2024-05-24 12:34



This announcement is made by Lepu Biopharma Co., Ltd. (the “Company”) on a voluntarybasis.


The board of directors of the Company (the “Board”) is pleased to announce that, threeclinical trial results of the Company’s innovative drug candidate and combination therapieswere selected to be presented at the 2024 American Society of Clinical Oncology (the“ASCO”) Annual Meeting, including our antibody drug conjugate (the “ADC”) MRG004A,combination therapy of MRG003 and HX008 and combination therapy of HX008 andniraparib.




1. Phase I/II first-in-human study to evaluate the safety, and efficacy of tissue factorADC MRG004A in patients with solid tumors


Tissue factor (“TF”) overexpression is associated with thrombosis, metastasis and poorprognosis in solid tumors, including cervical cancer (the “CC”) and pancreatic cancer(the “PC”). MRG004A is a novel TF-targeted site-specifically conjugated ADC. Weare going to present orally the safety and preliminary efficacy results from Phase I/IIMRG004A study in patients with advanced solid tumors at the ASCO Annual Meeting2024, which are summarized as follows:


63 patients were enrolled, with 43 patients in the dose-escalation phase (across 8 doselevels 0.3-2.6mg/kg) and 20 patients in the dose-expansion phase (15 patients at 2.0mg/kg and 5 patients at 2.4mg/kg).2Significant anti-tumor activity of MRG004A was observed in patients with pancreaticcancer (the “PC”). Among 12 evaluable patients with PC in the 2.0mg/kg cohort, whohave previously received median 3 lines of therapy, there were 4 partial responses(the “PR”) and 6 cases of stable disease (the “SD”), thus the objective response rate(the “ORR”) was 33.3% (4/12) and the disease control rate (the “DCR”) was 83.3%(10/12). Among them, 5 patients with PC of TF expression ≥50% and 3+ intensity and≤2 prior lines of therapy received MRG004A at 2mg/kg, 4 of them achieved PR and 1SD. Therefore, the ORR was 80% (4/5) and the DCR was 100% (5/5) in the high TFexpression PC. Also, MRG004A showed efficacy in triple-negative breast cancer (the“TNBC”) and CC patients. In 4 patients with heavily-treated TNBC, the ORR andDCR were 25% (1/4) and 50% (2/4), respectively. In 2 patients with CC with four priortherapy lines, 1 PR and 1 SD. 7.9% (5/63) patients had serious adverse events. Theevaluation of the dose expansion phase is still ongoing.


MRG004A demonstrated a manageable toxicity as well as striking antitumor activityacross multiple tumor types in heavily pretreated settings, including PC with highTF expression. These encouraging findings warrant further evaluation of MRG004A,particularly in the context of TF-overexpressed solid tumors.


Preliminary results of Phase I/II study to evaluate safety and efficacy ofcombination Pucotenlimab with Epidermal Growth Factor Receptor-ADC (the“EGFR-ADC”) MRG003 in EGFR-positive patients with solid tumors


Pucotenlimab (HX008) is a recombinant humanized PD-1 inhibitor approved formarketing in China, and MRG003 is an EGFR-ADC which has shown promisinganti-tumor activity in squamous cell carcinoma of the head and neck (the “SCCHN”)and nasopharyngeal carcinoma (the “NPC”) in multiple clinical studies. In thepreclinical studies, the combination of them has demonstrated a synergistic antitumoreffect. This study was aimed to assess the safety and efficacy of the combinationtherapy in patients with locally advanced or metastatic solid tumors known to expressEGFR. We have observed encouraging preliminary data, which will be presented orallyat the 2024 ASCO Annual Meeting as follows:


As of the cut-off date on 30 January 2024, 33 patients (9 NPC, 1 SCCHN and 3 othersolid tumors patients in Phase I, 14 NPC and 6 SCCHN patients in Phase II) wereenrolled in this study with a median age of 52, and 25 patients were male.


Out of the 27 evaluable patients, 17 patients achieved PR and 7 patients achieved SD,thus the ORR and DCR were 63.0% (95%CI:42.4, 80.6) and 88.9% (95%CI: 70.8, 97.7),respectively. In Phase II, among 9 evaluable EGFR-positive NPC patients progressionafter the first-line treatment of PD-1 plus platinum-based chemotherapy, 2 completeresponse (the “CR”), 5 PR and 2 SD were observed, and the ORR and DCR were 77.8%(95%CI:40.0, 97.2) and 100% (95%CI:66.4, 100), respectively. Five evaluable systemictreatment naïve EGFR-positive SCCHN patients, 3 PR and 1 SD were observed,and the ORR and DCR were 60% (95%CI:14.7, 94.7) and 80% (95%CI:28.4, 99.5),respectively. The duration of response (the “DOR”) and the progression-free survival(the “PFS”) in the study were immature. The longest patient treated has had a DORfor more than 17 months and it is still ongoing. Grade 3-4 common treatment-relatedadverse events (the “TRAEs”) occurred in 4 patients, primarily consisting of decreasedwhite blood cell count (9%) and hypokalemia (6%).


The Phase I/II study patients treated with HX008 in combination with MRG003demonstrated good tolerability and encouraging antitumor activity in NPC and SCCHN,especially in PD-1 treatment failed NPC patients. The Phase II study is currentlyongoing.




Results and exploratory biomarker analyses of a phase II study CHANGEABLE:combination of HX008 and Niraparib in germ-line-mutated metastatic breast cancer


The combination of niraparib and PD-1 inhibitor HX008 has demonstrated promisingantitumor activity with tolerable safety profile in metastatic breast cancer (the “MBC”)patients with germline BRCA1/2 mutations, even in patients with brain metastases.


As of January 12, 2024, 37 patients were enrolled and received the study regimen. In themain research cohort with BRCA1/2 mutations (n = 28), the ORR was 78.6% (22/28) and theDCR was 96.4%, with 3 patients having CR. The median PFS was 7.3 months (95%CI 4.2 to10.4).


The combination of niraparib and HX008 demonstrated maintained clinical benefit with nonew safety signals in MBC patients with germline BRCA1/2 mutations.


Warning: There is no assurance that MRG003 and MRG004A will ultimately be successfullydeveloped and marketed by the Company. Shareholders and potential investors of theCompany are advised to exercise caution when dealing in the shares of the Company.


By order of the Board

Lepu Biopharma Co., Ltd.

Dr. Pu Zhongjie

Chairman of the Board and Executive Director


Shanghai, the PRC

May 24, 2024