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.

Watching AI-discovered materials develop

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

Development Trends

Summary

Conclusion