Delving into the Latest Updates on JAB-3312 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Target

SHP2

Mechanism

SHP2 inhibitors(Src homology phosphotyrosyl phosphatase 2 inhibitors)

Therapeutic Areas

NeoplasmsRespiratory DiseasesDigestive System Disorders+ [3]

Active Indication

KRAS G12C mutant Non-small Cell Lung CancerEsophageal Squamous Cell CarcinomaSquamous Cell Carcinoma of Head and Neck+ [5]

Inactive Indication-

Originator Organization

Jacobio Pharmaceuticals Group Co., Ltd.

Active Organization

Beijing Jiakesi New Drug Development Co. Ltd.Startup

Inactive Organization

AbbVie, Inc.Jacobio Pharmaceuticals Group Co., Ltd.

Drug Highest PhasePhase 3

First Approval Date-

RegulationOrphan Drug (US)

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Structure/Sequence

Molecular FormulaC21H22ClN7S

InChIKeyGKGIGIUNYOFYHZ-LJQANCHMSA-N

CAS Registry2245082-05-5

This is a multicenter, open-label phase 1/2a study consisting of two parts: dose escalation phase and dose expansion phase. The objective of the dose escalation phase is to evaluate the safety, tolerability and pharmacokinetics of JAB-21822 in combination with JAB-3312 in patients with advanced solid tumors harboring KRAS p.G12C mutation and to determine the RP2D for the combination therapy. In the dose expansion phase, preliminary efficacy and safety of the combination therapy at the RP2D will be further explored in patients with specific cancer harboring KRAS p.G12C mutation.

Start Date14 Apr 2022

Sponsor / Collaborator

Beijing Jiakesi New Drug Development Co. Ltd.Startup

100 Clinical Results associated with JAB-3312

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100 Translational Medicine associated with JAB-3312

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100 Patents (Medical) associated with JAB-3312

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1

Literatures (Medical) associated with JAB-3312

22 Aug 2024·Journal of Medicinal Chemistry

Discovery of JAB-3312, a Potent SHP2 Allosteric Inhibitor for Cancer Treatment

Article

Author: Xu, Zilong ; Gao, Panliang ; Wang, Yanping ; Cai, Yang ; Han, Huifeng ; Wang, Yinxiang ; Zhang, Wei ; Wu, Xinping ; Long, Wei ; Ma, Cunbo ; Zhang, Lei ; Kang, Di

As an oncogenic phosphatase, SHP2 acts as a converging node in the RTK-RAS-MAPK signaling pathway in cancer cells and suppresses antitumor immunity by passing signals downstream of PD-1. Here, we utilized the extra druggable pocket outside the previously identified SHP2 allosteric tunnel site by the (6,5 fused), 6 spirocyclic system. The optimized compound, JAB-3312, exhibited a SHP2 binding K_d of 0.37 nM, SHP2 enzymatic IC₅₀ of 1.9 nM, KYSE-520 antiproliferative IC₅₀ of 7.4 nM and p-ERK inhibitory IC₅₀ of 0.23 nM. For JAB-3312, an oral dose of 1.0 mg/kg QD was sufficient to achieve 95% TGI in KYSE-520 xenograft model of mouse. JAB-3312 was well-tolerated in animal models, and a close correlation was observed between the plasma concentration of JAB-3312 and the p-ERK inhibition in tumors. Currently, JAB-3312 is undergoing clinical trials as a potential anticancer agent.

