News on AI-powered drug discovery
AI Drug Discovery companies with assets in preclinical and clinical trials
“All of life is dependent upon other life, and the closer we consider what constitutes living, the harder life becomes to define.”
By John Green, The Anthropocene Reviewed
News 🌀🐬🐟
Enveda raises $55M to accelerate drug discovery with AI
AI drug researcher XtalPi lists in Hong Kong amid U.S.-China rivalry
Germany’s Merck Bets on AI Drug-Design Partnerships, Rules Out Acquisitions – Interview
Lantern Pharma Receives Certificate of Patent from Japanese Patent Office (JPO) for Composition of Matter Covering Drug Candidate LP-284
FDA plans to release AI drug development guidance this year
EquiScore: a novel AI-based scoring method developed to enhance protein-ligand interaction predictions
How Pasqal and NVIDIA combined technologies can help tackle graph-based problems through a novel hybrid quantum algorithm, allowing to extract information from graph structures
This newsletter is part of a series of newsletters specifically on AI drug discovery companies with assets in preclinical and clinical trials.
Athos Therapeutics
Athos Therapeutics (2019, US) is a clinical stage biotech developing AI-based precision therapeutics for patients with autoimmune diseases and cancer. Their approach is based on the integration of medicinal chemistry and systems biology through ML. Their platform combines a biobank and a cloud based infrastructure for medicinal chemistry, analytical chemistry, molecular biology and 3D cellular analysis, offering an automated system for DNA, RNA, Protein Extraction, Efficacy and non GLP Safety studies and for Evaluating Efficacy on animal disease models.
In particular, the Athos platform consists of RHEA, for integrated and automated transcriptomics, TETHYS, an LC-MS-derived autonomous proteomics platform and DIONE, a proprietary deep machine learning framework for patient molecular subtyping and the development of precision therapeutics. The platform is fueled by over 25,000 human patient samples linked to clinical, pathologic and treatment outcome annotations from medical records curated from the Cleveland Clinic, The Crohn’s & Colitis Foundation and the Lahey Hospital & Medical Center.
Currently, they have the following assets in inflammatory bowel diseases, lupus and cancer:
ATH-063 for IBD, Lupus & Cancer in phase 1. ATH-063 is a first-in-class, oral, small molecule, a genomic regulator in development for the treatment of Inflammatory Bowel Diseases, other autoimmune diseases and solid cancers. ATH-063 acts both by suppressing pro-inflammatory responses and inducing direct mucosal healing through regulation of tight junction proteins. Blood-based proteomic and microbiome biomarker signatures are also being developed by Athos to correlate with ATH-063 effectiveness.
On April 27, 2023, Athos announced the first patient has been dosed in the company’s Phase I clinical trial of ATH-063 in Australia.
🚨 On March 5, 2024, Athos announced the “Autonomization of their AI and ML Platforms” (Disease Agnostic) and have recently completed their first human clinical trial of ATH-063 and moved into additional office space to accommodate their growing computational and AI/ML teams.
ATH-272 for Acute Myeloid Leukemia in preclinical phase.
ATH-293 for Atopic Dermatitis & CD, ATH-261 for Cancer and ATH-131 for IBD, SLE & Sjogren’s initiating the preclinical phase.
ATH-301 for Fibrosis (IPS), MM, ATH-501 for IBD, RA and ATH-601 for AD, IBD, EoE in drug discovery.
(IBD: Inflammatory Bowel Diseases, SLE: Systemic Lupus Erythematosus, CD: Celiac Disease, AD: Atopic Dermatitis, RA: Rheumatoid Arthritis, AML: Acute Myeloid Leukemia).
Athos Therapeutics has raised a total funding of $28M over 2 rounds.
3T Biosciences
3T Biosciences (2017) is an immunotherapy company developing the 3T-TRACE platform designed to overcome the challenges of advancing T-cell receptor (TCR)-based therapeutics. 3T-TRACE is a platform that combines high-diversity target libraries with active ML to identify novel targets and TCRs. This process identifies the most prevalent and immunogenic targets in solid tumors. Its expanded coverage and scale are applicable across all tumor types. Their ML identifies targets that are able to bind and activate T cell responses with high accuracy.
