AI-powered drug discovery: update (VIII)
AI-powered drug discovery: update (VIII)
✴️ Recursion, ✳️ Evotec, 🔷 MindRank, 🔶 HemoShear, ⚜️ Frontier Medicines, 🌀 LifeMine, 👾 EntheogeniX, 🔰Adapsyn, ✅ ENSEM and *️⃣ Denovicon
“In the calculus of the heart it is the ratio of positive to negative emotions that determines the sense of well- being.”
By Daniel Goleman, Emotional Intelligence: Why It Can Matter More Than IQ
For the previous newsletters of this series of updates specifically on AI drug discovery companies with assets in preclinical and clinical trials 👉
Index for “AI-powered drug discovery: update part VIII” 🧵
Recursion
Evotec
MindRank AI
HemoShear Therapeutics
Frontier Medicines
LifeMine Therapeutics
EntheogeniX Biosciences
Adapsyn Bioscience
ENSEM Therapeutics
Denovicon Therapeutics
✴️ Recursion Pharmaceuticals Inc (NASDAQ: RXRX)
Recursion (2013, Utah US) has built the world’s most advanced ultra-high throughput wet-lab and ML platform (target-agnostic drug-discovery engine), and generates proprietary, high-dimensional, multi-modal and relatable datasets of human cellular biology at massive scale, applying advanced ML approaches to reveal novel biological relationships. In particular, Recursion has at its headquarters clusters of robots that treat millions of cells per week with drugs, stain them with six dyes and then take pictures to capture and quantify as many morphological features as they can. By pushing these data through a ML pipeline, they hope to find relationships that are invisible to the human and to tease out clusters of effects that can guide their drug discovery.
So far, at Recursion, they have something like ~20 petabytes of proprietary high-dimensional data with assets in the following clinical trials:
REC-994 (an orally bioavailable small molecule superoxide scavenger) in Phase 2 for Cerebral Cavernous Malformation (CCM). The Symptomatic Cerebral Cavernous Malformation Trial of REC-994 (SYCAMORE).
Topline Phase 2 data readout in September 2024.
REC-2282 (a pan-histone deacetylase inhibitor) in Phase 2 for Neurofibromatosis Type 2 (NF2). Efficacy and Safety of REC-2282 in Patients With Progressive Neurofibromatosis Type 2 (NF2) Mutated Meningiomas (POPLAR-NF2).
Preliminary Phase 2 data readout in the fourth quarter of 2024.
REC-4881 (an orally bioavailable, non-ATP-competitive allosteric small molecule inhibitor of MEK1 and MEK2) in Phase 2 for Familial Adenomatous Polyposis (FAP). Evaluate REC-4881 in Patients With FAP (TUPELO).
Preliminary Phase 2 data readout in the first half of 2025.
REC-4881 for the potential treatment of advanced AXIN1/APC mutant cancers. A Study of REC-4881 in Participants With Cancers Which Have an AXIN1 or APC Mutation.
Preliminary Phase 2 data readout in the first half of 2025.
REC-3964 in Phase 1 for Clostridioides difficile Infection. REC-3964 represents a novel small molecule approach designed to selectively inhibit the toxin produced by Clostridioides difficile in the gastrointestinal tract.
Phase 2 study initiation in the fourth quarter of 2024 and preliminary data readout by the end of 2025.
REC-1245 (previously identified as Target γ) targets RBM39, a novel CDK12-adjacent target identified by the Recursion OS, for HR-Proficient Ovarian Cancers and Other Solid Tumors. As a result of their collaboration with Tempus (NASDAQ: TEM), they are leveraging genomic data across all tumor types to identify clinical biomarkers for patient expansion (already incorporating causal AI models into the Recursion OS trained using data from Tempus Labs after a data partnership was announced in 2023.
IND submission in the third quarter of 2024, Phase 1/2 initiation in the fourth quarter of 2024 and Phase 1 dose-escalation data readout by the end of 2025.
Undisclosed Indication in Fibrosis (Target Epsilon) from the fibrosis collaboration with Bayer (ETR: BAYN) which is now entering initial investigational new drug (IND) enabling studies.
