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As filed with the Securities and Exchange Commission on September 6, 2018August 5, 2022

Registration No. 333-      


UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
Washington,WASHINGTON, D.C. 20549

FORM S-3
REGISTRATION STATEMENT
UNDER
THE SECURITIES ACT OF 1933

Protagonist Therapeutics, Inc.
PROTAGONIST THERAPEUTICS, INC.
(Exact name of registrant as specified in its charter)

Delaware

(State or other jurisdiction of

incorporation or organization)
001-37852
(Commission File Number)
98-0505495

(I.R.S. Employer

Identification Number)

7707 Gateway Boulevard, Suite 140
Newark, CaliforniaCA 94560-1160
(510) 474-0170


(Address, including zip code, and telephone number, including

area code, of registrant'sregistrant’s principal executive offices)



Dinesh V. Patel, Ph.D.
President and Chief Executive Officer
Protagonist Therapeutics, Inc.
7707 Gateway Boulevard, Suite 140
Newark, CaliforniaCA 94560-1160
(510) 474-0170


(Name, address, including zip code, and telephone number, including

area code, of agent for service)



CopiesWith copies to:

Ryan A. Murr
Branden C. Berns
Gibson, Dunn & Crutcher LLP
555 Mission Street
San Francisco, CA 94105-0921
(415) 393-8373
Matthew Gosling
Executive Vice President, General Counsel
Protagonist Therapeutics, Inc.
7707 Gateway Boulevard, Suite 140
Newark, CA 94560-1160
(510) 474-0170
Kenneth L. Guernsey
Michael E. Tenta
Josh Seidenfeld
Cooley LLP
3175 Hanover Street
Palo Alto, CA 94304
(650) 843-5000



Approximate date of commencement of proposed sale to the public:
From time to time after this Registration Statementregistration statement becomes effective.

If the only securities being registered on this Form are being offered pursuant to dividend or interest reinvestment plans, please check the following box. o

If any of the securities being registered on this Form are to be offered on a delayed or continuous basis pursuant to Rule 415 under the Securities Act of 1933, as amended, other than securities offered only in connection with dividend or interest reinvestment plans, check the following box.    ý

box: ☒

If this Form is filed to register additional securities for an offering pursuant to Rule 462(b) under the Securities Act, please check the following box and list the Securities Act registration statement number of the earlier effective registration statement for the same offering. o

If this Form is a post-effective amendment filed pursuant to Rule 462(c) under the Securities Act, check the following box and list the Securities Act registration statement number of the earlier effective registration statement for the same offering. o

If this Form is a registration statement pursuant to General Instruction I.D. or a post-effective amendment thereto that shall become effective upon filing with the Commission pursuant to Rule 462(e) under the Securities Act, check the following box. o

If this Form is a post-effective amendment to a registration statement filed pursuant to General Instruction I.D. filed to register additional securities or additional classes of securities pursuant to Rule 413(b) under the Securities Act, check the following box. o

Indicate by check mark whether the registrant is a large accelerated filer, an accelerated filer, a non-accelerated filer, a smaller reporting company, or an emerging growth company. See the definitions of "large“large accelerated filer," "accelerated” “accelerated filer," "smaller” “smaller reporting company," and "emerging“emerging growth company"company” in Rule 12b-2 of the Exchange Act.

(Check one):
Large accelerated filero
Accelerated filerý
Non-accelerated filero
(Do not check if a
smaller reporting company)
Smaller reporting companyo


Emerging growth companyý


If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 7(a)(2)(B) of the Securities Act. ý

CALCULATION OF REGISTRATION FEE

        
 
Title of Each Class of Securities
to be Registered

 Amount to be
Registered(1)

 Proposed Maximum
Offering Price Per
Unit(2)

 Proposed Maximum
Aggregate Offering
Price(2)

 Amount of
Registration Fee(2)

 

Common Stock, par value $0.00001 per share

 2,750,000 $9.64 $26,510,000 $3,301

 

(1)
Consists of 2,750,000 shares of common stock that may be issued upon the exercise of outstanding warrants. Pursuant to Rule 416 under the Securities Act of 1933, as amended, the shares of common stock being registered hereunder include such indeterminate number of shares of common stock as may be issuable with respect to the shares of common stock being registered hereunder as a result of stock splits, stock dividends or similar transactions.

(2)
Pursuant to Rule 457(c), calculated on the basis of the average of the high and low prices per share of the registrant's Common Stock reported on the Nasdaq Global Market on September 4, 2018, a date within five business days prior to the filing of this registration statement.

The Registrantregistrant hereby amends this registration statement on such date or dates as may be necessary to delay its effective date until the Registrantregistrant shall file a further amendment thatwhich specifically states that this registration statement shall thereafter become effective in accordance with Section 8(a) of the Securities Act of 1933, as amended, or until this registration statement shall become effective on such date as the Securities and Exchange Commission, acting pursuant to said Section 8(a), may determine.





The information contained in this prospectus is not complete and may be changed. We may not sell these securities or accept an offer to buy these securities until the registration statement filed with the Securities and Exchange Commission is effective. This prospectus is not an offer to sell these securities and it is not soliciting offers to buy these securities in any statejurisdiction where such offer or sale is not permitted.


SUBJECT TO COMPLETION, DATED SEPTEMBER 6, 2018Subject to Completion, Dated August 5, 2022

PROSPECTUS

[MISSING IMAGE: lg_protagonist-pn.jpg]
2,750,000 SharesCOMMON STOCK


LOGOPREFERRED STOCK


Common StockDEBT SECURITIES

        This prospectus relates to the disposition from
WARRANTS
UNITS

From time to time, ofwe may issue, in one or more series or classes, up to 2,750,000 sharesan aggregate of $300,000,000 of our common stock, issuable uponpreferred stock, debt securities, warrants and/or units, at prices and on terms that we will determine at the exercise of outstanding warrants, which are held by the selling stockholders named in this prospectus. We are not selling any common stock under this prospectus and will not receive anytime of the proceeds fromoffering.
This prospectus provides you with a general description of the salesecurities we may offer. Each time we offer securities, we will provide specific terms of shares by the selling stockholders. We will, however, receive the net proceeds of any warrants exercised for cash.

        The selling stockholders identified in this prospectus, or their permitted transferees or other successors-in-interest that may be identifiedsecurities offered in a supplement to this prospectus. We may also authorize one or more free writing prospectuses to be provided to you in connection with these offerings. The prospectus supplement and any related free writing prospectus may also add, update or if required, a post-effective amendment to the registration statement of whichchange information contained in this prospectus. We may not sell any securities under this prospectus without delivery of the applicable prospectus supplement. If information in any prospectus supplement is a part, may offerinconsistent with the shares from time to time through public or private transactions at fixed prices, at prevailing market prices, at varying prices determined atinformation in this prospectus, then the timeinformation in that prospectus supplement will apply and will supersede the information in this prospectus.

You should read this prospectus, the applicable prospectus supplement and any related free writing prospectus carefully, as well as any documents incorporated by reference, before you invest in any of sale, or at privately negotiated prices. We provide more information about how the selling stockholders may sell theirsecurities being offered.
Our shares of common stock in the section entitled "Plan of Distribution" beginning on page 12 of this prospectus. We have agreed to pay certain expenses incurred in connection with the registration of these shares, however, we will not be paying any underwriting discounts or commissions in connection with any offering of common stock under this prospectus.

        Our common stock isare listed on the NASDAQThe Nasdaq Global Market under the symbol "PTGX." On September 4, 2018, the“PTGX.” The last reported sale price of our common stock on the NASDAQThe Nasdaq Global Market on August 2, 2022 was $9.51$10.63 per share.

We recommend that you obtain current market quotations for our common stock prior to making an investment decision.

Investing in our common stocksecurities involves a high degree of risk. You should review carefully the risks and uncertainties incorporated by reference hereindescribed under the heading "Risk Factors"“Risk Factors” contained in this prospectus beginning on page 5 of this4 and any applicable prospectus supplement, and under similar headings in the other documents that are filed after the date hereof and incorporated by reference into this prospectus.

Neither the Securities and Exchange Commission nor any state securities commission has approved or disapproved of these securities or determined if this prospectus is truthful or complete. Any representation to the contrary is a criminal offense.

The date

Prospectus dated            , 2022


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ABOUT THIS PROSPECTUS
This prospectus is a part of a registration statement on Form S-3 that we filed with the Securities and Exchange Commission (the “SEC” or the “Commission”) utilizing a “shelf” registration process. Under this shelf registration process, we may sell any combination of the securities described in this prospectus is                    , 2018.


Tablein one or more offerings up to a total dollar amount of Contents


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$300,000,000. This prospectus provides you with a general description of the securities we may offer.

Page

About this Prospectus

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Summary

1

Risk Factors

5

Forward-Looking Statements

5

Use of Proceeds

7

Selling Stockholders

8

Plan of Distribution

12

Legal Matters

15

Experts

15

Where You Can Find More Information

15

Incorporation of Certain Information by Reference

16


ABOUT THIS PROSPECTUS

        You should carefully readEach time we sell securities under this prospectus, anywe will provide a prospectus supplement that will contain specific information about the terms of that offering. We may also authorize one or more free writing prospectuses to be provided to you that may contain material information relating to these offerings. The prospectus supplement and any related free writing prospectus that we may authorize to be provided to you may also add, update or change information contained in this prospectus or in any documents that we have incorporated by reference into this prospectus. You should carefully read both this prospectus and any prospectus supplement together with the additional information described under "Wherethe headings “Where You Can Find More Information," before buying anyInformation” and “Incorporation of the securities being offered.

        You should rely only on the information contained in or incorporatedCertain Information by reference in this prospectus (as supplemented or amended). Reference.”

We have not authorized anyone to provide you with different information. This prospectus may be used only in jurisdictions where offers and sales of these securities are permitted. Theany information other than that contained in this prospectus, as well as the information filed previously with the SEC, andor incorporated by reference in this prospectus is accurate only as of the date of the document containing the information, regardless of the time of delivery of this prospectus orand any applicable prospectus supplement, oralong with the information contained in any salefree writing prospectuses we have authorized for use in connection with a specific offering. We take no responsibility for, and can provide no assurance as to the reliability of, our common stock.

any other information that others may give you. This prospectus containsis an offer to sell only the securities offered hereby, but only under circumstances and incorporates by reference market data and industry statistics and forecasts that are based on independent industry publications and other publicly available information. Although we believe that these sources are reliable, wein jurisdictions where it is lawful to do not guarantee the accuracy or completeness of this information and we have not independently verified this information. Although we are not aware ofso. This prospectus, any misstatements regarding the market and industry data presented inapplicable supplement to this prospectus and the documents incorporated herein by reference, these estimates involve risks and uncertainties and are subject to change based on various factors, including those discussed under the heading "Risk Factors" contained in the applicable prospectus supplement andor any related free writing prospectus and under similar headingsdo not constitute an offer to sell or the solicitation of an offer to buy any securities other than the registered securities to which they relate, nor do this prospectus, any applicable supplement to this prospectus or any related free writing prospectus constitute an offer to sell or the solicitation of an offer to buy securities in the other documents that are incorporated by reference into this prospectus. Accordingly, investorsany jurisdiction to any person to whom it is unlawful to make such offer or solicitation in such jurisdiction.

You should not place undue reliance on this information.

        This prospectus contains summaries of certain provisionsassume that the information contained in some of the documents described herein, but reference is made to the actual documents for complete information. All of the summaries are qualified in their entirety by the actual documents. Copies of some of the documents referred to herein have been filed, will be filed or will be incorporated by reference as exhibits to the registration statement of which this prospectus is a part, and you may obtain copies of those documents as described below under the section entitled "Where You Can Find More Information."

        Except as otherwise indicated herein or as the context otherwise requires, references in this prospectus to "Protagonist," "the company," "we," "us," "our" and similar references refer to Protagonist Therapeutics, Inc., a corporation under the laws of the State of Delaware.

        This prospectus and the information incorporated herein by reference include trademarks, service marks and trade names owned by us or other companies. All trademarks, service marks and trade names included or incorporated by reference into this prospectus, any applicable prospectus supplement or any related free writing prospectus areis accurate on any date subsequent to the propertydate set forth on the front of their respective owners.

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PROSPECTUS SUMMARY

This summary highlights selectedthe document or that any information contained elsewhere in this prospectus orwe have incorporated by reference herein and does not contain allis correct on any date subsequent to the date of the information that you need to consider in making your investment decision. You should carefully read the entiredocument incorporated by reference, even though this prospectus, any applicable prospectus supplement andor any related free writing prospectus includingis delivered, or securities are sold, on a later date.

Unless the risks of investingcontext otherwise requires, we use the terms “Protagonist,” the “company,” “we,” “us,” and “our” in this prospectus to refer to Protagonist Therapeutics, Inc. and, where appropriate, our securities discussed under the heading "Risk Factors" contained in the applicable prospectus supplement and any related free writingsubsidiaries.

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CAUTIONARY STATEMENT CONCERNING FORWARD-LOOKING STATEMENTS
This prospectus and under similar headings in the other documents that we have filed with the SEC that are incorporated by reference into this prospectus. You should also carefully read the information incorporated by reference into this prospectus, including our financial statements and related notes, and the exhibits to the registration statement of which this prospectus is a part, before making your investment decision.


Protagonist Therapeutics, Inc.

Overview

        We are a clinical stage biopharmaceutical company with a proprietary technology platform that enables the discovery and development of novel constrained peptide-based drug candidates that address significant unmet medical needs. Our product candidates are designed to affect critical steps in the biological pathways of particular diseases, for example, by blocking protein-protein interactions. We believe our peptide-based approach has advantages over alternative approaches such as small molecules and antibodies. Our clinical stage product candidates PTG-100 and PTG-200 are oral drugs that block biological pathways currently targeted by marketed injectable antibody drugs and offer targeted delivery to the gastrointestinal ("GI") tissue compartment. We believe that, as compared to antibody drugs, these product candidates have the potential to provide improved safety due to minimal exposure in the blood, increased convenience and compliance due to oral delivery, and the opportunity for the earlier introduction of targeted therapy.

        PTG-100, an oral, alpha-4-beta-7 ("a4b7") integrin antagonist, is being developed for potential treatment of inflammatory bowel disease ("IBD"), a GI disease consisting primarily of ulcerative colitis ("UC"), and Crohn's disease ("CD"). In March 2018, we announced the discontinuation of a global Phase 2b clinical trial for the treatment of moderate-to-severe UC. This decision followed a planned interim analysis by an independent Data Monitoring Committee ("DMC"). The interim data revealed an unusually high placebo rate of clinical remission that led to a futility decision and discontinuation of the trial. In August 2018, we announced that a re-read of the endoscopies from the study by the subcontractor of the contract research organization ("CRO") and a subsequent fully blinded re-read of the endoscopies by an independent third party confirmed that a subset of the initial endoscopy reads provided by the CRO were in error. If the re-read of endoscopy results had been utilized for the interim futility analysis, the trial would have continued. In addition, a pre-specified blinded histopathology analysis of colon biopsies supported the observations of clinical remission and endoscopy responses for PTG-100. Based on this entire analysis, we plan to discuss the next steps in advancing the clinical development of PTG-100 with the U.S. Food and Drug Administration ("FDA") and other global regulatory authorities in the second half of 2018.

        PTG-200 is a potential first-in-class oral, Interleukin-23 receptor ("IL-23R") antagonist for the treatment of IBD. It is currently in a Phase 1 healthy volunteer clinical study that was initiated in Australia in the fourth quarter of 2017. The IL-12/23 pathway blockade is an approach that has been validated through an FDA approved injectable antibody drug. We have entered into a worldwide license and collaboration agreement with Janssen Biotech, Inc. ("Janssen"), a Johnson & Johnson company, to co-develop and co-detail PTG-200 for all indications, including IBD. See the section below entitled "Janssen License and Collaboration Agreement" for additional information. In the fourth quarter of 2018, we expect an Investigational New Drug application ("IND") in the United States by Janssen that will support the initiation of a global Phase 2 study of PTG-200 in CD to be conducted in


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collaboration with Janssen. This IND filing would trigger a milestone payment from Janssen of $25 million under the Janssen License and Collaboration Agreement.

        Our novel peptides have potential applicability in a wide range of therapeutic areas in addition to GI diseases. We have applied our versatile platform outside of the GI disease areas and are developing PTG-300, an injectable hepcidin mimetic, for the potential treatment of anemia and iron overload in certain rare blood disorders, with an initial focus on beta-thalassemia. In the fourth quarter of 2017, we completed a successful Phase 1 study of PTG-300 in healthy volunteers which established pharmacodynamic-based clinical proof of concept. PTG-300 received an orphan drug designation from the FDA for the treatment of beta-thalassemia in March 2018. We completed discussions with U.S. and global regulatory agencies and filed an IND in the United States in the second quarter of 2018. We plan other global regulatory submissions to support the initiation of a global Phase 2 study of PTG-300 in patients with beta-thalassemia in the fourth quarter of 2018. Treatment of patients with myelodysplastic syndromes, hereditary hemochromatosis and polycythemia vera represent additional opportunities for future development of PTG-300.

        In addition, we continue to use our peptide technology platform to discover product candidates against targets in disease areas with significant unmet medical needs. In 2018, we anticipate initiating IND-enabling studies for a fourth product candidate, an oral peptide targeting a GI condition other than IBD.

        We have not generated any revenue from product sales and we do not currently have any products approved for commercialization. We have never been profitable and have incurred net losses in each year since inception and we do not anticipate that we will achieve sustained profitability in the near term. Our net losses were $8.7 million and $16.3 million for the three and six months ended June 30, 2018, respectively, and $15.0 million and $29.1 million for the three and six months ended June 30, 2017, respectively. As of June 30, 2018, we had an accumulated deficit of $117.9 million. Substantially all of our net losses have resulted from costs incurred in connection with our research and development programs and from general and administrative costs associated with our operations. We expect to continue to incur significant research, development and other expenses related to our ongoing operations and product development, including clinical development activities under the Janssen License and Collaboration Agreement, and as a result, we expect to continue to incur losses in the future as we continue our development of, and seek regulatory approval for, our product candidates.

Janssen License and Collaboration Agreement

        On May 26, 2017, we and Janssen, one of the Janssen Pharmaceutical Companies of Johnson & Johnson, entered into an exclusive license and collaboration agreement (the "Janssen License and Collaboration Agreement") for the clinical development, manufacture and potential commercialization of PTG-200 worldwide for the treatment of CD and UC. Janssen is a related party to us as Johnson & Johnson Innovation—JJDC, Inc., a significant stockholder of ours, and Janssen are both subsidiaries of Johnson & Johnson. During the third quarter of 2017, we received a non-refundable, upfront cash payment of $50.0 million from Janssen. We can also receive up to an additional $940.0 million in payments, including potential license option payments of $125.0 million at the Phase 2 interim analysis and $200.0 million at Phase 2 completion, and $615.0 million in other potential clinical development, regulatory approval and sales milestones. We and Janssen will co-develop and co-fund PTG-200 through Phase 2 clinical development. Janssen will be responsible for funding Phase 3 studies in CD and UC. We will receive double-digit tiered royalties on future net sales and retain the option to co-detail PTG-200 in the United States.


