Roche makes takeover bid for Poseida Therapeutics Inc

The boards of directors have already agreed on an offer price of US$9 per share in cash, equivalent to US$1bn. In addition, there is an option to receive a non-tradeable contingent value right (CVR) for up to an aggregate of US$4.00 per share in cash, which would increase the value of the transaction, which is expected to be completed in Q1/2025, to US$1.5bn.

Roche is thus killing two birds with one stone: In addition to half a dozen already partnered allogeneic CAR-T cell programmes in the field of haematological cancers, the pharma giant is also acquiring two allogeneic bispecific CAR-T cell assets plus not public programmes in the field of solid tumours, autoimmune diseases, and neurology, as well as manufacturing capabilities that allow production of  200 doses with one batch and delivery and gene editing technology platforms. These include the viral vector-free vector platform, which complements Roche’s AAV-based platform for gene therapies established in Europe. Roche had long focussed on bispecific antibodies due to the high manufacturing costs of autologous gene and cell therapies, but then, with the US$4.3bn take-over of Spark Therapeutics Inc in 2019, added gene therapies to its portfolio. With the acquisition of Poseida Therapeutics, Roche obvisously want to make CAR-T cell therapies a business case and maybe makes a second attempt with gene therapies, after two stopped haemophilia A gene therapies from Spark. An indication of continued interest in gene therapies is the acquisition of gene therapy drug delivery specialist Dyno Therapeutics for US$50m upfront in late October, whose technology could solve previous targeting problems with AAV-based gene therapies.

Although Genentech and Poseida spoke of the goal of developing next-generation CAR-T cell therapies, they preferably meant CAR-T cell therapies from donor cells that can be produced centrally.Poseida Therapeutics also has CAR-T cell therapies that are intended to bind to various receptors in solid tumours and thus increase tumour selectivity. Although the objective response rate is 70-90%, the rate of higher-grade cytokine reactions (CRS) is also very high.

Poseida’s lead programme, P-BCMA-ALLO1, is an allogeneic CAR-T therapy targeting B-cell maturation antigen (BCMA) and is being tested as a fourth-line therapy for relapsed/refractory multiple myeloma (MM) in Phase I/II trials. The second Phase I candidate, P-CD19CD20-ALLO1, is an allogeneic dual CAR-T in B-cell malignancies. FDA INDs have been recently filed to investigate this programme’s potential for patients with multiple sclerosis and systemic lupus erythematosus. In which Roche already has broad experience with anti-CD20 monoclonal antibodies. A second preclinical programme, P-CD70-ALLO1, with bispecific CAR-Ts for the treatment of multiple myeloma was also partnered prior to Roche’s offer.

Of particular interest to Roche should be Poseida’s Phase 1 programme P-MUC1C-Allo in solid tumours of epthelial origin such as breast, ovarian, colprectal, lung, pancreatic and renal cancer, which targets the mucin 1C cancer antigen overexpressed in solid tumours.It contains 3 transgenes: an anti-MUC1-C humanized scFv-based CAR, a DHFR drug selection gene to improve product homogeneity, and an iCasp9-based safety switch gene to allow for rapid ablation of the CAR-T if required. The graft-versus-host rejection that normally occurs with allogeneic therapies. In Poseida’s CAR-T cell candidates, rejection, which normally occurs in allogeneic therapies, is suppressed by knockout of the T cell receptor beta chain 1 gene and the β2-microglobulin gene eliminates the expression of MHC class I to attenuate host-vs-graft responses.Poseida is also developing the preclinical programme P-PSMA-ALLO1 targeting PSMA for prostate cancer.

To date, no CAR-T cell therapy has received approval for the treatment of solid tumours. Only the T-CR-T cell therapies targeting intracellular cancer antigens from British Adaptimmune Ltd have received the first accelerated approval for the treatment of sarcomas this year, and a BLA for a second candidate has already been applied for.Roche’s advantage from the acquisition would be severalfold: firstly, the acquired manufacturing capacities could be used for centralised and more cost-effective production, which would make CAR-T therapies immensely cheaper. Secondly, Roche is acquiring Poseida’s non-viral transposon-based DNA delivery system that enables the insertion of genes for two full length chimeric antigen receptors (CARs) into T stem cell memory cells (TSCM). This technology could also be used for Roche’s portfolio of haematological gene therapies. These are complemented by several preclinical in vivo gene therapy candidates based on Poseida’s proprietary genome editing platforms, including its non-viral transposon-based DNA delivery system, Cas-CLOVER™ Site-Specific Gene Editing System, Booster Molecule and nanoparticle gene delivery technologies, as well as in-house GMP cell therapy manufacturing.