AI-powered drug discovery: update (VI) 📁
Companies with assets in preclinical and clinical trials: A2A, Quiver, BigHat, Helix, Resonant, Metis, GV20, Soley, Deargen, Interprotein, Hotspot and SOM Biotech
For the previous newsletters of this series of updates specifically on AI drug discovery in preclinical and clinical trials 👉
Index for “AI-powered drug discovery: update part VI” 🗂️
A2A Pharmaceuticals
Q-State Biosciences acquired by Exponential Capital Management and rebranded to Quiver Bioscience
BigHat Biosciences
Helix Nanotechnologies
Resonant Therapeutics
Metis Pharmaceuticals
GV20 Therapeutics
Soley Therapeutics
Deargen
Interprotein Corporation
Hotspot Therapeutics
SOM Biotech
🔲 A2A Pharmaceuticals Inc
A2A Pharmaceuticals (2016) designs computationally optimized small molecule therapeutics for the treatment of cancer and antibiotic resistant bacterial infections. Their proprietary SCULPT platform allows systematic combinatorial unification of chemical groups into libraries against a pharmacological target. The SCULPT process builds and evaluates small molecule libraries that consist of thousands to millions of members (up to 100,000,000 molecules/target). Iterations are performed until candidates with optimal properties (potency and optimal ADMET properties) and matches to target features are obtained.
Their oncology programs (A2A04 target TACC3, TYK2 target A2A-01, YAP-TEAD target A2A-02, KRAS-degrader target A2A-03) are focused on inhibiting essential protein-protein interactions (PPIs) in leukemia and in diverse solid tumors. These interactions are critical for cancer progression, but non-essential in normal cells. The antibiotic programs (MLL-Menin target BMF-219/ in collaboration with Biomea Fusion, undisclosed/ in collaboration with Daewoong Pharmaceutical, KRX: 069620) target biosynthetic enzymes in gram-negative bacteria, in pathways not found in humans. The targets selected have no clinically used therapeutics, minimizing susceptibility to resistance; unlike the numerous follow-on antibiotics currently in development.
On January 13, 2021, A2A co-founded Biomea Fusion raised $56M. The syndicate was led by Cormorant Asset Management with participation from Boxer Capital of Tavistock Group, Janus Henderson Investors, Rock Springs Capital, RTW Investments, LP, Aisling Capital, Point Sur Investors, Logos Capital and Clifton Capital.
Biomea Fusion, Inc (BMEA) (2017, a spin-off company of A2A Pharmaceuticals) is a precision oncology company dedicated to developing innovative medicines targeting genomically defined alterations in both hematologic and solid cancers.
Their proprietary FUSION System platform is used to advance a pipeline of novel covalent therapies. Their lead product candidate, BMF-219 (in collaboration with A2A), is an orally bioavailable, potent and selective covalent inhibitor of MENIN (Menin: a scaffold protein that controls gene expression and cell signaling), an important transcriptional regulator known to play a direct role in oncogenic signaling in multiple cancers.
Regarding BMF-219, they are involved in the following clinical trials
COVALENT-111: a phase 1/2 clinical trial in healthy adults and adults with Type 2 diabetes.
COVALENT-112: A Phase 2 clinical trial for adults with stage 3 Type 1 Diabetes.
COVALENT-101: A phase 1 clinical trial for patients with relapsed or refractory AML, ALL, DLBCL, MM or CLL/SLL.
COVALENT-102: A phase 1/1b clinical trial for patients with KRAS mutant, unresectable, locally advanced/metastatic NSCLC, PDAC, and CRC.
Regarding BMF-500, a highly potent and selective, covalent, small molecule inhibitor of FLT3, that binds irreversibly to a reactive cysteine in the kinase active site, they are involved in the following clinical trial
COVALENT-103: A Phase 1 clinical trial for adults with FLT3 mutant Acute Leukemia.
Lately some analysts are wondering:
Finally, in May 2023, FDA cleared IND application for AI-discovered TACC3 PPI inhibitor in women’s cancer. The TACC3 PPI inhibitor, A2A-252, from A2A Pharma, is an investigational TACC3 protein-protein interaction inhibitor. The planned phase 1 trial for the drug candidate will recruit adults with high-grade ovarian, triple negative breast and endometrial cancers.
Sotirios Stergiopoulos MD, Edward Painter, Sridhar Vempati Ph. D, and Matthew Welsch Ph. D are the founders of A2A Pharmaceuticals.
