VTYX Ventyx Biosciences Inc

Ventyx Biosciences, Inc. (Nasdaq: VTYX) (“Ventyx”, “Company”), a clinical-stage biopharmaceutical company focused on developing innovative oral therapies for patients with autoimmune, inflammatory, and neurodegenerative diseases, today announced that data from the Phase 2 trial of its TYK2 inhibitor VTX958 in Crohn’s disease will be presented during the 20th Congress of the European Crohn’s and Colitis Organisation (ECCO) being held in Berlin, Germany from February 19-22, 2025.

“The Phase 2 data for VTX958 in Crohn’s disease represent an important milestone for TYK2 inhibition in inflammatory bowel disease,” said Raju Mohan, PhD, Founder and Chief Executive Officer. “This trial did not meet the primary endpoint of change from baseline in the Crohn’s disease activity index, or CDAI (symptomatic outcome), likely due to a higher-than-expected placebo response. We did, however, observe a robust, dose-dependent endoscopic response, which was also associated with improvements in key inflammatory markers, including C-reactive protein and fecal calprotectin. Based on precedents from other Phase 3 trials in Crohn’s disease, we believe that VTX958 has the potential to show greater placebo-adjusted clinical remission rates with longer duration of therapy, including potential for reduced placebo response on symptomatic measures. These results give us confidence that TYK2 inhibition via VTX958 has the potential to offer a safe and effective treatment for Crohn’s disease, an indication with high unmet need for oral therapies. We also see potential for development as an advanced combination therapy with other oral and biologic agents.”

“There remains great need in Crohn’s disease for new safe and effective oral therapies,” commented Silvio Danese, MD, PhD, Professor of Gastroenterology at Vita-Salute San Raffaele University, Milan, Italy. “These Phase 2 data suggest that VTX958 has the potential for disease-modifying benefit in Crohn’s disease, including strong effects on endoscopic response, an outcome measure increasingly preferred as a primary endpoint in Phase 2 trials based on its stringency and objectivity. The totality of the Phase 2 data for VTX958, including a favorable safety profile, warrant further investigation in future clinical trials for Crohn’s disease.”

Poster and Abstract Information:

Title:	Efficacy and safety of an oral tyrosine kinase 2 inhibitor VTX958 in moderately to severely active Crohn’s disease: a randomised, double-blind, placebo-controlled, phase 2 trial
Poster #	P1001
Session:	February 21, 2025, 12:40-1:40 PM CET; Poster Exhibition, Hall 2.2
Abstract:	Journal of Crohn's and Colitis, https://doi.org/10.1093/ecco-jcc/jjae190.1175

Phase 2 Trial OverviewThe randomized, double-blind, placebo-controlled Phase 2 trial (NCT05688852) was designed to evaluate the safety and efficacy of VTX958 in adults with moderately-to-severely-active Crohn’s disease. One hundred and nine (109) subjects were randomized 1:1:1 to placebo, VTX958 225 mg BID, or VTX958 300 mg BID for a 12-week induction treatment period, followed by a 40-week double-blind maintenance period. Baseline characteristics were comparable across treatment groups. The primary endpoint was the change in the Crohn’s Disease Activity Index (CDAI) from baseline to Week 12. Secondary endpoints included additional symptomatic and endoscopic (as measured by the simple endoscopic score for Crohn’s disease, or SES-CD) measures, as well as inflammatory biomarkers.

While the primary endpoint was not met, likely due to a higher-than-expected placebo response, improvements in endoscopic results were observed. These improvements were associated with reductions in key inflammatory biomarkers. VTX958 was well tolerated in this Phase 2 trial.

• Change in CDAI Score (Primary): Reductions in CDAI from baseline were observed with VTX958 at Week 12 (-134.1 points for VTX958 225 mg; -113.6 points for VTX958 300 mg); however, these results did not reach statistical significance, likely due to a higher-than-expected response in the placebo group (-104.3 points; p>0.05).

• Change in SES-CD Score: Reductions from baseline in the SES-CD score were observed with VTX958 225 mg (-3.5 points, p<0.0001) and VTX958 300 mg (-2.7 points, p=0.0005) compared to placebo (+2.1 points).

• Endoscopic Response: A greater proportion of participants on VTX958 achieved endoscopic response, defined as a ≥50% reduction from baseline in the SES-CD score, compared to placebo. Endoscopic response rates were robust and dose-dependent, with 24.3% of participants on VTX958 225 mg (p=0.0263) and 32.4% on VTX958 300 mg (p=0.0066) achieving endoscopic response at Week 12, compared to 5.7% of participants on placebo.

