Athersys Profile
Athersys, Inc. operates as a biotechnology company that focuses primarily on the field of regenerative medicine.
The company has established a portfolio of therapeutic product development programs to address significant unmet medical needs in multiple disease areas. The company's MultiStem (invimestrocel) cell therapy, a patented and proprietary allogeneic stem cell product candidate, is its lead platform product and is in late-stage clinical development. The company's most advanced therapeutic program focuses on the treatment of ischemic stroke, which is being evaluated in a pivotal Phase 3 clinical trial ongoing in the United States under a Special Protocol Assessment agreement (SPA), from the U.S. Food and Drug Administration (FDA), in Europe and in certain other international locations. The company's clinical development programs focus on treating critical care and other conditions where standard of care is limited or inadequate for many patients.
MultiStem received Regenerative Medicine Advanced Therapy (RMAT) designation for [the treatment of] both ischemic stroke and acute respiratory distress syndrome (ARDS). MultiStem treatment has shown the potential to enhance tissue repair and healing in multiple ways, including reducing inflammatory damage, protecting tissue that is at risk following acute or ischemic injury, and promoting formation of new blood vessels in regions of ischemic injury. These cells appear to be responsive to the environment in which they are administered, by homing to sites of injury and/or organs involved in injury response and providing active disease response. These cells also produce proteins that may provide benefit in both acute and chronic conditions and regulate other cell types.
The company has a collaboration with HEALIOS K.K. (Healios) to develop and commercialize MultiStem for the treatment of certain indications in Japan. Among other things, Healios has a license to the company's technology and is responsible for the development and commercialization of MultiStem for ischemic stroke and ARDS in Japan on an exclusive basis.
The company's lead program is its pivotal Phase 3 clinical trial to evaluate the potential for MultiStem treatment of patients who have suffered neurological damage from an ischemic stroke entitled, 'MultiStem Administration for Stroke Treatment and Enhanced Recovery Study-2' (MASTERS-2). The results from its completed Phase 2 study demonstrated favorable tolerability for MultiStem, consistent with the results from prior studies.
The company's MASTERS-2 trial treating ischemic stroke patients is ongoing in the United States and certain other international locations. The company received agreement from the FDA under a SPA that the design and planned analysis of MASTERS-2 adequately address the objectives necessary to support a regulatory submission. It is possible that following MASTERS-2 the company will conduct either a post-registry study or a confirmatory study, depending on the strength and robustness of the study outcome. The FDA granted the company Fast Track and RMAT designations for its clinical product for the treatment of ischemic stroke.
The design of MASTERS-2 has also received a Final Scientific Advice positive opinion from the European Medicines Agency (EMA) representing the EMA's agreement that successful results from the trial could result in registration and marketing approval of the MultiStem cell therapy. The company has also received Advanced Therapy Medicinal Product (ATMP) Certificate for Quality Data from the EMA.
On March 21, 2023, the company held a Type B meeting with the FDA to address proposed modifications to its primary and secondary endpoints for its MASTERS-2 clinical trial protocol.
The company has also worked closely with Healios to support its development efforts in Japan.
In August 2021, Healios reported top-line data from its ONE-BRIDGE study in Japan for patients with pneumonia-induced and COVID-induced ARDS. In April 2022, Healios announced that, while the Pharmaceuticals and Medical Devices Agency in Japan (PMDA) did not disagree with the efficacy and safety conclusions of the ONE-BRIDGE study, the PMDA advised Healios that additional supporting data is necessary for application for approval of MultiStem treatment for the ARDS indication in Japan. As a result of the guidance from the PMDA, Healios disclosed that it will continue discussions with the PMDA.
In January 2022, the company received approval from the FDA to use MultiStem product manufactured with its bioreactor-based technology in the study, an important development milestone. The company made the decision to suspend the MACOVIA study in June 2022. The company has data evaluating two different dosing levels of MultiStem. The company engaged with the Biomedical Advanced Research and Development Authority (BARDA) through a Request for Information process to explore the use of MultiStem for ARDS and other COVID co-morbidities. The company intends to take the next step with BARDA and participate in a Request for Proposal process.
