HongKong-October 19, 2023, Akeso (9926. HK) announced the publication of the phase 1a/1b first-in-human study (COMPASSION-01) evaluating cadonilimab (PD-1/CTLA-4 bispecific antibody) in patients with advanced solid tumors in Cell Reports Medicine, a sub-publication of Cell.

Full article: https://www.cell.com/cell-reports-medicine/fulltext/S2666-3791(23)00419-6#

The study findings revealed that cadonilimab reached a dose of 25 mg/kg every 3 weeks (Q3W) without encountering the maximum tolerated dose (MTD). The occurrence of severe immune-related adverse events (irAE) with a grade of 3 or higher was only 6.7%. These results indicate that cadonilimab exhibits a favorable safety and tolerability profile in the treatment of advanced solid tumors. Based on the study, a recommended dose of 6 mg/kg every 2 weeks (Q2W) was established. Remarkably, tumor response was observed in both PD-L1-positive and PD-L1-negative solid tumor populations, indicating that cadonilimab possesses unique efficacy advantages over PD-1/PD-L1 monoclonal antibodies and may have a broader range of potential indications. In conclusion,cadonilimab was found to have a favorable toxicity profile and promising efficacy for patients with solid tumors that were refractory/relapsed to standard therapies or for which no effective standard therapy was available.

Cadonilimab has been approved by the China National Medical Products Administration (NMPA) for recurrent or metastatic cervical cancer. Currently, Akeso has initiated/conducted a series of more than 60 clinical studies globally for patients with solid tumors that were refractory/relapsed to standard therapies or for which no effective standard therapy was available, covering more than 20 types of malignant tumors, including gastric cancer, hepatocellular carcinoma, lung cancer, cervical cancer, pancreatic cancer, renal cancer, esophageal squamous carcinoma, colorectal cancer, nasopharyngeal carcinoma, pleural mesothelioma, and other malignant tumors.

About Cadonilimab(PD-1/CTLA-4 bispecific antibody)

Cadonilimab is a first-in-class bispecific antibody that targets both PD-1 and CTLA-4 developed by Akeso. It is a symmetric tetravalent bispecific antibody with a crystallizable fragment (Fc)-null design. In addition to demonstrating biological activity similar to that of the combination of CTLA-4 and PD-1 antibodies, cadonilimab possesses higher binding avidity in a high-density PD-1 and CTLA-4 setting than in a low-density PD-1 setting, while a mono-specific anti-PD-1 antibody does not demonstrate this differential activity. With no binding to Fc receptors, cadonilimab shows minimal antibody-dependent cellular cytotoxicity, antibody-dependent cellular phagocytosis, and interleukin-6 (IL-6)/IL-8 release. These features all likely contribute to significantly lower toxicities of cadonilimab observed in the clinic. Higher binding avidity of cadonilimab in a tumor-like setting and Fc-null design may lead to better drug retention in tumors and contribute to better safety while achieving anti-tumor efficacy.

Cadonilimab has been approved by the China National Medical Products Administration for recurrent or metastatic cervical cancer. Cadonilimab has been included and recommended in multiple clinical guidelines such as CSCO. In its first 12 months on the market, cadonilimab generated impressive sales revenue of 1.15 billion RMB. Cadonilimab has been engaged in more than 60 ongoing clinical trials including investigator-initiated studies. Patient enrollment has been completed for the phase 3 study of cadonilimab for first-line treatment of advanced cervical cancer as well as a phase 3 study of cadonilimab in combination with chemotherapy as first-line therapy in gastric cancer. A phase 3 study of cadonilimab as an adjuvant treatment for hepatocellular carcinoma is ongoing. Furthermore, a Phase 3 study comparing cadonilimab with chemotherapy to tislelizumab Injection with chemotherapy is underway for the first-line treatment of PD-L1 expression-negative non-small cell lung cancer.

About Akeso, Inc.

Akeso (HKEX: 09926) is a commercial-stage biopharmaceutical company committed to discovering, developing, manufacturing, and commercializing innovative medicines that address significant medical needs globally. Since our inception , we have established a distinctive and integrated R&D innovation system with the comprehensive end-to-end drug development platform (ACE Platform) and bi-specific antibody drug development technology (Tetrabody) as the fundamental components, a GMP-compliant manufacturing system and a commercialization system with an advanced operation mode.

Akeso is actively developing a diverse pipeline of over 30 innovative assets in areas such as cancer, autoimmune disease, inflammation, metabolic disease, and other therapeutic fields. Among these, 19 assets have entered the clinical stage, with 3 innovative drugs already approved, NDAs for 4 drugs and 6 indications accepted, and 13 ongoing Phase III studies. Utilizing its proprietary Tetrabody technology, Akeso has successfully developed the first-in-class PD-1/CTLA-4 bispecific antibody drug to the market. Additionally, the company has five other innovative bispecific antibody drugs in the clinical stage, including ivonescimab (PD-1/VEGF), PD-1/LAG-3, TIGIT/TGF-Beta, PD-1/CD73, and claudin18.2/CD47 bispecific antibodies.

In June 2022, cadonilimab was approved by the NMPA and became the first commercialized bispecific IO drug globally. Another Akeso internally discovered and developed oncology product, penpulimab (a PD-1 antibody), was granted marketing approval in China in August 2021. In December 2022, Akeso entered into a collaboration and license agreement for up to US$5 billion with Summit Therapeutics to accelerate global development and commercialization of ivonescimab. In August, the NDA submission of ivonescimab was accepted by China's NMPA and granted Priority Review. Akeso is listed on the Main Board of the Stock Exchange of Hong Kong Limited.

Source: Akeso, Inc