Prometheus Biosciences Reports Positive Topline Phase 1 Data on Lead Therapeutic Candidate PRA023; Expands Indications to Include Systemic Sclerosis-Associated Interstitial Lung Disease (SSc-ILD)

Phase 1 trial achieved primary objective of safety and tolerability and demonstrated favorable outcomes on other key endpoints, including target engagement and immunogenicity

Discussion of Phase 1 results and rationale around SSc-ILD as new PRA023 indication to be presented in conference call scheduled today at 8:00 AM EST

SAN DIEGO, Dec. 07, 2021 (GLOBE NEWSWIRE) -- Prometheus Biosciences, Inc. (NASDAQ:RXDX), a clinical-stage biotechnology company pioneering a precision medicine approach for the discovery, development and commercialization of novel therapeutic and companion diagnostic products for the treatment of immune-mediated diseases, today reported positive topline results from its Phase 1 trial of PRA023 in healthy volunteers. It also announced that it is broadening its pipeline by adding a third indication for PRA023, Systemic Sclerosis-associated Interstitial Lung Disease (SSc-ILD), with the initiation of a Phase 2 clinical trial anticipated for the first quarter of 2022.

"Our design objective for PRA023 was to develop a competitive anti-TL1A antibody," said Mark McKenna, CEO and Chairman of Prometheus Biosciences. "Our Phase 1 data suggest that we have exceeded that objective, and we strongly believe that PRA023 has the potential to be a best-in-class TL1A inhibitor to address immune-mediated diseases."

The Phase 1 trial was a double-blind, placebo-controlled study which enrolled 69 healthy volunteers with 6 cohorts of subjects in the single ascending dose (SAD) phase and 3 cohorts of subjects in the multiple ascending dose (MAD) phase. The primary outcome measure was safety and tolerability over 14 weeks in the SAD and 18 weeks in the MAD. PRA023 was well-tolerated, with no safety signal identified during the study. There were no infusion reactions nor drug-related extension in infusion time, at doses of up to 1000 mg delivered intravenously over 30 minutes.

One of the secondary outcomes for the trial was the rate of immunogenicity associated with PRA023 after single and multiple doses, measured up to 14 and 18 weeks. Data demonstrated that < 20% of participants who received clinically relevant doses of PRA023 (1,000 mg for SAD cohort and 200 mg to 500 mg for MAD cohort) developed anti-drug antibodies (ADAs) through the prolonged follow up period. Immunogenicity had no apparent impact on safety outcomes, pharmacokinetics parameters, and pharmacodynamic (PD) parameter.

Importantly, PD analyses demonstrated robust target engagement. Prometheus designed PRA023 to bind to both the active trimeric form and the inactive monomeric form of TL1A to improve target coverage. The Phase 1 PD data demonstrated that target engagement by PRA023 was >4-fold higher, based on circulating levels of TL1A-PRA023 complexes, than would otherwise be expected if PRA023 only bound to trimeric TL1A. This suggests that PRA023 may provide improved TL1A neutralization and prevent active TL1A trimer formation from the available monomeric TL1A pool.

Additionally, Prometheus has achieved an industry-leading subcutaneous formulation of 200 mg/ml, a significant achievement that would support the use of auto-injectors for future registrational studies.

"PRA023's ability to potently bind and neutralize both the active and inactive forms of TL1A may lead to highly effective inhibition of TL1A." said Allison Luo, M.D., Chief Medical Officer of Prometheus. "We continue to enroll patients in our Phase 2a open-label study in Crohn's disease and our Phase 2 placebo-controlled study in ulcerative colitis, both of which are expected to read out topline data in the fourth quarter 2022."

"We believe that the design of PRA023, with its pleiotropic mechanism of action, including direct anti-fibrotic activity, has the potential to address unmet needs across a number of immune-mediated diseases," said Olivier Laurent, Chief Technology Officer and Head of R&D of Prometheus. "This Phase 1 data, which showed PRA023 was well-tolerated with robust target engagement, gives us confidence to pursue this potentially disease-modifying therapeutic candidate in other immune-mediated disorders by first expanding PRA023's development program to include SSc-ILD."

Systemic Sclerosis (SSc) is a rare autoimmune disorder characterized by progressive fibrosis of the skin and internal organs thought to result from inflammation and chronic immune activation. Lung involvement (SSc-ILD) is the leading cause of morbidity and mortality for individuals with the disorder. SSc-ILD is largely irreversible and therapeutic strategies have focused on slowing progression of the disorder.

"PRA023's therapeutic target, TL1A, has been shown to mediate both inflammation and – critical to our interest in SSc-ILD – fibrosis," added James R. Seibold, M.D., Clinical Lead of Prometheus' SSc-ILD program and a globally recognized key opinion leader in scleroderma. "In the last several years, numerous papers have been published linking TL1A to pulmonary fibrosis. Therefore, we believe that PRA023 offers significant promises for the treatment of this devastating disorder. Importantly, currently available therapeutics have had mixed results in clinical trials and do not appear to have robust impact on patient quality of life."

