Prometheus Biosciences Announces Positive Results for PRA023 in Both ARTEMIS-UC Phase 2 and APOLLO-CD Phase 2a Studies Enabling Pathway to Both First-in-Class and Best-in-Class Anti-TL1A mAb

– ARTEMIS-UC trial met primary endpoint with 26.5% of patients on PRA023 achieving clinical remission compared to 1.5% of patients on placebo at Week 12 (p<0.0001) –

– ARTEMIS-UC Cohort 1 met all ranked secondary endpoints –

– APOLLO-CD trial showed 26.0% endoscopic response and 49.1% clinical remission rates (p=0.002 and p<0.001, respectively, compared to prespecified historical placebo rates) –

– PRA023 demonstrated favorable safety and tolerability results across both studies with no safety signal identified –

– ARTEMIS-UC Cohort 1 interim analysis suggests a trend towards increased PRA023 response in CDx+ patients over all comers –

– PRA023 showed a significant impact on multiple markers of inflammation and fibrosis in APOLLO-CD –

– Prometheus intends to advance PRA023 into Phase 3 studies for UC and CD in 2023 –

– Conference call and webcast to discuss results today at 8:30 am ET –

SAN DIEGO, Dec. 07, 2022 (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 results from its ARTEMIS-UC Phase 2 and APOLLO-CD Phase 2a studies of PRA023 demonstrating strong efficacy and favorable safety results in both studies. Based on the totality of the data in these two studies, Prometheus intends to advance PRA023 into Phase 3 studies for ulcerative colitis (UC) and Crohn's disease (CD) in 2023.

Topline Results from the ARTEMIS-UC Phase 2 Study

Prometheus' Phase 2 ARTEMIS-UC clinical trial was a 12-week, double-blind, placebo-controlled, randomized study to evaluate the efficacy and safety of PRA023 in patients with moderate-to-severely active UC who have failed conventional or advanced therapy. PRA023 met the primary and all ranked secondary endpoints including clinical, endoscopic, histologic, and patient-reported outcome measures in the initial cohort (Cohort 1) of the trial. 68/68 (100%) of PRA023-treated patients completed the Cohort 1 study, compared to 60/67 (89.6%) in the placebo group. The topline results for the key endpoints were as follows:

• 26.5% of patients on PRA023 reached the primary endpoint of clinical remission (per modified Mayo Score), compared to 1.5% on placebo, for a placebo-adjusted clinical remission rate of 25.0% on the primary endpoint (p<0.0001)
• 36.8% of patients on PRA023 reached the secondary endpoint of endoscopic improvement (Mayo endoscopy subscore of ≤ 1), compared to 6.0% on placebo, for a placebo-adjusted endoscopic improvement rate of 30.8% on the secondary endpoint (p<0.0001)
• All secondary endpoints met with statistical significance
  
  

PRA023 was well tolerated in Cohort 1, with no treatment-emergent serious adverse events (SAEs), adverse events (AEs) leading to discontinuation, severe AEs, opportunistic infections or infusion reactions reported in the PRA023 treatment group. The only AE that occurred in more than two patients and at a higher frequency in the PRA023 group compared to placebo was COVID-19 (5/68 [7.4%] and 3/67 [4.5%], respectively).

Based upon confidence in its precision approach and speed to market, the company conducted an interim companion diagnostic (CDx) analysis of Cohort 1 to evaluate the effectiveness of the CDx candidate in ARTEMIS-UC. Although from limited patient numbers, data from the subset of patients who tested positive on the CDx in Cohort 1 (N=32) demonstrated a placebo-adjusted clinical remission rate of 37.5%, compared with the placebo-adjusted remission rate of 25.0% for all-comers. The expansion cohort (Cohort 2), which is statistically powered to further assess the treatment effect of PRA023 in CDx+ patients will continue to enroll, and the company expects results in the second quarter of 2023.

Results from the APOLLO-CD Phase 2a Study

Prometheus' Phase 2a APOLLO-CD clinical trial was a 12-week open-label study that enrolled 55 patients with moderate-to-severely active CD with endoscopically active disease who had failed conventional or biologic therapy. The study enrolled a highly refractory patient population with 70.9% of patients previously treated with at least one biologic therapy and 52.7% treated with two or more biologic therapies. The results on the key endpoints were as follows:

• 26.0% of patients on PRA023 achieved endoscopic response (p=0.002 compared to 12% prespecified historical placebo rate)
• 49.1% of patients on PRA023 achieved clinical remission (p<0.001 compared to 16% prespecified historical placebo rate)

PRA023 was well tolerated in the APOLLO-CD study. There were no treatment-emergent serious adverse events (SAE), adverse events (AE) leading to discontinuation, or severe AEs assessed as related to PRA023 by the investigator. There were no opportunistic infections or infusion reactions reported. AEs that occurred in more than two patients included COVID-19, urinary tract infection, CD, anemia, nasopharyngitis and fatigue.

