PLN-101095 / Pliant Therapeutics - LARVOL DELTA

Pliant Therapeutics…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 (GlobeNewswire) - "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)....Final data from this trial will be presented at an upcoming scientific conference....Company to accelerate development of PLN-101095 with initiation of a Phase 1b expansion trial in 2026."

New P1 trial • P1 data • Cholangiocarcinoma • Melanoma • Non Small Cell Lung Cancer • Squamous Cell Carcinoma of Head and Neck

Selective targeting of integrins avb8 and avb1 improves anti-tumor responses mediated by immune checkpoint inhibition (SITC 2025) - P1 | "Furthermore, analysis of spleens of EMT6 tumor bearing mice treated with PLN-101095 monotherapy or the combination with anti-PD1 showed enhanced numbers of IFNγ + producing neoantigen-specific T cells, compared to the anti-PD1 and control groups. These data provided rationale for an ongoing, first-in-human phase I clinical trial (NCT06270706) of PLN-101095 in combination with pembrolizumab in solid cancers."

Checkpoint inhibition • IO biomarker • Oncology • Solid Tumor • Squamous Cell Carcinoma • CD8 • GZMB • IFNG • SMAD3 • TGFB1

Pliant Therapeutics Provides Corporate Update and Reports Second Quarter 2025 Financial Results (GlobeNewswire) - "Second Quarter and Recent Developments:...Phase 1 trial of PLN-101095 in solid tumors continues to enroll:...The Phase 1 open-label, dose-escalation trial of PLN-101095 trial as monotherapy and in combination with pembrolizumab is in patients with solid tumors that are resistant to immune checkpoint inhibitors. The trial is currently dosing the fifth of five planned dose cohorts, evaluating PLN-101095 at 2000 mg administered twice daily (BID). Initial data from the two highest dose cohorts of the trial is expected by the end of 2025."

P1 data • Trial status • Solid Tumor

Pliant Therapeutics Announces Interim Phase 1 Data for PLN-101095 in Patients with Immune Checkpoint Inhibitor-Refractory Advanced Solid Tumors (GlobeNewswire) - P1 | N=77 | NCT06270706 | Sponsor: Pliant Therapeutics, Inc. | "The Company reported the following initial observations from the trial: Across all doses tested, PLN-101095 was generally well tolerated; Of the six patients treated at the 1000 mg BID dose of PLN-101095, three (50%) confirmed partial responses were observed. All three patients remain on treatment. Non-Small Cell Lung Cancer (NSCLC): Confirmed partial response with a 74% reduction in tumor size at Week 18; initial partial response was observed at Week 10; Cholangiocarcinoma: Confirmed partial response with a 48% reduction in tumor size at Week 42; initial partial response was observed at Week 34; Melanoma: Confirmed partial response with a 42% reduction in tumor size at Week 27; initial partial response was observed at Week 18."

P1 data • Oncology • Solid Tumor

Pliant Therapeutics Provides Corporate Update and Reports Fourth Quarter 2024 Financial Results (GlobeNewswire) - "Phase 1 trial of PLN-101095 in solid tumors continues to enroll, with interim data expected in the first quarter 2025....The trial is currently dosing the fourth of five planned dose cohorts in a Phase 1 open label dose-escalation trial of PLN-101095 as monotherapy and in combination with pembrolizumab in patients with solid tumors that are resistant to immune checkpoint inhibitors."

P1 data • Trial status • Oncology • Solid Tumor

PLN-101095 a selective inhibitor of integrins αvβ8 and αvβ1 augments the therapeutic benefits of immune checkpoint blockade therapy in human tumor histoculture model (SITC 2024) - P1 | "Explants in culture were treated with PLN either alone (50nM and 500nM), with nivolumab (anti PD-1 antibody, 132ug/ml) or in combination for 72 hours. Ethics Approval Donor tissue specimens along with matched blood sample were obtained from consented patients diagnosed with Head and neck squamous cell carcinoma (HNSCC). The Institutional Ethics Committee (IEC) from the sample collection centers approved the protocol (protocol # FCB-PROTOCOL-01) and informed consent for participation in the approved study was obtained from every donor."

Checkpoint block • Checkpoint inhibition • IO biomarker • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • GZMB • IFNG • IL10 • TGFB1 • TNFA

Pliant Therapeutics Provides Corporate Update and Reports Third Quarter 2024 Financial Results (GlobeNewswire) - "Pipeline Programs: Phase 1 trial of PLN-101095 in solid tumors is progressing with dosing of the third of five cohorts:...The Company has completed enrollment in the third of five cohorts in the Phase 1 open-label, dose-escalation trial. In this trial, PLN-101095 is being tested as monotherapy and in combination with pembrolizumab in patients with solid tumors that are resistant to immune checkpoint inhibitors. Preliminary data is expected in early 2025."

