About Cara Therapeutics

Cara Therapeutics, Inc. operates as a commercial-stage biopharmaceutical company. The company engages in leading a new treatment paradigm to improve the lives of patients suffering from pruritus. Product Portfolio Nephrology Franchise KORSUVA (difelikefalin) injection - Commercial Product In August 2021, the company’s lead product, KORSUVA injection, was approved by the U.S. Food and Drug Administration (FDA) for the treatment of moderate-to-severe pruritus associated with chronic kidney disease (CKD) in adults undergoing hemodialysis. In December 2021, the Centers for Medicare & Medicaid Services (CMS) granted Transition Drug Add-on Payment Adjustment, or TDAPA, to KORSUVA injection in the anti-pruritic functional category. TDAPA went into effect on April 1, 2022, for a minimum of two years. The commercial launch of KORSUVA injection commenced in April 2022. The company is partnering with CSL Vifor (CSL Vifor and its affiliated entities) to commercialize KORSUVA injection in dialysis patients with CKD-aP worldwide, excluding Japan (Maruishi/sub-licensee Winhealth Pharma and Kissei Pharmaceutical Co. Ltd. (Kissei)), and South Korea (Chong Kun Dang Pharmaceutical Corp. (CKDP)). In April 2022, the European Commission granted marketing authorization to difelikefalin injection under the brand name Kapruvia for the treatment of moderate-to-severe pruritus associated with chronic kidney disease in adult hemodialysis patients. The marketing authorization approves Kapruvia for use in all member states of the European Union (EU), as well as Iceland, Liechtenstein, and Norway. Kapruvia was also approved in the U.K. in April 2022. Commercial launches in Austria, Germany, Sweden, and Denmark have commenced and the company expects the remaining EU countries to launch in 2023. In August 2022, as part of the Access Consortium, difelikefalin injection was approved in Switzerland under the brand name Kapruvia, as well as in Singapore and Canada under the brand name KORSUVA. In November 2022, difelikefalin injection was approved in the last Access Consortium country, Australia, under the brand name KORSUVA. In addition, the company’s partner in Japan, Maruishi Pharmaceuticals Co. Ltd (Maruishi), announced positive Phase 3 top-line data in January 2022. Maruishi and its sublicensee Kissei confirmed the primary endpoint was achieved in a Japanese Phase 3 clinical study (double-blind, placebo-controlled period) of difelikefalin injection for the treatment of pruritus in hemodialysis patients. In the Phase 3 study, 178 patients were administered difelikefalin or placebo for 6 weeks followed by an open-label extension period of difelikefalin administration for 52 weeks. In September 2022, Maruishi submitted a New Drug Application in Japan for the approval of difelikefalin injection for the treatment of pruritus in hemodialysis patients. A final decision on the application is expected in the second half of 2023. In January 2023, Vifor Fresenius Medical Care Renal Pharma Ltd. and Winhealth Pharma signed a long-term exclusive licensing agreement for the co-development and commercialization of KORSUVA injection for the treatment of moderate-to-severe pruritus in adult patients undergoing hemodialysis in China. Summary of the Clinical Results for KORSUVA injection/Kapruvia: KORSUVA injection was approved by the FDA in August 2021 and is the first and only product approved for the treatment of moderate-to-severe pruritus associated with CKD in adult patients undergoing hemodialysis in the United States. It was approved based on the NDA filing that was supported by positive data from two pivotal Phase 3 trials – KALMTM-1, conducted in the United States, and KALM-2 conducted globally, as well as supportive data from an additional 32 clinical studies. In April 2020, the company announced positive top-line results from the double blinded KALM-2 pivotal Phase 3 trial of KORSUVA injection in hemodialysis patients with moderate-to-severe CKD-aP. In this trial, KORSUVA injection was generally well-tolerated with a safety profile consistent with that seen in KALM-1 and the KORSUVA clinical program in patients with CKD-aP. In May 2019, the company announced positive results from the double blinded phase of its KALM-1 pivotal Phase 3 trial of KORSUVA injection in hemodialysis patients with moderate-to-severe CKD-aP. KORSUVA Injection the U.S. Launch Progress In April 2022, the company’s partner CSL Vifor initiated the commercialization of KORSUVA injection in the United States. The launch was initially driven