🔳 Q-State Biosciences Inc acquired by Exponential Capital Management and rebranded to Quiver Bioscience
On July 5, 2023, Q-State Biosciences (2013, US) was acquired by Exponential Capital Management and rebranded to Quiver Bioscience as part of the company's continued evolution. Quiver utilizes scalable human disease models, novel AI and a best-in-world platform to drive therapeutic discovery with the mission of creating transformational medicines for patients living with disorders of the brain. The Quiver platform has been built and validated and is now poised to deliver the best possible medicines in areas of critical need such as chronic pain, neurodevelopmental disorders and neurodegeneration.
At Quiver they are using advanced single cell imaging and multi-omics, to build the world's most information-rich neuronal insight map "Genomic Positioning System" through proprietary engineering and AI/ML approaches. Their approach integrates cutting-edge scalable biology, state-of-the-art technology and engineering, and learning and surrogate models to identify novel therapeutic targets and the best candidate molecules to deliver new and meaningful therapeutics to patients.
In their pipeline you can find drug candidates for:
Seizure and Neurodevelopmental Disorders:
Dup15q Syndrome - UBE3A (ASO)/ Preclinical.
DEE13 - SCN8A (ASO)/ Discovery.
DEE4 - STXBP1 (ASO)/ Discovery.
SYNGAP (ASO)/ Discovery.
Tuberous Sclerosis Complex - TSC2 (Small Molecule)/ Discovery.
Fragile X Syndrome – FXS (Small Molecule / ASO)/ Discovery.
Chronic Pain Disorders
Nav1.7 (ASO)/ Preclinical. Nav1.7 is a genetically validated pain target outside of the opiate signaling pathway. Candidate ASOs are currently being considered for intractable cancer pain, small fiber neuropathy and moderate-to-severe lumbosacral radiculopathy.
Nav1.8 (ASO)/ Preclinical. Nav1.8 is a genetically validated pain target outside of the opiate signaling pathway. Candidate ASOs are currently being considered for intractable cancer pain, small fiber neuropathy, and moderate-to-severe lumbosacral radiculopathy.
Dual Nav1.7 / 1.8 (ASO)/ Discovery. Nav1.7 and Nav1.8 are genetically validated pain targets outside of the opiate signaling pathway. Candidate ASOs are currently being considered for intractable cancer pain, small fiber neuropathy, and moderate-to-severe lumbosacral radiculopathy.
Nav1.7 (Small Molecule)/ Discovery. Nav1.7 is a genetically validated pain target outside of the opiate signaling pathway. Candidate small molecules are currently being considered for osteoarthritis.
Moreover, they have collaborations with
QurAlis for an ALS Target (Small Molecule/ASO)/ Clinical.
At QurAlis they are focused on patients who have loss of STATHMIN-2 (STMN2), and patients who have a loss of Kv7, as well as patients with TDP-43 gain-of-function toxicity and autophagy impairment. Their lead therapeutic product candidates are:
QRL-201: a first-in-class molecule for the treatment of ALS that aims to restore STMN2 expression in ALS patients. And
QRL-101: a first-in-class Kv7 opener for the treatment of ALS that aims to reduce hyperexcitability-induced neurodegeneration.
On March 4, 2024, QurAlis announced preclinical data that showed the company's UNC13A splice-switching ASOs modulate UNC13A splicing and restore normal synaptic activities in ALS and FTD. QurAlis' ASOs prevented cryptic exon inclusion in UNC13A transcripts, increased UNC13A protein levels, and normalized localization of UNC13A protein at the synapse.
Vanqua Bio for a Parkinson's Disease Target (ASO)/Candidate ID.
Founded in 2019, Vanqua Bio is focused on discovering and developing next-generation medicines for neurodegenerative diseases, combining advanced insights into critical neuronal cell pathways with cutting-edge assays to advance needed therapies. Their lead program targets glucocerebrosidase (GCase) as a potential treatment for Parkinson’s disease and Dementia with Lewy Bodies. Additional programs address overactivation of the innate immune system in central and peripheral disorders, including Alzheimer’s disease.
On April 09, 2024, Vanqua Bio Announced First Patient Dosed in Phase 1 Clinical Trial Evaluating VQ-101, its Small Molecule GCase Activator for GBA-Parkinson’s Disease and Related Disorders.
On July 12, 2024, Biotech startup Vanqua Bio secured new funding.
Quiver also has partnerships with VERTEX, Takeda, GSK, UCB, Merck, Amgen, Bristol Myers Squibb, NIH, The Rett Syndrome Research Trust and The Silverstein Foundation.
◼️ BigHat Biosciences Inc
BigHat’s (2019, US) mission is to improve human health by making it far easier to design advanced, next-generation antibody therapeutics with their AI-enabled experimental platform (the Milliner™ platform), that integrates a high-speed characterization or “wet” lab with ML technologies to speed the antibody engineering process. When applied, these design capabilities have the potential to drive the development of new generations of safer and more effective treatments for patients suffering from today’s most challenging diseases.
