PRTH-101 / Incendia Therap - LARVOL DELTA

A Phase 1 Trial of PRTH-101, a monoclonal antibody targeting discoidin domain receptor 1 (DDR1), alone or in combination with pembrolizumab, for the treatment of thymic malignancies (ITMIG 2025) - No abstract available

Combination therapy • P1 data • Oncology • Thymic Carcinoma • Thymus Cancer • DDR1

A Pivotal Phase 2 Trial to Compare PRTH-101, a monoclonal antibody targeting discoidin domain receptor 1 (DDR1), in combination with an immune checkpoint inhibitor (ICI) and ICI alone, for the treatment of recurrent or metastatic thymic epithelial carcinoma (TEC) (ITMIG 2025) - No abstract available

Checkpoint inhibition • Combination therapy • Metastases • P2 data • Oncology • Thymic Epithelial Tumor • DDR1

Title: A Phase 1 trial of PRTH-101, a monoclonal antibody targeting discoidin domain receptor 1 (DDR1), alone or in combination with pembrolizumab, for the treatment of thymic malignancies.​ (GlobeNewswire) - "Two confirmed PRs, multiple patients with minor RECIST and quality of life improvements across tumor types, and multiple with prolonged stable disease beyond published expectations Correlation between DDR1 expression and PFS with PRTH-101 treatment, when dosed with and without pembrolizumab; Correlation of tumor responses to PRTH-101 and pembrolizumab to expression of their respective targets; Among all TEC patients (n=18 as of September 4, 2025), mPFS of 7.9 months (ongoing) vs. literature reports 4.2 months."

P1 data • Thymic Carcinoma

Title: A pivotal Phase 2 trial to compare PRTH-101, a monoclonal antibody targeting discoidin domain receptor 1 (DDR1), in combination with an immune checkpoint inhibitor (ICI) to ICI alone, for the treatment of recurrent or metastatic thymic epithelial carcinoma (TEC) (GlobeNewswire) - "Global registrational trial planned for 2026 in patients ≥12 years old with recurrent or metastatic TEC; Open-label two-cohort trial design (immune checkpoint inhibitor [ICI]-refractory and ICI-naïve) will evaluate PRTH-101 in combination with pembrolizumab versus pembrolizumab alone; Primary and secondary endpoints to include overall response rate, PFS, and safety, with exploratory assessments including advanced tumor imaging assessments, DDR1 and PD-L1 biomarker expression, and quality-of-life assessments; Trial design discussed with the FDA."

New P2 trial

Incendia Therapeutics Enrolls First Patient in Phase 1c Clinical Trial of PRTH-101, a Novel DDR1 Inhibitor (Businesswire) - "Incendia Therapeutics...announced that the first patient has been enrolled in the Phase 1c study of PRTH-101 for the treatment of patients with advanced or metastatic solid tumors....The Phase 1c study will evaluate the safety, tolerability and anti-tumor activity of PRTH-101 as both a monotherapy and in combination with KEYTRUDA (pembrolizumab)."

Trial status • Oncology • Solid Tumor

Discoidin domain receptor 1 (DDR1) expression is associated with degree of immune exclusion across epithelial tumors (AACR 2024) - "A first-in-human trial of PRTH-101, a DDR1-targeted therapeutic antibody, is underway... We developed a continuous scoring method to quantify the degree of immune exclusion in tumors based on the spatial distributions of lymphocytes, CD8+ T cells, and CD45+ immune cells from H&E and mIF images. DDR1 mRNA and protein expression are correlated with immune exclusion at both the pan-cancer and specific indication level. This adds additional insight into the role of DDR1 in human cancers and may be useful in selecting indications and stratifying patients for DDR1-targeted therapies."

Breast Cancer • Gastrointestinal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor • Triple Negative Breast Cancer • CD8 • DDR1 • PTPRC

Incendia Therapeutics Announces Upcoming Presentations at the American Association for Cancer Research 2024 (Businesswire) - "“The data continue to validate that Discoidin Domain Receptor 1 (DDR1), the target of Incendia’s PRTH-101 program that is currently in the clinic, is highly correlated with immune exclusion in the tumor microenvironment across epithelial tumors....DDR1 mRNA and protein expression levels are correlated with immune exclusion of lymphocytes, CD8+ T cells, and CD45+ immune cells across epithelial tumor types (R: 0.31-0.56, adjusted p values: 0.04-0.07). While the degree of the correlation varied by indication and immune cell type considered, pancreatic cancer exhibited the strongest correlation between the lymphocyte-based Immune Exclusion Scores (IES) and DDR1 mRNA and protein expression (R: 0.48-0.54, adjusted p values: 0.04-0.07)."

Preclinical • Oncology

Incendia Therapeutics Appoints Wendye Robbins, M.D., as Chief Executive Officer and Doses First Patient in Phase 1b Clinical Trial of PRTH-101, a Novel DDR1 Inhibitor (Businesswire) - "The company also announced that the first patient has been dosed with PRTH-101 in the Phase 1b multiple-ascending dose trial cohort for the treatment of patients with immune-excluded solid tumors....The Phase 1b clinical trial will evaluate PRTH-101 treatment across three different dose levels in combination with KEYTRUDA^® (pembrolizumab). The outcome of the trial will guide the company in determining the recommended Phase 2 dose for PRTH-101."

Trial status • Oncology • Solid Tumor

DDR1 expression is associated with a worse prognosis in intrahepatic cholangiocarcinoma (SITC 2023) - "Background Discoidin Domain Receptor 1 (DDR1) is a tyrosine kinase expressed on cancer cells that binds to collagen, is associated with T-cell exclusion and poor outcomes in several cancer types and is the target of investigational drug therapy PRTH-101...DDR1 expression is associated with higher levels of stroma, which contains collagen, the ligand of DDR1. The prevalence of high DDR1 expression and poor survival outcomes associated with this make iCCA a relevant tumor type for evaluating novel DDR1-targeted therapies."

Biliary Cancer • Cholangiocarcinoma • Gastrointestinal Cancer • Oncology • Solid Tumor • CD8 • DDR1 • FGFR • IDH1

A phase I first-in-human study of PRTH-101, an IgG1 monoclonal antibody targeting DDR1, as a monotherapy and combined with pembrolizumab in patients with advanced solid malignancies (ESMO 2023) - P1 | "Safety, efficacy, pharmacokinetic, and pharmacodynamic endpoints will be monitored and reported. DDR1 expression levels on tumors, circulating DDR1, molecular and cellular changes in the TME, and changes on CD8 PET imaging will also be assessed."

Clinical • IO biomarker • Metastases • Monotherapy • P1 data • Oncology • Solid Tumor • CD8 • DDR1

Incendia Therapeutics Announces Upcoming Presentations at the European Society for Medical Oncology Congress 2023 (Businesswire) - "Incendia Therapeutics...announced that it will have two poster presentations at the European Society for Medical Oncology (ESMO) Congress 2023, to be held in Madrid, Spain October 20-24, 2023. The company will present data on the expression of discoidin domain receptor 1 (DDR1) mRNA and protein across 20 tumor types and will provide a detailed overview of Incendia’s Phase 1 first-in-human clinical trial for its lead candidate PRTH-101 in patients with advanced solid tumors....DDR1 expression was uniformly low in mesenchymal tumors (median of 9 cells/mm2) compared to epithelial tumors (median of 2803 cells/mm2). Moderate correlation was observed between DDR1 mRNA expression and DDR1+ cell density across tumor types (R=0.48, p<0.0001). In epithelial tumors, both DDR1 mRNA and protein expression were correlated with the percentage of epithelium (R=0.37 and 0.56, respectively; both p<0.0001), with significant variance between tumor types."

Clinical • P1 data • Oncology • Solid Tumor

Parthenon Therapeutics Announces Publication in Journal for ImmunoTherapy of Cancer on the Role of PRTH-101 Inhibiting DDR1 in Immune Excluded Tumors (Businesswire) - "Parthenon Therapeutics...today announced that the Journal for ImmunoTherapy of Cancer (JITC) has published results from a collaboration between Parthenon Therapeutics, The University of Texas Health Center at Houston (UTHealth Houston) and George Washington University....Structural studies, including a PRTH-101/DDR1 co-crystal structure, identified the PRTH-101 epitope on DDR1; Culturing DDR1-expressing human cancer cells with PRTH-101 inhibited DDR1 autophosphorylation induced by collagen and the shedding of DDR1 fragments from the cell surface; PRTH-101 demonstrated the ability to potently inhibit the adhesion of DDR1-expressing cancer cells to collagen substrates, disrupting the physical barrier formed by aligned collagen fibers in tumors; The ability of PRTH-101 to inhibit functions of the extracellular component of DDR1 differentiates PRTH-101 from DDR1 kinase inhibitors..."

Preclinical • Oncology • Solid Tumor

A highly selective humanized DDR1 mAb reverses immune exclusion by disrupting collagen fiber alignment in breast cancer. (PubMed, J Immunother Cancer) - "This study not only paves a pathway for the development of PRTH-101 as a cancer therapeutic, but also sheds light on a new therapeutic strategy to modulate collagen alignment in the tumor ECM for enhancing antitumor immunity."

