lerociclib (G1T38) / Walvax, Pharmacosmos - LARVOL DELTA

NATIONAL MEDICAL PRODUCTS ADMINISTRATION GRANTED NEW DRUG APPLICATION APPROVAL FOR LEROCICLIB (GB491) (HKEXnews) - "The board of directors of the Company (the 'Board') is pleased to announce that, the China National Medical Products Administration (the 'NMPA') has granted the approval of the new drug applications ('NDA') for Lerociclib (GB491). Lerociclib is indicated for the treatment of adult patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2) negative ('HR+/HER2-') locally advanced or metastatic breast cancer in combination with: (i) an aromatase inhibitor as initial endocrine-based therapy; (ii) fulvestrant in patients with disease progression following endocrine therapy."

China approval • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer

PHARMACOSMOS ASSUMES GLOBAL RIGHTS TO LEROCICLIB OUTSIDE ASIA-PACIFIC (Pharmacosmos Press Release) - "Pharmacosmos A/S today announced that it has assumed the worldwide rights, excluding select Asia-Pacific territories, to the investigational oncology asset lerociclib....Following Pharmacosmos’ acquisition of G1 Therapeutics in September 2024, both license agreements have been concluded and the rights have transitioned back to Pharmacosmos....The compound holds the potential to be developed as a treatment for a number of solid tumors including hormone receptor-positive/HER2-negative (HR+/HER2−) advanced or metastatic breast cancer and hepatocellular carcinoma (HCC), the most common form of liver cancer....With full rights now consolidated, Pharmacosmos holds exclusive development and commercialization rights to lerociclib in all countries except Australia, Bangladesh, Mainland China, Hong Kong SAR, India, Indonesia, Macau SAR, Malaysia, Myanmar, New Zealand, Pakistan, the Philippines, Singapore, South Korea, Sri Lanka, Taiwan, Thailand, and Vietnam."

Commercial • Hepatocellular Cancer • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer

Lerociclib plus fulvestrant in patients with HR+/HER2- locally advanced or metastatic breast cancer who have progressed on prior endocrine therapy: LEONARDA-1 a phase III randomized trial. (PubMed, Nat Commun) - P3 | "These findings support lerociclib plus fulvestrant as a treatment option for patients with HR+/HER2- endocrine-resistant advanced breast cancer (ABC). (Funded by Genor Biopharma; LEONARDA-1 ClinicalTrials.gov identifier, NCT05054751.)."

Clinical • Journal • P3 data • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Lerociclib plus fulvestrant in patients with HR+/HER2− locally advanced or metastatic breast cancer who have progressed on prior endocrine therapy: LEONARDA-1 a phase III randomized trial (Nature, Nat Commun) - P3 | N=275 | LEONARDA-1 (NCT05054751) | Sponsor: Genor Biopharma Co., Ltd. | "Progression-free survival (PFS) assessed by investigators was significantly improved in lerociclib arm versus placebo arm (11.07 vs 5.49 months; hazard ratio, 0.451, 95% CI: 0.311-0.656, P = 0.000016), meeting the pre-specified primary endpoint. The secondary endpoints included PFS assessed by Blinded Independent Central Review (BICR), objective response rate (ORR), duration of response (DOR), disease control rate (DCR), clinical benefit rate (CBR), overall survival (OS), safety and tolerability and pharmacokinetic profile."

P3 data • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer

Lerociclib plus fulvestrant in patients with HR+/HER2− locally advanced or metastatic breast cancer who have progressed on prior endocrine therapy: LEONARDA-1 a phase III randomized trial (Nature, Nat Commun) - P3 | N=275 | LEONARDA-1 (NCT05054751) | Sponsor: Genor Biopharma Co., Ltd. | "Progression-free survival (PFS) assessed by investigators was significantly improved in lerociclib arm versus placebo arm (11.07 vs 5.49 months; hazard ratio, 0.451, 95% CI: 0.311-0.656, P = 0.000016), meeting the pre-specified primary endpoint. The secondary endpoints included PFS assessed by Blinded Independent Central Review (BICR), objective response rate (ORR), duration of response (DOR), disease control rate (DCR), clinical benefit rate (CBR), overall survival (OS), safety and tolerability and pharmacokinetic profile."

