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TRANSCENTA HOLDING - A Global Fully Integrated Biotherapeutics Company

Press Release

Transcenta Presents First Data from Phase 1 Study of pH-Dependent PDL1 Antibody MSB2311 in Patients with Pre-treated Advanced Solid Tumors and Select Hematological Malignancies

27 May, 2020

Transcenta Holding Limited ("Transcenta"), a global biotherapeutics company with fully-integrated capabilities in discovery, development and manufacturing of antibody-based therapeutics, announced today results reported for the first time from a Phase 1 - study (NCT04272944) of MSB2311, an investigational PDL1 targeting antibody with pH dependent and tumor recycling property developed by Transcenta's subsidiary Mabspace Biosciences (Suzhou) Co., Ltd, in the treatment of Chinese patients with pre-treated advanced solid tumors and select hematological malignancies. Initial results suggest a favorable safety profile across all MSB2311 doses evaluated. Investigators reported that patients achieved durable responses which persisted with one durable beyond 12 months at the time of this press release. The data was published as an abstract (Abstract #e15011) in the American Society of Clinical Oncology (ASCO) Virtual Scientific Program.

The study enrolled Chinese patients with various types of solid tumors who had relapsed or were refractory to established therapies and had not previously been treated with a PD(L)-1 targeting agents. Patients had received at least 2 prior lines of treatment before starting the dose.

"While the treatment of solid tumors with immunotherapy has significantly advanced over recent years, providing patients with alternative agent with deeper response and better tolerability remains critical," said Professor Lin Shen, the lead investigator from Beijing Cancer Hospital. "Initial findings for MSB2311 in this heavily pre-treated population support further study of this investigational tumor recycling immunotherapeutic."

The study was conducted in two parts: dose escalation (part 1) and dose expansion (part 2). Results of the study showed durable responses among patients with solid tumors (n=18) who were treated with MSB2311 across dose groups, ranging from 3 mg/kg-20 mg/kg every three weeks. At the 20 mg/kg dose (n=12), the objective response rate (ORR) was 33 percent (4/12); responses were deep and persisted. At the time of data cut-off, 75 percent (3/4) of patients who achieved a response remained in the study with an ongoing response. Additional dose expansion with alternative dosing regimen at 10 mg/kg every two weeks of the study is ongoing. In addition, 6 patients with hematological malignancy (three T cell lymphoma and three B cell lymphoma) were tested at 20 mg/kg. One of the three T cell lymphoma patients achieved partial response lasting for 6 weeks.  

"We are encouraged by the initial response of heavily pre-treated patients with solid tumors to MSB2311," said Jason Huang, M.D., Senior Vice President, Global Head of Clinical Development, Transcenta Holding. "MSB2311 is an example of one of our innovative antibodies where we look to harness our antibody engineering expertise to advance potentially new options for patients."

In the Phase 1 study, no dose limiting toxicity (DLT) was reported and maximum tolerated dose (MTD) has not been identified. The most common treatment emergent adverse events (TEAEs) ( >10%) included anemia, hypothyroidism, hyperglycemia, hypertriglyceridemia, nausea, vomiting, fatigue, malaise, pyrexia and cough.

About MSB2311

MSB2311 is an investigational pH-dependent humanized antibody targeting PDL1. PDL1 is involved in inhibiting the immune system's response to fight cancer, and PDL1 is expressed at significantly higher levels in tumor cells of people with solid tumors. MSB2311 employs engineered IgG1 which lacks FcR binding. It binds PDL1 on tumor cells and blocks the interaction of PDL1 and PD1, the receptor on T effector cells. In addition, the binding of MSB2311 to PDL1 results in internalization of MSB2311 and MSB2311 can dissociate from bound PDL1 when enter endosome with pH level lower than pH5.5. This allows MSB2311 to recycle to plasma membrane with the help of FcRn and be reused to bind with PDL1 on another tumor cell. Results from preclinical studies demonstrate that MSB2311 can inhibit tumor growth of PDL1 expressing tumor cells in syngeneic mouse-model.