P1 data • Trial status • Solid Tumor

Pliant Therapeutics Provides Corporate Update and Reports Second Quarter 2024 Financial Results (GlobeNewswire) - "Phase 1 trial of PLN-101095 in solid tumors is progressing with dosing of the third of five cohorts...The Company is currently enrolling the third of five cohorts in the Phase 1 open label, dose-escalation trial of PLN-101095 as monotherapy and in combination with pembrolizumab in patients with solid tumors that are resistant to immune checkpoint inhibitors. Preliminary data is expected in late 2024 or early 2025....Based on preclinical data, PLN-101325 may have the potential to treat additional indications in organ systems outside of muscle. The Company is currently generating additional evidence in support of potential expansion of the scope of PLN-101325 prior to initiating a Phase 1 trial."

P1 data • Preclinical • Trial status • Genetic Disorders • Muscular Dystrophy • Oncology • Solid Tumor

Selective targeting of integrins αVβ8 and αVβ1 within the dynamic ecosystem of pancreatic cancer to improve the overall anti-tumor response (AACR 2024) - "Finally, utilizing patient-derived models of metastatic PDA revealed that both PLN-104 and PLN-101095 significantly blocked tumour growth, improved the response to SoC chemotherapy Gemcitabine/Abraxane, and reduced metastatic spread to distant sites. In conclusion, these data provide scientific rationale for the design of future PLN-101095 and SoC chemotherapy as well as immunotherapy combinations in pancreatic cancer, with Phase I first-in-human oncology studies with PLN-101095 plus ICB already underway."

IO biomarker • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • CD8 • KRAS • PDX1 • TGFB1

A Phase 1 Study of PLN-101095 in Adults With Advanced or Metastatic Solid Tumors (clinicaltrials.gov) - P1 | N=77 | Recruiting | Sponsor: Pliant Therapeutics, Inc.

Combination therapy • Metastases • Monotherapy • New P1 trial • Oncology • Solid Tumor

Pliant Therapeutics Provides Corporate Update and Reports Fourth Quarter 2023 Financial Results (GlobeNewswire) - "Phase 1 trial of PLN-101095 in solid tumors is enrolling. This is a Phase 1 open label trial of PLN-101095, an oral, small molecule, dual selective inhibitor of αvβ8 and αvβ1 integrins designed to block TGF-β activation in the tumor microenvironment. The trial is currently dosing the third of five planned dose cohorts in a Phase 1 open label dose-escalation trial of PLN-101095 as monotherapy and in combination with pembrolizumab in patients with solid tumors that are resistant to immune checkpoint inhibitors. Preliminary data is expected in late 2024."

P1 data • Trial status • Solid Tumor

Selective targeting of integrins αVβ8 and αVβ1 within the dynamic ecosystem of pancreatic cancer to improve the overall anti-tumour response. (LCC 2024) - "Finally, utilizing patient-derived models of metastatic PDA revealed that both PLN-104 and PLN-101095 significantly blocked tumour growth, improved the response to standard of care (SoC) chemotherapy Gemcitabine/Abraxane, and reduced metastatic spread to distant sites. These data provide scientific rationale for the design of future PLN-101095 and SoC chemotherapy as well as immunotherapy combinations in pancreatic cancer, with Phase I first-in-human oncology studies with PLN-101095 plus ICB already underway."

IO biomarker • Fibrosis • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • CD8 • KRAS • PDX1 • TGFB1

Pliant Therapeutics Presentations at the Annual Meeting of the Society for Immunotherapy of Cancer Highlight PLN-101095, A Novel Inhibitor of Integrins αvβ8 and αvβ1 (GlobeNewswire) - "Pliant Therapeutics, Inc...presented three posters highlighting PLN-101095, a novel inhibitor of integrins αvβ8 and αvβ1. These posters were presented as part of the 38^th Annual Meeting of the Society for Immunotherapy of Cancer (SITC) held November 1 - 5, 2023...Pliant is conducting a first-in-human, open-label, dose-escalation study designed to evaluate the safety, tolerability, and pharmacokinetics of PLN-101095 as monotherapy and in combination with pembrolizumab in adult patients with advanced or metastatic solid tumors...PLN-101095 was shown to block the binding of cancer-associated fibroblasts (CAF) to the TGF-β latency-associated peptide (LAP) in a dose-dependent manner....Results showed that selective targeting of αvβ8 and αvβ1 with PLN-101095 or αvβ1 signaling with PLN-76104 potently inhibited primary tumor growth, spread and improve chemotherapy response in models of PDA."

