DDR1

The financial details of its deal with Variational AI were left vague, but we do know that Rakovina Therapeutics will pay a “low upfront fee” to begin work on each selected target. Five months after Rakovina Therapeutics pivoted toward artificial intelligence, the cancer-focused biotech has joined forces with Variational AI to identify new therapies against DNA-damage response (DDR) targets.The plan is for Variational AI to use its Enki platform to identify novel inhibitors of specific DDR kinase targets selected by Rakovina before handing the Canadian biotech a short list of potential drug candidates. Rakovina will then use the following 12 to 18 months to synthesize and evaluate the viability of these candidates as potential cancer therapies in its laboratories at the University of British Columbia, the biotech explained in a Sept. 17 release.The financial details were left vague, but we do know that Rakovina will pay a “low upfront fee” to begin work on each selected target as well as an exercise fee if it wants to acquire the rights to any resulting drugs. Further milestone payments could also be on the table.Variational AI describes Enki as “the first commercially available foundation model for small molecules to enable biopharmaceutical companies to discover novel, potent, safe, and synthesizable lead compounds for a small fraction of the time and cost versus traditional chemistry approaches.” Merck & Co. became an early user of the platform at the start of the year. Rakovina’s own R&D work remains in preclinical stages, with the biotech's pipeline led by a pair of dual-function DDR inhibitors aimed at PARP-resistant cancers. In March, the Vancouver-based company announced a “strategic evolution” that involved gaining access to the Deep Docking AI platform developed by University of British Columbia professor Artem Cherkasov, Ph.D., to identify DDR targets.“This collaboration is an ideal addition to our already established Deep Docking AI partnership as it expands Rakovina Therapeutics’ pipeline beyond our current focus of developing next-generation PARP inhibitors,” Rakovina Executive Chairman Jeffrey Bacha said in today’s release.“Leveraging Variational AI’s expertise in kinases where it overlaps with our DDR interest will significantly increase partnering opportunities as ‘big pharma’ maintains a close interest on novel therapies against these targets,” Bacha added.

Phase 1c study of PRTH-101 alone or in combination with KEYTRUDA® in patients with advanced or metastatic solid tumors will inform optimal design of the Phase 2/3 study PRTH-101 demonstrated favorable safety profile in Phase 1a and 1b studies CAMBRIDGE, MA, USA I September 10, 2024 I Incendia 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 enrolled in the Phase 1c study of PRTH-101 for the treatment of patients with advanced or metastatic solid tumors. “In our Phase 1a and 1b studies, we were able to select an optimal dose and identify potential biomarkers to carry forward” said Irena Webster, SVP Development and Operations of Incendia. “The data from this study will inform the design of the Phase 2/3 program, for which planning and global feasibility are currently underway.” Dr. Joseph Paul Eder, CMO, added “Incendia, with its outstanding team of investigators and investigative sites, has determined a recommended Phase 2 dose of PRTH 101. PRTH 101 has shown consistent safety as a single agent and in combination with pembrolizumab. We will now focus on tumor types that have demonstrated signs of clinical activity and patient benefits.” 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). About PRTH-101 PRTH-101 is a therapeutic antibody that targets DDR1, a collagen binding protein and kinase present on epithelial cells. Some tumor cells are believed to co-opt DDR1 – collagen binding to build an impenetrable barrier around the tumor. By allosterically disabling DDR1, PRTH-101 disrupts tumor associated collagen alignment to permit immune cell access into the tumor core. In preclinical experiments, PRTH-101 mediated DDR1 blockade has demonstrated 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 thymic, colorectal, pancreatic, 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 profile of 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 experimental therapeutics that reprogram the tumor microenvironment (TME). Incendia’s platform is based on rigorous, groundbreaking research involving spatial characterization of the tumor microenvironment, multi-omics data integration, and extensive preclinical testing. The Company’s most advanced experimental molecule, PRTH-101, is in a Phase 1c clinical trial for the treatment of patients with advanced solid tumors. For more information visit incendia.com and LinkedIn . SOURCE: Incendia Therapeutics

