Tvardi Therapeutics, Inc 8-K, filed Jun 30, 2022
Tvardi Therapeutics, Inc. (TVRD)
About this 8-K
Tvardi Therapeutics, Inc filed this 8-K on June 30, 2022, reporting on events of June 28, 2022.
Items reported
- Item 7.01: Regulation FD disclosure
- Item 8.01: Other events
- Item 9.01: Financial statements and exhibits
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CURRENT REPORT
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| Item 7.01. | Regulation FD Disclosure. |
On June 30, 2022, Cara Therapeutics, Inc. (the “Company”) issued a press release (the “Press Release”) announcing positive topline results from its KOMFORT Phase 2 clinical trial of oral difelikefalin for the treatment of moderate-to-severe pruritus associated with Notalgia Paresthetica (“NP”) patients. The Company will hold a conference call to discuss the results at 8:30 a.m. ET on June 30, 2022. A copy of the Press Release and the presentation (the “NP Presentation”) to be discussed on the conference call are furnished as Exhibit 99.1 and Exhibit 99.2, respectively, to this Current Report on Form 8-K and incorporated herein by reference.
On June 30, 2022, the Company made available an updated corporate presentation, which can be found on the Company’s website (the “Corporate Presentation”). The Corporate Presentation is furnished as Exhibit 99.3 and incorporated herein by reference.
The information furnished under this Item 7.01, including Exhibit 99.1, Exhibit 99.2 and Exhibit 99.3, shall not be deemed “filed” for purposes of Section 18 of the Securities Exchange Act of 1934 (the “Exchange Act”) or subject to the liabilities of that section, nor shall it be deemed to be incorporated by reference into any of the Company’s filings with the Securities and Exchange Commission (“SEC”) under the Exchange Act or the Securities Act of 1933, as amended, whether made before or after the date hereof, regardless of any general incorporation language in such a filing. The information shall not be deemed incorporated by reference into any other filing with the SEC made by the Company, regardless of any general incorporation language in such filing.
| Item 8.01. | Other Information. |
On June 30, 2022, the Company issued the Press Release announcing positive topline results from its KOMFORT Phase 2 clinical trial of oral difelikefalin for the treatment of moderate-to-severe pruritus associated with NP patients.
The Phase 2 multicenter, randomized, double-blind, placebo-controlled, 8-week study was designed to evaluate the efficacy and safety of oral difelikefalin for moderate-to-severe pruritus in approximately 120 patients with NP. Patients were randomized to oral difelikefalin 2 mg taken twice daily versus placebo for 8 weeks, followed by a 4-week active extension period.
Primary Endpoint
The primary efficacy endpoint was the change from baseline in the weekly mean of the daily 24-hour Worst Itch-Numeric Rating Scale (“WI-NRS”) score at Week 8. Other endpoints included the ≥4-point responder analysis, itch-related quality of life scores, and safety assessments.
Patients treated with oral difelikefalin achieved the primary endpoint (-4.0 difelikefalin versus -2.4 placebo, p=0.001) with significant improvement observed as early as Week 1 and sustained through Week 8.
Other Endpoints
A statistically significantly greater proportion of patients treated with oral difelikefalin achieved a ≥4-point improvement in WI-NRS score at Week 8 versus placebo (41% difelikefalin versus 18% placebo, p=0.007).
Safety and Tolerability
Oral difelikefalin was generally well tolerated with a safety profile consistent with that seen in earlier clinical trials. The most common treatment-emergent adverse events reported in ≥5% of patients treated with oral difelikefalin and greater than placebo were: nausea, headache, dizziness, constipation and urine output increased.
| Item 9.01. | Financial Statements and Exhibits. |
| (d) Exhibits |
| Exhibit No. | Description | |
| 99.1 | Press Release, dated June 30, 2022 | |
| 99.2 | NP Presentation, dated June 30, 2022 | |
| 99.3 | Corporate Presentation, dated June 30, 2022 | |
| 104 | Cover page interactive data file (formatted as Inline XBRL) |
SIGNATURES
Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.
| CARA THERAPEUTICS, INC. | ||
| By: | /s/ CHRISTOPHER POSNER | |
| Christopher Posner | ||
| President and Chief Executive Officer | ||
Date: June 30, 2022
Exhibit 99.1
Cara Therapeutics Announces Positive Topline Results from KOMFORT Phase 2 Trial of Oral Difelikefalin for the Treatment of Pruritus in Patients with Notalgia Paresthetica
– Study achieved primary endpoint of Worst Itch-Numeric Rating Scale score change from baseline at Week 8 (p=0.001) –
– Onset of action seen at Week 1 and sustained through Week 8 –
– Statistical significance achieved on the WI-NRS ≥4-point responder analysis at Week 8 (p=0.007) –
– Oral difelikefalin was well tolerated with a consistent safety profile –
– Conference call today at 8:30 a.m. ET –
STAMFORD, Conn., June 30, 2022 – Cara Therapeutics, Inc. (Nasdaq: CARA), a commercial-stage biopharmaceutical company leading a new treatment paradigm to improve the lives of patients suffering from pruritus, today announced positive topline results from its Phase 2 proof-of-concept clinical trial (KOMFORT) evaluating oral difelikefalin for the treatment of moderate-to-severe pruritus in patients with notalgia paresthetica (NP), a nerve disorder characterized by chronic pruritus of the upper to middle back.