Under the company's collaboration with Healios to develop and commercialize MultiStem for the treatment of certain indications in Japan, Healios has a license to its technology and is responsible for the development and commercialization of MultiStem for certain indications in Japan on an exclusive basis. Healios' license includes MultiStem cell therapy for ischemic stroke and ARDS in Japan and the use of the company's technology for Healios' organ bud program targeted to liver disease and other indications, as well as certain other rights, including a license for the use of its MultiStem product to treat certain ophthalmological indications and a license to treat diseases of the liver, kidney, pancreas, and intestinal tissue through administration of its products in combination with cells derived from induced pluripotent stem cells, or iPSC-derived cells. The company has provided manufacturing services and supplied Healios with clinical product for the licensed indications. Additionally, to assist Healios with the advancement of its ischemic stroke and ARDS programs in Japan, the company has granted to Healios, subject to the terms of the licensing agreement, a non-exclusive license to make and has made MultiStem for the treatment of ischemic stroke and ARDS solely for use in Japan.
In April 2020, the FDA authorized the initiation of a Phase 2 clinical trial evaluating MultiStem cell therapy for the early treatment of traumatic injuries, entitled, 'MultiStem Administration for Trauma Related Inflammation and Complications', or MATRICS-1 and the subsequent complications that result following severe trauma, and patient enrollment commenced in December 2020.
In August 2021, the company entered into a Comprehensive Framework Agreement for Commercial Manufacturing and Ongoing Support, or the Framework Agreement, with Healios, which better aligns the collaboration structure for potential commercial success in Japan. The Framework Agreement provides Healios, among other things, access to its manufacturing technology to enable Healios to manufacture MultiStem products using a qualified manufacturer, clarifies its role in providing support services to Healios necessary for regulatory approval, manufacturing readiness and commercial launch in Japan, provides for the deferral of certain milestones and royalties to enable Healios to invest in certain manufacturing activities, and expands Healios' license in Japan to include two new unspecified additional indications under certain conditions.
In January 2022, the company received FDA approval for use of its bioreactor manufactured 3D product for Phase 2 clinical trials.
Programs
By applying its proprietary MultiStem cell therapy product, the company established therapeutic product development programs treating neurological conditions, inflammatory and immune disorders, certain pulmonary conditions, cardiovascular disease, and other conditions where the standard of care is limited or inadequate for many patients. The company's lead programs focus in the critical care area, with treatment provided in hospitals often in intensive care situations. The company's programs in clinical development include the following:
Ischemic Stroke: The company is conducting a pivotal Phase 3 clinical trial of MultiStem cell therapy for the treatment of ischemic stroke, referred to as MASTERS-2. The company's MASTERS-2 clinical trial is a randomized, double-blind, placebo-controlled clinical trial designed to enroll 300 patients in the United States, and certain other international locations, who have suffered moderate to moderate-severe ischemic stroke. As of January 2023, the company was more than 50% enrolled in the trial with the highest quarterly enrollment rates that it has experienced during the trial. The company plans to provide an updated trial completion estimate in mid-2023.
The MASTERS-2 study has received several regulatory distinctions, including SPA, Fast Track and RMAT designations from the FDA, as well as a Final Scientific Advice positive opinion and ATMP Certificate for Quality data from the EMA.
In addition, Healios, the company's collaborator in Japan, conducted a clinical trial, TREASURE, evaluating the safety and efficacy of the administration of MultiStem cell therapy for the treatment of ischemic stroke. In May 2022, Healios reported topline results for the TREASURE study.
ARDS: In January 2019 and January 2020, the company announced summary results and one-year follow up results, respectively, from its exploratory clinical study of the intravenous administration of MultiStem cell therapy to treat patients who are suffering from ARDS, which is referred to as the MUST-ARDS study. The study results demonstrated a predictable and favorable tolerability profile. Importantly, there were lower mortality and greater ventilator-free days, or VFD, and ICU-free days in the MultiStem-treated patient group compared to the placebo group. In April 2019, the MultiStem cell therapy received Fast Track designation for the treatment of ARDS, and in September 2020, RMAT designation was received for the same program. In April 2020, in response to the COVID-19 pandemic, the FDA authorized the initiation of a Phase 2/3 pivotal study to assess the safety and efficacy of MultiStem therapy in subjects with moderate to severe ARDS, or the MACOVIA study. The MACOVIA study features an open-label lead-in dose escalation portion of the study, followed by double-blinded, randomized, placebo-controlled study cohorts, and the study is designed to enroll up to approximately 400 patients at leading pulmonary critical care centers throughout the United States. During 2021, the company amended the protocol with the FDA to adjust the scope of the MACOVIA study to include subjects with ARDS induced by pathogens other than COVID-19. The company received approval from the FDA to use MultiStem product manufactured with its bioreactor-based technology in the study, an important product development milestone. The company has suspended initiating new sites and enrolling patients in the Phase 2 part of the MACOVIA trial prior to enrolling patients using its bioreactor-based technology. The company has data evaluating two different dosing levels of MultiStem.
