AI-powered drug discovery: update (II)
AI-powered drug discovery: update (II)
MetaphysicalCells: A newsletter about Science, Technology and AI Drug Discovery
This article is part of a series of articles dedicated to AI-drug discovery progress of drug candidates in preclinical and clinical phase. For the previous newsletter:
"DNA test may reveal your ancestry, but there is no DNA test for character."
By Abhijit Naskar (Visvavatan: 100 Demilitarization Sonnets)
Index for “AI-powered drug discovery: update part II” 📇
PharmCADD
PsychoGenics
Relation Therapeutics
Engine Biosciences
Micar Innovation
Ochre Bio
Syntekabio
Fog Pharma
InveniAI
BioMap
Neuron23
Nimbus Therapeutics
PharmCADD Co, Ltd,팜캐드
PharmCADD (Busan, Pusan-jikhalsi, South Korea 2019) is a company with an AI and Quantum Physics-based drug discovery platform, the Pharmulator and PharmVAC. Pharmulator is the consolidated drug discovery platform consisting of five core modules: Protein/RNA 3D Structure Prediction, Drug Generation, Virtual Screening, Quantum Calculation and Toxicity Prediction to generate candidates with higher potential. And PharmVAC is the vaccine development platform, an integration of AI assisted RNA structure modeling and Drug Delivery Systems. It provides optimal solutions to the users and clients to design, analyze and visualize more probable RNA sequences for any vaccine candidates.
They have an ongoing Phase 2a clinical study in collaboration with EYEGENE for a Covid19 vaccine and several cancer and autism discovery and preclinical studies. In particular during 2023, FarmCAD and the Pusan National University’s ‘Cancer Cell Diversity Molecular Control Research Center signed an MOU for the development of innovative anticancer drugs and Isu Abxis (pioneering the discovery of engineered antibody-based immunotherapy to target tumors and rare diseases) and PharmCAD jointly announced a ‘target protein-drug mechanism of action’ at EACR.
PharmCADD has raised a total funding of $22M over 1 round from 10 investors.
PsychoGenics Inc
PsychoGenics (1999, US) (Subsidiaries: Psylin Neurosciences Inc, Elto Pharma Inc) is a an experienced preclinical CRO for central nervous system (CNS) disorders (Abuse Liability, ALS, Alzheimer’s Disease, Anxiety and Autism). PsychoGenics offer services ranging from sectioning to microdialysis to EEG. They have a proprietary suite of automated Cube platforms that combine ML, computer vision and proprietary bioinformatics. They offer the following AI Cubes (in vivo AI platforms):
SmartCube® is a cutting-edge automated testing platform that guides mice through a series of challenges using custom hardware, integrating computer vision and AI to extract behavioral and physiological insights. This system boasts several advantages over conventional behavioral testing methods, including: High-Throughput: Capable of screening tens of thousands of compounds for CNS activity. High-Content: Collects millions of data points and thousands of features, leveraging proprietary ML algorithms to identify subtle phenotypic distinctions often imperceptible through standard tests.
NeuroCube® is designed to evaluate the impact of treatments on motor impairment disorders and pain. It provides a view of a rodent’s movements, highlighting the differences between a normal and an impaired mouse employing computer vision to detect changes in gait geometry (e.g., stride length, base width) and dynamics (e.g., swing time, speed).
eCube® is a pharmaco-EEG platform (to record actigraphy and quantitative EEG (qEEG) from different brain regions of unanesthetized mice before and after drug administration) that collects data from novel compounds and subsequently compares their signatures against a comprehensive database of marketed drugs. This process enables the prediction of the therapeutic utility of these compounds. eCube® works in synergy with SmartCube. The raw data and the derived features from the brain signals and biometrics are used to train a ML classifier, which can be used to identify novel compounds with the desired EEG profile and activity. eCube® can also be used to phenotype disease models, including autism spectrum disorders, rare genetic epilepsies, Huntington’s disease, Alzheimer’s disease, and more.
PhenoCube® is an innovative platform where mice are observed continuously, day and night, allowing for the tracking of their behaviors (including social interactions, cognitive abilities, motor skills and circadian rhythms) over an extended period. The cognitive behaviors detected can be employed to identify compounds with the potential to treat cognitive impairment associated with disorders such as schizophrenia, Alzheimer’s disease and ADHD.
In 2023, PGI (PsychoGenics Inc and its discovery arm, PGI Drug Discovery LLC are collectively known as PsychoGenics) was recognized by Scientist.com as a top marketplace supplier for 2023, and also announced that it has entered into an exclusive license agreement with Roche to obtain global development, manufacturing, and commercialization rights to RO7117997.
