Cara Therapeutics Reports Fourth Quarter and Full Year 2021 Financial Results KORSUVA (difelikefalin) injection U.S. commercial launch on track for April 2022 with extensive pre-launch activities completed Initiation of

Reports Fourth Quarter and Full Year 2021 Financial Results

KORSUVA (difelikefalin) injection U.S.

commercial launch on track for April 2022 with extensive pre-launch activities completed

Initiation of Oral KORSUVA (difelikefalin) Phase

3 pruritus programs in non-dialysis dependent advanced chronic kidney disease and atopic dermatitis expected in 1Q 2022

Phase 3 programs to be highlighted in virtual

R&D event on March 11, 2022 at 1:00 pm ET

Conference call today at 4:30 p.m. ET

STAMFORD, Conn., Mar. 1, 2022 - Cara

Therapeutics, Inc. (Nasdaq: CARA), an early commercial-stage biopharmaceutical company leading a new treatment paradigm to improve

the lives of patients suffering from pruritus, today announced financial results and operational highlights for the fourth quarter and

full year ended December 31, 2021.

"Cara Therapeutics made excellent progress

in 2021 executing on our strategic priorities, underscored by our first FDA approval -- KORSUVA (difelikefalin) injection, the

first and only therapy approved for the treatment of pruritus associated with chronic kidney disease in adults undergoing hemodialysis,"

said Christopher Posner, President and Chief Executive Officer of Cara Therapeutics. "We have been collaborating with our partner

Vifor Pharma to optimize the U.S. commercial launch, which is on track for April 2022. To that end, Vifor has been conducting an

extensive array of pre-launch activities and we have a clear path to reimbursement."

Mr. Posner continued, "Our Oral KORSUVA

(difelikefalin) platform continues to advance in multiple pruritus indications. We are initiating Phase 3 programs in the first quarter

of this year for Oral KORSUVA (difelikefalin) in pruritus associated with advanced chronic kidney disease and atopic dermatitis. We look

forward to discussing these trials during our virtual R&D event on March 11. In addition, we continue to progress our two Phase

2 proof-of-concept studies for the treatment of pruritus associated with notalgia paresthetica and primary biliary cholangitis, for which

we expect to have top-line data in the second quarter and second half of 2022, respectively. With the planned imminent U.S. launch of

KORSUVA injection, an Oral KORSUVA (difelikefalin) pipeline with significant market opportunity and a firm financial foundation, we believe

we are poised to make substantial progress in 2022 that will position us for long-term growth as we strive to become a category-defining

leader in the treatment of chronic pruritus."

Fourth Quarter and Recent Developments:

Leadership Appointment

In November 2021, the Company appointed board

member Christopher Posner as President and Chief Executive Officer. Mr. Posner has more than 23 years of global pharmaceutical management,

sales and product launch experience. He joined the Company from LEO Pharma, Inc., the U.S. affiliate of LEO Pharma A/S, a global

leader in medical dermatology, where he served as President and Chief Executive Officer.

KORSUVA Injection: Chronic Kidney Disease-Associated

Pruritus: Hemodialysis

Following the August 2021 FDA approval of

KORSUVA (difelikefalin) injection for the treatment of moderate-to-severe pruritus associated with chronic kidney disease (CKD)

in adults undergoing hemodialysis, the Company has been collaborating with its commercial partner, Vifor Pharma, to prepare for the U.S.

commercial launch in April 2022. Vifor's field force of roughly 100 representatives has been trained on the package insert,

conducting disease state education for pruritus in CKD, and focused on patient identification with key prescribers and dialysis organizations.

Sufficient launch quantities of KORSUVA injection are manufactured and ready to be shipped from the distribution center to wholesalers.

In December 2021, the U.S. Centers for Medicare &

Medicaid Services (CMS) granted Transitional Drug Add-On Payment Adjustment (TDAPA) to KORSUVA injection in the anti-pruritic functional

category. TDAPA will apply to KORSUVA injection beginning April 1, 2022, for two years. TDAPA enables payment for new injectable

end-stage renal disease (ESRD)-related therapies to be reimbursed outside of the ESRD Prospective Payment System (PPS) bundle.

In February 2022, the European Medicines

Agency's (EMA) Committee for Medicinal Products for Human Use (CHMP) recommended approval of Kapruvia (difelikefalin)

for the treatment of moderate-to-severe pruritus associated with CKD in hemodialysis patients. The CHMP opinion is the basis for the European

Commission's final decision regarding marketing authorization for Kapruvia . The European Commission decision for

EU Marketing Authorization is expected in the second quarter of 2022.