“We are pleased to have demonstrated clinical proof of concept for oral difelikefalin in the treatment of pruritus associated with notalgia paresthetica,” said Joana Goncalves, M.D., Chief Medical Officer at Cara Therapeutics. “These topline results coupled with the results from our other programs support the broad development of oral difelikefalin across disease areas regardless of the underlying cause of pruritus. We look forward to completing our data analyses and discussing next steps with the U.S. Food and Drug Administration.”
“With no approved treatments available for notalgia paresthetica, the condition is challenging to manage and burdensome for patients,” said Mark Lebwohl, M.D., the lead investigator and Professor and Dean for Clinical Therapeutics and Chairman Emeritus of the Department of Dermatology at Icahn School of Medicine at Mount Sinai. “These are encouraging results that underscore the potential for oral difelikefalin to be the first treatment option to address pruritus associated with notalgia paresthetica.”
Phase 2 Proof-of-Concept Trial Design & Topline Results
The Phase 2 multicenter, randomized, double-blind, placebo-controlled, 8-week study was designed to evaluate the efficacy and safety of oral difelikefalin for moderate-to-severe pruritus in approximately 120 patients with NP. Patients were randomized to oral difelikefalin 2 mg taken twice daily versus placebo for 8 weeks, followed by a 4-week active extension period.
The primary efficacy endpoint was the change from baseline in the weekly mean of the daily 24-hour Worst Itch-Numeric Rating Scale (WI-NRS) score at Week 8. Other endpoints included the ≥4-point responder analysis, itch-related quality of life scores, and safety assessments.
Patients treated with oral difelikefalin achieved the primary endpoint (-4.0 difelikefalin vs. -2.4 placebo, p=0.001) with significant improvement observed as early as Week 1 and sustained through Week 8.
In addition, a statistically significantly greater proportion of patients treated with oral difelikefalin achieved a ≥4-point improvement in WI-NRS score at Week 8 vs. placebo (41% difelikefalin vs. 18% placebo, p=0.007).
Oral difelikefalin was generally well tolerated with a safety profile consistent with that seen in earlier clinical trials. The most common treatment-emergent adverse events reported in ≥5% of patients treated with oral difelikefalin and greater than placebo were: nausea, headache, dizziness, constipation and urine output increased.
Conference Call & Webcast
Cara management will host a conference call and live webcast today at 8:30 a.m. ET to discuss the positive topline results.
To participate in the conference call, please dial (855) 445-2816 (domestic) or (484) 756-4300 (international) and refer to conference ID 6999079. A live webcast of the call can be accessed under "Events & Presentations" in the News & Investors section of the Company's website at www.CaraTherapeutics.com.
An archived webcast recording will be available on the Cara website beginning approximately two hours after the call.
About Pruritus Associated with Notalgia Paresthetica
Notalgia paresthetica (NP) is a common, although under-recognized, chronic, sensory neuropathy affecting the upper back.1 It is estimated that chronic pruritus affects up to 13% of the population in the United States, and about 8% of these patients suffer from neuropathic itch, including NP.2,3 One of the hallmark features of NP is chronic pruritus, which can be significantly burdensome and undermines the affected patients’ quality of life and overall well-being.3 The exact etiology of NP still has not been fully elucidated; however, it is widely accepted that NP is a sensory neuropathy caused by alteration and damage to thoracic spinal nerves.3
The management of NP is challenging and is often resistant to multiple therapies. There is currently no approved treatment for NP and conventional treatments for pruritus, such as antihistamines and topical steroids, are largely ineffective.4
References:
| 1. | Matthew Howard, Lukas Sahhar, Frank Andrews, Ralph Bergman and Douglas Gin. Notalgia paresthetica: a review for dermatologists. International J of Dermatology 2018,57, 388-392. |
| 2. | Manuel P. Pereira, Hannah Lüling, Annette Dieckhöfer, Sabine Steinke, Claudia Zeidler and Sonja Ständer. Brachioradial Pruritus and Notalgia Paraesthetica: A Comparative Observational Study of Clinical Presentation and Morphological Pathologies. Acta DV 2018; 98:82-88. |
| 3. | Mollanazar, N.K., Koch, S.D. & Yosipovitch, G. Epidemiology of Chronic Pruritus: Where Have We Been and Where Are We Going?. Curr Derm Rep 4, 20–29 (2015) |
| 4. | Mirna Šitum, Maja Kolić, Nika Franceschi and Marko Pećina. Notalgia Paresthetica. Acta Clin Croat 2018; 57:721-725. |
| 5. | Ahmed Ansari, David Weinstein & Naveed Sami. Notalgia paresthetica: treatment review and algorithmic approach. Journal of Dermatological Treatment 2019. |
About Cara Therapeutics
Cara Therapeutics is a commercial-stage biopharmaceutical company leading a new treatment paradigm to improve the lives of patients suffering from pruritus. The Company’s novel KORSUVA™ (difelikefalin) injection is the first and only FDA-approved treatment for moderate-to-severe pruritus associated with chronic kidney disease in adults undergoing hemodialysis. The Company is developing an oral formulation of difelikefalin and has initiated Phase 3 programs for the treatment of pruritus in patients with non-dialysis dependent advanced chronic kidney disease and atopic dermatitis. The Company has completed the placebo-controlled phase of a Phase 2 proof-of-concept trial of oral difelikefalin for the treatment of moderate-to-severe pruritus in patients with notalgia paresthetica. A Phase 2 proof-of-concept trial in primary biliary cholangitis patients with moderate-to-severe pruritus is ongoing. For more information, visit www.CaraTherapeutics.com and follow the company on 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, 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 candidates, the potential for the Company’s product candidates to be alternatives in the therapeutic areas investigated, including NP, and the potential for oral difelikefalin to address additional pruritic indications, the size and growth of the potential markets for pruritus management, the Company’s expected cash reach, and the potential impact of COVID-19 on the Company’s clinical development and regulatory timelines and plans. Because such statements are subject to risks and uncertainties, actual results may differ materially from those expressed or implied by such forward-looking statements. 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, 2021 and its other documents subsequently filed with or furnished to the Securities and Exchange Commission. 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.