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Company Information

        Protagonist Pty Limited (Protagonist Australia) was incorporated in Australia in September 2001. We were incorporated under the laws of the State of Delaware in 2006, under the name Protagonist Therapeutics, Inc., and became the parent of Protagonist Australia pursuant to a transaction in which all of the issued and outstanding capital stock of Protagonist Australia was exchanged for shares of our common stock and Series A preferred stock. Our principal executive offices are located at 7707 Gateway Boulevard, Suite 140, Newark, California 94560. Our telephone number is (510) 474-0170. Our website address is www.protagonist-inc.com. The information contained in, or accessible through, our website does not constitute part of this prospectus, should not be relied on in determining whether to make an investment decision, and the inclusion of our website address in this prospectus is an inactive textual reference only.

        The Protagonist logo and other trademarks or service marks of Protagonist Therapeutics, Inc. appearing in this prospectus are the property of Protagonist Therapeutics, Inc. Other trademarks, service marks or trade names appearing in this prospectus are the property of their respective owners. We do not intend our use or display of other companies' trade names, trademarks or service marks to imply a relationship with, or endorsement or sponsorship of us by, these other companies.

Private Placement

        On August 6, 2018, we entered into a securities purchase agreement, pursuant to which we agreed to sell and issue to the selling stockholders warrants to purchase an aggregate of 2,750,000 shares of Common Stock (each, a "Warrant," and collectively, the "Warrants"). Each Warrant is exercisable from August 8, 2018 until August 8, 2023. Warrants to purchase 1,375,000 shares of Common Stock have an exercise price of $10.00 per share (the "Class A Warrants") and Warrants to purchase 1,375,000 shares of Common Stock have an exercise price of $15.00 per share (the "Class B Warrants"). The exercise price and number of shares of Common Stock issuable upon the exercise of the Warrants (the "Warrant Shares") is subject to adjustment in the event of any stock dividends and splits, reverse stock split, recapitalization, reorganization or similar transaction, as described in the Warrants. Under certain circumstances, the Warrants will be exercisable on a "cashless" basis.

        In connection with the issuance and sale of the Warrants, we granted certain registration rights with respect to the Warrants and the Warrant Shares, pursuant to a Registration Rights Agreement by and among us and the selling stockholders (the "Rights Agreement").

        As required by the Rights Agreement, we agreed to, among other things, (i) file a registration statement with the SEC to cover the resale of the Warrant Shares by the selling stockholders, (ii) use commercially reasonable efforts to cause such registration statement to become effective following the filing thereof and (iii) take all other actions as may be necessary to keep such registration statement continuously effective during the timeframes set forth in the Rights Agreement.

        The registration statement of which this prospectus is a part relates to the resale of the Warrant Shares that may be issued to the selling stockholders in connection with the exercise of the Warrants issued in the foregoing private placement. Shares of common stock that may be offered under this prospectus will be fully paid and non-assessable.


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The Offering

Common stock offered by selling stockholders

2,750,000 shares

Term of offering

Each selling stockholder will determine when and how it will sell the common stock offered in this prospectus, as described in "Plan of Distribution."

Use of proceeds

We will not receive any proceeds from the sale of shares of our common stock by the selling stockholders.

Risk factors

See the section below entitled "Risk Factors" for a discussion of factors you should carefully consider before deciding to invest in our common stock.

Nasdaq Global Market Symbol

PTGX

        The selling stockholders named in this prospectus may offer and sell up to 2,750,000 shares of our common stock. Our common stock is currently listed on The Nasdaq Global Market under the symbol "PTGX." Shares of common stock that may be offered under this prospectus will be fully paid and non-assessable. We will not receive any of the proceeds of sales by the selling stockholders of any of the common stock covered by this prospectus. Throughout this prospectus, when we refer to the shares of our common stock being registered on behalf of the selling stockholders for offer and resale, we are referring to the shares of common stock issued to the selling stockholders in connection with the exercise of Warrants issued in our private placement as described above. When we refer to the selling stockholders in this prospectus, we are referring to the selling stockholders identified in this prospectus and, as applicable, their permitted transferees or other successors-in-interest that may be identified in a supplement to this prospectus or, if required, a post-effective amendment to the registration statement of which this prospectus is a part.


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RISK FACTORS

        Investing in our common stock involves a high degree of risk. Before deciding whether to invest in our securities, you should consider carefully the risks and uncertainties described under the heading "Risk Factors" contained in our most recent Annual Report on Form 10-K and in our most recent Quarterly Report on Form 10-Q, as well as any amendments thereto reflected in subsequent filings with the SEC, which are incorporated by reference into this prospectus in their entirety, together with other information in this prospectus, the documents incorporated by reference and any free writing prospectus that we may authorize for use in connection with this offering. The risks described in these documents are not the only ones we face, but those that we consider to be material. There may be other unknown or unpredictable economic, business, competitive, regulatory or other factors that could have material adverse effects on our future results. Past financial performance may not be a reliable indicator of future performance, and historical trends should not be used to anticipate results or trends in future periods. If any of these risks actually occurs, our business, financial condition, results of operations or cash flow could be seriously harmed. This could cause the trading price of our common stock to decline, resulting in a loss of all or part of your investment. Please also read carefully the section below entitled "Forward-Looking Statements."


FORWARD-LOOKING STATEMENTS

        This prospectus, the documents incorporated by reference any applicable prospectus supplement and any free writing prospectus that we have authorized for use in connection with this offeringherein contain forward-looking statements, including statements regarding our future financial condition, business strategy and plans and objectives of management for future operations. Forward-looking statements include all statements that are not historical facts. In some cases, you can identify forward-looking statements by terminology such as "believe," "will," "may," "estimate," "continue," "anticipate," "intend," "should," "plan," "might," "approximately," "expect," "predict," "could," "potentially"“believe,” “will,” “may,” “estimate,” “continue,” “anticipate,” “intend,” “should,” “plan,” “might,” “approximately,” “expect,” “predict,” “could,” “potentially” or the negative of these terms or other similar expressions. Forward-looking statements appear in a number of places throughout this prospectus, the documents incorporated by reference and any free writing prospectus that we have authorized for use in connection with this offering and include statements regarding our intentions, beliefs, projections, outlook, analyses or current expectations concerning, among other things, the potential for our programs, the timing of our clinical trials, the potential for eventual regulatory approval and commercialization of our product candidates and our potential receipt of milestone payments and royalties under our collaboration agreement with Janssen, the potential outcome of any litigation or proceeding,agreements; future operating results or the ability to generate sales, income or cash flow, and the impact of the ongoing COVID-19 pandemic, are forward-looking statements.

Discussions containing these forward-looking statements may be found, among other places, in the section of this prospectus under the heading “Risk Factors” and in the sections entitled "Risk Factors," "Business"“Business” and "Management's“Management’s Discussion and Analysis of Financial Condition and Results of Operations"Operations” incorporated by reference from our most recent Annual Report on Form 10-K and ourany subsequent Quarterly Reports on Form 10-Q, as well as any amendments thereto, filed with SEC.the U.S. Securities and Exchange Commission (the “SEC”). These statements relate to future events or our future financial performance and involve known and unknown risks, uncertainties and other factors that could cause our actual results, levels of activity, performance or achievement to differ materially from those expressed or implied by these forward-looking statements. These statements reflect our current views with respect to future events and are based on assumptions and subject to risks and uncertainties. Given these risks and uncertainties, you should not place undue reliance on these forward-looking statements. We discuss in greater detail many of these risks under the heading "Risk Factors"“Risk Factors” and elsewhere in this prospectus and in our most recent Annual Report on Form 10-K and any subsequent Quarterly Reports on Form 10-Q, as well as any amendments thereto reflected in subsequent filings with the SEC and in the other documents incorporated by reference herein, and elsewhere in this prospectus.herein. Also, these forward-looking statements represent our estimates and assumptions only as of the date of the document containing the applicable statement and, except as required by law, we undertake no obligation to update or revise publicly any forward-looking statements, whether as a result of new information, future events or otherwise.


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In addition, statements that "we believe"such as “we believe” and similar statements reflect our beliefs and opinions on the relevant subject. These statements are based upon information available to us as of the date of this prospectus, and while we believe such information forms a reasonable basis for such statements, such information may be limited or incomplete, and our statements should not be read to indicate that we have conducted an exhaustive inquiry into, or review of, all potentially available relevant information. These statements are inherently uncertain and investors are cautioned not to unduly rely upon these statements.


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We are a biopharmaceutical company with peptide-based new chemical entities rusfertide, PN-943 and PN-235 in different stages of Contentsdevelopment, all derived from the Company’s proprietary discovery technology platform. Our clinical programs fall into two broad categories of diseases; (i) hematology and blood disorders, and (ii) inflammatory and immunomodulatory diseases.
Corporate Information

Our principal executive offices are located at 7707 Gateway Boulevard, Suite 140, Newark, California 94560. Our telephone number is (510) 474-0170. Our website address is www.protagonist-inc.com. References to our website address do not constitute incorporation by reference of the information contained on the website, and the information contained on the website is not part of this document. We have included our website in this prospectus solely as an inactive textual reference.

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RISK FACTORS
Investing in our securities involves risks. You should carefully consider the risks, uncertainties and other factors described in our most recent Annual Report on Form 10-K, as supplemented and updated by subsequent Quarterly Reports on Form 10-Q and Current Reports on Form 8-K that we have filed or will file with the SEC, and in other documents which are incorporated by reference into this prospectus, as well as the risk factors and other information contained in or incorporated by reference into any accompanying prospectus supplement before investing in any of our securities. Our business, financial condition, results of operations, cash flows or prospects could be materially and adversely affected by any of these risks. The risks and uncertainties described in the documents incorporated by reference herein are not the only risks and uncertainties that you may face.
For more information about our SEC filings, please see “Where You Can Find More Information” and “Incorporation of Certain Information by Reference.”

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USE OF PROCEEDS

        The selling stockholders will receive all of

Except as described in any applicable prospectus supplement or in any free writing prospectuses we have authorized for use in connection with a specific offering, we currently intend to use the net proceeds from salesthe sale of the common stock sold pursuant to this prospectus. However, upon any exercise of Warrants for cash, the selling stockholders would paysecurities offered by us an exercise price of $10.00 per share of common stock in the case of Class A Warrants, and $15.00 per share of common stock in the case of Class B Warrants, subject to any adjustment pursuant to the terms of the Warrants. We expect to use any such Warrant exercise proceeds primarilyhereunder for working capital and general corporate purposes. Under certain circumstances,purposes, which may include, among other things, funding research and development, clinical trials, vendor payables, potential regulatory submissions, hiring additional personnel and capital expenditures. Our expected use of proceeds from the Warrants are exercisable on a cashless basis by net exercise. If anysale of the Warrants are exercisedsecurities offered hereby represents our current intentions based on a cashless basis,our present plans and business condition. As of the date of this prospectus, we would not receive any cash paymentcannot predict with certainty all of the particular uses for the proceeds to be received from the sale of the securities offered hereby or the amounts that we will actually spend on the uses set forth above.
Pending the use of the net proceeds, we may invest the proceeds in interest-bearing, investment-grade securities, certificates of deposit or government securities. When we offer and sell the securities to which this prospectus relates, the prospectus supplement related to such offering will set forth our intended use of the proceeds, if any, received from the sale of such securities.

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SECURITIES WE MAY OFFER
This prospectus contains summary descriptions of the securities we may offer from time to time. These summary descriptions are not meant to be complete descriptions of each security. The particular terms of any security will be described in the applicable selling stockholder upon any such cashless exerciseprospectus supplement.

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DESCRIPTION OF CAPITAL STOCK
The description below of a Warrant.


Tableour capital stock and provisions of Contents


SELLING STOCKHOLDERS

        Weour amended and restated certificate of incorporation (our “certificate of incorporation”) and amended and restated bylaws (our “bylaws”) are registeringsummaries and are qualified by reference to our certificate of incorporation and our bylaws which are filed as exhibits to the resaleregistration statement of 2,750,000which this prospectus is part, and by the applicable provisions of Delaware law. For more information on how you can obtain our certificate of incorporation and our bylaws, see the heading “Where You Can Find More Information.”

As of the date of this prospectus, our certificate of incorporation, authorizes us to issue up to 90,000,000 shares of common stock, which$0.00001 par value per share, and 10,000,000 shares of preferred stock, $0.00001 par value per share. As of June 30, 2022, 48,683,931 shares of common stock were outstanding and no shares of preferred stock were outstanding.
Common Stock
Voting Rights
Holders of our common stock are issuable uponentitled to one vote for each share held on all matters submitted to a vote of stockholders, including the exerciseelection of Warrants held bydirectors, and do not have cumulative voting rights. Accordingly, the selling stockholders identified belowholders of a majority of the outstanding shares of common stock entitled to permit eachvote in any election of them, or their permitted transferees ordirectors can elect all of the directors standing for election, if they so choose, other successors-in-interestthan any directors that holders of any preferred stock we may issue may be entitled to elect.
Dividend Rights
Subject to preferences that may be identifiedapplicable to any then outstanding preferred stock, holders of common stock are entitled to receive ratably those dividends, if any, as may be declared by the board of directors out of legally available funds.
Liquidation
In the event of our liquidation, dissolution or winding up, the holders of common stock will be entitled to share ratably in the assets legally available for distribution to stockholders after the payment of or provision for all of our debts and other liabilities, subject to the prior rights of any preferred stock then outstanding.
Rights and Preferences
Holders of common stock have no preemptive or conversion rights or other subscription rights and there are no redemption or sinking funds provisions applicable to the common stock. The rights, preferences and privileges of holders of common stock are subject to and may be adversely affected by the rights of the holders of shares of any series of preferred stock that we may designate and issue in the future.
Anti-Takeover Effects of Delaware Law and our Certificate of Incorporation and Bylaws
Some provisions of Delaware law, our certificate of incorporation and our bylaws contain provisions that could make the following transactions more difficult: an acquisition of us by means of a tender offer; an acquisition of us by means of a proxy contest or otherwise; or the removal of our incumbent officers and directors. It is possible that these provisions could make it more difficult to accomplish or could deter transactions that stockholders may otherwise consider to be in their best interest or in our best interests, including transactions which provide for payment of a premium over the market price for our shares.
These provisions, summarized below, are intended to discourage coercive takeover practices and inadequate takeover bids. These provisions are also designed to encourage persons seeking to acquire control of us to first negotiate with our board of directors. We believe that the benefits of the increased protection of our potential ability to negotiate with the proponent of an unfriendly or unsolicited proposal to acquire or restructure us outweigh the disadvantages of discouraging these proposals because negotiation of these proposals could result in an improvement of their terms.

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Undesignated Preferred Stock — The ability to authorize undesignated preferred stock makes it possible for our board of directors to issue preferred stock with voting or other rights or preferences that could impede the success of any attempt to change control of us. These and other provisions may have the effect of deterring hostile takeovers or delaying changes in control or management of our company.
Stockholder Meetings — Our bylaws provide that a special meeting of stockholders may be called only by our chairman of the board, chief executive officer or president, or by a resolution adopted by a majority of our board of directors.
Requirements for Advance Notification of Stockholder Nominations and Proposals — Our bylaws establish advance notice procedures with respect to stockholder proposals to be brought before a stockholder meeting and the nomination of candidates for election as directors, other than nominations made by or at the direction of the board of directors or a committee of the board of directors.
Elimination of Stockholder Action by Written Consent — Our certificate of incorporation and our bylaws eliminate the right of stockholders to act by written consent without a meeting.
Staggered Board — Our board of directors is divided into three classes. The directors in each class will serve for a three-year term, one class being elected each year by our stockholders. This system of electing and removing directors may tend to discourage a third-party from making a tender offer or otherwise attempting to obtain control of us, because it generally makes it more difficult for stockholders to replace a majority of the directors.
Removal of Directors — Our certificate of incorporation provides that no member of our board of directors may be removed from office by our stockholders except for cause and, in addition to any other vote required by law, upon the approval of not less than two thirds of the total voting power of all of our outstanding voting stock then entitled to vote in the election of directors.
Stockholders Not Entitled to Cumulative Voting — Our certificate of incorporation does not permit stockholders to cumulate their votes in the election of directors. Accordingly, the holders of a majority of the outstanding shares of our common stock entitled to vote in any election of directors can elect all of the directors standing for election, if they choose, other than any directors that holders of our preferred stock may be entitled to elect.
Delaware Anti-Takeover Statute — We are subject to Section 203 of the Delaware General Corporation Law, which prohibits persons deemed to be “interested stockholders” from engaging in a supplement “business combination” with a publicly held Delaware corporation for three years following the date these persons become interested stockholders unless the business combination is, or the transaction in which the person became an interested stockholder was, approved in a prescribed manner or another prescribed exception applies. Generally, an “interested stockholder” is a person who, together with affiliates and associates, owns, or within three years prior to the determination of interested stockholder status did own, 15% or more of a corporation’s voting stock. Generally, a “business combination” includes a merger, asset or stock sale, or other transaction resulting in a financial benefit to the interested stockholder. The existence of this provision may have an anti-takeover effect with respect to transactions not approved in advance by the board of directors.
Choice of Forum — Our certificate of incorporation provides that, unless we consent in writing to the selection of an alternative form, the Court of Chancery of the State of Delaware is the exclusive forum for the following types of actions or proceedings under Delaware statutory or common law: (1) any derivative action or proceeding brought on our behalf; (2) any action asserting a claim of breach of a fiduciary duty or other wrongdoing by any of our directors, officers, employees or agents to us or our stockholders; (3) any action asserting a claim against us arising pursuant to any provision of the General Corporation Law of the State of Delaware or our certificate of incorporation or bylaws; (4) any action to interpret, apply, enforce or determine the validity of our certificate of incorporation or bylaws; or (5) any action asserting a claim governed by the internal affairs doctrine. This provision does not apply to suits brought to enforce a duty or liability created by the Exchange Act or any other claim for which the U.S. federal courts have exclusive jurisdiction. Our certificate of incorporation also provides that any person or entity purchasing or otherwise acquiring any interest in shares of our capital stock will be deemed to have notice of and to have consented