by independent and mid-size dialysis organizations coupled with product stocking at the wholesaler level. In the third quarter of 2022, large dialysis organizations, or LDOs, came on-line driving a significant quarter-to-quarter increase in order volume from the wholesaler. Specifically, Fresenius placed large orders to drive the trial and adoption of KORSUVA injection across its entire network of clinics. In the third quarter of 2022, CSL Vifor also contracted the sales force of Fresenius Renal Pharmaceuticals, a division of Fresenius Medical Care North America, to complement CSL Vifor’s sales force in selling into Fresenius clinics in the United States. After the initial inventory building at both the wholesaler and certain clinics (primarily, Fresenius), the company has started to see shipments to dialysis organizations reflect true end-user demand versus the stocking activity seen in prior quarters. Oral Difelikefalin in Non-Dialysis-Dependent Chronic Kidney Disease (NDD-CKD) Associated Pruritus CKD-aP (chronic kidney disease associated pruritus) is a frequent and wearisome symptom in patients with NDD-CKD. The company initiated a Phase 3 program with oral difelikefalin for the treatment of pruritus in NDD-CKD, specifically in patients diagnosed with Stage IV and V advanced CKD. There are approximately 1.2 million patients diagnosed with Stage IV and V CKD in the United States and approximately 300,000 of these patients suffer from moderate-to-severe pruritus. In the first quarter of 2022, the company initiated the Phase 3 NDD-CKD program. The Phase 3 program consists of two identical trials (the U.S. and global), KICK 1 and KICK 2. Each trial is expected to enroll approximately 400 patients, who will be randomized 1:1 to either oral difelikefalin 1 mg once daily or matching placebo. The study population will include adult patients suffering from moderate-to-severe pruritus with advanced CKD in Stages IV or V, not on dialysis. The company expects to report top-line results from this program in the second half of 2024. Dermatology Franchise Oral difelikefalin for the Treatment of Moderate-to-Severe Pruritus Associated with Atopic Dermatitis (AD) In April 2021, the company announced top-line data from its Phase 2 KARE clinical trial. The KARE Phase 2 trial was a randomized, double-blind, placebo-controlled study designed to evaluate the efficacy and safety of oral difelikefalin for moderate-to-severe pruritus in 401 adult subjects with AD-aP. In the first quarter of 2022, the company initiated a Phase 3 program for the treatment of moderate-to-severe pruritus in AD patients. The pivotal Phase 3 program for difelikefalin in AD comprises two studies: KIND 1 and KIND 2 and will investigate the use of oral difelikefalin as adjunctive treatment to topical corticosteroids. The KIND 1 study will be composed of two parts: Part A and Part B. KIND 1 and KIND 2 will be double-blind, controlled, 12-week studies with patients allowed to roll-over into open label 52-week extensions. The company expects to release top-line results for both KIND 1 Part B and KIND 2 in the first half of 2025. Oral Difelikefalin for the Treatment of Moderate-to-Severe Pruritus Associated with Notalgia Paresthetica (NP) In June 2022, the company announced positive top-line results from the proof-of-concept Phase 2 KOMFORT trial of oral difelikefalin for the treatment of pruritus in patients with NP. KOMFORT was a Phase 2 randomized, double-blind, placebo-controlled trial designed to evaluate the efficacy and safety of oral difelikefalin for moderate-to-severe pruritus in 125 adult patients with NP and moderate-to-severe pruritus. Patients were randomized to receive oral difelikefalin 2 mg twice daily (BID) vs. matching placebo for eight weeks followed by a 4-week open-label active extension period and follow-up visit approximately 14 days after the last dose of the study drug. In November 2022, the company had a positive interaction with the FDA leading to the initiation of a Phase 2/3 program for the treatment of chronic pruritus associated with NP. In February 2023, the results of the company’s KOMFORT Phase 2 trial were published in the New England Journal of Medicine. In the first quarter of 2023, the company initiated a Phase 2/3 program for the treatment of moderate-to-severe pruritus in NP patients. The Phase 2/3 program for difelikefalin in NP will comprise two studies: KOURAGE 1 and KOURAGE 2. The KOURAGE 1 study will be composed of two parts: Part A and Part B. KOURAGE 1 and KOURAGE 2 will be double-blind, placebo-controlled, 