On 4 January 2023, Boehringer Ingelheim and 3T Biosciences announced they have entered into a new strategic collaboration and licensing agreement focused on discovering and developing next-generation life-changing cancer immunotherapies.
🚨 On March 7, 2024, 3T Biosciences announced that it has entered into multiple additional collaborations with leading academic centers and principal investigators to further fuel 3T’s best-in-class 3T-TRACE pHLA target discovery platform. These collaborations provide access to high quality patient samples and corresponding critical data to enable the identification of novel cancer targets of interest, including pancreatic, bladder, breast, head and neck, and colorectal cancers.
Based in South San Francisco, 3T Biosciences is led by an experienced management team and supported by top investors including Westlake Village BioPartners, Lightspeed Venture Partners and the Parker Institute for Cancer Immunotherapy. 3T Biosciences has raised a total funding of $40M.
Arpeggio Biosciences
Arpeggio Biosciences (2017, US) combines proprietary biological assay and ML algorithms that, together, enable rapid, high-resolution snapshots of cellular dynamics following drug treatment. These snapshots are then analyzed to reveal the biological networks that determine a drug’s function and guide therapeutic development. In this way, Arpeggio measures thousands of mRNA changes each time in order to profile a potential drug (+125,000 Curated Compounds, +150,000 Chemotranscriptomes Generated and +2.3B mRNAs Measured). Then they match a drug’s network effect to a disease network without ever needing to reduce it to a single protein.
The GRETA™ platform allows them to sequence global mRNA 300-fold cheaper and faster than traditional technologies and they have created the world's largest database of chemotranscriptomics, discovering an entirely new chemical grammar.
In Arpeggio’s pipeline you can find:
A novel small molecule that significantly represses NRF2 in KEAP1-mutant tumors (a negative regulator of the NRF2 transcription factor)/ Lung Cancer.
🚨 In April 2024, Arpeggio shared updates on the NRF2 degrader (discovered with their AI + Transcriptomics platform) leading to regression of aggressive adenocarcinoma tumors in vivo.
A potent GPX4 inhibitor/ Sarcoma.
🚨 In April 2024, Arpeggio shared updates on the GPX4 inhibitor. The GPX4 inhibitor combined with a checkpoint inhibitor (anti-PDL1) dramatically slowed the progression of sarcoma in mice.
A novel treatment of CKD by blocking ferroptosis/ Chronic Kidney Disease.
🚨 On May 29, 2024, Slone Partners, an executive search firm for life sciences and healthcare organizations, announced the placement of Kevin Eastwood as Chief Business Officer at Arpeggio Biosciences.
Arpeggio Biosciences has raised a total of $20.4M in funding over 4 rounds.
Juvena Therapeutics
Juvena Therapeutics (2017, US) is a computationally-driven biopharmaceutical company decoding secreted proteins for chronic and age-related diseases. Juvena’s platform mines thousands of proteins secreted by human stem cells, screens their potential to restore tissue homeostasis and engineers novel biologic medicines into life-saving treatments and treat myopathies and metabolic diseases.
They are achieving this through a fully integrated, end-to-end artificial intelligence-enabled platform that combines a diverse protein library, in silico mapping of secreted proteins to specific disease phenotypes, in vitro human cell screening, in vivo pharmacology, and protein engineering capabilities. The JuvNET Platform is a first-of-its-kind platform that takes a fully integrated approach by combining in silico, in vitro, in vivo, and protein engineering techniques (AI, quantitative proteomics, multi-omics and robotics-enabled high-content imaging and screening) to translate the body’s natural secreted proteins into life-saving medicines. Currently, they are working on:
JUV-161 is a recombinant fusion protein to agonistically target MAPK/ERK and PI3K/AKT regenerative cascades. To advance the preclinical development of JUV-161, Juvena Therapeutics developed a pan-inducible, TREDT960I transgenic mouse model containing a human genomic segment containing exons 11-15 of DMPK gene with 960 interrupted CTG repeats (CUG960) under direction of the tetO (tet-responsive element) promoter. This panCUG960/+ murine model encompasses the key aspects of DM1 muscle deterioration, as shown using both functional and histological testing to confirm distal muscle wasting and RNA foci accumulation in impacted tissue.