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to this choice of forum provision. It is possible that a court of law could rule that the choice of forum provision contained in our certificate of incorporation is inapplicable or unenforceable if it is challenged in a proceeding or otherwise.
Amendment of Charter Provisions — The amendment of any of the above provisions, except for the provision making it possible for our board of directors to issue preferred stock, would require approval by holders of at least two thirds of the total voting power of all of our outstanding voting stock.
The provisions of Delaware law, our certificate of incorporation and our bylaws could have the effect of discouraging others from attempting hostile takeovers and, as a consequence, they may also inhibit temporary fluctuations in the market price of our common stock that often result from actual or rumored hostile takeover attempts. These provisions may also have the effect of preventing changes in the composition of our board and management. It is possible that these provisions could make it more difficult to accomplish transactions that stockholders may otherwise deem to be in their best interests.
Transfer Agent and Registrar
The transfer agent and registrar for our common stock is American Stock Transfer & Trust Company, LLC. The transfer agent’s address is 6201 15th Avenue, Brooklyn, New York 11219. The transfer agent for any series of preferred stock that we may offer under this prospectus will be named and described in the prospectus supplement for that series.
Listing
Our common stock is listed on The Nasdaq Global Market under the symbol “PTGX.” The applicable prospectus supplement will contain information, where applicable, as to any other listing, if any, on the Nasdaq Global Market or if required,any securities market or other exchange of the preferred stock covered by such prospectus supplement.
Preferred Stock
Our board of directors may, without further action by our stockholders, fix the rights, preferences, privileges and restrictions of up to an aggregate of 10,000,000 shares of preferred stock in one or more series and authorize their issuance. These rights, preferences and privileges could include dividend rights, conversion rights, voting rights, terms of redemption, liquidation preferences, sinking fund terms and the number of shares constituting any series or the designation of such series, any or all of which may be greater than the rights of our common stock. The issuance of our preferred stock could adversely affect the voting power of holders of our common stock and the likelihood that such holders will receive dividend payments and payments upon liquidation. In addition, the issuance of preferred stock could have the effect of delaying, deferring or preventing a post-effective amendmentchange of control or other corporate action.
The following summary of terms of our preferred stock is not complete. You should refer to the provisions of our certificate of incorporation and bylaws and the resolutions containing the terms of each class or series of the preferred stock which have been or will be filed with the SEC at or prior to the time of issuance of such class or series of preferred stock and described in the applicable prospectus supplement. The applicable prospectus supplement may also state that any of the terms set forth herein are inapplicable to such series of preferred stock, provided that the information set forth in such prospectus supplement does not constitute material changes to the information herein such that it alters the nature of the offering or the securities offered.
We will fix the designations, voting powers, preferences and rights of the preferred stock of each series we issue under this prospectus, as well as the qualifications, limitations or restrictions thereof, in the certificate of designation relating to that series. We will file as an exhibit to the registration statement of which this prospectus is a part, to resell or otherwise disposewill incorporate by reference from reports that we file with the SEC, the form of these sharesany certificate of designation that describes the terms of the series of preferred stock we are offering. We will describe in the manner contemplatedapplicable prospectus supplement the terms of the series of preferred stock being offered, including, to the extent applicable:

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the title and stated value;

the number of shares we are offering;

the liquidation preference per share;

the purchase price;

the dividend rate, period and payment date and method of calculation for dividends;

whether dividends will be cumulative or non-cumulative and, if cumulative, the date from which dividends will accumulate;

the procedures for any auction and remarketing;

the provisions for a sinking fund;

the provisions for redemption or repurchase, if applicable, and any restrictions on our ability to exercise those redemption and repurchase rights;

any listing of the preferred stock on any securities exchange or market;

whether the preferred stock will be convertible into our common stock, and, if applicable, the conversion price, or how it will be calculated, and the conversion period;

whether the preferred stock will be exchangeable into debt securities, and, if applicable, the exchange price, or how it will be calculated, and the exchange period;

voting rights of the preferred stock;

preemptive rights;

restrictions on transfer, sale or other assignment;

whether interests in the preferred stock will be represented by depositary shares;

a discussion of material United States federal income tax considerations applicable to the preferred stock;

the relative ranking and preferences of the preferred stock as to dividend rights and rights if we liquidate, dissolve or wind up our affairs;

any limitations on the issuance of any class or series of preferred stock ranking senior to or on a parity with the series of preferred stock as to dividend rights and rights if we liquidate, dissolve or wind up our affairs; and

any other specific terms, preferences, rights or limitations of, or restrictions on, the preferred stock.
If we issue shares of preferred stock under this prospectus, the section entitled "Planshares will be fully paid and non-assessable.
The issuance of Distribution"preferred stock could adversely affect the voting power of holders of common stock and reduce the likelihood that common stockholders will receive dividend payments and payments upon liquidation. The issuance could have the effect of decreasing the market price of the common stock. The issuance of preferred stock also could have the effect of delaying, deterring or preventing a change in control of us.

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DESCRIPTION OF DEBT SECURITIES
The paragraphs below describe the general terms and provisions of the debt securities we may issue. When we offer to sell a particular series of debt securities, we will describe the specific terms of the securities in a supplement to this prospectus, including any additional covenants or changes to existing covenants relating to such series. The prospectus supplement also will indicate whether the general terms and provisions described in this prospectus (asapply to a particular series of debt securities. You should read the actual indenture if you do not fully understand a term or the way we use it in this prospectus.
We may offer senior or subordinated debt securities. Each series of debt securities may have different terms. The senior debt securities will be issued under one or more senior indentures, dated as of a date prior to such issuance, between us and the trustee identified in the applicable prospectus supplement, as amended or supplemented from time to time. We will refer to any such indenture throughout this prospectus as the “senior indenture.” Any subordinated debt securities will be issued under one or more separate indentures, dated as of a date prior to such issuance, between us and the trustee identified in the applicable prospectus supplement, as amended or supplemented from time to time. We will refer to any such indenture throughout this prospectus as the “subordinated indenture” and to the trustee under the senior or subordinated indenture as the “trustee.” The senior indenture and the subordinated indenture are sometimes collectively referred to in this prospectus as the “indentures.” The indentures will be subject to and governed by the Trust Indenture Act of 1939, as amended (the “Trust Indenture Act”). We included copies of the forms of the indentures as exhibits to our registration statement and they are incorporated into this prospectus by reference.
If we issue debt securities at a discount from their principal amount, then, for purposes of calculating the aggregate initial offering price of the offered securities issued under this prospectus, we will include only the initial offering price of the debt securities and not the principal amount of the debt securities.
We have summarized below the material provisions of the indentures and the debt securities, or indicated which material provisions will be described in the related prospectus supplement. The prospectus supplement relating to any particular securities offered will describe the specific terms of the securities, which may be supplementedin addition to or different from the general terms summarized in this prospectus. Because the summary in this prospectus and amended).

in any prospectus supplement does not contain all of the information that you may find useful, you should read the documents relating to the securities that are described in this prospectus or in any applicable prospectus supplement. Please read “Where You Can Find More Information” to find out how you can obtain a copy of those documents. Except as otherwise indicated, the terms of the indentures are identical. As used under this caption, the term “debt securities” includes the debt securities being offered by this prospectus and all other debt securities issued by us under the indentures.

General
The selling stockholders may sell some, all or none of their shares. We indentures:

do not knowlimit the amount of debt securities that we may issue;

allow us to issue debt securities in one or more series;

do not require us to issue all of the debt securities of a series at the same time; and

allow us to reopen a series to issue additional debt securities without the consent of the holders of the debt securities of such series.
Unless we give you different information in the applicable prospectus supplement, the senior debt securities will be unsubordinated obligations and will rank equally with all of our other senior unsecured and unsubordinated indebtedness. Payments on the subordinated debt securities will be subordinated to the prior payment in full of all of our senior indebtedness, as described under “Description of Debt Securities — Subordination” and in the applicable prospectus supplement.
Each indenture provides that we may, but need not, designate more than one trustee under an indenture. Any trustee under an indenture may resign or be removed and a successor trustee may be appointed to act with respect to the series of debt securities administered by the resigning or removed trustee. If two or more persons are acting as trustee with respect to different series of debt securities, each trustee shall be a

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trustee of a trust under the applicable indenture separate and apart from the trust administered by any other trustee. Except as otherwise indicated in this prospectus, any action described in this prospectus to be taken by each trustee may be taken by each trustee with respect to, and only with respect to, the one or more series of debt securities for which it is trustee under the applicable indenture.
The prospectus supplement for each offering will provide the following terms, where applicable:

the title of the debt securities and whether they are senior or subordinated;

the aggregate principal amount of the debt securities being offered, the aggregate principal amount of the debt securities outstanding as of the most recent practicable date and any limit on their aggregate principal amount, including the aggregate principal amount of debt securities authorized;

the price at which the debt securities will be issued, expressed as a percentage of the principal and, if other than the principal amount thereof, the portion of the principal amount thereof payable upon declaration of acceleration of the maturity thereof or, if applicable, the portion of the principal amount of such debt securities that is convertible into common stock or other securities of ours or the method by which any such portion shall be determined;

if convertible, the terms on which such debt securities are convertible, including the initial conversion price or rate and the conversion period and any applicable limitations on the ownership or transferability of common stock or other securities of ours received on conversion;

the date or dates, or the method for determining the date or dates, on which the principal of the debt securities will be payable;

the fixed or variable interest rate or rates of the debt securities, or the method by which the interest rate or rates is determined;

the date or dates, or the method for determining the date or dates, from which interest will accrue;

the dates on which interest will be payable;

the record dates for interest payment dates, or the method by which such dates will be determined;

the persons to whom interest will be payable;

the basis upon which interest will be calculated if other than that of a 360-day year of twelve 30-day months;

any make-whole amount, which is the amount in addition to principal and interest that is required to be paid to the holder of a debt security as a result of any optional redemption or accelerated payment of such debt security, or the method for determining the make-whole amount;

the place or places where the principal of, and any premium or make-whole amount, and interest on, the debt securities will be payable;

where the debt securities may be surrendered for registration of transfer or conversion or exchange;

where notices or demands to or upon us in respect of the debt securities and the applicable indenture may be served;

the times, prices and other terms and conditions upon which we may redeem the debt securities;

any obligation we have to redeem, repay or purchase the debt securities pursuant to any sinking fund or analogous provision or at the option of holders of the debt securities, and the times and prices at which we must redeem, repay or purchase the debt securities as a result of such obligation;

the currency or currencies in which the debt securities are denominated and payable if other than United States dollars, which may be a foreign currency or units of two or more foreign currencies or a composite currency or currencies and the terms and conditions relating thereto, and the manner of determining the equivalent of such foreign currency in United States dollars;

whether the principal of, and any premium or make-whole amount, or interest on, the debt securities of the series are to be payable, at our election or at the election of a holder, in a currency or currencies other than that in which the debt securities are denominated or stated to be payable, and other related terms and conditions;

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whether the amount of payments of principal of, and any premium or make-whole amount, or interest on, the debt securities may be determined according to an index, formula or other method and how longsuch amounts will be determined;

whether the selling stockholdersdebt securities will holdbe in registered form, bearer form, or both, and (i) if in registered form, the shares before selling them,person to whom any interest shall be payable, if other than the person in whose name the security is registered at the close of business on the regular record date for such interest, or (ii) if in bearer form, the manner in which, or the person to whom, any interest on the security shall be payable if otherwise than upon presentation and we currently have no agreements, arrangements or understandings withsurrender upon maturity;

any restrictions applicable to the selling stockholders regarding theoffer, sale or delivery of securities in bearer form and the terms upon which securities in bearer form of the series may be exchanged for securities in registered form of the series and vice versa, if permitted by applicable laws and regulations;

whether any debt securities of the series are to be issuable initially in temporary global form and whether any debt securities of the series are to be issuable in permanent global form with or without coupons and, if so, whether beneficial owners of interests in any such permanent global security may, or shall be required to, exchange their interests for other dispositiondebt securities of the series, and the manner in which interest shall be paid;

the identity of the depositary for securities in registered form, if such series are to be issuable as a global security;

the date as of which any debt securities in bearer form or in temporary global form shall be dated if other than the original issuance date of the first security of the series to be issued;

the applicability, if any, of the defeasance and covenant defeasance provisions described in this prospectus or in the applicable indenture;

whether and under what circumstances we will pay any additional amounts on the debt securities in respect of any tax, assessment or governmental charge and, if so, whether we will have the option to redeem the debt securities in lieu of making such a payment;

whether and under what circumstances the debt securities being offered are convertible into common stock or other securities of ours, as the case may be, including the conversion price or rate and the manner or calculation thereof;

the circumstances, if any, specified in the applicable prospectus supplement, under which beneficial owners of interests in the global security may obtain definitive debt securities and the manner in which payments on a permanent global debt security will be made if any debt securities are issuable in temporary or permanent global form;

any provisions granting special rights to holders of securities upon the occurrence of such events as specified in the applicable prospectus supplement;

if the debt securities of such series are to be issuable in definitive form only upon receipt of certain certificates or other documents or satisfaction of other conditions, then the form and/or terms of such certificates, documents or conditions;

the name of the applicable trustee and the nature of any material relationship with us or any of our affiliates, and the percentage of debt securities of the class necessary to require the trustee to take action;

any deletions from, modifications of or additions to our events of default or covenants with regard to such debt securities and any change in the right of any trustee or any of the holders to declare the principal amount of any of such debt securities due and payable;

applicable CUSIP numbers; and

any other terms of such debt securities not inconsistent with the shares.provisions of the applicable indenture.
We may issue debt securities that provide for less than the entire principal amount thereof to be payable upon declaration of acceleration of the maturity of the debt securities. We refer to any such debt

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securities throughout this prospectus as “original issue discount securities.” The shares covered herebyapplicable prospectus supplement will describe the United States federal income tax consequences and other relevant considerations applicable to original issue discount securities, including the portion of the principal amount thereof to be payable upon declaration of acceleration of the maturity of the debt securities.
Except as described in the indentures under “Compliance with Consolidation Provisions” and “Successor Entity” or as may be offered fromset forth in any prospectus supplement, the debt securities will not contain any provisions that (i) would limit our ability to incur indebtedness or (ii) would afford holders of debt securities protection in the event of (a) a highly leveraged or similar transaction involving us, or (b) a change of control or reorganization, restructuring, merger or similar transaction involving us that may adversely affect the holders of the debt securities. In the future, we may enter into transactions, such as the sale of all or substantially all of our assets or a merger or consolidation, that may have an adverse effect on our ability to service our indebtedness, including the debt securities, by, among other things, substantially reducing or eliminating our assets.
Our governing instruments do not define the term “substantially all” as it relates to the sale of assets. Additionally, Delaware cases interpreting the term “substantially all” rely upon the facts and circumstances of each particular case. Consequently, to determine whether a sale of “substantially all” of our assets has occurred, a holder of debt securities must review the financial and other information that we have disclosed to the public.
We will provide you with more information in the applicable prospectus supplement regarding any deletions, modifications, or additions to the events of default or covenants that are described below, including any addition of a covenant or other provision providing event risk or similar protection.
Payment
Unless we give you different information in the applicable prospectus supplement, the principal of, and any premium or make-whole amount, and interest on, any series of the debt securities will be payable at the corporate trust office of the trustee. We will provide you with the address of the trustee in the applicable prospectus supplement. We may also pay interest by mailing a check to the address of the person entitled to it as it appears in the applicable register for the debt securities or by wire transfer of funds to that person at an account maintained within the United States.
All monies that we pay to a paying agent or a trustee for the payment of the principal of, and any premium or make-whole amount, or interest on, any debt security will be repaid to us if unclaimed at the end of two years after the obligation underlying payment becomes due and payable. After funds have been returned to us, the holder of the debt security may look only to us for payment, without payment of interest for the period which we hold the funds.
Denomination, Interest, Registration and Transfer
Unless otherwise described in the applicable prospectus supplement, the debt securities of any series will be issuable in denominations of $1,000 and integral multiples of $1,000.
Subject to the limitations imposed upon debt securities that are evidenced by a computerized entry in the records of a depository company rather than by physical delivery of a note, a holder of debt securities of any series may:

exchange them for any authorized denomination of other debt securities of the same series and of a like aggregate principal amount and kind upon surrender of such debt securities at the corporate trust office of the applicable trustee or at the office of any transfer agent that we designate for such purpose; and

surrender them for registration of transfer or exchange at the corporate trust office of the applicable trustee or at the office of any transfer agent that we designate for such purpose.
Every debt security surrendered for registration of transfer or exchange must be duly endorsed or accompanied by a written instrument of transfer satisfactory to the applicable trustee or transfer agent. Payment of a service charge will not be required for any registration of transfer or exchange of any debt

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securities, but we or the trustee may require payment of a sum sufficient to cover any tax or other governmental charge payable in connection therewith. If in addition to the applicable trustee, the applicable prospectus supplement refers to any transfer agent initially designated by us for any series of debt securities, we may at any time rescind the designation of any such transfer agent or approve a change in the location through which any such transfer agent acts, except that we will be required to maintain a transfer agent in each place of payment for such series. We may at any time bydesignate additional transfer agents for any series of debt securities.
Neither we, nor any trustee, will be required to:

issue, register the selling stockholders. Astransfer of or exchange debt securities of any series during a result,period beginning at the opening of business 15 days before the day that a notice of redemption of less than all the outstanding debt securities of the same series is mailed and ending at the close of business on the day of such mailing;

register the transfer of or exchange any debt security, or portion thereof, so selected for redemption, in whole or in part, except the unredeemed portion of any debt security being redeemed in part; and

issue, register the transfer of or exchange any debt security that has been surrendered for repayment at the option of the holder, except the portion, if any, of such debt security not to be so repaid.
Merger, Consolidation or Sale of Assets
The indentures provide that we cannot estimatemay, without the consent of the holders of any outstanding debt securities, (i) consolidate with, (ii) sell, lease or convey all or substantially all of our assets to, or (iii) merge with or into, any other entity provided that:

either we are the continuing entity, or the successor entity, if other than us, assumes the obligations (a) to pay the principal of, and any premium or make-whole amount, and interest on, all of the debt securities and (b) to duly perform and observe all of the covenants and conditions contained in each indenture;

the holders of any outstanding debt securities shall be entitled to receive upon conversion or exchange of such debt securities the number of securities or property to which a holder of the number of shares of common stock or other securities of the Company deliverable upon conversion or exchange of such debt securities would have been entitled had such conversion or exchange occurred immediately prior to the transaction; and

an officers’ certificate and legal opinion covering such conditions are delivered to each applicable trustee.
Covenants
Existence.   Except as described therein under “Company May Consolidate, Etc.,” the indentures require us to do or cause to be done all things necessary to preserve and keep in full force and effect our existence, rights and franchises. However, the indentures do not require us to preserve any right or franchise if we determine that any right or franchise is no longer desirable in the conduct of our business.
Provision of financial information.   The indentures require us to (i) within 30 days of each of the selling stockholders will beneficially own after termination of sales under this prospectus. In addition, eachrespective dates by which we are required to file our annual reports, quarterly reports and other documents with the SEC, file with the trustee copies of the selling stockholdersannual report, quarterly report and other documents that we file with the SEC under Section 13 or 15(d) of the Exchange Act and (ii) file with the trustee and the SEC any additional information, documents and reports regarding compliance by us with the conditions and covenants of the indentures, as required.
Additional covenants.   The applicable prospectus supplement will set forth any of our additional covenants relating to any series of debt securities.

