity for any of our product candidates for which we seek this status could limit our commercial opportunity, and if our competitors are able to obtain orphan product exclusivity before we do, we may not be able to obtain approval for our competing products for a significant period.

Regulatory authorities in some jurisdictions, including the ~~European Union~~U.S. and the ~~United States,~~European Union, may designate drugs for relatively small patient populations as orphan drugs. ~~Generally,~~While certain of our product candidates, including AMT-130 have received orphan drug designation, there is no guarantee that we will be able to receive such designations in the future. The FDA may grant orphan designation to multiple sponsors for the same compound or active molecule and for the same indication. If another sponsor receives FDA approval for such product before we do, we would be prevented from launching our product in the U.S. for the orphan indication for a period of at least seven years unless we can demonstrate clinical superiority.

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Moreover, while orphan drug designation neither shortens the development or regulatory review time, nor gives the product candidate advantages in the regulatory review or approval process, generally, if a product with an orphan drug designation subsequently receives the first marketing approval for the relevant indication, the product is entitled to a period of market exclusivity, which precludes the ~~EMA~~FDA or ~~FDA~~the EMA from approving another marketing application for the same drug for the same indication for that period. The FDA and the EMA, however, may subsequently approve a similar drug or same drug, in the case of the U.S., for the same indication during the first ~~product's~~product’s market exclusivity period if the FDA or the EMA concludes that the later drug is clinically superior in that it is shown to be safer or more effective or makes a major contribution to patient care. Orphan exclusivity in the U.S. also does not prevent the FDA from approving another product that is considered to be the same as our product candidates for a different indication or a different product for the same orphan indication. If another product that is the same as ours is approved for a different indication, it is possible that third-party payors will reimburse for products off-label even if not indicated for the orphan condition. Moreover, in the U.S. the exact scope of orphan drug exclusivity is currently uncertain and evolving due to a recent court decision.

Orphan drug exclusivity may be lost if the ~~EMA~~FDA or ~~FDA~~the EMA determines that the request for designation was materially defective, or if the manufacturer is unable to assure sufficient quantity of the drug to meet the needs of patients with the rare disease or condition or if the incidence and prevalence of patients who are eligible to receive the drug in these markets materially increase. The inability to obtain or failure to maintain adequate product exclusivity for our product candidates could have a material adverse effect on our business prospects, results of operations and financial condition.

Our focus on developing gene therapies makes it difficult to determine the availability and utility of the orphan drug regime to our product candidates. Regulatory criteria with respect to orphan products are evolving, especially in gene therapy. By example, in the U.S., whether two gene therapies are considered to be the same for the purpose of determining clinical superiority was updated via a final guidance document specific to gene therapies, and depends on a number of factors, including the expressed transgene, the vector, and other product or product candidate features. Depending on the products, whether two products are ultimately considered to be the same may be determined by FDA on a case-by-case basis, making it difficult to make predictions regarding when the FDA might be able to make an approval of a product effective and whether periods of exclusivity will effectively block competitors seeking to market products that are the same or similar to ours for the same intended use. Accordingly, whether any of our gene therapies will be deemed to be the same as another product or product candidate is uncertain.

As appropriate, we intend to seek ~~all~~ available periods of regulatory exclusivity for our product candidates. However, there is no guarantee that we will be granted these periods of regulatory exclusivity or that we will be able to maintain these periods of exclusivity.

The FDA grants product sponsors certain periods of regulatory exclusivity, during which the agency may not approve, and in certain instances, may not accept, certain marketing applications for competing drugs. For example, biologic product sponsors may be eligible for twelve years of exclusivity from the date of approval, seven years of exclusivity for drugs that are designated to be orphan drugs, and/or a six-month period of exclusivity added to any existing exclusivity period ~~or patent life~~ for the submission of FDA requested pediatric data. While we intend to apply for all periods of market exclusivity that we may be eligible for, there is no guarantee that we will ~~receive all~~be granted any such periods of market exclusivity. By example, regulatory authorities may determine that our product candidates are not eligible for periods of regulatory exclusivity for various reasons, including a determination by the FDA that a BLA approval does not constitute a first licensure of the product. Additionally, under certain circumstances, the FDA may revoke the period of market exclusivity. Thus, there is no guarantee that we will be able to maintain a period of market exclusivity, even if granted. In the case of orphan designation, other benefits, such as tax credits and exemption from user fees may be available. If we are not able to obtain or maintain orphan drug designation or any period of market exclusivity to which we may be entitled, we ~~will~~could be materially harmed, as we will potentially be subject to greater market competition and may lose the benefits associated with programs. It is also possible that periods of exclusivity will not adequately protect our product candidates from competition. For instance, even if we receive twelve years of exclusivity from the FDA, other applicants will still be able to submit and receive approvals for versions of our product candidates through a full BLA.

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If we do not obtain or maintain periods of market exclusivity, we may face competition sooner than otherwise anticipated. For instance, in the U.S., this could mean that a competing biosimilar product may be able to apply to the FDA and obtain approval either as a biosimilar to one of our products or even as an interchangeable product. This may require that we undertake costly and time-consuming patent litigation, to the extent available, or defend actions brought by the biosimilar applicant for declaratory judgment. If a biosimilar product does enter the market, it is possible that it could be substituted for one of our product candidates, especially if it is available at a lower price.

It is also possible that, at the time we obtain approval of our product candidates, regulatory laws and policies around exclusivities may have changed. For instance, there have been efforts to decrease the U.S. period of exclusivity to a shorter timeframe. Future proposed budgets, international trade agreements and other arrangements or proposals may affect periods of exclusivity.

If any of our product candidates receive regulatory approval, we and/or our partners will be subject to extensive regulatory requirements. Failure to fulfill and comply with the applicable regulatory requirements could result in regulatory enforcement actions that would be detrimental to our business.

Following any regulatory approval, the FDA and the EMA may impose certain post-approval requirements related to a product. Specifically, any approved products will be subject to continuing and comprehensive regulation concerning the product’s design, testing, manufacture, safety, efficacy, recordkeeping, labeling, storage, approval, advertising, promotion, sale, and distribution. Regulatory authorities may also require post-marketing testing, known as Phase 4 testing, a risk evaluation and mitigation strategy, and surveillance to monitor the effects of an approved product or place conditions on an approval that could restrict the distribution or use of the product. Failure to comply with any of these requirements could result in regulatory, administrative, or other enforcement action, which would be detrimental to our business.

For instance, the FDA and other government agencies closely regulate the post-approval marketing and promotion of approved products, including off-label promotion, industry-sponsored scientific and educational activities, and on the Internet and social media. Approved products may be marketed only for the approved indications and in accordance with the provisions of the approved labeling. Failure to comply with regulatory promotional standards could result in actions being brought against us by these agencies.

Moreover, if a company obtains FDA approval for a product via the accelerated approval pathway, the company would be required to conduct a post-marketing confirmatory trial to verify and describe the clinical benefit in support of full approval. FDA can require that this confirmatory trial be commenced prior to FDA granting a product accelerated approval. An unsuccessful post-marketing study or failure to complete such a study could result in the expedited withdrawal of the FDA’s marketing approval for a product using a statutorily defined streamlined process.

Changes to some of the conditions established in an approved application, including changes in labeling, indications, manufacturing processes or facilities, may require a submission to and approval by the FDA or the EMA, as applicable, before the change can be implemented. A New Drug Application (“NDA”)/BLA or MAA supplement for a new indication typically requires clinical data similar to that in the original application. The applicable regulatory authorities would review such supplement using similar procedures and actions as in reviewing NDAs/BLAs and MAAs.

Adverse event reporting and submission of periodic reports is required following marketing approval. Regulatory authorities may withdraw product approvals or request product recalls, as well as impose other enforcement actions, if a company fails to comply with regulatory standards, if it encounters problems following initial marketing, or if previously unrecognized problems are subsequently discovered.

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In addition, the manufacture, testing, packaging, labeling, and distribution of products after approval will need to continue to conform to cGMPs. Drug and biological product manufacturers, including us, and certain of their subcontractors are subject to periodic unannounced inspections by the FDA or the EMA for compliance with cGMPs. Accordingly, manufacturers must continue to expend time, money, and effort in the areas of production and quality control to maintain compliance with cGMPs. In addition, prescription drug manufacturers in the U.S. must comply with applicable provisions of the Drug Supply Chain Security Act and provide and receive product tracing information, maintain appropriate licenses, ensure they only work with other properly licensed entities and have procedures in place to identify and properly handle suspect and illegitimate products. If we or any of our contractors are unable to comply with the requirements that are applicable to drug manufacturers, we or they may be subject to regulatory enforcement, or may need to conduct a recall or take other corrective actions, which could result in material harm to us or our products.

Where we partner with third parties for the development, approval, and marketing of a product, such third parties will be subject to the same regulatory obligations as we will. However, as we will not control the actions of the applicable third parties, we will be reliant on them to meet their contractual and regulatory obligations. Accordingly, actions taken by any of our partners could materially and adversely impact our business.

Risks Related to ~~Our~~ Commercialization

If we, or our ~~collaborator~~commercial partners, are unable to successfully commercialize our product candidates or experience significant delays in doing so, our business ~~will~~could be materially harmed.

Our ability to generate revenues from our product ~~revenues~~candidates will depend on the successful development and eventual commercialization of our product candidates. The success of our product candidates will depend on many factors, including:

●

successful completion of preclinical studies and clinical ~~trials;~~

trials, and other work required by regulators;

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receipt and maintenance of marketing approvals from applicable regulatory authorities;

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~~our ability to timely manufacture sufficient quantities according to required quality specifications;~~

obtaining and maintaining patent and trade secret protection and non-patent, ~~orphan drug exclusivity~~exclusivities for our product candidates;

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~~obtaining and~~ maintaining regulatory ~~approval for~~approvals using our manufacturing facility in Lexington, Massachusetts;

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launch and commercialization of our products, if approved, whether alone or in collaboration with others;

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identifying and engaging effective distributors or resellers on acceptable terms in jurisdictions where we plan to utilize third parties for the marketing and sales of our product candidates;

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acceptance of our products, if approved, by patients, the medical community, and ~~third party~~third-party payers;

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effectively competing with existing therapies and gene therapies based on safety and efficacy ~~profile;~~

profiles;

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the strength of our marketing and distribution;

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~~achieve value based~~the achievement optimal pricing ~~levels~~ based on durability of expression, safety, and efficacy;

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the ultimate content of the regulatory authority approved label, including the approved clinical indications, and any limitations or warnings;

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any distribution or use restrictions imposed by regulatory authorities;

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~~obtaining~~the interaction of our products with any other medicines that patients may be taking or the restriction on the use of our products with other medicines;

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the standard of care at the time of product approval;

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the relative convenience and ~~maintaining~~ease of administration of our products;

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obtaining healthcare coverage and adequate ~~reimbursement; and~~

reimbursement of our products;

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any price concessions, rebates, or discounts we may need to provide;

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complying with any applicable post-approval commitments and requirements, and maintaining a continued acceptable overall safety ~~profile.~~

profile; and

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obtaining adequate reimbursement for the total patient population and each subgroup to sustain a viable commercial business model in U.S. and EU markets.

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Even if our product candidates are approved, they may be subject to limitations that make commercialization difficult. There may be limitations on the indicated uses and populations for which the products may be marketed. They may also be subject to other conditions of approval, may contain significant safety warnings, including boxed warnings, contraindications, and precautions, may not be approved with label statements necessary or desirable for successful commercialization, or may contain requirements for costly post-market testing and surveillance, or other requirements, including the submission of a risk evaluation and mitigation strategy (“REMS”) to monitor the safety or efficacy of the products. Failure to achieve or implement any of ~~these~~the above elements could result in significant delays or an inability to successfully commercialize our product candidates, which could materially harm our business.

The affected populations for our gene therapies may be smaller than we or third parties currently project, which may affect the size of our addressable markets. *

Our projections of the number of people who have the diseases we are seeking to treat, as well as the subset of people with these diseases who have the potential to benefit from treatment with our therapies, are estimates based on our knowledge and understanding of these ~~diseases.~~diseases and may change. The total addressable market opportunities for these therapies will ~~ultimately~~ depend upon many factors, including the diagnosis and treatment criteria included in the final label, if approved for sale in specified indications, acceptance by the medical community, patient consent, patient access and product pricing and ~~reimbursement. For example, after obtaining marketing authorization for Glybera from the EMA in 2013, various national European authorities denied~~ reimbursement, ~~under national insurance schemes.~~among other factors.

Prevalence estimates are frequently based on information and assumptions that are not exact and may not be appropriate, and the methodology is forward-looking and speculative. For example, the addressable markets for certain of our AAV-based gene therapies may be impacted by the prevalence of neutralizing antibodies to the capsids, which are an integral component of our gene therapy constructs. Patients that have pre-existing antibodies to a particular capsid might not be eligible for administration of a gene therapy that includes this particular capsid. Moreover, neutralizing antibodies may be developed by a patient following administration of the product, which may render the patient ineligible for subsequent dosing. The use of such data to support addressable market estimates involves risks and uncertainties and is subject to change based on various factors. Our estimates may prove to be incorrect and new studies and information may change the estimated incidence or prevalence of the diseases we seek to address. The number of patients with the diseases we are targeting may turn out to be lower than expected or may not be otherwise amenable to treatment with our products, reimbursement may not be sufficient to sustain a viable business for all sub-populations being studied, or new patients may become increasingly difficult to identify or access, any of which ~~would~~could adversely affect our results of operations and our business.

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The addressable market for AAV-based gene therapies are also impacted by the prevalence of neutralizing antibodies to the capsids, which are an integral component of our gene therapy constructs. Patients that have pre-existing antibodies to a particular capsid are generally not eligible for administration of a gene therapy that includes this particular capsid. For example, our AMT-061 gene therapy candidate for hemophilia B patients incorporates an AAV5 capsid. In our Phase I/II clinical study of AMT-060, we screened patients for preexisting anti-AAV5 antibodies to determine their eligibility for the trial. Three of the ten patients screened for the study tested positive for anti-AAV5 antibodies on reanalysis, and none of the three tested positive for certain ill-effects from the AAV-based gene therapy, implying that patients who have neutralizing antibodies may be eligible for AAV5-mediated gene transfer. However, we only have been able to test a limited sample of patients and have limited clinical and pre-clinical data, and it is possible that future clinical studies may not confirm these results. This may limit the addressable market for AMT-061 and any future revenues derived from the sale of the product.

Any approved gene therapy we seek to offer may fail to achieve the degree of market acceptance by physicians, patients, third party payers and others in the medical community necessary for commercial success.

Doctors may be reluctant to accept a gene therapy as a treatment option or, where available, choose to continue to rely on existing ~~symptomatic~~ treatments. The degree of market acceptance of any of our product candidates that receive marketing approval in the future will depend on many factors, including:

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the efficacy and potential advantages of our therapies compared with alternative treatments;

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our ability to convince payers of the long-term cost-effectiveness of our therapies and, consequently, the availability of ~~third party~~third-party coverage and adequate reimbursement;

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the cost of treatment with gene therapies, including ours, in comparison to traditional chemical and small molecule treatments;

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the limitations on use and label requirements imposed by regulators;

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the convenience and ease of administration of our gene therapies compared with alternative treatments;

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the willingness of the target patient population to try new therapies, especially a gene therapy, and of physicians to administer these therapies;

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the strength of marketing and distribution support;

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the prevalence and severity of any side effects;

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limited access to site of service that can perform the product preparation and administer the infusion; and

●

any restrictions by regulators on the use of our products.

