becotatug vedotin (MRG003) / Lepu Med - LARVOL DELTA

Becotatug vedotin vs. chemotherapy in pre-heavily treated advanced nasopharyngeal carcinoma: A randomized, controlled, multicenter, open-label study. (ASCO 2025) - P2 | "Clinical Trial Registration Number: NCT05126719 The abstract will be released to the public on May 31, 2025 at 8:00 AM EDT"

Clinical • Late-breaking abstract • Metastases • Nasopharyngeal Carcinoma • Oncology • Solid Tumor

CS5007: A novel EGFR and HER3 dual-targeted antibody-drug conjugate (ADC) with potent antitumor activity in preclinical studies (AACR 2025) - "For instance, MRG003, an EGFR-targeted ADC, has shown encouraging clinical outcomes in NPC and HNSCC...Daiichi's HER3-ADC, U3-1402, has shown promising clinical results in advanced EGFR-mutant NSCLC, confirming HER3 as a valid therapeutic target for ADC. Additionally, BL-B01D1, an EGFR/HER3 bispecific ADC, has shown encouraging phase 1 data in advanced cancers... CS5007 is a promising dual-targeted ADC that demonstrates potent antitumor efficacy with a favorable safety and PK profile. These preclinical findings support its further IND-enabling studies and clinical investigations for the treatment of various advanced solid tumors."

Preclinical • Colorectal Cancer • Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • ERBB3

MRG003 CLINICAL TRIAL RESULTS SELECTED AS LBA FOR ORAL PRESENTATION AT 2025 ASCO ANNUAL MEETING (HKEXnews) - "The board of directors of the Company is pleased to announce that, the results of the pivotal Phase IIb study for the treatment of recurrent or metastatic nasopharyngeal cancer ('R/M NPC') for our drug candidate MRG003, an innovative antibody drug conjugate ('ADC') drug candidate independently developed by us targeting epidermal growth factor receptor ('EGFR'), was selected as 'late breaking abstract (LBA)' for oral presentation at the 2025 American Society of Clinical Oncology (the 'ASCO') Annual Meeting."

Late-breaking abstract • P2b data • Nasopharyngeal Carcinoma

UPDATE ON NEW DRUG APPLICATION OF MRG003 (HKEXnews) - "As disclosed in the Announcement, we have received the Acceptance Notice...issued by China National Medical Products Administration ('NMPA') in relation to the acceptance of the NDA of MRG003 in September 2024, and has been granted priority review by the Centre for Drug Evaluation ('CDE') of the NMPA (the 'Priority Review'). The authority is currently proceeding with the clinical and pharmaceutical evaluation of MRG003 in an orderly manner. Based on the latest communication between the Company and the authority, in order to submit relevant supplementary information, the Company has voluntarily withdrawn the previous NDA of MRG003, and has already supplemented relevant application materials and prepared the eCTD documents. The Company will resubmit an NDA for MRG003 on March 4, 2025 and will use its best endeavors to work with the authority in its subsequent review procedures to obtain the NDA approval."

China filing • Priority review • Nasopharyngeal Carcinoma

Preliminary results of phase II study to evaluate safety and efficacy of combination pucotenlimab with epidermal growth factor receptor-ADC (EGFR-ADC) MRG003 in recurrent or metastatic nasopharyngeal carcinoma (R/M-NPC) (ESMO Asia 2024) - P1/2 | "It may provide an efficacious salvage treatment option for R/M-NPC pts who had failed anti-PD-(L)1 and platinum-based therapy. Further follow-up is ongoing."

Clinical • Metastases • P2 data • Nasopharyngeal Carcinoma • Oncology • Solid Tumor • EGFR

Lepu Biotech (02157.HK)’s new drug marketing application for drug candidate MRG003 was accepted by the Food and Drug Administration [Google translation] (Yahoo Finance) - "Lepu Biotech...announced that it has received an 'Acceptance Notice' from the State Food and Drug Administration, and the new drug marketing application for its candidate drug MRG003 has been accepted. MRG003 has also been included in priority review by the NMPA Center for Drug Evaluation (CDE)....The new drug marketing application for the treatment of recurrent or metastatic nasopharyngeal carcinoma (R/M NPC) has been accepted. After the State Food and Drug Administration accepts the drug registration application for MRG003, MRG003 still needs to go through technical review, clinical trial on-site inspection, production on-site inspection and other procedures. It can only be marketed after obtaining NDA approval. The company will make every effort to promote the commercialization of MRG003 in the future."