MEDIA CONTACT:
Annie Spinetta
6 Degrees
973-768-2170
aspinetta@6degreespr.com
INVESTOR CONTACT:
Iris Francesconi, Ph.D.
Cara Therapeutics
203-406-3700
investor@caratherapeutics.com
Exhibit 99.2
KOMFORT Phase 2 Topline Data: Oral Difelikefalin for Pruritus in Notalgia Paresthetica JUNE 2022 The KOMFORT Phase 2 study evaluated the efficacy and safety of oral difelikefalin for moderate to severe pruritus in adult su bje cts with notalgia paresthetica (NP). Oral difelikefalin is an investigational drug product and its safety and efficacy have not been fully evaluated by any regulatory authority. The FDA approved KORSUVA Π( difelikefalin ) injection for the treatment of moderate - to - severe pruritus (itching) associated with chronic kidney disease (CKD - aP ) in adults undergoing hemodialysis (HD).
2 Confidential. For internal use only. Forward Looking Statements Statements contained in this presentation 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 timing of the Company’s planned clinical trials, potential results of ongoing and planned clinical trials, the Company’s planned future regulatory submissions and potential future regulatory approvals, timing of future regulatory and development milestones for the Company’s product candidates, the potential for the Company’s product candidates to be an alternative for Notalgia Paresthetica, the size and growth of the potential markets for Notalgia Paresthetica, the potential for oral difelikefalin to address additional pruritic indications, and the potential impact of COVID - 19 on the Company’s clinical development and regulatory timelines and plans. Because such statements are subject to risks and uncertainties, actual results may differ materially from those expressed or implied by such forward - looking statements. 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, 2021 and its other documents subsequently filed with or furnished to the Securities and Exchange Commission. All forward - looking statements contained in this presentation 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.
3 Confidential. For internal use only. Advancing our late - stage pipeline in multiple indications 1. Approved in the EU with the tradename KapruviaTM. 2. Commercialization rights to difelikefalin in defined indications - Japan : Maruishi Pharmaceutical Co, LTD; South Korea: Chong Kun Dang Pharmaceuticals. 3. Vifor Fresenius Medical Care Renal Pharma (VFMCRP) has commercial rights under a profit - share arrangement in the US and a royalty arr angement ex - US. HD CKD - aP : Hemodialysis Chronic Kidney Disease - associated Pruritus; NDD - CKD - aP : Non - Dialysis Dependent Chronic Kidney Disease associated Pruritus; Pruritus NP: Notalgia Paresthetica associated Pruritus; Pruritus PBC: Primary Biliary Cholangitis associated Pruritus 3 STAGE OF DEVELOPMENT Program Indication Phase 1 Phase 2 Phase 3 Approved Commercial Rights (ex - Japan and S. Korea) 2 KORSUVA TM Injection 1 Pruritus HD - CKD VFMCRP 3 Oral difelikefalin Pruritus NDD - CKD (stages IV - V) Cara Oral difelikefalin Pruritus Atopic Dermatitis Cara Oral difelikefalin Pruritus NP Cara Oral difelikefalin Pruritus PBC Cara
4 Confidential. For internal use only. Notalgia Paresthetica: A Sizable Market Opportunity 13% of US adults (18+) with chronic pruritus 1,2 8% of US chronic pruritus patients with neuropathic itch incl. NP 3 24% of US patients with NP under DERM care 4 - 6 34M US adults with chronic pruritus 1,2 2.7M of the US adults with neuropathic itch incl. NP 3 >650K addressable patients with NP 4 - 6 Sizable Patient Population Widely Underdiagnosed No FDA - Approved Therapies Source: 1. US Census Bureau 2020 population projection; 2. Mollanazar NK et al., Current Derm Report 2015: 4;20 - 29 ; 3. Pereira P. et al., Acta DV 2018; 98:82 - 88; 4. Syneos Health qualitative primary research of US dermatologists, Feb 2022; 5. Syneos Health quantitative research of derm office administrators, March 2022; 6. IQVIA, KOMODO, and RxDataScience Apollo claims database
5 Confidential. For internal use only. 5 Source: 1. Pereira Manuel et al ActaDV 2018; 98:82 - 88, 2. Howard et al Int J of Derm 2018; 57; 388 - 392. NP is a sensory neuropathic syndrome characterized by chronic pruritus 1 Pruritus is burdensome and impairs quality of life 1 No FDA - approved treatments; off label treatments are either ineffective or have tolerability issues. 2 Notalgia Paresthetica: A Significant Unmet Need
6 Confidential. For internal use only. Notalgia Paresthetica • Likely due to mechanical irritation along the spinal cord • Believed to be caused by compression of the dorsal branches of the spinal nerves (T2 - T6) • Leads to circumscribed pruritus between the scapulae, usually unilateral but occasionally bilateral Notalgia Paresthetica Source: Pereira Manuel et al ActaDV 2018; 98:82 - 88. Hachisuka et al Pain 2018; 159(3): 603 - 609.