A failure to gain market acceptance for any of the above reasons, or any reasons at all, by a gene therapy for which we receive regulatory approval would likely hinder our ability to recapture our substantial investments in that and other gene therapies and could have a material adverse effect on our business, financial condition, and results of operation.

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If the market opportunities for our product candidates are smaller than we believe they are, our product revenues may be adversely affected, and our business may suffer.

We focus our research and product development on treatments for severe genetic and orphan diseases. Our understanding of both the number of people who have these diseases, as well as the subset of people with these diseases who have the potential to benefit from treatment with our product candidates, are based on estimates. These estimates may prove to be incorrect and new studies may reduce the estimated incidence or prevalence of these diseases. The number of patients in the U.S., the EU and elsewhere may turn out to be lower than expected, may not be otherwise amenable to treatment with our products or patients may become increasingly difficult to identify and access, any of which could adversely affect our business, financial condition, results of operations and prospects.

Further, there are several factors that could contribute to making the actual number of patients who receive other potential products less than the potentially addressable market. These include the lack of widespread availability of, and limited reimbursement for, new therapies in many underdeveloped markets. Further, the severity of the progression of a disease up to the time of treatment, especially in certain degenerative conditions, could diminish the therapeutic benefit conferred by a gene therapy. Lastly, certain patients’ immune systems might prohibit the successful delivery of certain gene therapy products to the target tissue, thereby limiting the treatment outcomes.

Ethical, legal, and social issues associated with genetic testing may reduce demand for any gene therapy products for which we obtain marketing approval.

Prior to receiving certain gene therapies, patients may be required to undergo genetic testing. Genetic testing has raised concerns regarding the appropriate utilization and the confidentiality of information provided by genetic testing. Genetic tests for assessing a person’s likelihood of developing a chronic disease have focused public attention on the need to protect the privacy of patient’s underlying genetic information. For example, concerns have been expressed that insurance carriers and employers may use these tests to discriminate based on genetic information, resulting in barriers to the acceptance of genetic tests by consumers. This could lead to governmental authorities restricting genetic testing or calling for limits on or regulating the use of genetic testing, particularly for diseases for which there is no known cure. Any of these scenarios could decrease demand for any products for which we obtain marketing approval.

If we, or our commercial partners, obtain approval to commercialize any of our product candidates outside of the U.S., a variety of risks associated with international operations could materially adversely affect our business.

We expect that we will be subject to additional risks in commercializing any of our product candidates outside the U.S., including:

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different regulatory requirements for approval of drugs and biologics in foreign countries;

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reduced protection for intellectual property rights;

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unexpected changes in tariffs, trade barriers and regulatory requirements which may make it more difficult or expensive to export or import products and supplies to or from the U.S.;

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economic weakness, including inflation, or political instability in particular foreign economies and markets;

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compliance with tax, employment, immigration, and labor laws for employees living or traveling abroad;

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foreign currency fluctuations, which could result in increased operating expenses and reduced revenues, and other obligations incident to doing business in another country;

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workforce uncertainty in countries where labor unrest is more common than in the U.S.;

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production shortages resulting from any events affecting raw material supply or manufacturing capabilities abroad; and

●

business interruptions resulting from geopolitical actions, including war and terrorism or natural disasters including earthquakes, typhoons, floods, and fires.

We face substantial competition, ~~which~~and others may ~~result in others discovering, developing~~discover, develop, or ~~commercializing~~commercialize competing products before or more successfully than we do.

The development and commercialization of new biotechnology and biopharmaceutical products, including gene therapies, is highly competitive. We may face intense competition with respect to our current and future product candidates ~~as well as with respect to any product candidates that we may seek to develop or commercialize in the future,~~ from large and specialty pharmaceutical companies and biotechnology companies worldwide, who, like us, currently market and sell products or are pursuing the development of products for the treatment of ~~many~~rare diseases.

Table of ~~the disease indications for which we are developing our product candidates.~~ Contents

Potential competitors also include academic institutions, government agencies and other public and private research organizations that conduct research, seek patent protection, and establish collaborative arrangements for research, development, manufacturing, and commercialization. In recent years, there has been a significant increase in commercial and scientific interest and financial investment in gene therapy as a therapeutic approach, which has intensified the competition in this area.

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We face worldwide competition from larger pharmaceutical companies, specialty pharmaceutical companies and biotechnology firms, universities and other research institutions and government agencies that are ~~aware of numerous companies~~developing and commercializing pharmaceutical products. Our key competitors focused on developing ~~gene~~ therapies in various indications, including AGTC, Abeona Therapeutics, Adverum Biotechnologies, Asklepios BioPharmaceutical, Audentes Therapeutics, AveXis, Bayer, BioMarin, Bioveratiy, bluebird bio, Dimension Therapeutics, Errant Gene Therapeutics, Expression Therapeutics,include among others, Pfizer, Freeline Therapeutics, ~~Genethon, Genzyme, GlaxoSmithKline, Homology Medicines, Lysogene, Megenics, Milo Therapeutics, Nightstarx, Pfizer, REGENXBIO, Renova Therapeutics, Retrosense~~Intellia Therapeutics, Sangamo ~~BioSciences, Shire, Solid~~ Biosciences, Voyager Therapeutics, Passage Bio, Roche, PTC Therapeutics, Prilenia Therapeutics, CombiGene, Caritas Therapeutics, Alnylam, Wave Life Sciences, Bayer AG (AskBio), Amicus Therapeutics, 4D Molecular Therapeutics, Sanofi, Idorsia, Amicus, Spark, ~~Therapeutics, Takara,~~Takeda, Chiesi, CANbridge, Abeona, Annexon, Vico, Alexion (AZ), Neurona, Combigene, NeuExcell, EpiBlok, Biogen, ionis, Eisai and Voyager, as well as several companies addressing other methods for modifying genes and regulating gene expression. We may also face competition with respect to the treatment of some of the diseases that we are seeking to target with our gene therapies from protein pharmaceuticals under development at pharmaceutical and biotechnology companies such as Amgen, Bayer, Biogen, BioMarin, Genzyme, Novartis, Novo Nordisk, Pfizer, Shire, and numerous other pharmaceutical and biotechnology firms.Lexeo.

Our commercial opportunity could be reduced or eliminated if our competitors develop and commercialize products that are safer, more effective, have fewer or less severe side effects, are more convenient or are less expensive than the products that we develop. Our competitors also may obtain FDA, EMA, or other regulatory approval for their products more rapidly than we do, which could result in our competitors establishing a strong market position before we are able to enter the market. A competitor approval may also prevent us from entering the market if the competitor receives any regulatory exclusivities that block our product candidates. Because we expect that gene therapy patients may generally require only a single administration, we believe that the first gene therapy product to enter the market for a particular indication will likely enjoy a significant commercial advantage and may also obtain market exclusivity under applicable orphan drug regimes.

Many of the companies with which we are competing or may compete in the future have significantly greater financial resources and expertise than we do in research and development, manufacturing, preclinical testing, conducting clinical trials, obtaining regulatory approvals, and marketing approved products. Moreover, actions taken in connection with the Reorganization to streamline our product portfolio may hamper our ability to remain competitive. Mergers and acquisitions in the pharmaceutical and biotechnology industries may result in more resources being concentrated among a smaller number of our competitors. Smaller and other early-stage companies may also prove to be significant competitors, particularly through collaborative arrangements with large and established companies. These third parties compete with us in recruiting and retaining qualified scientific and management personnel, establishing clinical trial sites and patient registration for clinical trials, as well as in acquiring technologies complementary to, or necessary for, our programs.

Risks Related to Our Dependence on Third Parties

We rely, and expect to continue to rely, on third parties to conduct, supervise, and monitor our preclinical studies and clinical trials, and those third parties may not perform satisfactorily, including failing to meet deadlines in the conduct and completion of such trials or failing to comply with regulatory requirements.

We rely on third parties, study sites, and others to conduct, supervise, and monitor our preclinical and clinical trials for our product candidates and do not currently plan to independently conduct clinical or preclinical trials of any other potential product candidates. We expect to continue to rely on third parties, such as CROs, clinical data management organizations, medical and scientific institutions, and clinical and preclinical investigators, to conduct our preclinical studies and clinical trials.

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While we have agreements governing the activities of such third parties, we have limited influence and control over their actual performance and activities. For instance, our third-party service providers are not our employees, and except for remedies available to us under our agreements with such third parties we cannot control whether or not they devote sufficient time and resources to our ongoing clinical, non-clinical, and preclinical programs. If these third parties do not successfully carry out their contractual duties, meet expected deadlines or conduct our ~~collaboration~~preclinical studies or clinical trials in accordance with ~~BMS is not successful~~regulatory requirements or our stated protocols, if they need to be replaced or if ~~BMS designates~~the quality or ~~develops fewer targets than permitted under~~accuracy of the data they obtain is compromised due to the failure to adhere to our ~~collaboration agreement,~~protocols, regulatory requirements or for other reasons, our ~~development plans, financial position and opportunities for growth~~trials may be adversely affected. *

repeated, extended, delayed, or terminated, we may not be able to obtain, or may be delayed in obtaining, marketing approvals for our product candidates, we may not be able to, or may be delayed in our efforts to, successfully commercialize our product candidates, or we or they may be subject to regulatory enforcement actions. As a result, our results of operations and the commercial prospects for our product candidates would be harmed, our costs could increase and our ability to generate revenues could be delayed. To ~~earn all milestone payments and royalties potentially due under our collaboration with BMS,~~the extent we are ~~dependent on BMS electing~~unable to ~~designate~~successfully identify and ~~actively pursue target indications covered by~~manage the ~~collaboration and~~performance of third-party service providers in the future, our achievement of all development, clinical and regulatory milestones under the collaboration. If BMS designates or actively pursues fewer development targets, utilizes contract research organizations, instead of our organization, to conduct non-clinical and pre-clinical studies, or if we fail to achieve a significant number of the applicable milestones, the total payments we receive under this collaborationbusiness may be materially ~~lower than~~and adversely affected. Our third-party service providers may also have relationships with other entities, some of which may be our competitors, for whom they may also be conducting trials or other therapeutic development activities that could harm our competitive position.

Our reliance on these third parties for development activities reduces our control over these activities. Nevertheless, we are ~~potentially payable.~~responsible for ensuring that each of our studies is conducted in accordance with the applicable protocol, legal, regulatory, and scientific standards, and our reliance on third parties does not relieve us of our regulatory responsibilities. For example, we will remain responsible for ensuring that each of our trials is conducted in accordance with the general investigational plan and protocols for the trial. We must also ensure that our preclinical trials are conducted in accordance with GLPs, as appropriate. Moreover, the FDA and comparable foreign regulatory authorities require us to comply with GCPs for conducting, recording, and reporting the results of clinical trials to assure that data and reported results are credible and accurate and that the rights, integrity, and confidentiality of trial participants are protected. Regulatory authorities enforce these requirements through periodic inspections of trial sponsors, clinical and preclinical investigators, and trial sites. If we or any of our third-party service providers fail to comply with applicable GCPs or other regulatory requirements, we or they may be subject to enforcement or other legal actions, the data generated in our trials may be deemed unreliable and the FDA or comparable foreign regulatory authorities may require us to perform additional studies.

In addition, we will be required to report on certain financial interests of our third-party investigators if these relationships exceed certain financial thresholds or meet other criteria. The FDA or comparable foreign regulatory authorities may question the integrity of the data from those clinical trials conducted by investigators who may have conflicts of interest.

We cannot assure that, upon inspection by a given regulatory authority, such regulatory authority will determine that any of our trials complies with the applicable regulatory requirements. In addition, our clinical trials must be conducted with product candidates that were produced under GMP conditions. Failure to comply with these regulations may require us to repeat clinical trials, which would delay the regulatory approval process. We also are required to register certain clinical trials and post the results of certain completed clinical trials on a government-sponsored database, ClinicalTrials.gov, within specified timeframes. Failure to do so can result in enforcement actions and adverse publicity.

Agreements with third parties conducting or otherwise assisting with our clinical or preclinical studies might terminate for a variety of reasons, including a failure to perform by the third parties. If any of our relationships with these third parties terminate, we may not be able to enter into arrangements with alternative providers or to do so on commercially reasonable terms. Switching or adding additional third parties involves additional costs and requires management time and focus. In addition, there is a natural transition period when a new third party commences work. As a result, if we need to enter into alternative arrangements, it could delay our product development activities and adversely affect our business. Though we carefully manage our relationships with our third parties, there can be no assurance that we will not encounter challenges or delays in the future or that these delays or challenges will not have a material adverse impact on our business, financial condition and prospects, and results of operations.

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We also rely on other third parties to store and distribute our products for the clinical and preclinical trials that we conduct. Any performance failure on the part of our distributors could delay the development, marketing approval, or commercialization of our product candidates, producing additional losses and depriving us of potential product revenue.

We rely on third parties for important aspects of our development programs. If these parties do not perform successfully or if we are unable to ~~maintain any of our collaboration arrangements, or~~ enter into ~~new~~or maintain key collaborations or other contractual arrangements, our business could be adversely affected.

We have in the past entered into, and expect in the future to enter into, collaborations with other companies and academic research institutions with respect to important elements of our ~~commercial and~~ development programs. ~~For example,~~Any collaboration we ~~have a collaboration agreement with BMS for the development and commercialization of gene therapies for cardiovascular and potentially other diseases.~~

~~Our existing collaboration, and any future collaborations we~~ enter into may pose several risks, including the following:

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collaborators have significant discretion in determining the efforts and resources that they will apply to these collaborations;

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we ~~generally~~may have limited or no control over the design or conduct of clinical trials sponsored by ~~our current~~ collaborators;

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we may be hampered from entering into collaboration arrangements if we are unable to obtain consent ~~form~~from our ~~licensor~~licensors to enter into sublicensing arrangements of technology we have ~~licensed from such licensors;~~

in-licensed;

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if ~~our collaborators do~~any collaborator does not conduct the clinical trials they sponsor in accordance with regulatory requirements or stated protocols, we will not be able to rely on the data produced in such trials in our further development efforts;

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collaborators may not perform their obligations as expected;

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collaborators may also have relationships with other entities, some of which may be our competitors;

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collaborators may not pursue development and commercialization of any product candidates or may elect not to continue or renew development or commercialization programs based on clinical trial results, changes in the ~~collaborators'~~collaborators’ strategic focus or available funding, or external factors, such as an acquisition, that divert resources or create competing priorities;

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collaborators may delay clinical trials, provide insufficient funding for a clinical trial program, stop a clinical trial, or abandon a product candidate, repeat or conduct new clinical trials or require a new formulation of a product candidate for clinical testing;

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collaborators could develop, independently or with third parties, products that compete directly or indirectly with our products or product candidates, if, for instance, the collaborators believe that competitive products are more likely to be successfully developed or can be commercialized under terms that are more economically attractive than ours;

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our collaboration arrangements may impose restrictions on our ability to undertake other development efforts that may appear to be attractive to us;

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product candidates discovered in collaboration with us may be viewed by our collaborators as competitive with their own product candidates or products, which may cause collaborators to cease to devote resources to the commercialization of our product candidates;

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a collaborator with marketing and distribution rights that achieves regulatory approval may not commit sufficient resources to the marketing and distribution of such product or products;

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disagreements with collaborators, including over proprietary rights, contract interpretation or the preferred course of development, could cause delays or termination of the research, development or commercialization of product candidates, lead to additional responsibilities for us, delay or impede reimbursement of certain expenses or result in litigation or arbitration, any of which would be time-consuming and expensive;

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collaborators may not properly maintain or defend our intellectual property rights or may use our proprietary information in such a way as to invite litigation that could jeopardize or invalidate our rights or expose us to potential litigation;

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collaborators may infringe the intellectual property rights of third parties, which may expose us to litigation and potential liability; and

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collaborations may in some cases be terminated for the convenience of the collaborator and, if terminated, we could be required to expend additional funds to pursue further development or commercialization of the applicable product or product candidates.

