PLIANT THERAPEUTICS, INC.

Oncology Program

PLN-101095 is an oral, small molecule, dual selective inhibitor of αvβ8 and αvβ1 integrins designed to overcome checkpoint resistance by blocking TGF-β activation in the tumor microenvironment. Pliant is currently conducting FORTIFY, a Phase 1a/1b open-label, dose-escalation and indication expansion trial (NCT0670706), to evaluate the safety, tolerability, pharmacokinetics, and preliminary evidence of antitumor activity of PLN-101095, in combination with pembrolizumab, in patients with immune checkpoint inhibitor (ICI)-refractory advanced or metastatic solid tumors.

•Enrollment continues in FORTIFY, a Phase 1b indication expansion trial. FORTIFY will enroll up to 102 patients across three cohorts including non-small cell lung cancer (NSCLC), clear cell renal cell carcinoma (ccRCC) and tumors with high tumor mutational burden. Patients are treated for 14 days with PLN-101095 dosed at 1,000 mg twice daily as monotherapy, after which pembrolizumab is added as combination therapy. Enrollment remains strong, progressing ahead of schedule. Interim data is expected in 2027.

•Oral presentation at AACR of updated PLN-101095 Phase 1 data highlights monotherapy biomarker data showing a coordinated T-cell reactivation cascade in responders. In July, at the American Association for Cancer Research’s (AACR) Drug Discovery and Development conference, the Company reviewed encouraging PLN-101095 Phase 1 monotherapy biomarker data. As previously reported, all responding patients showed large increases in plasma interferon gamma (IFN-γ), a modulator of anti-tumor immunity, after 14 days of monotherapy with PLN-101095. Updated data show that blocking of αvβ8 by PLN-101095 also resulted in increases in CXCL9, a recruiter of T cells, and granzyme-B, a marker for cytotoxic arming in responding patients. Increased IFN-γ, CXCL9 and granzyme-B after PLN-101095 monotherapy signals a shift in the tumor microenvironment that could potentially resensitize tumors to pembrolizumab. Importantly, no non-responders experienced increases in these biomarkers.