Preclinical • Trial status • Oncology • Solid Tumor

Selective targeting of integrins αVβ8 and αVβ1 within the dynamic ecosystem of pancreatic cancer to improve the overall anti-tumor response (SITC 2023) - "Finally, utilizing patient-derived models of metastatic PDA revealed that PLN-101095 significantly blocked tumor growth, improved the response to SoC chemotherapy Gemcitabine/Abraxane, and reduced the number and size of lung metastases. Conclusions These data demonstrate that PLN-101095 significantly enhances ICB or SoC chemotherapy response in advanced PDA models and provide scientific rationale for future combination studies testing PLN-101095 in pancreatic cancer."

IO biomarker • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • CD8 • KRAS • PDX1 • TGFB1

Phase 1a trial of PLN-101095, an integrin αvβ8 and αvβ1 inhibitor, as monotherapy and in combination with pembrolizumab, in treatment-resistant patients with advanced or metastatic solid tumors (SITC 2023) - "Enrolled patients will have demonstrated primary or acquired resistance to pembrolizumab and for assessing anti-tumor activity and pharmacodynamic effects. This trial design enables the efficient conduct of dose escalation trials involving ICI-sensitizing drugs in patients with resistance to ICIs."

Clinical • Combination therapy • IO biomarker • Metastases • Monotherapy • P1 data • Oncology • Solid Tumor • CD8 • TGFB1

Integrin αvβ1 is expressed in multiple solid tumor types and drives the adhesion of cancer associated fibroblast to latent TGF-β (SITC 2023) - "Conclusions Here, we demonstrate that the TGF-β activating integrin αvβ1 is expressed by multiple human cancer types, is present on primary human CAFs, and mediates CAF interaction with latent TGF-β. A first-in-human clinical trial investigating the combination of PLN-101095 with ICB is currently underway."

Breast Cancer • Gastrointestinal Cancer • Oncology • Ovarian Cancer • Ovarian Serous Adenocarcinoma • Pancreatic Cancer • Solid Tumor • CAFs • TGFB1

Pliant Therapeutics Announces Three Presentations at the Annual Meeting of the Society for Immunotherapy of Cancer (GlobeNewswire) - "Pliant Therapeutics, Inc...today announced three presentations at the upcoming 38th Annual Meeting of the Society for Immunotherapy of Cancer (SITC) taking place November 1 - 5, 2023 at the San Diego Convention Center in San Diego, California."

P1 data • Preclinical • Oncology • Solid Tumor

Pliant Therapeutics Provides Corporate Update and Reports First Quarter 2023 Financial Results (GlobeNewswire) - "Initiation of BEACON-IPF, a Phase 2b trial of bexotegrast in patients with IPF, expected in mid-2023. BEACON-IPF is a 52-week, multinational, randomized, placebo-controlled trial evaluating bexotegrast at doses of 160 mg or 320 mg in approximately 270 patients with IPF; INTEGRIS-PSC Phase 2a 12-week clinical data expected in the third quarter of 2023...approximately 84 patients with primary sclerosing cholangitis (PSC); Initiation of a Phase 1 first-in-human trial of PLN-101095 in oncology expected in the second quarter of 2023...Initiation of a Phase 1 trial in patients with solid tumors that are resistant to immune checkpoint inhibitors is expected in the second quarter of 2023; Muscular dystrophy program progressing through IND enabling activities. PLN-101325 is a monoclonal antibody designed to act as an allosteric agonist of the integrin α7β1. An IND submission for Duchenne muscular dystrophy (DMD) is expected in 2023."

IND • New P1 trial • New P2b trial • P2a data • Duchenne Muscular Dystrophy • Idiopathic Pulmonary Fibrosis • Muscular Dystrophy • Oncology • Respiratory Diseases • Solid Tumor

Pliant Therapeutics Announces FDA Clearance of Investigational New Drug Application for PLN-101095, A Novel Integrin Inhibitor for the Treatment of Solid Tumors (GlobeNewswire) - "Pliant Therapeutics, Inc...announced that the U.S. Food and Drug Administration (FDA) has cleared the company’s Investigational New Drug (IND) application for PLN-101095, an oral, small molecule, dual selective inhibitor of integrins αvβ8 and αvβ1. A Phase 1 first-in-human study evaluating PLN-101095 in patients with solid tumors that are resistant to immune checkpoint inhibitors (ICIs) is expected to initiate in the second quarter of 2023."

IND • New P1 trial • Oncology • Solid Tumor