Considering Manufacturing and Commercial Advantages, Poseida Makes Strategic Shift Towards Allogeneic CAR-T Products

San Diego-based Poseida Therapeutics had always set its goal to move into allogeneic products. In its Q3 earnings announcement yesterday, the company officially announced its strategic shift to an allogeneic CAR-T BCMA clinical program for multiple myeloma.

“While data in the autologous trial showed meaningful responses and a favorable safety profile, the Company’s strategic focus has long been on allogeneic CAR-T therapies, leveraging the learnings of the autologous CAR-T program to provide benefits beyond those of autologous CAR-T, including a more desirable off-the-shelf product profile for future commercialization while maintaining the tolerability advantage of our autologous product candidate,” the company said in a statement.

Allogeneic CAR T-Cell Therapy 

CAR-T cell therapy is a mode of treatment that uses engineered T cells to fight cancer. These cells can either come from the patient (autologous CAR-T therapy) or a donor (allogeneic CAR-T therapy).

While autologous approaches are promising, there are significant challenges. The cells extracted from patients must be shipped, engineered, and re-infused in the patient within a short span of time. Besides, it is labor-intensive and quite expensive. Kymriah, the first CAR-T cell therapy approved in the US, is currently priced at $475,000.

On the contrary, ‘off-the-shelf’ allogeneic treatments have many potential advantages. Since the cells can be extracted from donors and stored in bulk, they can be modified and infused in multiple patients in a short time.

Poseida believes that allogeneic CAR-T is the future and is therefore winding down its lead autologous candidate for multiple myeloma—P-BCMA-101, which is currently in a Phase 1 expansion trial. Instead, it is going to focus on advancing P-BCMA-ALLO1, its first allogeneic CAR-T product for which it recently received IND clearance from the FDA.

The company said that P-BCMA-ALLO1 has the potential to deliver up to hundreds of doses per manufacturing run, thereby dramatically reducing both clinical trial costs and ultimately commercial product cost compared to the autologous P-BCMA-101 program.

“The initiation of our P-BCMA-ALLO1 clinical trial represents the beginning of a long-planned strategic transition to what we believe is the ‘holy grail’ of cell therapy for oncology, a fully allogeneic CAR-T with a fully-humanized heavy chain BCMA binder and a high percentage of T_SCM cells which we believe are the key to success,” said Eric Ostertag, M.D., Ph.D., Chief Executive Officer of Poseida.

“While we believe the P-BCMA-101 autologous program has competitive advantages and would be approvable, one long-term strategic benefit of that program has been to inform our highly-differentiated allogeneic approach. With the P-BCMA-ALLO1 clinical program now underway and with very high confidence in our allogeneic platform, we will begin a planned wind down of P-BCMA-101.”

However, Poseida has to overcome the life-threatening complications associated with allogeneic CAR T cells like graft-versus-host disease to obtain market success.

Author

Rajaneesh K. Gopinath