TP-2021

Pictured: J&J's building in Switzerland/iStock, yuelan J&J announced Wednesday its late-stage experimental drug seltorexant met all primary and secondary endpoints in a Phase III study of patients with major depressive disorder with insomnia symptoms. Seltorexant, a selective antagonist of the orexin-2 receptor, showed both a statistically significant and clinically meaningful improvement in depressive symptoms based on the Montgomery-Asberg Depression Rating Scale (MADRS) total score at day 43, while improving sleep disturbance outcomes in patients who had a prior inadequate response to SSRI/SNRI antidepressants alone. The drug was safe and well-tolerated, with similar rates of adverse events across both treatment and placebo arms, according to J&J. The results are being presented at this week’s American Society of Clinical Psychopharmacology (ASCP) annual meeting in Miami. Instead of including all MDD patients in the trial in an all-comers approach, J&J utilized a precision-based strategy targeting those also suffering from insomnia. Around 60% of major depressive disorder (MDD) patients suffer from insomnia symptoms, despite standard-of-care treatment with oral antidepressants. “Seltorexant has the potential to fill a significant unmet need for new therapies to treat patients experiencing depression and insomnia, and most importantly, to improve outcomes and quality of life for these patients,” Andrew Krystal, psychiatry professor at University of California, San Francisco Weill Institute for Neurosciences, said in a statement. J&J has another MDD candidate in a Phase III trial—a kappa-opioid receptor antagonist for MDD patients suffering from anhedonia, the inability to feel pleasure and interest in life. This targeted-patient strategy is gaining traction as J&J and biotech Alto Neuroscience attempt the improve the low success rate for psychiatric drugs with a precision approach. While J&J is choosing patients based on specific symptoms, Alto is utilizing biomarkers like cognitive tests and brain scans to identify the right patients for their MDD asset. At ASCP, J&J is also presenting data from a Phase IV study of Spravato, its already-approved nasal spray for adults with treatment-resistant (TRD) and MDD with suicidal thoughts or actions as an adjunctive treatment. The study is testing the ketamine-based drug as a monotherapy for TRD. Meaningful improvements to depressive symptoms were seen in less than 24 hours after the first dose and sustained through four weeks of treatment. While the drug’s efficacy is “exciting,” the issue is the delivery and required safety monitoring, Graig Suvannevejh, senior biopharma and biotech equity research analyst at Mizuho Americas, told BioSpace in a previous interview. Patients go into a doctor’s office to receive the nasal spray, then stay and be monitored for two hours before being allowed to leave. “It’s not a user-friendly drug,” Suvannevejh said, noting that it can still be a very good option for a hard-to-treat population. Kate Goodwin is a freelance life science writer based in Des Moines, Iowa. She can be reached at kate.goodwin@biospace.com and on LinkedIn.

Topline efficacy and safety results from KOURAGE 1 Part A portion of notalgia paresthetica (NP) pivotal program now expected by the end of 2Q24STAMFORD, Conn., May 13, 2024 (GLOBE NEWSWIRE) -- Cara Therapeutics, Inc. (Nasdaq: CARA), a development-stage biopharmaceutical company leading a new treatment paradigm to improve the lives of patients suffering from pruritus, today announced financial results and operational highlights for the first quarter ended March 31, 2024. “Our notalgia paresthetica (NP) pivotal clinical program is progressing ahead of schedule and we now expect to report topline efficacy and safety results from KOURAGE 1 Part A by the end of the second quarter of 2024,” said Christopher Posner, President and Chief Executive Officer of Cara Therapeutics. “We believe the medical dermatology community’s interest in our clinical program underscores the significant unmet need for an effective and safe anti-pruritic treatment for the sizeable NP patient population. We look forward to rapidly advancing the ongoing Phase 2/3 program of our differentiated asset, oral difelikefalin, in this common but under-explored sensory neuropathy.” KOURAGE Update KOURAGE 1 Part A is the dose-finding portion of the Phase 2/3 clinical program evaluating oral difelikefalin for the treatment of moderate-to-severe pruritus in patients with NP. The Company enrolled 214 patients and expects topline efficacy and safety results from KOURAGE 1 Part A by the end of the second quarter of 2024. Part A is not powered for statistical significance. This readout will provide key information, specifically the dose and sample size to initiate the Phase 3 pivotal portion of the program – Part B of KOURAGE 1 and the second study KOURAGE 2. Final topline results from the first pivotal study are expected by the end of 2025 with the second pivotal study results in early 2026. In March 2024, the Company hosted a virtual event, Meet the NP Experts, featuring a panel of leading dermatologists and key opinion leaders to discuss the unmet need in NP and the potential of oral difelikefalin. A replay of the webcast is available under “Events & Presentations” in