Cara Therapeutics Reports First Quarter 2021 Financial Results - U.S. Food and Drug Administration (FDA) Accepts New Drug Application (NDA) Filing and Grants Priority Review for KORSUVA Injection in CKD-aP - - Conference

Reports First Quarter 2021 Financial Results

- U.S. Food and Drug Administration (FDA)

Accepts New Drug Application (NDA) Filing and Grants Priority Review for KORSUVA Injection in CKD-aP -

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

STAMFORD, Conn., May 10, 2021 - Cara

Therapeutics, Inc. (Nasdaq: CARA), a biopharmaceutical company focused on developing and commercializing new chemical entities designed

to alleviate pruritus by selectively targeting peripheral kappa opioid receptors (KORs), today announced financial results and operational

highlights for the first quarter ended March 31, 2021.

"During the first quarter of the year, we

were very pleased with the FDA acceptance, with Priority Review, of our first NDA filing for our lead product candidate, KORSUVA

Injection, for the treatment of moderate-to-severe pruritus in hemodialysis patients. With an expected Prescription Drug User Fee Act

(PDUFA) target action date of August 23, 2021, we remain focused, along with our commercial partner, Vifor Pharma, on preparation

for the U.S. launch of KORSUVA Injection in the second half of 2021, if approved," said Derek Chalmers, Ph.D., D.Sc., President

and Chief Executive Officer of Cara Therapeutics. "In addition, we continue to progress our Oral KORSUVA programs across a number

of late-stage trials in patient populations where effective treatment of pruritus remains a significant unmet need. Having now generated

Phase 2 data in pre-dialysis CKD patients and, more recently in mild-to-moderate atopic dermatitis patients in our KARE Phase 2 trial,

we hope to initiate Phase 3 programs in both clinical indications by year-end."

First Quarter and Recent Developments:

KORSUVA Injection: Chronic Kidney Disease-Associated

Pruritus (CKD-aP): Hemodialysis

In February 2021, the FDA accepted the filing

of the NDA for KORSUVA Injection for the treatment of moderate-to-severe pruritus in hemodialysis patients. Shortly after this decision,

the FDA granted Priority Review for the NDA filing of KORSUVA Injection in March 2021 with an expected PDUFA target action date of

August 23, 2021. Following these decisions, the potential approval and U.S. commercial launch of KORSUVA Injection could take place

in the second half of 2021. If approved, KORSUVA Injection would be the first treatment for CKD-aP in hemodialysis patients.

In October 2020, the Company entered

into a license agreement with Vifor (International) Ltd. (Vifor) under which it granted Vifor an exclusive license to commercialize KORSUVA

Injection for the treatment of pruritus in hemodialysis patients in the United States under a Cara 60%, Vifor 40% profit-sharing

arrangement. Under the terms of the agreement, upon U.S. regulatory approval of KORSUVA Injection, the Company will be eligible

to receive a $50.0 million common stock investment at a 20% premium to the 30-day trailing average price of the Company's

common stock as of such date. In addition, the Company is eligible to receive payments of up to $240.0 million upon the achievement

of certain sales-based milestones.

In March 2021, the Company and Vifor Fresenius

Medical Care Renal Pharma Ltd. (VFMCRP) announced that the European Medicines Agency (EMA) accepted to review the Marketing Authorization

Application (MAA) for difelikefalin injection for the treatment of pruritus associated with chronic kidney disease in hemodialysis patients.

The EMA will review the application under the centralized marketing authorization procedure. If approved, difelikefalin would receive

marketing authorization in all member states of the European Union (EU), as well as in Iceland, Liechtenstein, and Norway. The EMA is

expected to render a decision on the EU MAA in the second quarter of 2022.

Oral KORSUVA: Non-Dialysis Dependent (NDD)

In April 2021, the Company held an End of

Phase 2 Meeting with the FDA to discuss the results of the Phase 2 trial of Oral KORSUVA in NDD CKD-aP and the potential Phase 3 program.