• Combined Endoscopic Response and Clinical Remission: A greater proportion of participants on VTX958 achieved both clinical remission (CDAI score <150) and endoscopic response compared to placebo (18.9% VTX958 300 mg vs. 2.9% placebo; p=0.0408), indicating that participants with an endoscopic response also achieved improvement in their clinical signs and symptoms.

• Combined Clinical-Biomarker Response: A greater proportion of participants on VTX958 achieved a clinical-biomarker response (43.2% VTX958 300 mg vs. 14.3% placebo; p=0.0105). Clinical-biomarker response was defined as a ≥100 point reduction in CDAI score or CDAI score <150 combined with a ≥50% reduction from baseline in C-reactive protein and/or fecal calprotectin.

Based on these results, and recognizing the unmet need and opportunity for a safe and effective oral TYK2 inhibitor as early-line therapy in Crohn’s disease, we are continuing the analysis of the Phase 2 data including data from the 52-week treat-through long-term extension phase. Full analysis of the Phase 2 data is expected to inform future development strategy and partnership opportunities for VTX958 in Crohn's disease.

About Ventyx BiosciencesVentyx Biosciences is a clinical-stage biopharmaceutical company developing innovative oral therapies for patients with autoimmune, inflammatory, and neurodegenerative diseases. Our expertise in medicinal chemistry, structural biology, and immunology enables the discovery of differentiated oral small molecule therapeutics for conditions with high unmet medical need, and our extensive experience in clinical development allows the rapid progression of these drugs through clinical trials. Our lead portfolio of NLRP3 inhibitors includes VTX2735, a peripherally restricted NLRP3 inhibitor in Phase 2 development for recurrent pericarditis, and VTX3232, a CNS-penetrant NLRP3 inhibitor in Phase 2 development for neurodegenerative and cardiometabolic diseases. Our inflammatory bowel disease portfolio includes tamuzimod (VTX002), an S1P1R modulator, and VTX958, a TYK2 inhibitor, both of which have completed Phase 2 clinical trials. For more information on Ventyx, please visit our website at https://ventyxbio.com.

Forward-Looking Statements

Ventyx cautions you that statements contained in this press release regarding matters that are not historical facts are forward-looking statements. These statements are based on Ventyx’s current beliefs and expectations. Such forward-looking statements include, but are not limited to, statements regarding: the potential for VTX958 to be an active agent for Crohn’s disease and the potential to be evaluated further as a monotherapy or in combination regimen; the continued analysis of the discordance between symptomatic and endoscopic response data, and any ability to draw conclusions therefrom; management’s plans with respect to the commitment of internal resources toward further analysis, or development, including future studies partnerships or other sources of non-dilutive financing, for VTX958 in Crohn’s disease; and a change in study design for VTX958 in Crohn’s would yield greater placebo-adjusted clinical remission rates or a reduction in placebo response on symptomatic measures.

The inclusion of forward-looking statements should not be regarded as a representation by Ventyx 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 Ventyx’s business, including, without limitation: whether any insights can be derived from the analysis of the discordance between symptomatic and endoscopic response data in the Phase 2 trial; potential delays in the commencement, enrollment and completion of clinical trials; Ventyx’s dependence on third parties in connection with product manufacturing, research and preclinical and clinical testing; disruptions in the supply chain, including raw materials needed for manufacturing and animals used in research, delays in site activations and enrollment of clinical trials; the results of preclinical studies and clinical trials; early clinical trials not necessarily being predictive of future results; interim results not necessarily being predictive of final results; the potential of one or more outcomes to materially change as a trial continues and more patient data become available and following more comprehensive audit and verification procedures; regulatory developments in the United States and foreign countries; unexpected adverse side effects or inadequate efficacy of Ventyx’s product candidates that may limit their development, regulatory approval and/or commercialization, or may result in recalls or product liability claims; Ventyx’s ability to obtain and maintain intellectual property protection for its product candidates; the use of capital resources by Ventyx sooner than expected; and other risks described in Ventyx’s prior press releases and Ventyx’s filings with the Securities and Exchange Commission (SEC), including in Part II, Item 1A (Risk Factors) of Ventyx’s Quarterly Report on Form 10-Q for the quarter ended September 30, 2024, filed on or about November 7, 2024, and Ventyx’s 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 Ventyx 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.

Investor Relations Contact:Joyce AllaireManaging DirectorLifeSci AdvisorsIR@ventyxbio.com