🚨 On January 23, 2024, Juvena Therapeutics announced that the FDA granted Orphan Drug designation to the company’s flagship candidate, JUV-161, an investigational therapeutic for the treatment of Myotonic Dystrophy Type 1, a rare, multi-systemic, autosomal dominant inherited disease and the most common form of adult muscular dystrophy.
A novel preclinical obesity asset, JUV-112, that uniquely enhances lipid metabolism to induce weight loss through a non appetite-suppressing mechanism.
And other anti Obesity (Muscle Target) and undisclosed candidates.
Juvena Therapeutics has raised $52.7M.
Artivila Therapeutics
Artivila Therapeutics (2018, China) is a leading biotechnology company that focuses on empowering innovative drug discovery with an AI platform eLEAD: an advanced AIDD (Artificial Intelligence Driven Drug Discovery) and a CADD (Computer Aided Drug Design) drug discovery platform, covering all stages in the R&D lifecycle. Artivila is currently focused on Autoimmune diseases (Ignite (ARD-885) Refresh, Jump), Neurodegenerative diseases (Sunrise, Lift) and Cancers (MM01 (ARD-198), Climb, Leap), where there is a huge unmet need for treatment.
Their most advanced programs are:
Ignite (ARD-885) in preclinical development for autoimmune diseases and
MM01 (ARD-198) in preclinical development for cancer.
Artivila Therapeutics has raised a total funding of $22.8M over 1 round from 5 investors.
More News 🦚🦩
Antibody design enters the AI era: Nature.com
Discovery of antimicrobial peptides in the global microbiome with machine learning: Cell
The Alliance for Artificial Intelligence in Healthcare (AAIH)
Recursion Pharmaceuticals (RXRX): Catalysts Are Coming And Success Is A Must
Exscientia plc Sued for Securities Law Violations - Contact Levi & Korsinsky Before June 25, 2024 to Discuss Your Rights
Insilico Medicine
Insilico Medicine (Founded 2014, Hong Kong, New York) offers the Pharma.AI platform, a fully integrated drug discovery software suite that can: 1) discover new targets with PandaOmics, enabling multi-omics target discovery and deep biology analysis to considerably reduce required time, 2) design new drugs with Chemistry42, to find novel lead-like molecules through automated ML de-novo drug design and scalable engineering platform, 3) predict the outcomes of clinical trials with inClinico, enabling to predict clinical trials success rate and recognize the weak points in trial design, while adopting the best practices in the industry, and 4) for biologics they offer Generative Biologics, an advanced AI-powered platform that is capable of designing and optimizing different types of biologics including peptides, nanobodies and antibodies tailored for specific targets (Insilico Medicine 10 Years of AI Drug Discovery Innovation). They have the following drug candidates in development:
INS018_055 currently in phase 2 trials for the treatment of the lung disease idiopathic pulmonary fibrosis: A small-molecule TNIK inhibitor targets fibrosis in preclinical and clinical models
ISM3091
On September 12, 2023, Exelixis—an oncology company innovating next-generation medicines—and Insilico Medicine announced that they have entered into an exclusive license agreement granting Exelixis global rights to develop and commercialize ISM3091.
Currently, they also co-developed in partnership with Fosun pharma, a first-in-class orally available small molecule inhibitor of QPCTL, a regulator of the CD47-SIRPα axis, as cancer immunotherapy. Interestingly, in under 40 days since the collaboration announcement, the two companies nominated their first preclinical drug candidate ISM004-1057D, a potential first-in-class small molecule inhibitor that targets QPCTL. The preliminary results demonstrated potent enzymatic inhibitory activity, strong efficacy and synergistic effects with other therapies. They filed an IND application with the NMPA in China in April 2023 and expect to initiate Phase I clinical trials.
