Part I [Item 1. Business](index=8&type=section&id=Item%201.%20Business.) Cara Therapeutics is a clinical-stage biopharmaceutical company developing KORSUVA (CR845/difelikefalin) for pruritus, focusing on regulatory approval, U.S. commercialization, and expanding oral formulations [Overview](index=8&type=section&id=Overview) Cara Therapeutics is a clinical-stage biopharmaceutical company developing KORSUVA for pruritus, which has shown efficacy in CKD-aP trials, and is financed through equity and license agreements with no products currently for sale - The company's primary focus is on developing and commercializing treatments for pruritus by targeting peripheral kappa opioid receptors (KORs)[14](index=14&type=chunk) - The lead product candidate is **KORSUVA (CR845/difelikefalin)**, a first-in-class KOR agonist[14](index=14&type=chunk) - KORSUVA injection has demonstrated statistically significant reductions in itch intensity in Phase 3 and Phase 2 trials for hemodialysis patients with moderate-to-severe CKD-aP[15](index=15&type=chunk) - The company has partnered with Vifor Fresenius Medical Care Renal Pharma (VFMCRP) to commercialize KORSUVA injection in dialysis patients worldwide, excluding the U.S., Japan, and South Korea; Cara retains U.S. rights and will co-promote with VFMCRP in U.S. Fresenius Medical Care clinics[15](index=15&type=chunk) - The company has no products currently available for sale and has financed its operations primarily through equity/debt sales and payments from license agreements[18](index=18&type=chunk) [Recent Developments](index=8&type=section&id=Recent%20Developments) In late 2019, the company saw a CFO/CSO resignation, adopted a new inducement plan, and secured a license for oral KORSUVA technology, following a **$136.5 million** public offering and a manufacturing agreement - Dr. Mani Mohindru, former CFO and Chief Strategy Officer, resigned effective December 20, 2019[19](index=19&type=chunk) - Entered into a non-exclusive license agreement with Enteris Biopharma on August 20, 2019, for its Peptelligence® technology to develop, manufacture, and commercialize oral products[23](index=23&type=chunk) - Completed a follow-on public offering on July 29, 2019, raising net proceeds of **$136.5 million** from the sale of 6,325,000 shares at **$23.00** per share[25](index=25&type=chunk) - Entered into a Master Manufacturing Services Agreement with Patheon UK Limited on July 8, 2019, for non-exclusive manufacturing services for drug products[27](index=27&type=chunk) [The Market Opportunity](index=10&type=section&id=The%20Market%20Opportunity) The company targets significant market opportunities in pruritus (CKD-aP, AD, CLD-aP) and post-operative nausea and vomiting (PONV), where millions are affected with limited or no approved treatments - Chronic Kidney Disease-Associated Pruritus (CKD-aP) affects a significant portion of the **37 million** people with CKD in the U.S.; approximately **40%** of the **3.2 million** global dialysis patients experience moderate to severe pruritus, with no approved treatments in the U.S. or Europe[33](index=33&type=chunk)[34](index=34&type=chunk)[35](index=35&type=chunk) - Pruritus associated with Atopic Dermatitis (AD) is a defining feature of the condition, which affects up to **25%** of children and **2-5%** of adults, negatively impacting quality of life[36](index=36&type=chunk) - Chronic Liver Disease-Associated Pruritus (CLD-aP) is a common symptom for millions of Americans with CLD; in 2013, approximately **2.5 million** patients with CLD received a prescription for an anti-pruritic, yet there are no approved therapies for CLD-aP in the U.S.[39](index=39&type=chunk)[40](index=40&type=chunk) - Post-Operative Nausea and Vomiting (PONV) is a significant factor in hospital length of stay, with estimated annual costs in the U.S. around **$1 billion**; over **700 million** units of PONV drugs were sold in the U.S. in 2017[42](index=42&type=chunk) [Our Strategy](index=13&type=section&id=Our%20Strategy) The company's strategy focuses on advancing KORSUVA injection for CKD-aP towards approval, building a U.S. sales force, expanding Oral KORSUVA into other pruritic conditions, and seeking partnerships for I.V. CR845 for acute pain/PONV - Advance KORSUVA injection for moderate-to-severe CKD-aP in hemodialysis patients, with top-line data from the global KALM-2 Phase 3 study expected in **Q2 2020**[44](index=44&type=chunk)[46](index=46&type=chunk) - Build a specialty sales and marketing organization to commercialize KORSUVA injection for CKD-aP in U.S. dialysis centers, if approved[47](index=47&type=chunk) - Expand the use of Oral KORSUVA into other pruritic indications, including non-dialysis stage III-V CKD-aP, CLD-aP, and Atopic Dermatitis (AD), with top-line data from Phase 2 trials in CLD-aP and AD expected in **2020**[48](index=48&type=chunk) - Seek partnerships for further development and commercialization of I.V. CR845/difelikefalin for acute post-operative pain and/or PONV, following positive top-line data from a Phase 2/3 trial[49](index=49&type=chunk) [Our Product Candidates](index=17&type=section&id=Our%20Product%20Candidates) The company's pipeline centers on CR845/difelikefalin in injectable (KORSUVA) and oral forms, with KORSUVA injection in Phase 3 for CKD-aP (Breakthrough Therapy Designation) and oral forms in Phase 2 for other pruritic conditions | Program | Product Candidate | Primary Indication | Status | | :--- | :--- | :--- | :--- | | Pruritus | KORSUVA (CR845/ difelikefalin) Injection | Pruritus CKD – Hemodialysis | KALM-2 (Global) Phase 3 ongoing; KALM-1 completed; Phase 3 safety trials ongoing; Breakthrough Therapy Designation granted | | | Oral KORSUVA (CR845/difelikefalin) | Pruritus CKD (Stage III - V) | Phase 2 trial completed; topline data reported | | | Oral KORSUVA (CR845/difelikefalin) | Pruritus CLD – PBC | Phase 2 efficacy trial ongoing | | | Oral KORSUVA (CR845/difelikefalin) | Pruritus AD | Phase 2 efficacy trial ongoing | | Post-Op Setting | CR845/difelikefalin Injection | Acute Post-Operative Pain/PONV | Adaptive Phase 2/3 trial completed; top-line data reported | - KORSUVA injection for CKD-aP: The KALM-1 pivotal Phase 3 trial met its primary and all secondary endpoints; the global KALM-2 trial is fully enrolled, with top-line data expected in **Q2 2020**; an NDA filing is anticipated in the second half of **2020**[56](index=56&type=chunk)[60](index=60&type=chunk)[61](index=61&type=chunk) - Oral KORSUVA for non-dialysis CKD-aP: A Phase 2 trial met its primary endpoint at the **1.0 mg** dose, showing a statistically significant reduction in itch scores versus placebo; the company plans an End of Phase 2 meeting with the FDA to initiate a Phase 3 program in **H2 2020**[70](index=70&type=chunk)[71](index=71&type=chunk) - Oral KORSUVA for CLD-aP and AD: Phase 2 trials are ongoing for pruritus in patients with Primary Biliary Cholangitis (PBC) and Atopic Dermatitis (AD), with top-line data for both expected in **2020**[74](index=74&type=chunk)[77](index=77&type=chunk)[78](index=78&type=chunk) - I.V. CR845 for Post-Operative Pain/PONV: A Phase 2/3 trial showed statistically significant pain relief at the **1.0 mcg/kg** dose and significant reductions in PONV at both **0.5** and **1.0 mcg/kg** doses[81](index=81&type=chunk)[82](index=82&type=chunk)[83](index=83&type=chunk) [Collaboration and License Agreements](index=26&type=section&id=Collaboration%20and%20License%20Agreements) The company has key partnerships, notably with VFMCRP for KORSUVA injection in dialysis patients globally (ex-U.S., Japan, South Korea), and agreements with Maruishi and CKDP for specific territories - **VFMCRP Agreement:** Granted VFMCRP a license to commercialize KORSUVA injection for pruritus in dialysis patients worldwide (ex-U.S., Japan, South Korea); Cara received a **$50M** upfront payment and Vifor purchased **$20M** of common stock; Cara is eligible for up to **$470M** in regulatory and commercial milestones, plus tiered double-digit royalties; in the U.S., the companies will co-promote in FMCNA clinics under a profit-sharing arrangement[93](index=93&type=chunk)[94](index=94&type=chunk)[96](index=96&type=chunk) - **Maruishi Agreement:** Granted Maruishi an exclusive license for CR845/difelikefalin in Japan for acute pain and uremic pruritus; Cara received a **$15.0M** upfront fee and is eligible for up to **$10.5M** in milestones, plus tiered royalties[97](index=97&type=chunk)[98](index=98&type=chunk) - **CKDP Agreement:** Granted CKDP an exclusive license for CR845/difelikefalin in South Korea; Cara received a **$0.6M** upfront payment and is eligible for up to **$3.8M** in milestones, plus tiered royalties[99](index=99&type=chunk)[100](index=100&type=chunk) [Manufacturing and License Agreements](index=30&type=section&id=Manufacturing%20and%20License%20Agreements) The company has secured agreements with Enteris Biopharma for oral formulation technology and Patheon UK Limited for non-exclusive commercial manufacturing of KORSUVA injection - **Enteris Biopharma:** Entered a non-exclusive license for Enteris's Peptelligence® technology for oral drug delivery; Cara paid an **$8.0 million** upfront fee (**$4.0M** cash, **$4.0M** stock) and is obligated to pay future milestones and low-single digit royalties[105](index=105&type=chunk)[106](index=106&type=chunk)[107](index=107&type=chunk) - **Patheon UK Limited:** Established a Master Manufacturing Services Agreement (MSA) for non-exclusive manufacturing of drug products; related agreements govern the commercial supply of CR845/difelikefalin injection at Patheon's Monza, Italy and Greenville, North Carolina sites[113](index=113&type=chunk)[117](index=117&type=chunk) [Sales and Marketing](index=32&type=section&id=Sales%20and%20Marketing) Cara Therapeutics plans to establish its own U.S. commercial organization for KORSUVA injection in dialysis, while out-licensing ex-U.S. rights, with market research indicating strong physician interest due to efficacy and safety - The company plans to build its own commercial organization and distribution capability in the U.S. for KORSUVA injection in the dialysis setting[119](index=119&type=chunk) - For Oral KORSUVA, the company plans to develop and commercialize on its own in the U.S. while exploring partnerships for ex-U.S. territories[119](index=119&type=chunk) - Market research indicates a clear unmet need for managing CKD-aP among dialysis patients, with physicians impressed by CR845/difelikefalin's efficacy and safety profile[121](index=121&type=chunk)[122](index=122&type=chunk)[123](index=123&type=chunk)[124](index=124&type=chunk) - Market research for PONV suggests anesthesiologists view CR845's novel mechanism and efficacy favorably, particularly for high-risk patients and