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Events of Default, Notice and Waiver
Unless the applicable prospectus supplement states otherwise, when we refer to “events of default” as defined in the indentures with respect to any series of debt securities, we mean:

default in the payment of any installment of interest on any debt security of such series continuing for 90 days;

default in the payment of principal of, or any premium or make-whole amount on, any debt security of such series as and when the same shall become due and payable, whether at maturity, upon redemption, by declaration or otherwise;

default in making any sinking fund payment as required for any debt security of such series as and when due and payable;

default in the performance or breach of any covenant or warranty in the debt securities or in the indenture by us continuing for 90 days after written notice as provided in the applicable indenture, but not of a covenant added to the indenture solely for the benefit of a series of debt securities issued thereunder other than such series;

bankruptcy, insolvency or reorganization, or court appointment of a receiver, liquidator or trustee of us; and

any other event of default provided with respect to a particular series of debt securities.
Notice of any such default shall be given to us by the trustee, or to us and the trustee by the holders of at least 25% in principal amount of the outstanding debt securities of that series. The written notice shall specify such default and require us to cause such indebtedness to be discharged or cause such acceleration to be rescinded or annulled and shall state that such notice is a “Notice of Default” under such indenture.
If an event of default occurs and is continuing with respect to debt securities of any series outstanding, then the applicable trustee or the holders of 25% or more in principal amount of the debt securities of that series will have the right to declare the principal amount of all the debt securities of that series to be due and payable. However, at any time after such a declaration of acceleration has been made, but before a judgment or decree for payment of the money due has been obtained by the applicable trustee, the holders of at least a majority in principal amount of outstanding debt securities of such series or of all debt securities then outstanding under the applicable indenture may rescind and annul such declaration and its consequences if:

we have sold, transferreddeposited with the applicable trustee all matured installments of interest upon and the principal of (and premium, if any, on) all the outstanding debt securities of such series that shall have become other than by acceleration (with interest upon such principal and premium, if any, and upon overdue installments of interest), plus applicable fees, expenses, disbursements and advances of the applicable trustee; and

all events of default, other than the non-payment of accelerated principal (and premium, if any) and accrued and unpaid interest on debt securities of such series, have been cured or waived.
The indentures require each trustee to give notice to the holders of debt securities within the later of 90 days after of a default occurs and 30 days after it is actually known to a trustee or written notice of it is received by the trustee, unless such default has been cured or waived. However, the trustee may withhold notice if specified persons of such trustee consider such withholding to be in the interest of the holders of debt securities. The trustee may not withhold notice of a default in the payment of principal, any premium or interest on any debt security of such series or in the payment of any sinking fund installment in respect of any debt security of such series.
The indentures provide that holders of debt securities of any series may not institute any proceedings, judicial or otherwise, disposedwith respect to such indenture or for any remedy under the indenture, unless the trustee fails to act for a period of 90 days after the trustee has received a written request to institute proceedings in respect of an event of default from the holders of 25% or more in principal amount of the outstanding debt securities of such series, as well as an offer of indemnity reasonably satisfactory to the trustee. However, this provision will not prevent any holder of debt securities from instituting suit for the enforcement of

16


payment of the principal of, and any premium or make-whole amount, and interest on, such debt securities at the respective due dates thereof.
The indentures provide that, subject to provisions in each indenture relating to its duties in the case of a default, a trustee has no obligation to exercise any of its rights or powers at the request or direction of any holders of any series of debt securities then outstanding under the indenture, unless the holders have offered to the trustee reasonable security or indemnity. The holders of at least a majority in principal amount of the outstanding debt securities of any series or of all debt securities then outstanding under an indenture shall have the right to direct the time, method and place of conducting any proceeding for any remedy available to the applicable trustee, or of exercising any trust or power conferred upon such trustee. However, a trustee may refuse to follow any direction which:

is in conflict with any law or the applicable indenture;

may involve the trustee in personal liability; or

may be unduly prejudicial to the holders of debt securities of the series not joining the proceeding.
Within 120 days after the close of each fiscal year, we will be required to deliver to each trustee a certificate, signed by one of our several specified officers, stating whether or not that officer has knowledge of any default under the applicable indenture. If the officer has knowledge of any default, the notice must specify the nature and status of the default.
Modification of the Indentures
The indentures provide that no modifications or amendments may, without the consent of each affected holder, impair the right of any holder of any debt security to (i) receive payment of the principal of (and premium, if any) and interest on the debt securities, as provided in the debt securities or indentures, on or after the respective due dates expressed in the debt securities or the indentures (or in the case of redemption, on the redemption date) or (ii) institute suit for the enforcement of any such payment on or after such respective dates or redemption date. Furthermore, no modification or amendment may, without the consent of the holders of all of the debt securities affected by the modification or amendment:

change the stated maturity of the principal of, or any premium or make-whole amount on, or any installment of principal of or interest on, any such debt security, or reduce the amount of interest payable thereon or principal thereof; or

reduce the percentage in principal amount of any outstanding debt securities necessary to modify or amend the applicable indenture with respect to such debt securities.
The holders of a majority in aggregate principal amount of the outstanding debt securities of each affected series may, on behalf of all holders of debt securities of that series, waive, insofar as that series is concerned, our compliance with material restrictive covenants of the applicable indenture.
We and our respective trustee may make modifications and amendments of an indenture without the consent of any holder of debt securities, including for any of the following purposes:

to evidence the succession of another person to us as obligor under such indenture in compliance with the Trust Indenture Act;

to add to our covenants for the benefit of the holders of all or any series of debt securities or to surrender any right or power conferred upon us in such indenture;

to add events of default for the benefit of the holders of all or any series of debt securities;

to add or change any provisions of an indenture (i) to change or eliminate restrictions on the payment of principal of, or premium or make-whole amount, or interest on, debt securities in bearer form, (ii) to permit or facilitate the issuance of debt securities in uncertificated form, or (iii) that otherwise does not adversely affect the interests of the holders of the debt securities of any series in any material respect;

to establish the form or terms of debt securities of any series;

17



to provide for the acceptance of appointment by a portionsuccessor trustee or facilitate the administration of the trusts under an indenture by more than one trustee; and

to cure any ambiguity, defect or inconsistency in an indenture.
Subordination
Unless otherwise provided in the applicable prospectus supplement, subordinated debt securities will be subject to the following subordination provisions.
Upon any distribution to our creditors in a liquidation, dissolution or reorganization, the payment of the principal of and interest on any subordinated debt securities will be subordinated to the extent provided in the applicable indenture in right of payment to the prior payment in full of all senior debt. However, our obligation to make payments of the principal of and interest on such subordinated debt securities otherwise will not be affected. No payment of principal or interest will be permitted to be made on subordinated debt securities at any time if a default on senior debt exists that permits the holders of such senior debt to accelerate its maturity and the default is the subject of judicial proceedings or we receive notice of the default. After all senior debt is paid in full and until the subordinated debt securities are paid in full, holders of subordinated debt securities will be subrogated to the rights of holders of senior debt to the extent that distributions otherwise payable to holders of subordinated debt securities have been applied to the payment of senior debt. The subordinated indenture will not restrict the amount of senior debt or other indebtedness of ours. As a result of these subordination provisions, in the event of a distribution of assets upon insolvency, holders of subordinated debt securities may recover less, ratably, than our general creditors.
The term “senior debt” will be defined in the applicable indenture as the principal of and interest on, or substantially similar payments to be made by us in respect of, other outstanding indebtedness, whether outstanding at the date of execution of the applicable indenture or subsequently incurred, created or assumed. The prospectus supplement may include a description of additional terms implementing the subordination feature.
No restrictions will be included in any indenture relating to subordinated debt securities upon the creation of additional senior debt.
If this prospectus is being delivered in connection with the offering of a series of subordinated debt securities, the accompanying prospectus supplement or the information incorporated in this prospectus by reference will set forth the approximate amount of senior debt outstanding as of the end of our most recent fiscal quarter.
Discharge, Defeasance and Covenant Defeasance
Unless otherwise indicated in the applicable prospectus supplement, the indentures allow us to discharge our obligations to holders of any series of debt securities issued under any indenture when:

either (i) all securities of such series have already been delivered to the applicable trustee for cancellation; or (ii) all securities of such series have not already been delivered to the applicable trustee for cancellation but (a) have become due and payable, (b) will become due and payable within one year, or (c) if redeemable at our option, are to be redeemed within one year, and we have irrevocably deposited with the applicable trustee, in trust, funds in such currency or currencies, currency unit or units or composite currency or currencies in which such debt securities are payable, an amount sufficient to pay the entire indebtedness on such debt securities in respect of principal and any premium or make-whole amount, and interest to the date of such deposit if such debt securities have become due and payable or, if they have not, to the stated maturity or redemption date;

we have paid or caused to be paid all other sums payable; and

an officers’ certificate and an opinion of counsel stating the conditions to discharging the debt securities have been satisfied has been delivered to the trustee.
Unless otherwise indicated in the applicable prospectus supplement, the indentures provide that, upon our irrevocable deposit with the applicable trustee, in trust, of an amount, in such currency or currencies,

18


currency unit or units or composite currency or currencies in which such debt securities are payable at stated maturity, or government obligations, or both, applicable to such debt securities, which through the scheduled payment of principal and interest in accordance with their terms will provide money in an amount sufficient to pay the principal of, and any premium or make-whole amount, and interest on, such debt securities, and any mandatory sinking fund or analogous payments thereon, on the scheduled due dates therefor, the we may elect either:

to defease and be discharged from any and all obligations with respect to such debt securities; or

to be released from our obligations with respect to such debt securities under the applicable indenture or, if provided in the applicable prospectus supplement, our obligations with respect to any other covenant, and any omission to comply with such obligations shall not constitute an event of default with respect to such debt securities.
When we use the term “government obligations,” we mean securities that are:

direct obligations of the United States or the government that issued the foreign currency in which the debt securities of a particular series are payable, for the payment of which its full faith and credit is pledged; or

obligations of a person controlled or supervised by and acting as an agency or instrumentality of the United States or other government that issued the foreign currency in which the debt securities of such series are payable, the payment of which is unconditionally guaranteed as a full faith and credit obligation by the United States or such other government, which are not callable or redeemable at the option of the issuer thereof and shall also include a depository receipt issued by a bank or trust company as custodian with respect to any such government obligation or a specific payment of interest on or principal of any such government obligation held by such custodian for the account of the holder of a depository receipt. However, except as required by law, such custodian is not authorized to make any deduction from the amount payable to the holder of such depository receipt from any amount received by the custodian in respect of the government obligation or the specific payment of interest on or principal of the government obligation evidenced by such depository receipt.
Unless otherwise provided in the applicable prospectus supplement, if after we have deposited funds and/or government obligations to effect defeasance or covenant defeasance with respect to debt securities of any series, (i) the holder of a debt security of such series is entitled to, and does, elect under the terms of the applicable indenture or the terms of such debt security to receive payment in a currency, currency unit or composite currency other than that in which such deposit has been made in respect of such debt security, or (ii) a conversion event occurs in respect of the currency, currency unit or composite currency in which such deposit has been made, the indebtedness represented by such debt security will be deemed to have been, and will be, fully discharged and satisfied through the payment of the principal of, and premium or make-whole amount, and interest on, such debt security as they become due out of the proceeds yielded by converting the amount so deposited in respect of such debt security into the currency, currency unit or composite currency in which such debt security becomes payable as a result of such election or such cessation of usage based on the applicable market exchange rate.
When we use the term “conversion event,” we mean the cessation of use of:

a currency, currency unit or composite currency both by the government of the country that issued such currency and for the settlement of transactions by a central bank or other public institutions of or within the international banking community;

the European Currency Unit both within the European Monetary System and for the settlement of transactions by public institutions of or within the European Communities; or

any currency unit or composite currency other than the European Currency Unit for the purposes for which it was established.
Unless otherwise provided in the applicable prospectus supplement, all payments of principal of, and any premium or make-whole amount, and interest on, any debt security that is payable in a foreign currency that ceases to be used by its government of issuance shall be made in United States dollars.

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The applicable prospectus supplement may further describe the provisions, if any, permitting such defeasance or covenant defeasance, including any modifications to the provisions described above, with respect to the debt securities of or within a particular series.
Conversion Rights
The terms and conditions, if any, upon which the debt securities are convertible into common stock or other securities of ours will be set forth in the applicable prospectus supplement. The terms will include whether the debt securities are convertible into shares of common stock sinceor other securities of ours, the date on which it provided information for this table.

        Beneficial ownership is determined in accordance withconversion price, or manner of calculation thereof, the rulesconversion period, provisions as to whether conversion will be at the issuing company’s option or the option of the SECholders, the events requiring an adjustment of the conversion price and includes votingprovisions affecting conversion in the event of the redemption of the debt securities and any restrictions on conversion.

Global Securities
The debt securities of a series may be issued in whole or investment powerin part in the form of one or more global securities that will be deposited with, or on behalf of, a depository identified in the applicable prospectus supplement relating to such series. Global securities, if any, issued in the United States are expected to be deposited with The Depository Trust Company (“DTC”), as depository. We may issue global securities in either registered or bearer form and in either temporary or permanent form. We will describe the specific terms of the depository arrangement with respect to our common stock. Generally, a series of debt securities in the applicable prospectus supplement relating to such series. We expect that unless the applicable prospectus supplement provides otherwise, the following provisions will apply to depository arrangements.
Once a global security is issued, the depository for such global security or its nominee will credit on its book-entry registration and transfer system the respective principal amounts of the individual debt securities represented by such global security to the accounts of participants that have accounts with such depository. Such accounts shall be designated by the underwriters, dealers or agents with respect to such debt securities or by us if we offer such debt securities directly. Ownership of beneficial interests in such global security will be limited to participants with the depository or persons that may hold interests through those participants.
We expect that, under procedures established by DTC, ownership of beneficial interests in any global security for which DTC is the depository will be shown on, and the transfer of that ownership will be effected only through, records maintained by DTC or its nominee, with respect to beneficial interests of participants with the depository, and records of participants, with respect to beneficial interests of persons who hold through participants with the depository. Neither we nor the trustee will have any responsibility or liability for any aspect of the records of DTC or for maintaining, supervising or reviewing any records of DTC or any of its participants relating to beneficial ownership interests in the debt securities. The laws of some states require that certain purchasers of securities take physical delivery of such securities in definitive form. Such limits and laws may impair the ability to own, pledge or transfer beneficial interest in a global security.
So long as the depository for a global security or its nominee is the registered owner of such global security, such depository or such nominee, as the case may be, will be considered the sole owner or holder of the debt securities represented by the global security for all purposes under the applicable indenture. Except as described below or in the applicable prospectus supplement, owners of beneficial interest in a global security will not be entitled to have any of the individual debt securities represented by such global security registered in their names, will not receive or be entitled to receive physical delivery of any such debt securities in definitive form and will not be considered the owners or holders thereof under the applicable indenture. Beneficial owners of debt securities evidenced by a global security will not be considered the owners or holders thereof under the applicable indenture for any purpose, including with respect to the giving of any direction, instructions or approvals to the trustee under the indenture. Accordingly, each person "beneficially owns" sharesowning a beneficial interest in a global security with respect to which DTC is the depository must rely on the procedures of our common stockDTC and, if such person is not a participant with the depository, on the procedures of the participant through which such person has or shares with othersowns its interests, to exercise any rights of a holder under the right to vote those shares or to disposeapplicable indenture. We understand that, under existing industry practice, if DTC requests any action of them,holders or if an owner of a beneficial interest in a global security desires to give or take any action which a holder is entitled to give or take under the person hasapplicable indenture, DTC would authorize the rightparticipants holding the

20


relevant beneficial interest to acquire votinggive or disposition rights within 60 days.

        The informationtake such action, and such participants would authorize beneficial owners through such participants to give or take such actions or would otherwise act upon the instructions of beneficial owners holding through them.

Payments of principal of, and any premium or make-whole amount, and interest on, individual debt securities represented by a global security registered in the table below andname of a depository or its nominee will be made to or at the footnotes thereto regarding sharesdirection of common stock tothe depository or its nominee, as the case may be, beneficially owned afteras the offering assumesregistered owner of the sale of all shares being offered byglobal security under the selling stockholders under this prospectus. The percentage of shares owned prior to and after the offering is based on 24,085,588 shares of common stock outstanding as of August 15, 2018. This information has


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been obtained from the selling stockholders or in Schedules 13G or 13D and other public documents filed with the SEC.

 
 Prior to Offering  
 After Offering(3) 
Name and Address
 Number of
Shares
Beneficially
Owned(1)
 Percentage of
Shares
Beneficially
Owned
 Number of
Shares
Offered(2)
 Number of
Shares
Beneficially
Owned
 Percentage of
Shares
Beneficially
Owned
 

BVF Partners L.P.

  3,867,967(4) 16.1% 1,250,000  2,617,967  10.9%

44 Montgomery Street, 40th Floor

                

San Francisco, CA 94104

                

Farallon Capital Offshore Investors II, LP

  1,829,684(5) 7.6% 746,200  1,083,484  4.5%

c/o Farallon Capital Management, L.L.C.

                

One Maritime Plaza, #2100

                

San Francisco, CA 94111

                

Farallon Capital Institutional Partners, LP

  764,500(6) 3.2% 292,500  472,000  2.0%

c/o Farallon Capital Management, L.L.C.

                

One Maritime Plaza, #2100

                

San Francisco, CA 94111

                

Farallon Capital Partners, LP

  723,300(7) 3.0% 277,500  445,800  1.9%

c/o Farallon Capital Management, L.L.C.

                

One Maritime Plaza, #2100

                

San Francisco, CA 94111

                

Farallon Capital Institutional Partners II, LP

  132,000(8) *  52,500  79,500  * 

c/o Farallon Capital Management, L.L.C.

                

One Maritime Plaza, #2100

                

San Francisco, CA 94111

                

Four Crossings Institutional Partners V, L.P.

  113,100(9) *  45,000  68,100  * 

c/o Farallon Capital Management, L.L.C.

                

One Maritime Plaza, #2100

                

San Francisco, CA 94111

                

Farallon Capital F5 Master I, L.P.

  92,600(10) *  37,500  55,100  * 

c/o Farallon Capital Management, L.L.C.

                

One Maritime Plaza, #2100

                

San Francisco, CA 94111

                

Farallon Capital Institutional Partners III, LP

  90,400(11) *  33,800  56,600  * 

c/o Farallon Capital Management, L.L.C.

                

One Maritime Plaza, #2100

                

San Francisco, CA 94111

                

Farallon Capital (AM) Investors, LP

  44,300(12) *  15,000  29,300  * 

c/o Farallon Capital Management, L.L.C.

                

One Maritime Plaza, #2100

                

San Francisco, CA 94111

                

*
Less than 1%

(1)
applicable indenture. Under the terms of the Warrants,applicable indenture, we and the trustee may treat the persons in whose name debt securities, including a global security, are registered as the owners thereof for the purpose of receiving such payments. Consequently, neither we nor the trustee have or will have any responsibility or liability for the payment of such amounts to beneficial owners of debt securities including principal, any premium or make-whole amount, or interest. We believe, however, that it is currently the policy of DTC to immediately credit the accounts of relevant participants with such payments, in amounts proportionate to their respective holdings of beneficial interests in the relevant global security as shown on the records of DTC or its nominee. We also expect that payments by participants to owners of beneficial interests in such global security held through such participants will be governed by standing instructions and customary practices, as is the case with securities held for the account of customers in bearer form or registered in street name, and will be the responsibility of such participants. Redemption notices with respect to any debt securities represented by a global security will be sent to the depository or its nominee. If less than all of the debt securities of any series are to be redeemed, we expect the depository to determine the amount of the interest of each participant in such debt securities to be redeemed to be determined by lot. Neither we, the trustee, any paying agent nor the security registrar for such debt securities will have any responsibility or liability for any aspect of the records relating to or payments made on account of beneficial ownership interests in the global security for such debt securities or for maintaining any records with respect thereto.
Neither we nor the trustee will be liable for any delay by the holders of a global security or the depository in identifying the beneficial owners of debt securities, and we and the trustee may conclusively rely on, and will be protected in relying on, instructions from the holder of a global security or the depository for all purposes. The rules applicable to DTC and its participants are on file with the SEC.
If a depository for any debt securities is at any time unwilling, unable or ineligible to continue as depository and we do not appoint a successor depository within 90 days, we will issue individual debt securities in exchange for the global security representing such debt securities. In addition, we may at any time and at our sole discretion, subject to any limitations described in the applicable prospectus supplement relating to such debt securities, determine not to have any of such debt securities represented by one or more global securities and in such event will issue individual debt securities in exchange for the global security or securities representing such debt securities. Individual debt securities so issued will be issued in denominations of $1,000 and integral multiples of $1,000.
The debt securities of a series may also be issued in whole or in part in the form of one or more bearer global securities that will be deposited with a depository, or with a nominee for such depository, identified in the applicable prospectus supplement. Any such bearer global securities may be issued in temporary or permanent form. The specific terms and procedures, including the specific terms of the depositary arrangement, with respect to any portion of a series of debt securities to be represented by one or more bearer global securities will be described in the applicable prospectus supplement.
No Recourse
There is no recourse under any obligation, covenant or agreement in the applicable indenture or with respect to any security against any of our or our successor’s past, present or future shareholders, employees, officers or directors.