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If ~~our collaborations do~~any collaboration does not result in the successful development and commercialization of products or if ~~one of our collaborators terminates its~~a collaborator were to terminate an agreement with us, we may not receive future research funding or milestone or royalty payments under ~~the~~that collaboration, and we may lose access to important technologies and capabilities of the collaboration. All the risks relating to product development, regulatory approval and commercialization described herein also apply to the activities of ~~our~~any development collaborators.

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Risks Related to Our Intellectual Property

We rely on licenses of intellectual property from third parties, and such licenses may not provide adequate rights, may be open to multiple interpretations or may not be available in the future on commercially reasonable terms or at all, and our licensors may be unable to obtain and maintain patent protection for the technology or products that we license from them.

We currently are heavily reliant upon licenses of proprietary technology from third parties that isare important or necessary to the development of our technology and products, including technology related to our manufacturing process, our vector platform, our gene cassettes, and the therapeutic genes of interest we are using. These and other licenses may not provide adequate rights to use such technology in all relevant fields of use. Licenses to additional ~~third party~~third-party technology that may be required for our development programs may not be available in the future or may not be available on commercially reasonable terms, which could have a material adverse effect on our business and financial condition.

In some circumstances, we may not have the right, or have otherwise given up the right, to control the preparation, filing and prosecution of patent applications, or to maintain the patents, covering technology that we own or license from third parties. In addition, some of our agreements with our licensors require us to obtain consent from the licensor before we can enforce patent rights, and our licensor may withhold such consent or may not provide it on a timely basis. Therefore, we cannot be certain that these patents and applications will be prosecuted and enforced in a manner consistent with the best interests of our ~~business.~~business which may materially impact any revenue that may be due to us in connection with such patents. In addition, if third parties who license patents to us fail to maintain such patents, or lose rights to those patents, the rights we have licensed may be reduced or eliminated.

Our intellectual property licenses with third parties may be subject to disagreements over contract interpretation, which could narrow the scope of our rights to the relevant intellectual property or technology or increase our financial or other obligations to our licensors.

The agreements under which we license intellectual property or technology from third parties are complex, and certain provisions in such agreements may be susceptible to multiple interpretations. The resolution of any contract interpretation disagreement that may arise could narrow what we believe to be the scope of our rights to the relevant intellectual property or technology or increase what we believe to be our financial or other obligations under the relevant agreement, either of which could have a material adverse effect on our business and financial condition.

If we fail to comply with our obligations in our intellectual property licenses with third parties, we could lose rights that are important to our business.

We in-license intellectual property from third parties that is material to our product candidates, including technology related to our manufacturing process, our vector platform, and the therapeutic genes and gene cassettes we are using. Our licensing arrangements with third parties may impose diligence, development and commercialization timelines, milestone payment, royalty, insurance, and other obligations on us. If we fail to comply with these obligations, our counterparties may have the right to terminate these agreements either in part or in whole, in which case we might not be able to develop, manufacture or market any product that is covered by these agreements or may face other penalties under the agreements. Such an occurrence could materially adversely affect the value of the product candidate being developed under any such ~~agreement.~~agreement or may otherwise result in reputational damage to our business. Termination of these agreements or reduction or elimination of our rights under these agreements may result in our having to negotiate new or amended agreements with less favorable terms or cause us to lose our rights under these agreements, including our rights to important intellectual property or technology.

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We rely, in part, upon a combination of forms of intellectual property, including in-licensed and owned patents ~~trade secret protection and confidentiality agreements~~ to protect our intellectual property. Our success depends in a large part on our ability to obtain and maintain this protection in the U.S., the European Union, ~~the United States~~ and other countries, in part by filing patent applications related to our novel technologies and product candidates. Our patents may not provide us with any meaningful commercial protection, prevent competitors from competing with us or otherwise provide us with any competitive advantage. ~~Our~~The patents we own currently are and may become subject to future patent opposition or similar proceedings. Additionally, the patent prosecution process is expensive, time-consuming, and uncertain, and in certain instances we have chosen, and in the future we may choose, not to file and prosecute all necessary or desirable patent applications. For example, our defense of certain patent cases in each of Canada, the United Kingdom, the Netherlands and the U.S. pertaining to licensed rights of etranacogene dezaparvovec was assumed by CSL Behring on October 11, 2023. These oppositions and future patent oppositions may result in loss of scope of some claims or the entire patent and, with respect to our rights under the CSL Agreement, could affect CSL’s successful commercialization of HEMGENIX® and, in turn, could negatively impact our financial position. Additionally, our competitors may be able to circumvent our owned or licensed patents by developing similar or alternative technologies or products in a non-infringing manner.

Successful challenges to our patents may result in loss of exclusivity or freedom to operate or in patent claims being narrowed, invalidated, or held unenforceable, in whole or in part, which could limit our ability or the ability of our licensees to stop others from using or commercializing similar or identical technology and products, or limit the duration of the patent protection of our technology and products.

The patent prosecution process is expensive, time-consuming and uncertain, and we may not be able to file and prosecute all necessary or desirable patent applications at a reasonable cost or in a timely manner. It is also possible that we will fail to identify patentable aspects of our research and development output before it is too late to obtain patent protection. Additionally, given the amount of time required for the development, testing and regulatory review of new product candidates, patents protecting such candidates might expire before or shortly after such candidates are commercialized. As a result, our owned and licensed patent portfolio may not provide us with sufficient rights to exclude others from commercializing products similar or identical to ours.

The patent position of biotechnology and pharmaceutical companies generally is highly uncertain, involves complex legal and factual questions and has in recent years been the subject of much litigation. In addition, the laws of foreign countries may not protect our rights to the same extent as the laws of the ~~United States.~~U.S. For example, EU patent law with respect to the patentability of methods of treatment of the human body is more limited than U.S. law. Publications of discoveries in the scientific literature often lag the actual discoveries, and patent applications in the ~~United States~~U.S. and other jurisdictions are typically not published until 18 months after their priority date, or in some cases at all. Therefore, we cannot know with certainty whether we were the first to make the inventions or that we were the first to file for patent protection of the inventions claimed in our owned or licensed patents or pending patent applications. As a result, the issuance, scope, validity, enforceability, and commercial value of our patent rights are highly uncertain. Our pending and future patent applications may not result in patents being issued that protect our technology or products, in whole or in part, or which effectively prevent others from commercializing competitive technologies and products. Changes in either the patent laws or interpretation of the patent laws in the European Union, the ~~United States~~U.S. or other countries may diminish the value of our patents or narrow the scope of our patent protection. Our inability to obtain and maintain appropriate patent protection for any one of our products could have a material adverse effect on our business, financial condition, and results of operations.

Competitors may infringe on our owned or licensed patents or other intellectual property. To counter infringement or unauthorized use, we may be required to file infringement claims, which can be expensive and time consuming. An adverse result in any litigation proceeding could put one or more of our patents at risk of being invalidated, maintained in a more narrowly amended form or interpreted narrowly.

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Even if resolved in our favor, litigation or other legal proceedings relating to intellectual property claims may cause us to incur significant expenses, increase our operating losses, reduce available resources, and could distract our technical and management personnel from their normal responsibilities. In addition, there could be public announcements of the results of hearings, motions or other interim proceedings or developments, which could have an adverse effect on the price of our ordinary shares.

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Third parties may initiate legal proceedings alleging that we are infringing their intellectual property rights, the outcome of which would be uncertain and could have a material adverse effect on the success of our business. For example, outside of the U.S. two of the patents we own are subject to patent opposition. If these or future oppositions are successful or if we are found to otherwise infringe a third party's intellectual property rights, we could be required to obtain a license from such third party to continue developing and marketing our products and technology. We may not be able to obtain the required license on commercially reasonable terms or at all. Even if we could obtain a license, it could be non-exclusive, thereby giving our competitors access to the same technologies licensed to us. We could be forced, including by court order, to cease commercializing the infringing technology or product or otherwise to cease using the relevant intellectual property. In addition, we could be found liable for monetary damages, including treble damages and ~~attorneys'~~attorneys’ fees if we are found to have willfully infringed a patent. A finding of infringement could prevent us from commercializing our product candidates or force us to cease or materially modify some of our business operations, which could materially harm our business. Claims that we have misappropriated the confidential information or trade secrets of third parties could have a similar negative impact on our business.

In addition, legal proceedings relating to intellectual property claims, with or without merit, are unpredictable and generally expensive and time-consuming and is likely to divert significant resources from our core business, including distracting our technical and management personnel from their normal responsibilities. Furthermore, because of the substantial amount of discovery required in connection with intellectual property litigation, there is a risk that some of our confidential information could be compromised by disclosure during this type of litigation.

For example, we are aware of patents or patent applications owned by third parties that relate to some aspects of our programs that are still in development. In some cases, because we have not determined the final methods of manufacture, the method of administration or the therapeutic compositions for these programs, we cannot determine whether rights under such ~~third party patents~~third-party positions will be needed. In addition, in some cases, we believe that the claims of these patents are invalid or not infringed or will expire before commercialization. However, if such patents are needed and found to be valid and infringed, we could be required to obtain licenses, which might not be available on commercially reasonable terms, or to cease or delay commercializing certain product candidates, or to change our programs to avoid infringement.

If we are unable to protect the confidentiality of our proprietary information and know-how, the value of our technology and products could be adversely affected.

In addition to seeking patent protection, we also rely on other proprietary rights, including protection of trade secrets, know-how and confidential and proprietary information. To maintain the confidentiality of our trade secrets and proprietary information, we enter into confidentiality agreements with our employees, consultants, collaborators and other third parties who have access to our trade secrets. Our agreements with employees also provide that any inventions conceived by the individual while rendering services to us will be our exclusive property. However, we may not obtain these agreements in all circumstances, and individuals with whom we have these agreements may not comply with their terms. The assignment of intellectual property rights may not be self-executing, or the assignment agreements may be breached, and we may be forced to bring claims against third parties, or defend claims that they may bring against us, to determine the ownership of what we regard as our intellectual property. In addition, in the event of unauthorized use or disclosure of our trade secrets or proprietary information, these agreements, even if obtained, may not provide meaningful protection, particularly for our trade secrets or other confidential information. To the extent that our employees, consultants, or contractors use technology or know-how owned by third parties in their work for us, disputes may arise between us and those third parties as to the rights in related inventions.

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Adequate remedies may not exist in the event of unauthorized use or disclosure of our confidential information including a breach of our confidentiality agreements. Enforcing a claim that a party illegally disclosed or misappropriated a trade secret is difficult, expensive, and time consuming, and the outcome is unpredictable. In addition, some courts in and outside of the U.S. are less willing or unwilling to protect trade secrets. If any of our trade secrets were to be lawfully obtained or independently developed by a competitor or other third party, we would have no right to prevent them from using that technology or information to compete with us. The disclosure of our trade secrets or the independent development of our trade secrets by a competitor or other third party would impair our competitive position and may materially harm our business, financial condition, results of operations, stock price and prospects.

Our reliance on third parties may require us to share our trade secrets, which could increase the possibility that a competitor will discover them or that our trade secrets will be misappropriated or disclosed.

Because we collaborate from time to time with various organizations and academic research institutions on the advancement of our gene therapy platform, we must, at times, share trade secrets with them. We seek to protect our proprietary technology in part by entering into confidentiality agreements and, if applicable, materials transfer agreements, collaborative research agreements, consulting agreements or other similar agreements with our collaborators, advisors, and consultants prior to beginning research or disclosing proprietary information. These agreements typically limit the rights of the third parties to use or disclose our confidential information, such as trade secrets. Despite the contractual provisions employed when working with third parties, the need to share trade secrets and other confidential information increases the risk that such trade secrets become known by our competitors, are inadvertently incorporated into the technology of others, or are disclosed or used in violation of these agreements. Given that our proprietary position is based, in part, on our know-how and trade secrets, a competitor's discovery of our trade secrets or other unauthorized use or disclosure would impair our competitive position and may have a material adverse effect on our business.

In addition, these agreements typically restrict the ability of our collaborators, advisors, and consultants to publish data potentially relating to our trade secrets. Our academic collaborators typically have rights to publish data, if we are notified in advance and may delay publication for a specified time ~~in order~~ to secure our intellectual property rights arising from the collaboration. In other cases, publication rights are controlled exclusively by us, although in some cases we may share these rights with other parties. We also conduct joint research and development programs that may require us to share trade secrets under the terms of our research and development partnerships or similar agreements.

Some courts inside and outside the ~~United States~~U.S. are less willing or unwilling to protect trade secrets. If any of our trade secrets were to be lawfully obtained or independently developed by a competitor, we would have no right to prevent them, or those towith whom they communicate, ~~it,~~ from using that technology or information to compete with us.

Intellectual property rights do not necessarily address all potential threats to our competitive advantage.

The degree of future protection afforded by our intellectual property rights is uncertain because intellectual property rights have limitations and may not adequately protect our business or permit us to maintain a competitive advantage. For example:

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others may be able to make gene therapy products that are similar to our product candidates or utilize similar gene therapy technology but that are not covered by the claims of the patents that we own or have licensed;

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we or our licensors or future collaborators might not have been the first to make the inventions covered issued patents or pending patent applications that we own or have licensed;

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we or our licensors or future collaborators might not have been the first to file patent applications covering certain of our inventions;

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others may independently develop similar or alternative technologies or duplicate any of our technologies without infringing our intellectual property rights;

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it is possible that our pending patent applications will not lead to issued patents;

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issued patents that we own or have licensed may be held invalid or unenforceable, as a result of legal challenges by our competitors;

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our competitors might conduct activities in countries where we do not have patent rights and then use the information learned from such activities to develop competitive products for sale in our major commercial markets;

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we may not develop additional proprietary technologies that are patentable; and

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the patents of others may have an adverse effect on our business.

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The occurrence of any of these events could seriously harm our business.

Risks Related to Pricing and Reimbursement

We and our commercial partner face uncertainty related to insurance coverage of, and pricing and reimbursement for, HEMGENIX® and other product candidates for which we may receive marketing approval.

We anticipate that the cost of treatment using our product candidates will be significant. We expect that most patients and their families will not be capable of paying for our products themselves. There will be no commercially viable market for our product candidates without reimbursement from third party payers, such as government health administration authorities, private health insurers and other organizations. Even if there is a commercially viable market, if the level of ~~third party~~third-party reimbursement is below our expectations, most patients may not be able to afford treatment with our products and our revenues and gross margins will be adversely affected, and our business will be harmed.