as a potential new rescue therapy option[126](index=126&type=chunk) [Intellectual Property](index=34&type=section&id=Intellectual%20Property) The company's IP strategy focuses on wholly-owned patent protection for CR845/difelikefalin, with U.S. patents expiring no earlier than **2027** (potential extension) and new oral formulation patents potentially extending to **2039** - The company wholly owns its patent portfolio for its synthetic peptide amide kappa opioid agonists[136](index=136&type=chunk) - The portfolio includes fifteen issued U.S. patents covering CR845/difelikefalin composition and methods of use; the earliest U.S. patent is expected to expire no earlier than **2027**, with potential for a **5-year** extension under the Hatch-Waxman Act[136](index=136&type=chunk) - Patent applications have been filed internationally for novel oral formulations of CR845/difelikefalin, which if granted, would expire no earlier than **2039**[127](index=127&type=chunk) - Patents for CR845/difelikefalin have been granted in **31** European countries and other key markets including Australia, Canada, China, and Japan, expiring no earlier than **November 12, 2027**[136](index=136&type=chunk) [Competition](index=38&type=section&id=Competition) Cara Therapeutics faces intense competition from large pharmaceutical and biotech companies, with no approved CKD-aP products in the U.S., and a fragmented market for chronic pruritus and PONV - The company faces competition from large pharmaceutical and biotech companies with greater financial and technical resources[144](index=144&type=chunk) - For CKD-aP, there are no approved products in the U.S., but competitors include Sanwa Kagaku Kenkyusho and Toray Industries (nalfurafine, approved in Japan)[148](index=148&type=chunk)[149](index=149&type=chunk) - For chronic pruritus, competitors with product candidates include Menlo Therapeutics (serlopitant), Trevi (nalbuphine ER), and Vanda (tradipitant)[150](index=150&type=chunk) - The PONV market is highly fragmented with numerous generic products; I.V. CR845/difelikefalin would likely be used as an add-on therapy for high-risk patients[151](index=151&type=chunk) [Manufacturing](index=40&type=section&id=Manufacturing) The company relies entirely on third-party contract manufacturers for all product supplies, with a non-exclusive commercial manufacturing agreement in place with Patheon for KORSUVA (CR845/difelikefalin) injection - The company has no manufacturing facilities and relies on third parties for all manufacturing needs[152](index=152&type=chunk) - A non-exclusive commercial manufacturing agreement is in place with Patheon for KORSUVA (CR845/difelikefalin) injection[152](index=152&type=chunk) - Product candidates are manufactured using reliable synthetic processes from readily available starting materials, amenable to scale-up without special equipment[153](index=153&type=chunk) [Government Regulation and Product Approval](index=42&type=section&id=Government%20Regulation%20and%20Product%20Approval) The company's operations are subject to extensive U.S. and international regulations, including a lengthy drug approval process, with KORSUVA injection having FDA Breakthrough Therapy Designation, and ongoing post-approval compliance requirements - The drug approval process in the U.S. requires extensive preclinical and clinical testing (Phase 1, 2, 3) to establish safety and efficacy before an NDA can be submitted to the FDA[158](index=158&type=chunk)[160](index=160&type=chunk)[162](index=162&type=chunk) - The FDA granted Breakthrough Therapy Designation to KORSUVA injection for CKD-aP in hemodialysis patients, which is intended to expedite the development and review process[174](index=174&type=chunk)[175](index=175&type=chunk) - If approved, product candidates may be regulated as a "controlled substance" by the DEA, which imposes strict registration, security, and recordkeeping requirements[182](index=182&type=chunk)[183](index=183&type=chunk) - The company is subject to federal and state healthcare laws, including the Anti-Kickback Statute, False Claims Act, and data privacy laws like HIPAA, which restrict business practices[189](index=189&type=chunk)[190](index=190&type=chunk)[192](index=192&type=chunk) - Commercial success depends on securing coverage and adequate reimbursement from government payers (Medicare, Medicaid) and private insurers, who are increasingly focused on cost-containment[201](index=201&type=chunk)[202](index=202&type=chunk) [Item 1A. Risk Factors](index=61&type=section&id=Item%201A.%20Risk%20Factors) The company faces substantial risks including significant financial losses, dependency on KORSUVA injection's success, clinical and regulatory uncertainties, intense competition, reliance on third parties, intellectual property challenges, and evolving healthcare laws - **Financial Risks:** The company has a history of significant net losses (**$106.4M** in 2019) and an accumulated deficit of **$400.7M** as of Dec 31, 2019; it anticipates continued losses and will require additional funding to complete development and commercialization efforts[220](index=220&type=chunk)[228](index=228&type=chunk) - **Product Dependency:** The business is substantially dependent on the success of its lead candidate, KORSUVA (CR845/difelikefalin) injection; failure to complete Phase 3 trials, receive regulatory approval, or successfully