Roche doubles down on Poseida

After another stumble in TIGIT, Roche is already looking towards the next thing: allogeneic Car-T. The company has spent $1bn up front on Poseida, building on a licensing deal signed in 2022.

One question is what Roche wants that it doesn’t already have from the original tie up. The Swiss group highlighted Poseida’s manufacturing capability, as well as one Car-T in particular that was outside the original deal, P-MUC1C-ALLO1. Roche is also getting two early-stage non-viral gene therapy projects in hereditary angioedema (HAE) and haemophilia, which might have been a draw, as the big pharma already has a strong presence in the latter.

However, there are big questions around allogeneic Car-T – not least whether therapy can produce durable responses.

Allo allo

Poseida’s most advanced project is the BCMA-targeting P-BCMA-ALLO1; this was named in the $110m 2022 tie up, along with the bispecific P-CD19CD20-ALLO1.

But the jury is still out on P-BCMA-ALLO1. Data at last year’s ASH meeting looked cherrypicked, while a more recent update, at the International Myeloma Society meeting in September, found an ORR of 54% across the intent-to-treat population. However, Poseida homed in on a cohort of patients who got what it termed the optimised lymphodepletion regimen – here, the ORR was 91% among 23 patients.

Either way, Poseida has fallen well behind; it had once hoped to get an autologous BMCA-targeting Car-T filed with regulators in 2020.

Meanwhile, the first clinical data on P-CD19CD20-ALLO1 are expected next year. This project is being tested initially in B-cell malignancnies, although there are also plans for trials in multiple sclerosis and lupus, which might be more tempting for Roche.

As for the aforementioned solid tumour contender P-MUC1C-ALLO1, that has produced one partial response among four evaluable patients with various cancers. Since then, Poseida announced plans to test higher lymphodepletion regimens in its phase 1 trial; an update is expected this year.

One project that might not go any further is P-BCMACD19-ALLO1, on which Roche turned down an option in September. Before Tuesday’s deal, the big pharma still had a chance to opt in on a CD70-directed asset.

Poseida’s allogeneic Car-T pipeline

Source: OncologyPipeline, company presentation.

Poseida’s preclinical HAE and haemophilia assets, meanwhile, could be a bonus for Roche. The group already has a haemophilia A blockbuster in the form of Hemlibra, but a previous attempt to get into gene therapy, via the acquisition of Spark Therapeutics, has fallen flat.

Poseida’s hopefuls use non-viral lipid nanoparticle delivery, which could help avoid some of the problems of current gene therapies – although the assets still have a long way to go.

The deal terms include a non-tradeable contingent value right (CVR) of up to $4 per share. $2 will be payable upon a pivotal trial start for P-BCMA-ALLO1 (by December 2028); $1 upon the first sale of P-BCMA-ALLO1 (by December 2031); and $1 upon an autoimmune pivotal trial start for P-CD19CD20-ALLO1 (by December 2034).

If all of these are hit, the acquisition's value will creep up to $1.5bn. This is small change for Roche, but represents a huge premium for Poseida, whose market cap was just $279m on Monday. It’ll be a while before it becomes apparent whether this was a panic buy, or a justified investment.