China filing • Priority review • Nasopharyngeal Carcinoma

Lepu Biotech’s ADC pipeline has made significant progress [Google translation] (iis.aastocks.com) - "...MRG003 has completed patient enrollment in the NPC phase IIb registration clinical study and is expected to apply for an NDA in China in the second half of the year.....The company is currently conducting Phase II trials and has observed good data, which is planned to be presented at the 2024 ESMO Asia Annual Meeting."

China filing • P2 data • Nasopharyngeal Carcinoma • Solid Tumor

Lepu Bio-B(02157): MRG003 successfully obtained FDA approval as a breakthrough therapy for the treatment of R/M NPC (Zhitong Finance) - "According to the Zhitong Finance APP, Lepu Bio-B (02157) announced that the company's drug candidate MRG003 (an epidermal growth factor receptor (EGFR) targeted antibody drug conjugate (ADC) candidate and the company's core product) has recently been granted Breakthrough Therapy Designation (BTD) by the U.S. Food and Drug Administration (FDA) for the treatment of recurrent or metastatic nasopharyngeal carcinoma (R/M NPC). Previously, MRG003 has been granted BTD by the Center for Drug Evaluation (CDE) of the State Drug Administration of the People's Republic of China, Orphan Drug Designation (ODD) by the FDA, and Fast Track Designation (FTD) by the FDA for the treatment of R/M NPC. The company has also completed the enrollment of patients in the Phase IIb registration clinical study of MRG003 for nasopharyngeal carcinoma (NPC), and the company expects to submit a new drug application in China soon."

Breakthrough therapy • Enrollment closed • Fast track • Orphan drug • Head and Neck Cancer • Nasopharyngeal Carcinoma • Oncology • Solid Tumor

A Phase II Study of MRG003 Injection Combined With Pucotenlimab Injection ± Cisplatin Injection in the Neoadjuvant Treatment Locally Advanced EGFR-positive Head and Neck Squamous Cell Carcinoma (clinicaltrials.gov) - P2 | N=30 | Not yet recruiting | Sponsor: Lei Liu

Metastases • New P2 trial • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

A Phase II Study of Anti-EGFR Antibody-drug Conjugate (ADC) Combine With CDK4/6 Inhibitors Posterior Line in the Treatment of Recurrent/Metastatic CDKN2A Gene Variant Head and Neck Squamous Cell Carcinoma (clinicaltrials.gov) - P2 | N=30 | Not yet recruiting | Sponsor: Lei Liu

Metastases • New P2 trial • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

Preliminary results of phase I/II study to evaluate safety and efficacy of combination pucotenlimab with epidermal growth factor receptor-ADC (EGFR-ADC) MRG003 in patients with EGFR positive solid tumors. (ASCO 2024) - P1/2 | "The Phase I/II study pts treated with HX008 in combination with MRG003 demonstrated good tolerability and encouraging antitumor activity in NPC and SCCHN, especially in PD-1 treatment failed NPC pts. The Phase II study is currently ongoing. Research Sponsor: Shanghai Miracogen Inc."

Clinical • P1/2 data • Anemia • Dermatology • Head and Neck Cancer • Hematological Disorders • Nasopharyngeal Carcinoma • Oncology • Pruritus • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • EGFR

A systematic review of antibody-drug conjugates and bispecific antibodies in head and neck squamous cell carcinoma and nasopharyngeal carcinoma: Charting the course of future therapies. (PubMed, Cancer Treat Rev) - "ADC and BsAb antibodies show promise in R/M HNSCC and NPC. Results are premature by small sample sizes and lack of control arm. ADC mainly caused myelosuppression and a pneumonitis case, and BsAb IRR. Further research is warranted in this setting."