the Investors section of the Company’s website, www.CaraTherapeutics.com. 1Q24 KORSUVA Injection U.S. Update In the first quarter of 2024, KORSUVA® (difelikefalin) injection generated net sales of approximately $1.8 million and the Company recorded collaborative revenue of approximately $800,000, which represented the Company’s share of the profit from sales of KORSUVA injection. Wholesalers shipped 111,720 vials to dialysis centers during the first quarter of 2024. On March 31, 2024, the Transitional Drug Add-On Payment Adjustment (TDAPA) period for KORSUVA injection expired. After the TDAPA period, KORSUVA injection is reimbursed through the ESRD PPS bundle. First Quarter 2024 Financial Results Cash, cash equivalents and marketable securities at March 31, 2024 totaled $69.8 million compared to $100.8 million at December 31, 2023. The decrease in the balance primarily resulted from $30.5 million of cash used in operating activities. For the first quarter of 2024, net loss was $30.7 million, or $(0.56) per basic and diluted share, compared to net loss of $26.7 million, or ($0.49) per basic and diluted share, for the same period in 2023. Revenues: Total revenue was $2.1 million and $6.2 million for the three months ended March 31, 2024 and 2023, respectively. Revenue primarily consisted of: $0.8 million and $2.8 million of collaborative revenue related to our share of the profit from CSL Vifor’s sales of KORSUVA injection to third parties during the three months ended March 31, 2024 and 2023, respectively.$0.6 million and $3.2 million of commercial supply revenue related to sales of KORSUVA injection to CSL Vifor during the three months ended March 31, 2024 and 2023, respectively.$0.6 million of other revenue related to royalty payments earned in conjunction with ex U.S. sales of KORSUVA/Kapruvia under agreements with CSL Vifor and Maruishi Pharmaceuticals Co. Ltd., or Maruishi, during the three months ended March 31, 2024, which were sold under the Purchase and Sale agreement with HCRX Investments Holdco, L.P. and Healthcare Royalty Partners IV, L.P., or the HCR Agreement, and considered non-cash. There was no other revenue during the three months ended March 31, 2023. Cost of Goods Sold: Cost of goods sold was $0.6 million and $2.6 million for the three months ended March 31, 2024 and 2023, respectively, related to commercial supply revenue for KORSUVA injection sales to CSL Vifor. Research and Development (R&D) Expenses: R&D expenses were $22.0 million for the three months ended March 31, 2024 compared to $24.3 million in the same period of 2023. The lower R&D expenses in 2024 were primarily due to decreases in stock-based compensation expense, payroll and related costs, travel costs and other related conference costs as well as lower costs associated with the discontinuation of our atopic dermatitis and advanced chronic kidney disease programs, partially offset by increases related to the oral difelikefalin NP program. General and Administrative (G&A) Expenses: G&A expenses were essentially flat at $6.8 million for the three months ended March 31, 2024 compared to $6.9 million in the same period of 2023. Restructuring Expenses: Restructuring expenses were $2.4 million for the three months ended March 31, 2024 which were related to our strategic prioritization of NP and the associated workforce reduction in the 2024 period. There were no restructuring expenses recorded during the three months ended March 31, 2023. Other Income, net: Other income, net was approximately $1.0 million for each of the three months ended March 31, 2024 and 2023. Non-cash interest expense on liability related to sales of future royalties and milestones: Non-cash interest expense was $2.0 million which represented imputed interest on the carrying value of the liability associated with the HCR Agreement and the amortization of the related issuance costs associated with the HCR Agreement for the three months ended March 31, 2024. There was no non-cash interest expense for the three months ended March 31, 2023. Financial Guidance Cara expects that our current unrestricted cash and cash equivalents and available-for-sale marketable securities will be sufficient to fund our currently anticipated operating plan into 2026. Our current operating plan assumes certain costs related to our planned pivotal trials in NP. About the KOURAGE Phase 2/3 Clinical Program in Notalgia Paresthetica KOURAGE is a Phase 2/3 clinical program evaluating oral difelikefalin for the treatment of moderate-to-severe pruritus in patients with notalgia paresthetica (NP). The program is comprised of two studies – KOURAGE 1 and KOURAGE 2 – which will likely be double-blind, placebo-controlled, 8-week studies with patients allowed to roll-over into open-label 52-week extensions. KOURAGE 1 is composed of two parts. The dose-finding portion of KOURAGE 1 (Part A) includes 214 patients who are randomized equally to four arms (0.25 mg BID, 1.0 mg BID, 2.0 mg BID, placebo BID). Part A is not powered for statistical significance. Part B and KOURAGE 2 will likely be double-blind, placebo-controlled, 8-week studies with patients randomized 1:1 to either difelikefalin or matching placebo. The primary endpoint for both the dose-finding portion of KOURAGE 1 (Part A) and the two pivotal studies