News Release

Prometheus Biosciences Commences Dosing in Multiple Ascending Dose (MAD) Portion of Ongoing Phase 1a Clinical Study of PRA023

March 3, 2021

- PRA023 is a TL1A antibody targeting both inflammation and fibrosis in patients with ulcerative colitis and Crohn's disease -

- PRA023 is being developed to be used in combination with a companion diagnostic to identify responders in novel precision medicine approach -

SAN DIEGO, March 3, 2021 /PRNewswire/ -- Prometheus Biosciences, Inc. ("Prometheus"), a biotechnology company pioneering a precision medicine approach for the discovery, development, and commercialization of novel therapeutic and companion diagnostic products for the treatment of inflammatory bowel disease (IBD), today announced that dosing has commenced in the multiple ascending dose (MAD) portion of the ongoing Phase 1a clinical trial of PRA023 in normal healthy volunteers. PRA023, the company's lead product candidate, is a humanized IgG1 monoclonal antibody (mAb) that has been shown to block tumor necrosis factor (TNF)-like ligand 1A (TL1A). PRA023 is being developed for the treatment of the two most common forms of IBD, ulcerative colitis (UC) and Crohn's disease (CD).

In December 2020, Prometheus commenced dosing in the single ascending dose (SAD) portion of the Phase 1a trial in normal healthy volunteers, following authorization of the company's Investigational New Drug Application (IND) by the United States Food and Drug Administration (FDA).

"We are excited to continue progressing our anti-TL1A therapy, PRA023, through both the SAD and MAD portions of our Phase 1a trial as a targeted treatment for patients suffering from ulcerative colitis and Crohn's disease, " said Allison Luo, MD, Chief Medical Officer of Prometheus. "We have now dosed three cohorts of the SAD portion of the study and PRA023 has been well-tolerated to date. Assuming favorable safety results in this trial, we expect to commence a Phase 2 trial of PRA023 in moderate-to-severe UC and a Phase 1b trial in moderate-to-severe CD later this year."

The ongoing Phase 1a clinical trial for PRA023 is a single center, double-blind, placebo-controlled trial to determine the safety, tolerability, pharmacokinetics, and pharmacodynamics of PRA023 in normal healthy volunteers.

About PRA023, an Anti-TL1A mAb

PRA023 is an IgG1 humanized mAb that has been shown to block TL1A. Third-party antibody programs against TL1A have been shown to reduce both intestinal inflammation and fibrosis in preclinical studies, and this target has been clinically-validated in a third-party Phase 2a clinical trial in UC. PRA023 binds both soluble and membrane-associated human TL1A with high affinity and specificity and has the potential to substantially improve outcomes for moderate-to-severe IBD patients predisposed to increased TL1A. Prometheus is developing PRA023 for the two most common forms of IBD, ulcerative colitis (UC) and Crohn's disease (CD).

About Inflammatory Bowel Disease (IBD)

IBD is a complex disease with many contributing factors, including genetic, environmental and immunologic, and is estimated to affect over 2,000,000 people in the United States and over 5,000,000 people globally. UC and CD are two of the most common forms of IBD. Both UC and CD are chronic, relapsing, remitting, inflammatory conditions of the GI tract that begin most commonly during adolescence and young adulthood. UC involves the innermost lining of the large intestine, and symptoms include abdominal pain and diarrhea, frequently with blood and mucus. CD can affect the entire thickness of the bowel wall and all parts of the GI tract from mouth to anus. CD symptoms include abdominal pain, diarrhea, and other more systemic symptoms such as weight loss, nutritional deficiencies, and fever.

The current standard of care for the treatment of patients with moderate-to-severe IBD is typically anti-inflammatory agents; however, none of these therapies address fibrosis, or scarring, in IBD. Since the approval of the first anti-TNF agent for the treatment of CD in 1998, the availability of JAK inhibitors and newer biological agents, including anti-integrin and anti-IL12/23, has improved the care of moderate-to-severe IBD (JAK inhibitors in UC only). However, these subsequently approved therapies have generally failed to demonstrate a clinical remission effect size of more than 15% relative to placebo. Moreover, among those patients who do respond to therapy, up to 45% will lose response over time. Current therapies used for the treatment of UC and CD apply a one-size-fits-all approach without regard to biologic variations amongst patients, and substantial unmet need remains.

About Prometheus Biosciences, Inc.

Prometheus Biosciences, Inc. is a privately held biotechnology company pioneering a precision medicine approach for the discovery, development, and commercialization of novel therapeutic and companion diagnostic products for the treatment and diagnosis of IBD. The company's precision medicine platform, Prometheus360, combines proprietary bioinformatics discovery methods with one of the world's largest gastrointestinal bioinformatics databases to identify novel therapeutic targets and develop therapeutic candidates to engage those targets. Prometheus is guided by its board of directors, led by Chairman Tachi Yamada, M.D., and a scientific advisory board composed of key opinion leaders in IBD, including Stephan Targan, M.D., William Sandborn, M.D. and Dermot P. McGovern, M.D., Ph.D. Prometheus recently completed a $130 million equity financing led by Eventide Asset Management and RTW Investments, with participation from new investors including Perceptive Advisors, Cowen Healthcare Investments, Cormorant Capital, Point72 Asset Management and Irving Investors.

Prometheus is headquartered in San Diego, CA.