8-week studies with patients allowed to roll-over into open label 52-week extensions. The company expects to release top-line results for both KOURAGE 1 Part B and KOURAGE 2 in the first half of 2026. Other Program(s) Oral Difelikefalin for the Treatment of Chronic Liver Disease-Associated Pruritus (CLD-aP), Including PBC The company had been evaluating oral difelikefalin in PBC to establish a proof-of-concept in CLD-aP. In June 2019, the company announced the initiation of a proof-of-concept Phase 2 trial of oral difelikefalin for the treatment of pruritus in patients with hepatic impairment due to PBC. The Phase 2 multicenter, randomized, double-blind, placebo-controlled 16-week trial was designed to evaluate the safety and efficacy of 1 mg of oral difelikefalin taken twice daily (BID) vs. placebo in approximately 60 patients with PBC and moderate-to-severe pruritus. Based on slow enrollment due primarily to COVID-19, the company makes a strategic decision to discontinue and unblind the proof-of-concept Phase 2 clinical trial of oral difelikefalin for the treatment of pruritus in patients with PBC. At this time, the company plans to focus its resources on its nephrology and dermatology franchises. Collaboration and License Agreements Vifor (International) Ltd. (Vifor International) In October 2020, the company entered into a license agreement with Vifor International, or Vifor Agreement No. 1, under which the company granted Vifor International an exclusive license solely in the United States to use, distribute, offer for sale, promote, sell and otherwise commercialize KORSUVA (difelikefalin) injection for all therapeutic uses relating to the inhibition, prevention or treatment of itch associated with pruritus in hemodialysis and peritoneal dialysis patients in the United States. Under Vifor Agreement No. 1, the company retains all rights with respect to the clinical development of, and activities to gain regulatory approvals of, KORSUVA (difelikefalin) injection in the United States. Vifor Agreement No. 1 provides full commercialization rights in dialysis clinics to Vifor International in the United States under a profit-sharing arrangement. In May 2022, Vifor International assigned its rights and obligations under the license agreement and a supply agreement, as permitted under the agreements, to Vifor Fresenius Medical Care Renal Pharma Ltd. The company’s rights and obligations under these agreements were unaffected by this assignment, and the assignment did not affect its economic rights under the agreements with Vifor International. In August 2022, Vifor Pharma Group (which includes Vifor International) was acquired by CSL Limited and subsequently renamed CSL Vifor as part of the acquisition. The acquisition of Vifor Pharma Group did not affect any of the company’s rights and obligations pursuant to these agreements. Vifor Fresenius Medical Care Renal Pharma Ltd. In May 2018, the company entered into a license agreement, or Vifor Agreement No. 2, with Vifor Fresenius Medical Care Renal Pharma Ltd. under which it has granted Vifor Fresenius Medical Care Renal Pharma Ltd. a license to seek regulatory approval to commercialize, import, export, use, distribute, offer for sale, promote, sell and otherwise commercialize KORSUVA (difelikefalin) injection for all therapeutic uses to prevent, inhibit or treat itch associated with pruritus in hemodialysis and peritoneal-dialysis patients worldwide (excluding the United States, Japan and South Korea). The company retained full development and commercialization rights for KORSUVA injection for the treatment of CKD-aP in dialysis patients in the United States except in the dialysis clinics of Fresenius Medical Care North America, or FMCNA, where Vifor Fresenius Medical Care Renal Pharma Ltd. will promote KORSUVA injection under a profit-sharing arrangement. In connection with Vifor Agreement No. 2, the company also has a related supply agreement with Vifor Fresenius Medical Care Renal Pharma Ltd., or the Vifor Fresenius Medical Care Renal Pharma Ltd. Supply Agreement, pursuant to which it retains the right to make and has made KORSUVA (difelikefalin) injection worldwide (excluding the United States, Japan and South Korea), or the Territory, for commercial sale by Vifor Fresenius Medical Care Renal Pharma Ltd. in or outside the Territory, and for supply of KORSUVA (difelikefalin) injection to Vifor Fresenius Medical Care Renal Pharma Ltd. The Vifor Fresenius Medical Care Renal Pharma Ltd. Supply Agreement will co-terminate with Vifor