🚨 On May 15, 2024, Insilico Medicine completed first-in-patient dose for its novel QPCTL inhibitor for solid tumors in collaboration with Fosun Pharma
🚨 In January 2024, Menarini Group and Insilico Medicine (and Stemline Therapeutics, Inc. a wholly-owned subsidiary of the Menarini Group) entered a global exclusive license agreement for a novel KAT6 inhibitor for potential breast cancer treatment and other oncology indications. The novel molecule was designed by Insilico’s R&D team with the help of its Pharma Generative AI platform, to inhibit KAT6A and block endocrine receptor (ER) at the transcriptional level, giving it the potential to overcome resistance to endocrine therapies due to mutation or ligand-independent constitutive activation of ER.
🚨 On April 25 2024, Insilico Medicine announced that it has received approval from the FDA for its IND application for ISM3412, a small molecule inhibitor of MAT2A for the potential treatment of MTAP deleted cancers designed with Insilico's generative AI platform.
Finally, 🚨 on May 1, 2024 Insilico published the Discovery of a Novel and Potent Cyclin-Dependent Kinase 8/19 (CDK8/19) Inhibitor for the Treatment of Cancer (the compound 12).
This molecule demonstrated not only decent enzymatic and cellular activities but also remarkable selectivity in CDK and kinome panels. Besides, compound 12 also displayed favorable ADME profiles including low CYP1A2 inhibition, acceptable clearance, and high oral bioavailability in multiple preclinical species. Robust in vivo PD and efficacy studies in mice models further demonstrated its potential use as mono- and combination therapy for the treatment of cancers.
🚨 Moreover, on May 20 2024 Insilico and NVIDIA unveiled a new LLM transformer for solving biological and chemical tasks, called nach0, that it draws from a dataset that includes abstract texts extracted from PubMed and patent descriptions derived from the U.S. Patent and Trademark Office related to the chemistry domain. Namely, 100 million documents that became 355 million tokens worth of abstracts and 2.9 billion patents, as well as molecular structures using simplified molecular-input line-entry systems (SMILES).
BenevolentAI
BenevolentAI (Founded 2013, London, UK) (AMS:BAI) has a powerful computational R&D platform that at its core sits their Knowledge Graph, which captures the interconnectivity of all relevant available data and scientific literature. Moreover, their platform offers Data-driven target identification, Precision medicine for endotype-specific drug discovery and Molecular Design to reach high-quality clinical candidates in fewer iterations.
They have an advanced in-house pipeline (more than 20 programs so far):
BEN2293, a Pan-Trk antagonist (TRK tropomyosin receptor kinase) for atopic Dermatitis was being studied in a Phase I/II proof-of-concept, randomized, first-in-human clinical trial in adult patients with mild to moderate disease.
Unfortunately, it has failed secondary efficacy measurements in Phase IIa.
BEN-28010, an oral brain penetrant CHK1 inhibitor, is under development and in 2024 completed all IND-enabling studies.
BEN-8744 is currently in phase 1 for ulcerative colitis.
🚨 On May 16, 2024, AstraZeneca selected a new heart failure target with BenevolentAI.
BenevolentAI’s strategic collaboration with AstraZeneca began in 2019, and originally focused on discovering potential new treatments for idiopathic pulmonary fibrosis (IPF) and chronic kidney disease (CKD). The collaboration was expanded in January 2022 to two new disease areas, Heart Failure and Systemic Lupus Erythematosus (SLE), demonstrating how the Benevolent Platform can be applied across multiple therapeutic areas.
🚨 On Apr 23, 2024, BenevolentAI (eleven months after restructuring and planning to launch software products) laid off another 30% of staff and closed its US office.
Exscientia
Exscientia (Founded 2012, Oxford, UK) (NASDAQ: EXAI) is combining genetic data and global literature in ML models and anticipates and confirms disease-target associations, and then records responses in real patient samples. In 2023, after a prioritization strategy, Exscientia decided to strengthen the company’s focus, and to partner or discontinue the internal development of programmes outside of core focus, and to continue with:
the Sanofi collaboration (first milestone achieved in the Sanofi collaboration),
the new collaboration with Merck KGaA (already initiated with 3 programmes),
GTAEXS617 (CDK7) currently in Phase 1/2 adaptive trial in patients with advanced solid tumors, and
EXS74539 (LSD1), IND submission expected in the first quarter of 2024.
