FoRx Therapeutics’ Post

GenFleet gets China NMPA nod to start phase I/II trial of GFH375 to treat advanced solid tumour with KRAS G12D mutation

We highly recommend this new excellent ADC review paper published in Nature Reviews Clinical Oncology. The authors of this paper highlight advances in each ADC component (the monoclonal antibody, payload, linker and conjugation chemistry) and provide more-detailed discussions on selected examples of emerging novel ADCs of each format, enabled by engineering of one or more of these components. Several emerging ADC formats exist, including bispecific ADCs, conditionally active ADCs (also known as probody–drug conjugates), immune-stimulating ADCs, protein-degrader ADCs and dual-drug ADCs, and each offers unique capabilities for tackling these various challenges. Probody–drug conjugates are expected to have improved tumour specificity, whereas bispecific ADCs and dual-drug ADCs have the potential to combat drug resistance and tumour heterogeneity. Integrating immune-stimulating ADCs and protein-degrader ADCs with current treatment regimens might enable multimodal treatment, potentially through several distinct mechanisms of action. The first and corresponding author is Dr./Prof. Kyoji Tsuchikama at The University of Texas Health Science Center at Houston (UTHealth Houston). He was also an invited speaker of our Society’s 2021 mAbTalk Symposium with the theme of “New Horizon of Antibody Drug Conjugate (ADC)”. By the way, our society’s official journal, Antibody Therapeutics (2022 CiteScore: 6.4) calls for papers regarding “Antibody-Drug Conjugates for Cancer Treatment”. You are welcome to submit your ADC manuscripts to our journal. You may know more detailed information from the link below to the website of call for papers announcement. The deadline for submitting manuscripts for this ADC focused collection will be extended to August 31, 2024. https://lnkd.in/eU87q8zn   #antibodies #antibody #antibodytherapeutics #mabs #mab #antibodydiscovery #adc #adcs #antibodydrugconjugates

This ADC review article looks so interesting to me.

Very excited to announce that the last first-author paper from my Ph.D. training is published (total 9 publications from my Ph.D. training)! For this study, we applied a computational drug repurposing approach to identify candidates for four low-survival cancers. Our results were enriched for drug candidates that had been used in clinical trials or performed well in the PRISM drug screen. Additionally, we found that pamidronate and nimodipine, drugs predicted to be efficacious against the brain tumor glioblastoma (GBM), inhibited the growth of GBM cell lines and cells isolated from a patient-derived xenograft (PDX). https://lnkd.in/ezBPC8Mi

Exciting 𝐜𝐥𝐢𝐧𝐢𝐜𝐚𝐥 𝐭𝐫𝐢𝐚𝐥 𝐧𝐞𝐰𝐬 from Incendia Therapeutics! The Breakout Ventures portfolio company has initiated the Phase Ic trial of their groundbreaking DDR1 inhibitor to target metastatic solid tumors. 𝐍𝐞𝐰𝐬 𝐚𝐭 𝐚 𝐠𝐥𝐚𝐧𝐜𝐞: 🔬 Incendia Therapeutics' PRTH-101 targets collagen-binding protein DDR1 to disrupt tumor collagen alignment, allowing immune cell access into the tumor core. 🧫 High DDR1-associated collagen barriers are present in cancers like thymic, colorectal, pancreatic, ovarian, non-small cell lung cancer, and glioma. 💊 The trial will enroll up to 270 patients to evaluate the safety, tolerability, dosing, and anti-tumor activity of PRTH-101, which will be tested as a monotherapy and in combination with Merck's Keytruda. Keep an eye out for future updates - this study paves the way for future Phase II/III trials, with global feasibility already underway. 𝐑𝐞𝐚𝐝 𝐭𝐡𝐞 𝐟𝐮𝐥𝐥 Precision Medicine Online 𝐚𝐫𝐭𝐢𝐜𝐥𝐞: https://lnkd.in/d4Z5MG_D 𝐑𝐞𝐚𝐝 Incendia Therapeutics' 𝐫𝐞𝐥𝐞𝐚𝐬𝐞: https://lnkd.in/dFZ3wBMi

In oncology, systemic drug delivery methods often fall short to deliver to the target site, especially in difficult-to-access tumors such as pancreatic, biliary, brain, lung, or bladder cancer. Learn how the emergence of trans-arterial micro-perfusion (#TAMP) has enabled a new era of precision medicine, with significant advantages in the management of challenging malignancies. https://lnkd.in/e_TYNmtG By Shaun R. Bagai, CEO, RenovoRx Inc.