Further, in 2019, Healios initiated the ONE-BRIDGE study in Japan for patients with pneumonia-induced and COVID-induced ARDS and, in August 2021, Healios reported top-line data from the ONE-BRIDGE study. In April 2022, Healios announced that, while the PMDA did not disagree with the efficacy and safety conclusions of the ONE-BRIDGE study, the PMDA advised Healios that additional supporting data is necessary for application for approval of MultiStem treatment for the ARDS indication in Japan. As a result of the guidance from the PMDA, Healios disclosed that it will continue discussions with PMDA.
Trauma: In April 2020, the FDA authorized the initiation of a Phase 2 clinical trial evaluating MultiStem cell therapy for the early treatment of traumatic injuries and the subsequent complications that result following severe traumatic injury, and patient enrollment commenced in December 2020. This first-ever study of a cell therapy for the treatment of a wide range of traumatic injuries is being conducted by UTHealth at the Memorial Hermann-Texas Medical Center in Houston, Texas, one of the busiest Level 1 trauma centers in the United States. The study is being supported under a grant awarded to the McGovern Medical School at UTHealth from the Medical Technology Enterprise Consortium, and the Memorial Hermann Foundation is providing additional funding. The study is a randomized, double-blind, placebo-controlled Phase 2 clinical trial estimated to enroll approximately 150 severely injured trauma patients within hours of hospitalization who have survived initial treatment and are admitted to the ICU.
MultiStem Therapy - A Novel Therapeutic Modality
The company is developing its MultiStem cell therapy, a proprietary non-embryonic, allogeneic stem cell product candidate, that has potential utility for treating a broad range of diseases and could have widespread application in the field of regenerative medicine. Potential applications of MultiStem cell therapy include the treatment of critical care indications, neurological conditions, inflammatory and immune disorders, certain pulmonary conditions, cardiovascular disease, and other conditions where the standard of care is limited or inadequate for many patients. The company has open Investigational New Drugs (INDs) for the study of MultiStem administration in distinct clinical indications, and several clinical trials are ongoing.
MultiStem cell therapy is a patented biologic product that is manufactured from human stem cells obtained from adult bone marrow, although these cells may alternatively be obtained from other tissue sources. The product consists of a special class of human stem cells that have the ability to express a range of therapeutically relevant proteins and other factors, as well as from multiple cell types. Factors expressed by the cells have the potential to deliver a therapeutic benefit in several ways, such as the reduction of inflammation, regulation of immune system function, protection of damaged or injured tissue, the formation of new blood vessels in regions of ischemic injury and augmentation of tissue repair and healing in other ways.
Neurological Injury and Disease - MultiStem for Ischemic Stroke
The primary focus of the company's regenerative medicine program is MultiStem administration for the treatment of neurological injury as a result of acute or chronic conditions.
The company has published research with independent collaborating investigators that demonstrates that MultiStem administration conveys biological benefits in preclinical models of ischemic stroke, as well as other models of neurological damage and injury, including TBI, neonatal hypoxic ischemia (a cause of neurological damage in infants), and spinal cord injury. It also conducted preclinical work in other neurological areas and has been awarded grants from time-to-time in the support of this work, including the potential of MultiStem cells to address chronic conditions, such as Multiple Sclerosis (MS) or Parkinson's disease. The company's research has shown that MultiStem cells convey benefits through distinct mechanisms, including reducing inflammatory damage, protecting at risk tissue at the site of injury, and through direct neurotrophic effects that stimulate the recovery of damaged neurons.
The company's initial clinical focus in the neurological area involves evaluating MultiStem administration to treat ischemic stroke.
The company completed its first clinical study in ischemic stroke, MASTERS-1, which was a randomized, placebo-controlled Phase 2 clinical trial exploring the administration of MultiStem to patients that have suffered an ischemic stroke in the United States and Europe. The results of this study demonstrated favorable tolerability for MultiStem, consistent with prior clinical studies in other indications. The company has an ongoing pivotal Phase 3 clinical trial, referred to as MASTERS-2, which if successful and if the product is approved for commercialization, could make therapy available to most stroke patients in contrast to other therapies (e.g., tPA), which have substantially shorter treatment windows.