P3 data • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer

The clinical benefits of CDK 4/6 inhibitors and biomarker interactions on HR+/HER2- advanced breast cancer patients: an updated pairwise meta-analysis of randomized controlled trials and network meta-analysis (SABCS 2024) - " To address these issues, we conducted a systematic review and a pairwise meta-analysis of randomized controlled trials of oral CDK4/6 inhibitors, including palbociclib, ribociclib, abemaciclib, dalpiciclib, and lerociclib. In conclusion, the PIK3CA mutation status emerges as a promising biomarker for the use of CDK4/6 inhibitors in HR+ and HER2-advanced breast cancer patients with endocrine therapy-naive breast cancer. This finding suggests the potential for future targeted and effective treatments. Moreover, the similar efficacy of currently approved CDK4/6 inhibitors for patients with HR+/HER2- advanced breast tumors provides a strong foundation for further research and development in this field."

Biomarker • Metastases • Retrospective data • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2 • PIK3CA • TP53

LEONARDA-1: GB491 Combined With Fulvestrant for HR+ HER2- Locally Advanced or Metastatic Breast Cancer (clinicaltrials.gov) - P3 | N=275 | Completed | Sponsor: Genor Biopharma Co., Ltd. | Recruiting ➔ Completed

Trial completion • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2

LEONARDA-2: Lerociclib plus letrozole versus placebo plus letrozole in HR+/HER2- advanced or metastatic breast cancer. (ASCO 2024) - P3 | "Background: Following promising outcomes in hormone receptor (HR)-positive, HER2-negative endocrine-resistant advanced breast cancer (BC) with lerociclib plus fulvestrant, this study assesses the efficacy and safety of lerociclib and letrozole in HR+/HER2- advanced or metastatic BC. Lerociclib with letrozole had an excellent safety profile and significantly prolonged PFS in HR+/HER2- advanced or metastatic BC patients. This benefit was consistent across all clinically relevant subgroups, suggesting lerociclib as a viable first-line therapeutic option with a favorable benefit-risk balance."

Clinical • Metastases • Breast Cancer • Cardiovascular • Hematological Disorders • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Leukopenia • Neutropenia • Oncology • Solid Tumor • Venous Thromboembolism • HER-2

G1 Therapeutics and Deimos Biosciences Announce Global (Excluding Asia-Pacific) License Agreement for Lerociclib for Radioprotective Uses (GlobeNewswire) - "G1 Therapeutics, Inc...and Deimos Biosciences...announced a global licensing agreement (excluding the Asia-Pacific region) for lerociclib for radioprotective uses....Deimos Biosciences has the exclusive rights to develop, manufacture, and commercialize lerociclib for certain radioprotective uses in the US, Europe, Japan, and all other global markets, excluding the Asia-Pacific region, which G1 has already licensed to Genor Biopharma....Under the terms of the agreement, G1 is expected to receive shares of Deimos Biosciences’ common stock representing 10% of Deimos Biosciences’ outstanding equity capitalization on a fully diluted basis, in addition to a 20% royalty on aggregate annual net sales of lerociclib."

Licensing / partnership • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor

G1 Therapeutics and Pepper Bio Announce Global (Excluding Asia-Pac) License Agreement for Lerociclib (GlobeNewswire) - "G1 Therapeutics, Inc...and Pepper Bio...announced a global licensing agreement (excluding the Asia-Pacific region) for lerociclib for all indications except for certain radioprotectant uses....Pepper Bio will gain exclusive rights to develop, manufacture, and commercialize lerociclib for all indications except for certain radioprotectant uses in the US, Europe, Japan, and all other global markets, excluding the Asia-Pacific region, which G1 has already licensed to Genor Biopharma....Under the terms of the agreement, G1 is expected to receive upfront payments totaling mid-single-digit millions within 12 months and is eligible to receive a maximum of $135M upon achievement of development and commercial milestones in up to three indications."

