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Watching AI-discovered materials develop

It's been a decade since AI entered the drug discovery race, but where are we in the pipeline of drugs discovered by AI-powered drug discovery platforms? In this post, we'll summarize the targets and trends in their development.
medichem
Heejin Jung, R&D Strategy Team Lead
2024.08.13min read
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Trends in the development of AI-discovered compounds

It's been a decade since AI entered the drug discovery race, but where are we in the pipeline of drugs discovered by AI-based drug discovery platforms? In this post, we'll summarize the targets of these new drugs and their development trends.

Insilico Medicine sets the ball rolling

There are currently more than 500 known AI drug discovery companies, with more than 80% founded since 2012, when deep learning was a major trend. Atomwise, Exscientia, AbCellera, Flatiron Health, BenevolentAI, and Recursion Pharmaceuticals are some of the earliest AI companies. Then comes Insilico Medicine, the most notable company, founded in 2014. And in 2019, the start of AI-discovered substances. In just 21 days, They discover a molecule targeting DDR1 and successfully make in vitro/in vivo predictions. In the same year, Deep Genomics also uses its AI platform to find a specific genetic mutation and design a compound to target it, announcing DPG12P1 after 18 months of research.

Around 2020-2022, compounds from the above-mentioned companies are selected as preclinical candidates, with dozens of compounds entering clinical trials by 2022.

Development Trends

Here are the targets and progress of nine representative companies as of 2024.