Journal • Review • Head and Neck Cancer • Nasopharyngeal Carcinoma • Oncology • Pneumonia • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

Lepu Biopharma Co, Ltd. Announces Results of Three Clinical Trials Presented at 2024 Asco Meeting Announces Presentation of Three Clinical Trial Results at 2024 Asco Annual Meeting [Google translation] (Zonebourse) - P1/2 | N=18 | NCT05688605 | Sponsor: Shanghai Miracogen Inc. | "Preliminary results of the phase I/II study to evaluate the safety and efficacy of the combination of Pucotenlimab with epidermal growth factor receptor-ADC (EGFR-ADC) MRG003 in EGFR patients -positive patients with solid tumors....As of the January 30, 2024 cutoff, 33 patients (9 patients with NPC, 1 with SCCHN and 3 other solid tumors in phase I, 14 patients with NPC and 6 with SCCHN in phase II) were enrolled in this study, with a median age of 52 years, and 25 patients were male. Of the 27 evaluable patients, 17 patients achieved a PR and 7 patients achieved an SD, so the ORR and DCR were 63.0% (95% CI: 42.4, 80.6) and 88.9, respectively. % (95% CI: 70.8, 97.7)."

P1/2 data • Head and Neck Cancer • Nasopharyngeal Carcinoma • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • EGFR

Lepu Bio-B (02157.HK): MRG003 for the treatment of recurrent/metastatic nasopharyngeal carcinoma (R/M NPC) completed the enrollment of key registration phase IIb clinical trials [Google translation] (jrj.com) - "Lepu Bio-B...announced that the company’s drug candidate MRG003, an epidermal growth factor receptor ('EGFR')-targeting antibody drug conjugate ('ADC') ) drug candidate and the company's core product) has recently successfully completed the enrollment of all subjects in the pivotal registration Phase IIb clinical trial for the treatment of recurrent or metastatic nasopharyngeal carcinoma ('R/M NPC')."

Enrollment closed • Head and Neck Cancer • Nasopharyngeal Carcinoma • Oncology • Solid Tumor

Efficacy and safety of a novel anti-EGFR ADC MRG003 in recurrent or metastatic squamous cell carcinoma of the head and neck patients (ESMO 2023) - P2 | "Conclusions MRG003 was well tolerated with a manageable safety profile, and showed promising efficacy in 2/3-line R/M SCCHN pts who failed prior platinum and PD-1/L1inhibitor. A phase III study is currently ongoing to further explore the efficacy of MRG003 in compared with cetuximab/methotrexate in this setting."

Clinical • IO biomarker • Metastases • Head and Neck Cancer • Oncology • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

MRG003: A novel EGFR-targeted antibody-drug conjugant (ADC) for recurrent/metastatic nasopharyngeal carcinoma (ESMO 2023) - P2 | "Conclusions MRG003 demonstrated promising antitumor activity in the late line r/m NPC patients, and with an acceptable tolerance and manageable safety profile. Based on numerically higher ORR and potentially better efficacy than 2.0 mg/kg group and well tolerated safety profile, 2.3mg/kg is the recommended dose for further pivotal study."

Metastases • Nasopharyngeal Carcinoma • Oncology • Solid Tumor

A Study to Evaluate the Efficacy and Safety of MRG003 in Patients With Recurrent Metastatic Nasopharyngeal Carcinoma (clinicaltrials.gov) - P2 | N=238 | Recruiting | Sponsor: Shanghai Miracogen Inc. | N=151 ➔ 238 | Trial completion date: Oct 2023 ➔ Feb 2025 | Trial primary completion date: Mar 2023 ➔ Oct 2024

Enrollment change • Metastases • Trial completion date • Trial primary completion date • Nasopharyngeal Carcinoma • Oncology • Solid Tumor

Changes in Hong Kong stocks | Lepu Bio-B (02157) is now up over 5%, and the expected HNSCC data readout in the second half of the year may become a key catalyst [Google translation] (Zhitong Finance) - "It is reported that MRG003 (EGFR targeting ADC) is currently undergoing pivotal clinical trials in 3L nasopharyngeal carcinoma (NPC) and 2L head and neck squamous cell carcinoma (HNSCC), and its PhII data may be presented at the European Society for Medical Oncology Congress in 2023 disclosure."

