1, 2022
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Delaware | ||||
| | | 75-3175693 (I. R. S. Employer Identification No.) | |
4 Stamford Plaza
107 Elm Street
Stamford, Connecticut 06902
(203) 406-3700
(Address, including zip code, and telephone number, including area code, of registrant’s principal executive offices)
Derek Chalmers, Ph.D., D.Sc.
Chief Executive Officer
Cara Therapeutics, Inc.
4 Stamford Plaza
107 Elm Street
Stamford, Connecticut 06902
(203) 406-3700
(Name, address, including zip code, and telephone number, including area code, of agent for service)
Copies to:
Babak Yaghmaie
Darren DeStefano
Cooley LLP
1114 Avenue of the Americas
New York, NY 10036-7798 (212) 479-6000
From time to time after the effective date of this Registration Statement
(Approximate date of commencement of proposed sale to the public)
| 4 Stamford Plaza 107 Elm Street, 9th Floor Stamford, Connecticut 06902 (203) 406-3700 | |
| Christopher Posner Chief Executive Officer Cara Therapeutics, Inc. 4 Stamford Plaza 107 Elm Street, Ninth Floor Stamford, Connecticut 06902 (203) 406-3700 | |
| Copies to: Darren DeStefano Nicolas H.R. Dumont Cooley LLP 11951 Freedom Drive, 14th Floor Reston, VA 20190-5640 (703) 456-8000 | |
| From time to time after the effective date of this Registration Statement (Approximate date of commencement of proposed sale to the public) | |
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Large accelerated filer ☒ | | Accelerated filer ☐ | ||||
| Non-accelerated filer ☐ | | Smaller reporting company ☐ | | ||
| | | | Emerging Growth Company ☐ | |
CALCULATION OF REGISTRATION FEE
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Title of each class of securities to be registered | Amount to be | Proposed Maximum Offering Price per Unit | Proposed Maximum Aggregate Offering Price | Amount of Registration Fee (1) | ||||
Common Stock, par value $0.001 per share | (2) | (3) | (3) | — | ||||
Preferred Stock, par value $0.001 per share | (2) | (3) | (3) | — | ||||
Debt Securities | (2) | (3) | (3) | — | ||||
Warrants | (2) | (3) | (3) | — | ||||
Total | (2) | $250,000,000 | $28,999 | |||||
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1, 2022
300,000,000
2022.
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Our most advanced product candidateKORSUVA
In September 2015, we initiated our Phase 3 program for I.V. CR845 in postoperative pain with the dosing of the first subjects in an adaptive pivotal trial in patients undergoing a range of abdominal surgeries. The trial protocol initially included three dose levels of I.V. CR845 (1.0 ug/kg, 2.0 ug/kg and 5.0 ug/kg), which were compared to placebo with an interim conditional power assessment to identify optimal doses to be used to complete the enrollment of this trial.
In June 2016, we modified the trial protocol and resumed the trial as a three-arm trial, testing two doses of CR845 (1.0 ug/kg and 0.5 ug/kg) versus placebo, based on a safety review by us, the trial’s Independent Data Monitoring Committee and theonly U.S. Food and Drug Administration, or FDA, of unblinded safety data from-approved treatment for moderate-to-severe pruritus associated with chronic kidney disease, or CKD, in adults undergoing hemodialysis. We are developing an Oral KORSUVA (difelikefalin) formulation and plan to initiate Phase 3 programs in the first 90quarter of 2022 for the treatment of pruritus in patients dosed. The safety reviewwith atopic dermatitis, or AD, and non-dialysis-dependent chronic kidney disease, or NDD-CKD. Phase 2 trials of Oral KORSUVA (difelikefalin) are ongoing in primary biliary cholangitis, or PBC, and notalgia paresthetica, or NP, patients with moderate-to-severe pruritus.
