- AXL and BRD4 are highly biologically relevant oncogenic and epigenetic targets, respectively, implicated in numerous indications including both hematological and solid malignancies, but have historically been very challenging to drug.
- Model Medicine's Galileo™ Platform has discovered multiple chemotypes novel to AXL and BRD4 that demonstrate nanomolar or low micromolar activity in in vitro validation studies.
- Guided by indication-specific Target Product Profiles, the company plans to rapidly move the most promising compounds to preclinical proof-of-concept.
Model Medicines, a pharmatech company working to transform the drug discovery and development industry using artificial intelligence (AI), today announced the launch of its oncology programs. The programs are focused on the discovery and development of therapeutics against two oncogenic and epigenetic targets – AXL and BRD4 – with applications in numerous indications, including both hematological and solid malignancies. The Company reported the discovery of several chemotypes that display nanomolar or low micromolar activity against AXL and BRD4, and which represent entirely new pharmacophores for these targets. This announcement follows the company's Q2 2022 announcement that its AI-discovered lead compound, MDL-001, developed in collaboration with world-renowned researchers at Scripps Research and the Icahn School of Medicine at Mount Sinai, demonstrated preclinical proof-of-concept and best-in-class characteristics as a potential broad spectrum infectious disease therapeutic.
The AXL signaling pathway has been demonstrated to drive cancer cell survival, proliferation, migration, and invasion. BRD4 inhibition is known to repress the expression of multiple oncogenes in both hematological and solid malignancies. Together, AXL and BRD4 are two of the highest potential oncology targets under active research by the pharmaceutical industry due to their association with numerous indications, many with high unmet medical need. However, a small molecule therapeutic specific to BRD4 or AXL has yet to be approved by the FDA. Thus, it is clear that new approaches to AXL and BRD4 small molecule drug development are required.
Model Medicines' discovery of multiple new chemotypes with activity against these high value targets represents a significant breakthrough. The rapid discovery of these therapeutic candidates was enabled by the Company's Galileo™ Drug Discovery Platform. Bastiaan Bergman, PhD, Vice President of Engineering at Model Medicines, noted, "The Company's AI-Drug Discovery Platform has now established a track record of better, faster, cheaper, and repeatable drug discovery – identifying drugs with novel activity against numerous targets validated in indications ranging from oncology to infectious disease to gut dysmotility. In the case of oncology, the lack of historical success in developing drugs against AXL and BRD4 necessitated a new approach. In a matter of weeks, we were able to leverage our platform to move from target selection, to in silico discovery, to in vitro validation of multiple hits with drug-like properties – demonstrating the platform's potential to make novel discoveries in a timeframe and at a cost previously unimaginable in the industry."
"Model Medicines was launched with the goal of building a technology-driven pharmaceutical company that would transform pharmacoeconomic models of drug development and discover best-in-class therapeutics against the most difficult to drug targets and most difficult to treat diseases. The rapid discovery of multiple compounds with novel activity against two high value oncology targets, combined with the previously reported potential of MDL-001 to improve treatment options across a wide variety of infectious diseases demonstrates the platform's and team's ability to work across broad areas of biology and human disease. We are looking forward to combining our uniquely innovative approach to drugging critical oncology targets with the world's best translational scientists and drug developers in the search for more effective cancer treatments." remarked Daniel J. Haders II, PhD, Co-Founder and CEO of Model Medicines.