November 16, 2020, 3D Medicines Inc. announced the New Drug Application (NDA) of Envafolimab (KN035), a recombinant humanized PD-L1 single-domain antibody, which has reached the strategic collaboration with Alphamab Biopharmaceuticals Co., Ltd. (9966.HK) and Simcere Pharmaceutical Group Ltd. (2096.HK). The application has been officially submitted to the National Medical Products Administration (NMPA), and the indications are for the treatment of microsatellite instability (MSI-H) in advanced colorectal cancer, gastric cancer, and other mismatch repair defective (dMMR) advanced solid cancers that have failed previous standard treatment.

Envafolimab (KN035) is a recombinant humanized PD-L1 single-domain antibody Fc fusion protein injection independently developed by Alphamab. 3D Medicines is responsible for the global clinical R&D and commercialization for Envafolimab (KN035) across cancer indications, and Simcere is responsible for the commercial promotion in mainland China. Envafolimab (KN035) is the world's first single-domain antibody for immuno-oncology, and is expected to become the world's first PD-L1 inhibitor given via subcutaneous injection on the market. Compared with the PD-1/PD-L1 antibody currently on the market and under development, it has obvious differentiation advantages including good safety, subcutaneous injection, stability at room temperature, further easily realizing dosing, greatly shortening dosing time, and better improving patients’ quality of life. In such, it is a key step towards the goal of long-term management of cancer as a chronic illness.

The NDA filing is based on the data from a pivotal Phase II clinical trial (NCT03667170) of Envafolimab (KN035) for MSI-H/dMMR advanced solid cancers. The primary endpoint of the single-arm, open-label clinical trial is the confirmed objective response rate (ORR) as evaluated by the Blinded Independent Review Committee (BIRC). MSI-H status for colorectal cancer (CRC) and gastric cancer (GC) was confirmed by central pathology, while the dMMR status for other cancers was assessed by local pathology.

A total of 103 patients were recruited in the trial. The BIRC-assessed Objective Response Rate (ORR) in all patients (n = 103) was 42.7%, and the ORR in CRC patients (n = 65) was 43.1%. The ORR in GC patients (n = 18) was 44.4% and the ORR in patients with other solid cancers (n = 20) was 40.0%. The median Duration of Response (DOR) by BIRC in all patients was not reached at the time of the analysis, and the DOR at the 12-month mark was 92.2%. The median Progression-free Survival (PFS) was 11.1 months. The median Overall Survival (OS) has not been reached and the OS at the 12-month mark was 74.6%. The incidence of Grade 3 or 4 treatment-related adverse events (TRAEs) was 16%, and no TRAE resulted in death. The incidence of Grade 3 or 4 immune-related adverse event was 8%, with no immune-related pneumonia, colitis, nephritis, and neurotoxicity. 9% of patients had injection-site reactions, all of which were grade 1 or 2.

John Gong, M.D., Ph.D., Chairman and CEO of 3D Medicines Inc., commented, “After signing the collaboration agreement with Alphamab in February 2016, we have been rapidly pushing forward the global clinical development of Envafolimab (KN035). Since the first patient dosed in the U.S., nearly 1,000 patients have been recruited globally in our clinical trials, proving the safety and efficacy of Envafolimab (KN035). With the concerted efforts of our partners, we have finally reached the historic moment of filing the New Drug Application for Envafolimab (KN035). Taking it as the starting point, we will make further efforts for the research and development of more innovative drugs, and strive to provide cancer patients in China and the world with more effective, more accessible, and more convenient options of  immuno-oncology drugs, in ways to achieve our vision of ‘helping people with cancer live longer and better’."

Dr. Ting Xu, Founder, Chairman and CEO of Alphamab Oncology, commented, “KN035 is the first single domain antibody submitted for marketing authorization by Alphamab Oncology，and it is expected to become the world's first subcutaneous injectable PD-(L)1 inhibitor. This application shows Alphamab Oncology's leading edge in differentiated innovation. We look forward to the approval of KN035; In colloaboration with our partners, 3D Medicines and Simcere, we plan to further develop KN035 in other major indications and rapidly penetrate the market, so as to benefit more patients. At the same time, we will continue to develop more safe, effective and globally competitive innovative drugs. "

Mr. Ren Jinsheng, Chairman and CEO of Simcere commented, “We are pleased to achieve this important milestone with our three-way collaboration between Alphamab and 3D Medicines to advance Envafolimab (KN035). Given the positive results of the Envafolimab (KN035) antibody in clinical trials already underway and its unique method of dosing, we believe it will bring additional clinical benefits to patients, significantly improving drug compliance. We are also confident in the commercial prospect for this product in China and that the three parties will further promote the expansion of its clinical indications and benefit more patients."

About Envafolimab (KN035)

Envafolimab (KN035) is a PD-L1 single-domain antibody Fc fusion protein independently developed by Alphamab. Based on the unique design, KN035 has advantages in safety, convenience and compliance, and can be used for patients who are not suitable for intravenous infusion with a lower medical cost. On March 30, 2020, Alphamab, 3D Medicines and Simcere reached a three-way strategic collaboration. Alphamab, as the original research party, is responsible for production and quality, 3D Medicines is responsible for global clinical development in the field of oncology, registration and commercialization abroad, and Simcere is responsible for the exclusive commercial promotion of the product in mainland China. At present, KN035 has been simultaneously tested in clinical trials for multiple cancer indications in China, the United States and Japan, and the research for multiple indications have entered the registration/ clinical Phase III. KN035 has been awarded orphan drug qualification by FDA in the United States for the treatment of advanced biliary tract cancer.

About 3D Medicines

3D Medicines, Inc. is a clinical-stage biopharmaceutical company with a mission to help people with cancer live longer and better. Envisioning a future when cancer is managed as a chronic disease, 3D Medicines focuses on the development of personalized immuno-oncology drugs, helping cancer patients live with prolonged survival time and a better quality of life. 3D Medicines has established a pipeline with innovative biological and small-molecule anti-cancer drugs, as well as a professional team capable of global development, registration and commercialization operation.

About Alphamab Oncology

Alphamab Oncology is a biopharmaceutical company focusing on innovative biologics medicine for oncology. On December 12, 2019, the Company was listed in the mainboard of Hong Kong Stock Exchange with stock code 9966.

Alphamab has fully integrated proprietary biologics platforms in bi-specifics and protein engineering. Its pipeline includes eight anti-tumor drug candidates including mainly bi-specifics, and a Covid-19 multifunctional antibody. Four products have advanced into phase I-III clinical trials in China, the United States, and Japan.

The Company also has state-of-the-art manufacturing capabilities designed and built to meet NMPA and EU/FDA’s cGMP standards and a complete quality system which has passed the on-site inspection of a European Union qualified person. Alphamab Oncology is committed to building a global leading, multi-dimensional drug development and commercialization platform, focusing on multifunctional biological innovative drugs, and to benefit patients in China and around the world.

About Simcere

imcere Pharmaceutical Group （stock code: 2096.HK) is rapidly transitioning to an innovation and R&D-driven pharmaceutical company, with a mission of “providing today’s patients with medicines of the future.” It has established a national key laboratory of translational medicine and innovative pharmaceuticals. Simcere focuses on oncology (including cell therapy), central nervous system disease and autoimmune disease therapeutic areas, with a diversified product portfolio and industry-leading capabilities. Its vigorous in-house R&D efforts and extensive R&D collaborations have made it a strategic cooperation partner with world leading pharmaceutical companies and biotechnology companies, in an effort to bring more global life science breakthroughs to China.