IND submission in early 2025 and Phase 1 healthy volunteer study data readout by the end of 2025.
Dozens of internal and partner programs in early stages with the first LLM and causal model driven programs entering the Recursion pipeline.
Moreover, Recursion Pharmaceuticals Inc (RXRX), that went public in April 2021, had so far the following transformational partnerships with leading large pharma companies:
⏺ In 2020, a strategic collaboration was announced to leverage Recursion’s purpose-built AI-guided drug discovery platform and Bayer’s (OTCMKTS: BAYRY) small molecule compound library and deep scientific expertise to discover and develop new treatments for fibrotic diseases of the lung, kidney, heart and more.
On November 10, 2023, Bayer and Recursion expanded their oncology research partnership and may launch up to seven oncology programmes. Their first joint oncology project is now expected to advance rapidly towards Lead Series nomination.
Bayer will be the first beta-user of their LOWE LLM-orchestrated workflow software, which will be integrated across the collaboration and offer a more exploratory, and intuitive research environment for scientists on both sides.
LOWE is an LLM agent, that represents the next evolution of the Recursion OS (Recursion Operating System, OS), that supports drug discovery programs by orchestrating complex workflows that chain together a variety of steps and tools, from finding significant relationships within Recursion’s Maps of Biology and Chemistry to generating novel compounds and scheduling them for synthesis and experimentation.
⏺ On December 7, 2021, Recursion announced a transformational collaboration with Roche (SWX: RO) and Genentech, in order for Recursion to work with both Roche and Genentech's R&D units to leverage technology-enabled drug discovery through the Recursion OS.
On October 2, 2023, just over one and a half years into the exciting collaboration with Roche and Genentech, Recursion announced that they have reached the first milestone: after building fit-for-purpose oncology maps for their partner spanning whole-genome arrayed CRISPR knockouts and hundreds of thousands of small molecules, they have identified and validated the first hit series for this particular disease, and Roche has exercised the Small Molecule Validation Program Option.
⏺ On June 12, 2023, Recursion acquired the two emerging Canadian AI drug-discovery firms: Cyclica and Valence. Subsequently, Recursion announced a collaboration and a $50M investment from NVIDIA.
⏺ On January 8, 2024, Nvidia Corp. (NVDA) doubled down on AI powered drug discovery and development, announcing an expanded partnership with Amgen Inc (AMGN) and Recursion Pharmaceuticals Inc (Nvidia dives deeper into AI drug development with Amgen, Recursion partnerships). Amgen’s subsidiary deCODE Genetics is building out a supercomputer to create genomics “foundation models”—models trained on massive datasets to tackle a variety of jobs—to fuel drug discovery. deCode will power its new genomics foundation models with Nvidia’s supercomputer and BioNeMo generative AI platform. Recursion is also joining the party and will be the first third-party addition to the BioNeMo platform, adding its Phenom-Beta program for wider use.
⏺ On May 12, 2024, it was announced that NVIDIA bought $70M of shares in RXRX 0.00%↑. Recursion Pharmaceuticals collaborates with NVIDIA to accelerate drug discovery using AI technology. Their newest supercomputer, BioHive-2, powered by 504 NVIDIA H100 Tensor Core GPUs, delivers 2 exaflops of AI performance—nearly 5x faster than their previous system (Recursion Pharmaceuticals is at the forefront of AI-driven drug discovery!).
Recursion’s BioHive-2 is the largest system in the pharmaceutical industry and ranks No. 35 on the latest TOP500 list of the world’s fastest supercomputers.
⏺ On June 24, 2024, Helix announced is providing Recursion Pharmaceuticals access to its vast clinico-genomic data to drive drug discovery innovation (Helix and Recursion to Leverage Clinico-Genomics for Drug Discovery).
⏺ On August 08, 2024, Recursion Pharmaceutical and Exscientia plc announced that the two companies have entered into a definitive agreement, combining Recursion with Exscientia in an approximately $850M (in cash and cash equivalents between the two companies as of the end of Q2 2024) merger.