MediLink Therapeutics and Roche have formed a global collaboration to develop YL211, an innovative #antibody-drug conjugate targeting #solidtumors. The agreement grants Roche exclusive rights for #YL211's development and commercialization, potentially worth nearly $1 billion. YL211 is a cutting-edge ADC specifically targeting c-Mesenchymal epithelial transition factor (c-Met), a key player in #tumor growth and #metastasis. It represents a new hope in addressing the significant unmet medical needs of #cancer patients.  https://lnkd.in/dTnGdZ4s

Cytokine therapy in oncology is coming of age. Interleukin-12 (IL-12), a cell signaling molecule that helps the immune system identify and respond to threats, has been tried before but caused unacceptable toxicity. Xilio developed a "stealth" IL-12 molecule, where, rather than activating immune responses all over the body, IL-12 is activated by the tumor microenvironment and thus only actives signaling within tumors. Early data from their phase 1 trial (n=9 patients) did not reach a dose-limiting toxicity, even at almost 100x the dose-limit of unmodified recombinant IL-12. I'm looking forward to more advances in targeted cytokine therapies from Xilio Therapeutics, Inc. and others. Excellent work! #oncology #cytokines #cancer #immuneSystem #CytokineTherapy https://buff.ly/48w0WDy +++ 👋 I’m Chris, a passionate medical writer, strategist, and founder of Quill Science LLC dedicated to bridging the gap between science and its impact with accurate and compelling narratives. 🌐 For a scientific partner led by curiosity and desire to improve health, please check out Quill Science and book a discovery call: https://buff.ly/3TNRiY5

MRTX1133：A First-in-class KRAS-G12D inhibitor Author: Miao Xu Reviewer & Editor: Lisha Wang [Full article]:https://lnkd.in/dNtfp2vu MRTX1133 is an orally available small-molecule inhibitor of KRASG12D, currently in early clinical development at Mirati Therapeutics for treating patients with advanced solid tumors harboring a KRAS G12D mutation, including non-small cell lung cancer (NSCLC), colorectal cancer (CRC), and pancreatic adenocarcinoma. Preclinical studies demonstrated that the compound binds to the KRASG12D protein in both its active and inactive states, while showing no affinity for KRAS wild-type tumor cells. Mirati Therapeutics used their G12C inhibitor, Adagrasib, as a starting point, retaining the core structure while optimizing each component through extensive structure-based drug design. After numerous rounds of optimization, they ultimately obtained MRTX1133 with a million-fold increase in activity. Based on the research work published in J. Med. Chem. from Mirati Therapeutics, this article presents and analyzes the optimization process of MRTX1133, highlighting the key factors that contributed to the significant enhancement in its activity. [Full article]:https://lnkd.in/dNtfp2vu product.pharmablock.com PharmaBlock Group; PharmaBlock (USA), Inc.

Congratulations to PharmAbcine Inc.! The company announced the initiation of patient dosing in the Phase 1a/b clinical trial of PMC-309 in patients with advanced or metastatic solid tumors. PMC-309 is an IgG1 monoclonal antibody with specific binding to VISTA in immunosuppressive cells, exhibiting excellent binding affinity at various pH conditions within the tumor microenvironment. By inhibiting VISTA, PMC-309 presents a differentiated mechanism of action contributing to anti-cancer effects through activation of T cells, activation of monocytes, and proliferation of M1 macrophages. #mabs https://lnkd.in/ePqzTH7u