Digest 8/6/23
Surveying great inventors and businesses
Axial: https://linktr.ee/axialxyz
Axial partners with great founders and inventors. We invest in early-stage life sciences companies such as Appia Bio, Seranova Bio, Delix Therapeutics, Simcha Therapeutics, among others often when they are no more than an idea. We are fanatical about helping the rare inventor who is compelled to build their own enduring business. If you or someone you know has a great idea or company in life sciences, Axial would be excited to get to know you and possibly invest in your vision and company . We are excited to be in business with you - email us at info@axialvc.com
Genomics for target identification. Proteomics for target validation.
Until a dataset comparing protein expression/proteoforms in disease across enough people, using proteomics for drug development might be more impactful to selling the proteomics tool itself. Measuring the central dogma as you go down to proteins becomes increasingly complex. Measuring a static genome is more tractable than measuring a dynamic proteome across many diseases/patients.
Chemical proteomics powered by ABPP/affinity-based assays is offering new mechanistic insights for validated genetic targets. Mapping potential drug binding sites & estimating relative binding affinities across the proteome. For example, activity-based protein profiling (ABPP) relies on electrophilic probes to target a specific protein site and measure activity as well as figuring out MoAs for drug candidates.
As mass spec improves and new probes as developed, proteomics is building more accurate maps of drug-target interactions. Reducing potential off-target effects, providing drug targets currently inaccessible due to their large size/sub-cellular localization, and confirming a supposed mechanism-of-action.
Comprehensive Mapping of Electrophilic Small Molecule-Protein Interactions in Human Cells from the Cravatt lab https://chemrxiv.org/engage/chemrxiv/article-details/64788e6ebe16ad5c5748dcec
Expansion Therapeutics:
- Founded in 2016 to develop small molecules targeting RNA
- ID'ing druggable RNA structures
- Building a pipeline to treat myotonic dystrophy type 1 (targeting splicing), ALS & FTD (translation), and tauopathies
Orforglipron
A non-peptide GLP-1R agonist in Phase III clinical trials for obesity & type 2 diabetes
Identified through high-throughput screening, with origins from Chugai and now developed Eli Lilly
https://www.nejm.org/doi/full/10.1056/NEJMoa2302392
Scientist Stories: Walter Gilbert, Reminisces of Genomics
"By asking a novel question that you don't know the answer to, you discover whether you can formulate a way of finding the answer, and you stretch your own mind, and very often you learn something new."
- Walter Gilbert, Nobel Prize winner for inventing DNA sequencing