The TechBio merger will bring together Recursion OS and Exscientia’s generative AI drug design and chemistry automation capabilities to industrialize drug discovery & deliver high quality medicines at lower prices of a diverse portfolio of clinical and near-clinical programs.
Finally, Benzinga just reported
“Recursion Pharmaceuticals's RXRX short percent of float has fallen 4.97% since its last report. The company recently reported that it has 50.37 million shares sold short, which is 24.88% of all regular shares that are available for trading. Based on its trading volume, it would take traders 13.1 days to cover their short positions on average.” (How Is The Market Feeling About Recursion Pharmaceuticals?)
✳️ Evotec SE
Evotec SE (ETR: EVT) is a global biotechnology company committed to advancing drug discovery and development with a premium data analysis (SaaS) platform, Evotec’s PanHunter (a multi-omics data analysis platform), that is a web-based platform that combines peer-reviewed statistical analysis algorithms with the potential for ML and AI capabilities. By working with a user-friendly graphical interface, it enables in-depth analysis across multi-omics data sets with a flexibility that can address just a few entries or correlate millions of data points with ease. They also have a proprietary molecular patient database (E.MPD, Evotec‘s Molecular Patient Database) with over 15k samples and they also have PanOmics platform with over 200k samples (multi-omics data generation at an industrialized scale).
Evotec, headquartered in Hamburg, Germany and established as Evotec BioSystems GmbH in 1993, has the following assets in clinical development:
Neuroscience & Pain
CNTX 6016 Pain (CB2) in collaboration with Centrexion in Phase I
CNTX-6016 is under development for the treatment of neuropathic pain, and acts by targeting the cannabinoid receptor 2.
EVT8683/BMS986419 Neurodegeneration (elF2b) in collaboration with BMS in Phase I
Metabolic
BAY3401016 Alport Syndrome (Sema3A) in collaboration with Bayer (ETR: BAYN) in Phase I
On June 29, 2023, Evotec announced that it received a €2M milestone payment from Bayer AG, which is triggered by the first patient dosed in the clinical Phase I study of a kidney disease programme stemming from the Evotec-Bayer multi-target research collaboration in kidney diseases. The drug candidate, a monoclonal antibody targeting the protein Semaphorin-3A (“Sema3A”) is being developed as a potential first-to-market treatment for Alport syndrome, a rare genetic kidney disease.
Immunology & Inflammation
TPM502 Celiac Disease in collaboration with Topas Therapeutics in Phase II
On May 25, 2023, Topas Therapeutics, a clinical stage biotech company developing novel antigen-specific immune tolerance therapies to treat autoimmune disorders, announced the launch of a Phase 2a clinical study (NCT05660109) evaluating the safety, tolerability and pharmacodynamics of TPM502 in patients with celiac disease.
TPM203 Pemphigus Vulgaris in collaboration with Topas Therapeutics in Phase I
On December 18, 2019, Evotec spin-off Topas Therapeutics GmbH announced that the first patient has been enrolled in a first-in-human Phase 1 trial evaluating TPM203 in patients with pemphigus vulgaris, an orphan autoimmune disease.
EVT401 Immunology & Inflammation (P2X7) in collaboration with CONBA Group in Phase I
On May 02, 2012, Evotec announced the grant of a development and marketing license on EVT 401, a selective, small molecule P2X7 antagonist, for human indications with exception of ophthalmological, chronic obstructive pulmonary disease and endometriosis in China.
Oncology
CT7001 (CDK7) in collaboration with Carrick in Phase II
On October 18, 2023, Carrick Therapeutics, an oncology-focused biopharmaceutical company, announced that the first patient has been dosed in its Phase 2 clinical trial evaluating the novel combination of Carrick's samuraciclib (CT7001), an oral and first-in-class inhibitor of CDK7, and the Menarini Group's oral selective estrogen receptor degrader (SERD), elacestrant, in patients with CDK4/6i resistant HR+, HER2- metastatic breast cancer.