7 Confidential. For internal use only. KOMFORT: POC Phase 2 Study Design 8 Weeks TREATMENT RUN - IN 7 Days END OF TREATMENT 1:1 Randomization SCREEN KORSUVA : 0.25 mg BID Baseline Mean WI - NRS ≥ 5 Placebo BID Oral difelikefalin : 2 mg BID Primary Endpoint Change from baseline in the weekly mean of the daily 24 - hr Worst Itch - Numeric Rating Scale (WI - NRS) at Week 8 Other Endpoints Proportion of patients achieving ≥4 - point improvement in WI - NRS at Week 8 Safety Assessments QoL assessments 4 Week Active Extension Ongoing Oral difelikefalin is an investigational drug product and its safety and efficacy have not been fully evaluated by any regulatory authority. The F DA approved KORSUVA Œ ( difelikefalin ) injection for the treatment of moderate - to - severe pruritus (itching) associated with chronic kidney disease (CKD - aP ) in adults undergoing hemodialysis (HD).
8 Confidential. For internal use only. Patient Disposition Placebo (N=63) DFK 2 mg BID (N=63) Total Randomized (N=126) Received Study Treatment 63 (100%) 62 (98.4%) Completed 57 (90.5%) 49 (77.8%) Discontinued 6 (9.5%) 14 (22.2%) Adverse event 4 (6.3%) 12 (19.0%) Lost to follow - up 2 (3.2%) 1 (1.6%) Patient withdrew consent 0 1 (1.6%)
9 Confidential. For internal use only. Patient Demographics & Disease Characteristics Female, n (%) 42 (66.7%) 48 (77.4%) Age - Mean (SD) 60.2 (11.8) 59.3 (12.4) Race, n (%) White 56 (88.9%) 49 (79.0%) Black 4 (6.3%) 10 (16.1%) Other 3 (4.8%) 3 (4.8%) BMI – Mean (SD) 28.7 (5.2) 29.7 (5.8) Placebo (N=63) DFK 2 mg BID (N=62) Duration of NP ( yrs ) – Mean (SD) 8.15 (7.4) 8.9 (10.4) Baseline WI - NRS – Mean (SD) 7.6 (1.4) 7.6 (1.4)
10 Confidential. For internal use only. Primary Endpoint: Change from Baseline in Daily WI - NRS at Week 8 (ITT) -5 -4 -3 -2 -1 0 Placebo (N = 63) DFK 2 mg BID (N = 62) *** ** *** *** ** LS Means from MMRM with terms for treatment, week, treatment by week interaction, and baseline WI - NRS score Missing data imputed using multiple imputation (MI) under missing at random (MAR) assumption Weeks Change from Baseline Baseline 1 2 3 4 5 6 7 8 ** P = .001 at Week 8 Significant improvement observed with difelikefalin vs placebo at all timepoints * P< .05; ** P< .01; *** P< .001 *** ***
11 Confidential. For internal use only. ≥ 4 - point Improvement in WI - NRS ( ITT ) 1 8 7 8 11 16 20 18 3 30 43 44 44 41 41 41 0 10 20 30 40 50 1 2 3 4 5 6 7 8 Weeks Placebo (N = 63) DFK 2 mg BID (N = 62) *** *** *** ** * ** Estimated percentages & P - values from a logistic regression with terms for treatment and baseline WI - NRS score Subjects with missing weekly WI - NRS scores for a particular week are categorized as non - responders % of Subjects Significant improvement observed with DFK vs placebo starting at Week 2 * P< .05; ** P< .01; *** P< .001 **
12 Confidential. For internal use only. Summary of Adverse Events Patients with at least one TEAE, n (%) 32 (50.6%) 35 (56.5%) Patients with at least one severe TEAE, n (%) 1 (1.6%) 0 Patients with at least one serious TEAE, n (%) 0 0 Patients with TEAE resulting in treatment discontinuation, n (%) 4 (6.3%) 12 (19.4%) Placebo (N=63) DFK 2 mg BID (N=62) Safety analyses performed in the safety population, defined as all randomized patients who received ≥1 dose of study drug bas ed on actual treatment received.