commercialize this product would have a material adverse impact[234](index=234&type=chunk)[235](index=235&type=chunk) - **Clinical & Regulatory Risks:** The regulatory approval process is lengthy and unpredictable; clinical trials may be delayed or fail, and undesirable side effects could halt development or lead to a restrictive label; Breakthrough Therapy Designation does not guarantee a faster review or approval[250](index=250&type=chunk)[254](index=254&type=chunk)[262](index=262&type=chunk)[266](index=266&type=chunk) - **Commercialization Risks:** The company faces significant competition, has no commercial infrastructure, and must achieve market acceptance and adequate reimbursement from payers, which is uncertain[300](index=300&type=chunk)[305](index=305&type=chunk)[311](index=311&type=chunk) - **Third-Party Reliance:** The company relies on third-party CROs for clinical trials and contract manufacturers for product supply; failure of these parties to perform satisfactorily could delay development and commercialization[323](index=323&type=chunk)[330](index=330&type=chunk) - **Intellectual Property Risks:** The ability to protect proprietary rights is difficult and costly; patents may be challenged, circumvented, or may expire before product commercialization, and the company may face infringement lawsuits from third parties[392](index=392&type=chunk)[408](index=408&type=chunk)[413](index=413&type=chunk) [Item 1B. Unresolved Staff Comments](index=135&type=section&id=Item%201B.%20Unresolved%20Staf%20Comments.) The company reports that it has no unresolved staff comments from the SEC - None[471](index=471&type=chunk) [Item 2. Properties](index=135&type=section&id=Item%202.%20Properties.) The company's principal offices are located in Stamford, Connecticut, occupying approximately **24,000 square feet** of leased office space, with the lease expiring in November 2023 - The company's principal offices are in a leased space of approximately **24,000 square feet** in Stamford, Connecticut[472](index=472&type=chunk) - The current office lease expires in **November 2023**[472](index=472&type=chunk) [Item 3. Legal Proceedings](index=135&type=section&id=Item%203.%20Legal%20Proceedings.) The company is not currently a party to any legal proceedings that would have a material adverse effect on its business, operating results, or financial condition - The company is not currently a party to any material legal proceedings[473](index=473&type=chunk) [Item 4. Mine Safety Disclosures](index=135&type=section&id=Item%204.%20Mine%20Safety%20Disclosures.) This item is not applicable to the company - Not applicable[475](index=475&type=chunk) Part II [Item 5. Market for Registrant's Common Equity, Related Stockholder Matters and Issuer Purchases of Equity Securities](index=135&type=section&id=Item%205.%20Market%20for%20Registrant's%20Common%20Equity,%20Related%20Stockholder%20Matters%20and%20Issuer%20Purchases%20of%20Equity%20Securities.) Cara Therapeutics' common stock trades on The Nasdaq Global Market under "CARA", with no cash dividends ever paid or anticipated, and a stock performance graph comparing its return to relevant indices - The company's common stock is traded on The Nasdaq Global Market under the symbol "**CARA**"[478](index=478&type=chunk) - The company has never declared or paid cash dividends and does not anticipate doing so in the foreseeable future[481](index=481&type=chunk) | | 12/31/2014 | 12/31/2015 | 12/31/2016 | 12/31/2017 | 12/31/2018 | 12/31/2019 | | :--- | :--- | :--- | :--- | :--- | :--- | :--- | | Cara Therapeutics, Inc. | 100.00 | 169.11 | 93.18 | 122.77 | 130.39 | 161.58 | | Nasdaq Biotechnology | 100.00 | 111.42 | 87.26 | 105.64 | 95.79 | 119.17 | | Nasdaq Composite | 100.00 | 105.73 | 113.66 | 145.76 | 140.10 | 189.45 | [Item 6. Selected Financial Data](index=137&type=section&id=Item%206.%20Selected%20Financial%20Data.) This section presents selected financial data for the five years ended December 31, 2019, showing increased revenue to **$19.9 million** in 2019, a widened net loss to **$106.4 million**, and growth in total assets and stockholders' equity | (in thousands) | 2019 | 2018 | 2017 | 2016 | 2015 | | :--- | :--- | :--- | :--- | :--- | :--- | | **Total revenue** | $19,886 | $13,469 | $911 | $86 | $3,803 | | **Research and development** | $113,820 | $75,531 | $48,524 | $49,253 | $21,221 | | **General and administrative** | $17,745 | $15,320 | $11,872 | $9,233 | $7,770 | | **Net loss** | $(106,373) | $(74,013) | $(58,125) | $(57,280) | $(24,690) | | **Net loss per share** | $(2.49) | $(2.06) | $(1.86) | $(2.10) | $(1.00) | | (in thousands) | As of Dec 31, 2019 | As of Dec 31, 2018 | | :--- | :--- | :--- | | **Cash, cash equivalents and marketable securities** | $218,165 | $182,779 | | **Total assets** | $232,959 | $190,823 | | **Total liabilities** | $46,246 | $57,193 | | **Total stockholders' equity** | $186,713 | $133,630 | [Item 7. Management's Discussion and Analysis of Financial Condition and Results of Operations](index=140&type=section&id=Item%207.