AV078 Tuberous Sclerosis Complex (mTORC1) in collaboration with Aeovian Pharmaceuticals in Phase II
AV078 is a central nervous system-penetrant selective mTORC1 inhibitor in development for tuberous sclerosis complex (TSC) epilepsy.
In March 2024, Hevolution Foundation announced an investment of $20M as the lead investor for a $50M Series A financing extension in Aeovian Pharmaceuticals, to help Berkeley, CA-based Aeovian advance its innovative platform of selective mTORC1 inhibitors, and hopefully foster several promising therapies for diseases of aging.
IMT-009 (CD161) in collaboration with Immunitas in Phase I
On April 8, 2024, Immunitas Therapeutics, a clinical stage precision immunotherapy company, presented preclinical data supporting the combination potential of IMT-009 with anti-PD1 immunotherapy at the American Association for Cancer Research Annual Meeting (AACR 2024) in San Diego, California.
IMT-009 is a fully human, Fc-attenuated IgG1 monoclonal antibody that binds to CD161 and blocks its interaction with its ligand, CLEC2D.
IMT-009 is under evaluation in a Phase 1/2a clinical trial for use as a monotherapy and combination treatment for solid tumor and hematological malignancies.
EVT801 (VEGF3) in collaboration with Kazia Therapeutics in Phase I
On May 1, 2024, Kazia Therapeutics Limited (NASDAQ: KZIA), a biotechnology company specializing in oncology, announced that the Safety Review Team of the EVT801 Phase 1 clinical trial has concluded that the primary and secondary objectives of stage 1 of the trial have successfully been met (Evotec partner Kazia reports the successful completion of the EVT801 Phase 1 clinical trial in advanced cancer patients).
Moreover, at Evotec they started the following collaborations in 2024:
In January 2014, Owkin and Evotec (NASDAQ: EVO) entered into an AI-powered strategic partnership in oncology, immunology and inflammation.
On April 30, 2024, Evotec and Bayer (ETR: BAYN) announced that they have updated the focus of their strategic collaboration to developing innovative precision treatments for cardiovascular diseases (Bayer and Evotec collaborate to advance precision cardiology).
In May 2024, Evotec exited gene therapy, closing Austria R&D plant.
On May 28, 2024, Evotec announced the extension of its 20-year collaboration with CHDI Foundation, Inc, a privately funded nonprofit biomedical research organization exclusively dedicated to collaboratively developing therapeutics that will substantially improve the lives of those affected by Huntington’s disease (Evotec and CHDI Foundation extend strategic drug discovery collaboration in Huntington’s disease).
On June 03, 2024, Evotec and QIAGEN (NYSE: QGEN) announced a collaboration to leverage QIAGEN’s OmicSoft Land Databases through Evotec’s PanOmics data access and analysis platform PanHunter. Combining comprehensive data sets with advanced analytics capabilities will enable enhanced multi-omics data insights, better disease understanding and more precise therapeutic interventions (Evotec and QIAGEN enter software collaboration for enhanced multi-omics data insights).
On 12 June 12, 2024, Evotec announced that has reached important scientific progress within its neuroscience collaboration with Bristol Myers Squibb (NYSE: BMY) triggering a research payment of $20M to Evotec (Evotec announces progress in neuroscience collaboration with Bristol Myers Squibb).
On July 8, 2024, Evotec announced that its biologics segment, Just – Evotec Biologics, Inc., has expanded its strategic partnership with Sandoz (SWX: SDZ) (Just – Evotec Biologics expands tech partnership for biosimilars with Sandoz).
On July 10, 2024, Evotec announced it has entered into a multi-year master research collaboration and option and license agreement with Pfizer. Under the agreement, Evotec and Pfizer (ETR: PFE) will initially focus on early discovery research for metabolic and infectious diseases (Evotec and Pfizer collaborate to advance drug discovery in France).
At the end of July 2024, SynaptixBio announced the expansion of its collaboration with Evotec, which began in April 2022, for the purpose of expanding the pipeline with additional drug candidates for the treatment of hypomyelination with atrophy of the basal ganglia and cerebellum, also called H-ABC (SynaptixBio Ltd and Evotec SE expand collaboration).