They have an advanced pipeline of therapeutics towards the clinic:
Solid Cancers, Next-gen ADC (Next-generation antibody–drug conjugates)
Solid Cancers, Next-gen T cell engager (antibodies engineered to redirect the immune system's T cells to recognise and kill cancer cells)
Inflammatory Disease, IgG antagonist
Solid Cancers, Next-gen ADC
Half-life Extension, VHH (Single-domain antibodies, or nanobodies, derived from camelid heavy-chain antibodies are called VHH antibodies, where VHH stands for "variable heavy domain of heavy chain")
Not Disclosed, VHH in collaboration with Amgen (NASDAQ: AMGN).
On January 11, 2022, BigHat Biosciences announced the successful completion of the first stage of a previously undisclosed research collaboration and licensing agreement with Amgen applying BigHat’s platform for multi-objective optimization of a next-generation antibody. Achievement of this first milestone shows that BigHat’s platform has the potential to effectively and efficiently design high-quality therapeutic antibodies. Its platform can synthesize, express, purify and characterize antibodies in a fraction of the time compared to traditional labs to guide the search for better molecules.
Not Disclosed, in collaboration with Merck (NYSE: MRK).
On November 29, 2022, BigHat Biosciences announced a collaboration with Merck, known as MSD outside of the United States and Canada, to apply the company’s technology to design candidates for up to three drug discovery programs.
Moreover, on Dec. 5, 2023, AbbVie Inc. (NYSE: ABBV) and BigHat Biosciences announced a research collaboration to discover and develop next-generation therapeutic antibodies in oncology and neuroscience (AbbVie and BigHat Biosciences Announce Research Collaboration to Leverage Artificial Intelligence and Machine Learning to Discover Next-Generation Therapeutic Antibodies). Working closely with AbbVie, BigHat will utilize its Milliner™ platform, to guide the design and selection for high quality antibodies for multiple therapeutic targets.
On April 24, 2024, BigHat Biosciences announced a novel collaboration with Janssen Biotech Inc, a Johnson & Johnson company (BigHat Biosciences Enters into Strategic Collaboration to Leverage Machine Learning in Antibody Discovery & Design). This strategic collaboration combines the drug discovery, clinical development and data science expertise from Johnson & Johnson (NYSE: JNJ) with BigHat’s Milliner™ platform, to guide the design and selection for high-quality antibodies for multiple Neuroscience therapeutic targets. The agreement was facilitated by Johnson & Johnson Innovation.
BigHat is backed by Section 32, Andreessen Horowitz, 8VC, Amgen Ventures, Bristol Myers Squibb, Quadrille, Grids Capital, AME Cloud Ventures, Innovation Endeavors and Gaingels, and has raised over $100M. Their latest funding round was raised on July 20, 2022.
◻️ Helix Nanotechnologies Inc
Helix (2013, US) is building next-generation mRNA technologies, vaccines and therapies to augment the immune system’s power to fight disease. Helix by utilizing AI to help cure genetic diseases, is focused on building a universal interface to the immune system to tap into the innate power of the human body to fight disease. HelixNano is a Y Combinator and venture backed biotech startup.
On March 20, 2024, HelixNano announced that its subsidiary HelixNano Australia has received Human Research Ethics Committee (HREC) approval in Australia for its Phase 1 clinical trial of HN-0001, a second-generation COVID-19 mRNA vaccine candidate specifically designed to prevent COVID-19 in immunosuppressed and immunocompromised populations. The first Phase 1 clinical trial participants are anticipated to be dosed in April 2024.
The HN-0001 mRNA vaccine was generated from 4basebio’s synthetic DNA, opDNA™ platform. 4Basebio PLC (LON: 4BB) is a world-leading expert in cutting edge, innovative technologies and services for life sciences and diagnostics, and is enabling next generation cell and gene therapies and vaccines with its technologies and solutions. They are able to design, manufacture and supply application-specific synthetic DNA or mRNA as well as targeted non-viral vectors for the delivery of nucleic acid payloads. Their proprietary non-viral delivery system, Hermes™, is a nanoparticle vector that can be customized to target cells or tissues of interest for a range of applications. This combines the safety and efficiency of lipid-based nanoparticles (LNPs) with the specificity of a targeting system, addressing the shortcoming associated with both viral vectors and non-targeted LNPs.
4basebio will continue to support HelixNano with the manufacture of GMP synthetic DNA planned for later in 2024.