%20Management's%20Discussion%20and%20Analysis%20of%20Financial%20Condition%20and%20Results%20of%20Operations.) In 2019, revenue increased to **$19.9 million**, while net loss widened to **$106.4 million** due to higher R&D and G&A expenses, with the company ending 2019 with **$218.2 million** in cash, sufficient into H2 2021 | (in thousands) | 2019 | 2018 | 2017 | | :--- | :--- | :--- | :--- | | **Total Revenue** | $19,886 | $13,469 | $911 | | **R&D Expense** | $113,820 | $75,531 | $48,524 | | **G&A Expense** | $17,745 | $15,320 | $11,872 | | **Net Loss** | $(106,373) | $(74,013) | $(58,125) | - The increase in R&D expense in 2019 was primarily due to costs for Phase 3 trials of KORSUVA injection, Phase 2 trials of Oral KORSUVA, and an **$8.0 million** upfront payment for the Enteris License Agreement[543](index=543&type=chunk) - The company ended 2019 with **$218.2 million** in cash, cash equivalents, and marketable securities; management expects these funds to be sufficient to finance operations into the second half of **2021**[561](index=561&type=chunk)[575](index=575&type=chunk) - Net cash used in operating activities was **$109.2 million** in 2019, compared to **$22.3 million** in 2018; the increase was primarily due to higher net loss and changes in deferred revenue[581](index=581&type=chunk)[582](index=582&type=chunk) - Net cash provided by financing activities was **$142.6 million** in 2019, mainly from a public offering that raised net proceeds of **$136.5 million**[590](index=590&type=chunk)[558](index=558&type=chunk) [Item 7A. Quantitative and Qualitative Disclosures About Market Risk](index=165&type=section&id=Item%207A.%20Quantitative%20and%20Qualitative%20Disclosures%20About%20Market%20Risk.) The company's primary market risk is interest rate fluctuations on its investment portfolio, which is conservatively managed with **$199.9 million** in marketable securities as of December 31, 2019, mitigating significant impact from rate changes - The company's main market risk is interest rate risk on its portfolio of cash and marketable securities[618](index=618&type=chunk) - As of December 31, 2019, the company had **$199.9 million** invested in marketable securities, including corporate bonds, commercial paper, and U.S. government obligations with maturities through December 2021[617](index=617&type=chunk) - Due to the conservative nature and short duration of its investments, a hypothetical **1% increase** in interest rates would result in an immaterial decrease in the fair value of the investment portfolio[620](index=620&type=chunk) - Credit quality risk is managed through an investment policy that specifies credit standards and limits exposure to any single issuer or investment type[621](index=621&type=chunk) [Item 8. Financial Statements and Supplementary Data](index=167&type=section&id=Item%208.%20Financial%20Statements%20and%20Supplementary%20Data.) This section contains the company's audited financial statements for FY2019, including Balance Sheets, Statements of Comprehensive Loss, Stockholders' Equity, and Cash Flows, along with the independent auditor's unqualified opinion - Includes the Report of Independent Registered Public Accounting Firm (Ernst & Young LLP), which provides an unqualified opinion on the financial statements and the effectiveness of internal control over financial reporting[628](index=628&type=chunk)[629](index=629&type=chunk)[640](index=640&type=chunk) - The critical audit matter identified was Revenue Recognition, specifically the complexity and judgment involved in estimating the total research and development costs to complete obligations under a license agreement, which impacts the timing of revenue recognition[633](index=633&type=chunk) - Presents the audited Balance Sheets, Statements of Comprehensive Loss, Statements of Stockholders' Equity, and Statements of Cash Flows[625](index=625&type=chunk) [Item 9. Changes in and Disagreements with Accountants on Accounting and Financial Disclosure](index=242&type=section&id=Item%209.%20Changes%20in%20and%20Disagreements%20with%20Accountants%20on%20Accounting%20and%20Financial%20Disclosure.) The company reports that there have been no changes in or disagreements with its accountants on any matter of accounting principles or practices, financial statement disclosure, or auditing scope or procedure - None[928](index=928&type=chunk) [Item 9A. Controls and Procedures](index=242&type=section&id=Item%209A.%20Controls%20and%20Procedures.) Management concluded that disclosure controls and internal control over financial reporting were effective as of December 31, 2019, a conclusion affirmed by the independent auditor, with no material changes reported - Management concluded that disclosure controls and procedures were effective as of **December 31, 2019**[929](index=929&type=chunk) - Management concluded that internal control over financial reporting was effective as of **December 31, 2019**, based on the COSO framework[931](index=931&type=chunk) - Ernst & Young LLP, the independent auditor, has audited and confirmed the effectiveness of the company's internal control over financial reporting[932](index=932&type=chunk) - There were no material changes in internal control over financial reporting during the fourth quarter of **2019**[933](index=933&type=chunk) [Item 9B. Other Information](index=242&type=section&id=Item%209B.%20Other%20Information.) The company reports that there is no other information to disclose for this item - None[936](index=936&type=chunk) Part III [Item 10. Directors, Executive Officers and Corporate Governance](index=244&type=section&id=Item%2010.