13 Confidential. For internal use only. Most Commonly Reported TEAEs Nausea 7 (11.1%) 8 (12.9%) Abdominal pain* 8 (12.7%) 7 (11.3%) Headache 3 (4.8%) 7 (11.3%) Dizziness 2 (3.2%) 7 (11.3%) Constipation 4 (6.3%) 6 (9.7%) Urine output increased # 1 (1.6%) 5 (8.1%) Treatment - emergent Adverse Events at ≥5% frequency; n (%) Safety analyses performed in the safety population, defined as all randomized patients who received ≥1 dose of study drug bas ed on actual treatment received. *includes PTs abdominal pain, abdominal pain upper, abdominal discomfort, abdominal pain lower; #includes urine output increa sed and pollakiuria Placebo (N=63) DFK 2 mg BID (N=62)
14 Confidential. For internal use only. KOMFORT Phase 2 Summary • Oral difelikefalin demonstrated strong anti - pruritic effect in patients with Notalgia Paresthetica – Primary endpoint met demonstrating statistically significant superiority of difelikefalin versus placebo in Daily WI - NRS at Week 8 – Rapid onset of action with significant improvements achieved at Week 1 and sustained through Week 8 – Significantly greater proportion of patients on difelikefalin had ≥ 4 - point improvement starting at Week 2 • Oral difelikefalin was generally well tolerated with a consistent safety profile • Next steps planned to include finalizing additional data analyses and engaging with FDA on path forward Oral difelikefalin is an investigational drug product and its safety and efficacy have not been fully evaluated by any regulatory authority. The F DA approved KORSUVA Œ ( difelikefalin ) injection for the treatment of moderate - to - severe pruritus (itching) associated with chronic kidney disease (CKD - aP ) in adults undergoing hemodialysis (HD).
Exhibit 99.3
Cara Therapeutics CORPORATE PRESENTATION JUNE 2022
Forward Looking Statements Statements contained in this presentation 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 ability to successfully commercialize KORSUVA injection and Kapruvia , planned future regulatory submissions and potential future regulatory approvals, the Company’s ability to obtain and maintain coverage and adequate reimbursement for KORSUVA injection, the performance of our commercial partners, including Vifor Pharma, 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 candidates, the potential for the Company’s product candidates to be alternatives in the therapeutic areas investigated, the size and growth of the potential markets for pruritus management, the Company’s expected cash reach, and the potential impact of COVID - 19 on the Company’s clinical development and regulatory timelines and plans. Because such statements are subject to risks and uncertainties, actual results may differ materially from those expressed or implied by such forward - looking statements. 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, 2021 and its other documents subsequently filed with or furnished to the Securities and Exchange Commission. All forward - looking statements contained in this presentation 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. 2
Transform the way pruritus is treated to bring quality to the lives of those who suffer. OUR MISSION:
Millions of US patients could benefit from a chronic pruritus therapy 4 SYSTEMIC Non - Dialysis Dependent CKD (Stage 4 - 5) 3 - 7 Chronic Liver Disease 8 - 12 Atopic Dermatitis 13 - 15 Notalgia Paresthetica 16 - 19 DERMATOLOGICAL NEUROLOGICAL HD - Dependent Chronic Kidney Disease (CKD) 1 - 2 30 0K 3 M 12 M >650K Estimated US Addressable Pruritis Population 200K 1..National Institute of Diabetes and Digestive and Kidney Diseases. https://www.niddk.nih.gov/health - information/health - statist ics/kidney - disease. 2. Pisoni et al. Pruritus in haemodialysis patients: international results from the Dialysis Outcomes and Practice Patterns Study (DOPPS). Nephrology Dialysis Transplantation (2006); 21(12): 3495 - 3505. 3. Centers for Disease Control and Prevention https://nccd.cdc.go v/ckd/detail.aspx?Qnum=Q372. 4. DataMonitor 5. States Renal Data System https://adr.usrds.org/2020/chronic - kidney - disease/1 - ckd - in - the - general - population. 6. Wong SJY et al. Decisions about Renal Replacement Therapy in Patients with Advanced Kidney Disease in the US D epa rtment of Veterans Affairs, 2000 – 2011. Clin Journal of Am Soc Neprol . 2016. 11(10): 1825 - 1833. 7. Sukul N et al. Pruritus and patient reported outcomes in non - dialysis CKD. Clin J Am Soc Neprhol 2019. 673 - 681. 8.Centers for Disease Control and Prevention https://www.cdc.gov/nchs/fastats/liver - disease.htm 9. Odea S et al. Prevalence of p ruritus in patients with chronic liver disease: A multicenter study. Hepatology Research. 2018. 28(3): E252 - E262. 10. Fujino H et al. Pruritus in patients with chronic liver disease and serum autotaxin levels in patients with primary biliary cholangitis. BMC Gastroenterology. 2019. 19:169. 11. Yoshikawa et al. Pruritus is com mo n in patients with chronic liver disease and is improved by nalfurafine hydrochloride. Scientific Reports. 2021. 11:3015. 12. Data on file. 13. National Eczema Assocaition . https://nationaleczema.org/eczema/types - of - eczema/atopic - dermatitis/ 14. DRG Analysis. 15. Mollanazar NK, Smith PK, Yosipovitch G. Mediators of chronic pruritus in atopic dermatitis: getting the itch out? Clin Rev Allergy Immunol. (2016) 51:263 – 92. 16. US Census Bureau 2020 population projection; 17. Pereira P. et al., Acta DV 2018 ; 98:82 - 88; 18. Mollanazar N.K. et al., Acta Clin Croat 2018; 57:721 - 725e.; 19. Syneos market research and Apollo claims database