In January 2022, the Company's licensing

partner Maruishi Pharmaceutical Co., Ltd., and its sublicensee Kissei Pharmaceutical Co., Ltd., announced the primary and secondary

endpoints were achieved in a Japanese Phase 3 clinical trial (double-blind, placebo-controlled period) of difelikefalin injection for

the treatment of pruritus in hemodialysis patients. Difelikefalin was generally well-tolerated in the trial.

Oral KORSUVA (difelikefalin): Pruritus Associated

with Non-Dialysis Dependent Advanced Chronic Kidney Disease

In April 2021, the Company held an End-of-Phase

2 Meeting with the FDA to discuss the results of the Phase 2 clinical trial of Oral KORSUVA (difelikefalin) in non-dialysis dependent

chronic kidney disease-associated pruritus and the potential Phase 3 program. Based on meeting guidance, the FDA indicated the acceptability

of Stage 5 pre-dialysis CKD patients as a viable patient population for a Phase 3 trial.

In November 2021, the FDA provided the Company

with written guidance indicating the patient population can be expanded to include the group of Stage 4 pre-dialysis patients with advanced

CKD in a Phase 3 program consisting of two Phase 3 clinical trials. The Company expects to initiate this Phase 3 program in the first

quarter of 2022. The Phase 3 program will be discussed during the virtual R&D event on March 11, 2022.

Oral KORSUVA (difelikefalin): Atopic Dermatitis

In October 2021, the Company announced the

results from the KARE Phase 2 clinical trial of Oral KORSUVA (difelikefalin) for the treatment of moderate-to-severe pruritus in mild-to-severe

atopic dermatitis (AD) patients. The results were presented as a late-breaking presentation at the 2021 European Academy of Dermatology

and Venereology (EADV) Virtual Congress by Brian Kim, MD, Associate Professor of Dermatology and Co-Director of the Center for the Study

of Itch and Sensory Disorders at Washington University School of Medicine.

The Company expects to initiate a Phase 3 clinical

program of Oral KORSUVA (difelikefalin) in AD patients in the first quarter of 2022. The Phase 3 program will be discussed during the

virtual R&D event on March 11, 2022.

Oral KORSUVA (difelikefalin): Chronic Liver

Disease-Associated Pruritus: Primary Biliary Cholangitis

The Company is currently conducting a Phase 2

clinical trial of Oral KORSUVA (difelikefalin) for the treatment of pruritus in patients with hepatic impairment due to primary biliary

cholangitis (PBC). The trial is evaluating the safety and efficacy of Oral KORSUVA (difelikefalin) (1.0 mg tablet, twice daily) versus

placebo for 16 weeks. The Company continues to screen patients in this ongoing Phase 2 trial and, primarily due to the ongoing effects

of the COVID-19 pandemic on patient enrollment, now expects to report top-line data in the second half of 2022.

Oral KORSUVA (difelikefalin): Notalgia Paresthetica

The Company is evaluating the efficacy and safety

of Oral KORSUVA (difelikefalin) for moderate-to-severe pruritus in approximately 120 subjects with notalgia paresthetica (NP) in a Phase

2 multicenter, randomized, double-blind, placebo-controlled 8-week trial. Subjects are randomized to receive Oral KORSUVA (difelikefalin)

2.0 mg twice daily versus placebo for 8 weeks, followed by a 4-week active extension period. The primary efficacy endpoint is the change

from baseline in the weekly mean of the daily 24-hour WI-NRS score at week 8 of the treatment period. Secondary endpoints include change

from baseline in itch-related quality of life scores and a change from baseline in itch-related sleep disturbance subscale at the end

The Company expects to report top-line data from

this trial in the second quarter of 2022.

COVID-19 Impacts and Business Operations

Due to the ongoing COVID-19 pandemic and in accordance

with the FDA's updated guidance for conducting clinical trials, the Company has implemented numerous clinical and operational measures

to prioritize the health and safety of patients, employees and study investigators and minimize potential disruptions to its ongoing clinical

trials. The Company is working closely with its clinical and commercial manufacturing partners to continue to ensure sufficient supply

of KORSUVA is available for the commercial launch of KORSUVA injection and its ongoing and planned clinical trials.

Expected 2022 Milestones:

Upcoming Meeting Activities:

The Company expects to make presentations at the

following upcoming conferences:

As previously announced, the Company will be hosting