Agreement No. 2. In January 2023, Vifor Fresenius Medical Care Renal Pharma Ltd. and Winhealth Pharma signed a long-term exclusive licensing agreement for the co-development and commercialization of KORSUVA injection for the treatment of moderate-to-severe pruritus in adult patients undergoing hemodialysis in China. Maruishi Pharmaceutical Co., Ltd. (Maruishi) In April 2013, the company entered into a license agreement with Maruishi, or the Maruishi Agreement, under which the company granted Maruishi an exclusive license to develop, manufacture and commercialize drug products containing difelikefalin in Japan in the acute pain and uremic pruritus fields. Maruishi has a right of first negotiation for any other indications for which the company develops difelikefalin and, under certain conditions, Maruishi may substitute another pruritus indication for the uremic pruritus indication originally included in its license from the company. Maruishi is required to use commercially reasonable efforts, at its expense, to develop, obtain regulatory approval for and commercialize difelikefalin in Japan. The company is required to use commercially reasonable efforts, at its expense, to develop, obtain regulatory approval for and commercialize difelikefalin in the United States. In January 2022, Maruishi and its sublicensee Kissei confirmed the primary endpoint was achieved in a Japanese Phase 3 clinical study (double-blind, placebo-controlled period) of difelikefalin injection for the treatment of pruritus in hemodialysis patients. In the Phase 3 study, 178 patients were administered difelikefalin or placebo for 6 weeks followed by an open-label extension period of difelikefalin administration for 52 weeks. The primary endpoint, change in itch NRS score, and the secondary endpoint, change in itching scores of Shiratori severity criteria, were significantly improved from baseline compared to the placebo group. Difelikefalin was well-tolerated. In September 2022, Maruishi submitted a New Drug Application in Japan for approval of difelikefalin injection for the treatment of pruritus in hemodialysis patients. A final decision on the application is expected in the second half of 2023. Chong Kun Dang Pharmaceutical Corporation (CKDP) In April 2012, the company entered into a license agreement with CKDP, or the CKDP Agreement, under which it granted CKDP an exclusive license to develop, manufacture and commercialize drug products containing difelikefalin in South Korea. CKDP is required to use commercially reasonable efforts, at its expense, to develop, obtain regulatory approval for and commercialize difelikefalin in South Korea. The company is required to use commercially reasonable efforts, at its expense, to develop, obtain regulatory approval for and commercialize difelikefalin in the United States. Manufacturing and License Agreements Polypeptide Laboratories S.A.(PPL) In July 2021, the company entered into an Active Pharmaceutical Ingredient, or API, Commercial Supply Agreement with Polypeptide Laboratories S.A. (PPL), that defines each party’s responsibilities with respect to PPL’s manufacture and supply of API for the difelikefalin injection product candidate. Under the API Commercial Supply Agreement, PPL shall manufacture API at its facility for sale and supply to the company, in the amounts as set forth in purchase orders to be provided by it. The company will be required to purchase its requirements of API for each year of the term of the agreement, based on internal forecasts. The API Commercial Supply Agreement will continue until the fifth anniversary of the approval by the FDA of the NDA for KORSUVA injection, unless the API Commercial Supply Agreement is earlier terminated, and will automatically be extended for successive five-year periods unless either party gives notice to the other party of its intention to terminate. Enteris Biopharma, Inc. (Enteris) In August 2019, the company entered into a Non-Exclusive License Agreement, or the Enteris License Agreement, with Enteris. Pursuant to the Enteris License Agreement, Enteris granted to the company a non-exclusive, royalty-bearing license, including the right to grant sublicenses, under certain proprietary technology and patent rights related to or covering formulations for oral delivery of peptide active pharmaceutical ingredients with functional excipients to enhance permeability and/or solubility, known as Enteris’s Peptelligence technology, to develop, manufacture and commercialize products using such technology worldwide, excluding Japan and