Government authorities and other ~~third party~~third-party payers, such as private health insurers and health maintenance organizations, decide for which medications they will pay ~~for~~ and, subsequently, establish reimbursement levels. Reimbursement systems vary significantly by country and by region, and reimbursement approvals must be obtained on a country-by-country basis. Government authorities and ~~third party~~third-party payers have attempted to control costs by limiting coverage and the amount of reimbursement for particular medications and ~~procedures.~~procedures and negotiating or requiring payment of manufacturer rebates. Increasingly, third party payers require drug companies to provide them with predetermined discounts from list prices, are exerting influence on decisions regarding the use of particular treatments and are limiting covered indications. ~~Additionally,~~

Moreover, payment methodologies may be subject to changes in healthcare legislation and regulatory initiatives. For example, the Center for Medicare & Medicaid Innovation at the Centers for Medicare & Medicaid Services (“CMS”) may develop new payment and delivery models, such as bundled payment models. In addition, recently there has been heightened governmental scrutiny over the manner in which manufacturers set prices for their marketed products, which has resulted in several U.S. Congressional inquiries and proposed and enacted federal and state legislation designed to, among other things, bring more transparency to drug pricing, reduce the cost of prescription drugs under government payor programs, and review the relationship between pricing and manufacturer patient assistance programs. Most recently, on August 16, 2022, the Inflation Reduction Act of 2022, or IRA, was signed into law. Among other things, the IRA requires manufacturers of certain drugs to engage in price negotiations with Medicare (with the maximum fair prices for the first year of the negotiation program being initially applicable in 2026), with prices that can be negotiated subject to a cap; imposes rebates for certain drugs under Medicare Part B and Medicare Part D to penalize price increases that outpace inflation (first due in 2023); and replaces the Part D coverage gap discount program with a new discounting program (beginning in 2025). We expect that additional U.S. federal healthcare reform measures will be adopted in the ~~United States~~future, any of which could limit the amounts that the U.S. federal government will pay for healthcare products and ~~some foreign jurisdictions, legislative and regulatory changes regarding the healthcare system and insurance coverage, particularly considering the new U.S. presidential administration,~~services, which could result in ~~more rigorous coverage criteria~~reduced demand for our product candidates or additional pricing pressures and ~~downward~~could seriously harm our business.

Individual states in the U.S. have also increasingly passed legislation and implemented regulations designed to control pharmaceutical and biological product pricing, including price or patient reimbursement constraints, discounts, restrictions on certain product access and marketing cost disclosure and transparency measures, and, in some cases, designed to encourage importation from other countries and bulk purchasing. Legally mandated price controls on payment amounts by third-party payors or other restrictions could seriously harm our business. In addition, regional healthcare authorities and individual hospitals are increasingly using bidding procedures to determine what pharmaceutical products and which suppliers will be included in their prescription drug healthcare programs. This could reduce the ultimate demand for our product candidates or put pressure on ~~drug prices,~~our product pricing. Furthermore, there has been increased interest by third-party payors and governmental authorities in reference pricing systems and publication of discounts and list prices. Prescription drugs and biological products that are in violation of these requirements will be included on a public list. These reforms could reduce the ultimate demand for our product candidates or put pressure on our product pricing and could seriously harm our business.

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In the EU, similar political, economic, and regulatory developments may affect our ability to profitably ~~sell~~commercialize our product candidates, if approved. In addition to continuing pressure on prices and cost containment measures, legislative developments at the EU or member state level may result in significant additional requirements or obstacles that may increase our operating costs. The delivery of healthcare in the EU, including the establishment and operation of health services and the pricing and reimbursement of medicines, is almost exclusively a matter for national, rather than EU, law and policy. National governments and health service providers have different priorities and approaches to the delivery of health care and the pricing and reimbursement of products in that context. In general, however, the healthcare budgetary constraints in most EU member states have resulted in restrictions on the pricing and reimbursement of medicines by relevant health service providers. Coupled with ever-increasing EU and national regulatory burdens on those wishing to develop and market products, this could prevent or delay marketing approval of our product candidates, restrict or regulate post-approval activities and affect our ability to commercialize our product candidates, if approved. In markets outside of the U.S. and EU, reimbursement and healthcare payment systems vary significantly by country, and many countries have instituted price ceilings on specific products and therapies.

We cannot predict the likelihood, nature or extent of government regulation that may arise from future legislation or administrative or judicial action in the U.S., the EU, or any ~~products for which~~other jurisdiction. If we ~~obtain marketing approval.~~or any third parties we may engage are slow or unable to adapt to changes in existing requirements or the adoption of new requirements or policies, or if we or such third parties are not able to maintain regulatory compliance, our product candidates may lose any regulatory approval that may have been obtained and we may not achieve or sustain profitability.

The pricing review period and pricing negotiations for new medicines take considerable time and have uncertain results. Pricing review and negotiation usually ~~begins~~begin only after the receipt of regulatory marketing approval, and some authorities require approval of the sale price of a product before it can be marketed. In some markets, particularly the countries of the European Union, prescription pharmaceutical pricing remains subject to continuing direct governmental control and to drug reimbursement programs even after initial approval is granted and price reductions may be imposed. Prices of medical products may also be subject to varying price control mechanisms or limitations as part of national health systems if products are considered not cost-effective or where a drug ~~company's~~company’s profits are deemed excessive. In addition, pricing and reimbursement decisions in certain countries can lead to mandatory price reductions or additional reimbursement restrictions in other countries. Because of these restrictions, any product candidates for which we may obtain marketing approval may be subject to price regulations that delay or prohibit our or our ~~partners'~~partners’ commercial launch of the product in a particular jurisdiction. In addition, we or ~~our collaborators~~any collaborator may elect to reduce the price of our products to increase the likelihood of obtaining reimbursement approvals. If countries impose prices which are not sufficient to allow us or ~~our collaborators~~any collaborator to generate a profit, we or ~~our collaborators~~any collaborator may refuse to launch the product in such countries or withdraw the product from the market. If pricing is set at unsatisfactory levels, or if the price decreases, our business could be harmed, possibly materially. If we fail to obtain and sustain an adequate level of coverage and reimbursement for our products by third party payers, our ability to market and sell our products ~~would~~could be adversely affected and our business ~~would~~could be harmed.

Due to the generally limited addressable market for our target orphan indications and the potential for our therapies to offer therapeutic benefit in a single administration, we face uncertainty related to ~~pricing and reimbursement for these~~our product candidates. *

The relatively small market size for orphan indications and the potential for long-term therapeutic benefit from a single administration present challenges to pricing review and negotiation of our product candidates for which we may obtain marketing authorization. Most of our product candidates target rare diseases with relatively small patient populations. If we are unable to obtain adequate levels of reimbursement relative to these small markets, our ability to support our development and commercial infrastructure and to successfully market and sell our product candidates for which we may obtain marketing approval ~~will~~could be adversely affected.

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We also anticipate that many or all of our gene therapy product candidates may provide long-term, and potentially curative benefit, with a single administration. This is a different paradigm than that of many other pharmaceutical therapies, which often require an extended course of treatment or frequent administration. As a result, governments and other payers may be reluctant to provide the significant level of reimbursement that we seek at the time of administration of our gene therapies or may seek to tie reimbursement to clinical evidence of continuing therapeutic benefit over time. ~~Although it is possible that~~Additionally, there may be situations in which our product candidates will need to be administered ~~only~~more than once, ~~there may be situations in which re-administration is required,~~ which may further complicate the pricing and reimbursement for these treatments. In addition, considering the anticipated cost of these therapies, governments and other payers may be particularly restrictive in making coverage decisions. These factors could limit our commercial success and materially harm our business.

Risks Related to Our Financial Position and Need for Additional Capital

We had net losses in the years ended December 31, 2023 and 2022, have incurred significant losses ~~to date,~~in previous years and expect to incur losses during the current and over the next several years and may never achieve or maintain profitability.*

We had a net loss of ~~$51.8~~$65.6 million in the ~~nine~~three months ended ~~September 30, 2017, $73.4~~March 31, 2024, and a net loss of $308.5 million in ~~full~~the year ~~2016 and $82.1~~ended December 31, 2023. We incurred a gain of $329.6 million in ~~2015.~~year ended December 31, 2021; however, such gain was primarily attributable to one-time license revenue from CSL Behring. We have incurred significant losses in the years prior to 2021. As of ~~September 30, 2017,~~March 31, 2024, we had an accumulated deficit of ~~$447.8~~$956.0 million. ~~To date,~~In the past, we have financed our operations primarily through the sale of equity securities and convertible debt, venture loans, ~~through~~ upfront payments from our collaboration partners and, to a lesser extent, subsidies and grants from governmental agencies and fees for services. We expect to finance our operations in 2024 and into the second quarter of 2027 primarily from our existing cash, cash equivalents, and cash resources. We have devoted substantially all our financial resources and efforts to research and development, including preclinical studies and clinical trials. ~~A significant portion of potential consideration under our agreement with BMS is contingent on achieving research, development, regulatory and sales milestones.~~ We expect to continue to incur significant expenses and losses over the next several years, and our net losses may fluctuate significantly from quarter to quarter and year to year.

We anticipate that ~~our expenses~~we will ~~increase substantially~~continue to incur net losses for the foreseeable future as we:

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~~prepare for a pivotal study for AMT-061,~~continue to fund AMT-130 in its ongoing clinical trials and advance our ~~gene therapy candidate in hemophilia B~~;

~~advance the preclinical development and initiate a clinical study for AMT-130, our product candidate in Huntington’s disease;~~

~~progress research programs of additional~~other product candidates ~~targeting liver-directed, CNS~~into clinical development;

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incur the costs associated with the manufacturing of preclinical, clinical and ~~cardiovascular disorders;~~

~~conduct any additional trials or tests beyond those originally anticipated to confirm the safety or efficacy~~commercial supplies of our product candidates;

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seek ~~marketing approval~~regulatory approvals for any product candidates that successfully complete clinical trials;

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~~acquire or in-license rights to new therapeutic targets or product candidates;~~

~~build clinical, medical, regulatory affairs, development and commercial infrastructure in the United States;~~

maintain, expand and protect our intellectual property ~~portfolio, including in-licensing in license~~portfolio;

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hire additional ~~intellectual property rights from third parties; and~~

personnel to support our business;

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~~incur cost to terminate or retain employees related to restructuring~~enhance our ~~operations.~~

operational, financial and management information systems and personnel; and

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incur legal, accounting and other expenses operating as a public company.

WeWhile we expect that, as a result of the Reorganization, we will realize some cost savings and reduce our ~~collaborator~~operating expenses, we may never succeed in ~~these activities~~materially reducing our operating expenses and, even if we do, may never generate revenues that are sufficient to achieve or sustain profitability. Even if we do achieve profitability, we may not be able to sustain or increase profitability on a quarterly or annual basis. Our failure to become and remain profitable would depress the value of our company and could impair our ability to raise capital, expand our business, maintain our research and development efforts, diversify our product offerings, or even continue our operations.

We will ~~likely~~ need to raise additional funding in order to advance the development of our product candidates, which may not be available on acceptable terms, or at all. Failure to obtain capital when needed may force us to delay, limit or terminate our product development efforts or other operations which could have a material adverse effect on our business, financial ~~conditions,~~condition, results of operations and cash flows. *

We expect to incur significant expenses in connection with our ~~on-going~~ongoing activities and ~~that~~ we will ~~likely~~ need to obtain substantial additional funding in ~~connection with~~order to fund the development of our product pipeline and support our continuing operations. In addition, we have based our estimate of our financing requirements on assumptions that may prove to be wrong, and we could use our capital resources sooner than we currently expect.

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Adequate capital may not be available to us when needed or may not be available on acceptable terms. Our ability to obtain additional debt financing may be limited by covenants we have made under our ~~Loan and Security Agreement~~2023 Amended Facility with Hercules ~~Technology Growth Capital, Inc. (“Hercules”)~~ and our pledge to Hercules of substantially all our assets as collateral. Our ability to obtain additional equity financing may be limited by our shareholders’ willingness to approve the issuance of additional share capital. If we raise additional capital through the sale of equity or convertible debt securities, our ~~shareholders'~~shareholders’ ownership interest ~~will~~could be diluted, and the terms of these securities may include liquidation or other preferences that adversely affect the rights of holders of our ordinary shares.

If we raise additional funds through collaborations, strategic alliances, or marketing, distribution, or licensing arrangements with third parties, we may have to issue additional equity, relinquish valuable rights to our technologies, future revenue streams, products, or product candidates, or grant licenses on terms that may not be favorable to us. If we are unable to raise capital when needed or on attractive terms, we could be forced to delay, reduce, or further eliminate our research and development programs or any future commercialization efforts, which would have a negative impact on our financial condition, results of operations and cash flows. ~~If our collaboration with BMS is not successful, our development plans, financial position and opportunities for growth may be adversely affected.~~

The issuance of additional sales of our ordinary shares, or the perception that such issuances may occur, including through our “at the market” offering, could cause the market price of our ordinary shares to fall.

We have entered into the Sales Agreement with Leerink for the offer and sale of up to 5 million ordinary shares from time to time through Leerink, as our sales agent, pursuant to a prospectus supplement to the base prospectus dated May 15, 2017. Leerink is not required to sell any specific number or dollar amount of our ordinary shares, but will use its reasonable efforts, as our agent and subject to the terms of the Sales Agreement, to sell that number of shares upon our request. Sales of the ordinary shares, if any, may be made by any means permitted by law and deemed to be an “at the market” offering as defined in Rule 415 of the Securities Act, and will generally be made by means of brokers' transactions on the NASDAQ Global Select Market or otherwise at market prices prevailing at the time of sale, or as otherwise agreed with Leerink.

We may terminate the Sales Agreement at any time. For the three months ended September 30, 2017, we did not sell any ordinary shares under our “at the market” (“ATM”) program. Whether we choose to terminate the Sales Agreement or affect future sales under our ATM program will depend upon a variety of factors, including, among others, market conditions and the trading price of our ordinary shares relative to other sources of capital. The issuance from time to time of these new ordinary shares through our ATM program or in any other equity offering, or the perception that such sales may occur, could have the effect of depressing the market price of our ordinary shares.

~~Our issuance of ordinary shares under our ATM program may be dilutive, and there may be future dilution of our ordinary shares.~~

After giving effect to the issuance of ordinary shares under our ATM offering program and the receipt of the expected net proceeds and the use of those proceeds, there may be a dilutive effect on our estimated earnings per share and funds from operations per share in years during which an offering is ongoing. The actual amount of potential dilution cannot be determined at this time and will be based on numerous factors. The market price of our ordinary shares could decline because of issuances of a large number of shares of our ordinary shares after this offering or the perception that such issuances could occur.

~~Our management will have broad discretion with respect to the use of the proceeds resulting from the issuance of ordinary shares under our ATM program.~~

Our management has significant flexibility in applying the net proceeds we expect to receive from the issuance of ordinary shares under our ATM program. We intend to use the net proceeds from this offering for general corporate purposes, which may include ~~capital expenditures, working capital and general and administrative expenses~~. However, because the net proceeds are not required to be allocated to any specific investment or transaction, investors cannot determine at the time of issuance the value or propriety of our application of the net proceeds, and investors may not agree with our decisions. In addition, our use of the net proceeds from the offering may not yield a significant return or any return at all. The failure by our management to apply these funds effectively could have an adverse effect on our financial condition, results of operations or the trading price of our ordinary shares.

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Our existing and any future indebtedness could adversely affect our ability to operate our business.