The FDA indicated the acceptability of Stage 5 pre-dialysis CKD patients as a viable patient population for a Phase 3 trial. The FDA also

indicated the potential to use data from Cara's previous trials of KORSUVA Injection in dialysis patients to support an approval

based on a single Phase 3 clinical trial of Oral KORSUVA in the Stage 5 pre-dialysis population. The Company currently plans to initiate

its Phase 3 program by year-end 2021. The Company also intends to continue discussions with the FDA on the potential inclusion of earlier

stage CKD patients in the Phase 3 program.

Oral KORSUVA: Atopic Dermatitis (AD)

In April 2021, the Company announced top-line

results from its Phase 2 KARE dose-ranging clinical trial of Oral KORSUVA for the treatment of moderate-to-severe pruritus in mild-to-severe

atopic dermatitis patients. The study did not meet its primary endpoint of Worst Itch - Numeric Rating Scale (WI-NRS) change from

baseline at week 12 or secondary endpoint of 4-point responder analysis in the intent to treat (ITT) patient population. However, in a

pre-specified analysis of mild-to-moderate (BSA <10%) AD patients (64% of ITT patient population), the study met its primary endpoint

of WI-NRS change and secondary endpoint of 4-point responder analysis in this patient population. Additionally, a statistically significant

improvement was demonstrated in the 4-point responder analysis, which we expect will be the Phase 3 registrational endpoint, in mild-to-moderate

AD patients, with 32% of KORSUVA-treated patients achieving a greater than 4-point reduction vs. 19% in placebo group (p=0.03). Oral KORSUVA

was generally well-tolerated across all doses.

The Company intends to request an End of Phase

2 Meeting with the FDA to be held in the second half of 2021 and, subject to discussions with the FDA, aims to initiate a Phase 3 program

by the end of the year.

Oral KORSUVA: Chronic Liver Disease-Associated

Pruritus (CLD-aP): Primary Biliary Cholangitis (PBC)

The Company is currently conducting a Phase 2

trial of Oral KORSUVA for the treatment of pruritus in patients with hepatic impairment due to PBC. The trial is evaluating the safety

and efficacy of Oral KORSUVA (1.0 mg tablet, twice daily) versus placebo for 16 weeks. The Company continues to screen patients in this

ongoing Phase 2 trial and aims to have top-line data in the second half of 2021.

Oral KORSUVA: Notalgia Paresthetica (NP)

In January 2021, the Company initiated a

Phase 2 trial of Oral KORSUVA for the treatment of moderate-to-severe pruritus in patients suffering from NP, a nerve disorder characterized

by chronic pruritus of the upper back. The Company is actively enrolling patients in this trial.

The Phase 2 multicenter, randomized, double-blind,

placebo-controlled 8-week study is designed to evaluate the efficacy and safety of Oral KORSUVA for moderate-to-severe pruritus in approximately

120 subjects with NP. Subjects will be randomized to receive Oral KORSUVA 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 of week 8.

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

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

of KORSUVA is available for its ongoing and planned clinical trials.

Based on guidelines from the Centers for

Disease Control and Prevention and the State of Connecticut, all Cara employees continue to work remotely, and business travel

has been restricted.

Upcoming Meeting Activities

The Company expects to make presentations at the

following upcoming conferences:

First Quarter 2021 Financial Results

Cash, cash equivalents and marketable securities

at March 31, 2021 totaled $228.3 million compared to $251.5 million at December 31, 2020. The decrease in the balance primarily

resulted from cash used in operating activities of $23.7 million, partially offset by proceeds of $0.7 million from the exercise of stock

For the three months ended March 31, 2021,

net loss was $23.3 million, or $0.47 per basic and diluted share, compared to a net loss of $28.9 million, or $0.62 per basic and diluted

share, for the same period in 2020.

Revenues: Total revenue was $1.9 million

for the three months ended March 31, 2021, compared to $8.1 million during the same period of 2020. Total revenue primarily consisted

of $1.9 million of license and milestone fees, and collaborative revenue during the three months ended March 31, 2021, which related

to the milestone payment the Company earned from Maruishi Pharmaceutical Co. Ltd.'s (Maruishi) first initiation of a Phase 3 trial

for uremic pruritus in Japan under the agreement with Maruishi. The Company recognized $8.0 million of license and milestone fees revenue

during the three months ended March 31, 2020, which related to the license fees earned in connection with the agreement with VFMCRP.