Today at General Catalyst, we are excited to announce our investment in Parabilis Medicines' (fka FogPharma) $145M Series E funding round. Approximately 85% of the human proteome is undruggable, posing a significant barrier to therapeutic innovation.1 Parabilis Medicines is paving the way to universal druggability with its novel precision medicine platform, HeliconTM, which unlocks previously undruggable targets in cancer. We believe Parabilis Medicines' novel technology holds considerable promise for cancer patients underserved by traditional approaches.
The phrase to “drug the undruggable,'' coined by Dr. Verdine, has inspired a renaissance of oncology discovery, and brought together the co-founders of Parabilis Medicines, Greg Verdine, WeiQing Zhou, Sir David Lane, and Dr. John McGee.
With the company’s TCF-blocking β-catenin inhibitor in clinical development, Dr. Mathai Mammen, President, CEO, and chairman is leading Parabilis Medicines' team of scientists, clinicians, and company builders in developing a potential therapy for cancer patients whose disease results from activation of the Wnt/β-catenin pathway.
Accessing Challenging Intracellular Targets with HeliconTM Therapeutics
HeliconTM are hyperstabilized ɑ-helical polypeptide therapeutics that are cell permeable, have broad tissue distribution, are highly specific, and have broad target accessibility. By combining these key traits of small molecules and antibody drugs, we believe HeliconTM therapeutics have the potential to enable access to challenging intracellular targets.
Parabilis Medicines' lead HeliconTM therapeutics, FOG-001, is a first-in-class direct TCF-blocking β-catenin inhibitor. Dysregulated Wnt/β-catenin pathway signaling is correlated with the development of many types of cancers.2 FOG-001 is differentiated from previously described Wnt pathway modulators because it directly binds β-catenin and inhibits the canonical Wnt pathway at the most downstream node, thus abrogating the signaling pathway by which most, if not all, Wnt pathway mutations drive oncogenesis.
Advancing Novel Cancer Therapies through Universal Druggability
With this funding, Parabilis Medicines aims to support further FOG-001 studies and advance its pipeline of novel HeliconTM therapeutics. The General Catalyst Health Assurances thesis is strongly aligned with Parabilis Medicines' mission to provide potentially life-improving therapies that target previously inaccessible drivers of disease, and we are grateful to have the opportunity to partner with Parabilis Medicines.
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1. Pathmanathan, S., Grozavu, I., Lyakisheva, A., & Stagljar, I. (2022). Drugging the undruggable proteins in cancer: A Systems Biology Approach. Current Opinion in Chemical Biology, 66, 102079.https://doi.org/10.1016/j.cbpa.2021.07.004.
2. Patel, S., Alam, A., Pant, R., & Chattopadhyay, S. (2019). Wnt Signaling and Its Significance Within the Tumor Microenvironment: Novel Therapeutic Insights. Frontiers Immunology, 10. https://doi.org/10.3389/fimmu.2019.02872.