  Program Ownership Target Indication 2019 2020 2021 2022 2023
BenevolentAI BEN-8744 Whole PDE10 Ulcerative Colitis     Discovery Preclinical Phase 1
BEN-28010 Whole CHK1 Glioblastoma Multiforme     Discovery Preclinical Preclinical
BEN-34712 Whole RAR⍺β ALS       Discovery Preclinical
- Whole - Parkinson's disease       Discovery Discovery
- Whole - Fibrosis       Discovery Discovery
Partnered Program Co-owner w/ AstraZeneca - Chronic Kidney Disease         Discovery
- Co-owner w/ AstraZeneca - Idiopathic Pulmonary Fibrosis         Discovery
- Co-owner w/ Merck - Oncology         Discovery
- Co-owner w/ Merck - Neurology         Discovery
- Co-owner w/ Merck - Immunology         Discovery
BEN-2293 Whole TrkA, TrkB, and TrkC Atopic Dermatitis Discovery Preclinical Phase 1 Phase 2 terminated
BEN-9160 Whole Bcr-Abl ALS         Preclinical
- Whole - Inflammatory bowl disease (IBD)         Discovery
- Whole - Antiviral         Discovery
- Whole - Oncology         Discovery
- Whole - Oncology         Discovery
- Whole - NASH         Discovery
- Whole - Oncology         Discovery
- Whole - Parkinson's disease         Discovery
- Whole - Inflammation         Discovery
Exscientia EXS21546 Majority, w/ Evotec A2aR High Adenosine Signature Cancers   Preclinical Phase 1 Phase 1/2 Phase 1/2 (terminated)
- Whole HPK1 Immuno-Oncology     Discovery unknown  
EXS74539 Whole LSD1 Oncology, AML, SCLC     Discovery Discovery Preclinical
EXS73565 Whole MALT1 Oncology, Hematology     Discovery Discovery Preclinical
- Whole - Oncology     Discovery unknown  
- Whole - Oncology     Discovery unknown  
- Whole - Oncology     Discovery unknown  
- Whole - Oncology     Discovery unknown  
- Whole Mpro COVID-19     Discovery Preclinical unknown
- Whole - Anti-infective     Discovery unknown  
- Whole NLRP3 Inflammation and Immunity     Discovery Preclinical unknown
GTAEXS617 Co-owner w/ Apeiron CDK7 Transcriptionally addicted cancers     Preclinical Preclinical Phase 1/2
EXS4318 Out-licensed, BMS PKC-theta inflammatory and immunologic diseases   Preclinical Preclinical Preclinical Phase 1
- Co-owner - Oncology     Discovery Discovery unknown
- Co-owner ENPP1 Oncology     Preclinical Discovery unknown
- Co-owner ENPP1 HPP     Preclinical Discovery unknown
- Co-owner - Inframmation and immunity     Discovery Discovery unknown
- Co-owner - Inflammation and Immunity     Discovery Discovery unknown
- Co-owner - Oncology     Discovery Discovery unknown
- Co-owner - Oncology     Discovery Discovery unknown
- Co-owner - Psychiatry     Preclinical Discovery unknown
Insilico Medicine INS018_055 Whole TNIK IPF   Discovery Preclinical Phase 1 Phase 2
- Whole TNIK Kidney fibrosis     Discovery Preclinical Preclinical
- - TNIK Skin Fibrosis     Discovery Discovery unknown
- Whole TNIK IPF (inhalable)     Discovery Discovery Preclinical
ISM012 Whole PHD1/2 Anemia of Chronic Kedney Disease     Discovery Preclinical Phase 1
- Whole PHD1/2 Infammatory bowl disease (IBD)     Discovery Preclinical Phase 1
ISM8207 Co-owner w/ Fosun QPCTL Immuno-oncology     Discovery Preclinical Phase 1
- Co-owner w/ Fosun - Diabetic neuphropathy, FSGS     Discovery unknown  
ISM3312 - 3CLpro COVID-19     Discovery Preclinical Phase 1
ISM3412 Whole MAT2A MTAP-/-cancer     Discovery Preclinical Preclinical
ISM9274 Whole CDK12/13 Solid tumors     Discovery Discovery Preclinical
ISM027 Whole cMYC Solid tumors         Discovery
ISM022 Whole CDK8 AML, Solid tumors     Discovery Discovery unknown
ISM023 Whole PARP7 Solid tumors     Discovery Discovery unknown
ISM3091 Out-licensed, Exelixis USP1 BRCA-mutant cancer     Discovery Preclinical Phase 1
ISM5939 Whole ENPP1 solid tumors     Discovery Discovery Preclinical
ISM5043 Out-licensed, Menarini KAT6 ER+/HER2-breast cancer         Preclinical
ISM4525 Whole DGKA Solid tumors         Preclinical
ISM8001 Whole FGFR2/3 Solid tumors         Preclinical
ISM016 Whole NLRP3 Gout flare     Discovery Discovery Discovery
ISM6331 Whole TEAD Solid tumors         Preclinical
Recursion Pharmaceuticals REC-4881 Whole MEK1 and MEK2 Familial Adenomatous Polyposis   Preclinical Phase 1 Phase 1 Phase 2
