DDR1

Researchers are exploiting a unique biological feature of glioblastoma to gain a better understanding of how this puzzling brain cancer develops and how to target new treatments against it. The team developed human and mouse models of glioblastoma oncostreams and examined multiple factors in the tumor microenvironment that could impact how oncostreams develop and how to reverse them. Researchers at the University of Michigan Health Rogel Cancer Center are exploiting a unique biological feature of glioblastoma to gain a better understanding of how this puzzling brain cancer develops and how to target new treatments against it. The team, led by senior author Pedro Lowenstein, M.D., Ph.D., Richard Schneider Collegiate Professor of Neurosurgery at Michigan Medicine, had previously identified oncostreams as a key feature in glioblastoma development and in more aggressive disease. These highly active, elongated, spindle-like cells move throughout tissue in complicated patterns. The accumulation of oncostreams found throughout a tumor serve as the basis for cancerous cells' behavior, determining how tumors grow and invade normal tissue. In this new study, published in Advanced Science, the team developed human and mouse models of glioblastoma oncostreams and examined multiple factors in the tumor microenvironment that could impact how oncostreams develop and how to reverse them. Utilizing this model, they also identified a potential inhibitor, DDR1-IN-1, which appears to dismantle oncostreams. Preliminary studies in a mouse model of glioma showed the DDR1 inhibitor led to better survival. This suggests a potential pathway for additional research. Glioblastoma is an aggressive cancer, with only a 5% survival rate beyond two years. In large part, it's because even when surgery is possible, it's often difficult to remove all the cancerous cells. Radiation and chemotherapy have limited effectiveness, and no other treatment options have been developed in decades. This work will hopefully lead to new clinical trials, like the phase I trial of dual vector gene therapy, supported in part by the Rogel Cancer Center, which was published recently in The Lancet Oncology. "This model has deepened our understanding of how glioblastoma cells grow and invade and has led to the identification of a potential new therapeutic target," said Syed M. Faisal, Ph.D., a postdoctoral fellow in Lowenstein's lab and the first author of the study. "Understanding the mechanism of how glioblastoma grows and migrates is essential to developing new and better treatments," Lowenstein said. "Our oncostream model will be a valuable tool for gaining new insights into how glioma invades. It will allow us to test potential new therapeutic strategies that undermine the cellular and molecular foundations of glioblastoma malignancy." Additional authors: Jarred E. Clewner, Brooklyn Stack, Maria L. Varela, Andrea Comba, Grace Abbud, Sebastien Motsch, Maria G. Castro Funding for this work is from National Institutes of Health grants: R37-NS094804, R01-NS105556, R01-NS122536, R01-NS124167, R01-NS122165, R21-NS123879-01, R01-NS076991, R01-NS096756, R01-NS082311, R01-NS122234, R01-NS127378, R01-EB022563, U01-CA224160, R01-CA243916; RNA Biomedicine; Rogel Cancer Center; Ian's Friends Foundation; Leah's Happy Hearts Foundation; Pediatric Brain Tumor Foundation; Smiles for Sophie Forever Foundation; ChadTough Foundation.

