Thread by @Biotech2k1

1/ Looking at Hypoimmune from $SANA

This is the data release from the NHP data.

2/ First demonstration of the survival of allogeneic iPSCs transplanted into an immunocompetent non-human primate model without the need for immune suppression

3/ Transplanting allogeneic cells into a primate without immune suppression represents a key step toward widespread treatment of disease using engineered cells

4/ “These findings represent a major breakthrough in cell transplantation, as demonstration of immune evasion and durable cell survival in non-human primates with a healthy immune system has not been achieved before,” said Steve Harr, Sana’s President and Chief Executive Officer

5/ “Since the debut of organ, tissue, and cellular transplantation, immune rejection of allogeneic transplants has been a significant challenge preventing widespread utilization of these therapies.

6/ Our team has now shown the potential of these gene-modified cells in multiple animal models, and the next step is to apply this technology in humans in several therapeutic contexts, with our first investigational new drug (IND) application as early as next year.”

7/ In this study, allogeneic iPSCs were transplanted intramuscularly into healthy NHPs without immunosuppression (n=8), split into two cohorts. The first cohort received unmodified allogeneic iPSCs, while the second cohort received HIP-modified allogeneic iPSCs.

8/ The unmodified cells disappeared rapidly in all NHPs, with significant T cell activation and antibody production. The HIP-modified iPSCs survived in all four monkeys for the duration of the study (up to four months at data lock),

9/ and there was no evidence of a systemic immune response, including no T cell activation, antibody production, or NK cell activity (p<0.007 comparing cell survival, p<0.0001 comparing T cell activation and antibody production).

10/ Six weeks after the initial dose, the dosing was reversed, or crossed over, so that the NHPs received the opposite type of cells in another site in the body.

11/ Unmodified iPSCs again evoked a rapid systemic immune response in all NHPs, with activation of T cells and antibody production, and disappeared within days.

12/ Importantly, HIP-modified cells continued to survive in another site in the body, despite the immune response against unmodified cells. Separately, HIP-modified iPSCs were transplanted into the four NHPs that had previous T cell and antibody responses to unmodified cells.

13/ In these animals, there was no evidence of immune response and the HIP modified cells again survived through the end of the study (p<0.006 comparing cell survival, p<0.0001 comparing T cell activation and antibody production).

14/ These data, showing survival for HIP-modified iPSCs despite either an ongoing or pre-existing immune response, suggest the potential to use HIP-modified cells in patients with auto-immune disorders and to re-administer HIP-modified cells.