RO7117997 is an IND-ready Equilibrative Nucleoside Transporter 1 (ENT1) inhibitor discovered in partnership with Roche using PsychoGenics’ AI-enabled phenotypic screening platforms. PsychoGenics intends to evaluate RO7117997 as a potential treatment for several psychiatric and neurological conditions, starting with sleep and seizure disorders.
🏌️ On March 6, 2024, the Christopher & Dana Reeve Foundation (a leading nonprofit organization dedicated to curing spinal cord injury by funding innovative research and improving the quality of life for individuals and families impacted by paralysis) announced three new spinal cord injury (SCI) research grants totaling $3.1M. Two of these grants have been awarded to NeuroRestore (a research, innovation and treatment center that develops and applies bioengineering strategies involving neurosurgical interventions to restore neurological functions|) and the third grant was received by PsychoGenics.
For more Back to the future: From target-selective drug design to AI-enabled polypharmacology by PsychoGenics.
Relation Therapeutics Ltd
Relation Therapeutics in the UK (2019) utilizes GPU accelerated generative ML techniques to combine data from human genetics, single-cell omics, functional genomics and ML in a single, engineered design to transform drug discovery (ActiveGraph ML). Relation is also pioneering a “Lab-in-the-Loop” that can integrate active learning at every step of drug discovery, from predicting cell states to the validation of new targets.
They use human genetics and proprietary omics generated directly from patient tissue to understand the genetic basis of clinical phenotypes (Multi-modal patient data). In this way they build rich maps of disease biology from which they discover novel targets. They deploy interventional experiments with a range of perturbation technologies to test the role of a gene in driving cellular phenotype of disease. Their lab integrates tissue profiling, single-cell and spatial transcriptomics, sequencing and target validation. Then the Lab-in-the-Loop approach, developed in partnership with NVIDIA, leverages hyperscale compute to enable them class-leading ML platforms, across target identification, prioritization and validation, as well as experimental design. In every case, they use the most appropriate methods, including generative and large language models and graph neural networks.
So far, they have built Osteomics, the world’s largest functional, single-cell bone atlas. Together with clinical observation studies they plan to develop a fundamental understanding of cellular bone homeostasis using patient-derived samples, while studying osteoporosis.
On February 22, 2023, Relation announced the opening of its flagship integrated wet–dry laboratory and offices—that comprise 5,500 sq ft—located at the heart of London’s Knowledge Quarter.
🥍 On March 14, 2024, Relation Therapeutics secured $35M (for a total of $65.3M) of new seed financing led by DCVC and co-lead NVentures, NVIDIA’s venture arm. This latest round was led by DCVC and co-led by NVIDIA's venture arm, NVentures, with participation from initial seed lead Magnetic Ventures, existing investors Khosla Ventures, and Abcam founder Jonathan Milner and new investors ARK Invest and Deerfield Management Company.
Engine Biosciences Pte Ltd
Engine Biosciences (2014) is a venture-backed San Francisco and Singapore based technology company pioneering network biomedicine. Based in Singapore, Engine integrates ML and high-throughput biology to identify key genetic interactions within complex disease networks, pinpointing targets and therapeutics for biomarker-defined patient populations. Engine’s proprietary platforms, NetMAPPR (ML-enabled network biology) and CombiGEM (combinatorial genetics experimentation), are engineered for drug hunters and clinical developers to discover and optimize precision medicines, and have been used so far for multiple internal programs, like for example
ENB-812 (IND-enabling) an inhibitor of PKMYT1, which Engine has overseen since 2019 after discovering PKMYT1, a synthetic lethal target utilizing novel biomarkers.
ENB-824 (Solid tumors, inc. Lung, Liver), ENB-838 (Solid tumors, inc. Ovarian, Colorectal, Lung), ENB-255 (Triple negative breast cancer) in preclinical phase. And
Several novel biomarkers for external clinical compounds:
CDK12 silencing leads to up to 17X sensitivity to PARPi (FDA-approved).
Biomarker leads to 150X sensitivity to PKMYT1 inhibitor.
Biomarker sensitization and selective anti-cancer efficacy demonstrated in in vivo isogenic models.
Biomarker leads to 100X sensitivity to clinical BET inhibitors. And
Anti-cancer efficacy observed in biomarker-mutant tumors in vivo.
In 2023, Engine Biosciences announced the completion of a $27M Series A extension, led by Polaris Partners, with participation from both new and existing investors, bringing the total funds raised since inception to $86M, to advance development of precision oncology medicines and novel biomarkers for patient selection.