Carcell (Kemagene) Leads Global Advancement in Mature Red Blood Cell Therapeutics

On September 13, 2022, Pablo J. Cagnoni, President and Chief Executive Officer of Rubius Therapeutics (“Rubius”), stated during a conference call with investors and media that progress achieved with its next-generation red blood cell-based cell conjugation platform was driving a technological restructuring of its Red Cell Therapeutics program. This signifies that Rubius will abandon its first-generation engineered red blood cell technology based on hematopoietic stem cell gene modification and shift its focus to mature red blood cell therapies.

Non-damaging Red Blood Cell Therapy was pioneered by Dr. Shi Jiahai during his postdoctoral research under Professor Harvey Lodish at the Whitehead Institute. The first generation of this therapy was based on engineered red blood cells derived from genetically modified hematopoietic stem cells, which also served as one of the foundational technologies for Rubius Therapeutics, later founded by Harvey Lodish. In 2015, Dr. Shi returned to City University of Hong Kong to continue developing next-generation technologies. By early 2021, he successfully developed a next-generation mature red blood cell therapy that no longer requires hematopoietic stem cells. Instead, it directly utilizes effector molecules covalently linked to the surface of mature red blood cells, enabling them to mimic antigen-presenting cells to activate anti-tumor immune responses, or to carry autoantigens to suppress hypersensitivity reactions.

In August 2021, the next-generation mature red blood cell therapy initiative secured seed funding from EVX Ventures, a Singapore-based biopharmaceutical incubator, leading to the establishment of Carcell (hereinafter referred to as “Carcell”). Headquartered in Shanghai Waigaoqiao, Carcell is dedicated to developing next-generation cell and gene therapies using novel delivery systems such as engineered red blood cells and lipid nanoparticles.

Compared with first-generation technologies, the next-generation mature red blood cell (RBC) therapy causes no damage to RBCs, significantly extends the in vivo half-life of RBC-based drugs, and enables better control over both the drug loading capacity and the types of drugs loaded per RBC. The Kemexin team has successfully loaded three different protein drugs onto a single RBC while maintaining their respective biological activities. Furthermore, the team has demonstrated that this next-generation mature RBC therapy can effectively inhibit PD-1 non-responsive tumor types in animal models within the context of cancer immunotherapy. Additionally, Kemexin has shown that the pharmacokinetics (PK) of engineered RBCs in animals are similar to those of normal RBCs, providing preliminary validation of their superior safety profile.

According to Rubius, due to the iteration of its technological platform, the new therapy delivers a higher effective dose by leveraging prolonged circulation time and administering higher cell doses. Furthermore, owing to its greater versatility, the new therapy can be engineered to display diverse payloads, immunomodulators, small molecules, and proteins on the cell surface to enhance potency. In addition, the next-generation manufacturing process utilizes blood bank donations as raw materials, eliminating the need for stem cell differentiation or genetic engineering, thereby significantly reducing production costs.

The founder of Kemeixin stated, “These ideas align perfectly with Kemeixin’s practices and have been effectively validated.” Rubius’s transformation further demonstrates Kemeixin’s leadership and forward-thinking approach in the field of red blood cell therapy. In China, we are capable of conducting basic research that is slightly ahead of the global curve and holds significant potential for medical translation. We anticipate that innovative engineered red blood cell drug delivery technologies, characterized by enhanced safety and efficacy, will shine brightly in the fields of tumor immunology and autoimmune diseases as the technology gradually matures.