P2 data • Head and Neck Cancer • Nasopharyngeal Carcinoma • Oncology • Solid Tumor

A Study to Evaluate MRG003 vs Cetuximab/Methotrexate in in the Treatment of Patients With RM-SCCHN (clinicaltrials.gov) - P3 | N=180 | Not yet recruiting | Sponsor: Shanghai Miracogen Inc.

Metastases • New P3 trial • Head and Neck Cancer • Oncology • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

"Lepu reckons it can do better with MRG003 (acquired with Miracogen). Ph2 swimmers in nasopharyngeal, though ph3 is in head & neck (?) #ADC23" (@JacobPlieth)

A Study of MRG003 in the Treatment of Patients With EGFR-positive Advanced or Metastatic Solid Tumors (clinicaltrials.gov) - P1/2 | N=18 | Recruiting | Sponsor: Shanghai Miracogen Inc.

Combination therapy • Metastases • New P1/2 trial • Head and Neck Cancer • Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • EGFR

MRG003, a Novel EGFR Targeted ADC for Recurrent/ Metastatic Nasopharyngeal Carcinoma (ADC London 2023) - "• Discover MRG003, is a novel EGFR targeted ADC • Outlining Phase II clinical study design in NPC • Encouraging efficacy observed in recurrent and metastatic NPC patients with manageable safety • Discussing Breakthrough Treatment Designation (BTD) granted by NMPA to MRG003 for NPC"

Metastases • Nasopharyngeal Carcinoma • Oncology • Solid Tumor • EGFR

Lepu Bio-B(02157): China National Medical Products Administration granted breakthrough therapy designation for MRG003 for the treatment of recurrent or metastatic nasopharyngeal carcinoma [Google translation] (Zhitong Finance) - "Zhitong Finance APP News, Lepu Bio-B (02157) announced that on September 29, 2022, the Center for Drug Evaluation of the State Drug Administration of the People's Republic of China granted MRG003 breakthrough therapy designation for the treatment of recurrent or metastatic disease. Nasopharyngeal cancer....According to the announcement, MRG003 is an epidermal growth factor receptor-targeted antibody drug conjugate candidate and the company's core product."

Non-US regulatory • Head and Neck Cancer • Nasopharyngeal Carcinoma • Oncology • Solid Tumor

[VIRTUAL] FIH phase I dose escalation and dose expansion study of anti-EGFR ADC MRG003 in patients with advanced solid tumors (ESMO 2021) - "The Ph I study of MRG003 showed manageable safety profile and encouraging antitumor activity in pts with advanced heavily pretreated solid tumors including NPC and SCCHN, which will be further investigated in Ph II studies. After comprehensive evaluation of the safety data from all pts enrolled in the Ph Ib, MRG003 is expected to have improved safety and tolerability at 2.0 mg/kg compared to 2.5 mg/kg. The sponsor will further explore 2.0 mg/kg as the possible RP2D in future Ph II studies."

Clinical • P1 data • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck

Evaluation of Safety of Treatment With Anti-Epidermal Growth Factor Receptor Antibody Drug Conjugate MRG003 in Patients With Advanced Solid Tumors: A Phase 1 Nonrandomized Clinical Trial. (PubMed, JAMA Oncol) - P1 | "The findings of this nonrandomized clinical trial suggest that MRG003 showed a manageable safety profile and promising antitumor activity in patients with EGFR-positive NPC and SCCHN. Clinicaltrials.gov Identifier: NCT04868344."

Clinical • Journal • P1 data • Cardiovascular • Colorectal Cancer • Febrile Neutropenia • Gastrointestinal Cancer • Head and Neck Cancer • Heart Failure • Hematological Disorders • Leukopenia • Nasopharyngeal Carcinoma • Neutropenia • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • EGFR