Licensing / partnership • Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer • Solid Tumor

A Study of Lerociclib in Participants With Advanced Breast Cancer (clinicaltrials.gov) - P2 | N=100 | Terminated | Sponsor: EQRx, Inc. | Trial completion date: May 2026 ➔ Nov 2023 | Active, not recruiting ➔ Terminated; The study is being closed based on corporate changes at EQRx and is not related to any efficacy or safety issues with lerociclib.

Metastases • Trial completion date • Trial termination • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2 • PGR

CDK4/6 Inhibition With Lerociclib is a Potential Therapeutic Strategy for the Treatment of Pediatric Sarcomas. (PubMed, J Pediatr Surg) - "Inhibition of CDK 4/6 activity with lerociclib was efficacious in traditional 2D sarcoma cell culture as well as in 3D bioprints. Lerociclib holds promise and warrants further investigation as a novel therapeutic strategy for management of these heterogenous groups of tumors."

Journal • Eye Cancer • Oncology • Pediatrics • Retinal Disorders • Retinoblastoma • Sarcoma • Solid Tumor

Comparison of Letrozole With Lerociclib Versus Letrozole With Placebo Control in Patients With Advanced/Metastatic or Recurrent, Grade 1 or Grade 2 Endometrial Cancer (clinicaltrials.gov) - P3 | N=0 | Withdrawn | Sponsor: EQRx International, Inc. | N=320 ➔ 0 | Active, not recruiting ➔ Withdrawn

Combination therapy • Enrollment change • Metastases • Trial withdrawal • Endometrial Cancer • Oncology • Solid Tumor

Comparison of Letrozole With Lerociclib Versus Letrozole With Placebo Control in Patients With Advanced/Metastatic or Recurrent, Grade 1 or Grade 2 Endometrial Cancer (clinicaltrials.gov) - P3 | N=320 | Active, not recruiting | Sponsor: EQRx International, Inc. | Recruiting ➔ Active, not recruiting

Combination therapy • Enrollment closed • Metastases • Endometrial Cancer • Oncology • Solid Tumor

A Study of Lerociclib in Participants With Advanced Breast Cancer (clinicaltrials.gov) - P2 | N=100 | Active, not recruiting | Sponsor: EQRx, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2 • PGR

LEONARDA-1: Phase III randomized study of lerociclib plus fulvestrant in patients with HR+, HER2- locally advanced or metastatic breast cancer that has progressed on prior endocrine therapy. (ASCO 2023) - P3 | "Pre-/peri-menopausal pts also received goserelin. Lerociclib at 150mg twice daily plus fulvestrant significantly improved PFS and ORR and demonstrated a favorable tolerable safety profile in pts with HR+ / HER2- endocrine-resistant advanced BC. Clinical trial information: NCT05054751."

Clinical • Metastases • P3 data • Anemia • Breast Cancer • Hematological Disorders • HER2 Breast Cancer • Leukopenia • Neutropenia • Oncology • Solid Tumor • Thrombocytopenia • HER-2

Genor Biopharma : The latest research data of Lerociclib(GB491) was selected by ASCO Daily News Column, Genor Biopharma’s CDK4/6 inhibitor recognized at globe (Market Screener) - P3 | N=270 | LEONARDA-1 (NCT05054751) | Sponsor: Genor Biopharma Co., Ltd. | "Genor Biopharma...announced that the latest research data of LEONARDA-1 were selected by 2023 ASCO for the ASCO Daily Release, which was published in the ASCO Daily News Column on its website on May 25 (EST)....In the ITT population, the ORR was 23.4% in the lerociclib/fulvestrant group versus 8.7% in the fulvestrant/placebo group. Incident grade 4 neutropenia was low, and no cases of febrile neutropenia or grade 3/4 diarrhea were observed."

P3 data • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor

A Study of [14C]GB491 in Male Healthy Subjects (clinicaltrials.gov) - P1 | N=6 | Completed | Sponsor: Genor Biopharma Co., Ltd.