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DESCRIPTION OF WARRANTS
The following description, together with the additional information we may include in any applicable prospectus supplements, summarizes the material terms and provisions of the warrants that we may offer under this prospectus and the related warrant agreements and warrant certificates. While the terms summarized below will apply generally to any warrants that we may offer, we will describe the particular terms of any series of warrants in more detail in the applicable prospectus supplement. If we indicate in the prospectus supplement, the terms of any warrants offered under that prospectus supplement may differ from the terms described below. Specific warrant agreements will contain additional important terms and provisions and will be incorporated by reference as an exhibit to the registration statement, which includes this prospectus.
General
We may issue warrants for the purchase of common stock, preferred stock and/or debt securities in one or more series. We may issue warrants independently or together with common stock, preferred stock and/or debt securities, and the warrants may be attached to or separate from these securities.
We will evidence each series of warrants by warrant certificates that we will issue under a separate warrant agreement. We will enter into the warrant agreement with a warrant agent. We will indicate the name and address of the warrant agent in the applicable prospectus supplement relating to a particular series of warrants.
We will describe in the applicable prospectus supplement the terms of the series of warrants, including:

the offering price and aggregate number of warrants offered;

the currency for which the warrants may be purchased;

if applicable, the designation and terms of the securities with which the warrants are issued and the number of warrants issued with each such security or each principal amount of such security;

if applicable, the date on and after which the warrants and the related securities will be separately transferable;

in the case of warrants to purchase debt securities, the principal amount of debt securities purchasable upon exercise of one warrant and the price at, and currency in which, this principal amount of debt securities may be purchased upon such exercise;

in the case of warrants to purchase common stock or preferred stock, the number of shares of our common stock thator preferred stock, as the case may be, acquired by a selling stockholderpurchasable upon anythe exercise of a Warrant is generally limited toone warrant and the extent necessary to ensure that, followingprice at which these shares may be purchased upon such exercise, such selling stockholder would not, together with its affiliates andexercise;

the effect of any merger, consolidation, sale or other persons or entities whose beneficial ownershipdisposition of our common stock would be aggregated with such selling stockholderbusiness on the warrant agreement and the warrants;

the terms of any rights to redeem or call the warrants;

any provisions for purposes of Section 13(d) ofchanges to or adjustments in the Exchange Act, beneficially own in excess of 9.99% of the totalexercise price or number of shares of our common stock then issued and outstanding and/or the then combined voting power of all of our voting securities (the

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    "Blockers"); provided, that such Blocker is waivable by the selling stockholder upon notice to us up to a 19.99% maximum. As noted in footnote (2), the number of shares shown under the column titled "Number of Shares Offered" is shown without regard to the foregoing limitations on exercise.

(2)
The number of shares offered hereby, for each selling stockholder, consists solely of the shares issuable upon exercise of the Class A Warrantswarrants;

the periods during which, and Class B Warrants issuedplaces at which, the warrants are exercisable;

the manner of exercise;

the dates on which the right to such selling stockholder. The sharesexercise the warrants will commence and expire;

the manner in which the warrant agreement and warrants may be modified;

federal income tax consequences of holding or exercising the warrants;

the terms of the securities issuable upon exercise of the warrants will become eligible for sale bywarrants; and

any other specific terms, preferences, rights or limitations of or restrictions on the selling stockholders under this prospectus only as the warrants are exercised. In addition, the numberwarrants.

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DESCRIPTION OF UNITS
We may issue units comprised of shares offered hereby shown under the column titled "Number of Shares Offered" includes the maximum number of shares issuable upon the exercise of the Warrants without regard to the limitations on exercise described in footnote (1) above.

(3)
Assumes sale of all shares available for sale under this prospectus and no further acquisitions of shares by the selling stockholders.

(4)
Consists of (i) 1,209,268 outstanding shares of common stock, owned by Biotechnology Value Fund, L.P. ("BVF") and 577,541 shares of commonpreferred stock, issuable upon the exercise ofdebt securities and warrants held by BVF, (ii) 951,770 outstanding shares of common stock owned by Biotechnology Value Fund II, L.P. ("BVF2")in any combination. We may issue units in such amounts and 454,455 shares of common stock issuable upon the exercise of warrants held by BVF2, (iii) 199,196 outstanding shares of common stock owned by Biotechnology Value Trading Fund OS, L.P. ("Trading Fund OS") and 88,264 shares of common stock issuable upon the exercise of warrants held by Trading Fund OS, (iv) 98,347 outstanding shares of common stock owned by Investment 10, LLC ("INV10") and 44,748 shares of common stock issuable upon the exercise of warrants held by ("INV10") and (v) 159,386 outstanding shares of common stock owned by MSI BVF SPV, L.L.C. ("MSI" and together with BVF, BVF2, Trading Fund OS and INV10, the "BVF Investment Entities") and 84,992 shares of common stock issuable upon the exercise of warrants held by MSI. BVF Partners L.P. ("BVF Partners") is the general partner of BVF and BVF2, and the investment manager of each of Trading Fund OS, INV10 and MSI, and may be deemed to beneficially own the shares held by the BVF Investment Entities. BVF, Inc.,in as the general partner of BVF Partners, may be deemed to beneficially own the shares beneficially owned by BVF Partners. Mark Lampert,many distinct series as a director and officer of BVF, Inc., may be deemed to beneficially own the shares beneficially owned by BVF, Inc.

(5)
Consists of (i) 1,083,484 outstanding shares of common stock owned by Farallon Capital Offshore Investors II, LP ("FCOI II") and (ii) 746,200 shares of common stock issuable upon the exercise of warrants held by FCOI II. Each of Philip D. Dreyfuss, Michael B. Fisch, Richard B. Fried, David T. Kim, Monica R. Landry, Michael G. Linn, Rajiv A. Patel, Thomas G. Roberts, Jr., William Seybold, Andrew J.M. Spokes, John R. Warren and Mark C. Wehrly (collectively, the "Managing Members"), as a managing member or senior managing memberwe wish. This section outlines certain provisions of the general partner, share votingunits that we may issue. If we issue units, they will be issued under one or more unit agreements to be entered into between us and dispositive powera bank or other financial institution, as unit agent. The information described in this section may not be complete in all respects and is qualified entirely by reference to the unit agreement with respect to the shares held by FCOI II. Eachunits of any particular series. The specific terms of any series of units offered will be described in the applicable prospectus supplement. If so described in a particular supplement, the specific terms of any series of units may differ from the general description of terms presented below. We urge you to read any prospectus supplement related to any series of units we may offer, as well as the complete unit agreement and unit certificate that contain the terms of the Managing Members disclaims beneficial ownershipunits. If we issue units, forms of unit agreements and unit certificates relating to such shares exceptunits will be incorporated by reference as exhibits to the registration statement, which includes this prospectus.
Each unit that we may issue will be issued so that the holder of the unit is also the holder of each security included in the unit. Thus, the holder of a unit will have the rights and obligations of a holder of each included security. The unit agreement under which a unit is issued may provide that the securities included in the unit may not be held or transferred separately, at any time or at any time before a specified date. The applicable prospectus supplement may describe:

the designation and terms of the units and of the securities comprising the units, including whether and under what circumstances those securities may be held or transferred separately;

any provisions of the governing unit agreement;

the price or prices at which such units will be issued;

the applicable United States federal income tax considerations relating to the units;

any provisions for the issuance, payment, settlement, transfer or exchange of the units or of the securities comprising the units; and

any other terms of the units and of the securities comprising the units.
The provisions described in this section, as well as those described under “Description of Capital Stock,” “Description of Debt Securities” and “Description of Warrants” will apply to the securities included in each unit, to the extent of his or her pecuniary interest therein.

(6)
Consists of (i) 472,000 outstanding shares of common stock owned by Farallon Capital Institutional Partners, LP ("FCIP")relevant and (ii) 292,500 shares of common stock issuable upon the exercise of warrants held by FCIP. Eachas may be updated in any prospectus supplements.
Issuance in Series
We may issue units in such amounts and in as many distinct series as we wish. This section summarizes terms of the Managing Members, as a managing member or senior managing memberunits that apply generally to all series. Most of the general partner, share votingfinancial and dispositive powerother specific terms of your series will be described in the applicable prospectus supplement.
Unit Agreements
We will issue the units under one or more unit agreements to be entered into between us and a bank or other financial institution, as unit agent. We may add, replace or terminate unit agents from time to time. We will identify the unit agreement under which each series of units will be issued and the unit agent under that agreement in the applicable prospectus supplement.
The following provisions will generally apply to all unit agreements unless otherwise stated in the applicable prospectus supplement:
Modification without Consent
We and the applicable unit agent may amend any unit or unit agreement without the consent of any holder:

to cure any ambiguity, including modifying any provisions of the governing unit agreement that differ from those described below;

23



to correct or supplement any defective or inconsistent provision; or

to make any other change that we believe is necessary or desirable and will not adversely affect the interests of the affected holders in any material respect.
We do not need any approval to make changes that affect only units to be issued after the changes take effect. We may also make changes that do not adversely affect a particular unit in any material respect, even if they adversely affect other units in a material respect. In those cases, we do not need to obtain the approval of the holder of the unaffected unit; we need only obtain any required approvals from the holders of the affected units.
Modification with Consent
We may not amend any particular unit or a unit agreement with respect to any particular unit unless we obtain the shares held by FCIP. Eachconsent of the Managing Members disclaims beneficial ownershipholder of such shares exceptthat unit, if the amendment would:

impair any right of the holder to exercise or enforce any right under a security included in the extentunit if the terms of his or her pecuniary interest therein.

(7)
Consiststhat security require the consent of (i) 445,800 outstanding shares of common stock owned by Farallon Capital Partners, LP ("FCP") and (ii) 277,500 shares of common stock issuable uponthe holder to any changes that would impair the exercise or enforcement of warrants held by FCP. Eachthat right; or

reduce the percentage of outstanding units or any series or class the Managing Members, as a managing memberconsent of whose holders is required to amend that series or senior managing member ofclass, or the general partner, share voting and dispositive powerapplicable unit agreement with respect to that series or class, as described below.
Any other change to a particular unit agreement and the shares heldunits issued under that agreement would require the following approval:

if the change affects only the units of a particular series issued under that agreement, the change must be approved by FCP. Eachthe holders of

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    the Managing Members disclaims beneficial ownership of such shares except to the extent of his or her pecuniary interest therein.

(8)
Consists of (i) 79,500 outstanding shares of common stock owned by Farallon Capital Institutional Partners II, LP ("FCIP II") and (ii) 52,500 shares of common stock issuable upon the exercise of warrants held by FCIP II. Each a majority of the Managing Members,outstanding units of that series; or

if the change affects the units of more than one series issued under that agreement, it must be approved by the holders of a majority of all outstanding units of all series affected by the change, with the units of all the affected series voting together as one class for this purpose.
These provisions regarding changes with majority approval also apply to changes affecting any securities issued under a unit agreement, as the governing document.
In each case, the required approval must be given by written consent.
Unit Agreements Will Not Be Qualified under Trust Indenture Act
No unit agreement will be qualified as an indenture, and no unit agent will be required to qualify as a managing member or senior managing membertrustee, under the Trust Indenture Act. Therefore, holders of units issued under unit agreements will not have the protections of the general partner, share voting and dispositive powerTrust Indenture Act with respect to their units.
Mergers and Similar Transactions Permitted; No Restrictive Covenants or Events of Default
The unit agreements will not restrict our ability to merge or consolidate with, or sell our assets to, another corporation or other entity or to engage in any other transactions. If at any time we merge or consolidate with, or sell our assets substantially as an entirety to, another corporation or other entity, the shares heldsuccessor entity will succeed to and assume our obligations under the unit agreements. We will then be relieved of any further obligation under these agreements.
The unit agreements will not include any restrictions on our ability to put liens on our assets, nor will they restrict our ability to sell our assets. The unit agreements also will not provide for any events of default or remedies upon the occurrence of any events of default.
Governing Law
The unit agreements and the units will be governed by FCIP II. EachDelaware law.

24


Form, Exchange and Transfer
Unless the accompanying prospectus supplement states otherwise, we will issue each unit in global — i.e., book-entry — form only. Units in book-entry form will be represented by a global security registered in the name of a depositary, which will be the holder of all the units represented by the global security. Those who own beneficial interests in a unit will do so through participants in the depositary’s system, and the rights of these indirect owners will be governed solely by the applicable procedures of the Managing Members disclaims beneficial ownership of such shares except todepositary and its participants. We will describe book-entry securities, and other terms regarding the extent of his or her pecuniary interest therein.

(9)
Consists of (i) 68,100 outstanding shares of common stock owned by Four Crossings Institutional Partners V, L.P. ("Four CIP V")issuance and (ii) 45,000 shares of common stock issuable upon the exercise of warrants held by Four CIP V. Eachregistration of the Managing Members,units in the applicable prospectus supplement.
Unless the accompanying prospectus supplement states otherwise, each unit and all securities comprising the unit will be issued in the same form.
If we issue any units in registered, non-global form, the following will apply to them.
The units will be issued in the denominations stated in the applicable prospectus supplement. Holders may exchange their units for units of smaller denominations or combined into fewer units of larger denominations, as a managerlong as the total amount is not changed.

Holders may exchange or senior managertransfer their units at the office of the general partner, share votingunit agent. Holders may also replace lost, stolen, destroyed or mutilated units at that office. We may appoint another entity to perform these functions or perform them ourselves.

Holders will not be required to pay a service charge to transfer or exchange their units, but they may be required to pay for any tax or other governmental charge associated with the transfer or exchange. The transfer or exchange, and dispositive powerany replacement, will be made only if our transfer agent is satisfied with the holder’s proof of legal ownership. The transfer agent may also require an indemnity before replacing any units.

If we have the right to redeem, accelerate or settle any units before their maturity, and we exercise our right as to less than all those units or other securities, we may block the exchange or transfer of those units during the period beginning 15 days before the day we mail the notice of exercise and ending on the day of that mailing, in order to freeze the list of holders to prepare the mailing. We may also refuse to register transfers of or exchange any unit selected for early settlement, except that we will continue to permit transfers and exchanges of the unsettled portion of any unit being partially settled. We may also block the transfer or exchange of any unit in this manner if the unit includes securities that are or may be selected for early settlement.
Only the depositary will be entitled to transfer or exchange a unit in global form, since it will be the sole holder of the unit.
Payments and Notices
In making payments and giving notices with respect to our units, we will follow the shares held by Four CIP V. Each ofprocedures as described in the Managing Members disclaims beneficial ownership of such shares except to the extent of his or her pecuniary interest therein.

(10)
Consists of (i) 55,100 outstanding shares of common stock owned by Farallon Capital F5 Master I, L.P. ("FCF5M") and (ii) 37,500 shares of common stock issuable upon the exercise of warrants held by FCF5M. Each of the Managing Members, as a manager or senior manager of the general partner, share voting and dispositive power with respect to the shares held by FCF5M. Each of the Managing Members disclaims beneficial ownership of such shares except to the extent of his or her pecuniary interest therein.

(11)
Consists of (i) 56,600 outstanding shares of common stock owned by Farallon Capital Institutional Partners III, LP ("FCIPIII") and (ii) 33,800 shares of common stock issuable upon the exercise of warrants held by FCIPIII. Each of the Managing Members, as a managing member or senior managing member of the general partner, share voting and dispositive power with respect to the shares held by FCIPIII. Each of the Managing Members disclaims beneficial ownership of such shares except to the extent of his or her pecuniary interest therein.

(12)
Consists of (i) 29,300 outstanding shares of common stock owned by Farallon Capital (AM) Investors, LP ("FCAMI") and (ii) 15,000 shares of common stock issuable upon the exercise of warrants held by FCAMI. Each of the Managing Members, as a managing member or senior managing member of the general partner, share voting and dispositive power with respect to the shares held by FCAMI. Each of the Managing Members disclaims beneficial ownership of such shares except to the extent of his or her pecuniary interest therein.
applicable prospectus supplement.

25


PLAN OF DISTRIBUTION

We are registeringmay sell the shares of common stock issuable to the selling stockholders upon the exercise of the selling stockholders' Warrants to permit the resale of such shares of common stock by such holderssecurities from time to time afterpursuant to underwritten public offerings, negotiated transactions, block trades or a combination of these methods. We may sell the date of this prospectus. We will not receive any of the proceeds from the sale by the selling stockholders of the shares of common stock. We will bear all fees and expenses incidentsecurities to our obligationor through underwriters or dealers, through agents, or directly to register such shares of common stock.

        Each selling stockholder, which may include donees, pledgees, transferees or other successors-in-interest selling shares of common stock or interests in shares of common stock received after the date of this prospectus from a selling stockholder as a gift, pledge, partnership distribution or other transfer, may, from time to time, sell, transfer or otherwise dispose of any or all of its shares of common stock or interests in shares of common stock on any stock exchange, market or trading facility on which the shares are traded or in private transactions. These dispositions may be at fixed prices, at prevailing market prices at the time of sale, at prices related to the prevailing market price, at varying prices determined at the time of sale, or at privately negotiated prices.

        A selling stockholder may use any one or more of the following methods when disposing of shares or interests therein:

    ordinary brokerage transactions and transactions in which the broker-dealer solicits purchasers;

    block trades in which the broker-dealer will attempt to sell the shares as agent, butpurchasers. We may position and resell a portion of the block as principal to facilitate the transaction;

    purchases by a broker-dealer as principal and resale by the broker-dealer for its own account;

    an exchange distribution in accordance with the rules of the applicable exchange;

    privately negotiated transactions;

    to the extent permitted by law, short sales effected after the date the registration statement of which this prospectus is a part is declared effective by the SEC;

    through the writing or settlement of options or other hedging transactions, whether through an options exchange or otherwise;

    through agreements between broker-dealers and the selling stockholders to sell a specified number of such shares at a stipulated price per share;

    a combination of any such methods of sale; and

    any other method permitted by applicable law.

        The selling stockholders may, from time to time, pledge or grant a security interest in some or all of the shares of common stock owned by them and, if they default in the performance of their secured obligations, the pledgees or secured parties may offer and sell the shares of common stock, from time to time, under this prospectus, or under an amendment to this prospectus under Rule 424(b) or other applicable provision of the Securities Act amending the list of selling stockholders to include the pledgee, transferee or other successors in interest as selling stockholders under this prospectus. The selling stockholders also may transfer the shares of common stock in other circumstances, in which case the pledgees, transferees or other successors in interest will be the selling beneficial owners for purposes of this prospectus.

        In connection with the sale of our common stock or interests therein, the selling stockholders may enter into hedging transactions with broker-dealers or other financial institutions, which may in turn engage in short sales of the common stock in the course of hedging the positions they assume. The selling stockholders may also sell shares of our common stock short and deliver thesedistribute securities to close


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out their short positions, or loan or pledge the common stock to broker-dealers that in turn may sell these securities. The selling stockholders may also enter into options or other transactions with broker-dealers or other financial institutions or the creation of one or more derivative securities which require the delivery to each such broker-dealer or other financial institution of shares offered by this prospectus, which shares such broker-dealer or other financial institution may resell pursuant to this prospectus (as supplemented or amended to reflect such transaction).