Accomplished biopharmaceutical executive with proven track record in drug development and fundraising to lead company through its next phase Phase 1b of PRTH-101 in combination with KEYTRUDA® in patients with advanced solid tumors underway CAMBRIDGE, Mass.--(BUSINESS WIRE)-- Incendia Therapeutics, a precision oncology company discovering and developing a novel class of therapies that reprogram the tumor microenvironment (TME), today announced the appointment of Wendye Robbins, M.D., as Chief Executive Officer. Dr. Robbins is a pharmaceutical executive with more than 20 years of experience pioneering drug discovery and leading the growth of companies at all stages of development. 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. “I am delighted to welcome Dr. Robbins to Incendia. Her extensive business acumen and strong record of success in progressing therapeutic candidates through regulatory approvals will be invaluable as we advance our pipeline of first-in-class TME-focused drug candidates including PRTH-101 now currently being evaluated in a Phase 1b clinical study,” said Michael Kauffman, M.D., Ph.D., Chairman of the Board. 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. “As the Phase 1a single agent study of PRTH-101 continues with early evidence of anti-tumor activity and good tolerability, we are pleased to initiate the Phase 1b trial of PRTH-101. Cancer patients suffering from immune excluded tumors remain in need of effective therapies,” said Wendye Robbins, M.D., President and Chief Executive Officer of Incendia. “I look forward to leading this talented team to further advance our portfolio of novel anti-cancer therapies that reprogram the tumor microenvironment.” Dr. Robbins is a seasoned biopharmaceutical leader with more than two decades of industry experience. Dr. Robbins has shepherded multiple small and large molecule therapeutics through development and has a track record of building nascent life sciences companies with investors. She has served as an independent director for RAPT Therapeutics (RAPT) since 2019. She has raised approximately $2 billion in capital across the many companies she has supported. Dr. Robbins received her B.S. from the Haas School of Business, University of California, Berkeley, followed by an M.D. from the Medical College of Pennsylvania. She completed a medical internship at the Hospital of the University of Pennsylvania and a residency in Anesthesiology and Critical Care Medicine and a Fellowship in Pain Medicine at the Johns Hopkins University School of Medicine. She is board certified in Anesthesiology. Dr. Robbins maintained a part time role as Associate Professor at Stanford University School of Medicine during her early years in biotechnology. About PRTH-101 PRTH-101 is a therapeutic antibody that allosterically modulates DDR1, a collagen binding protein and kinase that plays a secondary role in wound healing. Some tumor cells are believed to co-opt DDR1 – collagen binding to build an impenetrable barrier around the tumor. By disabling DDR1, PRTH-101 disrupts tumor associated collagen alignment thus allowing immune cells access to the tumor core. The Company’s preclinical research has demonstrated that PRTH-101 mediated DDR1 blockade may have have both single agent anti-tumor activity as well as marked augmentation of checkpoint inhibitor function. Tumor types that express high levels of DDR1-associated collagen barriers include colorectal, ovarian, glioma, 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 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. View source version on businesswire.com: Contacts Investor Contact Argot Partners 212-600-1902 incendia@argotpartners.com Source: Incendia Therapeutics View this news release online at:

CAMBRIDGE, Mass.--(BUSINESS WIRE)-- Incendia Therapeutics, a precision oncology company discovering and developing a novel class of therapies that reprogram the tumor microenvironment (TME), today announced that it will present three posters at the Society for Immunotherapy of Cancer (SITC) 38th Annual Meeting, to be held in San Diego, California November 1-5, 2023. “We look forward to presenting three posters at SITC which validate our approach to block Discoidin Domain Receptor 1 (DDR1) and advance our understanding of and ability to detect immune exclusion in solid tumors,” said Laura Dillon, PhD, VP, Translational Medicine & Bioinformatics at Incendia Therapeutics. “We are encouraged by the human tumor data in intrahepatic cholangiocarcinoma (iCCA), which demonstrate a correlation of high DDR1 expression with worse prognosis in all stages of disease. 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.” Presentation Details for SITC 2023 are as follows: Title: DDR1 expression is associated with a worse prognosis in intrahepatic cholangiocarcinoma Poster number: 1486 Presenter: Travis Clifton, MD, Co-founder, Head of Clinical Sciences Time: Saturday, November 4, 12:15-1:45 PM PDT and 5:30-7:00 PM PDT (3:15-4:45 PM EDT and 8:30-10 PM EDT) Location: Poster Hall (Exhibit Hall B) Title: The epithelium-stroma interface serves as a barrier to immune cell infiltration across tumor immune phenotypes in epithelial cancers Poster number: 1497 Presenter: Laura Dillon, Ph.D., VP, Translation Medicine & Bioinformatics Time: Friday, November 3, 12:15-1:45 PM PDT and 5:30-7:00 PM PDT (3:15-4:45 PM EDT and 8:30-10 PM EDT) Location: Poster Hall (Exhibit Hall B) Title: Comparison of multiplex immunofluorescence and H&E-based approaches for characterization of the tumor microenvironment Poster number: 1287 Presenter: Fredrick Gootkind, M.S., Senior Associate Scientist Time: Friday, November 3, 12:15-1:45 PM PDT and 5:30-7:00 PM PDT (3:15-4:45 PM EDT and 8:30-10 PM EDT) Location: Poster Hall (Exhibit Hall B) 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. The company’s lead program, PRTH-101, is a monoclonal antibody targeting Discoiding Domain Receptor 1 (DDR1). It seeks to break down collagen barriers in solid tumors to promote tumor killing by the immune system, therby overcoming recalcitrant tumors. PRTH-101 is currently being evaluated in Phase 1 clinical trials (NCT05753722). For more information visit incendia.com and LinkedIn.