As of ~~September 30, 2017,~~December 31, 2023, we had ~~$20.0~~$100.0 million of outstanding principal of borrowings under ~~our Loan and Security Agreement with Hercules,~~the 2023 Amended Facility, which we are required to repay in ~~monthly principal installments~~full in January 2027. We might not be able to finance our operations into the second quarter of 2027 from ~~December 2018 through May 2020.~~our existing cash, cash equivalents, and cash resources if we are not able to refinance the 2023 Amended Facility prior to the January 2027 maturity date. We could in the future incur additional debt obligations beyond our borrowings from Hercules. Our existing loan obligations, together with other similar obligations that we may incur in the future, could have significant adverse consequences, including:

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requiring us to dedicate a portion of our cash resources to the payment of interest and principal, reducing money available to fund working capital, capital expenditures, research and development and other general corporate purposes;

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increasing our vulnerability to adverse changes in general economic, industry and market conditions;

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subjecting us to restrictive covenants that may reduce our ability to take certain corporate actions or obtain further debt or equity financing;

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limiting our flexibility in planning for, or reacting to, changes in our business and the industry in which we compete; and

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placing us at a disadvantage compared to our competitors that have less debt or better debt servicing options.

We may not have sufficient funds and may be unable to arrange for additional financing to pay the amounts due under our existing loan obligations. Failure to make payments or comply with other covenants under ~~our existing debt~~2023 Amended Facility could result in an event of default and acceleration of amounts due. Under ~~our agreement with Hercules,~~the 2023 Amended Facility, the occurrence of an event that would reasonably be expected to have a material adverse effect on our business, operations, assets, or condition is an event of default. If an event of default occurs and the lender accelerates the amounts due, we may not be able to make accelerated payments, and the lender could seek to enforce security interests in the collateral securing such indebtedness, which includes substantially all our assets.

Our 2023 Amended Facility bears a variable interest rate with a fixed floor. The U.S. Federal Reserve has raised, and may in the future further raise, interest rates to combat the effects of recent high inflation. An increase in interest rates by the Federal Reserve has and could in the future cause the prime rate to increase, which has and could in the future increase our debt service obligations. Significant increases in such obligations could have a negative impact on our financial position or operating results, including cash available for servicing our indebtedness, or result in increased borrowing costs in the future

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Our business development strategy may not produce the cash flows expected or could result in additional costs and challenges.

In July 2021, we acquired uniQure France and its lead program, now known as AMT-260, targeting refractory MTLE, and may, from time to time, enter into strategic transactions consistent with our business development objectives. Any acquisition or strategic transaction could expose us to unknown liabilities and risks, and we may incur additional costs and expenses necessary to address an acquired company’s failure to comply with laws and governmental rules and regulations. We could incur additional costs related to resources necessary to align our business practices and operations with that of the acquired company. Moreover, we cannot be sure that the anticipated or intended benefits of any acquisition or strategic transaction would be realized in a timely manner, if at all.

Risks Related to Other Legal Compliance Matters

Our relationships with employees, customers and ~~third-party payers will be~~third parties are subject to applicable ~~anti-kickback, anti-bribery, fraud and abuse and other~~ laws and regulations, the non-compliance of any of which could ~~expose us to criminal sanctions, civil penalties, contractual damages, reputational harm~~have a material adverse effect on our business, financial condition, and ~~diminished profits and future earnings.~~results of operations.

Healthcare providers, physicians, other practitioners, and third-party payers will play a primary role in the recommendation and prescription of any products for which we obtain marketing approval. Our future arrangements with third party payers and customers may expose us to broadly applicable anti-bribery laws, including the Foreign Corrupt Practices Act, as well as fraud and abuse and other U.S. and international healthcare laws and regulations that may constrain the business or financial arrangements and relationships through which we would be able to market, sell and distribute any products for which we obtain marketing approval.

Efforts to ensure that our business arrangements with third parties will comply with applicable laws and regulations ~~will~~could involve substantial costs. If our operations, or the activities of our collaborators, distributors or other third-party agents are found to be in violation of any of these laws or any other governmental regulations that may apply to us, we may be subject to significant civil, criminal, and administrative penalties, damages, fines, imprisonment, exclusion ~~of products~~ from participation in government funded healthcare programs and the curtailment or restructuring of our operations.

IfAdditionally, we ~~fail to comply with environmental, health and safety laws and regulations, we could become subject to fines or penalties or incur costs that could harm our business.~~

We are subject to ~~numerous environmental, health~~various labor and safety laws and regulations, including those governing laboratory procedures and the handling, use, storage, treatment and disposal of hazardous materials and wastes. Our operations involve the use of hazardous and flammable materials, including chemicals and biological materials. Our operations also produce hazardous waste products. We cannot eliminate the risk of contamination or injury from these materials. We also could incur significant costs associated with civil or criminal fines and penalties for failure to comply with such laws and regulations.

Although we maintain employer's liability insurance to cover us for costs and expenses we may incur due to injuries to our employees resulting from the use of hazardous materials, this insurance may not provide adequate coverage against potential liabilities. We do not maintain insurance for environmental liability or toxic tort claims that may be asserted against us in connection with our storage or disposal of biological, hazardous or radioactive materials.

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~~In addition, we may incur substantial costs to comply with current or future environmental, health and safety~~employment laws and regulations. These ~~current or future~~ laws and regulations ~~may impair our research, development~~relate to matters such as employment discrimination, wage and hour laws, requirements to provide meal and rest periods or ~~production efforts. Our failure~~other benefits, family leave mandates, employee and independent contractor classification rules, requirements regarding working conditions and accommodations to ~~comply~~certain employees, citizenship or work authorization and related requirements, insurance and workers’ compensation rules, healthcare laws, scheduling notification requirements and anti-discrimination and anti-harassment laws. Complying with these laws and regulations, ~~also~~including ongoing changes thereto, subjects us to substantial expense and non-compliance could expose us to significant liabilities. In particular, we are subject to allegations of Sarbanes-Oxley whistleblower retaliation and employment discrimination and retaliation, and we may ~~result~~ in ~~substantial fines, penalties~~the future be subject to additional claims of non-compliance with similar or other ~~sanctions.~~laws and regulations.

The costs associated with an alleged or actual violation of any of the foregoing could be substantial and could cause irreparable harm to our reputation or otherwise have a material adverse effect on our business, financial condition, and results of operations.

We are subject to laws governing data protection in the different jurisdictions in which we operate. The implementation of such data protection regimes is complex, and should we fail to fully comply, we may be subject to penalties that may have an adverse effect on our business, financial condition, and results of operations.

Many national, international, and state laws govern the privacy and security of health information and other personal and private information. They often differ from each other in significant ways. For instance, the EU has adopted a comprehensive data protection law called the EU General Data Protection Regulation that took effect in May 2018. The UK has, following its exit from the EU, substantially adopted the EU General Data Protection Regulation into its domestic law through the UK General Data Protection Regulation (collectively with the EU General Data Protection Regulation, and related EU and UK e-Privacy laws, the “GDPR”). The GDPR, together with the national legislation of the UK (including the Data Protection Act 2018) and EU member states governing the processing of personal data, impose strict obligations and restrictions on the ability to collect, use, analyze and transfer personal information, including health data from clinical trials and adverse event reporting.

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GDPR obligations applicable to us may include, in many circumstances, obtaining the (opt-in) consent of the individuals to whom the personal data relates; providing GDPR-prescribed data processing notices to individuals; complying with restrictions regarding the transfer of personal data out of the EU or the UK (as applicable) (including to the US); implementing and maintaining data protection policies and procedures; restrictions regarding the use of certain innovative technologies; providing data security breach notifications to supervisory authorities and affected individuals under tight timescales; and implementing security and confidentiality measures. Supervisory authorities in the different EU member states and the UK may interpret the GDPR and national laws differently and impose additional requirements. Guidance on implementation and compliance practices are often updated or otherwise revised. All of this adds to the complexity of processing personal information and remaining compliant with the GDPR.

The GDPR allows EU and UK supervisory authorities to impose penalties for non-compliance of up to the greater of EUR 20.0 million and 4% of annual worldwide gross revenue of the corporate group in question. (There are similar caps in GBP under the UK GDPR.). Supervisory authorities in the EU and UK may potentially levy such fines directly upon on the non-compliant entity and/or on the parent company of the non-compliant entity. Supervisory authorities also possess other wide-ranging powers, including conducting unannounced inspections of our facilities and system (so-called “dawn raids”), and issuing “stop processing” orders to us. Separate from regulatory enforcement actions, individuals may bring private actions (including potentially group or representative actions) against us. There is no statutory cap in the GDPR on the amount of compensation or the damages which individuals may recover.

Overall, the significant costs of GDPR compliance, risk of regulatory enforcement actions and private litigation under, and other burdens imposed by the GDPR as well as under other regulatory schemes throughout the world related to privacy and security of health information and other personal and private data could have an adverse impact on our business, financial condition, and results of operations.

Product liability lawsuits could cause us to incur substantial liabilities and to limit commercialization of our therapies.

We face an inherent risk of product liability related to the testing of our product candidates in human clinical trials and in connection with product sales. If we cannot successfully defend ourselves against claims that our product candidates or products or the procedures used to administer them to patients caused injuries, we will incur substantial liabilities. Regardless of merit or eventual outcome, liability claims may result in:

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decreased demand for any product candidates or products that we develop or sell;

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injury to our reputation and significant negative media attention;

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negative publicity or public opinion surrounding gene therapy;

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withdrawal of clinical trial ~~participants;~~

participants or sites, or discontinuation of development programs;

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significant costs to defend the related litigation;

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substantial monetary awards to trial participants or patients;

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loss of revenue;

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initiation of investigations, and enforcement actions by regulators; and product recalls, withdrawals, revocation of approvals, or labeling, marketing, or promotional restrictions;

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reduced resources of our management to pursue our business strategy; and

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the inability to further develop or commercialize any products that we develop.

~~Dependent~~Depending upon the country where the clinical trial is conducted, we currently hold ~~a maximum of €6,000,000 and minimum of €2,000,000 in clinical trial insurance coverage in the aggregate, with a~~coverages ranging from EUR 500,000 to EUR 10,000,000 per ~~incident limit of €450,000 to €1,000,000 with respect to the clinical studies we conduct.~~occurrence. Such coverage may not be adequate to cover all liabilities that we may incur. We may need to increase our insurance coverage as we expand our clinical trials. In addition, insurance coverage is increasingly expensive. We may not be able to maintain insurance coverage at a reasonable cost or in an amount adequate to satisfy any liability that may arise. In the event insurance coverage is insufficient to cover liabilities that we may incur, it could have a material adverse effect on our business, financial condition, and results of operations.

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Healthcare legislative and regulatory reform measures may have a material adverse effect on our financial operations.

Our industry is highly regulated and changes in law may adversely impact our business, operations, or financial results. The Patient Protection and Affordable Care Act, as amended by the Health Care and Education Reconciliation Act, or the PPACA, is a sweeping measure intended to, among other things, expand healthcare coverage within the U.S., primarily through the imposition of health insurance mandates on employers and individuals and expansion of the Medicaid program. Several provisions of the law may affect us and increase certain of our costs.

In addition, other legislative changes have been adopted since the PPACA was enacted. These changes include aggregate reductions in Medicare payments to providers of 2% per fiscal year, which went into effect on April 1, 2013, Congress subsequently has extended the period over which these reductions are in effect. While President Biden previously signed legislation temporarily to eliminate this reduction through the end of 2021, a 1% payment adjustment was implemented from April 1 – June 30, 2022, and a 2% payment adjustment took effect beginning July 1, 2022. In January 2013, President Obama signed into law the American Taxpayer Relief Act of 2012, which, among other things, further reduced Medicare payments to several types of providers and increased the statute of limitations period for the government to recover overpayments to providers from three to five years. These laws may result in additional reductions in Medicare and other healthcare funding, which could have a material adverse effect on our customers and, accordingly, our financial operations.

We anticipate that the PPACA, as well as other healthcare reform measures that may be adopted in the future, may result in more rigorous coverage criteria and additional downward pressure on pricing and the reimbursement our customers may receive for our products, and increased manufacturer rebates. Further, there have been, and there may continue to be, judicial and Congressional challenges to certain aspects of the PPACA. For example, the U.S. Tax Cuts and Jobs Act of 2017 includes a provision repealing, effective January 1, 2019, the tax-based shared responsibility payment imposed by the Affordable Care Act on certain individuals who fail to maintain qualifying health coverage for all or part of a year that is commonly referred to as the “individual mandate”. Additional legislative and regulatory changes to the PPACA, its implementing regulations and guidance and its policies, remain possible in the 118^th U.S. Congress and under the Biden Administration. However, it remains unclear how any new legislation or regulation might affect the prices we may obtain for any of our product candidates for which regulatory approval is obtained. Any reduction in reimbursement from Medicare and other government programs may result in a similar reduction in payments from private payers. The implementation of cost containment measures or other healthcare reforms may prevent us from being able to generate revenue, attain profitability or commercialize our products.

Our future growth may depend, in part, on our ability to penetrate markets outside of the U.S. and Europe where we would be subject to additional regulatory burdens and other risks and uncertainties.

Our future profitability may depend, in part, on our ability to commercialize current or future drug candidates in foreign markets for which we may rely on collaborations with third parties. We are not permitted to market or promote any of our drug candidates before we receive regulatory approval from the applicable regulatory authority in that foreign market. To obtain separate regulatory approval in many other jurisdictions we must comply with numerous and varying regulatory requirements of such jurisdictions regarding safety and efficacy and governing, among other things, clinical trials, manufacturing, commercial sales, pricing and distribution of our drug candidates, and we cannot predict success in these jurisdictions.

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Our internal computer systems, or those of our collaborators or other contractors or consultants, may fail or suffer security breaches, which could result in a material disruption of our product development programs.

Our internal computer systems and those of our current and any future collaborators and other contractors or consultants are vulnerable to damage from computer viruses, unauthorized access, natural disasters, terrorism, war and telecommunication and electrical failures. The size and complexity of our information technology systems, and those of our collaborators, contractors and consultants, and the large amounts of confidential information stored on those systems, make such systems vulnerable to service interruptions or to security breaches from inadvertent or intentional actions by our employees, third-party vendors and/or business partners, or from cyber-attacks by malicious third parties. Cyber-attacks are increasing in their frequency, sophistication, and intensity, and have become increasingly difficult to detect. Cyber-attacks could include the deployment of harmful malware, ransomware, denial-of-service attacks, social engineering, and other means to affect service reliability and threaten the confidentiality, integrity, and availability of information. Cyber-attacks also could include phishing attempts or e-mail fraud to cause payments or information to be transmitted to an unintended recipient. Our hybrid remote work policy may increase our vulnerability to such risks.

While we have experienced and addressed system failures, cyber-attacks, and security breaches in the past, we have not experienced a system failure, accident, cyber-attack, or security breach that has resulted in a material interruption in our operations to date. In the future, such events could result in a material disruption of our development programs and our business operations, whether due to a loss of our trade secrets, data, or other proprietary information or other similar disruptions. Additionally, any such event that leads to unauthorized access, use or disclosure of personal information, including personal information regarding our patients or employees, could harm our reputation, cause us not to comply with federal and/or state breach notification laws and foreign law equivalents and otherwise subject us to liability under laws and regulations that protect the privacy and security of personal information. Security breaches and other inappropriate access can be difficult to detect, and any delay in identifying them may lead to increased harm of the type described above. We may need to devote significant resources to protect against security breaches or to address problems caused by a cyber-attack or security breach. While we have implemented security measures to protect our information technology systems and infrastructure, there can be no assurance that such measures will prevent service interruptions or security breaches that could adversely affect our business and the further development and commercialization of our product and product candidates could be delayed.

See Part I, Item 1C, Cybersecurity, in our Annual Report for more information regarding our cybersecurity risk management, strategy and governance.

