From The Editor | June 23, 2022

Novartis' T-Charge Platform Spotlights Auto CAR-Ts


By Erin Harris, Editor-In-Chief, Cell & Gene
Follow Me On Twitter @ErinHarris_1


You don’t have search long and hard for news in the CGT sector about companies concentrating on developing and manufacturing allogeneic, or off-the-shelf- therapies. Take Poseida Therapeutics for example. The broad platform technology company boasts auto and allo CAR T-cell therapies for oncology and beyond as well as in vivo and ex vivo gene therapies. In Episode 26 of Cell & Gene: The Podcast, Poseida Therapeutics’ CEO, Mark Gergen, and I talked about the clinical-stage biopharma’s plan to develop allogeneic versions of all of its hematological and solid tumor product candidates.

There are no FDA-approved allogeneic CAR-T therapies … yet. Earlier this month, I wrote about Precision Biosciences and its quest to become the first FDA-approved off-the-shelf CAR T therapy with its lead candidate, PBCAR0191, as a potential allogeneic CD19 CAR-T for the growing autologous CAR T relapsed patient population with aggressive lymphomas. And, we’ve covered the development and manufacturing challenges associated with both auto and allo CAR-T. Indeed, autologous cell therapies are approved, proven, and lifesaving, living drugs. They are also very costly to manufacture. Scale up of manufacturing for allogeneic cells is like the techniques used to make protein drugs and other large-scale cell derived materials while autologous cells require scale out, the production of many individual products at the same time. So it makes sense why so many innovator companies are focusing on allogenic therapies.

Enter Novartis’ T-Charge Platform

Good or bad, Novartis’ Kymriah is well documented. And, now, it’s the pharma’s T-Charge platform that has some biotechs clamoring for partnership. According to Novartis, T-Charge is a next-generation CAR-T platform, innovated at the Novartis Institutes for BioMedical Research (NIBR), that will serve as the foundation for various new investigational CAR-T cell therapies in the Novartis pipeline. Unlike autologous CAR-T therapies, Novartis’ T-Charge process sees most of the CAR- T cell expansion occurring within the patient’s body thereby reducing the time the cells spend ex vivo helps preserve the naive and stem cell memory T cells. At last year’s American Society of Hematology Annual Meeting & Exposition (ASH), Novartis presented early clinical data from ongoing Phase I clinical trials with YTB323 (anti-CD19) and PHE885 (anti-BCMA), the first Novartis CAR-T cell therapies developed using this platform. Initial efficacy data showed a complete response rate of 73% (95% CI: 44.9, 92.2) at month three for the 15 patients with diffuse large B-cell lymphoma (DLBCL) who received dose level two of YTB323. For the 11 patients with multiple myeloma who received the two highest doses of PHE885, the best overall response was 100%.

Jeff Legos, Ph.D., Novartis’ global head of oncology and hematology development has been quoted as saying that with T-Charge, the company aims to reduce the manufacturing timeline for immune cells to less than two days and thus cut the overall timeline “from vein to door” by at least half. Besides a shortened timeline, T cells made from the platform are more potent and have better ability to self-proliferate inside the body. Therefore, a therapy would need fewer cells.

Novartis has not disclosed the biotechs interested in partnership, as no agreements have been made to date. The company does not have plans to attempt to adapt it for allogeneic therapies. They are focused on hematology but have not ruled out solid tumors.