        The aggregate proceeds to the selling stockholders from the sale of the common stock offered by them will be the purchase price of the common stock less discounts or commissions, if any. Each of the selling stockholders reserves the right to accept and, together with its agents from time to time, to reject, in whole or in part, any proposed purchase of common stock to be made directly or through agents. We will not receive any of the proceeds from this offering.

        The selling stockholders also may resell all or a portion of the shares in open market transactions, rather than under this prospectus, in reliance upon Rule 144 under the Securities Act, provided that they meet the criteria and conform to the requirements of that rule.

        The selling stockholders and any underwriters, broker-dealers or agents that participate in the sale of the common stock or interests therein may be "underwriters" within the meaning of Section 2(11) of the Securities Act. Any discounts, commissions, concessions or profit they earn on any resale of the shares may be underwriting discounts and commissions under the Securities Act. Selling stockholders who are "underwriters" within the meaning of Section 2(11) of the Securities Act will be subject to the prospectus delivery requirements of the Securities Act.

        To the extent required, the shares of our common stock to be sold, the names of the selling stockholders, the respective purchase prices and public offering prices, the names of any agents, dealer or underwriter, and any applicable commissions or discounts with respect to a particular offer will be set forth in an accompanying prospectus supplement or, if appropriate, a post-effective amendment to the registration statement that includes this prospectus.

        If underwriters are used in the sale, the shares of common stock will be acquired by the underwriters for their own account and may be resold from time to time in one or more transactions:


at a fixed price or prices, which may be changed;

at market prices prevailing at the time of sale;

at prices related to such prevailing market prices; or

at negotiated prices.
We may also sell equity securities covered by this registration statement in an “at the market offering” as defined in Rule 415 under the Securities Act. Such offering may be made into an existing trading market for such securities in transactions at other than a fixed price, either:

on or through the facilities of The Nasdaq Global Market or any other securities exchange or quotation or trading service on which such securities may be listed, quoted or traded at the time of sale; and/or

to or through a market maker otherwise than on The Nasdaq Global Market or such other securities exchanges or quotation or trading services.
Such at the market offerings, if any, may be conducted by underwriters acting as principal or agent.
A prospectus supplement or supplements (and any related free writing prospectus that we may authorize to be provided to you) will describe the terms of the offering of the securities, including, negotiatedto the extent applicable:

the name or names of any underwriters, dealers or agents, if any;

the purchase price of the securities and the proceeds we will receive from the sale;

any options under which underwriters may purchase additional securities from us;

any agency fees or underwriting discounts and other items constituting agents’ or underwriters’ compensation;

any public offering price;

any discounts or concessions allowed or re-allowed or paid to dealers; and

any securities exchange or market on which the securities may be listed.
Only underwriters named in the prospectus supplement are underwriters of the securities offered by the prospectus supplement.
If underwriters are used in the sale, they will acquire the securities for their own account and may resell the securities from time to time in one or more transactions at a fixed public offering price or at varying prices determined at the time of sale. In connection with any such underwritten sale of shares of common stock, underwriters may receive compensation from the selling stockholders, for whom they may act as agents, in the form of discounts, concessions or commissions. If the selling stockholders use an underwriter or underwriters to effectuate the sale of shares of common stock, we and/or they will execute an underwriting agreement with those underwriters at the time of sale of those shares of common stock. To the extent required by law, the names of the underwriters will be set forth in a prospectus supplement or, if appropriate, a post-effective amendment to the registration statement that includes the prospectus supplement and the accompanying prospectus used by the underwriters to sell those securities. The obligations of the underwriters to purchase those shares of common stockthe securities will be subject to the conditions set forth in the applicable underwriting agreement. We may offer the securities to the public through underwriting syndicates represented by managing underwriters or by underwriters without a syndicate. Subject to certain conditions, precedent, and unless otherwise specified in a prospectus supplement, the underwriters will be obligated to purchase all of the shares of common stocksecurities offered by suchthe prospectus supplement if any of such shares of common stock are purchased.supplement. Any public offering price and any discounts or concessions allowed or re-allowed or paid to dealers may be changedchange from time to time.

We may use underwriters with whom we have advised the selling stockholders that the anti-manipulation rules of Regulation M under the Exchange Act may apply to sales of sharesa material relationship. We will describe in the marketprospectus supplement, naming the underwriter, the nature of any such relationship.

We may sell securities directly or through agents we designate from time to time. We will name any agent involved in the offering and to the activities of the selling stockholders and their affiliates. The selling stockholders may indemnify any broker-dealer that participates in transactions involving the sale of securities, and we will describe any commissions we will pay the sharesagent in the prospectus supplement. Unless the prospectus supplement states otherwise, our agent will act on a best-efforts basis for the period of its appointment.

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We may authorize agents or underwriters to solicit offers by certain types of institutional investors to purchase securities from us at the public offering price set forth in the prospectus supplement pursuant to delayed delivery contracts providing for payment and delivery on a specified date in the future. We will describe the conditions to these contracts and the commissions we must pay for solicitation of these contracts in the prospectus supplement.
We may provide agents and underwriters with indemnification against certaincivil liabilities including liabilities arising under the Securities Act.


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        We are requiredrelated to pay certain fees and expenses incurred by us incidentofferings pursuant to the registration of the shares of common stock of the selling stockholders. We have agreed to indemnify the selling stockholders against certain losses, claims, damages and liabilities,this prospectus, including liabilities under the Securities Act, or contribution with respect to payments that the agents or underwriters may make with respect to these liabilities. Agents and underwriters may engage in transactions with, or perform services for, us in the selling stockholdersordinary course of business.

All securities we offer, other than our shares of common stock, will be new issues of securities with no established trading market. Any underwriters may make a market in these securities, but will not be entitledobligated to contribution.do so and may discontinue any market making at any time without notice. We may be indemnified bycannot guarantee the selling stockholders against certain losses, claims, damages and liabilities, including liabilities under the Securities Act that may arise from any written information furnished to us by the selling stockholders specifically for use in this prospectus, or we may be entitled to contribution.

        We have agreed with the selling stockholders to keep the registration statement of which this prospectus constitutes a part effective until the earlier of (1) such time as allliquidity of the shares covered by this prospectus have been disposed of pursuant totrading markets for any securities.

Any underwriter may engage in overallotment, stabilizing transactions, short covering transactions and penalty bids in accordance with Regulation M under the registration statement or pursuant to Rule 144Exchange Act. Overallotment involves sales in excess of the Securities Actoffering size, which create a short position. Stabilizing transactions permit bids to purchase the underlying security so long as the stabilizing bids do not exceed a specified maximum. Short covering transactions involve purchases of the securities in the open market after the distribution is completed to cover short positions. Penalty bids permit the underwriters to reclaim a selling concession from a dealer when the securities originally sold by the dealer are purchased in a stabilizing or (2) August 8, 2020.

covering transaction to cover short positions. Those activities may cause the price of the securities to be higher than it would otherwise be. If commenced, the underwriters may discontinue any of the activities at any time. These transactions may be effected on any exchange or over-the-counter market or otherwise.
Any underwriters who are qualified market makers on The Nasdaq Global Market may engage in passive market making transactions in the securities on The Nasdaq Global Market in accordance with Rule 103 of Regulation M, during the business day prior to the pricing of the offering, before the commencement of offers or sales of the securities. Passive market makers must comply with applicable volume and price limitations and must be identified as passive market makers. In general, a passive market maker must display its bid at a price not in excess of the highest independent bid for such security; if all independent bids are lowered below the passive market maker’s bid, however, the passive market maker’s bid must then be lowered when certain purchase limits are exceeded. Passive market making may stabilize the market price of the securities at a level above that which might otherwise prevail in the open market and, if commenced, may be discontinued at any time.

27


LEGAL MATTERS

        Cooley LLP will pass upon

Certain legal matters, including the validitylegality of the securities offered, pursuant towill be passed upon for us by Gibson, Dunn & Crutcher LLP, San Francisco, California. Additional legal matters may be passed upon for us or any underwriters, dealers or agents, by counsel that we will name in the applicable prospectus supplement.
EXPERTS
Ernst & Young LLP, independent registered public accounting firm, has audited our consolidated financial statements as of December 31, 2021 and 2020 and for each of the years then ended, included in our Annual Report on Form 10-K for the year ended December 31, 2021, and the effectiveness of our internal control over financial reporting as of December 31, 2021, as set forth in their reports, which are incorporated by reference in this prospectus and elsewhere in the registration statement.


Our financial statements are incorporated by reference in reliance on Ernst & Young LLP’s report, given on their authority as experts in accounting and auditing.
EXPERTS

The financial statements for the year ended December 31, 2019 incorporated in this registration statementprospectus by reference to the Annual Report on Form 10-K for the year ended December 31, 20172021 have been so incorporated in reliance on the report of PricewaterhouseCoopers LLP, an independent registered public accounting firm, given on the authority of said firm as experts in auditing and accounting.


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WHERE YOU CAN FIND MORE INFORMATION

We file annual, quarterly and other reports, proxy statements and other information with the SEC. Our SEC filings are available to the public over the Internet at the SEC’s website at www.sec.gov. Our Annual Report on Form 10-K, Quarterly Reports on Form 10-Q, and Current Reports on Form 8-K, including any amendments to those reports, and other information that we file with or furnish to the SEC pursuant to Section 13(a) or 15(d) of the Exchange Act can also be accessed free of charge through the Internet. These filings will be available as soon as reasonably practicable after we electronically file such material with, or furnish it to, the SEC.
This prospectus is part of a registration statement that we filed with the SEC. This prospectus does not contain all of theomits some information set forthcontained in the registration statement in accordance with SEC rules and regulations. You should review the information and exhibits toin the registration statement. Forstatement for further information with respect toabout us and our subsidiaries and the securities we are offering underoffering. Statements in this prospectus concerning any document we refer youfiled as an exhibit to the registration statement or that we otherwise filed with the SEC are not intended to be comprehensive and are qualified by reference to these filings. You should review the exhibitscomplete document to evaluate these statements.

29


INCORPORATION OF CERTAIN INFORMATION BY REFERENCE
The SEC allows us to incorporate by reference the information and schedulesreports we file with it, which means that we can disclose important information to you by referring you to these documents. The information incorporated by reference is an important part of this prospectus, and information that we file after the date hereof with the SEC will automatically update and supersede the information already incorporated by reference. We are incorporating by reference the documents listed below:


our Quarterly Reports on Form 10-Q for the quarters ended March 31, 2022, filed with the SEC on May 5, 2022, and June 30, 2022, filed with the SEC on August 4, 2022;

our Current Reports on Form 8-K filed with the SEC on February 22, 2022, March 23, 2022, March 31, 2022 and June 2, 2022; and

the description of our common stock set forth in our registration statement on Form 8-A, filed with the SEC on August 9, 2016, including any amendments thereto or reports filed for the purposes of updating this description, including Exhibit 4.7 to our Annual Report on Form 10-K for the fiscal year ended December 31, 2021, filed with the SEC on February 28, 2022.
All documents we file with the SEC pursuant to Sections 13(a), 13(c), 14 or 15(d) of the Exchange Act shall be deemed incorporated by reference in this prospectus and to be a part of this prospectus from the date of filing of those documents, with the exception of any portion of any report or document that is not deemed “filed” under such provisions on or after the date of this prospectus, until the earlier of the date on which: (1) all of the securities registered hereunder have been sold; or (2) the registration statement. Neitherstatement of which this prospectus is a part has been withdrawn.
Under no circumstances will any information filed under Items 2.02 or 7.01 of Current Report on Form 8-K be deemed incorporated herein by reference unless such Form 8-K expressly provides to the contrary.
Upon written or oral request, we nor any agent, underwriterwill provide without charge to each person to whom a copy of the prospectus is delivered a copy of the documents incorporated by reference herein (other than exhibits to such documents unless such exhibits are specifically incorporated by reference herein). You may request a copy of these filings, at no cost, by writing, calling or dealer hasemailing us at the contact information set forth below. We have authorized any personno one to provide you with different information. We are not making an offer of these securitiesany information that differs from that contained in this prospectus. Accordingly, we take no responsibility for any state where the offer is not permitted.other information that others may give you. You should not assume that the information in this prospectus is accurate as of any date other than the date onof the front cover of this prospectus.
Protagonist Therapeutics, Inc.
7707 Gateway Boulevard, Suite 140
Newark, CA 94560-1160
(510) 474-0170

30

Protagonist Therapeutics, Inc.
[MISSING IMAGE: lg_protagonist-pn.jpg]
COMMON STOCK
PREFERRED STOCK
DEBT SECURITIES
WARRANTS
UNITS
PROSPECTUS
           , 2022

The information in this prospectus supplement is not complete and may be changed. We may not sell these securities until the registration statement filed with the Securities and Exchange Commission is effective. This prospectus supplement is not an offer to sell these securities and is not soliciting an offer to buy these securities in any state where the offer or sale is not permitted.
SUBJECT TO COMPLETION, DATED AUGUST 5, 2022
PROSPECTUS SUPPLEMENT
(To prospectus dated            , 2022)
[MISSING IMAGE: lg_protagonist-pn.jpg]
Up to $100,000,000 of Shares
Common Stock
We have entered into an Open Market Sale AgreementSM (the “sales agreement”) with Jefferies LLC (“Jefferies”) relating to the sale of shares of our common stock offered by this prospectus supplement and the accompanying prospectus. In accordance with the terms of the sales agreement, we may offer and sell shares of our common stock, $0.00001 par value per share, from time to time having an aggregate offering price of up to $100.0 million through Jefferies, acting as our sales agent.
Our common stock is traded on The Nasdaq Global Market under the symbol “PTGX.” On August 2, 2022, the last reported sale price of our common stock was $10.63 per share.
Sales of our shares, if any, under this prospectus supplement and the accompanying prospectus may be made in sales deemed to be an “at the market offering” as defined in Rule 415(a)(4) promulgated under the Securities Act of 1933, as amended (the “Securities Act”). Jefferies is not required to sell any specific number or dollar amount of securities, but will act as a sales agent using commercially reasonable efforts consistent with its normal trading and sales practices, on mutually agreed terms between Jefferies and us. There is no arrangement for funds to be received in any escrow, trust or similar arrangement.
Jefferies will be entitled to compensation under the terms of the sales agreement at a fixed commission rate of up to 3% of the gross sales price per share sold under the sales agreement. See “Plan of Distribution” beginning on page S-11 for additional information regarding Jefferies’ compensation. In connection with the sale of common stock on our behalf, Jefferies will be deemed to be an “underwriter” within the meaning of the Securities Act and the compensation of Jefferies will be deemed to be underwriting commissions or discounts. We have also agreed to provide indemnification to Jefferies against certain liabilities, including liabilities under the Securities Act or the Securities Exchange Act of 1934, as amended (the “Exchange Act”). See section titled “Plan of Distribution” on page S-11 of this prospectus regardlesssupplement.
Investing in our securities involves a high degree of risk. See “Risk Factors” beginning on page S-6 of this prospectus supplement and under similar headings in the other documents that are incorporated by reference into this prospectus supplement.
Neither the Securities and Exchange Commission nor any state securities commission has approved or disapproved of these securities, or determined if this prospectus supplement or the accompanying prospectus are truthful or complete. Any representation to the contrary is a criminal offense.
Jefferies
           , 2022


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S-2
S-3
S-4
S-6
S-8
S-9
S-11
S-13
S-13
S-14
S-15

S-1


ABOUT THIS PROSPECTUS SUPPLEMENT
This prospectus supplement relates to the offering of shares of our common stock. Before buying any of the timeshares of deliverycommon stock that we are offering, we urge you to carefully read this prospectus supplement, together with the information incorporated by reference as described under the headings “Where You Can Find More Information” and “Incorporation of Certain Information by Reference”, the accompanying prospectus and any free writing prospectus that we have authorized for use in connection with this offering. These documents contain important information that you should consider when making your investment decision. In general, when we refer only to the prospectus, we are referring to both the prospectus supplement and the accompanying prospectus combined.
This prospectus describes the terms of this offering of shares of common stock and also adds to and updates information contained in the documents incorporated by reference into this prospectus. To the extent there is a conflict between the information contained in this prospectus, on the one hand, and the information contained in any document incorporated by reference into this prospectus that was filed with the Securities and Exchange Commission (“SEC”) before the date of this prospectus, on the other hand, you should rely on the information in this prospectus. If any statement in one of these documents is inconsistent with a statement in another document having a later date — for example, a document incorporated by reference into this prospectus — the statement in the document having the later date modifies or supersedes the earlier statement.
We have not, and Jefferies has not, authorized any other person to provide you with information that is in addition to or different from that contained or incorporated by reference in this prospectus, along with the information contained in any permitted free writing prospectuses we have authorized for use in connection with this offering. Neither we nor Jefferies take any responsibility for, or can provide any assurance as to the reliability of, any information other than the information contained or incorporated by reference in this prospectus or any permitted free writing prospectuses we have authorized for use in connection with this offering. You should assume that the information appearing in this prospectus is accurate only as of the date on the front cover of this prospectus.
Our business, financial condition, results of operations and prospects may have changed since that date. Information contained on, or accessible through, our website is not part of this prospectus. We and Jefferies are offering to sell, and seeking offers to buy, shares of common stock only in jurisdictions where offers and sales are permitted. The distribution of this prospectus and the offering of the common stock in certain jurisdictions may be restricted by law. Persons outside the United States who come into possession of this prospectus must inform themselves about, and observe any restrictions relating to, the offering of the common stock and the distribution of this prospectus outside the United States. This prospectus does not constitute, and may not be used in connection with, an offer to sell, or a solicitation of an offer to buy, any securities offered by this prospectus by any person in any jurisdiction in which it is unlawful for such person to make such an offer or solicitation.
Unless the context otherwise requires, we use the terms “Protagonist,” the “company,” “we,” “us,” and “our” in this prospectus to refer to Protagonist Therapeutics, Inc. and, where appropriate, our subsidiaries.

S-2


PROSPECTUS SUPPLEMENT SUMMARY
The following summary of our business highlights certain of the information contained elsewhere in, or incorporated by reference into, this prospectus supplement and the accompanying prospectus. This summary is not complete and does not contain all of the information that you should consider before deciding whether to invest in shares of our common stock. You should carefully read this entire prospectus supplement and the accompanying prospectus, including any information incorporated by reference, which are described under the headings “Where You Can Find Additional Information” and “Incorporation of Certain Information by Reference” herein and therein. In particular, you should carefully consider the risks and uncertainties described under the heading “Risk Factors” in this prospectus supplement and in the accompanying prospectus, as well as those contained in the other documents incorporated by reference herein and any related free writing prospectus.
Company Overview
We are a biopharmaceutical company with peptide-based new chemical entities rusfertide, PN-943 and PN-235 in different stages of development, all derived from the Company’s proprietary discovery technology platform. Our clinical programs fall into two broad categories of diseases; (i) hematology and blood disorders, and (ii) inflammatory and immunomodulatory diseases.
Corporate Information
Our principal executive offices are located at 7707 Gateway Boulevard, Suite 140, Newark, California 94560. Our telephone number is (510) 474-0170. Our website address is www.protagonist‑inc.com. References to our website address do not constitute incorporation by reference of the information contained on the website, and the information contained on the website is not part of this document. We have included our website in this prospectus supplement solely as an inactive textual reference.

S-3


THE OFFERING
Common stock offered by us pursuant to this prospectus supplement
Shares of our common stock having an aggregate offering price of up to $100.0 million.
Common stock to be outstanding immediately after this
offering
Up to 58,091,268 shares of our common stock, assuming sales of 9,407,337 shares of our common stock in this offering at a public offering price of $10.63 per share, which was the last reported sale price per share of our common stock on the Nasdaq Global Market on August 2, 2022. The actual number of shares of our common stock issued will vary depending on the sales price under this offering.
Plan of distribution
“At the market offering” that may be made from time to time through our sales agent, Jefferies. See “Plan of Distribution” on page S-11 of this prospectus supplement.
Use of proceeds
We currently intend to use the net proceeds from this offering for working capital, capital expenditures and general corporate purposes, which may include, among other things, funding research and development, clinical trials, vendor payables, potential regulatory submissions, hiring additional personnel and capital expenditures. See “Use of Proceeds” on page S-8 of this prospectus supplement.
Risk factors
Investing in our common stock involves significant risks. Please read the information contained in and incorporated by reference under the heading “Risk Factors” on page S-6 of this prospectus supplement and page 4 of the accompanying prospectus and under similar headings in the other documents that are filed after the date hereof and incorporated by reference into this prospectus supplement, together with the other information included in or incorporated by reference into this prospectus supplement and the accompanying prospectus, before deciding whether to invest in our common stock.
Nasdaq Global Market
symbol
“PTGX”
The number of shares of common stock to be outstanding after this offering is based on 48,683,931 shares of our common stock outstanding as of June 30, 2022 and excludes:

5,564,352 shares of common stock issuable upon the exercise of stock options issued and outstanding under our 2016 Equity Incentive Plan (the “2016 Plan”), as of June 30, 2022, having a weighted average exercise price of $19.96 per share;

737,340 shares of common stock issuable upon the vesting of outstanding restricted stock units, under the 2016 Plan, as of June 30, 2022;

219,000 shares of common stock issuable upon the vesting of outstanding performance stock units, under the 2016 Plan, as of June 30, 2022;

an aggregate of 817,303 shares of common stock, subject to increase on an annual basis, reserved for future issuance under the 2016 Plan, as of June 30, 2022;

944,197 shares of common stock issuable upon the exercise of stock options issued and outstanding under our Amended and Restated 2018 Inducement Plan, as amended (the “Inducement Plan”), as of June 30, 2022, having a weighted average exercise price of $22.38 per share;

S-4



28,750 shares of common stock issuable upon the vesting of outstanding restricted stock units, under the Inducement Plan, as of June 30, 2022;

an aggregate of 601,042 shares of common stock reserved for future issuance under the Inducement Plan, as of June 30, 2022;

316,572 shares of common stock issuable upon the exercise of stock options issued and outstanding under our 2007 Equity Incentive Plan, as of June 30, 2022, having a weighted average exercise price of $3.38 per share;

1,285,068 shares of our common stock reserved for future issuance under our 2016 Employee Stock Purchase Plan, as of June 30, 2022;

2,750,000 shares of common stock issuable upon the exercise of warrants outstanding as of June 30, 2022, at a weighted average exercise price of $12.50 per share; and

400,000 shares of common stock issuable upon the exercise of warrants outstanding as of June 30, 2022, at a weighted average exercise price of $0.00001 per share.
Unless otherwise indicated, all information in this prospectus supplement assumes no exercise of outstanding stock options or warrants or vesting of restricted stock units or performance stock units as of June 30, 2022.

S-5


RISK FACTORS
Investing in our securities involves risks. You should carefully consider the risks, uncertainties and other factors described in our most recent Annual Report on Form 10-K, as supplemented and updated by subsequent Quarterly Reports on Form 10-Q and Current Reports on Form 8-K that we have filed or will file with the SEC, and in other documents which are incorporated by reference into this prospectus supplement, including the risk factors and other information contained in or incorporated by reference into this prospectus supplement before investing in any of our securities. Our business, financial condition, results of operations, cash flows or prospectus supplement could be materially adversely affected by any of these risks. The risks and uncertainties described in the documents incorporated by reference herein are not the only risks and uncertainties that you may face.
Risks Relating to this Offering
We have broad discretion as to the use of proceeds from this offering and may not use the proceeds effectively.
Our management will retain broad discretion as to the allocation of the proceeds and may spend these proceeds in ways in which you may not agree. We intend to use the net proceeds, if any, from this offering for working capital, capital expenditures and general corporate purposes, which may include, among other things, funding research and development, clinical trials, vendor payables, potential regulatory submissions, hiring additional personnel and capital expenditures. Our management will have considerable discretion in the application of the net proceeds, and you will not have the opportunity, as part of your investment decision, to assess whether the proceeds are being used appropriately. The failure of our management to apply these funds effectively could result in unfavorable returns and uncertainty about our prospects, each of which could cause the price of our common stock to decline.
You may experience immediate and substantial dilution in the net tangible book value per share of the common stock you purchase.
The price per share of common stock being offered may be higher than the net tangible book value per share of our outstanding common stock prior to this offering. Assuming that an aggregate of 9,407,337 shares of common stock are sold at a price of $10.63 per share, the last reported sale price of shares of our common stock on The Nasdaq Global Market on August 2, 2022, for aggregate gross proceeds of approximately $100 million, and after deducting commissions and estimated offering expenses payable by us, new investors in this offering would incur immediate dilution of $4.34 per share. In addition, you may also experience additional dilution after this offering on any future equity issuances, including the issuance of common stock in connection with the 2016 Plan or the Inducement Plan. To the extent we raise additional capital by issuing equity securities, our stockholders will experience substantial additional dilution. See “Dilution” for additional information.
You may experience future dilution as a result of future equity offerings.
In order to raise additional capital, we expect to in the future offer additional shares of our common stock or other securities convertible into or exchangeable for our common stock. We cannot assure you that we will be able to sell shares or other securities in any other offering at a price per share that is equal to or greater than the price per share paid by investors in this offering, and investors purchasing shares or other securities in the future could have rights superior to existing stockholders. The price per share at which we sell additional shares of our common stock or other securities convertible into or exchangeable for our common stock in future transactions may be higher or lower than the price per share in this offering.
The actual number of shares of common stock we will issue under the sales agreement, at any one time or in total, is uncertain.
Subject to certain limitations in the sales agreement and compliance with applicable law, we have the discretion to deliver a placement notice to Jefferies at any time throughout the term of the sales agreement. The number of shares of common stock that are sold by Jefferies after delivering a placement notice will fluctuate based on the market price of the shares of common stock during the sales period and limits we set with Jefferies. Because the price per share of each share sold will fluctuate based on the market price of

S-6


shares of our common stock during the sales period, it is not possible at this stage to predict the number of shares of common stock that will be ultimately issued.
The shares of common stock offered hereby will be sold in “at the market offerings,” and investors who buy common stock at different times will likely pay different prices.
Investors who purchase shares in this offering at different times will likely pay different prices, and so may experience different outcomes in their investment results. We will have discretion, subject to market demand, to vary the timing, prices, and numbers of shares sold, and there is no maximum sales price. Pursuant to the parameters set by our board of directors, there will be a minimum sales price for shares of our common stock sold in this offering, which will limit our ability to make sales if the public trading price of our common stock drops below that minimum sales price. Such minimum sales price may be below the price paid by investors in this offering. Further, our board of directors will retain the ability to increase or decrease such minimum sales price in the future. Investors may experience a decline in the value of their shares as a result of share sales made at prices lower than the prices they paid.

S-7


USE OF PROCEEDS
We will retain broad discretion over the use of the net proceeds, if any, from the sale of the securities offered hereby. We may issue and sell shares of common stock having aggregate sales proceeds of up to $100,000,000 from time to time. Because there is no minimum offering amount required as a condition to close this offering, the actual total public offering amount, commissions and proceeds to us, if any, are not determinable at this time.
We intend to use the net proceeds from the sale by us of the securities to which this prospectus.

prospectus supplement relates for working capital, capital expenditures and general corporate purposes, which may include, among other things, funding research and development, clinical trials, vendor payables, potential regulatory submissions, hiring additional personnel and capital expenditures.

Pending the use of the net proceeds, we may invest the proceeds in interest-bearing, investment-grade securities, certificates of deposit or government securities.

S-8


DILUTION
Dilution represents the difference between the amount per share of common stock paid by purchasers of shares of common stock in this offering and the as-adjusted net tangible book value per share of our common stock immediately after this offering. The data in this section are derived from our balance sheet as of June 30, 2022. Net tangible book value per share of common stock is equal to our total tangible assets less the amount of our total liabilities, divided by the sum of the number of shares of common stock outstanding as of June 30, 2022, excluding shares of common stock underlying outstanding options. Our net tangible book value as of June 30, 2022 was $268.0 million, or $5.50 per share of common stock.
After giving effect to the assumed sale of shares of common stock in the aggregate amount of $100,000,000 at an assumed offering price of $10.63 per share, which was the last reported sale price per share of our common stock on The Nasdaq Global Market on August 2, 2022, and after deducting commissions and estimated offering expenses payable by us, our as-adjusted net tangible book value as of June 30, 2022 would have been $365.4 million, or $6.29 per share of common stock. This would represent an immediate increase in net tangible book value to existing stockholders of $0.79 per share of common stock and immediate dilution in pro forma to purchasers of shares of common stock in this offering of $4.34 per share of common stock. The following table illustrates this dilution per share of common stock:
Assumed public offering price per share of common stock$10.63
Net tangible book value per share of common stock as of June 30, 2022$5.50
Increase in net tangible book value per share of common stock attributable to new investors$0.79
As-adjusted net tangible book value per share of common stock immediately after this
offering
$6.29
Dilution per share of common stock to new investors$4.34
The table above assumes, for illustrative purposes, that an aggregate of 9,407,337 shares of our common stock are sold at a price of $10.63 per share, the last reported sale price of our common stock on the Nasdaq Global Market on August 2, 2022, for aggregate gross proceeds of $100 million. The shares sold in this offering, if any, will be sold from time to time at various prices. An increase of $1.00 per share in the price at which the shares are sold from the assumed offering price of $10.63 per share shown in the table above, assuming all of our common stock in the aggregate amount of $100 million during the term of the sales agreement with Jefferies is sold at that price, would result in an increase in the dilution in net tangible book value per share to new investors in this offering to $4.25 per share, after deducting commissions and estimated aggregate offering expenses payable by us. A decrease of $1.00 per share in the price at which the shares are sold from the assumed offering price of $10.63 per share shown in the table above, assuming all of our common stock in the aggregate amount of $100 million during the term of the sales agreement with Jefferies is sold at that price, would result in a decrease in the dilution in net tangible book value per share to new investors in this offering to $4.44 per share, after deducting commissions and estimated aggregate offering expenses payable by us. This information is supplied for illustrative purposes only and may differ based on the actual offering price and the actual number of shares offered.
The above discussion and table are based on 48,683,931 shares of our common stock outstanding as of June 30, 2022 and exclude:

5,564,352 shares of common stock issuable upon the exercise of stock options issued and outstanding under the 2016 Plan, as of June 30, 2022, having a weighted average exercise price of $19.96 per share;

737,340 shares of common stock issuable upon the vesting of outstanding restricted stock units, under the 2016 Plan, as of June 30, 2022;

219,000 shares of common stock issuable upon the vesting of outstanding performance stock units, under the 2016 Plan, as of June 30, 2022;

an aggregate of 817,303 shares of common stock, subject to increase on an annual basis, reserved for future issuance under the 2016 Plan, as of June 30, 2022;

S-9



944,197 shares of common stock issuable upon the exercise of stock options issued and outstanding under the Inducement Plan, as of June 30, 2022, having a weighted average exercise price of $22.38 per share;

28,750 shares of common stock issuable upon the vesting of outstanding restricted stock units under the Inducement Plan, as of June 30, 2022;

an aggregate of 601,042 shares of common stock reserved for future issuance under the Inducement Plan, as of June 30, 2022;

316,572 shares of common stock issuable upon the exercise of stock options issued and outstanding under our 2007 Equity Incentive Plan, as of June 30, 2022, having a weighted average exercise price of $3.38 per share;

1,285,068 shares of our common stock reserved for future issuance under our 2016 Employee Stock Purchase Plan, as of June 30, 2022;

2,750,000 shares of common stock issuable upon the exercise of warrants outstanding as of June 30, 2022, at a weighted average exercise price of $12.50 per share; and

400,000 shares of common stock issuable upon the exercise of warrants outstanding as of June 30, 2022, at a weighted average exercise price of $0.00001 per share.
To the extent that options or warrants outstanding as of June 30, 2022 have been or may be exercised, restricted stock units or performance units outstanding as of June 30, 2022 continue to vest, or other shares are issued, investors purchasing our common stock in this offering may experience further dilution. In addition, we may choose to raise additional capital due to market conditions or strategic considerations even if we believe we have sufficient funds for our current or future operating plans. To the extent that additional capital is raised through the sale of equity or convertible debt securities, the issuance of these securities could result in further dilution to our stockholders.

S-10


PLAN OF DISTRIBUTION
We have entered into a sales agreement with Jefferies, under which we may offer and sell up to $100,000,000 of our shares of common stock from time to time through Jefferies acting as agent. Sales of our shares of common stock, if any, under this prospectus supplement and the accompanying prospectus will be made by any method that is deemed to be an “at the market offering” as defined in Rule 415(a)(4) under the Securities Act.
Each time we wish to issue and sell our shares of common stock under the sales agreement, we will notify Jefferies of the number of shares to be issued, the dates on which such sales are anticipated to be made, any limitation on the number of shares to be sold in any one day and any minimum price below which sales may not be made. Once we have so instructed Jefferies, unless Jefferies declines to accept the terms of such notice, Jefferies has agreed to use its commercially reasonable efforts consistent with its normal trading and sales practices to sell such shares up to the amount specified on such terms. The obligations of Jefferies under the sales agreement to sell our shares of common stock are subject to a number of conditions that we must meet.
The settlement of sales of shares between us and Jefferies is generally anticipated to occur on the second trading day following the date on which the sale was made. Sales of our shares of common stock as contemplated in this prospectus supplement will be settled through the facilities of The Depository Trust Company or by such other means as we and Jefferies may agree upon. There is no arrangement for funds to be received in an escrow, trust or similar arrangement.
We will pay Jefferies a commission of up to 3% of the aggregate gross proceeds we receive from each sale of our shares of common stock. Because there is no minimum offering amount required as a condition to close this offering, the actual total public offering amount, commissions and proceeds to us, if any, are not determinable at this time. In addition, we have agreed to reimburse Jefferies for the fees and disbursements of its counsel, payable upon execution of the sales agreement, in an amount not to exceed $75,000, in addition to certain ongoing disbursements of its legal counsel. We estimate that the total expenses for the offering, excluding any commissions or expense reimbursement payable to Jefferies under the terms of the sales agreement, will be approximately $300,000. The remaining sale proceeds, after deducting any other transaction fees, will equal our net proceeds from the sale of such shares.
Jefferies will provide written confirmation to us before the open on The Nasdaq Global Market on the day following each day on which our shares of common stock are sold under the sales agreement. Each confirmation will include the number of shares sold on that day, the aggregate gross proceeds of such sales and the proceeds to us.
In connection with the sale of our shares of common stock on our behalf, Jefferies will be deemed to be an “underwriter” within the meaning of the Securities Act, and the compensation of Jefferies will be deemed to be underwriting commissions or discounts. We have agreed to indemnify Jefferies against certain civil liabilities, including liabilities under the Securities Act. We have also agreed to contribute to payments Jefferies may be required to make in respect of such liabilities.
The offering of our shares of common stock pursuant to the sales agreement will terminate upon the earlier of (i) the sale of all shares of common stock subject to the sales agreement and (ii) the termination of the sales agreement as permitted therein. We and Jefferies may each terminate the sales agreement at any time upon ten trading days’ prior notice.
This summary of the material provisions of the sales agreement does not purport to be a complete statement of its terms and conditions. The sales agreement has been filed as an exhibit to our Registration Statement on Form S-3 of which this prospectus supplement forms a part.
Jefferies and its affiliates may in the future provide various investment banking, commercial banking, financial advisory and other financial services for us and our affiliates, for which services they may in the future receive customary fees. In the course of its business, Jefferies may actively trade our securities for its own account or for the accounts of customers, and, accordingly, Jefferies may at any time hold long or short positions in such securities.

S-11


A prospectus supplement and the accompanying prospectus in electronic format may be made available on a website maintained by Jefferies, and Jefferies may distribute the prospectus supplement and the accompanying prospectus electronically.

S-12


LEGAL MATTERS
Gibson, Dunn & Crutcher LLP, San Francisco, California will pass upon the validity of the shares of common stock offered hereby. Latham & Watkins LLP is counsel for Jefferies in connection with this offering.
EXPERTS
Ernst & Young LLP, independent registered public accounting firm, has audited our consolidated financial statements as of December 31, 2021 and 2020 and for each of the years then ended, included in our Annual Report on Form 10-K for the year ended December 31, 2021, and the effectiveness of our internal control over financial reporting as of December 31, 2021, as set forth in their reports, which are incorporated by reference in this prospectus and elsewhere in the registration statement. Our financial statements are incorporated by reference in reliance on Ernst & Young LLP’s report, given on their authority as experts in accounting and auditing.
The financial statements for the year ended December 31, 2019 incorporated in this prospectus supplement by reference to the Annual Report on Form 10-K for the year ended December 31, 2021 have been so incorporated in reliance on the report of PricewaterhouseCoopers LLP, an independent registered public accounting firm, given on the authority of said firm as experts in auditing and accounting.

S-13


WHERE YOU CAN FIND MORE INFORMATION
We file annual, quarterly and currentspecial reports, proxy statements and other information with the SEC. You may readSEC, and copy any document we filehave filed with the SEC ata registration statement on Form S-3 under the SEC's public reference room at 100 F Street, N.E., Washington, D.C., 20549. Please callSecurities Act of 1933, as amended (the “Securities Act”) with respect to the SEC at 1.800.SEC.0330 forsecurities offered by this prospectus. This prospectus, which forms part of the registration statement, does not contain all of the information included in the registration statement, including its exhibits and schedules. For further information onabout us and the operation ofsecurities described in this prospectus, you should refer to the public reference room. registration statement, its exhibits and schedules and our reports, proxies, information statements and other information filed with the SEC.
Our SEC filings are also available to the public aton the SEC'sInternet, through a database maintained by the SEC at
http://www.sec.gov. We also maintain a website at http://www.sec.gov.

www.protagonist-inc.com. We have included our website address for the information of prospective investors and do not intend it to be an active link to our website. Information contained on our website does not constitute a part of this prospectus (or any document incorporated by reference herein).

