International Stem Cell Corp.

Pictured: Collage of a brain and stem cells/Taylor Tieden for BioSpace Could stem cell therapies make the Parkinsonian brain generate dopamine again? Some companies, including BlueRock Therapeutics and International Stem Cell Corporation, are banking on it. Parkinson’s disease is currently treated with dopamine replacement agents, but the efficacy of these drugs is limited and they come with challenging side effects. Some in the stem cell field say these new therapies, though early-stage, could ultimately be a better, safer option. In a March 2024 report, GlobalData touted the “early promise” of cell therapies to address the motor and non-motor symptoms of Parkinson’s disease with minimal adverse effects. ‘Resetting the Clock’ With more than 10 million people around the world living with Parkinson’s disease, the treatment market is currently valued at $5.56 billion and is expected to reach $6.63 billion by 2029. A progressive disease of the nervous system, Parkinson’s is characterized by the degradation of neurons in the part of the brain that controls movement. The loss of these neurons slows the production of dopamine, leading to a combination of motor symptoms, including writhing movements, resting tremors and muscle stiffness, which can be lessened with levodopa and dopamine-agonists—drugs that behave like dopamine. The disease also brings non-motor symptoms, including depression, hyposmia, dysphasia and psychosis. Levodopa is currently the “gold standard” treatment for Parkinson’s. Although it provides a dopamine kick, the drug is laden with severe adverse effects, including hallucinations, dyskinesia and loss of impulse control. These side effects can occur a dopamine response is stimulated in several parts of the brain through medication, Agnete Kirkeby, a stem cell scientist at Lund University and the University of Copenhagen, told BioSpace. Levodopa also provides only a small window of relief for patients, Kirkeby said. In an emailed statement to BioSpace, GlobalData analysts Lorraine Palmer and Christie Wong said early clinical trials of stem cell transplantation in Parkinson’s have shown a reduction in motor and non-motor symptoms. “However, the subject size of these clinical trials have been small and were not powered to measure statistical significance,” they said, adding that large-scale, pivotal trials will be required to investigate how safely and how well the therapies work. “Currently, there are no therapies which recover lost dopaminergic neurons so if cell therapies do end up meeting their hopes of replacing dopaminergic neurons,” they could be market changers, Palmer and Wong said. During her postdoctoral days at Lund, Kirkeby, along with her supervisor, designed a method to grow transplantable dopamine cells from embryonic stem cells. “When we transplant the cells, we transplant [them] to a very particular region of the brain that is involved in motor control,” she explained. Kirkeby is currently leading a preclinical study of STEM-PD sponsored by Lund, a stem-cell therapy intended to replace lost dopamine neurons in the brains of Parkinson’s patients. Cambridge, Mass.–based BlueRock Therapeutics, a Bayer subsidiary, is also developing a stem cell–based therapy, called bemdaneprocel. “You can think about it almost like you’re resetting the clock for those people who live with Parkinson’s disease by providing them cells, which have the potential to integrate and re-establish some of the neural networks and circuitry in that part of the brain,” Ahmed Enayetallah, head of development at BlueRock, told BioSpace. Cell Therapies for Parkinson’s in the Pipeline There are currently seven stem cell therapies for Parkinson’s disease in Phase I clinical trials or later. Three of these—sponsored by BlueRock, Celavie Biosciences and International Stem Cell Corporation—have completed and published results. In the Phase I trial of bemdaneprocel, neuronal progenitor stem cells derived from donors were transplanted into 12 patients, whose progress was monitored for 18 months. During the first year, the patients were treated with immunosuppressive drugs. The cells survived and bemdaneprocel was tolerated by patients throughout the trial period, Enayetallah said, even after immunosuppression was discontinued. The trial met multiple clinical endpoints and broadened the window at which the patients experienced relief from disease symptoms, he added. Unlike with current treatments, Enayetallah said, there were no reported cases of dyskinesia or other adverse events except gastrointestinal bleeding and seizure, which he attributed to the surgical procedure and not the therapy itself. Having a one-time treatment for Parkinson’s disease would be a paradigm shift, Enayetallah said. Another therapy, ISC-hpNSC, is in development by California-based International Stem Cell Corporation. Upon completion of a Phase I trial, patients’ ON-Time—a period where Parkinson’s medications like levodopa bring about good motor control—increased by 65% over two years, and OFF-Time decreased by 55% within the same period, the company reported in June 2021. The cells were well-tolerated with no serious adverse events. With therapies such as these, Kirkeby said it is possible that the cells could overgrow and generate too many cells in the brain, but so far, neither trials of STEM-PD nor bemdaneprocel have recorded this adverse effect. And while stem cell therapies are currently aimed at relieving the motor symptoms of Parkinson’s, Enayetallah said bemdaneprocel’s trial results hint at improved quality of life and psychiatric outcomes. Kirkeby also indicated that her lab is working on stem cell therapies that would target non-motor symptoms such as cognitive impairment. Enayetallah noted that therapeutic development in Parkinson’s is “incredibly challenging” and plagued with the highest failure rates in drug development. However, he said, the results of BlueRock’s Phase I trial are a significant step toward bringing a “transformational therapy” to patients. “Cell therapy in neurology is something that hasn’t been explored to that extent before. We’re paving the road here.” Patience Asanga is a Nigeria-based freelance science journalist who writes about the environment, biotechnology and life sciences.