Climate change as well as corporate responsibility initiatives, including environmental, social and governance (ESG) matters, may impose additional costs on our business and expose us to new risks.

Greenhouse gases may have an adverse effect on global temperatures, weather patterns, and the frequency and severity of extreme weather and natural disasters. Such events could have a negative effect on our business. Concern over the impact of climate change may result in new or additional legislative and regulatory requirements to reduce or mitigate the effects of climate change on the environment, which could result in increases in taxes, transportation costs and utilities, among other expenses. Moreover, natural disasters and extreme weather conditions may impact the productivity of our facilities, the ability of the patients in our clinical trials to maintain compliance with trial protocols or access clinical trial sites, the operation of our supply chain, or consumer buying patterns. The occurrence of any of these events could have a material adverse effect on our business.

ESG and sustainability initiatives continue to attract political and social attention have resulted in both existing and pending international agreements and national, regional, and local legislation, regulatory measures, reporting obligations and policy changes. There is increasing societal pressure in some of the countries in which we operate to limit greenhouse gas emissions as well as other global initiatives focused on climate change. These agreements and measures, including the Paris Climate Accord, may require, or could result in future legislation, regulatory measures or policy changes that would require operational changes, taxes, or purchases of emission credits to reduce emission of greenhouse gases from our operations, which may require the that we dedicate additional resources toward compliance with these measures and result in substantial capital expenditures. Furthermore, increasing attention on ESG matters has resulted in governmental investigations, and public and private litigation, which could increase our costs or otherwise adversely affect our business or results of operations.

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In addition, organizations that provide information to investors on corporate governance and related matters have developed ratings processes for evaluating companies and investment funds based on ESG and sustainability metrics. Such ratings are used by investors to inform their investment and voting decisions. Unfavorable ESG ratings may lead to increased negative investor sentiment toward us, which could have a negative impact on the price of our securities and our access to and costs of capital. In addition, investors, particularly institutional investors, use these scores to benchmark companies against their peers and if a company is perceived as lagging, take actions to hold these companies and their boards of directors accountable. Board diversity is an ESG topic that is, in particular, receiving heightened attention by investors, stockholders, lawmakers and listing exchanges. Certain states have passed laws requiring companies to meet certain gender and ethnic diversity requirements on their boards of directors. We may face reputational damage in the event our corporate responsibility initiatives or objectives, do not meet the standards set by our investors, stockholders, lawmakers, listing exchanges or other constituencies, or if we are unable to achieve an acceptable ESG or sustainability rating from third-party rating services.

The effects of climate change or any or all of these ESG and sustainability initiatives may result in significant operational changes and expenditures, reduced demand for our products, cause us reputational harm, and could materially adversely affect our business, financial condition, and results of operations.

Risks Related to Employee Matters and Managing Our Growth

Our future success depends on our ability to retain key executives, ~~and~~ technical staff, and other employees and to attract, retain and motivate qualified personnel.

Our future growth and success will depend in large part on our continued ability to attract, retain, manage, and motivate our employees. The loss of the services of any member of our senior management or the inability to hire or retain experienced management personnel could adversely affect our ability to execute our business plan and harm our operating results. We are highly dependent on hiring, training, retaining, and motivating key personnel to lead our research and development, clinical operations, and manufacturing efforts. Although we have entered into employment agreements with our key personnel, each of them may terminate their employment on short notice. We do not maintain key person insurance for any of our senior management or employees.

The loss of the services of our key employees could impede the achievement of our research and development objectives and seriously harm our ability to successfully implement our business strategy. Furthermore, replacing senior management and key employees may be difficult and may take an extended period because of the limited number of individuals in our industry with the breadth and depth of skills and experience required to successfully develop gene therapy products. ~~Competition to hire from this~~

The competition for qualified personnel in the pharmaceutical field is intense, and there is a limited pool isof qualified potential employees to recruit. Due to this intense ~~and~~competition, we may be unable to ~~hire, train,~~continue to attract and retain the qualified personnel necessary for the development of our business or ~~motivate these key personnel on acceptable terms.~~

to recruit suitable replacement personnel. If we are unable to continue to attract and retain high quality personnel, our ability to pursue our business may be harmed and our growth strategy ~~will~~may be limited.

Additionally, we are reliant on our employees, contractors, consultants, vendors, and other parties with whom we have relationships to behave ethically and within the requirements of the law. The failure of any employee or other such third parties to act within the bounds of the applicable laws, regulations, agreements, codes and other requirements, or any misconduct or illegal actions or omissions by such persons, could materially damage our business.

In October 2023, we commenced the Reorganization to reprioritize our portfolio of development candidates, conserve financial resources and better align our workforce with current business needs. We may encounter challenges in the execution of these efforts, and these challenges could impact our financial results.

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Although we believe that these actions will reduce operating costs, we cannot guarantee that the Reorganization will achieve or sustain the targeted benefits, or that the benefits, even if achieved, will be adequate to meet our long-term expectations. As a result of the Reorganization, we will incur additional costs in the near term, including cash expenditures for employee transition, notice period and severance payments, employee benefits, and related facilitation costs. Additional risks associated with the continuing impact of the Reorganization include employee attrition beyond our intended reduction in force and adverse effects on employee morale (which may also be further exacerbated by actual or perceived declining value of equity awards), diversion of management attention, adverse effects to our reputation as an employer (which could make it more difficult for us to hire and retain new employees in the future), potential understaffing and potential failure or delays to meet development targets due to the loss of qualified employees or other operational challenges. If we do not realize the expected benefits of our restructuring efforts on a timely basis or at all, our business, results of operations and financial condition could be adversely affected.

Risks Related to Our Ordinary Shares

The price of our ordinary shares has been and may in the future be volatile and fluctuate substantially.*

Our share price has been and may in the future be volatile. From the start of trading of our ordinary shares on the ~~NASDAQ~~Nasdaq Global Select Market on February 4, 2014 through ~~October 31, 2017,~~May 2, 2024 the sale price of our ordinary shares ranged from a high of ~~$36.38~~$82.49 to a low of ~~$4.72.~~$4.39. The closing price on ~~October 30, 2017,~~May 2, 2024, was ~~$15.42~~$4.68 per ordinary share. ~~The~~

In recent years, the stock market in general and the market for shares of smaller biopharmaceutical companies in particular have experienced ~~extreme volatility~~significant price and volume fluctuations that ~~has~~have often been unrelated or disproportionate to changes in the operating performance of ~~particular companies.~~the companies whose stock is experiencing those price and volume fluctuations. The market price for our ordinary shares may be influenced by many factors, including:

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the success of competitive products or technologies;

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results of clinical trials of our product candidates or those of our competitors;

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public perception and market reaction to our interim data from clinical trials;

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public perception of gene therapy;

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interactions with the FDA on the design of our clinical trials and regulatory endpoints;

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regulatory delays and greater government regulation of potential products due to adverse events;

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regulatory or legal developments in the ~~European Union,~~EU, the ~~United States~~U.S., and other countries;

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developments or disputes concerning patent applications, issued patents or other proprietary rights;

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the recruitment or departure of key personnel;

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changes to our business, including pipeline reprioritizations and restructurings;

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the level of expenses related to any of our product candidates or clinical development programs;

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the results of our efforts to discover, develop, acquire or ~~in- license~~in-license additional product candidates or products;

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actual or anticipated changes in estimates as to financial results, development timelines or recommendations by securities analysts;

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variations in our financial results or those of companies that are perceived to be similar to us;

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changes in the structure of healthcare payment systems;

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market conditions in the pharmaceutical and biotechnology sectors; ~~and~~

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mergers, acquisitions, licensing, and collaboration activity among our peer companies in the pharmaceutical and biotechnology sectors;

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general economic, industry and market ~~conditions.~~

conditions; and

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the other factors described in this “Risk Factors” section.

~~An active trading market for our ordinary shares may not be sustained.~~

Although our ordinary shares are listed on The NASDAQ Global Select Market, an active trading market for our shares may not be sustained. If an active market for our ordinary shares does not continue, it may be difficult for our shareholders to sell their shares without depressingFollowing periods of such volatility in the market price ~~for~~of a company’s securities, securities class action litigation has often been brought against that company. Because of the ~~shares or sell their shares at all. Any inactive trading~~potential volatility of our stock price, we may become the target of securities litigation in the future. In addition, notwithstanding protective provisions in our articles of association and available to us under Dutch corporate law, market ~~for~~volatility may lead to increased shareholder activism if we experience a market valuation that activist investors believe is not reflective of the intrinsic value of our ordinary ~~shares may also impair~~shares. Activist campaigns that contest or conflict with our ~~ability to raise capital to continue to fund~~strategic direction or seek changes in the composition of our ~~operations by selling shares~~board of directors could have an adverse effect on our operating results and ~~may impair~~financial condition. Securities litigation or shareholder activism could result in substantial costs and divert management’s attention and resources from our ~~ability to acquire other companies or technologies by using our shares as consideration.~~business.

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Our directors, ~~named~~ executive officers, and major shareholders, if they choose to act together, will continue to have a significant degree of control with respect to matters submitted to shareholders for approval. *

Our directors, ~~named~~ executive ~~offices~~officers and major shareholders holding more than 5% of our outstanding ordinary shares, in the aggregate, beneficially own approximately ~~31.2%~~26.5% of our issued shares (including such shares to be issued in relation to exercisable options to purchase ordinary shares) as ~~at September 30, 2017.~~of March 31, 2024. As a result, if these shareholders were to choose to act together, they may be able, as a practical matter, to control many matters submitted to our shareholders for approval, as well as our management and affairs. For example, these persons, if they choose to act together, could control the election of the board of directors and the approval of any merger, consolidation, or sale of all or substantially all our assets. These shareholders may have interests that differ from those of other of our shareholders and conflicts of interest may arise.

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Provisions of our articles of association or Dutch corporate law might deter acquisition bids for us that might be considered favorable and prevent or frustrate any attempt to replace our board.

Under Dutch law, various protective measures are possible and permissible within the boundaries set by Dutch statutory and case law. Certain provisions of our articles of association may make it more difficult for a third party to acquire control of us or effect a change in our board. These provisions include:

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the staggered three-year terms of our ~~directors;~~

non-executive directors as a result of which only approximately one-third of our non-executive directors may be subject to election or re-election in any one year;

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a provision that our directors may only be ~~removed~~dismissed or suspected at a general meeting of shareholders by a two-thirds majority of votes cast representing more than half of ~~the issued share capital~~our outstanding ordinary shares;

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a provision that our executive directors may only be appointed upon binding nomination of the ~~Company (unless the removal was proposed~~non-executive directors, which can only be overruled by the ~~board);~~general meeting of shareholders with a two-thirds majority of votes cast representing at least 50% of our outstanding ordinary shares; and

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a requirement that certain matters, including an amendment of our articles of association, may only be brought to our shareholders for a vote upon a proposal by our board.

Moreover, according to Dutch corporate law, our board can invoke a cooling-off period of up to 250 days in the event of an unsolicited takeover bid or certain shareholder activism. During a cooling-off period, our general meeting of shareholders would not be able to dismiss, suspend or appoint directors (or amend the provisions in our articles of association dealing with those matters) except at the proposal of our board.

We do not expect to pay dividends in the foreseeable future.

We have not paid any dividends since our incorporation. Even if future operations lead to significant levels of distributable profits, we currently intend ~~that~~those earnings, if any, will be reinvested in our business and that dividends will not be paid until we have an established revenue stream to support continuing dividends. Accordingly, shareholders cannot rely on dividend income from our ordinary shares and any returns on an investment in our ordinary shares will likely depend entirely upon any future appreciation in the price of our ordinary shares.

~~We are an "emerging growth company," and the reduced disclosure requirements applicable to emerging growth companies may make our ordinary shares less attractive to investors.~~

We are an emerging growth company, as defined in the Jumpstart Our Business Startups Act of 2012 (“JOBS Act”) and may remain an emerging growth company for up to five years from our initial public offering. For so long as we remain an emerging growth company, we are permitted and intend to rely on exemptions from certain disclosure requirements that are applicable to other public companies that are not emerging growth companies. These exemptions include:

~~not being required to comply with the auditor attestation requirements in the assessment of our internal control over financial reporting; and~~

not being required to comply with any requirement that may be adopted by the Public Company Accounting Oversight Board regarding mandatory audit firm rotation or a supplement to the auditor's report providing additional information about the audit and the financial statements.

If some investors find our ordinary shares less attractive because of our reliance on these exemptions, trading market for our ordinary shares may be less active and our share price may be more volatile.

~~We ceased to qualify as a foreign private issuer as of January 1, 2017, and therefore must comply with the Exchange Act, which will result in additional legal, accounting and other expenses.~~

Beginning in January 2017, we must comply with the Exchange Act reporting and other requirements applicable to U.S. domestic filers, which are more detailed and extensive than the requirements for foreign private issuers to which we were previously subject. In addition, we are now required to report our financial results under U.S. GAAP, including our historical financial results, which have previously been prepared in accordance with International Financial Reporting Standards (“IFRS”). We have made changes in our corporate governance practices in accordance with various SEC and NASDAQ rules. The transition to U.S. GAAP reporting has required additional expenditures, and the related regulatory, compliance and insurance costs to us may be significantly higher than the costs we incurred as a foreign private issuer.

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If we fail to maintain an effective system of internal controls, we may be unable to accurately report our results of operations or prevent fraud or fail to meet our reporting obligations, and investor confidence and the market price of our ordinary shares may be materially and adversely affected.

If we fail to maintain the adequacy of our internal control over financial reporting, we may not be able to conclude on an ongoing basis that we have effective internal control over financial reporting. If we fail to maintain effective internal control over financial reporting, we could experience material misstatements in our financial statements and fail to meet our reporting obligations, which would likely cause investors to lose confidence in our reported financial information. This could in turn limit our access to capital markets, harm our results of operations, and lead to a decline in the trading price of our ordinary shares. Additionally, ineffective internal control over financial reporting could expose us to increased risk of fraud or misuse of corporate assets and subject us to potential delisting from The ~~NASDAQ~~Nasdaq Global Select Market, regulatory investigations and civil or criminal sanctions. Our reporting and compliance obligations may place a significant strain on our management, operational and financial resources, and systems for the foreseeable future.

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We ~~qualify as a passive foreign investment company as of December 31, 2016~~have in the past qualified and in the future may qualify as a passive foreign investment company, ~~in the future,~~ which may result in adverse U.S. federal income tax ~~consequence~~consequences to U.S. holders.

~~Based on our average value of our gross assets, our cash and cash equivalents as well as~~A corporation organized outside the ~~price of our shares we qualify~~U.S. generally will be classified as a passive foreign investment company (“PFIC”) ~~for U.S. federal income tax for 2016. A corporation organized outside the United States generally will be classified as a PFIC~~ for U.S. federal income tax purposes in any taxable year in which at least 75% of its gross income is passive income or on average at least 50% of the gross value of its assets is attributable to assets that produce passive income or are held to produce passive income. Passive income for this purpose generally includes dividends, interest, royalties, rents and gains from commodities and securities transactions. Based on our average value of our gross assets, our cash and cash equivalents as well as the price of our ordinary shares, we expect to be classified as a PFIC for U.S. federal income tax for 2023. Our status in any taxable year will depend on our assets and activities in each year, and because this is a factual determination made annually after the end of each taxable year, there can be no assurance that we will continue to qualify as a PFIC in future taxable years. The market value of our assets may be determined in large part by reference to the market price of our ordinary shares, which is likely to fluctuate, and may fluctuate considerably given that market prices of biotechnology companies have been especially volatile. If we were considered a PFIC for the current taxable year or any future taxable year, a U.S. holder would be required to file annual information returns for such year, whether the U.S. holder disposed of any ordinary shares or received any distributions in respect of ordinary shares during such year. In certain circumstances a U.S. holder may be able to make certain tax elections that would lessen the adverse impact of PFIC status; however, to make such elections the U.S. holder will usually have to have been provided information about the company by us, and we do not intend to provide such information.