The revised trial is enrolling up to 450 patients undergoing a range of abdominal surgeries, all of which aremoderate-to-severe pruritus associated with moderate-to-severe postoperative pain, withinCKD in adults undergoing hemodialysis in the United States. The primary efficacy measure is
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the ChangeWe expect commercial launch of KORSUVA injection in Pain Intensity over the 24-hour postoperative period, using the patient-reported Numeric Rating Scale, or NRS, score collected at pre-specified time points through 24 hours. Postoperative nauseaApril 2022 and vomiting is also being evaluated as a secondary efficacy measure. The impact of I.V. CR845 treatment on inflammatory biomarkers is also being explored. An interim conditional power analysis of our adaptive Phase 3 trial of I.V. CR845 for postoperative pain is expectedassociated revenues in the second quarter of 2017.
Based on previous guidance from the FDA, we believe we will require 1,500 total exposures2022.
We are also developing an oral version of CR845, or Oral CR845, for acute and chronic pain. In the second quarter of 2014, we initiated a Phase 1 trial of a tablet formulation of Oral CR845, for which we announced positive top-line data in the fourth quarter of 2014. In August 2015, we advanced our tablet formulation of Oral CR845 into a Phase 2a clinical trial in patients with osteoarthritis, or OA, of the knee or hip. The Phase 2a trial was a single-blind, randomized, multiple ascending dose trial designed to evaluate the safety, pharmacokinetics, or PK, and effectiveness of Oral CR845 tablets dosed over a two-week treatment period in 80 OA patients experiencing moderate-to-severe pain, defined as >4 on an 11-point NRS at baseline. In December 2015, we announced positive top-line results from this Phase 2a trial. The results showed a dose-related reduction in mean baseline pain score up to 34% after two weeks, with a statistically significant reduction in mean rescue medication for the top 5.0 mg dose group of approximately 80%. The results of the Phase 2a clinical trial established therapeutic doses and a dosing regimen for a larger randomized, double-blind, placebo-controlled Phase 2b trial, which we initiated during the third quarter of 2016. The Phase 2b trial is a trial of three tablet strengths of CR845, 1.0 mg, 2.5 mg and 5.0 mg, dosed twice-daily over an eight-week treatment period in approximately 330 OA patients experiencing moderate-to-severe pain across the United States. The primary efficacy endpoint is the change from baseline at week eight, with respect to the weekly mean of the daily pain intensity score using an NRS. We expect to report top-line data in the second quarter of 2017.
CR845 has exhibited anti-pruritic, or anti-itch, potency in standard preclinical models. In the fourth quarter of 2014, we reported positive top-line dose-ranging pharmacokinetic, or PK, and safety data from a Phase 1b clinical trial, which was part A of a Phase 2 proof-of-concept trial of I.V. CR845 for the treatment of uremic pruritus, an intractable systemic itch condition with high prevalencecommercialize KORSUVA injection in dialysis patients with chronic kidney disease for which there are no approved therapeuticsassociated pruritus, or CKD-aP, in the United States.U.S. under profit share agreements. We have partnered with VFMCRP to commercialize KORSUVA worldwide, excluding Japan (Maruishi Pharmaceutical Co. Ltd., or Maruishi/sub-licensee including Kissei Pharmaceutical Co. Ltd., or Kissei), and South Korea (Chong Kun Dang Pharmaceutical Corp., or CKDP). VFMCRP is a leading nephrology commercial organization with a significant presence in nephrology offices and dialysis centers. We are launching KORSUVA injection into a highly concentrated market. The dialysis market in the U.S. is dominated by two key providers, Fresenius and Davita, which combined control about 75% of the market. In July 2015, we reported positive top-line efficacy resultsaddition, about 80% of the CKD hemodialysis patients are insured by Medicare.