%20Directors,%20Executive%20Of%20icers%20and%20Corporate%20Governance.) Information concerning directors, executive officers, and corporate governance is incorporated by reference from the company's 2020 Annual Meeting Proxy Statement - Information is incorporated by reference from the **2020** Annual Meeting Proxy Statement[939](index=939&type=chunk) [Item 11. Executive Compensation](index=244&type=section&id=Item%2011.%20Executive%20Compensation.) Information concerning executive compensation is incorporated by reference from the company's 2020 Annual Meeting Proxy Statement - Information is incorporated by reference from the **2020** Annual Meeting Proxy Statement[940](index=940&type=chunk) [Item 12. Security Ownership of Certain Beneficial Owners and Management and Related Stockholder Matters](index=244&type=section&id=Item%2012.%20Security%20Ownership%20of%20Certain%20Beneficial%20Owners%20and%20Management%20and%20Related%20Stockholder%20Matters.) Information concerning security ownership and equity compensation plans is incorporated by reference from the company's 2020 Annual Meeting Proxy Statement - Information is incorporated by reference from the **2020** Annual Meeting Proxy Statement[941](index=941&type=chunk) [Item 13. Certain Relationships and Related Transactions and Director Independence](index=244&type=section&id=Item%2013.%20Certain%20Relationships%20and%20Related%20Transactions%20and%20Director%20Independence.) Information concerning related party transactions and director independence is incorporated by reference from the company's 2020 Annual Meeting Proxy Statement - Information is incorporated by reference from the **2020** Annual Meeting Proxy Statement[942](index=942&type=chunk) [Item 14. Principal Accountant Fees and Services](index=244&type=section&id=Item%2014.%20Principal%20Accountant%20Fees%20and%20Services.) Information concerning principal accountant fees and services is incorporated by reference from the company's 2020 Annual Meeting Proxy Statement - Information is incorporated by reference from the **2020** Annual Meeting Proxy Statement[943](index=943&type=chunk) Part IV [Item 15. Exhibits, Financial Statement Schedules](index=244&type=section&id=Item%2015.%20Exhibits,%20Financial%20Statement%20Schedules.) This section lists the documents filed as part of the Annual Report on Form 10-K, including financial statements, schedules, and a detailed list of exhibits such as corporate governance documents and material contracts - Lists the Financial Statements of Cara Therapeutics, Inc. included in the filing[945](index=945&type=chunk) - States that all other financial statement schedules are omitted because they are not applicable or the required information is already included in the financial statements or notes[949](index=949&type=chunk) - Provides a detailed list of exhibits filed with the report, including the Amended and Restated Certificate of Incorporation, material license and manufacturing agreements, and executive officer certifications[950](index=950&type=chunk)[952](index=952&type=chunk)[953](index=953&type=chunk)

Targeting Pruritus with Novel Peripherally-Restricted Kappa Agonist Therapeutics November 2019 Forward Looking Statements 2 This presentation contains certain forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. In some cases, you can identify forward-looking statements by the words "anticipate," "believe," "continue," "estimate," "expect," "objective," "ongoing," "plan," "propose," "potential," "projected", or "up-coming" and/or the negative of these terms, ...

Cara Therapeutics, Inc. (NASDAQ:CARA) Q3 2019 Results Earnings Conference Call November 5, 2019 4:30 PM ET Company Participants Jane Urheim - Stern Investor Relations Derek Chalmers - President & Chief Executive Officer Mani Mohindru - Chief Financial Officer & Chief Strategy Officer Conference Call Participants Chris Howerton - Jefferies David Amsellem - Piper Jaffray Annabel Samimy - Stifel Pete Stavropoulos - Cantor Fitzgerald Esther Hong - Janney Chris Howerton - Jefferies Operator Good afternoon, and w ...

Table of Contents UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, D.C. 20549 FORM 10-Q ☒ QUARTERLY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 FOR THE QUARTERLY PERIOD ENDED SEPTEMBER 30, 2019 OR ☐ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 COMMISSION FILE NUMBER 001-36279 CARA THERAPEUTICS, INC. (Exact name of registrant as specified in its charter) Delaware 75-3175693 (State or other jurisdiction of incorporation ...

Cara Therapeutics, Inc. (NASDAQ:CARA) Q2 2019 Earnings Conference Call August 7, 2019 4:30 PM ET Company Participants Jane Urheim - Stern Investor Relations Derek Chalmers - President & Chief Executive Officer Mani Mohindru - Chief Financial Officer & Chief Strategy Officer Conference Call Participants Jason Gerberry - Bank of America David Amsellem - Piper Jaffray Nick Rubino - Stifel Charles Duncan - Cantor Fitzgerald Alan Carr - Needham & Company Esther Hong - Janney Operator Good afternoon and welcome t ...

UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, D.C. 20549 FORM 10-Q ☒ QUARTERLY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 FOR THE QUARTERLY PERIOD ENDED JUNE 30, 2019 OR ☐ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 COMMISSION FILE NUMBER 001-36279 CARA THERAPEUTICS, INC. (Exact name of registrant as specified in its charter) Delaware 75-3175693 (State or other jurisdiction of incorporation or organization) (I.R.S ...