The company is also interested in the application of MultiStem for other neurological indications that represent areas of significant unmet medical need, such as traumatic brain injury (TBI), which represents the leading cause of disability among children and young adults, and a leading cause of death.
The company is also conducting preclinical work exploring the application of MultiStem treatment in other neurological indications and have presented data at leading scientific conferences that demonstrated that intravenous MultiStem administration one day after spinal cord injury (SCI), results in statistically significant and sustained improvements in gross locomotor function, fine locomotor function, and bladder control compared to control treated animals. The company has published findings that showed that MultiStem cell therapy was effective in improving the health and recovery of animals following an acute SCI. Intravenous administration of the company's cells one day after injury prevented loss of spinal cord tissue, resulting in significant improvement of walking function and urinary control. Further, it also published an article that provides further evidence that its cell therapy has the potential to provide benefit following hypoxic ischemia, an injury caused by oxygen deprivation to the brain before or during birth and a leading cause of cerebral palsy. The article also describes the biological mechanisms through which this cell therapy delivers benefit.
Inflammatory and Immunological Disorders - MultiStem for Acute Respiratory Distress, Trauma Complications, HSC Transplant Support, and Other Indications
In both preclinical and clinical studies, MultiStem cells have shown potent immunomodulatory properties, including the ability to reduce active inflammation through various modes of action, stimulate tissue repair, and restore immune system balance.
In January 2019 and January 2020, the company announced summary results and one-year follow up results, respectively from its exploratory MUST-ARDS clinical study of the intravenous administration of MultiStem cell therapy to treat patients who are suffering from ARDS. The study results provide further confirmation of tolerability associated with MultiStem treatment.
Further, in 2019, Healios initiated the ONE-BRIDGE study in Japan for patients with pneumonia-induced and COVID-induced ARDS and, in August 2021, Healios reported top-line data from the ONE-BRIDGE study. Healios continues ongoing consultations with the regulatory authorities to prepare for the potential application for manufacturing and marketing approval. The company is working with Healios to prepare the regulatory applications for approval and for potential commercialization in Japan.
The company and Healios have conducted thorough analyses of the data from the MUST-ARDS and ONE-BRIDGE studies. The studies had comparable patient populations receiving the same MultiStem dose amount shortly following an ARDS diagnosis. In April 2022, Healios announced that, while the PMDA did not disagree with the efficacy and safety conclusions of the ONE-BRIDGE study, the PMDA advised Healios that additional supporting data is necessary for application for approval of MultiStem treatment for the ARDS indication in Japan. As a result of the guidance from the PMDA, Healios disclosed that it will continue discussions with the PMDA.
In April 2020, the FDA authorized the initiation of a Phase 2 clinical trial evaluating MultiStem cell therapy for the early treatment of traumatic injuries and the subsequent complications that result following severe trauma. This first-ever study of a cell therapy for treatment for a variety of traumatic injuries is being conducted by UTHealth at the Memorial Hermann-Texas Medical Center in Houston, Texas, one of the busiest Level 1 trauma centers in the United States. This study is being supported under a grant awarded to the McGovern Medical School at UTHealth from the Medical Technology Enterprise Consortium, and the Memorial Hermann Foundation is providing additional funding. The study is a randomized, double-blind, placebo-controlled Phase 2 clinical trial estimated to enroll approximately 150 severely injured trauma patients within hours of hospitalization who have survived initial treatment and are admitted to the ICU.
The company completed a Phase 1 clinical trial examining the safety and tolerability of a single dose or repeat dosing of MultiStem cells administered intravenously to patients receiving a bone marrow or HSC transplant as part of their treatment of leukemia or other hematological condition. The trial was an open-label, multicenter trial that involved leading experts in the field of bone marrow transplantation.
The company was granted orphan drug designation by the FDA and the EMA for MultiStem treatment in the prevention of GvHD, and the MultiStem product was granted Fast Track designation by the FDA for prophylaxis therapy against GvHD following HSC transplantation. Subsequently, the company's registration study design received a positive opinion from the EMA through the Protocol Assessment/Scientific Advice procedure. Furthermore, the proposed registration study received SPA designation from the FDA, meaning that the trial is adequately designed to support a BLA submission for registration if it is successful.