First demonstration of the survival of allogeneic islet cells, cardiomyocytes, and retinal pigment epithelium cells transplanted into an immunocompetent non-human primate model without any immune suppression The islet autoimmune data suggest that cells with hypoimmune (HIP) edits evade allogeneic immune response and autoimmune response in a type 1 diabetes mouse model Transplanting allogeneic cells into a non-human primate without immune suppression represents a key step toward development of engineered cells for the treatment of disease SEATTLE, June 17, 2022 (GLOBE NEWSWIRE) -- Sana Biotechnology, Inc. (NASDAQ: SANA), a company focused on creating and delivering engineered cells as medicines, presented data showing survival of transplanted allogeneic, hypoimmune cells of several different types in a variety of locations in non-human primates (NHPs). The transplanted cells were induced pluripotent stem cell (iPSC)-derived cardiomyocytes, retinal pigment epithelium (RPE) cells, and islet cells, which were engineered to include Sana’s hypoimmune gene modifications that enable immune evasion. Data were presented by Sonja Schrepfer, M.D., Ph.D., Head of Hypoimmune Platform at Sana, during sessions at the International Society for Stem Cell Research (ISSCR) 2022 Annual Meeting taking place from Wednesday, June 15 through Sunday, June 19 in San Francisco. “These data, demonstrating that three types of transplanted cells are able to survive and function in NHPs without immunosuppression, highlight the transformative potential of Sana’s hypoimmune platform across a number of different cell types that can address a variety of diseases,” said Steve Harr, Sana’s President and Chief Executive Officer. “As an example, the use of allogeneic islet transplant has had limited success in treating type 1 diabetes due to morbidities from the necessary immunosuppression. In contrast, our data indicate that we successfully engineered HIP human pancreatic islet cells to evade immune recognition, and these cells persisted and normalized glucose levels in in vivo models. We are applying the hypoimmune platform to a number of programs in our pipeline, including SC291, our CD19 targeted allogeneic CAR T therapy for blood cancers, with a goal of an IND this year, and SC451, our islet cell program with a goal of an IND for the treatment of type 1 diabetes in 2023.” Transplanting cells or tissues from a donor to a different recipient currently requires intense immunosuppression to prevent rejection of the transplant. Sana’s HIP platform goal is to eliminate the need for immunosuppression by cloaking cells from immune recognition. The platform includes disruption of the major histocompatibility (MHC) class I and MHC class II expression to hide cells from the adaptive immune system, which includes antibody and T cell responses. These changes alone make cells susceptible to innate immune cell killing, in particular by natural killer (NK) cells. However, Sana’s HIP platform additionally provides for evasion from innate cell killing, including via the overexpression of CD47, a molecule that protects HIP-modified cells from innate cell killing involving either NK cells or macrophages. HIP-modified pluripotent stem cells can serve as the starting material for the differentiation of specialized cell types to serve as cell-based therapeutics. Sana’s goal is to use these HIP-modified cells to replace damaged or missing cells in the body in a number of different diseases, including, among others, cancer, type 1 diabetes, and cardiac disease. Survival of HIP-modified islet cells for type 1 diabetes Primary NHP pancreatic islet cells In this study, allogeneic primary pancreatic islet cells were HIP edited and transplanted intramuscularly into a healthy NHP without immunosuppression (n=1) as proof-of-concept. Islet cell survival was followed by in vivo bioluminescence imaging. The imaging showed that transplanted cells survived for the duration of the study (three months at data lock) with no evidence of a systemic immune response, including no T cell activation, antibody production, or NK cell activity as seen previously with other HIP edited cell types in NHPs (iPSC, cardiomyocytes, and RPE). Allogeneic unmodified primary pancreatic islet cells disappeared rapidly within 2 weeks. Autoimmune miceType 1 diabetes is a disease in which the patient’s immune system attacks and kills their pancreatic beta cells. Therefore, allogeneic transplanted cells in type 1 diabetes need to overcome both allogeneic and autoimmune rejection. Autoimmune diabetes arises spontaneously in non-obese diabetic (NOD) mice, and the pathophysiology of this disease shares many similarities with human type 1 diabetes. Since its development in 1980, this model has represented the gold standard of spontaneous disease models, allowing for investigation of autoimmune diabetes disease progression and susceptibility traits, as well as to test a wide array of potential treatments and therapies. In this study, syngeneic or allogeneic mouse islet cells were transplanted intramuscularly without immunosuppression into diabetic autoimmune mice (n=15), split into three cohorts. The first cohort received unmodified syngeneic islet cells, the second cohort received unmodified allogeneic islet cells, and the third cohort received allogeneic HIP islet cells. The unmodified cells disappeared rapidly in the allogeneic setting (within 10 days) as well as in the syngeneic setting (within two weeks) due to autoimmune recognition. Neither