KORSUVA™ Development Programs - KORSUVA™ Injection is in Phase 3 development for CKD-associated pruritus (CKD-aP) in hemodialysis patients, with positive topline data from the KALM-1 trial reported in May 2019 and topline data from the KALM-2 trial expected in 2H19[3] - Oral KORSUVA™ has multiple programs including a Phase 2 trial ongoing for CKD-aP in non-dialysis patients with data expected in 2H19, a Phase 2 trial expected to initiate in 2Q19 for chronic liver disease-associated pruritus, and a Phase 2 trial expected to initiate around mid-year 2019 for atopic dermatitis[3] - The FDA has conditionally accepted KORSUVA™ as the trade name for CR845 / difelikefalin for pruritic indications[8] Market Opportunity - Chronic kidney disease-associated pruritus (CKD-aP) affects approximately 40% to 50% of patients with renal failure[5] - Approximately 20% to 30% of patients with cholestatic liver disease experience pruritus[5] - In the U S, approximately 50% of the 20 million atopic dermatitis (AD) patients seek treatment for pruritus[6] - In the U S, approximately 50% of the 8 million psoriasis patients seek treatment for pruritus[7] - Approximately 60% to 70% of hemodialysis (HD) patients report pruritus[10] - Approximately 30% to 40% of hemodialysis patients with CKD-aP have moderate to severe itch intensity[10] - There are approximately 468,000 patients on dialysis in the US[11] KALM-1 Trial Results - In the KALM-1 Phase 3 trial, 51% of KORSUVA™-treated subjects achieved ≥3 point improvement in weekly mean of daily worst itching intensity NRS (WI-NRS) compared to 28% in the placebo group (p = 000019)[21] - In the KALM-1 Phase 3 trial, 39% of KORSUVA™-treated subjects achieved ≥4 point improvement in weekly mean of daily WI-NRS compared to 18% in the placebo group (p = 000032)[22] Financial Status - As of March 31, 2019, the company had $1561 million in cash and marketable securities[38]

Financial Data and Key Metrics Changes - For Q1 2019, the company reported a net loss of $22 million or $0.56 per share, compared to a net loss of $16.8 million or $0.51 per share in Q1 2018 [27] - R&D expenses increased to $23.6 million from $13.4 million in the same period of 2018, primarily due to higher clinical trial costs and increased stock compensation and payroll-related costs [28] - G&A expenses were $3.9 million in Q1 2019, slightly up from $3.7 million in Q1 2018, attributed to increased legal and consulting costs [29] - Cash and marketable securities totaled $15.1 million as of March 31, 2019, down from $182.8 million at the end of 2018, mainly due to cash used in operations of $27.5 million [30] Business Line Data and Key Metrics Changes - The lead drug candidate, KORSUVA, is advancing in clinical trials for chronic kidney disease-associated pruritus (CKD-aP) in hemodialysis patients, with two pivotal Phase III trials (KALM-1 and KALM-2) ongoing [6][10] - KORSUVA Injection has received breakthrough therapy designation from the FDA for CKD-aP, indicating significant unmet medical need [14] - The company is also progressing Oral KORSUVA in a Phase II trial for pre-dialysis CKD-aP patients, with plans to initiate additional trials for chronic liver disease and atopic dermatitis [9][25] Market Data and Key Metrics Changes - It is estimated that there are at least 2.5 million Stage III to V CKD patients in the U.S. suffering from pruritus, with current treatments primarily consisting of generic corticosteroids and antihistamines [22] - The company is targeting a significant market opportunity in pruritus across various patient populations, including those with chronic liver disease and atopic dermatitis [10][25] Company Strategy and Development Direction - The company aims to develop KORSUVA as a first-in-class therapeutic for hemodialysis patients suffering from pruritus, with multiple late-stage clinical readouts expected throughout the year [6][21] - The strategy includes expanding clinical trials to assess the efficacy of KORSUVA in various patient populations, thereby broadening its market potential [10][25] - The company is focused on meeting regulatory requirements and expediting the path to NDA filing through additional safety studies [20] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the progress of clinical programs and the potential of KORSUVA to address significant unmet needs in pruritus [26] - The company anticipates top-line data from KALM-1 and KALM-2 trials by the end of 2019, which will be critical for future development and commercialization efforts [21][41] - Management acknowledged the increased clinical trial expenses and revised cash runway guidance to extend into Q4 2020, reflecting the accelerated development plans [31] Other Important Information - The company has initiated a second open-label safety study to satisfy long-term safety exposure requirements per ICH guidelines, enrolling up to 400 patients [20] - The company plans to provide more details on the design of upcoming trials for chronic liver disease and atopic dermatitis as they are initiated [25] Q&A Session Summary Question: Expectations for long-term safety exposure requirements - Management indicated that standard ICH guidelines require 100 exposures at the one-year mark and 300 at the six-month mark [33] Question: Enrollment rate in KALM-2 and interim data analysis - Management stated that they do not provide specific enrollment updates but expect top-line data by the end of the year [41] Question: Specific patient subgroups for the liver study - Management noted that the focus will likely be on patients with primary biliary cholangitis due to the consistent and severe pruritus observed in this subgroup [46][47] Question: Commercial preparation strategy and timing - Management indicated that commercial preparations will begin after confirming efficacy in the first Phase III trial, with initial planning already underway [58][59] Question: Severity of CKD patients in the study - Management reported that the average patient has been on hemodialysis for 5 to 6 years and experiences moderate-to-severe pruritus [62]

