On May 8, 2023 Sana Biotechnology, Inc. (NASDAQ: SANA), a company focused on changing the possible for patients through engineered cells, reported financial results and business highlights for the first quarter 2023 (Press release, Sana Biotechnology, MAY 8, 2023, View Source [SID1234631177]).
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"Our initial human studies using Sana’s hypoimmune technology remain on track, as we have begun enrolling patients in our SC291 trial and expect to deliver data from two clinical studies in 2023," said Steve Harr, Sana’s President and Chief Executive Officer. "We are also making progress in our earlier-stage pipeline and are on pace to file two additional INDs later this year and potentially three more in 2024. The quality of our key hires, publications in high quality peer-reviewed journals, and presentations at important scientific conferences are recent validations of the science behind Sana’s programs. Our capital position and people give us the resources for multiple data read-outs with our current balance sheet, and we continue to be optimistic about our future, with the opportunity to see the potential of these medicines in patients starting this year."
Recent Corporate Highlights
Opportunity for clinical proof of concept for two different first-in-human studies, each with the potential for initial clinical data this year
SC291 is an ex vivo hypoimmune-modified CD19-directed allogeneic CAR T cell therapy. The goal of the hypoimmune platform is to overcome the immunologic rejection of allogeneic cells, which, if successful with SC291, may result in longer CAR T cell persistence and a higher rate of durable complete responses for patients with B-cell malignancies.
Received clearance from the Food and Drug Administration (FDA) to initiate a first-in-human Phase 1 study of SC291 in patients with B-cell malignancies (ARDENT).
Began enrollment in the ARDENT Phase 1 study.
Granted Fast Track Designation for SC291 by the FDA for the treatment of relapsed/refractory (r/r) large B-cell lymphoma and r/r chronic lymphocytic leukemia.
SC291 has the potential to serve as clinical proof-of-platform for other hypoimmune-modified CAR T cell candidates using validated CAR constructs in development at Sana for hematological malignancies, such as SC262 (CD22) and SC255 (BCMA). Sana’s goal is to file INDs for SC262 later this year and SC255 in 2024.
Sana is developing SC451, a hypoimmune-modified stem-cell derived islet cell therapy for patients with type 1 diabetes. SC451, which is engineered with Sana’s hypoimmune technology, has the potential to replace missing islet cells without immunosuppression in persons with type 1 diabetes by evading allogeneic and autoimmune responses.
Expect initial data later this year from an investigator-sponsored trial transplanting hypoimmune-modified primary human islet cells into type 1 diabetes patients. The goal of the study is to show cell survival and immune evasion without the need for any immunosuppression.
Sana’s goal is to file an IND for SC451 in 2024.
Published preclinical data in Nature Communications describing immune evasion, persistence, and durable anti-tumor activity of Sana’s hypoimmune-modified CD19-directed CAR T cells
Sana developed hypoimmune-modified CD19 targeted allogeneic CAR T cells and compared them to unmodified CD19-targeted allogeneic CAR T cells in a murine leukemia model with a humanized immune system.
Although both hypoimmune-modified and unmodified CAR T cells showed robust early tumor killing, cell durability was much greater in humanized mice treated with hypoimmune-modified cells. Hypoimmune-modified allogeneic CAR T cells persisted and removed all evidence of tumor for the duration of the study. Hypoimmune-modified CAR T cells also cleared all evidence of tumor after re-injection with cancer cells 90 days into the study. In contrast and consistent with the experience in patients to date, unmodified allogeneic CAR T cells show greatly reduced persistence and a high rate of tumor recurrence in this model.
These studies provide additional insight for SC291 and the allogeneic hypoimmune CAR T platform more broadly, including SC262 and SC255.
Published preclinical data in Science Translational Medicine demonstrating that Sana’s hypoimmune-modified pseudo-islets control type 1 diabetes
Sana developed hypoimmune-modified human islet cells, which cluster into effective endocrine organoids termed "pseudo islets" (p-islets) and studied these p-islets in multiple preclinical models.
Preclinical data showed that p-islets survive, persist, escape allogeneic rejection, and normalize blood glucose in diabetic models with humanized immune systems.
Two different murine models showed that the hypoimmune-modified cells can evade autoimmune rejection and normalize blood glucose. First, these cells were studied in the NOD mouse model, which is the standard model for autoimmunity in diabetes. Second, Sana created a humanized mouse model with immune cells from a diabetic person and transplanted pancreatic islet cells derived from the diabetic person’s stem cells. In both cases, unmodified pancreatic islet cells were rapidly cleared by the immune system. In contrast, hypoimmune-modified pancreatic islet cells survived, persisted, and provided sustained blood glucose control in both models.
These studies provide additional insight for SC451 in persons with type 1 diabetes.
Published preclinical data in Nature Biotechnology demonstrating that Sana’s hypoimmune-modified cells survive allogeneic transplant across several species, including non-human primates (NHPs) with normal immune systems, and remain fully functional
Sana developed hypoimmune-modified NHP induced pluripotent stem cells (iPSCs) and transplanted them into immune-competent NHPs. Results were compared to transplantation of unmodified iPSCs into immune-competent NHPs.
Data showed that hypoimmune-modified iPSCs survived for the duration of the study (16 weeks), while unmodified iPSCs disappeared within two weeks. There was an antibody and T cell response directed toward unmodified cells, but not hypoimmune-modified cells.