New P1 trial • Breast Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Genor Biopharma : Announces Poster of Results of the LEONARDA-1 Phase III clinical trial in advanced HR+/HER2- breast cancer at 2023 American Society of Clinical Oncology (ASCO) Annual Meeting (Market Screener) - "Genor Biopharma...announced today that the results of the LEONARDA-1 phase III clinical trial in advanced HR+/HER2- breast cancer will be posted for the first time at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, to be held from June 2 to June 6. LEONARDA-1 is a multicenter, randomized, double-blind, placebo-controlled Phase III clinical trial. The trial was designed to evaluate the efficacy and safety of GB491 (Lerociclib) in combination with Fluvestra versus Fluvestran in the treatment of patients with Hormone receptor (HR) positive and human epidermal growth factor receptor 2 (HER2) negative locally advanced or metastatic breast cancer patients with disease progression following previous endocrine therapy."

P3 data • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor

A Study of GB491 in Combination With Letrozole in Patients With HR Positive and HER2 Negative Advanced Breast Cancer (clinicaltrials.gov) - P3 | N=350 | Recruiting | Sponsor: Genor Biopharma Co., Ltd.

New P3 trial • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Comparison of Letrozole With Lerociclib Versus Letrozole With Placebo Control in Patients With Advanced/Metastatic or Recurrent, Grade 1 or Grade 2 Endometrial Cancer (clinicaltrials.gov) - P3 | N=320 | Recruiting | Sponsor: EQRx International, Inc. | Not yet recruiting ➔ Recruiting

Combination therapy • Enrollment open • Metastases • Endometrial Cancer • Oncology • Solid Tumor

Genor Biopharma : Announces Acceptance of New Drug Application in China for GB491 (Lerociclib) (Market Screener) - "Genor Biopharma...announced today that the China National Medical Products Administration (NMPA) has officially accepted the new drug application for GB491 (Lerociclib cyclin-dependent kinase 4/6 inhibitor) in combination with Fluvestran as the treatment of HR+/HER2- locally advanced or metastatic breast cancer patients with disease progression following previous endocrine therapy."

Non-US regulatory • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor

CDK4/6 inhibition with lerociclib (G1T38) delays acquired resistance to targeted therapies in preclinical models of non-small cell lung cancer (AACR 2019) - P1b/2; "Consistent with previous studies reporting frequent cell-cycle gene alterations in NSCLC, we show that lerociclib synergizes with TKIs targeting EGFR, ALK, and RET in lung cancer cell lines and enhances the efficacy of osimertinib and crizotinib in PDX models harboring EGFR or ALK mutations, respectively. Collectively, our results suggest a compelling rationale for utilizing lerociclib as a backbone therapy for multiple combination regimens in NSCLC. A phase 1b/2 clinical trial evaluating lerociclib plus osimertinib in EGFR-mutant NSCLC is ongoing (NCT03455829)."

Preclinical • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Thoracic Cancer

Combination therapies with CDK4/6 inhibitors to treat KRAS-mutant pancreatic cancer (AACR 2019) - P1; "...Supporting this hypothesis, we found that CDK4/6 inhibitors (e.g., palbociclib, abemaciclib, lerociclib) elicited single-agent activity in a subset of tested PDAC cell lines...Concurrent treatment with the potent and selective ERK1/2 inhibitor (ERKi) SCH772984 reversed resistance and increased sensitivity to palbociclib...We have also evaluated the combination of ERKi with palbociclib or the clinical-stage CDK4/6 inhibitor lerociclib (G1T38) in mouse models of PDAC, supporting our initiation of a phase Ib clinical trial of the ERK inhibitor ulixertinib/BVD-523 in combination with palbociclib in advanced metastatic pancreatic cancer (NCT03454035)...We also identified genes whose loss imparts a survival advantage, suggesting possible resistance mechanisms to single-agent CDK4/6 inhibition. In total, these data suggest that CDK4/6 inhibitors alone, or in combination, may benefit PDAC patients clinically."

Combination therapy • Late-breaking abstract • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Solid Tumor

EQRx Reports Fourth Quarter and Full Year 2022 Financial Results and Recent Corporate Progress (GlobeNewswire) - "Aumolertinib: MAAs accepted for review by MHRA and EMA for EGFR-mutated NSCLC....Plan to initiate a U.S.-led Phase 3 clinical trial for lerociclib in combination with letrozole for the first-line treatment of advanced endometrial cancer in the first half of 2023."

European regulatory • New P3 trial • Endometrial Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor