Parthenon Therapeutics, Inc.

CAMBRIDGE, Mass.--(BUSINESS WIRE)-- Incendia Therapeutics, formerly Parthenon Therapeutics, a precision oncology company discovering and developing a novel class of therapies that reprogram the tumor microenvironment (TME), today 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 (NCT05753722). “The tumor microenvironment is dramatically impacted by the over expression of DDR1 and its role in the alignment of collagen fibers, which ultimately prevents immune cells from being able to directly interact with tumors,” said Laura Dillon, Vice President of Translational Medicine and Bioinformatics at Incendia. “These data presented at ESMO further highlight the potential of PRTH-101 as a first-in-class DDR1 inhibitor that may address the unmet need in the numerous cancers with high DDR1 expression.” Presentation Details: Title: High DDR1 mRNA and Protein Expression Across Human Tumor Types Correlate with Epithelial Composition of the Tumor Microenvironment Lead author: Laura Dillon, Ph.D., Vice President, Translational Medicine and Bioinformatics at Incendia Therapeutics Presentation #: 2309P Presentation Time: Saturday, October 21, 12:00 - 1:00 PM CEST (6-7 AM ET) Translational Research (agnostic) Key Highlights: DDR1 is expressed in a high proportion of tumor cells across a range of epithelial tumor types, suggesting potentially broad application of DDR1-targeted therapies. A high proportion of tumor cells (median of 0.76) expressed DDR1 across all epithelial tumor types. 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. Title: A Phase 1 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 Lead author: Shiraj Sen, M.D., Ph.D., Medical Oncologist and Director of NEXT Oncology Dallas Presentation #: 1079TiP Presentation Time: Monday, October 23, 12:00 – 1:00 PM CEST (6-7 AM ET) (Investigational immunotherapy) Key Highlights: Discoidin domain receptor 1 (DDR1) is a collagen receptor that represents a promising therapeutic target due to its role in excluding lymphocytes from the tumor microenvironment (TME) by aligning collagen fibers. DDR1 expression is high in multiple cancer types and associated with worse survival. PRTH-101 is a humanized IgG1 antibody that binds to the extracellular domain of both membrane-bound and soluble DDR1. In preclinical models, PRTH-101 monotherapy resulted in disruption of aligned collagen fibers in the tumor stroma, increased infiltration of lymphocytes, and tumor growth inhibition. When PRTH-101 is combined with PD-1 inhibition, activated T cell infiltration is increased compared to PRTH-101 alone. This is a Phase 1 first-in-human study that will evaluate intravenous PRTH-101 +/- pembrolizumab in patients with advanced solid tumors. Safety, efficacy, pharmacokinetic, and pharmacodynamic endpoints will be monitored and reported. The first part of the study (Ph1a) seeks to identify the maximum tolerated dose (MTD) or optimal biologic dose (OBD), of PRTH-101 to determine the recommended phase 2 dose (RP2D). The second part (Ph1b) seeks to identify the MTD or OBD of PRTH-101 in combination with pembrolizumab to determine the PRTH-101 combination RP2D. The third part (Ph1c) consists of dose expansion in disease-directed cohorts to assess the anti-tumor efficacy of PRTH-101 monotherapy and/or combination therapy. About PRTH-101 PRTH-101 is a therapeutic antibody that specifically binds to and blocks discoidin domain receptor 1 (DDR1,) a protein expressed on tumor cells that binds collagen to make a physical barrier that prevents immune cells from interacting with and attacking tumor cells. By disabling DDR1, the collagen fibers lose alignment and loosen, creating gaps in the tumor barrier, thus allowing T-cells to enter and attack the tumor. Blockade of DDR1 represents a unique approach to stimulating immune-based antitumor activity, and in preclinical models such blockade shows both single agent anti-tumor activity as well as marked augmentation of immunity enhanced by PD-1 blockade. Tumor types that express high levels of DDR1-associated collagen barriers include colorectal, ovarian, and non-small cell lung cancer. Currently, there are no approved drugs that target DDR1. About Incendia Therapeutics Incendia Therapeutics is discovering and developing a novel class of anti-cancer therapies that reprogram the tumor microenvironment (TME). Recent research has shown that the interplay between tumor cells and their surrounding TME results in the creation of barriers that markedly attenuate the immune system’s ability to attack the tumor. Based on rigorous, groundbreaking research, Incendia is developing a portfolio of drug candidates to treat select patients at the appropriate/ideal stage in disease progression. For more information visit incendia.com and LinkedIn.

-International panel of cancer experts defined and aligned on priorities for immune exclusion biology research BOSTON--(BUSINESS WIRE)-- Parthenon Therapeutics, a precision oncology company discovering and developing a novel class of therapies that reprogram the tumor microenvironment (TME), today announced that the Journal for ImmunoTherapy of Cancer (JITC) has published results from an international panel of cancer experts convened to provide an initial consensus on the role of immune exclusion in cancer. The article “Developing a Definition of Immune Exclusion in Cancer: Results of a Modified Delphi Workshop,” identifies key characteristics of and issues relevant to the role immune exclusion plays in resistance to checkpoint therapy and is now available online. The work described in the paper was performed in collaboration with multiple US and international academic institutions. “Immune exclusion until now has not had a well-defined profile, but we know it exists across multiple tumor types,” said J. Paul Eder, MD, Chief Medical Officer of Parthenon Therapeutics. “In collaboration with academic leaders, Parthenon is pioneering how to recognize and define immune exclusion in cancer and understand the mechanisms underlying it. By modulating the tumor microenvironment and breaking down the barrier that tumors construct to protect them from an immune attack, we think we can overcome immune exclusion and thus, improve patient outcomes.” Parthenon recently initiated a Phase 1 trial for its lead candidate PRTH-101 first-in-human clinical trial in patients with immune-excluded solid tumors (NCT05753722). About PRTH-101 PRTH-101 is a therapeutic antibody that specifically binds to and blocks DDR1, a protein expressed on tumor cells that binds collagen to make a minimally permeable physical barrier that blocks immune cells from interacting with and attacking tumor cells. Thus, these “immune cell-excluded” solid tumors are resistant to attack by the immune system (as well as other existing therapies). By disabling DDR1, the collagen fibers lose alignment and loosen, creating gaps in the tumor barrier, thus allowing T-cells to enter and naturally attack the tumor. The creation of DDR1-directed collagen alignment does not appear to have a normal physiological surrogate and may therefore be unique to pathologies such as neoplasia, potentially allowing for relatively safe interventions. Thus, blockade of DDR1 represents a unique and “orthogonal” approach to stimulating the immune-based antitumor activity, and such blockade shows both single agent anti-tumor activity as well as marked augmentation of immunity enhanced by PD-1 blockade. Tumor types which show particularly high levels of DDR1-associated collagen barriers include colorectal, ovarian, and non-small cell lung cancer. Currently, there are no approved drugs that target DDR1. About Parthenon Therapeutics Parthenon Therapeutics is discovering and developing a novel class of anti-cancer therapies that reprogram the tumor microenvironment (TME). Recent research has shown that the interplay of many cancers and their TME results in the creation of unique, non-physiologic barriers that markedly attenuate immune system attack. One approach utilized by PRTH-101 is to break down these barriers to overcome recalcitrant cancers. Based on rigorous, groundbreaking research, Parthenon is developing a portfolio of drug candidates to treat selected patients at the appropriate/ideal stage in disease progression. For more information visit parthenontx.com and LinkedIn.

− The study will assess safety, tolerability and preliminary evidence of antitumor activity in patients with heavily pretreated solid tumors, including those with high levels of DDR1 expression and immune exclusion on tumor biopsy BOSTON--(BUSINESS WIRE)-- Parthenon Therapeutics, a precision oncology company discovering and developing a novel class of therapies that reprogram the tumor microenvironment (TME), today 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. PRTH-101 uniquely targets DDR1 and has demonstrated, in preclinical models, anti-tumor activity as a single agent and in combination with an anti-PD-1 checkpoint inhibitor. “The initiation of a Phase 1 trial for PRTH-101 is an important step forward for cancer patients with DDR1-associated tumors, immune-excluded solid tumors, that have been shown to respond poorly to existing immuno-therapies,” said J. Paul Eder, MD, Chief Medical Officer of Parthenon Therapeutics. “With no FDA-approved therapies that target DDR1-associated tumors, we believe that PRTH-101 could uniquely improve patient outcomes by breaking down the barrier that various types of tumors construct to protect them from immune attack. Parthenon continues to focus on an unmet need in cancer that hasn’t been successfully targeted therapeutically, namely, direct modulation of the tumor microenvironment to overcome immune exclusion.” About PRTH-101 PRTH-101 is a therapeutic antibody that specifically binds to and blocks DDR1, a protein expressed on tumor cells that binds collagen to make a physical barrier that prevents immune cells from interacting with and attacking tumor cells. By disabling DDR1, the collagen fibers lose alignment and loosen, creating gaps in the tumor barrier, thus allowing T-cells to enter and naturally attack the tumor. The creation of DDR1-directed collagen alignment does not appear to have a normal physiological surrogate and may therefore be unique to pathologies such as neoplasia, potentially allowing for relatively safe interventions. Thus, blockade of DDR1 represents a unique and “orthogonal” approach to stimulating the immune-based antitumor activity, and such blockade shows both single agent anti-tumor activity as well as marked augmentation of immunity enhanced by PD-1 blockade. Tumor types which show particularly high levels of DDR1-associated collagen barriers include colorectal, ovarian, and non-small cell lung cancer. Currently, there are no approved drugs that target DDR1. About the Phase 1 Trial The Phase 1 trial (NCT05753722) is a multi-center, open-label, dose escalation and dose expansion study that is expected to enroll up to 270 patients in the US with advanced or metastatic solid tumors. The goals of the study are to assess safety and tolerability of PRTH-101, evaluate anti-tumor activity in select indications alone and in combination with anti-PD-1 inhibitors, and determine dosing regimens for the Phase 2 clinical program. In addition to examining the clinical pro PRTH-101, the trial will evaluate DDR1 and pathway-related proteins as predictive biomarkers for patients whose tumors respond to treatment. About Parthenon Therapeutics Parthenon Therapeutics is discovering and developing a novel class of anti-cancer therapies that reprogram the tumor microenvironment (TME). Recent research has shown that the interplay of many cancers and their TME results in the creation of unique, non-physiologic barriers that markedly attenuate immune system attack. One approach utilized by PRTH-101 is to break down these barriers to overcome recalcitrant cancers. Based on rigorous, groundbreaking research, Parthenon is developing a portfolio of drug candidates to treat select patients at the appropriate/ideal stage in disease progression. For more information visit parthenontx.com and LinkedIn.