In 2021, Exscientia announced the first AI-designed molecule for immuno-oncology to enter human clinical trials. The A2a receptor antagonist EXS-21546 (blocks adenosine at the adenosine A2A receptor and notable adenosine A2A receptor antagonists include caffeine, theophylline and istradefylline) was co-invented and developed through a Joint Venture between Exscientia and Evotec.
In October 2023, the A2A candidate EXS21546 was discontinued after data from an unnamed peer clouded the candidate’s future.
In 2021, it was announced that their second molecule developed in collaboration between Exscientia and Japanese firm Sumitomo Dainippon Pharma, DSP-0038 (a selective serotonin 5-HT2A receptor antagonist and a serotonin 5-HT1A receptor agonist), was also about to enter Phase I trials in the US for the treatment of Alzheimer’s disease psychosis.
DSP-0038 as well as DSP-2342 (dual 5-HT2A/5-HT7 antagonist) and EXS4318 (PKC-theta) all are continuing in Phase 1 studies by partners Sumitomo Pharma and Bristol Myers Squibb.
The first drug designed with the help of AI technology to enter clinical trials was DSP-1181, announced in January 2020, by Exscientia and Sumitomo Pharma and used to treat obsessive compulsive disorder. The compound was discovered in silico and managed to reach clinical testing in 12 months, as opposed to the typical 5 years with traditional methods. However, the drug did not progress past Phase I and in July 2022 it was discontinued.
🚨 On May 21, 2024, Exscientia cut a quarter of staff while preserving the AI-generated pipeline. Unfortunately, the company was just sued for Securities Law Violations (Exscientia plc Sued for Securities Law Violations - Contact Levi & Korsinsky Before June 25, 2024 to Discuss Your Rights).
Lantern Pharma
Lantern Pharma Inc (Founded 2013, Texas US) (NASDAQ LTRN), is a clinical stage biopharmaceutical company using its proprietary RADR®, an AI and ML platform, to transform the cost and timeline of oncology drug discovery and development. RADR® (or Response Algorithm for Drug Positioning & Rescue) is a proprietary integrated data analytics, experimental biology, biotechnology and ML-based platform, used primarily to predict the potential response the patients will have to new drugs that the company is developing/repurposing.
In June 2023, Lantern Pharma received FDA clearance of IND Application for the drug candidate LP-184 in solid tumors. On September 26, 2023, Lantern dosed its first patient in a phase I trial of its drug LP-184 to treat advanced solid tumors.
On October 3, 2023, Lantern announced that the in vivo data highlighting the enhanced efficacy of its drug candidate LP-184 in glioblastoma were published in Clinical Cancer Research. LP-184 is a small molecule with favorable CNS penetration, that utilizes the mechanism of action known as synthetic lethality, to exploit common vulnerabilities in solid tumor and CNS cancers with DNA damage repair (DDR) deficiencies. In addition, Lantern’s AI platform, RADR, has highlighted overlapping gene dependency profiles between glioblastoma tumorigenesis and sensitivity to LP-184, such as EGFR activation pathways.
In February 2023, Lantern and TTC oncology—an emerging biotechnology company founded in 2015—Established an AI Collaboration to Expand the Clinical Development of Drug Candidate TTC-352. Phase 2 ready candidate, TTC-352, is a 🆕 selective human estrogen receptor partial agonist for the treatment of patients with metastatic estrogen receptor positive breast cancer. Others collaborations include: Actuate Therapeutics (Elraglusib, a GSK-3ϐ inhibitor).
🚨 On March 15, 2024, Lantern announced the dosing of the first two patients in the Phase 1 clinical trial evaluating Lantern’s investigational new drug LP-284 (a potent DNA alkylating agent that kills solid tumors) in patients with relapsed or refractory non-Hodgkin’s lymphoma, and other high-grade B-cell lymphomas as well as other select solid tumors and sarcomas.
🚨 On June 12, 2024, Lantern announced that the Japan Patent Office (JPO) has issued a Certificate of Patent for patent application no. 2021-513267 / registration no. 7489966 directed to Lantern Pharma’s drug candidate LP-284 ((+)N-hydroxy-N-(methylacylfulvene)urea).