The predictive power of the company's prespecified genetic markers was validated using an alternative Crohn's-specific CDx algorithm which showed 45.0% (9/20) endoscopic response relative to all-comers of 26% (13/50). While the original algorithm provided limited benefit on some of the endpoints, the alternative algorithm demonstrated enhanced performance across both clinical and endoscopic outcomes. The company plans to advance this alternative algorithm in registrational studies for CD.

In addition, a compelling reduction in markers of inflammation and fibrosis was observed between pre-treatment and post-treatment with PRA023, as measured by circulating cytokine levels, immunohistochemistry and gene expression in disease tissue.

"We are beyond enthusiastic with these study results and what they could mean for patients suffering from IBD. The performance of PRA023 in both UC and Crohn's patients has surpassed our expectations," said Mark McKenna, Chairman and CEO of Prometheus Biosciences. "We believe PRA023 and our precision medicine approach has the potential to change the paradigm of IBD treatment and we look forward to discussions with regulatory agencies as we prepare to advance into Phase 3 studies in Ulcerative Colitis and Crohn's Disease."

"PRA023 has clearly demonstrated clinical proof-of-concept in CD and remarkable efficacy for the treatment of UC," added Allison Luo, MD, Chief Medical Officer. "We are grateful to all of our investigators and patients for their participation and look forward to further evaluating PRA023 in Phase 3 studies with the goal of bringing this promising candidate to the market."

Next Steps

As a result of these positive data, Prometheus plans to advance PRA023 into pivotal development in 2023, following discussions with regulators. The full data sets from these studies will be presented at a future medical meeting.

Webcasting Information

Prometheus management will hold a call today, December 7, at 8:30 am ET to discuss both ARTEMIS-UC and APOLLO-CD Phase 2 results. Registration for the event as well as a live and archived webcast of the webcast and call will be available in the Events & Webcasts page of the Prometheus Biosciences website.

About PRA023: Pipeline in a Product Candidate

PRA023 is an IgG1 humanized monoclonal antibody 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 UC, CD, and systemic sclerosis-associated interstitial lung disease (SSc-ILD).

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. 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 potential of PRA023 to improve IBD treatment and to be both a first-in-class and best-in-class anti-TL1A mAb; the timing of results from Cohort 2 of the ARTEMIS-UC trial; plans to advance PRA023 into Phase 3 studies in UC and CD, including the timing thereof, as well as plans to use an alternative CDx algorithm for CD. The inclusion of forward-looking statements should not be regarded as a representation by Prometheus that any of its 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: topline results Prometheus reports are based on preliminary analysis of key efficacy and safety data, and such data may change following a more comprehensive review of the data related to the clinical trial and such topline data may not accurately reflect the complete results of a clinical trial; Prometheus' approach to the discovery and development of precision medicines based on Prometheus360 is unproven; interim results of a clinical trial such as with Cohort 1 CDx analysis do not predict final results and the clinical outcomes may materially change as patient enrollment in Cohort 2 continues, following more comprehensive reviews of the data, as follow-up on the outcome of any particular patient continues and as more patient data become available, including from from Cohort 2; potential delays in the commencement, enrollment and completion of clinical trials and preclinical studies; the results of clinical trials are not necessarily predictive of future results; Prometheus' dependence on third parties in connection with product manufacturing, research and preclinical and clinical testing; Prometheus' ability to develop companion diagnostics for its therapeutic product candidates; unexpected adverse side effects or inadequate efficacy of its product candidates that may limit their development, regulatory approval and/or commercialization, or may result in recalls or product liability claims; planned future trials of PRA023 may not support regulatory registration; regulatory developments in the United States and foreign countries; Prometheus' ability to maintain undisrupted business operations due to the COVID-19 pandemic, including delaying or otherwise disrupting its preclinical studies, 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.

Contacts:

Noel Kurdi

VP Investor Relations and Communications

(646) 241-4400

[email protected]

Media contact:

Juniper Point

Amy Conrad

(858) 914-1962

[email protected]