Hypoimmune-modified primary NHP pancreatic islet cells survived 40 weeks (duration of the study) after allogeneic transplantation into an immune-competent NHP versus less than one week for unmodified primary islet cells.
Hypoimmune-modified iPSCs were differentiated into pancreatic islet cells. Transplantation of hypoimmune-modified iPSC-derived pancreatic cells into allogeneic diabetic mice with a humanized immune system showed immune evasion after transplantation for the duration of the studies (4 weeks) and amelioration of diabetes and normalization of blood glucose levels.
Presented multiple abstracts at the 2023 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting highlighting ex vivo hypoimmune-modified allogeneic CAR T cells, as well as in vivo cell-specific delivery of genetic material using Sana’s in vivo fusogen platform
Presented preclinical data demonstrating that hypoimmune-modified CAR T cells provide lasting tumor control in immunocompetent allogeneic humanized mice even with tumor re-challenge.
Presented preclinical data in a late-breaking poster presentation demonstrating that the increased potency of CD8-targeted fusosomes enhances CAR transgene delivery to resting primary T cells.
Presented preclinical data demonstrating the effectiveness of Sana’s fully human CD19 CAR delivered by CD8-targeted fusosomes in tumor killing assays. These fusosomes led to similar levels of tumor control as ex vivo generated CD19 CAR T cells.
Presented preclinical data demonstrating increased potency of CD8-targeted fusosomes delivering a CD19 CAR with pre-treatment of resting T cells with IL-7, rapamycin, or both. Pre-treatment with these molecules led to increased anti-tumor efficacy through increased T cell transduction and greater CAR T cell expansion.
Strengthened Research and Development leadership with the appointment of two seasoned drug developers
Appointed Doug Williams, Ph.D., as President of Research and Development. Dr. Williams has over 30 years of experience leading R&D organizations – including at Biogen, Seattle Genetics (now Seagen), Amgen, and Immunex – and over the course of his career has participated in the development of over a dozen approved drugs including multiple blockbusters.
Appointed Gary Meininger, M.D., as Chief Medical Officer. Dr. Meininger has approximately 20 years of experience in drug development. Most recently, he was at Vertex as Senior Vice President, Head of Clinical Development for Vertex Cell and Genetic Therapies and previously was at Janssen and Merck. Dr. Meininger is currently the industry representative to the FDA’s Endocrine and Metabolic Drug Advisory Committee.
First Quarter 2023 Financial Results
GAAP Results
Cash Position: Cash, cash equivalents, and marketable securities as of March 31, 2023 were $355.1 million compared to $434.0 million as of December 31, 2022. The decrease of $78.9 million was primarily driven by cash used in operations of $79.2 million and cash used for the purchase of property and equipment of $2.2 million. Cash used in operations includes multiple cash payments that will not recur this year. In addition, our cash balance will increase by $6.1 million in July 2023 as the letter of credit related to the Fremont facility reduces from $6.7 million to $0.6 million in July 2023.
Research and Development Expenses: For the three months ended March 31, 2023, research and development expenses, inclusive of non-cash expenses, were $67.2 million compared to $72.7 for the same period in 2022. The decrease of $5.5 million was primarily due to a decline in costs to acquire technology, laboratory supplies, third-party manufacturing costs, and other research costs. These decreases were partially offset by increased clinical development costs, personnel-related costs, operating costs for our manufacturing facility in Bothell, Washington, and other allocated costs. Research and development expenses include non-cash stock-based compensation of $6.0 million and $5.7 million, for the three months ended March 31, 2023 and 2022, respectively.
Research and Development Related Success Payments and Contingent Consideration: For the three months ended March 31, 2023, we recognized an expense of $0.1 million and a gain of $55.4 million for the same period in 2022, in connection with the change in the estimated fair value of the success payment liabilities and contingent consideration in aggregate. The value of these potential liabilities may fluctuate significantly with changes in Sana’s market capitalization and stock price.
General and Administrative Expenses: General and administrative expenses for the three months ended March 31, 2023, inclusive of non-cash expenses, were $16.8 million compared to $14.4 million for the same period in 2022. The increase of $2.4 million was primarily due to operating costs for the previously planned manufacturing facility, formerly in research and development expense, and increased non-cash stock-based compensation and personnel-related expenses. General and administrative expenses include non-cash stock-based compensation of $2.8 million and $2.0 million, for the three months ended March 31, 2023 and 2022, respectively.
Net Loss: Net loss for the three months ended March 31, 2023 was $82.1 million, or $0.43 per share, compared to $31.4 million, or $0.17 per share, for the same period in 2022.
Non-GAAP Measures
Non-GAAP Operating Cash Burn: Non-GAAP operating cash burn for the three months ended March 31, 2023 was $74.8 million compared to $82.0 million for the same period in 2022. Non-GAAP operating cash burn is the decrease in cash, cash equivalents, and marketable securities, excluding cash inflows from financing activities, cash outflows from business development and non-recurring restructuring activities, and the purchase of property and equipment.
Non-GAAP Net Loss: Non-GAAP net loss for the three months ended March 31, 2023 was $82.0 million, or $0.43 per share, compared to $86.9 million, or $0.47 per share, for the same period in 2022. Non-GAAP net loss excludes non-cash expenses related to the change in the estimated fair value of contingent consideration and success payment liabilities.
A discussion of non-GAAP measures, including a reconciliation of GAAP and non-GAAP measures, is presented below under "Non-GAAP Financial Measures."