Insilico Medicine Names ISM1745 as Preclinical Candidate for MTAP-Deleted Cancers
Biotech firm Insilico Medicine has announced the nomination of ISM1745, a potentially groundbreaking treatment for PRMT5 and MAT2A in MTAP/p16-Deleted Cancers”>MTAP-deleted cancers, as a preclinical candidate (PCC). This marks the fifth PCC nomination by the company in 2024 alone, bringing their total since 2021 to an impressive 22. ISM1745 is notable for its unique structure, designed using Insilico’s AI-powered Chemistry42 engine, and its potential as a best-in-class MTA cooperative PRMT5 inhibitor.
PRMT5, a protein involved in crucial cellular processes, is often overexpressed in various cancers and linked to poor prognoses. In cancers with MTAP deletion, a specific genetic alteration, the accumulation of methylthioadenosine (MTA) makes tumor cells notably vulnerable to PRMT5 inhibition, presenting a unique target for treatment.
MTAP deletion occurs in about 15% of human cancers, with even higher rates in patients who have become resistant to standard treatments. This highlights a critical need for new therapies. ISM1745S novel scaffold, powered by Chemistry42, allows for unique interaction with this specific target in MTAP-deleted cancers. We’re excited about the promising preclinical results and look forward to further evaluating ISM1745 as another successful Insilico AI-driven programme.
— Feng ren, PhD, Co-CEO and Chief Scientific Officer of Insilico Medicine
Insilico scientists leveraged a structure-based generation strategy, starting with molecule designs produced by Chemistry42. after rigorous AI-powered evaluation based on various factors, including pharmacophores, druglikeness, and developability, ISM1745 emerged as the leading candidate. Preclinical data reveals ISM1745’s robust effectiveness at low doses in several animal models, demonstrating promise both as a standalone treatment and in combination with chemotherapy, targeted therapies, and immunotherapies.
The compound also exhibits excellent selectivity for MTAP-deleted cells compared to normal cells,minimizes the risk of drug-drug interactions,and displays favorable metabolic and pharmacokinetic profiles.
Insilico CEO Dr. Alex Zhavoronkov emphasized the reproducibility of Insilico’s programs, highlighting the nomination of ISM1745 as further evidence of this. He also reiterated the company’s commitment to leveraging generative AI to accelerate drug discovery and progress, ultimately improving patients’ outcomes.
Insilico has been at the forefront of AI-driven drug discovery since 2016, when they first published on using generative AI for novel molecule design. Their Pharma.AI platform has since evolved into a comprehensive toolkit for biology, chemistry, medicine development, and scientific research. This commitment to innovation is reflected in Insilico’s impressive portfolio of over 30 assets and 10 molecules with IND clearance.
Recently, Insilico published a groundbreaking paper in Nature Biotechnology outlining the entire development journey of ISM001-055, the company’s lead drug candidate, from AI-powered target discovery and molecule design through to Phase II clinical trials. Initial results from aPhase IIa trial (NCT05938920) of ISM001-055 have been promising, showing favorable safety and tolerability across all dose levels, and also dose-dependent betterment in lung function (forced vital capacity or FVC) after just 12 weeks.
## Archyde Exclusive: Insilico Medicine on the Frontier of AI-Driven Drug Discovery
**Interviewer:** Welcome to Archyde, Dr. [Alex Reed Name], Chief Scientific Officer at Insilico Medicine. Thank you for joining us today.
**Dr. [Alex Reed Name]:** It’s a pleasure to be here.
**Interviewer:** Insilico Medicine has just announced a meaningful milestone – the nomination of ISM1745 as a preclinical candidate for MTAP-deleted cancers. This marks your fifth PCC nomination this year alone.Could you elaborate on the meaning of this achievement, both for Insilico and the broader field of oncology?
**Dr.[Alex Reed Name]:** We are incredibly excited about ISM1745. This is another demonstration of Insilico’s commitment to leveraging the power of artificial intelligence (AI) to accelerate drug discovery.MTAP-deleted cancers are a challenging subtype with limited treatment options. ISM1745, designed using our proprietary AI-powered Chemistry42 engine, shows promising potential as a best-in-class MTA cooperative PRMT5 inhibitor.