Based on the results of this trial, during the fourth quarter of 2015 we completed a guidance meeting with the FDA. We have incorporated the feedback we received from the FDA in this guidance meeting in the overall design of our Phase 3 clinical trial program for I.V. CR845 for the treatment of uremic pruritus. In June 2016, we initiated a two-part Phase 2/3 adaptive design trial of I.V. CR845 in dialysis patients suffering from moderate-to-severe uremic pruritus. Part A of the trial, is a randomized, double-blind, placebo-controlled trial in approximately 160 patients of three doses of I.V. CR845 (0.5ug/kg, 1.0 ug/kg and 1.5 ug/kg) administered three times per week after dialysis over an 8-week period. Part B will be a randomized double-blind placebo-controlled trial in up to 240 patients of one optimized dose of I.V. CR845 administered three times per week after dialysis over a 12-week treatment period. The primary endpoint will be reduction in worst itching scores from baseline values measured on a standard NRS alongside secondary quantitative quality of life endpoints. We expect to report top-line data from Part A of this trial2 meetings, in the first quarter of 2017.
We have also initiated a PK safety trial of multiple doses2022, we plan to initiate two Phase 3 registrational programs of Oral CR845KORSUVA (difelikefalin) for the treatment of pruritus, one in hemodialysis patients to define bioequivalent tablet strengths to inform our ability to develop an oral tablet formulationNDD-CKD and the other in AD.
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uremic pruritus. We expect to complete this trialOral KORSUVA (difelikefalin) in the first quartertreatment of 2017, withNP, a neurologic pruritus in which chronic pruritus is the key manifestation of sensory neuropathic syndrome. This condition has no FDA-approved treatments nor robust data to support the use of any single therapy. We currently anticipate a readout expectedon this trial in the second quarter of 2017.
2022. We believe this program could provide insight on Oral KORSUVA’s (difelikefalin) potential in other chronic neurologic pruritus conditions. In addition, we have an ongoing Phase 2 study of Oral KORSUVA (difelikefalin) for the treatment of PBC for which we currently anticipate a readout in the second half of 2022. This program could provide insight into whether Oral KORSUVA (difelikefalin) has utility in other CLDs.
Since our inception and through December 31, 2016, we have raised an aggregate of approximately $237.6 million to fund our operations, including (1) proceeds of $75.2 million, net of underwriting discounts and commissions and offering expenses paid by us fromKORSUVA injection was approved in the sale of approximately 4.33 million shares of our common stock in our follow-on offering of our common stock, which closedU.S. in August 2015; (2) proceeds of $56.3 million, net of underwriting discounts and commissions and offering expenses paid by us, from the sale of 5.75 million shares of our common stock2021, with commercial launch expected in our initial public offering, which closed in February 2014; (3) proceeds of $65.9 million from the sale of shares of our convertible preferred stock prior to our initial public offering; (4) net proceeds of $7.4 million from debt financings; and (5) aggregate payments of $32.6 million pursuant to license agreements, primarily with Maruishi Pharmaceutical Co., Ltd. in Japan and Chong Kun Dang Pharmaceutical Corporation in South Korea, related to CR845 and an earlier product candidate for which development efforts ceased in 2007.
April 2022.
Cara commenced operations in 2004, and our primary activities to date have been organizing and staffing our company, developing our product candidates, including conducting preclinical studies and clinical trials of CR845-based product candidates, and raising capital. Additional information
solely as an inactive textual reference.
406-3700.
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certificateAmended and Restated Certificate of incorporation,Incorporation, or the Restated Certificate, our board of directors has the authority, without further action by the stockholders (unless such stockholder action is required by applicable law or the rules of any stock exchange or market on which our securities are then traded), to designate up to 5,000,000 shares of preferred stock in one or more series and to determine the designations, voting powers, preferences and rights of each series of the preferred stock, as well as the qualifications, limitations or restrictions thereof, including dividend rights, conversion rights, preemptive rights, terms of redemption or repurchase, liquidation preferences, sinking fund terms and the number of shares constituting any series or the designation of any series, any or all of which may be greater than the rights of the common stock. Any convertible preferred stock we may issue will be convertibleinto our common stock or exchangeable for our other securities. Conversion may be mandatory or at the holder’s option and would be at prescribed conversion rates.5
Warrants.