Cara is well positioned to seize the opportunity and drive significant immediate and future growth 5 First - and - only FDA - approved treatment for CKD - aP in HD Robust R&D engine with multiple pipeline indications Significant market opportunity & strong financial foundation to deliver growth strategy
STRONG COMMERCIAL POSITIONING & PARTNERSHIP FIRST INNOVATIVE PRODUCT TO RECEIVE TDAPA FIRST - AND - ONLY PRODUCT APPROVED FOR CKD - aP in HD KORSUVA Injection is poised for rapid uptake 6 Korsuva is indicated for the treatment of moderate - to - severe pruritus associated with chronic kidney disease (CKD - aP ) in adults undergoing hemodialysis (HD). Limitations of Use Korsuva has not been studied in patients on peritoneal dialysis and is not recommended for use in this population
KORSUVA Injection addresses significant unmet need in US CKD - aP hemodialysis market 1. National Institute of Diabetes and Digestive and Kidney Diseases. https://www.niddk.nih.gov/health - information/health - statistics/kidney - disease. 2. URSDS. https://adr.usrds.org/2021/end - stage - renal - disease/1 - incidence - prevalence - patient - characteristics - and - treatment - modalitie s 3. Pisoni et al. Pruritus in haemodialysis patients: international results from the Dialysis Outcomes and Practice Patterns Study (DOPPS). Nephrology Dialysis Transplan ta tion (2006); 21(12): 3495 - 3505. P atients on hemodialysis 1 - 2 ~500K With moderate - severe pruritus 2 40% Addressable Market ~200K 7
Concentrated dialysis market dynamics can facilitate rapid uptake 8 1. https://healthcareappraisers.com/2020 - outlook - dialysis - clinics - and - esrd/ 2. https://adr.usrds.org/2020/end - stage - renal - disease/9 - healthcare - expenditures - for - persons - with - esrd 3. Amgen Annual Report 2018, 2019, 2020 1 Major Payer • Medicare covers ~80% of CKD - HD patients 2 • 2nd drug in TDAPA • 1st drug Parsabiv - $1.4B revenue in 3 - yr period 3 2 Key Providers • Fresenius Medical Care and DaVita have a combined market share of ~75% 1
Partnership with Vifor Pharma can maximize launch potential 9 Leading commercial nephrology organization with turnkey infrastructure, including 100+ sales FTEs Strong relationships with US nephrology offices and dialysis centers, including joi nt venture with Fresenius Medical Care Contractual economics bring near term profitability for KORSUVA Injection
KORSUVA injection U.S. launch commenced in April 2022 and is progressing well 10 KORSUVA injection is available to order at all dialysis organizations nationwide Healthcare Providers and Patients are being educated and activated Product reimbursement via TDAPA is in place
Difelikefalin MOA has potentially broad application 11 Difelikefalin blocks itch response agnostic of itch trigger NEUROLOGICAL DERMATOLOGICAL SYSTEMIC DIFELIKEFALIN PRURITUS Kappa Receptor D CKD PBC AD NP Disease - specific Pruritogens Adapted from Pflugers Arch . 2013 December ; 465(12): doi:10.1007/s00424 - 013 - 1284 - 2. Peripheral Sensory Neurons
Oral difelikefalin has potential for long - term growth 1. Matterne U. et al. Prevalence, correlates and characteristics of chronic pruritus: a population - based crosssectional study. Acta Derm Venereol . 2011;91(6):674 - 9.2. Matterne U et al. Incidence and determinants of chronic pruritus: a population - based cohort study. Acta Derm Venereol . 2013;93(5):532 - 7. 3. Adapted from: Stander S. et al. Clinical classification of itch: a position paper of the international forum for the study of itch. Acta Derm Venereol 2007. 87: 291 - 294. Systemic Systemic Systemic Endocrine & Metabolic Chronic Kidney Disease (CKD) Primary Biliary Cholangitis (PBC) Infectious diseases Hematologic & lymphoproliferative diseases Visceral neoplasms Drug - induced pruritus Inflammatory Dermatoses - Atopic dermatitis (AD) Infectious dermatoses Autoimmune dermatoses Neoplasms Notalgia Paresthetica (NP) Brachioradial pruritus Post - herpetic Neuralgia Genodermatoses Dermatoses of pregnancy Systemic Neurological x x x Key Categori es of Chronic Pruritus 1 Dermatological 12
Advancing our late - stage pipeline in multiple indications 1. Approved in the EU with the tradename Kapruvia TM . 2 . Commercialization rights to difelikefalin in defined indications - Japan: Maruishi Pharmaceutical Co, LTD; South Korea: Chong Kun Dang Pharmaceuticals. 3 . Vifor Fresenius Medical Care Renal Pharma (VFMCRP) has commercial rights under a profit - share arrangement in the US and a royalty arr angement ex - US. HD CKD - aP : Hemodialysis Chronic Kidney Disease - associated Pruritus; NDD - CKD - aP : Non - Dialysis Dependent Chronic Kidney Disease associated Pruritus; Pruritus NP: Notalgia Paresthetica associated Pruritus; Pruritus PBC: Primary biliary cholangitis associated Pruritus 13 STAGE OF DEVELOPMENT Program Indication Phase 1 Phase 2 Phase 3 Approved Commercial Rights (ex - Japan and S. Korea) 2 KORSUVA TM Injection 1 Pruritus HD - CKD VFMCRP 3 Oral difelikefalin Pruritus NDD - CKD (stages IV - V) Cara Oral difelikefalin Pruritus Atopic Dermatitis Cara Oral difelikefalin Pruritus NP Cara Oral difelikefalin Pruritus PBC Cara