Product Development and Trials - KORSUVA (CR845/difelikefalin) injection has shown statistically significant reductions in itch intensity in Phase 2 trials for hemodialysis patients with moderate-to-severe CKD-associated pruritus (CKD-aP) and is currently in Phase 3 trials[170]. - KORSUVA (CR845/difelikefalin) injection has received Breakthrough Therapy Designation from the FDA in June 2017, indicating its potential in treating CKD-aP[179]. - The product candidate pipeline includes ongoing Phase 3 trials for KORSUVA (CR845/difelikefalin) injection in CKD-aP and Phase 2 trials for Oral KORSUVA in CKD and chronic liver disease[179]. - The first pivotal Phase 3 efficacy trial of KORSUVA (CR845/difelikefalin) injection for CKD-aP treatment in hemodialysis patients was initiated in Q1 2018, with top-line data expected in Q2 2019[182]. - KALM-1 Phase 3 trial enrolled over 350 hemodialysis patients across approximately 60 clinical sites, with top-line data expected in Q2 2019[184]. - The second Phase 3 trial (KALM-2) began in August 2018, aiming to enroll patients in the U.S. and multiple countries, with top-line data expected in H2 2019[185]. - A 52-week Phase 3 safety trial initiated in Q2 2017 is evaluating KORSUVA injection's long-term safety, with approximately 150 patients having completed at least six months of treatment[186]. - A new open-label Phase 3 safety trial was initiated in Q2 2019, expected to enroll up to 400 hemodialysis patients[187]. - The Phase 2 trial of Oral KORSUVA for CKD patients began in July 2018, with top-line data expected in H2 2019[194]. - The investigational new drug application for Oral KORSUVA for chronic liver disease-associated pruritus was submitted in Q4 2017, with a Phase 1 trial completed[198]. - A multi-dose Phase 2 trial for Oral KORSUVA in atopic dermatitis is expected to be initiated around mid-2019[201]. - CR845/difelikefalin is being investigated for acute postoperative pain relief, designed to avoid mu opioid receptor stimulation[202]. - CR845/difelikefalin injection achieved statistical significance for pain relief over 24 hours with the 1.0 mcg/kg dose versus placebo (p=0.032)[204]. - The Phase 2b trial of Oral CR845/difelikefalin showed a statistically significant 39% reduction in mean joint pain score for patients with OA of the hip on the 5.0 mg dose (p=0.043)[216]. Financial Performance - Total revenue recognized to date is $5.3 million from clinical development or regulatory milestone payments and sub-license fees[219]. - Total revenue for the three months ended March 31, 2019, was $4.38 million, a 100% increase compared to the same period in 2018[231]. - License and milestone fees revenue was $4.24 million for the three months ended March 31, 2019, with no revenue reported for the same period in 2018[232]. - Research and development (R&D) expenses totaled $23.61 million for the three months ended March 31, 2019, representing a 76% increase from $13.43 million in 2018[234]. - Direct clinical trial costs increased to $17.74 million, a 90% rise compared to $9.35 million in the prior year[234]. - Other income increased to $1.09 million for the three months ended March 31, 2019, a 250% increase from $311,000 in 2018[238]. - General and administrative expenses for the three months ended March 31, 2019, were $3.91 million, a 6% increase from $3.70 million in 2018[237]. - Net losses for the three months ended March 31, 2019, were $22.0 million, compared to $16.8 million for the same period in 2018, with an accumulated deficit of $316.3 million as of March 31, 2019[256]. Cash and Capital Management - The company had $156.1 million in unrestricted cash and cash equivalents as of March 31, 2019, sufficient to fund operations into Q4 2020[248]. - The company expects existing cash and cash equivalents will be sufficient to fund anticipated operating expenses into the fourth quarter of 2020[264]. - The company may need to raise additional capital to meet development objectives, particularly for I.V. and Oral CR845/difelikefalin, which could dilute existing stockholders' ownership[263]. - The company plans to use proceeds from its recent underwritten offering to fund clinical trials and research development activities, including Phase 3 programs for KORSUVA[246]. - As of March 31, 2019, the company had invested $142.0 million in marketable securities with a yield of approximately 2.65%[281]. - Net cash used in operating activities for the three months ended March 31, 2019, was primarily due to a net loss of $22.0 million and cash outflows from changes in operating assets and liabilities totaling $3.3 million[269]. - Net cash provided by investing activities was $26.4 million for the three months ended March 31, 2019, mainly from maturities of available-for-sale marketable securities[273]. Risks and Uncertainties - The successful development of product candidates is highly uncertain, with numerous risks associated with clinical trials and regulatory approvals[260]. - The company has incurred significant operating and net losses since inception, with expectations to continue incurring such losses in the near future[256]. - The anticipated operating expenses will increase due to ongoing development of KORSUVA (CR845/difelikefalin) injection and Oral KORSUVA, as well as the establishment of sales and marketing infrastructure[257]. - The safety profile of CR845/difelikefalin injection was generally well tolerated across multiple studies with no clinically significant changes in ECG characteristics[209]. - The most common adverse events reported for CR845/difelikefalin included dizziness (8%), headache (6%), dry mouth (6%), and constipation (12%)[216]. - CR845/difelikefalin injection demonstrated no significant respiratory safety events in a Phase 1 trial with 15 healthy volunteers[212]. - The company does not intend to develop Oral CR845/difelikefalin for OA pain independently and will seek potential partners for further development[218]. Regulatory and Collaboration Efforts - The company has filed a shelf registration statement for aggregate offerings of up to $300 million to fund future operations and clinical trials, effective since April 4, 2019[175]. - The company retains all rights to KORSUVA (CR845/difelikefalin) in the United States and will promote it in U.S. dialysis clinics under a profit-sharing agreement with VFMCRP[170]. - The company aims to establish additional collaborations for its product candidates to enhance commercialization efforts[163]. - The company is eligible for up to $470 million in regulatory and commercial milestone payments under the VFMCRP Agreement[250]. - Under the Maruishi Agreement, the company could earn up to $6.0 million in clinical development milestones and $4.5 million in regulatory milestones[251].

Cara Therapeutics, Inc. (NASDAQ:CARA) Q4 2018 Earnings Conference Call March 12, 2019 4:30 PM ET Company Participants Jane Urheim - Stern Investor Relations Derek Chalmers - President and Chief Executive Officer Mani Mohindru - Chief Financial Officer and Chief Strategy Officer Conference Call Participants Christopher Howerton - Jefferies & Company, Inc. Jason Gerberry - Bank of America Merrill Lynch David Amsellem - Piper Jaffray Charles Duncan - Cantor Fitzgerald & Co. Annabel Samimy - Stifel, Nicolaus & ...