Ventyx Biosciences Announces Positive Topline Phase 1 Data for its Selective Allosteric TYK2 Inhibitor VTX958

Ventyx Biosciences, Inc. recently announced positive data from the company’s Phase 1 single ascending dose (SAD) and multiple ascending dose (MAD) trial of VTX958, a novel and selective allosteric TYK2 inhibitor. The VTX958 Phase 1 SAD/MAD clinical trial was a two-part, randomized, double-blind, placebo-controlled dose-escalation study designed to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of single and multiple ascending doses. The study enrolled 96 adult healthy volunteers.

VTX958 was well tolerated across all 7 cohorts in the SAD portion and all 5 cohorts in the MAD portion of the Phase 1 trial with no discontinuations due to adverse events. No drug-related serious adverse events (SAEs) were reported. All treatment emergent adverse events (TEAEs) were classified as mild. No dose-limiting toxicities were identified and no dose-dependent trend in the frequency of TEAEs was observed. Additionally, there were no significant effects on hematological parameters, lipids/triglycerides and CPK laboratory values.

In both the SAD and the MAD portions of the trial, a dose-dependent increase in exposure was observed through all cohorts. In the MAD portion of the trial, VTX958 achieved TYK2 IC₅₀ and IC₉₀ coverage up to 24 hours. The exposures achieved by VTX958 demonstrated class-leading coverage of TYK2 IC₅₀ and IC₉₀ and its target cytokines, IL-12, IL-23 and IFNα.

In the MAD portion of the trial, pharmacodynamic (PD) activity was measured by the impact on TYK2-mediated target genes following an in vivo IFNα challenge, and by the IFNγ response to ex vivo IL-12/IL-18 stimulation of blood samples derived from all dosing cohorts. In both the in vivo IFNα challenge PD assay, as well as the ex vivo IFNγ response assay, VTX958 demonstrated robust dose-dependent PD, thereby confirming its impact on TYK2-mediated pathways and providing direct in vivo evidence of target engagement.

“Data from the Phase 1 trial of VTX958 demonstrate an excellent safety profile and class-leading TYK2 inhibition as measured by IC₅₀ and IC₉₀ coverage,” said William Sandborn, MD, President and Chief Medical Officer. “We believe these data will allow us to explore high levels of target inhibition in future clinical studies, which may support clinical differentiation in relevant disease populations, such as psoriasis, psoriatic arthritis and lupus. Additionally, we believe that our ability to achieve TYK2 target coverage throughout the day at levels typically associated with biologic therapies, may position VTX958 for success in disease indications that are expected to require higher therapeutic doses, such as Crohn’s disease. We look forward to advancing VTX958 into multiple Phase 2 trials, including psoriasis, Crohn’s disease and psoriatic arthritis, beginning in the fourth quarter of 2022.”

VTX958 is an oral, selective allosteric inhibitor of tyrosine kinase 2 (TYK2). TYK2 regulates both innate and adaptive immunity by mediating IFNα, IL-12 and IL-23 signaling. These targets have been clinically validated as relevant in the treatment of a broad range of immune-mediated diseases, including psoriasis, psoriatic arthritis, Crohn’s disease, ulcerative colitis and lupus. Selectively targeting inhibition of TYK2 without inhibition of other JAK family enzymes may reduce inflammation while preserving protective immune function. VTX958 was internally discovered and all commercial rights to the compound are owned by Ventyx.

Ventyx is a clinical-stage biopharmaceutical company focused on developing innovative oral medicines for patients living with autoimmune and inflammatory disorders. We believe our ability to efficiently discover and develop differentiated drug candidates will allow us to address important unmet medical need with novel oral therapies that can shift immunology markets from injectable to oral drugs. Our current pipeline includes three clinical-stage internally discovered programs targeting TYK2, S1P1R and NLRP3, positioning us to become a leader in the development of oral immunology therapies. Ventyx is headquartered in Encinitas, CA. For more information, visit www.ventyxbio.com.