Dosing of first MAD cohort in Phase 1 trial of O3R-5671 complete with no drug related adverse events

Pharmacokinetic profile demonstrates long half-life and low intersubject variability

Pharmacodynamic data from single ascending dose cohorts indicative of profound and sustained TNFα inhibition at low doses

Onco3R Therapeutics, a clinical-stage immunology and oncology biotech company dedicated to transforming patients’ lives with best-in-class medicines, announced the successful completion of the first multiple ascending dose (MAD) cohort of subjects in the Phase 1 trial of its novel SIK3 inhibitor O3R-5671. Four single ascending dose (SAD) cohorts have also been completed.

In each of the SAD cohorts, six subjects received a single oral dose of O3R-5671 between 5mg - 35mg. In the first MAD cohort, six subjects received 5mg O3R-5671 once a day for 14 days. Pharmacokinetic and safety data support investigating a higher dose in the second MAD cohort of the study, which is planned to initiate in early December.

Pharmacokinetic data generated to date demonstrate that O3R-5671 has a flat PK profile, a highly attractive attribute of this drug candidate, with a long half-life. Drug exposure in the SAD cohorts is dose proportional with low variability between subjects. A food effect cohort demonstrated that O3R-5671’s PK profile is consistent with or without food indicating that there will be no food restrictions in future patient clinical studies. Data from the first MAD cohort demonstrate that O3R-5671’s attractive PK profile is maintained at day 14 with drug exposure approximately two times higher than the same single 5mg dose.

The safety profile of O3R-5671 is highly encouraging with a low rate of drug related adverse events reported to date. Importantly, no drug related adverse events have been reported in the 25 and 35mg SAD cohorts or in the 5mg MAD cohort and there have been no clinically significant abnormalities on ECG, vital signs or physical examination.

Pharmacodynamic data from the SAD cohorts demonstrate that O3R-5671 potently inhibits TNFα in a dose dependent manner and that maximal inhibition (approximately 90%) is achieved between 25mg and 35mg, the highest dose that has been examined to date. Furthermore, drug levels 24 hours after dosing at 25 and 35mg doses maintained inhibition of TNFα by more than 75%.

“We are very encouraged by the PK, safety and PD data that have been generated to date in the first in human study of O3R-5671” said Pierre Raboisson, PhD, CEO and Founder of Onco3R Therapeutics. “These data exceed the expectations we had for O3R-5671 before we entered the clinic, and we are excited about the prospect of completing this important study and embarking on patient studies in 2026. In addition to potently inhibiting TNFα, our non-clinical data also demonstrate that O3R-5671 potently inhibits IL-23 and IL-12 which, along with TNFα, are implicated in the pathogenesis of a variety of autoimmune diseases including ulcerative colitis, Crohn’s disease and psoriasis.”

He added, “We are highly motivated to discover and develop drugs that will make significant improvements to the lives of patients living with autoimmune diseases and cancer. Specifically for patients with autoimmune diseases, O3R-5671 has the potential to become a safe, effective and convenient therapeutic option and we are looking forward to its continued development.”