Poseida Therapeutics, a clinical-stage biopharmaceutical company utilizing proprietary genetic engineering platform technologies to create cell and gene therapeutics with the capacity to cure, confirmed it has entered into a broad strategic collaboration and license agreement with Roche, focused on developing allogeneic CAR-T therapies directed to hematologic malignancies.

The global collaboration covers the research and development of multiple existing and novel “off-the-shelf” cell therapies against targets in multiple myeloma, B-cell lymphomas, and other hematologic indications.

“We are excited to partner and collaborate with Roche, one of the world’s largest biotechnology companies, which has a successful track record in the discovery, development, and commercialization of innovative medicines,” said Mark Gergen, Chief Executive Officer of Poseida.

“Roche is an ideal strategic partner for Poseida with its industry-leading R&D capabilities in oncology, complementary technologies and expertise, and global regulatory and commercial capabilities. Working together, we look forward to advancing novel allogeneic cell therapies based upon Poseida’s technologies for patients battling cancer.”

Complementary expertise
Under the agreement, Roche will receive from Poseida either exclusive rights or options to develop and commercialize a number of allogeneic CAR-T programs in Poseida’s portfolio that are directed to hematologic malignancies, including P-BCMA-ALLO1, an allogeneic CAR-T for the treatment of multiple myeloma and for which a Phase 1 study is underway, and P-CD19CD20-ALLO1, an allogeneic dual CAR-T for the treatment of B-cell malignancies with an IND expected in 2023.

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Interim data reported during the 2021 American Society of Hematology (ASH) Annual Meeting from its Phase 1/2 PRIME clinical trial of P-BCMA-101 for the treatment of relapsed/refractory multiple myeloma (R/R MM), demonstrated that P-BCMA-101, a non-viral transposon-based autologous CAR-T, was well tolerated and demonstrated strong anti-tumor activity in advanced, late line R/R MM patients. The learnings from P-BCMA-101 informed the development of Poseida’s first allogeneic program, P-BCMA-ALLO1 which is also being evaluated in R/R MM patients.

Poseida’s first fully allogeneic CAR-T cell product, P-BCMA-ALLO1 utilizes Poseida’s proprietary piggyBac® DNA delivery system and Cas-CLOVER™ site-specific gene editing system to create an allogeneic product that prevents both graft-vs-host and host-vs-graft diseases and also incorporates a next-generation BCMA binder. P-BCMA-ALLO1 manufacturing involves a proprietary “booster” molecule that allows for numerous doses to be produced from a single manufacturing run, while maintaining desirable Tscm cells, which can reach percentages in the 60-80% range.[1]

Building on complementary expertise and capabilities, the parties will also collaborate in a research program to create and develop next-generation features and improvements for allogeneic CAR-T therapies, from which they would jointly develop additional allogeneic CAR-T product candidates directed to existing and new hematologic targets.

For a subset of both the Poseida portfolio programs licensed or optioned to Roche and the parties’ future collaboration programs, Poseida will conduct the Phase 1 studies and manufacture clinical materials before transitioning the programs to Roche for further development and commercialization. Roche will be solely responsible for the late-stage clinical development and global commercialization of all products that are subject to the collaboration.

“We are excited to partner with Poseida to further explore the potential of allogeneic cell therapies to transform cancer care by developing off-the-shelf products that can address high unmet medical needs for a broad patient population,” said James Sabry, Global Head of Pharma Partnering at Roche.

“Poseida’s differentiated platform technologies complement our ongoing internal efforts and partnerships to discover and develop cell therapies as the next generation of medicines for patients,” Sabry added.

Under the agreement, Poseida will receive $110 million upfront and could receive up to $110 million in near-term milestones and other payments in the next several years. In addition, Poseida is eligible to receive research, development, launch, and net sales milestones and other payments potentially up to $6 billion in aggregate value, as well as tiered net sales royalties into the low double digits, across multiple programs.

“We are thrilled that Roche has embraced the opportunity to partner with us and use Poseida’s unique allogeneic approach to develop CAR-T product candidates,” said Devon J. Shedlock, Ph.D., Chief Scientific Officer, Cell Therapy at Poseida.

“Using our proprietary technologies and manufacturing process including our booster molecule, we have the potential to develop and manufacture a product with high levels of stem cell memory T cells, which are correlated with potent antitumor efficacy in the clinic, at a scale that can potentially reach more patients and enable broad commercial use.”

The effectiveness of the agreement is subject to clearance under the Hart-Scott-Rodino Antitrust Improvements Act (HSR Act).

Clinical trials
P-BCMA-ALLO1 Allogeneic CAR-T Cells in the Treatment of Subjects With Multiple Myeloma (MM) – NCT04960579
P-MUC1C-ALLO1 Allogeneic CAR-T Cells in the Treatment of Subjects With Advanced or Metastatic Solid Tumors – NCT05239143

Ostertag E. PiggyBac and High-Fidelity Gene Editing for Fully Allogeneic CAR-T. Corporate Presentation. April 2021.

Featured image: Researchers in a laboratory. Photo courtesy:© 2022 F. Hoffmann-La Roche Ltd – All rights reserved / Image used with permission

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