Finally, on August 03, 2024, Simply Wall St simply said that:
then in August 2023 it was announced that Evotec eyes 400 layoffs, citing 'challenging market'.
🔷 MindRank AI Ltd
MindRank (2021) is a top AI-driven biotech company in China with focus on “undruggable” targets, with R&D centers in China and UK, that in 2021 was Invited to Join the “NVIDIA Startup Acceleration Program”. Its AI platform consists of Molecule Pro (A molecule design and generation platform), Molecule Dance (A molecular dynamics platform to simulate protein movements) and PharmKG (A biomedical knowledge graph to assist drug discovery).
Currently they are working on the following assets:
MDR-001, Small Molecule GLP-1RA for Obesity (Phase II) and Type 2 Diabetes (Phase I),
In 2023, MindRank announced the dosing of the first cohort in China for the Phase IIa study of MDR-001, an oral small-molecule glucagon-like peptide 1 receptor agonist (GLP-1 RA), targeting obesity and type 2 diabetes mellitus (MindRank Announces the Commencement of Phase IIa Clinical Study of MDR-001 in China). The Phase I single-dose ramping study of MDR-001 has already been successfully completed, demonstrating favorable safety and pharmacokinetic characteristics. Notably, the different dose groups exhibit a clear linear relationship. The preclinical characteristics and advantages of MDR-001 have been effectively translated into clinical studies.
MRANK-106, Undisclosed, Oncology (IND-enabling),
In November 2023, they started conducting IND-enabling studies for their “first-in-class” preclinical candidate MRANK-106.
MRANK-108, Undisclosed, Oncology (IND-enabling),
In November 2023, they initiated the IND-enabling studies for their preclinical candidate MRANK-108.
MRANK-103, Molecular Glue, Oncology
On July 29, 2024, MindRank announced that its molecular glue project, MRANK-103, targeting the MYC signaling pathway and designed to regulate eukaryotic translation and transcription factors, has completed the nomination of preclinical candidate and begun the IND-Enabling studies (MindRank Begins IND-Enabling Studies of its AI-Designed Molecular Glue Drug Pipeline MRANK-103).
MRANK-023, Molecular Glue, Undisclosed (Optimization),
MRANK-111, Undisclosed, Obesity (Optimization) and
MRANK-603, Undisclosed, Undisclosed (Optimization).
Moreover, they have 10 more programs (Undisclosed) in co-development and they have designed as a service for public biotech two assets:
EMRANK-016, Allosteric Inhibitor, Oncology (IND-enabling) and
EMRANK-189, Undisclosed, Undisclosed (Optimization).
On January 19, 2024, MindRank and Henlius (2696.HK) announced a strategic collaboration to jointly develop two innovative healthcare solutions. One is an AI-driven antibody-drug conjugates (ADCs) drug discovery platform, which will expedite the research and development of next-generation ADCs with better clinical efficacy. The other solution is an AI-driven anti-aging therapy platform, which will be developed by leveraging MindRank's biomedical AI large language model (MindRank and Henlius (2696.HK) Announce Strategic Collaboration for AI-Driven Development of Next-Gen Antibody Drug Conjugates (ADCs) and Anti-Aging Therapy Platform).
On April 2, 2024, MindRank announced a strategic partnership with BioMetas Co, Ltd, based in Shanghai, for preclinical drug research and development to advance the construction of a next-generation AI+ drug research and development platform (MindRank and BioMetas Announce Strategic Partnership to Establish One-Stop Service Platform for AI+ Drug Research and Development).
On May 21, 2024, MindRank and Zhejiang Hisun Pharmaceutical Co, Ltd (“HISUN”, 600267.SH) signed a strategic cooperation agreement on AI-empowered small molecule drug discovery (MindRank and HISUN (600267.SH) Forge Strategic Partnership to Advance AI-Empowered Innovative Drug Discovery).
MindRank AI has raised a total of $49M.