REC-3599 Whole PKC and GSK3ß GM2 Gangliosidosis   Preclinical Phase 1 terminated  
REC-2282 Whole HDAC Neurofibromatosis Type 2   Preclinical Phase 1 Phase 1 Phase 3
REC-994 Whole antioxidant, no specific target Cerebral Cavemous Malformation   Preclinical Phase 1 Phase 1 Phase 2
REC-3964 Whole - Clostridium Difficile Colitis   Discovery Preclinical Preclinical Phase 1
- Whole - Neuroinflammation     Discovery Discovery unknown
- Whole - Batten Disease     Discovery unknown  
- Whole - Charcot-Marie-Tooth Disease Type 2     Discovery Discovery unknown
- Whole - Immune Checkpoint resistance in STK11-NSCLC     Preclinical Preclinical unknown
- Whole - Oncoloty     Discovery Discovery Discovery
25 programs - - Various     Preclinical unknown  
REC-4881 Whole - AXIN1 or APC Mutant Cancers         Phase 1
- - - Pulmonary Arterial Hypertension       Preclinical unknown
- Whole - -       Preclinical unknown
Immunotherapy Target Alpha Whole - Oncology       Discovery Discovery
Immunotherapy Target Beta Whole - Oncology       Discovery unknown
- Whole - Hepatocellular Carcinoma       Discovery unknown
- Whole RBM39 HR-proficient Ovarian Cancer RBM39         Preclinical
Immunotherapy Target Delta Whole - -         Preclinical
Relay Therapeutics RLY-4008 Whole FGFR2 (mutant+WT) FGFR2-altered cholangiocarcinoma (CCA) Discovery Phase 1 Phase 1 Phase 1 Phase 1/2
RLV-PI3K1047 (RLY-5836) Whole PI3Kα -     Discovery Preclinical Phase 1
RLY2608 Whole PI3Kα solid tumors with a PI3Kα mutation       Phase 1 Phase 1
- Whole PI3Kα -       Discovery unknown
RLY-2139 Whole CDK2 Oncology     Discovery Discovery unknown
- Whole ERα -         unknown
GDC-1971 Co-owner w/ Genentech SHP2 Cancers, expand into multiple combination Preclinical Phase 1 Phase 1 Phase 1 Phase 1
- Whole - Oncology     Discovery Discovery unknown
- Whole - Oncology     Discovery Discovery unknown
- Whole - Genetic disease     Discovery Discovery unknown
- Whole - Genetic disease     Discovery Discovery unknown
Schrödinger SDGR3 (SGR-1505) Whole MALT1 Relapsed or refractory B-cell lymphoma, chronic lymphocytic leukemia Discovery Discovery Preclinical Phase 1 Phase 1
SDGR1 Whole CDC7 Esophagial and Lung Cancers, Discovery Discovery Discovery unknown  
SGR-2921 Whole CDC7 Hematological cancers and solid tumors       Preclinical Phase 1
SDGR2 Whole WEE1 Ovarian, Pancreatic, Breast and Lung Cancers Discovery Discovery Discovery unknown  
SGR-3515 Whole WEE1/MYT1 Solid tumors       Discovery Preclinical
SDGR4 Co-owner w/ BMS HIF-2a Renal Cell Carcinoma   Discovery Discovery unknown  
SDGR5 Co-owner w/ BMS SOS1 KRAS-driven Cancers   Discovery Discovery Discovery Preclinical
- Co-owner w/ BMS - Oncology, Immunology, Neurology     Discovery unknown  
- Co-owner w/ BMS - Neurology         Discovery
- Co-owner w/ BMS - immunology          
- Whole LRRK2 Neurology       Discovery Discovery
- Whole PRMT5-MTA Oncology       Discovery Discovery
- Whole EFGR(C797S) Oncology       Discovery Discovery
- Whole - Oncology       Discovery Discovery
- Whole - Oncology       Discovery Discovery
- Whole NLRP3 Immunology       Discovery Discovery
- Whole - Immunology       Discovery Discovery
- Co-owner w/ BMS - Oncology       Discovery unknown
- Co-owner w/ BMS - Oncology       Discovery unknown
- Co-owner w/ BMS - Immunology       Discovery unknown
- Co-owner w/ BMS - Oncology, Immunology, Neurology       Discovery Discovery
- Co-owner w/ Takeda - Oncology       Discovery Discovery
- Co-owner w/ Takeda TYK2 Psoriasis         Phase 2
- Co-owner w/ Zai Lab - Oncology       Discovery unknown
- Co-owner w/ Lilly - Immunology       Discovery Discovery
- Co-owner w/ Ajax JAK2 Oncology         Discovery
- Co-owner w/ Bright Angel Therapeutics HSP90 Antifungal         Discovery
- Co-owner w/ loxo Therapeutics undisclosed oncology         Phase 1
- Co-owner w/  Morphic Therapeutic α4β7 IBD         Phase 2
- Co-owner w/  Morphic Therapeutic α4β7 GI indications         Discovery
- Co-owner w/  Morphic Therapeutic αvβ8 Solid tumors, fibrosis         Discovery
- Co-owner w/  Morphic Therapeutic - Pulmonary arterial hypertension         Discovery