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 have three poster presentations at the American Association for Cancer Research (AACR) Annual Meeting 2024, taking place April 5-10, 2024 in San Diego, California. “We look forward to presenting these posters at AACR, which highlight our work to characterize immune exclusion in the TME,” said Laura Dillon, PhD, Vice President of Translational Medicine & Bioinformatics at Incendia Therapeutics. “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. Additionally, they demonstrate the power of applying H&E-based biomarkers, driven by machine learning, to better interrogate the TME. We look forward to further exploring the potential of this technology, combined with our novel class of anti-cancer therapies, to better treat cancer patients by targeting the tumor microenvironment.” Presentation details for AACR 2024 are as follows: Title: Discoidin Domain Receptor 1 (DDR1) expression is associated with degree of immune exclusion across epithelial tumors Abstract Number: 2916 / 24 Presenting Author: Laura Dillon, Ph.D., Vice President of Translational Medicine & Bioinformatics at Incendia Therapeutics Session: The Tumor Microenvironment as a Drug Target Date and Time: Monday, April 8 from 1:30 - 5:00 PM PDT (4:30 – 8:00 PM EDT) Key Highlights: 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). This work provides additional insight into the role of DDR1 in human cancers and has utility for selecting indications and stratifying patients for DDR1-targeted therapies. Title: Machine learning-based identification of H&E-derived morphologic features associated with CD8+ T cell immune exclusion Abstract Number: 7392 / 20 Presenting Author: Yanchao Wang, Ph.D., Data Scientist at Incendia Therapeutics Session: Artificial Intelligence and Machine/Deep Learning 4 Date and Time: Wednesday, April 10 from 9:00 AM - 12:30 PM PDT (12:00 PM – 3:30 PM EDT) Key Highlights: Morphologic features derived from H&E images can be effective predictors of CD8-defined immune exclusion, providing an option for patient stratification by immune phenotype using widely available H&E images. We developed an Ens-L1-SVM model that identified 6 H&E features predictive of CD8-defined immune phenotypes. CD8-based immune phenotypes were classified by the Ens-L1-SVM model with an estimated accuracy of 97% using only the H&E-based features as input. Details on Incendia’s poster which is a collaboration with Alpenglow Biosciences: Title: 3D spatial quantification of lymphocyte infiltration and collagen features in the tumor microenvironment using a novel assay: 3D I/O Pro™ Abstract Number: 2309 / 20 Presenting Author: Bonnie Phillips, Ph.D., Director, Commercial Development at Alpenglow Biosciences Session: Liquid Biopsy and Precision Oncology Date and Time: Monday, April 8 from 9:00 AM - 12:30 PM PDT (12:00 PM – 3:30 PM EDT) Key Highlights: An end-to-end 3D spatial biology workflow, Alpenglow’s 3D I/O Pro™, was applied to colorectal cancer (CRC) tissues stained with nuclear and general protein fluorescent dyes to quantify lymphocyte density in tumor parenchyma and stroma and analyze collagen features, including orientation, within 3D regions of interest in the TME. The ratio of stromal to parenchymal lymphocytes (lymphocyte infiltration ratio) varied from 1.4 up to 9.1 in 3D volumes and 1 to 25 in 2D virtual sections taken throughout all 5 CRC samples. Qualitatively, areas with perpendicular collagen had more lymphocyte infiltration into the tumor parenchyma than areas with parallel collagen orientation. This work highlights how the 3D I/O Pro™ workflow can characterize tumors based on complex spatial relationships within the tumor microenvironment, and could have broad applicability in research and development of novel cancer therapies that target tumor fibrosis or other features of the TME. About Incendia Therapeutics Incendia Therapeutics is discovering and developing a novel class of experimental therapeutics that reprogram the tumor microenvironment (TME). Incendia’s platform is based on rigorous, groundbreaking research involving spatial characterization of the tumor microenvironment, multi-omics data integration, and extensive preclinical testing. The Company’s most advanced experimental molecule, PRTH-101, is in a Phase 1 clinical trial for the treatment of patients with advanced solid tumors. For more information visit incendia.com and LinkedIn.