Oral difelikefalin : expanding reach in non - dialysis CKD market 1. Makar M et al. Chronic kidney disease associated pruritus: a review. Kidney Blood Press Res 2021. 46:659 - 669. 2. Centers for Disease Control and Prevention https://nccd.cdc.gov/ckd/detail.aspx?Qnum=Q372. 3. DataMonitor 4. States Renal Data System https://adr.usrds.org/2020/chronic - kidney - disease/1 - ckd - in - the - general - population. 5. Wong SJY et a l. Decisions about Renal Replacement Therapy in Patients with Advanced Kidney Disease in the US Department of Veterans Affairs, 200 0 – 2011. Clin Journal of Am Soc Neprol . 2016. 11(10): 1825 - 1833. 6. Sukul N et al. Pruritus and patient reported outcomes in non - dialysis CKD. Clin J Am Soc Neprhol 2019. 673 - 681. 7. Mettang T and Kremer AE. Uremic Pruritus. Kidney International. 2015. 87:685 - 691 Pruritis control is a significant unmet need among non - dialysis CKD patients 1 There are no FDA - approved therapies and c urrent anti - pruritic approaches are inadequate 1 Approximately 1.2 million US patients have advanced (stage 4 - 5) non - dialysis CKD 2 - 5 ~30% advanced non - dialysis CKD patients experience moderate to severe pruritus 6 NDD - CKD 14
Phase 2 data provides path forward into Phase 3 NDD - CKD x Significant difference achieved between 1mg oral difelikefalin and placebo in WI - NRS score at Week 12 x Generally well - tolerated with safety profile consistent with clinical development program x Phase 2 findings and EOP2 discussion with FDA established dose and patient population in Advanced CKD for Phase 3 trial NDD - CKD Primary Endpoint Change From Baseline in WI - NRS Over Time 15
KICK 1 & KICK 2: Patient Population KICK1 US sites only, KICK 2 US and ex - US sites • Adults with advanced stage 4 and 5 CKD • Chronic Pruritus for at least 6 months prior to screening • Moderate to Severe Pruritus at Baseline (WI - NRS ≥ 5) • Allowed to be on stable treatment for itch including antihistamines and gabapentinoids STUDY PATIENT POPULATION STAGE 1 STAGE 2 STAGE 3 STAGE 4 STAGE 5 Normal Increased Risk Kidney Damage Reduced Function Oral Difelikefalin (KICK trials) Kidney failure Non Dialysis Dependent Dialysis Dependent NDD - CKD NDD - CKD 16
KICK 1 & KICK 2: Study Design 12 Weeks Efficacy Assessment Treatment Period Double Blind RUN - IN 7 Days Patients Re - Randomized to DFK or PBO RANDOMIZE (N = ~400; 1:1) SCREEN Placebo Placebo Baseline Mean WI - NRS > 5 DFK 1.0 mg once daily Up to 52 Weeks DFK 1.0 mg once daily Placebo DFK 1.0 mg once daily Placebo Long - term Safety Extension Treatment Period Double Blind • Quality of life including sleep • Safety assessments • % of subjects with ≥4 - point improvement from baseline in WI - NRS score at Week 12 PRIMARY ENDPOINT ADDITIONAL ENDPOINTS KICK1 US sites only, KICK 2 US and ex - US sites Topline Results: 2H2024 est. NDD - CKD 17
1. Correale CE et al. Atopic dermatitis: a review of diagnosis and treatment. Am Fam Physician. 1999. 60(4):1191 - 1198 2. Silverberg JI et al. Patient burden and quality of life in atopic dermatitis in US adults. Annals of Allergy, Asthma, and Immunology (2018). 121(3): 340 - 347 3. Legat FJ. Itch in atopic dermatitis – what is new? Front Med (Lausanne) 2021. 8:644760. 4. National Eczema Assocaition . https://nationaleczema.org/eczema/types - of - eczema/atopic - dermatitis/ 5. DRG Analysis. 6. Mollanazar NK, Smith PK, Yosipovitch G. Mediators of chronic pruritus in atopic dermatitis: getting the itch out? Clin Rev Allergy Immunol. (2016) 51:263 – 92. 7. Lipman et al. Current clinical options for the management of itch in atopic dermatitis. Clin Cosmet Investig Dermatol. 2021. 14:959 - 969 8. Kapur S et al. Atopic dermatitis. Allergy Asthma and Clin Immunol. 2018. 14(Suppl2):52. Oral difelikefalin: potential to address significant need for an oral antipruritic in atopic dermatitis (AD) 18 Pruritus is a hallmark of AD, often called “the itch that rashes” 1 Itch is considered the most burdensome AD symptom by patients, 2 strongly and negatively impacts quality of life 3 ~12M diagnosed patients that experience chronic pruritus 4 - 6 Targeting pruritus in AD remains unmet need AD
KARE STUDY: Phase 2 data in Atopic Dermatitis (AD) 19 x A nti - pruritic effect started at week 1 and was sustained through week 12 x Statistical significance achieved for the registration endpoint (4 - point responder) in mild - to - moderate AD population x The drug was generally well tolerated 0% 10% 20% 30% 40% % of Subjects 19% 32%* N = 79 N = 178 • All doses performed similarly (.25mg, .50 mg , 1.0mg) versus PBO Population: Mild to Moderate AD ( BSA <10) 4 - point Responder Analysis at Week 12 AD Placebo Difelikefalin P=0.033
