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

咨询合作     药物筛选中心（暨南大学），隶属于暨南大学药学院公共科研平台。中心拥有Echo550微量液体超声转移工作站等先进的自动化药物筛选仪器，前期支撑的多个激酶抑制剂已经产业转化及发表JMC等高水平论文。目前，筛选中心建有激酶、蛋白酶、HDAC、COX、GPCR、报告基因、病毒、细菌等筛选模型，能够开展肿瘤、神经系统疾病、心脑血管病、糖尿病、病毒和细菌感染性疾病等领域相关靶标、细胞、机制的筛选和研究，每天能够完成数万次的新药筛选反应。已建立的药物筛选模型1）蛋白水平：激酶：Abl, ABL(M351T), ABL(H396P), ABL(Y253F), ABL1 (E255K), ABL1 (G250E), ABL(Q252H), AKT1, AKT2, AKT3, ALK, ALK5, AuroraA, AuroraB, AXL, BRAF, BRAF(V599E), BTK, DDR1, DDR2, EGFR, EGFR (T790M), EGFR(L858R), EGFR(L861Q), EGFR(T790ML858R), EGFR(D746-750), EGFR(D746-750/T790M), Flt3, FLT3(D835Y), FGFR1, FGFR2, FGFR3, FGFR4, Her2, Her4, KIT, MET, IGF-1R, FGFR1, JAK1, JAK2, JAK3, MAPK10, MAPK14, mTOR, TrkA, TrkB, TrkC,TYK2, KDR, SRC, PDGFRa, PDGFRA(D842V), PDGFRb, RET, ZAK。蛋白酶：MMP-1, MMP-2, MMP-3, MMP-9, MMP-13, MMP-14, ADAM5, ADAM10, ADAMTS13, TACE/ADAM17, Furin, Cathepsin E, Cathepsin D, BACE-1, DDP4, DDP8, DDP9, HIV protease-1, PMVII，PMVIV。HDACs：HDAC1, HDAC2, HDAC3, HDAC4, HDAC5, HDAC6, HDAC7, HDAC8, HDAC9, HDAC10, HDAC11, Sirt1, Sirt2, Sirt3, Sirt4, Sirt5, Sirt6。2）肿瘤细胞活性：近500种肿瘤细胞系；基于Ba/F3的耐药模型3）抗病毒/菌药物筛选：EV71和HSV病毒活性筛选模型；金黄色葡萄球菌、大肠杆菌和沙门氏杆菌等4）体内药效：移植瘤模型对外服务1）体外活性筛选（单剂量抑制率；多剂量IC50）；2）体内药效；3）机制研究；4）药代动力学研究；5）化合物工艺优化、大量订制。  咨询合作