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The following table sets forth our ratio of earnings (loss) to fixed charges for each of the periods indicated. We do not have any preferred stock outstanding as of the date of this prospectus and did not have any preferred stock with required dividend payments during any of the periods presented below. Therefore, there are no preferred dividends included in our calculation of these ratios. The following table is qualified by the more detailed information appearing in the computation table set forth in Exhibit 12.1 to the registration statement of which this prospectus is part and our historical financial statements, including the notes to those financial statements, incorporated by reference in this prospectus.
Year Ended December 31, | ||||||||||||||||||||
2016 | 2015 | 2014 | 2013 | 2012 | ||||||||||||||||
( in thousands) | ||||||||||||||||||||
Pre-tax loss | $ | (57,748 | ) | $ | (25,087 | ) | $ | (17,946 | ) | $ | (3,993 | ) | $ | (6,302 | ) | |||||
Ratio of earnings to fixed charges (1) | N/A | N/A | N/A | N/A | N/A | |||||||||||||||
Coverage deficiency | $ | 57,748 | $ | 25,087 | $ | 17,946 | $ | 3,993 | $ | 6,302 |
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CONTENTS
11
We and
Demand Registration Rights
The holders of at least 20% of the registrable securities, as defined under the investor rights agreement, have the rightissued pursuant to make up to two demands that we file a registration statement to register all or a portion of their shares so long as the aggregate offering price of securities requested to be sold under such registration statement is at least $10,000,000, net of underwriting discounts and commissions and subject to specified exceptions.
Piggyback Registration Rights
If we register any securities for public sale, holders of registrable securities, as defined under the investor rights agreement, are entitled to written notice of the registration and will have the right to include their shares in the registration statement. The underwriters of any offering will have the right to limit the number of shares having registration rights to be included in the registration statement provided such registration does not include
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shares of any other selling stockholders, in which case any and all shares held by selling stockholders may be excluded from the offering.
Registration on Form S-3
If we are eligible to file a registration statement on Form S-3, the holders of at least 10% of the registrable securities, as defined under the investor rights agreement, have the right to demand up to twice per year that we file registration statements on Form S-3 so long as the aggregate offering price of the securities to be sold under the registration statement on Form S-3 is at least $5,000,000, net of underwriting discounts and commissions, and subject to specified exceptions.
Expenses of Registration; Indemnification
Generally, we are required to bear all registration expenses incurred in connection with the demand, Form S-3 and piggyback registrations described above, other than underwriting discounts and commissions. The investor rights agreement contains customary indemnification provisions with respect to registration rights.
Termination of Registration Rights
The demand, Form S-3 and piggyback registration rights discussed above will terminate if all of the holder’s registrable securities may be sold without restriction under Rule 144 of the Securities Act.
purchase agreement.
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delaying or preventing changes in control or management of our company. First, our board of directors is classified into three classes of directors. Under Delaware law, directors of a corporation with a classified board may be removed only for cause unless the corporation’s certificate of incorporation provides otherwise. Our Restated Certificate does not provide otherwise.provides that any director may be removed with cause by the affirmative vote of the holders of at least 66
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additional terms.
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Unless we otherwise specify in the applicable prospectus supplement, holders of the warrants may exercise the warrants by delivering the warrant certificate representing the warrants to be exercised together with specified information, and paying the required amount to the warrant agent in immediately available funds, as provided in the applicable prospectus supplement. We will set forth on the reverse side of the warrant certificate and in the applicable prospectus supplement the information that the holder of the warrant will be required to deliver to the warrant agent in connection with the exercise of the warrant.
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In compliance with guidelines of
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Unless otherwise indicatedunderwriters, dealers or agents, by counsel that we will name in the applicable prospectus supplement, certain legal matters in connection with the offering and the validity of the securities offered by this prospectus, and any supplement thereto, will be passed upon by Cooley LLP.
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SECURITIES ACT LIABILITY
InsofarCONTENTS
34
a criminal offense.
