Airuikai (glecirasib) / Jacobio Pharma, Allist - LARVOL DELTA

Glecirasib (JAB-21822, KRAS G12C inhibitor) (PRNewswire) - "Phase I/II data for the combination with SHP2 inhibitor has been accepted by a top-tier academic journal, with publication expected in H2 2025."

P1/2 data • Solid Tumor

A Phase II Study Evaluating JAB-21822 Monotherapy in Adult Patients With Pancreatic Cancer and Other Solid Tumors Harboring the KRAS p.G12C Mutation. (clinicaltrials.gov) - P2 | N=88 | Recruiting | Sponsor: Allist Pharmaceuticals, Inc. | Trial completion date: Nov 2025 ➔ Dec 2027 | Trial primary completion date: May 2025 ➔ Dec 2026

Monotherapy • Trial completion date • Trial primary completion date • Oncology • Pancreatic Cancer • Solid Tumor • CA 19-9 • KRAS • MSI

Jacobio’s KRAS G12C Inhibitor Glecirasib Approved for Market Launch (Jacobio Press Release) - "According to the official website of the National Medical Products Administration (NMPA), Jacobio Pharma...has received approval for its independently developed KRAS G12C inhibitor, glecirasib, to be launched on the market. The approved indication is for patients with non-small cell lung cancer (NSCLC) harboring KRAS G12C mutations who have received at least one prior systemic therapy. This approval triggers a milestone payment from Jacobio’s partner Shanghai Allist Pharmaceuticals Co., Ltd. (688578.SH), and Jacobio will receive a milestone payment of RMB 50 million."

China approval • Non Small Cell Lung Cancer

Glecirasib, a potent and selective covalent KRAS G12C inhibitor exhibiting synergism with cetuximab or SHP2 inhibitor JAB-3312. (PubMed, Cancer Res Commun) - P1/2, P3 | "Glecirasib could effectively inhibit HRAS G12C, NRAS G12C, and several G12C-inclusive KRAS double mutants that showed resistance to adagrasib. A new drug application for glecirasib has been submitted in China, seeking approval for the treatment of non-small cell lung cancer, supported by a pivotal phase 2 single-arm study (NCT05009329). Additionally, glecirasib is being explored in clinical trials in combination with cetuximab (phase 2, NCT05194995) and JAB-3312 (phase 3, NCT06416410)."

Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR • HRAS • KRAS • NRAS

JAB-3312, a Potent Allosteric SHP2 Inhibitor that Enhances the Efficacy of RTK/RAS/MAPK and PD-1 Blockade Therapies. (PubMed, Clin Cancer Res) - P1/2 | "JAB-3312 in combination with RTK/RAS/MAPK or PD-1 blockage therapies is a promising strategy that warrants further clinical investigation."

IO biomarker • Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR • KRAS

A Study of JAB-21822 in Advanced or Metastatic NSCLC With KRAS p.G12C and STK11 Co-mutation and Wild-type KEAP1 (clinicaltrials.gov) - P1/2 | N=104 | Recruiting | Sponsor: Allist Pharmaceuticals, Inc. | Trial primary completion date: Dec 2023 ➔ Feb 2026

Trial primary completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KEAP1 • KRAS • STK11

ABBISKO THERAPEUTICS AND ALLIST ENTER INTO A COOPERATION AGREEMENT TO EXPLORE ABSK043 IN COMBINATION GLECIRASIB FOR THE TREATMENT OF NSCLC (HKEXnews) - "...Abbisko Therapeutics...announced that it has entered into a cooperation agreement with Shanghai Allist Pharmaceuticals...to explore the combination of Abbisko Therapeutics’ investigational oral PD-L1 inhibitor, ABSK043, with Allist’s KRAS-G12C inhibitor, glecirasib, for the treatment of non-small cell lung cancer patients with KRAS-G12C mutation."

Licensing / partnership • Non Small Cell Lung Cancer

Glecirasib in KRASG12C-mutated nonsmall-cell lung cancer: a phase 2b trial. (PubMed, Nat Med) - P1/2 | "Glecirasib exhibited promising clinical efficacy and manageable safety profiles in these patient populations. ClinicalTrials.gov identifier: NCT05009329 ."

