Penpulimab Monoclonal Antibody (PD-1) Obtains Marketing Approval in China

Akeso, Inc. announced that the anti PD-1 monoclonal antibody drug Penpulimab monoclonal antibody injection co-developed by the Company with Sino Biopharmaceutical Limited, has obtained marketing approval by the National Medical Products Administration of China, for treatment of patients with relapsed or refractory ("r/r") classic Hodgkin's lymphoma ("cHL") after at least second-line systemic chemotherapy treatment.

This approval of Penpulimab by the NMPA is based on a multicenter, single-arm, open-label pivotal clinical trial. Patients enrolled were r/r cHL patients who had failed at least second-  line systemic chemotherapy and were administered 200 mg Penpulimab monoclonal antibody by intravenous injection once every two weeks until progress is made or reached unacceptable toxicity. The key research endpoint was the objective response rate ("ORR") evaluated by the independent radiology review committee ("IRRC") with reference to the Lugano 2014 lymphoma efficacy rating criteria.

The research shows that:

• The ORR assessed by IRRC was 89.4% (76/85) with 47.1% (40/85) patients achieved complete response (CR). The median follow-up time was 15.8 months. The 12-month duration of response ("DoR") was 74.9%. And 12-month progression-free survival ("PFS") was 72.1%.

• In terms of safety profile, the median exposure to Penpulimab antibody was 14.8 months, and 76.6% of patients were treated with Penpulimab antibody for 12 months or longer. Serious adverse events ("SAEs") associated with Penpulimab antibody was 10.6%, with no more than one patient experiencing a drug-related SAE. 26.6% of Grade 3 or higher adverse reactions had occurred, with equal to or greater than 2% of rash, hyperlipidemia, and lung infection. 4.3% of Grade 3 immune-related adverse events ("irAEs") had occurred, with no Grade 3 or higher irAEs.

Penpulimab  is currently the only new PD-1 monoclonal antibody that applies IgG1 subtype and is modified by Fc segment, which has a lower antigen binding dissociation rate and a unique binding epitope as demonstrated by analysis on crystal structure. These features allow Penpulimab to effectively and continuously block PD-1/PD-L1 binding, thus differentiates it from other PD-1 products on the market, and may allow Penpulimab to more effectively enhance immunotherapeutic efficacy and reduce immune-related adverse reactions, as demonstrated by improved safety profile in clinical data.

Penpulimab is Akeso's first innovative antibody protein drug that has been granted marking approval with  major research studies covering major oncology diseases such as liver cancer, gastric cancer, lung cancer, Hodgkin's lymphoma and nasopharyngeal carcinoma. In addition to the said approval for the treatment of cHL, Penpulimab has submitted 2 NDAs in China and 1 biologics license application ("BLA") in the U.S.:

In August 2021, NDA of Penpulimab for third-line treatment of metastatic nasopharyngeal carcinoma was submitted and was accepted by the NMPA.

In July 2021, NDA of Penpulimab for combined chemotherapy for first-line treatment of locally advanced or metastatic squamous non-small-cell lung cancer was submitted and was accepted by the NMPA.

In May 2021, Penpulimab for third-line treatment of metastatic nasopharyngeal carcinoma has been submitted to the Food and Drug Administration of the United States (FDA) for a BLA through the Real-Time Oncology Review (RTOR) program.