$250,000,000
| | | Page | | |||
| | | | S-i | | | |
| | | | S-1 | | | |
| | | | S-3 | | | |
| | | | S-4 | | | |
| | | | S-6 | | | |
| | | | S-8 | | | |
| | | | S-9 | | | |
| | | | S-11 | | | |
| | | | S-13 | | | |
| | | | S-13 | | | |
| | | | S-14 | | | |
| | | | S-14 | | |
| Assumed public offering price per share | | | | | | | | | | $ | 10.46 | | |
| Net tangible book value per share as of December 31, 2021 | | | | $ | 4.25 | | | | | | | | |
| Increase in net tangible book value per share attributable to this offering | | | | $ | 0.74 | | | | | | | | |
| As adjusted net tangible book value per share as of December 31, 2021, after giving effect to this offering | | | | | | | | | | $ | 4.99 | | |
| Dilution per share to investors purchasing our common stock in this offering | | | | | | | | | | $ | 5.47 | | |
Preferred Stock
Debt Securities
Warrants
2022
SEC registration fee | $ | 28,999 | ||
FINRA filing fee (if applicable) | * | |||
Accounting fees and expenses | * | |||
Legal fees and expenses | * | |||
Transfer agent fees and expenses | * | |||
Trustee fees and expenses | * | |||
Printing and miscellaneous expenses | * | |||
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Total | $ | * | ||
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| SEC registration fee | | | | $ | 27,810 | | |
| Accounting fees and expenses | | | | | * | | |
| Legal fees and expenses | | | | | * | | |
| Transfer agent fees and expenses | | | | | * | | |
| Trustee fees and expenses | | | | | * | | |
| Printing and miscellaneous expenses | | | | | * | | |
| Total | | | | $ | * | | |
II-1
Exhibit Number | | ||||
| Description of Document | | |||
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1.1(1) | | | Form of Underwriting Agreement | | |
| 1.2 | | | Open Market Sale AgreementSM, dated March 1, 2022, between the Registrant and Jefferies LLC | |
| 3.1(2) | | | | |
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3.2(3) | | | | ||
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4.1(4) | | | | ||
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4.2 | | | | ||
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4.3(1) | | | Form of Note | | |
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4.4 | | | | ||
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4.5 | | | | ||
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4.6 | | | | ||
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4.7(1) | | | Form of Specimen Preferred Stock Certificate and Certificate of Designations of Preferred Stock | | |
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4.8(5) | | | |||
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5.1 | | | | ||
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23.1 | | | | ||
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23.2 | | | | ||
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24.1 | | | | ||
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25.1(1) | | | Statement of Eligibility of Trustee under the Debt Indenture | | |
| 107 | | | |
(i)
(ii)
II-3
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, 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(6)
(7) That for purposes of determining any liability under the Securities Act, (i) the information omitted from the form of prospectus filed as part of the registration statement in reliance upon Rule 430A and contained in the form of prospectus filed by the registrant pursuant to Rule 424(b)(l) or (4) or 497(h) under the Securities Act shall be deemed to be a part of the registration statement as of the time it was declared effective; and (ii) 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 offing of such securities at that time shall be deemed to be the initialbona fide offering thereof.
(8) 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 in accordance with the rules and regulations prescribed by the Commission under Section 305(b)(2) of the Trust Indenture Act.
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| CARA THERAPEUTICS, INC. | ||||||
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| | | | By: | | | /s/ |
CHRISTOPHER POSNER Christopher Posner Chief Executive Officer | |
| Signature | | | Title | | | Date | |
| /s/
Christopher Posner | | | President, Chief Executive Officer and | | | March | |
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/s/
Thomas Reilly | | | Chief Financial Officer(Principal Financial and Accounting Officer) | | | March | | |
| /s/ MARTIN VOGELBAUM Martin Vogelbaum | | | Director | | | March 1, 2022 | |
| /s/ HARRISON M. BAINS, JR. Harrison M. Bains,
| | | Director | | | March | |
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/s/ JEFFREY IVES Jeffrey
| | | Director | | | March | | |
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/s/
Susan Shiff | | | Director | | | March | ||
1, 2022 | ||||||||
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INDEX TO EXHIBITS
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