AI로 발굴한 물질들의 개발 동향

AI가 신약개발 경쟁으로 뛰어든 지 10년이 지났습니다. 그동안 AI 기반 신약 개발 플랫폼이 발굴한 신약 파이프라인은 어디까지 진행되었을까요? 이번 포스팅에선 신약 물질들의 표적은 무엇이었고, 그들의 개발 동향은 어떠한지에 대해 정리하고자 합니다.

Insilico Medicine이 쏘아 올린 작은 공

현재 알려져 있는 AI 신약 개발 회사들은 약 500개 이상이며, 80% 이상이 딥러닝이 주요 트렌드가 된 2012년 이후 설립되었습니다. Atomwise, Exscientia, AbCellera, Flatiron Health, BenevolentAI, Recursion Pharmaceuticals 등이 대표적인 초기 AI 기업입니다. 이후 2014년 설립된 가장 주목할 만한 회사, Insilico Medicine이 등장합니다. Insilico medicine은 2019년에 AI 기반 물질 발굴의 신호탄을 쏘아 올렸습니다. 단 21일 만에 DDR1을 표적으로 하는 분자를 탐색하고 in vitro 및 in vivo 예측을 성공적으로 이끌어냈습니다. 같은 해 Deep Genomics 또한 AI 플랫폼으로 specific genetic mutation을 찾아냈고, 이를 표적으로 화합물을 디자인하여 18개월의 연구 끝에 DPG12P1를 발표했습니다.

2020-2022년에는 위에서 언급된 회사들의 물질들이 전 임상후보로 선정되면서, 2022년에는 수십 개의 AI로 발굴된 물질들이 임상시험에 진입하였습니다.

개발 동향

현재 2024년을 기준으로 대표적인 9개 기업의 타겟 및 진행 상황은 다음과 같습니다.

	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

요약

전체적인 임상 진입 파이프라인의 수는 schrodinger 가 압도적으로 많습니다.
AI 기반의 물질 발굴에서 가장 기대할 수 있는 부분인 target novelty를 반영할 경우 Insilico Medicine의 TNIK 저해제 개발을 선두로 볼 수 있습니다.
Recursion의 경우에도 임상 2상/3상이 동시 진행되고 있어 선두 그룹으로 볼 수 있지만, 타겟의 신규성 측면에선 Insiliso Medicine의 연구 결과가 가장 기대됩니다.
초기 AI 기업인 Exscientia & Benevolent는 각각 한 번의 실패를 경험했기에 소극적인 활동을 보이고 있습니다.
사실상 아직 AI로 발굴된 물질들 중에서는 임상 2상을 통과한 경우가 없다고 볼 수 있습니다.
AI는 discovery 단계에서 물질 발굴의 속도를 비약적으로 높여주는 것은 검증되었지만, 아직 임상에서의 성공으로 이어지지는 않는 모습입니다.

결론

AI가 후보 물질 discovery에서의 개발 기간 단축 및 개발 비용 절감에 큰 역할을 하면서 여러 AI 기반 신규 물질이 등장하고 있지만, 임상에서의 PoC(Proof-of-Concept)를 입증한 물질은 아직 없습니다. 여전히 시장이 성숙하지 못했고, 선두 그룹의 Follow-up이 필요한 단계입니다. 이는 AI 기술이 만능이 아니며, AI 기술을 뒷받침할 또다른 역량이 필요하다는 점을 시사합니다. 즉, AI 소프트웨어와 바이오의 유기적인 결합은 AI 기업의 독립적인 행보만으로는 부족하며, 여러 바이오 기업과의 협력을 통해서야 비로소 가능하다고 보여집니다. 성공적인 신약 개발의 선두 그룹에 히츠의 하이퍼랩이 중요한 도구로 사용되길 바랍니다.

AI로 발굴한 물질들의 개발 동향 살피기

AI로 발굴한 물질들의 개발 동향

Insilico Medicine이 쏘아 올린 작은 공

개발 동향

요약

결론