The U.S. federal income tax rules relating to PFICs are complex. U.S. holders are urged to consult their tax advisors with respect to the purchase, ownership and disposition of our shares, the possible implications to them of us being treated as a PFIC (including the availability of applicable election, whether making any such election would be advisable in their particular circumstances) as well as the federal, state, local and foreign tax considerations applicable to such holders in connection with the purchase, ownership, and disposition of our shares.

Any U.S. or other foreign judgments may be difficult to enforce against us in the Netherlands.

Although we ~~now~~ report as a U.S. domestic filer for SEC reporting purposes, we are ~~incorporated~~organized and existing under the laws of the Netherlands. Some of the members of our board and senior management reside outside the ~~United States.~~U.S. In addition, a significant portion of our assets are located outside the U.S. As a result, it may not be possible for shareholders to effect service of process within the ~~United States~~U.S. upon such persons or to enforce judgments against them or us in U.S. courts, including judgments predicated upon the civil liability provisions of the federal securities laws of the ~~United States.~~U.S. In addition, it is not clear whether a Dutch court would impose civil liability on us or any of our Board members in an original action based solely upon the federal securities laws of the ~~United States~~U.S. brought in a court of competent jurisdiction in the Netherlands.

The ~~United States~~U.S. and the Netherlands currently do not have a treaty providing for the reciprocal recognition and enforcement of judgments, other than arbitration awards, in civil and commercial matters. Consequently, a final judgment for payment given by a court in the ~~United States,~~U.S., whether or not predicated solely upon U.S. securities laws, would not automatically be recognized or enforceable in the Netherlands. To obtain a judgment which is enforceable in the Netherlands, the party in whose favor a final and conclusive judgment of the U.S. court has been rendered will be required to file its claim with a court of competent jurisdiction in the Netherlands. Such party may submit to the Dutch court the final judgment rendered by the U.S. court. If and to the extent that the Dutch court finds that the jurisdiction of the U.S. court has been based on grounds which are internationally acceptable and that proper legal procedures have been observed, the Dutch court will, in principle, give binding effect to the judgment of the U.S. court, unless such judgment contravenes principles of public policy of the Netherlands. Dutch courts may deny the recognition and enforcement of punitive damages or other awards. Moreover, a Dutch court may reduce the amount of damages granted by a U.S. court and recognize damages only to the extent that they are necessary to compensate actual losses or damages. Enforcement and recognition of judgments of U.S. courts in the Netherlands are solely governed by the provisions of the Dutch Civil Procedure Code.

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Therefore U.S. shareholders may not be able to enforce against us or our board members or senior management who are residents of the Netherlands or countries other than the ~~United States~~U.S. any judgments obtained in U.S. courts in civil and commercial matters, including judgments under the U.S. federal securities laws.

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The rights and responsibilities of our shareholders and directors are governed by Dutch law and differ in some important respects from the rights and responsibilities of shareholders under U.S. law.

~~Although we now report as~~We are a ~~U.S. domestic filer for SEC purposes,~~public company (naamloze vennootschap) organized under the laws of the Netherlands and our corporate affairs are governed by our articles of association and by the laws governing companies incorporated in the Netherlands. The rights of our shareholders and the responsibilities of members of our board under Dutch law are different than under the laws of some U.S. jurisdictions. In the performance of their duties, our board members are required by Dutch law to consider the interests of uniQure, its shareholders, its employees, and other stakeholders and not only those of our ~~shareholders.~~shareholders (as would be required under the law of most U.S. jurisdictions). As a result of these considerations, it is possible that some of these parties will have interests that are different from, or in addition to, your interests as a shareholder, and our directors may take actions that would be different than those that would be taken by a company organized under the law of some U.S. jurisdictions.

In addition, in accordance with our articles of association, approval of our shareholders is required before our board of directors can authorize the issuance of our ordinary shares in an equity financing. Our shareholders’ reluctance to approve such further issuances of ordinary shares could adversely affect our ability to raise capital and fund development programs and continued operations. There can be no assurance that Dutch law will not change in the future or that it will serve to protect investors in a similar fashion afforded under corporate law principles in the U.S., which could adversely affect the rights of investors.

We may be adversely affected by unstable market and economic conditions, such as inflation, which may negatively impact our business, financial condition and stock price.

Market conditions such as inflation, volatile energy costs, geopolitical issues, war, unstable global credit markets and financial conditions could lead to periods of significant economic instability, diminished liquidity and credit availability, diminished expectations for the global economy and expectations of slower global economic growth going forward. Our business and operations may be adversely affected by such instability, including any such inflationary fluctuations, economic downturns, volatile business environments and continued unstable or unpredictable economic and market conditions. Inflation in particular has the potential to adversely affect our liquidity, business, financial condition, and results of operations by increasing our overall cost structure. The existence of inflation in the economy has resulted in, and may continue to result in, higher interest rates and capital costs, shipping costs, supply shortages, increased costs of labor, weakening exchange rates and other similar effects. As a result of inflation, we have experienced, and may continue to experience, cost increases across our business. Although we may take measures to mitigate the impact of this inflation, if these measures are not effective our business, financial condition, results of operations and liquidity could be materially adversely affected. Even if such measures are effective, there could be a difference between the timing of when these beneficial actions impact our results of operations and when cost inflation is incurred.

Any such volatility and disruptions may have adverse consequences on us or the third parties on whom we rely. If economic and market conditions deteriorate or do not improve, it may make any future financing efforts more difficult to complete, more costly and more dilutive to our shareholders. Additionally, due to our volatile industry and industry-wide declining stock values, investors may seek to pursue non-biotech investments with steadier returns. Failure to secure any necessary financing in a timely manner or on favorable terms could have a material adverse effect on our operations, financial condition or stock price or could require us to delay or abandon development or commercialization plans.

If securities or industry analysts cease to publish or publish inaccurate or unfavorable research about our business, our share price and trading volume could decline.

The trading market for our common shares depends in part on the research and reports that securities or industry analysts publish about us or our business. If one or more of the analysts who cover us downgrades our common shares or publishes inaccurate or unfavorable research about our business, our share price may decline. If one or more of these analysts ceases coverage of our company or fails to publish reports on us regularly, demand for our shares could decrease, which might cause our share price and trading volume to decline.

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If we do not achieve our projected development and financial goals in the timeframes we announce and expect, the commercialization of our product candidates may be delayed and, as a result, our stock price may decline.

We estimate the timing of the accomplishment of various scientific, clinical, regulatory, and other product development goals, along with financial and other business-related milestones. From time to time, we publicly announce the expected timing of some of these milestones along with guidance as to our cash runway. These milestones may include the commencement or completion of scientific studies, clinical trials, the submission of regulatory filings and interactions with regulatory authorities, and approval timelines for commercial sales. All these milestones are based on a variety of assumptions that may prove to be untrue. The timing of our actual achievement of these milestones can vary dramatically compared to our estimates, in many cases for reasons beyond our control. If we do not meet these milestones, including those that are publicly announced, the development and commercialization of our products may be delayed, our business could suffer reputational harm and, as a result, our stock price may decline

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Item 2.Unregistered Sales of Equity Securities, ~~and~~ Use of Proceeds, and Issuer Purchases of Equity Securities

None.

Item 3.Defaults Upon Senior Securities

None.

Item 4.Mine Safety Disclosures

Not applicable.

Item 5.Other Information

During the three months ended March 31, 2024, no director or officer of the Company adopted or terminated a “Rule 10b5-1 trading arrangement” or “non-Rule 10b5-1 trading arrangement,” as each term is defined in Item 408(a) of Regulation S-K.

~~None.~~

Item 6.Exhibits

See the Exhibit Index immediately preceding the signature page to this Quarterly Report on Form 10-Q for a list of exhibits filed or furnished with this report, which Exhibit Index is incorporated herein by reference.

6469

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EXHIBIT INDEX




31.1*	Certification of Chief Executive Officer pursuant to Rule 13a-14(a) or 15d-14(a) of the Securities and Exchange Act of 1934, as amended, as adopted pursuant to Section 302 of the Sarbanes-Oxley Act of 2002.

31.2*	Certification of Chief Financial Officer pursuant to Rule 13a-14(a) or 15d-14(a) of the Securities and Exchange Act of 1934, as amended, as adopted pursuant to Section 302 of the Sarbanes-Oxley Act of 2002.

32.1±	Certification of Principal Executive Officer and Principal Financial Officer pursuant to 18 U.S.C. Section 1350, as adopted pursuant to Section 906 of the Sarbanes-Oxley Act of 2002.

101*	The following financial information from our Quarterly Report on Form 10-Q for the period ended March 31, 2024, filed with the Securities and Exchange Commission on May 7, 2024, is formatted in Inline Extensible Business Reporting Language (“iXBRL”): (i) Consolidated Balance Sheets; (ii) Consolidated Statements of Operations and Comprehensive Loss; (iii) Consolidated Statements of Shareholders’ Equity; (iv) Consolidated Statements of Cash Flows; and (v) Notes to Consolidated Financial Statements (tagged as blocks of text)

104*	The cover page from our Quarterly Report on Form 10-Q for the period ended March 31, 2024, filed with the Securities and Exchange Commission on May 7, 2024, is formatted in Inline Extensible Business Reporting Language (“iXBRL”)

* Filed herewith.

± Furnished herewith.

t Indicates a management contract or compensatory plan or arrangement.

~~EXHIBIT INDEX~~

3.1Amended Articles of Association (incorporated by reference to Exhibit 1.1 of the Company’s annual report on Form 10-K for the year ended December 31, 2016 (file no. 0001-36294) filed with the Securities and Exchange Commission).

~~10.1*Letter agreement dated October 26, 2017 between uniQure N.V. and Matthew Kapusta, amending Mr. Kapusta’s employment agreement dated December 9, 2014, as amended.~~

~~31.1*Rule 13a-14(a)/15d-14(a) Certification of Principal Executive Officer~~

~~31.2*Rule 13a-14(a)/15d-14(a) Certification of Principal Financial Officer~~

~~32.1±Section 1350 Certification of Principal Executive Officer and Principal Financial Officer~~

101*The following financial information from our Quarterly Report on Form 10-Q for the period ended September 30, 2017, filed with the Securities and Exchange Commission on August 8, 2017 is formatted in Extensible Business Reporting Language (“XBRL”): (i) Consolidated Balance Sheets; (ii) Consolidated Statements of Operations and Comprehensive Loss; (iii) Consolidated Statements of Shareholders’ Equity; (iv) Consolidated Statements of Cash Flows; and (v) Notes to Consolidated Financial Statements (tagged as blocks of text)

*Filed herewith.

~~±Furnished herewith~~

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SIGNATURE

Pursuant to the requirements of the Securities Exchange Act of 1934, as amended, the registrant has duly caused this report to be signed on its behalf by the undersigned thereunto duly authorized.


	UNIQURE N.V.
~~UNIQURE, N.V.~~

	By: /s/ Matthew Kapusta Matthew Kapusta Chief Executive Officer (Principal Executive ~~Officer and Principal Financial~~ Officer)


	By: /s/ Christian Klemt Christian Klemt Chief ~~Accounting~~Financial Officer (Principal Financial Officer)

~~Dated~~ ~~November 1, 2017~~Date: May 7, 2024

6671


☒	QUARTERLY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934

	For the quarterly period ended ~~September 30, 2017~~ March 31, 2024

	OR

☐	TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934

	For the transition period from _______ to _______

	Commission file number: 001-36294


Title of each class:	Trading Symbol(s)	Name of each exchange on which registered
Ordinary Shares, par value €0.05	QURE	The Nasdaq Stock Market LLC (The Nasdaq Global Select Market)

			Page
	PART I – FINANCIAL INFORMATION

Item 1	Financial Statements	4 2

Item 2	Management’s Discussion and Analysis of Financial Condition and Results of Operations	25 16

Item 3	Quantitative and Qualitative Disclosures About Market Risk	41 28

Item 4	Controls and Procedures	41
		28

	PART II – OTHER INFORMATION

Item 1	Legal Proceedings	42 29

Item 1A	Risk Factors	42 29

Item 2	Unregistered Sales of Equity Securities, ~~and~~ Use of Proceeds, and Issuer Purchases of Equity Securities	64 69

Item 3	Defaults Upon Senior Securities	64 69

Item 4	Mine Safety Disclosures	64 69

Item 5	Other Information	64 69

Item 6	Exhibits	64 69


	March 31,		December 31,
	2024		2023

	(in thousands, except share and per share amounts)
Current assets
Cash and cash equivalents	$	243,062	$	241,360
Current investment securities		312,621		376,532
Accounts receivable		10,717		4,193
Inventories, net		7,672		12,024
Prepaid expenses		18,839		15,089
Other current assets and receivables		3,092		2,655
Total current assets		596,003		651,853
Non-current assets
Property, plant and equipment, net of accumulated depreciation of $57.8 million as of March 31, 2024 and $55.7 million as of December 31, 2023		44,554		46,548
Operating lease right-of-use assets		27,695		28,789
Intangible assets, net, including in-process research and development asset of $57.8 million as of March 31, 2024 and $59.1 million as of December 31, 2023		59,111		60,481
Goodwill		25,795		26,379
Deferred tax assets, net		11,594		12,276
Other non-current assets		5,298		5,363
Total non-current assets		174,047		179,836
Total assets	$	770,050	$	831,689
Current liabilities
Accounts payable	$	5,231	$	6,586
Accrued expenses and other current liabilities		22,658		30,534
Current portion of contingent consideration		27,587		28,211
Current portion of operating lease liabilities		7,997		8,344
Total current liabilities		63,473		73,675
Non-current liabilities
Long-term debt		102,120		101,749
Liability from royalty financing agreement		405,398		394,241
Operating lease liabilities, net of current portion		26,983		28,316
Contingent consideration, net of current portion		14,625		14,795
Deferred tax liability, net		7,376		7,543
Other non-current liabilities		3,321		3,700
Total non-current liabilities		559,823		550,344
Total liabilities		623,296		624,019
Commitments and contingencies
Shareholders' equity
Ordinary shares, €0.05 par value: 80,000,000 shares authorized as of March 31, 2024 and December 31, 2023 and 48,492,357 and 47,833,830 ordinary shares issued and outstanding as of March 31, 2024 and December 31, 2023, respectively		2,919		2,883
Additional paid-in-capital		1,155,904		1,148,749
Accumulated other comprehensive loss		(56,042)		(53,553)
Accumulated deficit		(956,027)		(890,409)
Total shareholders' equity		146,754		207,670
Total liabilities and shareholders' equity	$	770,050	$	831,689