KIND 1 & KIND 2: Patient Population • Adults with AD - related pruritus not adequately controlled by topical therapy alone • Chronic AD - related Pruritus ≥6 weeks • Moderate to Severe Pruritus at Baseline (I - NRS ≥ 5) • Mild to severe Atopic Dermatitis: • IGA ≥ 2, BSA ≤20% • Patients need to be washed out of any medication that may impact itch and/or AD prior to screening • Stratification to BSA <10% and ≥10% STUDY PATIENT POPULATION Target Enrollment 1 5% Patient Population BSA ≥10% 8 5% Patient Population BSA <10% AD 20
KIND 1 Part A: Study Design 12 - Week Double Blind Treatment Period 1 - week Run - in Oral PBO BID + Vehicle PBO DFK 0.25 mg BID + TCS Baseline Mean I - NRS > 5 DFK 0.5 mg BID + TCS Oral PBO BID + TCS DFK 0.5 mg BID + TCS 52 - Week Open Label Safety Extension Period N=280 (~70/arm) KIND 1 Part A will include sites in North America only Internal Readout: 2H2023 est. CRITERIA • % of subjects with ≥4 - point improvement from baseline in WI - NRS score at Week 12 • Safety assessments INFORMATION • Dose • Sample size AD 21
KIND 1 Part B & KIND 2: Study Design KIND 1 Part B will include sites in North America only, while KIND 2 will include sites in North America and outside of Nor th America KIND 1 Part A DFK XX mg BID TCS Baseline Mean I - NRS > 5 Oral PBO BID + TCS DFK XX mg BID + TCS Up to 52 - Week Open Label Safety Extension Period 12 - Week Double Blind Treatment Period 1 - week Run - In READOUT Informs dosing & sample size • Quality of life including sleep • Skin assessment • Safety assessments • % of subjects with ≥4 - point improvement from baseline in WI - NRS score at Week 12 PRIMARY ENDPOINT ADDITIONAL ENDPOINTS Topline Results: 1H2025 est. AD 22
Oral difelikefalin: potential to address significant need in Notalgia Paresthetica (NP) 23 1. Howard M et al. Notalgia paresthetica: a review for dermatologists. Int J of Derm . 2017. 388 - 392. 2. US Census Bureau 2020 population projection; 3. Pereira P. et al., Acta DV 2018 ; 98:82 - 88; 4. Mollanazar N.K. et al., Acta Clin Croat 2018 ; 57:721 - 725 ; 5. Syneos Health qualitative primary research of US dermatologists, Feb 2022; 5. Syneos market research and Apollo claims database NP NP is a sensory neuropathic syndrome characterized by chronic pruritus 3 Pruritus is burdensome and impairs quality of life 1 Estimated >650K patients currently treated for NP 2 - 5 No FDA - approved treatments; off label treatments are either ineffective or have tolerability issues 1
24 Promising Phase 2 Data in First Well Controlled NP Study LS Means from MMRM with terms for treatment, week, treatment by week interaction, and baseline WI - NRS score Missing data imputed using multiple imputation (MI) under missing at random (MAR) assumption NP x Significant difference achieved between 2 mg BID oral difelikefalin and placebo in WI - NRS score at Week 8 x Rapid onset of action within Week 1 and sustained response through Week 8 x Significantly greater proportion of patients on difelikefalin with ≥ 4 - point improvement starting Week 2 x Generally well - tolerated with safety profile consistent with other clinical development programs Primary Endpoint Change From Baseline in WI - NRS at Week 8
Oral difelikefalin : potential in pruritus with Primary Biliary Cholangitis (PBC) 25 PBC 1. Carrion AF et al. Understanding and treating pruritus in primary biliary cholangitis. Clin Liver Dis 2018. 22:517 - 532. 2. Pin heiro NC et al. Refractory pruritus in primary biliary cirrhosis. BMJ Case Rep. 2013. doi:10.1136/bcr - 2013 - 200634 3. Lu M et al. Factors Associated with Prevalence and Treatment of Primary Biliary Cholangitis in United States Health Systems. Cli n Gastroenterol Hepatol (2018 Aug);16(8):1333 - 1341.e6. 4. Trivedi HD et al. Management of Pruritus in Primary Biliary Cholangitis: A Narrative Review. The Ame rican Journal of Medicine (2017) 130, 744e1 - 744e7 Pruritus is hallmark symptom of PBC and may be persistent and debilitating 1 Associated with severe fatigue, sleep disturbance, and mental health issues 2 No FDA - approved treatments Phase 2 Readout Anticipated 2H 2022 Addressable patient population of ~50K 3 - 4 , with opportunity to establish efficacy in other chronic liver diseases
Strong financial foundation to advance pipeline, enable long - term growth 26 Continued pipeline growth • We have the resources to continue development of the oral difelikefalin program $210M cash position Mar 31, 2022 • 54M shares outstanding and no debt • We do not expect to incur commercial costs related to KORSUVA Injection Cash runway into 1 st h al f 2024 • Runway does not include potential near term revenue from KORSUVA Injection profit split or commercial milestones • Contractual economics expected to bring near term profitability on KORSUVA I njection
x Kapruvia Injection approved in EU x Positive NP Phase 2 Topline Data 2022 Value C atalysts to D rive Long - term G rowth* 27 Q3 Q4 • PBC Phase 2 Topline Data (2H) x Initiation of Phase 3 in AD x Initiation of Phase 3 in NDD - CKD x KORSUVA Injection • TDAPA received • J - Code secured • Pricing announced KORSUVA Injection US Commercialization Launch April 2022 Q1 Q2 * Anticipated Timelines
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