cohort had a decrease in glucose levels. The HIP islet cells survived in all five diabetic mice for the duration of the study (one month at data lock), and glucose levels dropped, demonstrating therapeutic function of the HIP islet cells. Survival of HIP-modified cardiomyocytes (iPSC-derived)In this study, allogeneic iPSC-derived cardiomyocytes were transplanted without immunosuppression into the hearts of healthy NHPs split into two cohorts. The first cohort received unmodified allogeneic iPSC-derived cardiomyocytes (WT; n=2), while the second cohort received allogeneic HIP iPSC-derived cardiomyocytes (HIP; n=4). The unmodified cells were almost eliminated in all NHPs, with significant T cell activation in addition to antibody production and binding. The HIP cardiomyocytes survived in all four monkeys for the duration of the study (up to two months at data lock), and there was no evidence of a systemic immune response, including no T cell activation, antibody production, or NK cell activity. After two months, injection sites were recovered, and local immune cells were analyzed for their donor-specific cell recognition and killing. While local immune cells kill unmodified cardiomyocytes, HIP cardiomyocytes were not recognized by these immune cells. Survival of HIP-modified retinal pigmental epithelial (RPE) cells (iPSC-derived)In this study, allogeneic iPSC-derived RPEs were transplanted into the eye of healthy NHPs without immunosuppression split into two cohorts. The first cohort received unmodified allogeneic iPSC-derived RPE (WT; n=3), while the second cohort received allogeneic HIP iPSC-derived RPE (HIP; n=3). The unmodified cells were almost completely eliminated in all NHPs within three weeks, with significant T cell activation, antibody production and local microglial activation, demonstrating in this context that the eye is not an “immunoprivileged” site. The HIP RPE survived in all three monkeys for the duration of the study (three weeks at data lock), and there was no evidence of a systemic immune response, including no T cell activation, antibody production, microglial or NK cell activity. Two weeks after the initial dose, the NHPs were re-injected with the same cell type into the second eye, so that the NHPs received a total of two doses. Unmodified WT RPEs again evoked a rapid systemic immune response in all NHPs, with activation of T cells and antibody production, and cells almost completely eliminate within one week. HIP RPE cells continued to survive even after re-injection without stimulation of adaptive or innate immune responses. These data suggest the potential to re-administer HIP RPE cells. Sana intends to submit the data behind its presentations for publication in a peer-reviewed journal. About Hypoimmune PlatformSana’s hypoimmune platform is designed to create cells ex vivo that can “hide” from the patient’s immune system to enable the transplant of allogeneic cells without the need for immunosuppression. We are applying the hypoimmune technology to both pluripotent stem cells, which can then be differentiated into multiple cell types, and to donor-derived allogeneic T cells, with the goal of making potent and persistent CAR T cells at scale. Preclinical data demonstrates across a variety of cell types that these transplanted allogeneic cells are able to evade both the innate and adaptive arms of the immune system while retaining their activity. Our most advanced programs utilizing this platform include an allogeneic CAR T program targeting CD19+ cancers and stem-cell derived beta islet cells for patients with type 1 diabetes. About Sana BiotechnologySana Biotechnology, Inc. is focused on creating and delivering engineered cells as medicines for patients. We share a vision of repairing and controlling genes, replacing missing or damaged cells, and making our therapies broadly available to patients. We are a passionate group of people working together to create an enduring company that changes how the world treats disease. Sana has operations in Seattle, Cambridge, South San Francisco, and Rochester. For more information about Sana Biotechnology, please visit https://sana.com/. Cautionary Note Regarding Forward-Looking StatementsThis press release contains forward-looking statements about Sana Biotechnology, Inc. (the “Company,” “we,” “us,” or “our”) within the meaning of the federal securities laws, including those related to the company’s vision, progress, and business plans; expectations for its development programs, product candidates and technology platforms, including its pre-clinical, clinical and regulatory development plans and timing expectations; the potential ability to make allogeneic, hypoimmune cells, including iPSC-derived cardiomyocytes, RPE cells, and islet cells, that survive and evade the immune system without immunosuppression and the potential persistence and efficacy of such hypoimmune cells; and the Company’s expectations with respect to the submission and publication of data. All statements other than statements of historical facts contained in this press release, including, among others, statements regarding the Company’s strategy, expectations, cash runway and future financial condition, future operations, and prospects, are forward-looking statements. In some cases, you can identify forward-looking statements by terminology such as “aim,” “anticipate,” “assume,” “believe,” “contemplate,” “continue,” “could,” “design,” “due,” “estimate,” “expect,” “goal,” “intend,” “may,” “objective,” “plan,” “positioned,” “potential,” “predict,” “seek,” “should,” “target,” “will,” “would” and