**Interviewer:** For our audience who may not be familiar with the specific science, could you explain what PRMT5 is and why it’s a relevant target in MTAP-deleted cancers?
**Dr. [Alex Reed Name]:** PRMT5 is a crucial protein involved in various cellular processes, including gene expression regulation. In MTAP-deleted cancers, PRMT5 activity is frequently enough upregulated, contributing to disease progression.By targeting PRMT5, we aim to disrupt thes processes and possibly stall or even reverse tumor growth.
**Interviewer:** What makes ISM1745 stand out from other potential PRMT5 inhibitors currently in advancement?
**Dr. [Alex Reed Name]:** ISM1745’s unique structure is a direct result of our AI-driven drug design process. Chemistry42 analyzes vast amounts of data to identify and predict optimal drug candidates with enhanced efficacy and safety profiles. This targeted approach allows us to develop compounds like ISM1745 that are potentially more effective and specific than customary drug discovery methods.
**Interviewer:** With this fifth PCC nomination in 2024, Insilico medicine is clearly on a rapid trajectory. What are the next steps in the development of ISM1745?
**Dr. [Alex Reed Name]:** We will now focus on preclinical studies to further evaluate ISM1745’s safety and efficacy. our goal is to gather robust data that will support the initiation of clinical trials in MTAP-deleted cancer patients.
**Interviewer:** Thank you, Dr. [Alex Reed Name],for providing insights into this innovative research. We at Archyde will be following Insilico Medicine’s progress with great interest.
**Dr. [Alex Reed Name]:** Thank you for having me.
## Archyde Exclusive: Insilico Medicine on teh Frontier of AI-Driven Drug Revelation
**Archyde:** Today, we are joined by Dr. Feng Ren, Co-CEO and Chief Scientific Officer of Insilico Medicine, a leading force in the field of AI-powered drug discovery. dr. Ren, thank you for your time.
**Dr. Ren:** Thank you for having me. It’s a pleasure to be here.
**archyde:** Insilico has recently made headlines with the nomination of ISM1745 as a preclinical candidate for MTAP-deleted cancers. Could you tell our readers more about this exciting development?
**Dr. Ren:** Absolutely! ISM1745 is a testament to our unique platform that leverages artificial intelligence to accelerate and optimize the drug discovery process. MTAP deletion is a specific genetic alteration found in approximately 15% of human cancers, making these tumors sensitive to PRMT5 inhibition. ISM1745 is designed to target this vulnerability, offering a potential new treatment option for patients with limited therapeutic choices.
**Archyde:** what makes ISM1745 stand out from other PRMT5 inhibitors?
**Dr. Ren:** ISM1745’s unique scaffold, generated by our AI platform Chemistry42, allows for specific interaction with MTAP-deleted cancer cells. Preclinical data has shown its efficacy at low doses, both as a standalone treatment and in combination with other therapies. Importantly, it demonstrates strong selectivity for cancer cells while minimizing risks associated with off-target effects.
**Archyde:** This marks the fifth preclinical candidate nomination for Insilico in 2024 alone. What drives this remarkable pace of progress?
**Dr. Ren:** Our success lies in the power of our AI platform, Pharma.AI. It allows us to rapidly analyze vast datasets, identify promising targets, and design novel drug candidates with unprecedented speed and accuracy.
**Archyde:** Insilico has consistently demonstrated the reproducibility of its AI-powered drug discovery program.How critical is this element for the advancement of the field?
**Dr.Ren:** Reproducibility is absolutely essential for building trust and credibility within the scientific community and the broader healthcare landscape.
Our commitment to this principle is reflected in our transparent research practices and the consistent nomination of promising drug candidates like ISM1745.
**Archyde:** Looking ahead, what are your aspirations for Insilico’s role in the future of healthcare?
**Dr. Ren:** We envision a future where AI-powered drug discovery becomes the norm, accelerating the development of life-saving treatments for a wide range of diseases. at Insilico,we are dedicated to pushing the boundaries of what’s possible,translating scientific breakthroughs into tangible benefits for patients worldwide.
**Archyde:** Dr. Ren, thank you again for sharing your insights with us. It’s clear that Insilico Medicine is at the forefront of a truly transformative approach to drug discovery.
**dr. Ren:** Thank you.We’re excited to see what the future holds and are committed to making a lasting impact on human health.