Journal • P2b data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KRAS

JAB-21822-1006: Phase 1/2a Study of JAB-21822 Plus JAB-3312 in Patients with Advanced Solid Tumors Harboring KRAS P.G12C Mutation (clinicaltrials.gov) - P1/2 | N=240 | Recruiting | Sponsor: Allist Pharmaceuticals, Inc. | N=124 ➔ 240

Enrollment change • Colorectal Cancer • Hepatology • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor • KRAS

Jacobio Pharma Announces 2024 Annual Results (PRNewswire) - "Non-small cell lung cancer (NSCLC): Glecirasib is expected to be approved in the first half of 2025; Multi-tumor basket: The multi-tumor basket registration phase II trial of glecirasib for the treatment of pancreatic cancer, biliary tract cancer, gastric cancer, small bowel cancer, appendiceal cancer and other indications has been initiated in China."

China approval • Trial status • Appendix Cancer • Biliary Cancer • Gastric Cancer • Lung Cancer • Non Small Cell Lung Cancer • Pancreatic Cancer • Small Intestinal Carcinoma

JAB-21822 in Combination with Cetuximab in Patients with Advanced CRC and Other Solid Tumors with KRAS G12C Mutation (clinicaltrials.gov) - P1/2 | N=48 | Active, not recruiting | Sponsor: Allist Pharmaceuticals, Inc. | Trial primary completion date: Dec 2024 ➔ Dec 2025

Trial primary completion date • Appendix Cancer • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Small Intestinal Carcinoma • Solid Tumor • KRAS

Small molecules for Kirsten rat sarcoma viral oncogene homolog mutant cancers: Past, present, and future. (PubMed, Eur J Pharmacol) - "However, due to the lack of a binding pocket, KRAS has long been considered an undruggable target in recent decades until the discovery of Sotorasib (AMG510). With the approval of Glecirasib (JAB-21822), there are three approved small molecule inhibitors of KRAS, all of which are KRAS G12C inhibitors. At the same time, the limited clinical benefits and rapid emergence of drug resistance to the approved inhibitors have also promoted the emergence of more therapeutics, such as tri-complexes and proteolysis-targeting chimeras (PROTAC). In this paper, we summarize the development of KRAS inhibitors (KRASG12C, KRASG12D, and KRASmulti inhibitors, PROTAC, and tri-complex) and discuss the challenges and opportunities in the discovery of KRAS inhibitors in the hope of providing insights into the development of novel medications for KRAS."

Journal • Preclinical • Review • Colorectal Cancer • Hepatology • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor • Targeted Protein Degradation • EGFR • KRAS • mTOR

JAB-21822 Combined With Chemotherapy in Second-line KRAS G12C CRC (clinicaltrials.gov) - P2 | N=30 | Recruiting | Sponsor: Jian Li

New P2 trial • Colorectal Cancer • Oncology • Solid Tumor

Design, Structure Optimization, and Preclinical Characterization of JAB-21822, a Covalent Inhibitor of KRASG12C. (PubMed, J Med Chem) - "Biopharmaceutical optimization of the resulting leads to improve the solubility of the compounds and block the possible metabolic hotspots led to the identification of JAB-21822, a covalent KRASG12C inhibitor with high potency and excellent cross-species pharmacokinetic properties. JAB-21822 has finished the pivotal Phase II clinical trials in NSCLC, and a new drug application was submitted to the National Medical Products Administration in 2024."

Journal • Preclinical • Colorectal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • KRAS

Efficacy and safety of glecirasib (JAB-21822) monotherapy and in combination with cetuximab in patients with KRAS G12C-mutated advanced colorectal cancer. (ASCO-GI 2025) - P1/2 | "Glecirasib in combination with cetuximab demonstrated better efficacy compared with glecirasib monotherapy in advanced KRAS G12C mutated advanced CRC, while maintaining a favorable safety profile."

Clinical • Combination therapy • Metastases • Monotherapy • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • KRAS

KEAP1 mutations as key crucial prognostic biomarkers for resistance to KRAS-G12C inhibitors. (PubMed, J Transl Med) - "This research affirms KRAS-G12C inhibitors as promising treatments, especially for certain patient subgroups, and underscores KEAP1 mutations as key biomarkers for resistance. The findings highlight the urgent need for alternative therapeutic approaches in KEAP1-mutant patients and emphasize the role of molecular profiling in tailored treatment strategies."

Biomarker • Clinical • IO biomarker • Journal • Oncology • Solid Tumor • KEAP1 • KRAS • PD-L1 • STK11

The Registrational Clinical Data of Glecirasib was Published in Nature Medicine (PRNewswire) - P1/2 | N=311 | NCT05009329 | Sponsor: Jacobio Pharmaceuticals Co., Ltd. | "Jacobio Pharma...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."

P2 data • Non Small Cell Lung Cancer

…blockbuster new drugs expected to be approved for marketing in China in 2025 [Google translation] (Sohu.com) - "glecirasib from Jacobs: This is a KRAS G12C inhibitor used to treat locally advanced or metastatic non-small cell lung cancer with KRAS G12C mutations that have previously received at least one line of systemic treatment. The drug's marketing application has been accepted by the CDE and is expected to be approved in 2025."

China approval • Non Small Cell Lung Cancer

NUMER: Neoadjuvant Umbrella Trial for Patients With Unresectable Stage III NSCLC Harboring Rare Mutations. (clinicaltrials.gov) - P2 | N=120 | Recruiting | Sponsor: Sun Yat-sen University | Not yet recruiting ➔ Recruiting

Biomarker • Enrollment open • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Glecirasib Pancreatic Cancer Indication Received Orphan Drug Designation from EMA (Jacobio Press Release) - "Jacobio Pharma...announced that it’s in-house developed KRAS G12C inhibitor glecirasib has been granted orphan drug designation (ODD) by the European Medicines Agency (EMA)....The pivotal trial (NCT06008288) in the advanced KRAS G12C mutated PDAC and other solid tumors is ongoing in the 30 sites of China."

Orphan drug • Pancreatic Cancer

Jakos (01167.HK): Received RMB 173 million including down payment from exclusive external licensing agreement with Ellis [Google translation] (Yahoo Finance) - "Jakosi...announced that on August 30, its indirect non-wholly owned subsidiary Jakosi’s new drug research and development project was announced by Ellison on the KRAS G12C inhibitor Glecirasib (JAB-21822) and the SHP2 allosteric inhibitor JAB-3312. For the external licensing agreement entered into, a payment of RMB 173 million (the same below) has been received, including a down payment of RMB 150 million and partial compensation for research and development expenses and other payments."

Financing • Oncology

JAB-21822 (01167): First patient dosed in Phase IIa clinical study for KRAS G12C and STK11 co-mutation [Google translation] (Zhitong Finance) - "According to the Zhitong Finance APP, Jacobio Biopharma (01167) issued an announcement that the group completed the dosing of the first patient in a Phase IIa clinical study of KRAS G12C inhibitor (JAB-21822) for non-small cell lung cancer co-mutated with KRAS G12C and STK11 in China on August 31, 2022."

Trial status • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Efficacy of glecirasib in combination with JAB-3312 as a front-line treatment for patients with KRAS p.G12C mutated NSCLC with PD-L1 expression levels or co-mutations (ESMO 2024) - P1/2 | "Glecirasib plus JAB-3312 demonstrated a favorable ORR as a front-line treatment in KRAS p.G12C mutated NSCLC, regardless of PD-L1 expression. Co-mutations in SMARC family members may predict poor prognosis in this study population. More data will be presented at the incoming meeting."

Biomarker • Clinical • Combination therapy • IO biomarker • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KRAS • PD-L1 • TP53

Jacobio Receives Orphan Drug Designations for Glecirasib for Pancreatic Cancer in the U.S. (Jacobio Press Release) - "Jacobio Pharma (1167.HK) announced that its in-house developed KRAS G12C inhibitor glecirasib has received orphan drug designation for pancreatic cancer indication from FDA. Previously, glecirasib had been granted Breakthrough Therapy Designation by CDE (Center for Drug Evaluation, NMPA) for the treatment of second-line or above pancreatic cancer patients with KRAS G12C mutations."

Orphan drug • Pancreatic Cancer

Jacobio Pharma Presents Clinical Results of Glecirasib in Colorectal Cancer (PRNewswire) - P1b/2 | N=48 | NCT05194995 | P1/2 | N=311 | NCT05009329 | Sponsor: Jacobio Pharmaceuticals Co., Ltd. | "Jacobio Pharma...announced clinical results of its novel KRAS G12C inhibitor glecirasib monotherapy and in combination therapy with cetuximab to treat KRAS G12C mutant advanced CRC (colorectal cancer) in Second JCA- AACR Precision Medicine International Conference. In the monotherapy study, overall response rate (ORR) is 33.3% (11/33), disease control rate (DCR) is 90.9% (30/33), mPFS (median progression-free survival) is 6.9 months. In a trial of glecirasib with cetuximab, ORR is 62.8% (27/43), DCR is 93% (40/43). mPFS has not reached before the data cutoff date on May 23, 2023. The majority TRAEs (treatment related adverse event) are grades 1-2."

P1/2 data • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor