Peng Li’s Post

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.

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

GSK and iTeos Therapeutics revealed data Saturday from the Phase II GALAXIES Lung-201 platform Phase II study, showing that Jemperli and the investigational anti-TIGIT therapy belrestotug elicited promising response rates in patients with non-small cell lung cancer. After at least 5.6 months of follow-up, the combination treatment resulted in a confirmed objective response rate of approximately 60% for every dose. In iTeos’ news release of the data drop, the partners called this effect a “clinically meaningful improvement,” noting that it represented an increase of around 30% versus Jemperli (dostarlimab) alone. These data were presented at ESMO 2024. #biotech #biopharma #pharma #NSCLC #TIGIT

This ADC review article looks so interesting to me.

eFFECTOR Therapeutics, Inc. said it will halt development of tomivosertib in #lungcancer after the MNK inhibitor failed to significantly improve survival. https://lnkd.in/d3cMqd4y #biotechnology #cancer #clinicalresearch #clinicaltrials #drugdevelopment #oncology #pharmaceuticals

Mythic Therapeutics, Inc. announced promising initial results from the Phase 1 KisMET-01 study of MYTX-011, a novel cMET-targeting ADC, in treating advanced or metastatic non-small cell lung cancer (NSCLC). The study, presented at the ASCO Annual Meeting, showed MYTX-011 was well-tolerated with no dose-limiting toxicity and demonstrated nearly dose-proportional pharmacokinetics. The study continues to assess safety, tolerability, and preliminary anti-tumor activity, with further efficacy data to be presented in the future. The findings offer hope for patients with diverse cMET expression levels. #HemiBio Brian Fiske https://lnkd.in/epvx2gPC

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

What are some potential advantages of using Peptide Drug Conjugates in cancer therapy? Peptide Drug Conjugates offer several potential advantages in cancer therapy. These include: 1. Selectivity: Peptide Drug Conjugates can selectively target cancer cells or tumors, minimizing on-target off-tumor effects. 2. Modification of chemotherapeutic agents: Conjugating traditional chemotherapeutics to a peptide can modify the chemical properties of the cytotoxic agent, such as solubility, selectivity, and half-life, potentially improving the efficacy of standard therapies. 3. Versatility: #Peptide conjugation can be used on many molecules to create novel PDCs, and the conjugation of peptides with established chemotherapeutic molecules may improve the efficacy of standard therapies. 4. Biochemical stability: PDCs utilize a smaller molecular composition than other marketed anticancer drugs, contributing to PDC biochemical stability, cell membrane penetration, and overall efficacy. 5. Targeted organ delivery: Directed targeting of specific organs has been considered a crucial step in limiting side effects associated with traditional anticancer therapy. Overall, Peptide Drug Conjugates offer a more straightforward design, a high degree of selectivity, a broad range of targets, and a wide range of chemical and biological diversity compared to other cancer therapy strategies. However, there are several limitations to their implementation, and further research is needed to optimize their delivery and improve their systemic stability. #Cancer #Peptides #drugs #Oncology

Colorectal Cancer Pipeline Overview 2024: FDA Approvals and Key Companies involved by DelveInsight | Novartis, Pharma Oncology, Purple Biotech Ltd, Plus Therapeutics, Processa Pharma: (Las Vegas, Nevada, United States) As per DelveInsight’s assessment, globally, Colorectal Cancer pipeline constitutes 195+ key companies continuously working towards developing 200+ Colorectal Cancer treatment therapies, analysis of Clinical Trials, Therapies, Mechanism of Action, Route of Administration, and Developments analyzes … Continue reading → #Business #HealthMedicine #MarketingSales #ProfessionalServices

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