S-14


INCORPORATION OF CERTAIN INFORMATION BY REFERENCE

The SEC allows us to "incorporateincorporate by reference"reference the information and reports we file with it, which means that we can disclose important information to you by referring you to those documents instead of having to repeat the information in this prospectus.these documents. The information incorporated by reference is considered to bean important part of this prospectus, and later information that we file after the date hereof with the SEC will automatically update and supersede this information.the information already incorporated by reference. We incorporateare incorporating by reference the documents listed below and any future filings (including those made after the date of the initial filing of the registration statement of which this prospectus is a part and prior to the effectiveness of such registration statement) we will make with the SEC under Sections 13(a), 13(c), 14, or 15(d) of the Exchange Act until the termination of the offering of the shares covered by this prospectus (other than information furnished under Item 2.02 or Item 7.01 of Form 8-K):

    below:



our Quarterly ReportReports on Form 10-Q for the quarterquarters ended March 31, 2018,2022, filed with the SEC on May 9, 2018;

our Quarterly Report on Form 10-Q for the quarter ended5, 2022, and June 30, 2018,2022, filed with the SEC on August 7, 2018;4, 2022;


our current reportsCurrent Reports on Form 8-K filed with the SEC on February 27, 2018, 22, 2022, March 26, 2018, May 16, 2018, May23, 2022, March 31, 20182022 and August 7, 2018;June 2, 2022; and


the description of our common stock set forth in our registration statement on Form 8-A, filed with the SEC on August 9, 2016, including any amendments thereto or reports filed for the purposes of updating this description.

description, including Exhibit 4.7 to our Annual Report on Form 10-K for the fiscal year ended December 31, 2021, filed with the SEC on February 28, 2022.

All documents we file with the SEC pursuant to Sections 13(a), 13(c), 14 or 15(d) of the Exchange Act shall be deemed incorporated by reference in this prospectus and to be a part of this prospectus from the date of filing of those documents, with the exception of any portion of any report or document that is not deemed “filed” under such provisions on or after the date of this prospectus, until the earlier of the date on which: (1) all of the securities registered hereunder have been sold; or (2) the registration statement of which this prospectus is a part has been withdrawn.
Under no circumstances will any information filed under Items 2.02 or 7.01 of Current Report on Form 8-K be deemed incorporated herein by reference unless such Form 8-K expressly provides to the contrary.
Upon written or oral request, we will provide without charge to each person to whom a copy of the prospectus is delivered a copy of the documents incorporated by reference herein (other than exhibits to such documents unless such exhibits are specifically incorporated by reference herein). You canmay request a copy of these filings, at no cost, by writing, calling or telephoningemailing us at the following address or telephone number:

contact information set forth below. We have authorized no one to provide you with any information that differs from that contained in this prospectus. Accordingly, we take no responsibility for any other information that others may give you. You should not assume that the information in this prospectus is accurate as of any date other than the date of the front cover of this prospectus.

Protagonist Therapeutics, Inc.
7707 Gateway Boulevard, Suite 140
Newark, California 94560CA 94560-1160
(510) 474-0170
Attn: Chief Financial Officer

        This prospectus is part


S-15

UP TO $100,000,000
[MISSING IMAGE: lg_protagonist-pn.jpg]
Up to $100,000,000 of a registration statement we filed with the SEC. That registration statement and the exhibits filed along with the registration statement contain more information about us and the shares in this offering. Because information about documents referred to in this prospectus is not always complete, you should read the full documents which are filed as exhibits to the registration statement. You may read and copy the full registration statement and its exhibits at the SEC's public reference rooms or its website.

Shares
Common Stock
PROSPECTUS SUPPLEMENT
Jefferies
      , 2022


INFORMATION NOT REQUIRED IN THE PROSPECTUS

Item 14.   Other Expenses of Issuance and Distribution.
Distribution

The following sets forth the estimated costs and expenses all of which shall be bornepayable by the Registrant,us in connection with the offeringissuance and distribution of the securities pursuant to this Registration Statement:

being registered hereunder on Form S-3 (other than underwriting discounts and commissions, if any) are set forth below. Each item listed is estimated, except for the SEC registration fee.
Amount
To Be Paid
Securities and Exchange Commission registration fee$27,810
Printing fees and expenses*
Legal fees and expenses*
Accounting fees and expenses*
Transfer agent and registrar fees*
Miscellaneous fees and expenses*
Total$*

SEC Registration Fee

 $3,301 

Legal Fees and Expenses

 $125,000 

Accounting Fees

 $10,000 

Printing and Miscellaneous Fees

 $30,699 

Total

 $169,000 
*
Estimated expenses not presently known. Each prospectus supplement will reflect estimated expenses based on the amount of the related offering.

Item 15.   Indemnification of Directors and Officers.
Officers

Section 145 of the Delaware General Corporation Law authorizes a court to award, or a corporation'scorporation’s board of directors to grant, indemnity to directors and officers in terms sufficiently broad to permit such indemnification under certain circumstances for liabilities, including reimbursement for expenses incurred, arising under the Securities Act.

Act of 1933, as amended. Our amended and restated certificate of incorporation provides for indemnification of our directors, officers, employees and other agents to the maximum extent permitted by the Delaware General Corporation Law, and our amended and restated bylaws provide for indemnification of our directors, officers, employees and other agents to the maximum extent permitted by the Delaware General Corporation Law.

We have entered into indemnification agreements with our directors and officers whereby we have agreed to indemnify our directors and officers to the fullest extent permitted by law, including indemnification against expenses and liabilities incurred in legal proceedings to which the director or officer was, or is threatened to be made, a party by reason of the fact that such director or officer is or was a director, officer, employee or agent of Protagonist, provided that such director or officer acted in good faith and in a manner that the director or officer reasonably believed to be in, or not opposed to, the best interest of Protagonist. At present, there is no pending litigation or proceeding involving a director or officer of Protagonist regarding which indemnification is sought, nor is the registrant aware of any threatened litigation that may result in claims for indemnification.

We maintain insurance policies that indemnify our directors and officers against various liabilities arising under the Securities Act of 1933, as amended, and the Securities Exchange Act of 1934, as amended, that might be incurred by any director or officer in his capacity as such.

The underwriting agreement(s) that the Registrant may enter into may provide for indemnification by any underwriters of the Registrant, its directors, its officers who sign the registration statement and the Registrant'sRegistrant’s controlling persons for some liabilities, including liabilities arising under the Securities Act.

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Item 16.   Exhibits
A list of exhibits filed with this registration statement on Form S-3 is set forth on the Exhibit Index and Financial Statement Schedules

is incorporated herein by reference.
Exhibit
Number
Description of Exhibit
1.1*Form of Underwriting Agreement.
1.2***Open Market Sale AgreementSM, dated August 5, 2022, by and between Protagonist Therapeutics, Inc. and Jefferies LLC.
3.1Amended and Restated Certificate of Incorporation of the Registrant (incorporated by reference from Exhibit 3.1 to the Registrant’s Current Report on Form 8-K filed on August 16, 2016 (Commission File No. 001-37852)).
3.2Bylaws of the Registrant (incorporated by reference from Exhibit 3.2 to the Registrant’s Registration Statement on Form S-1, as amended, filed on August 1, 2016 (Commission File No. 333-212476)).
4.1Specimen stock certificate evidencing the shares of common stock (incorporated by reference from Exhibit 4.1 to the Registrant’s Registration Statement on Form S-1, as amended, filed on August 1, 2016 (Commission File No. 333-212476)).
4.2***
4.3***
4.4*Form of Warrant Agreement and Warrant Certificate.
4.5*Form of Unit Agreement and Unit Certificate.
5.1***
5.2***
23.1***
23.2***
23.3***
24.1***
25.1**Form T-1 Statement of Eligibility of Trustee for Senior Indenture under the Trust Indenture Act of 1939.
 25.2**Form T-1 Statement of Eligibility of Trustee for Subordinated Indenture under the Trust Indenture Act of 1939.
107***
(1)
PreviouslyTo be filed, if necessary, by amendment or as an exhibit to the Registrant'sa document to be incorporated or deemed to be incorporated by reference in this registration statement, including a Current Report on Form 8-K (File No. 001-37852)8-K.
**
To be filed in accordance with the Securities and Exchange Commission on August 16, 2016 and incorporated herein by reference.

requirements of Section 305(b)(2)
Previously filed as an exhibit to of the Registrant's Registration Statement on Form S-1,Trust Indenture Act of 1939, as amended, (File No. 333-212476), filed withand the Securities and Exchange Commission on August 1, 2016 and incorporated herein by reference.applicable rules thereunder.
***
Filed herewith.

(3)
Previously filed as an exhibit to the Registrant's Current Report on Form 8-K (File No. 001-37852) filed with the Securities and Exchange Commission on August 7, 2018 and incorporated herein by reference.

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Item 17.   Undertakings

The undersigned registrantsregistrant hereby undertakes:

(a)(1)   To file, during any period in which offers or sales are being made, a post-effective amendment to this registration statement:

(i)   toTo include any prospectus required by Section 10(a)(3) of the Securities Act of 1933;

1933, as amended (“Securities Act”);

(ii)   toTo reflect in the prospectus any facts or events arising after the effective date of the registration statement (or the most recent post-effective amendment thereof) which, individually or in the aggregate, represent a fundamental change in the information set forth in the registration statement. Notwithstanding the foregoing, any increase or decrease in volume of securities offered (if the total dollar value of securities offered would not exceed that which was registered) and any deviation from the low or high end of the estimated maximum offering range may be reflected in the form of prospectus filed with the Securities and Exchange Commission pursuant to Rule 424(b) if, in the aggregate, the changes in volume and price

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      represent no more than 20%a 20 percent change in the maximum aggregate offering price set forth in the "Calculation“Calculation of Registration Fee"Fee” table in the effective registration statement; and

(iii)   toTo include any material information with respect to the plan of distribution not previously disclosed in the registration statement or any material change to such information in the registration statement;

provided, however,, that the undertakings set forth in paragraphs (a)(1)(i), (a)(1)(ii) and (a)(1)(iii) of this section do not apply if the registration statement is on Form S-3, Form SF-3 or Form F-3 and the information required to be included in a post-effective amendment by those paragraphs is contained in reports filed with or furnished to the Securities and Exchange Commission by the registrant pursuant to Section 13 or Section 15(d) of the Securities Exchange Act of 1934, as amended (“Exchange Act”), that are incorporated by reference in the registration statement, or is contained in a form of prospectus filed pursuant to Rule 424(b) that is part of the registration statement.

            (b)statement;

(2)   That, for the purpose of determining any liability under the Securities Act, of 1933, each such post-effective amendment shall be deemed to be a new registration statement relating to the securities offered therein, and the offering of such securities at that time shall be deemed to be the initial bona fide offering thereof.

        (c)thereof;

(3)   To remove from registration by means of a post-effective amendment any of the securities being registered which remain unsold at the termination of the offering.

        (d)offering;

(4)   That, for the purpose of determining liability under the Securities Act of 1933 to any purchaser:

(i)   Each prospectus filed by the registrant pursuant to Rule 424(b)(3) shall be deemed to be part of the registration statement as of the date the filed prospectus was deemed part of and included in the registration statement; and

(ii)   Each prospectus required to be filed pursuant to Rule 424(b)(2), (b)(5), or (b)(7) as part of a registration statement in reliance on Rule 430B relating to an offering made pursuant to Rule 415(a)(1)(i), (vii), or (x) for the purpose of providing the information required by Section 10(a) of the Securities Act of 1933 shall be deemed to be part of and included in the registration statement as of the earlier of the date such form of prospectus is first used after effectiveness or the date of the first contract of sale of securities in the offering described in the prospectus. As provided in Rule 430B, for liability purposes of the issuer and any person that is at that date an underwriter, such date shall be deemed to be a new effective date of the registration statement relating to the securities in the registration statement to which that prospectus relates, and the offering of such securities at that time shall be deemed to be the initial bona fide offering thereof.Provided,thereof; provided, however, that no statement made in a registration statement or prospectus that is part of the registration statement or made in a document incorporated or deemed incorporated by reference into the registration statement or prospectus that is part of the registration statement will, as to a purchaser with a time of contract of sale prior to such effective date, supersede or modify any statement that was made in the registration statement or prospectus that was part of the registration statement or made in any such document immediately prior to such effective date.date;

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        (e)



(5)   That, for the purpose of determining liability of the registrant under the Securities Act of 1933 to any purchaser in the initial distribution of the securities, the undersigned registrant undertakes that in a primary offering of securities of the undersigned registrant pursuant to this registration statement, regardless of the underwriting method used to sell the securities to the purchaser, if the securities are offered or sold to such purchaser by means of any of the following communications, the undersigned registrant will be a seller to the purchaser and will be considered to offer or sell such securities to such purchaser:
(i)   Any preliminary prospectus or prospectus of the undersigned registrant relating to the offering required to be filed pursuant to Rule 424;
(ii)   Any free writing prospectus relating to the offering prepared by or on behalf of the undersigned registrant or used or referred to by the undersigned registrant;
(iii)   The portion of any other free writing prospectus relating to the offering containing material information about the undersigned registrant or its securities provided by or on behalf of the undersigned registrant; and
(iv)   Any other communication that is an offer in the offering made by the undersigned registrant to the purchaser;
(6)   That, for purposes of determining any liability under the Securities Act, of 1933, each filing of the registrant'sregistrant’s annual report pursuant to Section 13(a) or Section 15(d) of the Securities Exchange Act of 1934 (and, where applicable, each filing of an employee benefit plan'splan’s annual report pursuant to Section 15(d) of the Securities Exchange Act of 1934)Act) that is incorporated by reference in the registration statement shall be deemed to be a new registration statement relating to the securities offered therein, and the offering of such securities at that time shall be deemed to be the initial bona fide offering thereof.

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            (f)thereof;

(7)   Insofar as indemnification for liabilities arising under the Securities Act of 1933 may be permitted to directors, officers and controlling persons of the registrant pursuant to the foregoing provisions, or otherwise, the registrant has been advised that in the opinion of the Securities and Exchange Commission such indemnification is against public policy as expressed in the Securities Act and is, therefore, unenforceable. In the event that a claim for indemnification against such liabilities (other than the payment by the registrant of expenses incurred or paid by a director, officer or controlling person of the registrant in the successful defense of any action, suit or proceeding) is asserted by such director, officer or controlling person in connection with the securities being registered, the registrant will, unless in the opinion of its counsel the matter has been settled by controlling precedent, submit to a court of appropriate jurisdiction the question whether such indemnification by it is against public policy as expressed in the Securities Act and will be governed by the final adjudication of such issue.

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Tableissue;

(8)   That, for purposes of Contentsdetermining any liability under the Securities Act of 1933, the information omitted from the form of prospectus filed as part of this registration statement in reliance upon Rule 430A and contained in a form of prospectus filed by the registrant pursuant to Rule 424(b)(1) or (4) or 497(h) under the Securities Act of 1933 shall be deemed to be part of this registration statement as of the time it was declared effective;
(9)   That, for the purpose of determining any liability under the Securities Act of 1933, each post-effective amendment that contains a form of prospectus shall be deemed to be a new registration statement relating to the securities offered therein, and the offering of such securities at that time shall be deemed to be the initial bona fide offering thereof; and
(10)   To file an application for the purpose of determining the eligibility of the trustee to act under subsection (a) of Section 310 of the Trust Indenture Act of 1939 in accordance with the rules and regulations prescribed by the Securities and Exchange Commission under Section 305(b)(2) of the Trust Indenture Act of 1939.

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SIGNATURESSIGNATURES

Pursuant to the requirements of the Securities Act of 1933, the registrant certifies that it has reasonable grounds to believe that it meets all of the requirements for filing on Form S-3 and has duly caused this registration statement to be signed on its behalf by the undersigned, thereunto duly authorized, in the City of Newark, State of California, on September 6, 2018.

August 5, 2022.
PROTAGONIST THERAPEUTICS, INC.
By:
/s/ Dinesh V. Patel, Ph.D.
Dinesh V. Patel, Ph.D.
President, Chief Executive Officer and Director (Principal Executive Officer)
PROTAGONIST THERAPEUTICS, INC.



By:


/s/ DINESH V. PATEL, PH.D.

Dinesh V. Patel, Ph.D.
President, Chief Executive Officer and Director

POWER OF ATTORNEY

        KNOW ALL PERSONS BY THESE PRESENTS, that each

Each person whose individual signature appears below constituteshereby authorizes and appoints Dinesh V. Patel and Thomas P. O'Neil, his or her trueAsif Ali and lawful agent, proxy and attorney-in-fact, each acting alone,of them, with full power of substitution and resubstitution for himand full power to act without the other, as his or her true and lawful attorney in fact and agent to act in his or her name, place and stead and to execute in anythe name and all capacities,on behalf of each person, individually and in each capacity stated below, and to (i) act on, sign, and file with the SEC any and all amendments (including post-effective amendments) to this Registration Statement, including any and all post effective amendments and amendments thereto, and any registration statement together with all schedules and exhibits thereto, (ii) act on, sign and file such certificates, instruments, agreements and other documentsrelating to the same offering as maythis Registration Statement that is to be necessary or appropriate in connection therewith, (iii) act on and file any supplement to any prospectus included in this registration statement or any such amendment or any subsequent registration statement filedeffective upon filing pursuant to Rule 462(b) under the Securities Act of 1933, as amended, and (iv) take anyto file the same, with all exhibits thereto, and all actions which may be necessary or appropriateother documents in connection therewith, with the Securities and Exchange Commission, granting unto said attorneys in fact and agents, and each of them, full power and authority to be done, as fully for all intentsdo and purposes as he or she might or could do in person, hereby approving,perform each and every act and thing, ratifying and confirming all that such agent, proxysaid attorneys in fact and attorney-in-factagents or any of them or their or his substitute or substitutes may lawfully do or cause to be done by virtue thereof.

Pursuant to the requirements of the Securities Act of 1933, as amended, this Registration Statement and Power of Attorney has been signed by the following personsperson in the capacities and on the dates indicated:

date indicated.
Signature
Signatures
Title
Date




Date

/s/ DINESH V. PATEL, PH.D.

Dinesh V. Patel, Ph.D.
Dinesh V. Patel, Ph.D.
President, Chief Executive Officer and Director ((Principal Executive Officer)Officer)September 6, 2018August 5, 2022

/s/ THOMAS P. O'NEIL

Thomas P. O'NeilAsif Ali
Asif Ali


Chief Financial Officer ((Principal Financial andAnd Accounting Officer)Officer)

September 6, 2018
August 5, 2022

/s/ HAROLD E. SELICK, PH.D.

Harold E. Selick, Ph.D.
Harold E. Selick, Ph.D.


Director

Chairman of the Board of Directors

September 6, 2018
August 5, 2022

/s/ BRYAN GIRAUDO

Bryan Giraudo


Director


September 6, 2018

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Bryan Giraudo
Signatures
Title
Date





/s/ CHAITAN KHOSLA, PH.D.

Chaitan Khosla, Ph.D.
DirectorSeptember 6, 2018August 5, 2022

/s/ SARAH NOONBERG, M.D., PH.D.

Sarah Noonberg, M.D., Ph.D.
Sarah Noonberg, M.D., Ph.D.


Director

Director

September 6, 2018
August 5, 2022

/s/ ARMEN SHANAFELT, PH.D.

Armen Shanafelt, Ph.D.Sarah O’Dowd
Sarah O’Dowd


Director

Director

September 6, 2018
August 5, 2022

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SignatureTitleDate

/s/ WILLIAM D. WADDILL

William D. Waddill
William D. Waddill


Director

Director

September 6, 2018
August 5, 2022

/S/ LEWIS T. "RUSTY" WILLIAMS, M.D., PH.D.

s/ Lewis T. "Rusty" Williams, M.D., Ph.D.
Lewis T. Williams, M.D., Ph.D.


Director

Director

September 6, 2018
August 5, 2022


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