Prometheus plans to initiate the placebo-controlled ATHENA-SSc Phase 2 trial of PRA023 in SSc-ILD, with enrollment of approximately 100 patients who will be randomized 1:1 to either the active or placebo arm. The primary endpoint of the trial will be the change in forced vital capacity (FVC) at 50 weeks. Secondary endpoints will be change in quantitative interstitial lung disease by centrally-read high-resolution computed tomography (HRCT) and improvement in the American College of Rheumatology Combined Response Index in Diffuse SSc (ACR-CRISS) score. Prometheus has received clearance from the US FDA for the new Investigational New Drug Application in SSc-ILD and plans to initiate the ATHENA-SSc-ILD Phase 2 clinical trial in first quarter of 2022.

Conference Call and Webcast Information

Prometheus management will host a video webcast today at 8am EST to discuss today's news. The live webcast and archived replay may be accessed by here or by visiting the Events section of the Prometheus Biosciences website.

To participate in the Q&A session, please use the following dial-in information:

US and Canada Toll-Free Dial-In Number: (800) 903-6771

International Dial-In Number: (210) 874-7384

Conference ID: 9753616

About PRA023

PRA023 is an IgG1 humanized monoclonal antibody (mAb) that has been shown to block tumor necrosis factor (TNF)-like ligand 1A (TL1A). 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 expression. Prometheus is developing PRA023 for the treatment of immune-mediated diseases including Ulcerative colitis (UC), Crohn's disease (CD), and the newly identified systemic sclerosis-associated interstitial lung disease (SSc-ILD). The Company is currently conducting a Phase 2 trial in UC patients and a Phase 2a trial in CD patients, each utilizing a genetic-based companion diagnostic designed to identify patients who are predisposed to increased expression of TL1A and therefore potentially more likely to respond to PRA023. The company also plans to initiate a Phase 2 clinical trial for PRA023 in SSc-ILD in the first quarter of 2022.

About Prometheus Biosciences

Prometheus Biosciences, Inc. is a clinical-stage biotechnology company pioneering a precision medicine approach for the discovery, development, and commercialization of novel therapeutic and companion diagnostic products for the treatment of immune-mediated diseases, starting first with inflammatory bowel disease (IBD). The Company's precision medicine platform, Prometheus360™, combines proprietary machine learning-based analytical approaches with one of the world's largest gastrointestinal bioinformatics databases to identify novel therapeutic targets and develop therapeutic candidates to engage those targets.

Forward Looking Statements

Prometheus cautions readers that statements contained in this press release regarding matters that are not historical facts are forward-looking statements. These statements are based on the company's current beliefs and expectations. Such forward-looking statements include, but are not limited to statements regarding: the timing of initiation and design of Prometheus' Phase 2 clinical trial in SSc-ILD; the timing of topline data readout for the Phase 2 clinical trial in UC and its Phase 2a clinical trial in CD; and the potential therapeutic benefits of PRA023 and its ability to address a number of immune-mediated diseases. The inclusion of forward-looking statements should not be regarded as a representation by Prometheus that any of our plans will be achieved. Actual results may differ from those set forth in this press release due to the risks and uncertainties inherent in our business, including, without limitation: Prometheus' approach to the discovery and development of precision medicines based on Prometheus360™ is unproven; potential delays in the commencement, enrollment and completion of clinical trials and preclinical studies; Prometheus' dependence on third parties in connection with product manufacturing, research and preclinical and clinical testing; Prometheus' ability to develop companion diagnostics for our therapeutic product candidates; unexpected adverse side effects or inadequate efficacy of our product candidates that may limit their development, regulatory approval and/or commercialization, or may result in recalls or product liability claims; the results of preclinical studies and early clinical trials are not necessarily predictive of future results;; regulatory developments in the United States and foreign countries; Prometheus' ability to obtain and maintain intellectual property protection for our product candidates and maintain our rights under intellectual property licenses; Prometheus' ability to maintain undisrupted business operations due to the COVID-19 pandemic, including delaying or otherwise disrupting its clinical trials, manufacturing and supply chain; and other risks described in the company's prior press releases and filings with the Securities and Exchange Commission (SEC), including under the heading "Risk Factors" in Prometheus' most recent quarterly report on Form 10-Q and any subsequent filings with the SEC. You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof, and Prometheus undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date hereof. All forward-looking statements are qualified in their entirety by this cautionary statement, which is made under the safe harbor provisions of the Private Securities Litigation Reform Act of 1995.

Prometheus Biosciences Contact:

Noel Kurdi

VP Investor Relations and Communications

(646) 241-4400

[email protected]

Media Contact:

Jake Robison

CanaleComm, an Ashfield Health Company

(619) 849-5383

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