other similar expressions that are predictions of or indicate future events and future trends, or the negative of these terms or other comparable terminology. The Company has based these forward-looking statements largely on its current expectations, estimates, forecasts and projections about future events and financial trends that it believes may affect its financial condition, results of operations, business strategy and financial needs. In light of the significant uncertainties in these forward-looking statements, you should not rely upon forward-looking statements as predictions of future events. These statements are subject to risks and uncertainties that could cause the actual results to vary materially, including, among others, the risks inherent in drug development such as those associated with the initiation, cost, timing, progress and results of the Company’s current and future research and development programs, preclinical and clinical trials, as well as the economic, market and social disruptions due to the ongoing COVID-19 public health crisis. For a detailed discussion of the risk factors that could affect the Company’s actual results, please refer to the risk factors identified in the Company’s SEC reports, including but not limited to its Quarterly Report on Form 10-Q dated May 10, 2022. Except as required by law, the Company undertakes no obligation to update publicly any forward-looking statements for any reason. Investor Relations & Media:Nicole KeithInvestor.relations@sana.commedia@sana.com

BOSTON, May 31, 2022 /PRNewswire/ -- Erbi Biosystems, Inc., a global leader in dose-scale, fully automated microbioreactors for cell therapy development and manufacturing, today announced the appointment of Brad Hamilton to the position of Chief Scientific Officer, effective immediately. In this role, Mr. Hamilton will lead the company's scientific research efforts to advance product development, partner relationships, and commercialization. He was previously Chief Scientific Officer at GoodCell and Chief Technology Officer at ReproCELL. "Brad is an exceptional scientific leader in the industry, and I am excited to have him join Erbi's executive team. His knowledge and successes within the field of stem cell biology research will help us accelerate the delivery of tools and protocols that will revolutionize the manufacturing of emerging cell therapies," said Dr. Michael Chiu, CEO of Erbi Biosystems. "I'm delighted to join Erbi. The technology platform central to Erbi's flagship product is transformative, and I'm excited to facilitate its development and expansion into clinical cell therapy processes," said Mr. Hamilton. "It's an opportune time to deliver tools like the Breez to the community to support the development and manufacturing of these potentially life-saving cell therapies." Mr. Hamilton's scientific leadership in the industry spans more than 25 years, including his roles as the founder and Chief Scientific Officer at GoodCell and Chief Technology Officer for ReproCELL, a multinational stem cell company focused on developing novel stem cell technologies and therapies. His work as a founding scientist and Director of Research for Stemgent led to the development of groundbreaking RNA-mediated cellular reprogramming technologies and applications for the generation of induced pluripotent stem cells from clinically accessible samples such as human skin, blood, and urine. Prior to heading up scientific programs for GoodCell, ReproCELL, and Stemgent, he led research programs at RheoGene and Upstate Biotech (acquired by Millipore), focusing on developing novel discovery technologies such as orthogonal, inducible mammalian gene expression switches, and RNAi screening platforms. Mr. Hamilton holds an MS in Biotechnology from the University of Tennessee, Knoxville, and a BS in Biology from James Madison University. He is a member of the International Society of Stem Cell Research (ISSCR), the International Society for Cell and Gene Therapy (ISCT), and the American Society of Gene and Cell Therapy (ASGCT). About Erbi Biosystems Erbi Biosystems is revolutionizing cell therapy and bioprocessing process development with the Breez, a fully automated 2 mL TruePerfusion™ bioreactor that reduces by at least 1/3 the skilled labor required. The platform offers a 90% footprint reduction using disposable, functionally closed single-use cassettes with proprietary microfluidic technology processes capable of performing activation, transduction, intensified growth, and diafiltration steps. It offers closed-loop control of pH, total cell density (OD), dissolved oxygen, and CO2 measurements. The integrated online sensors and intuitive software deliver sophisticated feeding strategies, increased cell concentration, low shear, bubble-free mixing with high kLa resulting in performance far exceeding the static and benchtop reactors typically used today. A single 2mL volume cassette can deliver up to 400M (CHO and T-cells), sufficient for most development needs and a number of CAR-T clinical dose regimes. Erbi Biosystems has expanded into a 10,000 sq. ft. R&D and manufacturing facility north of Cambridge, Massachusetts. The company has systems installed across the US, Europe, and China. After doubling its employee headcount in 2021, the company is expected to maintain this growth in 2022 as it develops GMP compliant systems to address the clinical manufacturing needs.