Strategy
The key elements of the company's strategy are to advance its lead programs through clinical development to registration and commercialization; efficiently conduct clinical development to establish clinical proof-of-concept and biological activity for other applications of its product candidates; enter into arrangements with business partners to accelerate development and create value; efficiently explore new high potential therapeutic applications, leveraging third-party research collaborations and its results from related areas; and continue to expand its intellectual property portfolio.
Intellectual Property
The company's broad intellectual property portfolio consists of over 390 issued patents and more than 136 global patent applications around its stem cell technology, MultiStem product and supporting technologies. The intellectual property estate, which incorporates additional filings and may broaden over time, could provide coverage for its stem cell product candidates, manufacturing processes and methods of use through 2036 and beyond.
Research and Development
The company's research and development costs were $65.0 million for the year ended December 31, 2022.
Collaborations and Partnerships
Healios
The company has entered into a series of agreements with Healios, its collaborator in Japan. Under the collaboration that began in 2016, Healios is responsible for the development and commercialization of the MultiStem product for the licensed fields in the licensed territories, and the company provides support and other services to Healios, including preparations for commercial supply in Japan and the transfer of technology to a Japanese contract manufacturer.
In 2016, the company entered into a license agreement, or First License Agreement, with Healios to develop and commercialize MultiStem cell therapy for ischemic stroke in Japan and to provide Healios with access to its proprietary Multipotent Adult Progenitor Cell, or MAPC, technology for use in Healios' organ bud program worldwide, initially for transplantation to treat liver disease or dysfunction. Under the First License Agreement, Healios also obtained a right to expand the scope of the collaboration, and Healios exercised this right in 2018 when the company entered into the Collaboration Expansion Agreement, or CEA. Through the CEA, Healios expanded its First License Agreement to include ARDS in Japan and expanded the organ bud license to include additional transplantation indications covered under Healios organ bud technology; obtained a worldwide exclusive license, or the Ophthalmology License Agreement, for use of MultiStem product to treat certain ophthalmological indications; and obtained an exclusive license in Japan, or the Combination Product License Agreement, for use of the MultiStem product to treat diseases of the liver, kidney, pancreas and intestinal tissue through local administration of MultiStem cell therapy in combination with iPSC-derived cells.
The Ophthalmology License Agreement granted Healios worldwide, exclusive rights to treat certain ophthalmological diseases, by using either MultiStem cell therapy on a standalone basis or MultiStem in combination with retinal pigment epithelium cells derived from either iPSC or embryonic stem cells.
The Combination Product License Agreement granted Healios exclusive rights in Japan to treat diseases of the liver, kidney, pancreas, and intestinal tissue through local administration of MultiStem cell therapy in combination with iPSC-derived cells through certain delivery methods.
Additionally, the company has a right of first negotiation for commercialization of an organ bud product in North America, with such right expiring on the later of the date five years from the effective date of the First License Agreement; and 30 days after authorization to initiate clinical studies on an organ bud product under the first investigational new drug application or equivalent in Japan, North America or the European Union, or EU.
In 2017, the company signed a clinical trial supply agreement for delivering the planned manufacturing services for Healios' clinical trial in Japan treating ischemic stroke patients, which was amended in 2018 to also include the clinical trial supply for Healios' clinical trial treating ARDS patients. The company has successfully delivered all product required by Healios to complete the TREASURE and ONE-BRIDGE studies in 2019.
Also in 2017, the company entered into a technology transfer services agreement with Healios, in which Healios provides financial support to establish a contract manufacturer in Japan to manufacture product for Healios. At that time, the company also amended the First License Agreement to confer to Healios a limited license to manufacture MultiStem in the event that it is acquired by a third-party.
University of Minnesota
In 2003, the company acquired the exclusive rights to the MAPC technology originally developed at the University of Minnesota pursuant to a license agreement with the University. The company subsequently further developed this technology, including refining and establishing proprietary methods related to the manufacturing of the cells, creating new intellectual property and patents outside of the license. Based on the company's patent portfolio, and absent any continuations, renewals or extensions of existing patents, the last licensed patent to expire under this license agreement is expected to expire in 2036.
Government Regulation
The company's research and development activities are subject to stringent government regulation in the United States by the FDA, and in many instances, by corresponding foreign and state regulatory agencies.
In addition to regulations enforced by the FDA and international regulatory agencies, the company is subject to regulation under the Occupational Safety and Health Act, the Environmental Protection Act, the Toxic Substances Control Act, the Resource Conservation and Recovery Act, and other federal, state, or local regulations.
History
Athersys, Inc. was founded in 1995.