South Korea. Patheon UK Limited (Patheon): In July 2019, the company entered into a Master Services Agreement (MSA), with Patheon UK Limited (Patheon). The MSA governs the general terms under which Patheon, or one of its affiliates, will provide non-exclusive manufacturing services to the company for the drug products specified by it from time to time. Pursuant to the MSA, the company has agreed to order from Patheon at least a certain percentage of its commercial requirements for a product under a related Product Agreement. The MSA has an initial term ending December 31, 2024, and will automatically renew after the initial term for successive terms of two years each if there is a Product Agreement in effect, unless either party gives notice of its intention to terminate the MSA at least 18 months prior to the end of the then current term. Also in July 2019, the company entered into two related Product Agreements under the MSA, one with each of Patheon and Patheon Manufacturing Services LLC (Patheon Greenville) to govern the terms and conditions of the manufacture of commercial supplies of difelikefalin injection, the company’s lead product candidate. Pursuant to the Product Agreements, Patheon and Patheon Greenville will manufacture commercial supplies of difelikefalin injection at the Monza, Italy and Greenville, North Carolina manufacturing sites, respectively, from API supplied by it. Patheon and Patheon Greenville will be responsible for supplying the other required raw materials and packaging components, and will also provide supportive manufacturing services, such as quality control testing for raw materials, packaging components and finished product. Sales and Marketing For oral difelikefalin, the company plans to develop and commercialize its drug candidate in pruritus indications, such as NDD-CKD, AD, and NP, on its own in the United States, while exploring partnerships for development and commercialization in geographical territories outside the United States. The company has executed out-licensing agreements on KORSUVA injection and Kapruvia in the dialysis setting in the United States and the rest of the world. Per the terms of the associated licensing agreements, CSL Vifor will commercialize KORSUVA injection and Kapruvia. Strategy The key elements of the company's strategy include expanding its Nephrology Franchise by optimizing the commercial potential of KORSUVA injection and developing oral difelikefalin for the treatment of pruritus in earlier stages of chronic kidney disease; and building a Medical Dermatology Franchise by executing its late-stage clinical programs in Atopic Dermatitis and Notalgia Paresthetica. Intellectual Property The company owns the patent portfolio of eighteen issued U.S. patents covering kappa opioid receptor (KOR) agonists, sixteen of which cover composition of matter of difelikefalin and its uses; six of these include composition of matter claims directed to difelikefalin, and ten patents include claims to its uses. All of these U.S. patents covering difelikefalin and its uses are expected to expire no earlier than November 12, 2027. Additionally, three U.S. patents have been granted with claims to difelikefalin-like dimer compounds and their uses. The company has filed patent applications in the United States and internationally claiming novel oral formulations of difelikefalin. One U.S. patent with claims to oral formulations of difelikefalin has been granted and is expected to expire no earlier than September 13, 2039. The company has also filed U.S. and foreign patent applications for additional formulations of difelikefalin, which if granted, would be expected to expire no earlier than March 18, 2040. The company also relies on trade secrets and careful monitoring of its proprietary information to protect aspects of its business that are not amenable to, or that the company does not consider appropriate for, patent protection. Difelikefalin The company’s synthetic peptide amide kappa opioid agonist patent portfolio is wholly owned by it. The portfolio includes eighteen issued U.S. patents (U.S. Patent Nos. 7,402,564; 7,713,937; 7,727,963; 7,842,662; 8,217,007; 8,236,766; 8,486,894; 8,536,131; 8,906,859; 8,951,970; 9,321,810; 9,334,305; 9,359,399; 10,017,536; 10,138,270; 10,793,596; 10,913,769 and 11,033,629) with claims to compositions of a wide range of synthetic peptide amide kappa opioid agonists, including difelikefalin and related molecules, as well as formulations containing and methods of using these compounds. These patents claiming