Pliant Therapeutics Data From Phase 1 Dose Escalation Clinical Study Of PLN-101095 In Combination With Pembrolizumab Shows Anti-Tumor Activity; All Participants Demonstrate Large Increases In Plasma Interferon Gamma

Pliant Therapeutics, Inc. (Nasdaq: PLRX) today announced interim data from its Phase 1 dose escalation clinical trial evaluating PLN-101095, in combination with pembrolizumab, in patients with immune checkpoint inhibitor (ICI)-refractory advanced or metastatic solid tumors. PLN-101095 is an oral, small molecule, dual selective inhibitor of αvβ8 and αvβ1. It is the fourth clinical-stage drug candidate to be generated from Pliant's integrin-based drug development platform.

In a heavily pretreated patient population with advanced and/or metastatic solid tumors refractory to ICIs, PLN-101095 demonstrated anti-tumor activity in combination with pembrolizumab. Across the three highest dose cohorts, there were four responders consisting of one confirmed complete response (CR) and three partial responses (PR) (two confirmed, one unconfirmed) out of the 10 secondary ICI refractory patients. Clinical responses were observed in patients with cholangiocarcinoma, melanoma, head and neck squamous cell carcinoma and non-small cell lung cancer (NSCLC). The median time on treatment in these patients is 15 months, as of November 30th, 2025. Sixty percent of secondary refractory patients demonstrated stable disease or tumor reduction.

All responding patients showed large increases (4- to 13-fold vs. baseline) in plasma interferon gamma (IFN-γ) after a 14-day run-in period of monotherapy with PLN-101095. No non-responders showed meaningful increases in IFN- γ. PLN-101095 was generally well tolerated across all doses tested with few discontinuations (n=2) due to adverse events. PLN-101095 demonstrated a dose-dependent pharmacokinetic profile.

Sixteen patients with nine different tumor types were enrolled in five cohorts. Patients were treated for 14 days with PLN-101095 monotherapy administered orally at doses of 250 mg twice a day (BID) (n=1), 500 mg BID (n=2), 1000 mg BID (n=6), 1000 mg three times a day (TID) (n=4) or 2000 mg BID (n=3), followed by the addition of pembrolizumab at 200 mg administered intravenously every three weeks. Scans were conducted at baseline, Day 14, Week 10, and every 8 weeks thereafter.