Moreover, the Harmonic™ Clinical Trial is enrolling participants in a Phase 2 multi-center study to evaluate the investigational new drug called LP-300, in combination with carboplatin and pemetrexed in never smoker patients with relapsed advanced primary adenocarcinoma of the lung after treatment with tyrosine kinase inhibitors.
🚨 On May 6, 2024, Lantern Pharma has entered into a partnership with Oregon Therapeutics for optimizing the development of the cancer drug candidate, XCE853, through an AI-driven approach.
Verge Genomics
Verge Genomics (Founded 2015, California, US)—founded by Alice Zhang and Jason Chen—has an end-to-end ConVERGE discovery platform, that is a closed-loop ML system combining industry-leading proprietary human genomics with advanced computational tools, to predict new drugs with a higher probability of clinical success. Verge Genomics is the first AI-enabled drug discovery company that discovered a novel target (for investigational amyotrophic lateral sclerosis/ALS treatment) and developed it into a clinical candidate entirely in-house, in just four years.
Alice Zhang told the Financial Times that it has dosed its first patient with this novel therapy named VRG50635 (a small molecule inhibitor of PIKfyve/ a potent stimulator of ion channel ClC-2-activity and contributes to SGK1-dependent regulation of ClC-2) to target ALS, a neurodegenerative disease for which there is no known cure.
🚨 On March 25, 2024, Verge Genomics and Ferrer—an international B Corp pharmaceutical company with an increasing focus in rare neurological disorders—announced a strategic collaboration to co-develop VRG50635 in Europe, Central and South America, Southeast Asia and Japan (Verge Genomics and Ferrer Announce Agreement to Co-Develop Clinical-Stage ALS Therapy VRG50635).
In 2021 Verge Genomics announced a three-year collaboration with Eli Lilly in order to research and develop novel therapies for the treatment of ALS, a devastating motor neuron disease.
Verge Genomics CEO: Why I urge my employees to share their fears and vulnerabilities—and do the same with them
Relay Therapeutics
Relay Therapeutics (Founded 2015, Massachusetts, US) (NASDAQ: RLAY) deploys the Dynamo platform in three key phases of Motion-Based Drug Design: 1) to understand how to drug the protein-target of interest, 2) then transition into hit finding and lead generation to identify a chemical starting point, and 3) eventually pass to optimization to obtain a molecule that has the desired characteristics. So far, Relay Therapeutics is advancing three promising therapeutic candidates in early clinical trials:
RLY-4008 designed to be an oral small molecule—a selective inhibitor of FGFR2 frequently altered in certain cancers (Relay Therapeutics Announces Initial RLY-4008 (lirafugratinib) Data Demonstrating Durable Responses Across Multiple FGFR2-Altered Solid Tumors).
🚨 On 15 June 2024, Relay Therapeutics Announced Initial RLY-4008 (lirafugratinib) Data Demonstrating Durable Responses Across Multiple FGFR2-Altered Solid Tumors.
The data (two-part global Phase 1/2 ReFocus trial in patients with FGFR2-altered tumors) demonstrated activity across several sub-groups, including patients with FGFR2-fusion tumors and patients with FGFR2-altered HR+/HER2- breast cancer.
RLY-2608 designed to be the first allosteric, pan-mutant (H1047X, E542X and E545X) and isoform-selective PI3Kα inhibitor (Relay Therapeutics Announces Initial Clinical Data Demonstrating that RLY-2608 Selectively Targets Multiple PI3Kα Mutations).
🚨 On June 6, 2024, Relay Therapeutics announced a collaboration with Pfizer to study atirmociclib in combination with RLY-2608 and fulvestrant in patients with certain types of metastatic breast cancer.
GDC-1971 (formerly RLY-1971) designed to be an oral small molecule, potent and selective inhibitor of the protein tyrosine phosphatase SHP2 that binds and stabilizes SHP2 in its inactive conformation (into a worldwide license and collaboration agreement with Genentech).
🚨 On June 6, 2024, Relay Therapeutics Disclosed Three New Programs: two genetic disease programs for vascular malformations & Fabry disease and one precision oncology program – NRAS-specific inhibitor.
The company just said that it plans to start clinical development of Fabry disease treatment in the second half of 2025.
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