30

News (Medical) associated with JAB-3312

07 Jan 2025

·www.prnewswire.com

The Registrational Clinical Data of Glecirasib was Published in Nature Medicine

BEIJING, SHANGHAI and BOSTON, Jan. 6, 2025 /PRNewswire/ -- Jacobio Pharma (1167.HK), a clinical-stage oncology company focusing on undruggable targets announced today that the data from a registrational clinical trial of its independently developed KRAS G12C inhibitor glecirasib has been published in Nature Medicine (impact factor 58.7). In the article, Jaocbio disclosed, for the first time, the complete dataset of glecirasib in KRAS G12C mutant non-small cell lung cancer patients in the second line or above setting. The pivotal phase II trial of glecirasib monotherapy demonstrated impressive efficacy, including the confirmed objective response rate of 47.9% (56/117), a median progression-free survival of 8.2 months, and a median overall survival of 13.6 months. Glecirasib has a manageable safety profile. Gleciasib has a favorable gastrointestinal safety profile compared with other KRAS G12C inhibitors. The new drug application of glecirasib is currently under evaluation by the Center for Drug Evaluation of the National Medical Products Administration of China, and has been granted Priority Review Designation. Dr. Yinxiang Wang, Chairman and CEO of Jacobio, said: "It's our great honor to present the data from our pivotal trial in such as prestigious journal as Nature Medicine. The development of KRAS-related inhibitors is still in the early stages. We will continue to explore registration clinical trials with our partners of glecirasib in combo with SHP2 inhibitor JAB-3312 for the treatment of first-line NSCLC and accelerate the development of our other RAS programs such as Pan-KRAS inhibitor." About Glecirasib Glecirasib is a KRAS G12C inhibitor developed by Jacobio. A number of clinical trials of glecirasib are currently ongoing in China, the United States and Europe for patients with advanced solid tumors harboring KRAS G12C mutation. These include combination therapy trials with SHP2 inhibitor JAB-3312 in NSCLC and with cetuximab in colorectal cancer. The pancreatic cancer indication has obtained orphan drug designation in the United States and breakthrough therapy designation in China. About Jacobio Jacobio Pharma (1167.HK) is committed to developing and providing new and innovative products and solutions to improve people's health. Our pipeline revolves around novel molecular targets on six major signalling pathways: KRAS, immune checkpoints, tumor metabolism, P53, RB and MYC. We aim for our key projects to be among the top three in the world. Our vision is to become a global leader recognized for our impact in drug R&D together with our partners. Jacobio has R&D centers in Beijing, Shanghai and Boston with our Induced Allosteric Drug Discovery Platform (IADDP) and our iADC Platform. Please visit us at SOURCE Jacobio Pharma WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

Orphan DrugPhase 2Breakthrough TherapyClinical ResultPriority Review

27 Sep 2024

·www.echemi.com

Jacobio Pharma Secures €172 Million: Concerns Over Collaboration Behind Ailis’ Massive Investment Exposed!

On September 27, 2024, Jacobio Pharma (stock code: 1167.HK) attracted a lot of attention in the industry when it officially announced a major cooperation development - the successful acquisition of Shanghai Ellis Pharmaceutical Technology Co., LTD. (stock code: 688578.SH) received up to 172 million yuan in cooperation funds. This payment not only marks the depth and stability of the cooperation between the two parties, but also demonstrates the excellent strength and extensive influence of Gax in the field of innovative drug research and development. The composition of this cooperation is quite remarkable, including a down payment of 150 million yuan, which is a direct reflection of Ellis' high recognition and value of Gax's research and development results. In addition, there is also 22.79 million RMB as research and development cost compensation and other related payments, which will strongly support Gax's continued investment and innovation exploration in subsequent research and development projects. Looking back at the history of cooperation between the two parties, it all began with the signing of a landmark cooperation agreement on August 30, 2024.This initiative not only shows CAx's trust and respect for its partners, but also reflects its firm determination to promote the development of China and even the global medical and health cause. KRAS G12C inhibitor Golelexel, as a star drug in the field of tumor therapy in recent years, has won widespread praise worldwide for its unique mechanism of action and remarkable efficacy. The SHP2 inhibitor JAB-3312 is another effort of GaX in the field of precision medicine, and its precision strike ability for specific targets has brought new hope to many patients with refractory diseases. The introduction of these two drugs will undoubtedly inject new vitality into Ellis' product line and further consolidate its leading position in the pharmaceutical market. It is worth noting that this cooperation not only reflects the depth of cooperation between the two sides in the field of drug research and development, but also indicates that China's pharmaceutical industry is gradually moving toward a new stage of internationalization and high-end. As the global pharmaceutical market continues to integrate and competition intensifies, Chinese pharmaceutical companies are enhancing their core competitiveness by strengthening international cooperation, introducing advanced technology and management experience. The cooperation between Gax and Ellis has undoubtedly set a new benchmark for the internationalization of China's pharmaceutical industry.

AcquisitionLicense out/in

02 Sep 2024

·www.pharmaceutical-technology.com

Jacobio Pharma grants Allist rights to two assets in China

Jacobio Pharma chairman and CEO Dr Yinxiang Wang (right) and Jinxiang Du (left) at the agreement signing ceremony. Credit: JACOBIO PHARMACEUTICALS GROUP CO., LTD. Jacobio Pharma has out-licensed the China rights of its assets, glecirasib and JAB-3312, to Shanghai Allist Pharmaceuticals. Glecirasib is a Kirsten rat sarcoma glycine 12 to cysteine inhibitor. JAB-3312 is a Src homology-2 domain-containing protein tyrosine phosphatase 2 inhibitor. The agreement includes mainland China, Hong Kong, Macau and Taiwan rights. Jacobio is entitled to receive 200m yuan ($28m) in the near term, which includes 150m yuan in upfront payment and 50m yuan for research and development expenses and other payments The agreement also includes milestone payments of 700m yuan contingent upon meeting specific development, regulatory and commercial goals. See Also: RegenxBio touts positive data for rare disease drug RGX-121 Ocaliva approval in Europe withdrawn following data re-assessment Jacobio is entitled to receive tiered royalty payments on net product sales from Allist. Royalty payments for JAB-3312 could reach 20%. Allist will handle the commercialisation of the assets in China and cover subsequent expenditures for their clinical development. A new drug application for glecirasib monotherapy for second-line non-small cell lung cancer (NSCLC) with KRAS G12C mutation received priority review in May 2024 and breakthrough therapy designation in December 2022 in China. In April 2024, data from a Phase II study of glecirasib showed a confirmed objective response rate of 47.9% in second-line NSCLC patients. The disease control rate was 86.3%, with median progression-free survival of 8.2 months and median overall survival of 13.6 months. The first subject was recently dosed in a Phase III clinical trial of the glecirasib and JAB-3312 combination versus standard care. In addition to NSCLC, glecirasib is undergoing pivotal studies for second-line or above pancreatic cancer and in combination with cetuximab for colorectal cancer. Jacobio Pharma chairman and CEO Dr Wang Yinxiang stated: “Allist has strong commercialisation capabilities in the field of lung cancer, and the first indication for glecirasib submitted the new drug application is lung cancer. We believe that with the deep fit of the advantages of both parties, this collaboration will demonstrate great clinical and commercial value. “In addition to the co-operation with glecirasib, Allist also licensed-in the SHP2 inhibitor JAB-3312, the first SHP2 inhibitor entering a registrational trial globally. It is expected to become a first-line therapy in combo with glecirasib, which reflects Allist’s foresight into the future of pipelines.”

Phase 2Phase 3Breakthrough TherapyLicense out/inClinical Result

100 Deals associated with JAB-3312

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
KRAS G12C mutant Non-small Cell Lung Cancer	Phase 3	CN	Beijing Jiakesi New Drug Development Co. Ltd.Startup	07 Aug 2024
Colorectal Cancer	Phase 2	CN	Beijing Jiakesi New Drug Development Co. Ltd.Startup	14 Apr 2022
Pancreatic Ductal Carcinoma	Phase 2	CN	Beijing Jiakesi New Drug Development Co. Ltd.Startup	14 Apr 2022
Esophageal Squamous Cell Carcinoma	Phase 2	CN	Beijing Jiakesi New Drug Development Co. Ltd.Startup	30 Jan 2022
Squamous Cell Carcinoma of Head and Neck	Phase 2	CN	Beijing Jiakesi New Drug Development Co. Ltd.Startup	30 Jan 2022
Advanced Malignant Solid Neoplasm	Phase 2	US	Beijing Jiakesi New Drug Development Co. Ltd.Startup	23 Mar 2021
Non-Small Cell Lung Cancer	Phase 2	US	Beijing Jiakesi New Drug Development Co. Ltd.Startup	23 Mar 2021
Solid tumor	Preclinical	US	AbbVie, Inc.	14 Jul 2022
Advanced Malignant Solid Neoplasm	Preclinical	US	AbbVie, Inc.	23 Mar 2021
Non-Small Cell Lung Cancer	Preclinical	US	AbbVie, Inc.	23 Mar 2021

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT05288205 (ESMO2024) Manual	Phase 1/2	KRAS G12C mutant Non-small Cell Lung Cancer First line \|	102	Glecirasib plus JAB-3312	(sdvpxhkaun) = rrdrjqpqdw ivkzysvagt (bhbpfsbiam ) View more	Positive	14 Sep 2024
				Glecirasib plus JAB-3312 (PD-L1 TPS≥50%)	(sdvpxhkaun) = lqevsspsxo ivkzysvagt (bhbpfsbiam ) View more
NCT05288205 (PRNewswire) Manual	Phase 1/2	KRAS G12C mutant Non-small Cell Lung Cancer First line	194	JAB-21822+JAB-3312	(gyylluczfu) = pgflkbhuzk ypdsbwujhx (ijvovywtmd )	Positive	01 Jun 2024
				JAB-21822+JAB-3312 (frontline)	(hlrdkqibte) = xkjnznejfq aizuixjwmt (vykhppcrml ) View more
NCT05288205 (ASCO2024) Manual	Phase 1/2	KRAS G12C mutation Solid Tumors	179	Glecirasib 800 mg	(neevigwgkx) = ziyltdclod tgynfcfkxn (pbkzouzbeh ) View more	Positive	24 May 2024
NCT05288205 (ESMO 12023 \| ESMO 22023) Manual	Phase 1/2	KRAS G12C mutation Solid Tumors KRAS G12C	60	Glecirasib +JAB-3312	(daoioiycpk) = vbnxgtigho uzsfmulaga (jdmvxhgnqa ) View more	Positive	22 Oct 2023
				Glecirasib +JAB-3312 (KRAS G12Ci naïve NSCLC)	(zsydfluikd) = idwufaovog lqqyxwttnz (kbavlnitir ) View more