difelikefalin compositions are due to expire November 12, 2027. U.S. Patent No. 11,033,629 with claims to oral formulations of difelikefalin is due to expire September 13, 2039. The company has listed twelve of the patents claiming difelikefalin acetate and/or its uses in the Orange Book, a listing of patents relating to approved drug products maintained by the FDA. Difelikefalin acetate has been awarded a five-year data exclusivity from the approval date, i.e. until August 23, 2026, prohibiting the FDA from accepting an application for approval of a difelikefalin product from a generic manufacturer until after the exclusivity period expires. In addition, the company has submitted an application for a patent term extension of one of its difelikefalin U.S. patents, which if granted for the additional full five-year extension requested, would extend the patent term to November 12, 2032. Foreign applications relating to difelikefalin and related molecules, as well as formulations containing and methods of using these compounds, were filed in more than 40 foreign countries. National patents have been granted in 27 European countries, as well as in Australia, Brazil, Canada, China, Hong Kong, India, Israel, Japan, Malaysia, Mexico, New Zealand, the Russian Federation, Singapore, South Africa and South Korea. These granted foreign patents with claims to difelikefalin are due expire no earlier than November 12, 2027. The company also owns pending U.S. continuation and foreign patent applications with claims to oral formulations containing difelikefalin and medium chain fatty acid glycerides as absorption enhancers in Australia, Brazil, Canada, China, Europe, Japan, Hong Kong, Israel, India, South Korea, Malaysia, Mexico, New Zealand, the Philippines, the Russian Federation, Saudi Arabi, the United Arab Emirates, and South Africa. If granted, these patents would expire no earlier than September 13, 2029. In addition, the company owns pending U.S. and foreign patent applications with claims to oral formulations containing difelikefalin and oligosaccharides in Australia, Brazil, Canada, China, Europe, Japan, Hong Kong, Israel, India, South Korea, Malaysia, Mexico, New Zealand, the Philippines, the Russian Federation, Saudi Arabi, the United Arab Emirates, and South Africa. If granted, these patents would expire no earlier than March 18, 2041. Other Cara Patents and Patent Applications The company also owns several other U.S. patents, including U.S. Patent Nos. 7,741,350; 7,960,376; 7,960,377; and 8,211,926 with claims to other cannabinoid compounds and U.S. Patent No. 8,217,000 with claims to regulation of prolactin in mammals, including humans. Cara Trademark Applications and registrations The company owns the registered trademark ‘KORSUVA’ in the United States and in twelve foreign countries (Australia, Brazil, Canada, Israel, Japan, Kuwait, Mexico, New Zealand, Norway, South Korea, Switzerland, and the U.K.). In addition, the company owns three Japanese trademark applications for Katakana versions of ‘KORSUVA’ as may be pronounced in the Japanese language: ‘KORSUVA’ Katakana version 1: ‘ko-ru-su-ba’; Katakana version 2: ‘ko-ru-su-o-ba’; and Katakana version 3 ‘ko-o-su-ba’. Its trademark applications for ‘KORSUVA’ are pending in China and India. Additionally, the company owns the U.S. trademark application for ‘KAPRUVIA’ pending under an ‘Intent to Use’ designation, as well as the ‘KAPRUVIA’ trademark registered in all twenty-seven EU States (Austria, Belgium, Bulgaria, Croatia, Republic of Cyprus, the Czech Republic, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta, the Netherlands, Poland, Portugal, Romania, Singapore, Slovakia, Slovenia, Spain and Sweden) and fourteen additional countries: Albania, Australia, China, Iceland, Israel, Monaco, New Zealand, North Macedonia, Norway, the Russian Federation, Serbia, Switzerland, Turkey and the U.K. The company has applied for registration of the trademark ‘OPRUITY’ in the United States (which is pending under an Intent to Use designation) and in twenty other countries and regions: Australia, Brazil, Canada, China, EU, India, Israel, Japan, Malaysia, Mexico, New Zealand, Norway, the Russian Federation, Saudi Arabia, Singapore, South Korea, South Africa, Switzerland, the United Arab Emirates and the U.K. The company also owns the U.S. trademark application for ‘XAYLIANT’ pending under an ‘Intent to Use’ designation for use in future product(s) yet to be developed. History Cara Therapeutics, Inc. was founded in 2004. The company was incorporated in 2004.