Sana Biotechnology(SANA) - 2025 Q4 - Annual Report

Cell Therapy Development - The company is developing SC451, a HIP-modified stem cell-derived pancreatic islet cell therapy for type 1 diabetes (T1D), aiming for euglycemia without insulin injections or immunosuppression [24]. - The company plans to file an investigational new drug application (IND) for SC451 and begin a Phase 1 clinical trial as early as this year [30]. - The company suspended development of its allogeneic CAR T programs to focus on SC451 and SG293, believing this will have a greater impact on patients and shareholders [32]. - The company aims to leverage its ex vivo and in vivo cell engineering platforms to maximize the potential success of its therapies [33]. - The company retains worldwide rights to its product candidates, focusing on significant disease types including T1D and B cell cancers [38]. - The company is investing in scalable manufacturing processes and has partnered with CDMOs to ensure access to necessary facilities and reagents for its cell therapy programs [51]. - The focus on pancreatic islet cells is driven by high unmet medical needs and existing proof of concept in both human and animal models [58]. - The company is developing a proprietary protocol to differentiate hypoimmune iPSCs into mature, insulin-secreting islet cells, focusing on achieving greater purity and function compared to existing protocols [130]. - The company plans to transfer its manufacturing process to GMP facilities and expects to submit an IND and begin Phase 1 clinical trials for SC451 as early as this year [165]. Hypoimmune Technology - The HIP technology allows transplanted cells to evade immune recognition, which has been validated in preclinical studies and a first-in-human study [25][29]. - The company emphasizes the importance of hypoimmune technology to evade immune rejection, which is critical for developing impactful cell therapies [58]. - The company is developing hypoimmune technology that modifies cells to evade both adaptive and innate immune responses, focusing on iPSCs for therapeutic applications [65]. - Hypoimmune cells have been shown to survive and evade immune detection in various preclinical models, including NHPs, with some cells maintaining viability for up to 16 weeks without immunosuppression [90]. - The hypoimmune technology involves three key genome modifications: disruption of MHC class I and II expression, and overexpression of CD47 to enhance immune evasion [72]. - The company’s hypoimmune technology aims to create a universal cell type that can be used across various therapeutic applications, addressing the limitations of current immune rejection strategies [67]. - The survival of hypoimmune iPSCs in NHPs suggests potential for broader applications in allogeneic cell therapies without the need for lifelong immunosuppression [90]. - The company’s research highlights the importance of all three genome modifications in protecting cells from immune rejection following transplantation [75]. Clinical Outcomes and Efficacy - UP421, an allogeneic primary islet cell therapy, demonstrated survival and function for twelve months post-transplant in a T1D patient without immunosuppression, achieving the primary endpoint of safety [26][27]. - The Phase 1 trial for UP421, a HIP-modified allogeneic primary islet cell therapy, began in December 2024, focusing on safety and secondary endpoints related to cell survival and function [45]. - The first-in-human transplantation of UP421 demonstrated graft survival and function without immunosuppression, with detectable C-peptide production throughout the 12-month study [121]. - Comprehensive immune evasion was observed in HIP-modified pancreatic islet cells, supporting their potential for long-term function in transplantation [121]. - After transplantation of HIP-modified islet cells, the NHP achieved insulin independence for six months, with stable blood glucose levels and normalized serum C-peptide levels [99]. - C-peptide levels in the NHP were greater than 2 ng/ml one week post-transplantation and remained stable throughout the six-month follow-up [107]. - Long-term studies indicate that HIP-modified iPSC islet cells maintained blood glucose control for over 64 weeks, with no tumor formation or other histological abnormalities observed [146]. - Preclinical studies indicate that hypoimmune primary islets can mediate insulin independence in diabetic NHPs without the use of immunosuppression [74]. Gene Delivery and Manufacturing - The fusogen technology enables targeted delivery of diverse payloads, with preclinical studies demonstrating successful targeting of CD8, CD4, and CD3 T cells [186]. - The fusosome system has approximately twice the genetic capacity of commonly used AAV vectors, allowing for the delivery of larger payloads [193]. - Preclinical studies have shown that fusosomes can achieve a 56% genetic modification rate in human hepatocytes and a 55% reduction in circulating TTR protein levels [191]. - The company is developing the SG293 fusosome product candidate, targeting CD19+ cells to treat hematologic malignancies and autoimmune diseases [196]. - The platform aims to improve manufacturing consistency, scalability, and reduce costs compared to current autologous solutions [195]. - The company is investing in process development and manufacturing sciences to enable scalable production of in vivo therapies [170]. CAR T Cell Therapy - SG293, a next-generation in vivo CAR T product candidate, is being developed for B cell malignancies and autoimmune diseases, with initial clinical data expected as early as this year [31]. - The in vivo CAR T pipeline has advanced to SG293, which aims to improve safety and efficacy by enabling direct generation of CAR T cells in patients without the need for lymphodepleting chemotherapy [47]. - The company's T cell-targeted fusosome approach aims to improve CAR T cell therapy accessibility and effectiveness, potentially eliminating the need for ex vivo manufacturing [202]. - Preclinical data shows that fusosomes can efficiently deliver CAR genes to T cells, resulting in effective killing of CD19+ leukemia cells in culture and in vivo [207]. - Following administration of SG299, CAR-positive T cells reached peak expansion of approximately 30-45% of circulating T cells by day 7, with deep B cell depletion maintained for at least four weeks [209]. - The potential for durable B cell depletion without lymphodepletion has been demonstrated, suggesting a significant advancement in CAR T cell therapy [210].