Nothing Short of Remarkable

Remarkable! Not sure how else to describe it.??

We at Poseida have long held the belief that our highly differentiated approach to cell therapy is unique and that stem cell memory T cells (Tscm) are the ideal approach for cell therapy in oncology and beyond.?For those not as familiar with our story, Tscm cells are a subset of T cells that have unique properties: (i) they have the ability to engraft; (ii) they are very long-lived; (iii) they are multi-potent; (iv) they are self-replicating; (v) they have an ability to create wave-after-wave of more differentiated cells; and (vi) they have the potential to result in a product with a better safety and tolerability profile – to name just a few advantages. These attributes, among others, are what make Tscm cells the ideal cell type for cell therapy in our view.?

We announced an oral presentation at the annual meeting of the Society of Hematologic Oncology (SOHO) in Houston, where a case study was presented that validates our long-held belief in Tscm and the promise it portends – but with a twist that also has opened the door to a whole new approach for the next generation of cell therapy.

So, what was the finding?

The details can be found in the press release, but the high-level story is exciting.

We present the observation of a patient who was treated in 2020 in our original autologous BCMA CAR-T trial for multiple myeloma. After being treated with P-BCMA-101, the patient achieved a stringent complete response and stayed in a complete response for approximately two and a half years. At that point, the patient developed signs of relapse and was treated with several other therapies that had little to no impact on their disease. In late 2023, the patient was treated with a T Cell Engager (TCE) therapy targeting a different antigen (i.e. not BCMA). ?The patient only received several doses and did not complete a full course of the TCE treatment.

However, that is where things got interesting. It turns out that the patient still had engrafted P-BCMA-101 CAR-T cells even though it had been more than three years since their initial CAR-T treatment. Those CAR-T cells were apparently stimulated by the TCE, re-expanded to high levels, began killing tumor cells and put the patient back into a stringent complete response and off all other therapy, where they remain today. Simply astounding.?

So, why be so excited??

We think there are many reasons to be excited about this finding and the implications for the field – or at least for our high-Tscm allogeneic platform in particular.

First and foremost, the patient is back in a stringent complete response and doing great now approaching four years after they were originally treated, which is always a cause for celebration.

Second, the case study shows without a doubt that CAR-Tscm cells can engraft and last a long time in a patient. This is strong evidence of the importance and power of Tscm. For those not as familiar with T cell biology, these had to be engrafted Tscm cells as it is well known that other T cell subtypes simply do not live that long in vivo. The fact that the CAR-Tscm cells can persist, be stimulated, expand and kill tumor again after this long period is equally impressive and an unprecedented finding to our knowledge.

Third, the ability to stimulate CAR-T cells with a TCE in vivo is a potentially important and exciting finding with many implications for our platform and programs for the future.? Cool stuff to be sure.

So, where do we go from here??

We think this finding is exciting in many ways and we are already moving down the path of exploring its implications for our next generation of cell therapy.

While the case study was with our autologous CAR-T program, we believe these findings are applicable and exciting for our allogeneic approach. Followers of Poseida will know that we believe strongly that the future of cell therapy is allogeneic. We also believe that there are ways to leverage cell therapy in combination with bi-specific antibodies such as TCEs and this case study definitely underscores that belief. Importantly, with our proprietary technology and our ability to include many bells and whistles in our allogeneic cells, leveraging these findings into new and exciting approaches in allogeneic cell therapy is a natural next innovative step for us that others will struggle to be able to follow.

These findings have already pointed us in multiple directions to turn that belief into a tangible reality and generating additional intellectual property in the process.?We are planning for some additional disclosures at some upcoming scientific meetings and our Cell Therapy R&D Day to begin charting a course for where this could take us. If you follow cell therapy - watch this space.

“I love it when a plan comes together.”

I know there will be some who say that I make too much of this, that it is only a single case study of a single patient, or that it is autologous and not allogeneic so not translatable, but for those who have been following the Poseida story it is undeniable evidence of the potential in Tscm that we have been talking about for years. It supports our efforts to preserve the Tscm phenotype in all of our programs. We think it makes clear that Tscm is, indeed, the ideal cell type for cell therapies.

A special Thank You to the entire ‘A Team’ at Poseida for keeping the faith and continuing the mission for helping patients.? Stay tuned for our next episode.