How a Stepwise Clinical Strategy De-Risks Immune Evasion in Islet Cell Therapy

Steve Harr, MD, Sana Biotechnology’s (Sana) president and CEO, outlines the clinical development principles behind the company's gene-modified islet program in the 3rd segment of an interview with BioPharm International®. Dr Harr also explains why he believes a definitive cure for type 1 diabetes (T1D) is now a matter of execution rather than a scientific possibility.

Dr Harr describes 3 principles guiding Sana's cell therapy clinical strategy. First, early and open dialog with regulators and clinical development sites is essential, particularly given how much is still learned in first-in-human studies about what a cell therapy drug is. Second, patient selection is critical across broad disease indications in which phenotypic variability within a patient population can significantly affect outcomes. Third, teams should prioritize attacking the most relevant scientific question as rapidly as possible, taking down one risk at a time rather than attempting to resolve multiple unknowns simultaneously.

How did Sana design its first-in-human islet study to answer the most critical translational question?

Dr Harr explains that the company's use of gene-modified cadaveric islets at a conservative dose was a deliberate experimental design choice, not the end therapeutic goal. The approach was intended to answer a single question: does immune evasion without immunosuppression translate from animal models into humans? The 14-month survival data from the company’s study confirmed that this translation to humans does happen, he notes.

"I would argue now that a cure is inevitable," Dr Harr states, citing 3 converging bodies of evidence: James Shapiro's work demonstrating decades of insulin independence with transplanted islets under immunosuppression;¹ other researchers’ demonstration that stem-cell-derived islets can sustain insulin independence for years; and Sana Biotechnology's own demonstration of transplantation without immunosuppression.

Sana's ultimate goal, Dr Harr emphasizes, is a gene-modified, stem-cell-derived islet that can be manufactured at scale and broadly transplanted, delivering a single treatment resulting in no insulin, no immunosuppression, and no ongoing monitoring. He adds that success in T1D would likely establish a platform applicable to other diseases caused by missing or damaged cells.

Learn more about Sana Biotechnology’s work in segment 1 and segment 2 of Dr Harr’s interview.

About the speaker

Steve Harr, MD, President and CEO, Sana Biotechnology

Prior to co-founding Sana, Dr Harr served as chief financial officer and head of Corporate Development for Juno Therapeutics until its acquisition by Celgene in early 2018. He was a member of the board of directors of Loxo Oncology prior to its acquisition by Eli Lilly and Company in early 2019. Dr Harr also was a co-founder and member of the board of directors of JW Therapeutics, a cell therapy company in China. Prior to joining Juno, Dr Harr was at Morgan Stanley, as managing director and head of Biotechnology Investment Banking, and previously as a biotech research analyst and co-head of global healthcare research. He obtained his MD from Johns Hopkins University School of Medicine. He was an internal medicine resident at the University of California, San Francisco, and performed research at Harvard Medical School and Massachusetts General Hospital.

Reference

1. Kumar D, Tanwar R. World's first: stem cell therapy reverses diabetes. Stem Cell Res Ther. 2024;15(1):487. doi:10.1186/s13287-024-04036-0