Part B and KOURAGE 2 will likely be the proportion of patients with a ≥4-point improvement at Week 8 from baseline in the worst itch numeric rating scale. About Cara Therapeutics Cara Therapeutics is a development-stage biopharmaceutical company leading a new treatment paradigm to improve the lives of patients suffering from pruritus. The Company is developing an oral formulation of difelikefalin, a selective, peripherally acting, non-scheduled kappa opioid receptor agonist, for the treatment of chronic pruritus associated with notalgia paresthetica (NP), a common, underdiagnosed neuropathy affecting the upper back for which there are no FDA-approved therapies. The Company is conducting a Phase 2/3 clinical program in NP with topline results of the dose-finding portion expected by the end of the second quarter of 2024. Cara Therapeutics also developed an IV formulation of difelikefalin, which is approved in the United States, EU, and multiple other countries for the treatment of moderate-to-severe pruritus associated with advanced chronic kidney disease in adults undergoing hemodialysis. The IV formulation is out-licensed worldwide. For more information, visit www.CaraTherapeutics.com and follow the company on X (Twitter), LinkedIn and Instagram. Forward-looking Statements Statements contained in this press release regarding matters that are not historical facts are "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995. Examples of these forward-looking statements include statements concerning the Company’s planned future regulatory submissions and potential future regulatory approvals, future product launches, expected timing of the initiation, enrollment and data readouts from the Company’s planned and ongoing clinical trials, the potential results of ongoing clinical trials, timing of future regulatory and development milestones for the Company’s product candidate, the potential for the Company’s product candidate to be an alternative in the therapeutic areas investigated, including notalgia paresthetica, the size and growth of the potential markets for pruritus management such as notalgia paresthetica, the commercial potential of the Company’s product candidate, and the Company’s cash runway. Because such statements are subject to risks and uncertainties, actual results may differ materially from those expressed or implied by such forward-looking statements. The risks are described more fully in Cara Therapeutics’ filings with the Securities and Exchange Commission, including the “Risk Factors” section of the Company’s Annual Report on Form 10-K for the year ending December 31, 2023 and its other documents subsequently filed with or furnished to the Securities and Exchange Commission, including its Form 10-Q for the quarter ended March 31, 2024. All forward-looking statements contained in this press release speak only as of the date on which they were made. Cara Therapeutics undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made, except as required by law. CARA THERAPEUTICS, INC.CONDENSED CONSOLIDATED BALANCE SHEETS(in thousands)(unaudited) March 31, December 31, 2024 2023 Assets Current assets: Cash and cash equivalents$46,996 $ 51,775 Marketable securities 22,777 48,983 Accounts receivable, net - related party 1,718 2,765 Inventory, net 2,741 2,821 Income tax receivable 697 697 Other receivables 506 555 Prepaid expenses 5,790 8,154 Restricted cash - 408 Total current assets 81,225 116,158 Operating lease right-of-use assets 3,826 4,864 Property and equipment, net 3,548 3,322 Restricted cash, non-current 1,500 1,500 Total assets$90,099 $125,844 Liabilities and stockholders’ equity Current liabilities: Accounts payable and accrued expenses$14,875 $25,592 Operating lease liability, current 220 - Total current liabilities 15,095 25,592 Liability related to sales of future royalties and milestones, net 38,376 37,079 Operating lease liability, non-current 6,825 6,088 Total liabilities 60,296 68,759 Commitments and contingencies - - Stockholders' equity: Preferred stock - - Common stock 54 54 Additional paid-in capital 745,381 742,036 Accumulated deficit (715,441) (684,745)Accumulated other comprehensive loss (191) (260)Total stockholders’ equity 29,803 57,085 Total liabilities and stockholders’ equity$90,099 $125,844 CARA THERAPEUTICS, INC.CONDENSED CONSOLIDATED STATEMENTS OF OPERATIONS(amounts in thousands, except share and per share data)(unaudited) Three Months Ended March 31, 2024 2023 Revenue: Collaborative revenue$788 $2,750 Commercial supply revenue 640 3,191 Royalty revenue - 125 Clinical compound revenue 84 99 Other revenue 623 - Total revenue 2,135 6,165 Operating expenses: Cost of goods sold 620 2,590 Research and development 21,964 24,334 General and administrative 6,816 6,891 Restructuring 2,401 - Total operating expenses 31,801 33,815 Operating loss (29,666) (27,650) Other income, net 952 985 Non-cash interest expense on liability related to sales of future royalties and milestones (1,982) - Net loss$(30,696) $(26,665) Net loss per share: Basic and Diluted$(0.56) $(0.49) Weighted average shares: Basic and Diluted 54,588,090 53,872,038 MEDIA CONTACT:Annie Spinetta6 Degrees973-768-2170aspinetta@6degreespr.com INVESTOR CONTACT:Iris Francesconi, Ph.D.Cara Therapeutics203-406-3700investor@caratherapeutics.com