Journal • Breast Cancer • Oncology • Solid Tumor • DDR1

A First-in-human Study of PRTH-101 Monotherapy +/- Pembrolizumab in Subjects With Advanced Malignancies (clinicaltrials.gov) - P1 | N=270 | Recruiting | Sponsor: Parthenon Therapeutics, Inc. | Not yet recruiting ➔ Recruiting

Combination therapy • Enrollment open • Metastases • Monotherapy • Oncology • Solid Tumor

Parthenon Therapeutics Announces Data at the American Association for Cancer Research (AACR) Annual Meeting 2023 on Prevalence of Immune Exclusion in Solid Tumors to Support Phase 1 Clinical Trial of PRTH-101 (Businesswire) - P=NA | N=NA | "Parthenon Therapeutics...presented data at the AACR Annual Meeting 2023, on the high prevalence of immune exclusion in select solid tumor types. The data further support Parthenon’s planned Phase 1 clinical trial of lead candidate PRTH-101, a novel Discoidin Domain Receptor (DDR1) inhibitor which targets DDR1-directed collagen barriers in immune excluded tumors....The findings released today show that greater than 40% of patient tumors in triple negative breast cancer, non-small cell lung cancer, pancreatic ductal adenocarcinoma, and colorectal cancer are immune excluded based on both pathologist-defined immune phenotypes and image analysis. Moderate levels of immune exclusion were observed in ovarian cancer, and low levels in sarcoma subtypes."

Clinical data • Breast Cancer • Colorectal Cancer • Gastrointestinal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Sarcoma • Solid Tumor • Triple Negative Breast Cancer

Parthenon Therapeutics Announces Data at the American Association for Cancer Research (AACR) Annual Meeting 2023 on Prevalence of Immune Exclusion in Solid Tumors to Support Phase 1 Clinical Trial of PRTH-101 (Businesswire) - "Parthenon Therapeutics...today presented data at the AACR Annual Meeting 2023, on the high prevalence of immune exclusion in select solid tumor types. The data further support Parthenon’s planned Phase 1 clinical trial of lead candidate PRTH-101, a novel Discoidin Domain Receptor (DDR1) inhibitor which targets DDR1-directed collagen barriers in immune excluded tumors....These data were generated in collaboration with Institute Bergonié (PI: Antoine Italiano). The poster detailing these findings - #2108 - will be presented at the American Association of Cancer Research (AACR) Annual Meeting on Monday, April 17, 2023."

Parthenon Therapeutics Announces First Patient Dosed in Phase 1 Clinical Trial of PRTH-101, a Novel DDR1 Inhibitor for the Treatment of Immune-Excluded Solid Tumors (Businesswire) - "Parthenon Therapeutics...announced that the first patient has been dosed with PRTH-101 in a Phase 1, first-in-human clinical trial for patients with immune-excluded solid tumors. PRTH-101 is a first-in-class Discoidin Domain Receptor 1 (DDR1) antagonist monoclonal antibody that is expressed at very high levels in solid tumors with low levels of T cell infiltration. PRTH-101 is the first development candidate from Parthenon’s broad TME-focused pipeline to enter clinical development."

Trial status • Oncology • Solid Tumor

A First-in-human Study of PRTH-101 Monotherapy +/- Pembrolizumab in Subjects With Advanced Malignancies (clinicaltrials.gov) - P1 | N=270 | Not yet recruiting | Sponsor: Parthenon Therapeutics, Inc.

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

Parthenon Therapeutics Showcases New Precision Oncology Technology Designed to Breakdown Barriers in Immune-excluded Tumors (Businesswire) - "Patient-derived biomarker and preclinical data demonstrate significant opportunity to address immune-excluded tumors, such as colorectal, NSCLC, ovarian, pancreas, and TNBC; First in human clinical trial of lead asset, PRTH-101, expected to initiate 3Q23....Parthenon Therapeutics...unveiled its precision medicine approach to address cancers with hight unmet need, at the Stifel Healthcare Conference....'Our data have shown over 50% of solid tumors are immune-excluded, indicating a significant unmet need for these patients,' said Laurent Audoly, co-founder and Chief Executive Officer of Parthenon Therapeutics. 'We also presented our lead asset, PRTH-101, which targets DDR1 (Discoidin Domain Receptor 1) to open up the mechanical barrier that characterizes immune-excluded tumors, and thus make the tumors vulnerable to treatment'."

New trial • Preclinical • Breast Cancer • Colorectal Cancer • Gastrointestinal Cancer • Gynecologic Cancers • Lung Cancer • Non Small Cell Lung Cancer • Ovarian Cancer • Pancreatic Cancer • Solid Tumor • Triple Negative Breast Cancer