- Co-owner w/  NimbusTherapeutic HPK1 Immuno-oncology         Phase 1/2
- Co-owner w/ Otsuka - -         Discovery
- Co-owner w/ Sanofi - oncology         Discovery
- Co-owner w/ Structure Therapeutics APJR Pulmonary arterial hypertension         Phase 1
- Co-owner w/ Structure Therapeutics - -         Discovery
- Co-owner w/ Structure Therapeutics LPA1R Idiopathic pulmonary fibrosis         Preclinical
Insitro - Co-owner w/ BMS, TSC alliance - Genetic Epilepsies, ALS         Discovery
- Whole - Solid Tumors         Discovery
- Whole - MASLD, Obesity         Discovery
Verge Genomics VRG50635 Whole PIKfyve ALS   Discovery Preclinical Phase 1 Phase 1/2
- Whole - Parkinson's Disease       Discovery Discovery
- Whole - Parkinson's Disease       Discovery unknown
- Whole - Parkinson's Disease       Discovery unknown
- Whole - Frontotemporal Dementia       Discovery unknown
- Whole - Progressive Supranuclear Palsy       Discovery unknown
- Whole - Schizophrenia       Discovery Discovery
- Whole - Neurodegenerative Diseases       Discovery Discovery
- Whole - Undisclosed       Discovery unknown
- Whole PIKfyve COVID-19     Discovery Preclinical unknown
- - - Psoriasis         Discovery
- - - Atopic Dermititis         Discovery
- - - Crohn's Disease         Discovery
- - - Ulcerative Colitis         Discovery
Partnered Programs Co-owner w/ Lilly - ALS         Discovery
- Co-owner w/ Alexion - Neurodegenerative Diseases         Discovery
- Co-owner w/ Alexion - Neuromuscular Diseases         Discovery
Valo Health OPL-0301 - S1P1 agonist Heart failure and Acute Kidney Injury     Phase 1 Phase 2 Phase 2
OPL-0401 - ROCK 1/2 inhibitor Diabetic Retinopathy     Phase 1 Phase 2 Phase 2
OPAL-0022 - - Atherosclerosis     Discovery unknown  
OPAL-0004 - - Atherosclerosis, Giloblastoma     Discovery unknown  
OPAL-0018 - - Atherosclerosis     Discovery unknown  
OPAL-0003 - - Heart Failure, Giloblastoma     Discovery unknown  
OPL-0101 - - Immuno-Oncology   Discovery Preclinical unknown  
OPAL-0021 - - cancer     Discovery unknown  
OPAL-0015 - USP28 NSCLC, Squamous Cell Carcinoma, Targeted Defined Tumors     Discovery unknown  
OPAL-0024 - - Solid Tumors     Discovery unknown  
OPAL-0001 - PARP1 Medula/Glioblastoma Brain Tumors, Breast Cancer     Discovery unknown  
OPAL-0014 - - Pancreatic Ductal Adenocarcinoma (PDAC), Targeted Defined Tumors     Discovery unknown  
OPAL-0023 - - Defined Tumors, Immune Modulation     Discovery unknown  
OPAL-0012 - USP7 NSCLC     Discovery unknown  
OPAL-0016 - - Induced Neuropathy and Cardiomyopathy     Discovery unknown  
OPAL-0002 - - Neurodegenerative disorders     Discovery unknown  
OPAL-0006 - - Neurodegenerative: Oncology (metastatic)     Discovery unknown  
<BIOPHAMA TREND> expressed it beautifully like this

Summary

  • Schrodinger dominates the pipeline in terms of overall clinical progression.
  • However, Insilico Medicine's TNIK inhibitor can be seen as the leader when reflecting target novelty, which is the most promising aspect of AI-based drug discovery.
  • Recursion is also in Phase 2/3 clinical trials, but Insiliso Medicine's results are the most promising in terms of target novelty.
  • Early AI companies Exscientia & Benevolent have been passive as they have experienced one failure after another.
  • After all, none of the AI-discovered compounds have actually made it past Phase II.
  • While AI has shown promise in accelerating discovery, it does not guarantee success in the clinic.

Conclusion

Many AI-discovered substances are emerging with reduced development time and cost in discovery, but none have demonstrated POC in the clinic. This means that other capabilities are needed in addition to AI technology. It is still a new market and shows the need for F/U of the development trends of leading groups. In addition, I believe that the organic combination of AI software and Bio can be successfully led through cooperation with multiple companies rather than the independent actions of AI companies. I hope that HITS' Hyper Lab will be used as an important tool for the leading groups in successful drug development.

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