	September 30,		December 31,
	2017		2016
	in thousands, except share and per share amounts
Current assets
Cash and cash equivalents	$	88,934	$	132,496
Accounts receivable and accrued income		—		3,680
Accounts receivable and accrued income from related party		1,945		5,500
Prepaid expenses		689		996
Other current assets		747		1,274
Total current assets		92,315		143,946
Non-current assets
Property, plant and equipment, net		34,653		35,702
Intangible assets, net		9,027		8,324
Goodwill		522		465
Other non-current assets		2,469		1,828
Total non-current assets		46,671		46,319
Total assets	$	138,986	$	190,265
Current liabilities
Accounts payable	$	2,987	$	5,524
Accrued expenses and other current liabilities		10,165		9,766
Current portion of long-term debt		6,232		605
Current portion of deferred rent		724		684
Current portion of deferred revenue		4,249		6,142
Current portion of contingent consideration		1,017		—
Total current liabilities		25,374		22,721
Non-current liabilities
Long-term debt, net of current portion		14,353		19,631
Deferred rent, net of current portion		8,829		6,781
Deferred revenue, net of current portion		67,863		75,612
Contingent consideration, net of current portion		2,593		1,838
Other non-current liabilities		367		51
Total non-current liabilities		94,005		103,913
Total liabilities		119,379		126,634
Commitments and contingencies (see note 14)
Shareholders' equity
Ordinary shares, €0.05 par value: 60,000,000 shares authorized at September 30, 2017 and December 31, 2016 and 25,635,849 and 25,257,420 shares issued and outstanding at September 30, 2017 and December 31, 2016, respectively.		1,612		1,593
Additional paid-in-capital		471,648		464,653
Accumulated other comprehensive loss		(5,809)		(6,557)
Accumulated deficit		(447,844)		(396,058)
Total shareholders' equity		19,607		63,631
Total liabilities and shareholders' equity	$	138,986	$	190,265


	Three months ended September 30,				Nine months ended September 30,
	2017		2016		2017		2016
	in thousands, except share and per share amounts
License revenues	$	—	$	246	$	8	$	736
License revenues from related party		1,124		993		3,060		2,977
Collaboration revenues		—		1,850		4,638		4,835
Collaboration revenues from related party		1,136		4,132		2,817		7,419
Total revenues		2,260		7,221		10,523		15,967
Operating expenses:
Research and development expenses		(20,103)		(16,604)		(53,963)		(52,531)
Selling, general and administrative expenses		(5,584)		(5,113)		(17,352)		(20,245)
Total operating expenses		(25,687)		(21,717)		(71,315)		(72,776)
Other income		14,413		336		14,995		1,256
Other expense		(261)		—		(2,901)		—
Loss from operations		(9,275)		(14,160)		(48,698)		(55,553)
Interest income		10		14		33		51
Interest expense		(577)		(507)		(1,583)		(1,685)
Foreign currency gains / (losses), net		(681)		(496)		(1,845)		(1,764)
Other non-operating income, net		—		54		29		701
Loss before income tax expense		(10,523)		(15,095)		(52,064)		(58,250)
Income tax benefit / (expense)		278		(177)		278		(401)
Net loss	$	(10,245)	$	(15,272)	$	(51,786)	$	(58,651)
Other comprehensive loss, net of income tax:
Foreign currency translation adjustments net of tax impact of $0.3 million and $(0.2) million for the three months ended September 30, 2017 and 2016, respectively, and $0.3 million and $(0.4) million for the nine months ended September 30, 2017 and 2016, respectively.		22		2,801		748		3,380
Total comprehensive loss	$	(10,223)	$	(12,471)	$	(51,038)	$	(55,271)

Basic and diluted net loss per ordinary share	$	(0.40)		(0.61)		(2.03)		(2.35)
Weighted average shares used in computing basic and diluted net loss per ordinary share		25,632,642		25,142,660		25,546,225		24,972,839


						Accumulated
				Additional		other				Total
	Ordinary shares			paid-in		comprehensive		Accumulated		shareholders’
	No. of shares	Amount		capital		income/(loss)		deficit		equity
	in thousands, except share and per share amounts
Balance at December 31, 2016	25,257,420	$	1,593	$	464,653	$	(6,557)	$	(396,058)	$	63,631
Loss for the period	—		—		—		—		(51,786)		(51,786)
Other comprehensive income	—		—		—		748		—		748
Exercise of share options	294,929		15		1,021		—		—		1,036
Shares distributed during the period	83,500		4		(4)		—		—		—
Share-based compensation expense	—		—		5,978		—		—		5,978
Balance at September 30, 2017	25,635,849	$	1,612	$	471,648	$	(5,809)	$	(447,844)	$	19,607


						Accumulated
				Additional		other				Total
	Ordinary shares			paid-in		comprehensive		Accumulated		shareholders’
	No. of shares	Amount		capital		loss		deficit		equity
	(in thousands, except share and per share amounts)
Balance at December 31, 2022	46,968,032	$	2,838	$	1,113,393	$	(58,291)	$	(581,931)	$	476,009
Loss for the period	—		—		—		—		(77,227)		(77,227)
Other comprehensive income	—		—		—		5,797		—		5,797
Exercises of share options	10,055		1		86		—		—		87
Restricted and performance share units distributed during the period	566,091		30		(30)		—		—		—
Share-based compensation expense	—		—		8,061		—		—		8,061
Issuance of ordinary shares relating to employee stock purchase plan	2,495		—		44		—		—		44
Balance at March 31, 2023	47,546,673	$	2,869	$	1,121,554	$	(52,494)	$	(659,158)	$	412,771

Balance at December 31, 2023	47,833,830	$	2,883	$	1,148,749	$	(53,553)	$	(890,409)	$	207,670
Loss for the period	—		—		—		—		(65,618)		(65,618)
Other comprehensive loss, net	—		—		—		(2,489)		—		(2,489)
Restricted share units distributed during the period	658,527		36		(36)		—		—		—
Share-based compensation expense	—		—		7,191		—		—		7,191
Balance at March 31, 2024	48,492,357	$	2,919	$	1,155,904	$	(56,042)	$	(956,027)	$	146,754


	At March 31, 2024
	Amortized cost		Gross unrealized holding gains		Gross unrealized holding losses		Estimated fair value

	(in thousands)
Current investments:
Government debt securities (held-to-maturity)	$	312,621	$	12	$	—	$	312,633
Total	$	312,621	$	12	$	—	$	312,633

	At December 31, 2023
	Amortized cost		Gross unrealized holding gains		Gross unrealized holding losses		Estimated fair value

	(in thousands)
Current investments:
Government debt securities (held-to-maturity)	$	376,532	$	139	$	—	$	376,671
Total	$	376,532	$	139	$	—	$	376,671


	Quoted prices in active markets (Level 1)		Significant other observable inputs (Level 2)		Significant unobservable inputs (Level 3)		Total		Classification in consolidated balance sheets
		in thousands
At December 31, 2016
Assets:
Cash and cash equivalents	$	132,496	$	—	$	—	$	132,496
Total assets		132,496		—		—		132,496
Liabilities:
Derivative financial instruments - debt		—		—		11		11	Accrued expenses and other current liabilities
Derivative financial instruments - related party		—		—		51		51	Other non-current liabilities
Contingent consideration		—		—		1,838		1,838
Total liabilities	$	—	$	—	$	1,900	$	1,900
At September 30, 2017
Assets:
Cash and cash equivalents	$	88,934	$	—	$	—	$	88,934
Total assets		88,934		—		—		88,934
Liabilities:
Derivative financial instruments - debt		—		—		3		3	Accrued expenses and other current liabilities
Derivative financial instruments - related party		—		—		35		35	Other non-current liabilities
Contingent consideration		—		—		3,610		3,610
Total liabilities	$	—	$	—	$	3,648	$	3,648



			Derivative
	Contingent		financial
	consideration		instruments		Total
	in thousands
Balance at December 31, 2016	$	1,838	$	62	$	1,900
(Gains) / losses recognized in profit or loss		2,704		(29)		2,675
Amounts due (presented in Accrued expenses and other current liabilities)		(1,181)		—		(1,181)
Currency translation effects		249		5		254
Balance at September 30, 2017	$	3,610	$	38	$	3,648


	Quoted prices in active markets (Level 1)		Significant other observable inputs (Level 2)		Significant unobservable inputs (Level 3)		Total		Classification in Consolidated balance sheets

		(in thousands)
At December 31, 2023
Assets:
Cash and cash equivalents	$	241,360	$	—	$	—	$	241,360	Cash and cash equivalents
Restricted cash		3,184		—		—		3,184	Other non-current assets
Total assets	$	244,544	$	—	$	—	$	244,544
Liabilities:
Contingent consideration		—		—		43,006		43,006	Contingent consideration
Consideration for post-acquisition services		—		—		457		457	Other non-current liabilities
Total liabilities	$	—	$	—	$	43,463	$	43,463
At March 31, 2024
Assets:
Cash and cash equivalents	$	243,062	$	—	$	—	$	243,062	Cash and cash equivalents
Restricted cash		3,167		—		—		3,167	Other non-current assets
Total assets	$	246,229	$	—	$	—	$	246,229
Liabilities:
Contingent consideration		—		—		42,212		42,212	Contingent consideration
Consideration for post-acquisition services		—		—		498		498	Other non-current liabilities
Total liabilities	$	—	$	—	$	42,710	$	42,710


		~~September 30,~~
	~~2017~~
	~~in thousands~~
~~Change in fair value~~
~~Moving out of all milestones by 6 months~~	$	~~(231)~~
~~Increasing the POS for the first milestone by 20%~~		~~1,103~~
~~Decreasing the POS for the first milestone by 20%~~		~~(1,103)~~
~~Reducing the discount rate from 14.5% to 4.5%~~		~~1,004~~
~~Increasing the discount rate from 14.5% to 24.5%~~		~~(590)~~


		~~December 31,~~
	~~2016~~
	~~in thousands~~
~~Change in fair value~~
~~Moving out of all milestones by 6 months~~	$	~~(209)~~
~~Increasing the POS for the first milestone by 20%~~		~~367~~
~~Decreasing the POS for the first milestone by 20%~~		~~(367)~~
~~Reducing the discount rate from 30% to 20%~~		~~638~~
~~Increasing the discount rate from 30% to 40%~~		~~(309)~~


	Amount of
	contingent
	consideration
		2024
	(in thousands)
Balance at December 31, 2023	$	43,006
Change in fair value (presented within research and development expenses)		165
Currency translation effects		(959)
Balance at March 31, 2024	$	42,212


	March 31,		December 31,
	2024		2023

	(in thousands)
Raw materials	$	6,331	$	7,157
Work in progress		1,341		4,109
Finished goods		—		758
Inventories	$	7,672	$	12,024


	Accrued
	termination
	benefits
	in thousands
Balance at December 31, 2016	$	1,148
Accrued through profit and loss		1,677
Payments		(1,812)
Currency translation effects		88
Balance at September 30, 2017	$	1,101


		Amount of liability
		(in thousands)
Balance as of December 31, 2023 (includes $1.4 million presented as "Accrued expenses and other current liabilities)	$	395,678
Royalty payments to Purchaser		(1,437)
Liability owed to the Purchaser (presented as "Accrued expense and other current liabilities")		(1,205)
Interest expense for the period		12,362
Liability related to the royalty financing agreement	$	405,398



			Weighted-average
	Unrecognized		remaining
	compensation		period for
	costs		recognition
Award type	in thousands		in years
Share options	$	7,041	2.52
Restricted share units		4,003	1.64
Performance share units		3,747	1.84
Total	$	14,791	2.11


	Unrecognized		Weighted average
	share-based		remaining
	compensation		period for
	expense		recognition
	(in thousands)		(in years)
Award type
Share options	$	20,743	2.56
Restricted share units		27,981	1.99
Performance share units		80	0.61
Total	$	48,804	2.23


	2014 plan
		Weighted average
	Options	exercise price

Outstanding at December 31, 2016	1,812,766	$	12.47
Granted	949,350	$	6.17
Forfeited	(348,697)	$	7.95
Expired	(164,106)	$	14.46
Exercised	(8,125)	$	7.49
Outstanding at September 30, 2017	2,241,188	$	10.38
Fully vested and exercisable	820,522	$	12.58
Outstanding and expected to vest	1,420,666	$	9.10

Total weighted average grant date fair value of options issued during the period (in $ million)		$	3.5
Grants during the period to directors and officers	641,250	$	6.43
Proceeds from option sales (in $ million)			—


	Options
	Number of	Weighted average
	ordinary shares	exercise price

Outstanding at December 31, 2023	4,974,030		23.25
Granted	930,900	$	5.59
Forfeited	(71,437)	$	21.26
Expired	(11,584)	$	37.61
Outstanding at March 31, 2024	5,821,909	$	20.42
Thereof, fully vested, and exercisable on March 31, 2024	3,054,242	$	25.70
Thereof, outstanding and expected to vest after March 31, 2024	2,767,667	$	14.60
Outstanding and expected to vest after December 31, 2023	2,098,557	$	23.38


	Three months ended March 31,
Assumptions	2024	2023
Expected volatility	70%	70%
Expected terms	10 years	10 years
Risk free interest rate	4.32%	4.10%
Expected dividend yield	0%	0%


	Three months ended September 30,		Nine months ended September 30,
Assumptions	2017	2016	2017	2016
Expected volatility	80%	75%	75% - 80%	75%
Expected terms (in years)	10 years	10 years	10 years	10 years
Risk free interest rate	2.40% - 2.48%	1.52% - 1.89%	2.40% - 2.81%	0.16% - 1.96%
Expected dividends	0%	0%	0%	0%


		RSU
			Weighted average
			grant-date fair
	Number of shares		value
Non-vested at December 31, 2016		307,063	$	9.11
Granted		428,350	$	6.00
Vested		(25,000)	$	18.21
Forfeited		(38,550)	$	7.15
Non-vested at September 30, 2017		671,863	$	6.90

Total weighted average grant date fair value of RSUs issued during the period (in $ million)			$	2.6
Grants during the period to directors and officers		255,000	$	5.95


	Other plans
			Weighted average
	Options		exercise price

Outstanding at December 31, 2016		187,500	$	17.93
Granted		300,000	$	6.90
Expired		(62,500)	$	27.82
Outstanding at September 30, 2017		425,000	$	8.69
Fully vested and exercisable		39,062	$	12.98
Outstanding and expected to vest		385,938	$	8.25

Total weighted average grant date fair value of options issued during the period (in $ million)			$	1.2


	2012 plan
		Weighted average
	Options	exercise price

Outstanding at December 31, 2016	483,006	€	5.13
Exercised	(286,804)	€	3.07
Forfeited	(5,000)	€	3.07
Expired	(9,000)	€	3.07
Outstanding, fully vested and exercisable at September 30, 2017	182,202	€	8.52


	Lexington		Amsterdam		Total
	in thousands
2017 (three months remaining)	$	453	$	—	$	453
2018		1,849		1,963		3,812
2019		1,903		1,963		3,866
2020		1,956		1,963		3,919
2021 and beyond		6,899		21,595		28,494
Total minimum lease payments	$	13,060	$	27,484	$	40,544

Deferred rent related to lease incentives	$	5,739	$	3,814	$	9,553
Current portion		724		—		724


			Less than 1		Between 1		Between 2
	Undefined		year		and 2 years		and 5 years		Over 5 years		Total
	in thousands
Debt obligations (including $3.6 million interest payments)	$	—	$	7,888	$	8,848	$	6,869	$	—	$	23,605
Operating lease obligations		—		3,308		3,852		11,877		21,507		40,544
Contingent consideration (nominal amount)		15,949		—		—		—		—		15,949
Total	$	15,949	$	11,196	$	12,700	$	18,746	$	21,507	$	80,098