MultiStem (invimestrocel) / Athersys, Healios - LARVOL DELTA

Completion of Formal Regulatory Consultation for ARDS and Agreement on the Global Phase 3 Trial (REVIVE-ARDS Study) (Healios Press Release) - "HEALIOS K.K...has completed regulatory consultations for the conditional and time-limited approval application in Japan for its investigational treatment for Acute Respiratory Distress Syndrome (ARDS), and is proceeding with preparations toward the submission. We are pleased to announce that, following a formal consultation with the Pharmaceuticals and Medical Devices Agency (PMDA) that took place this week regarding the post-approval confirmatory study, we have reached an agreement regarding the inclusion of Japanese patients in the upcoming global Phase 3 trial (REVIVE-ARDS study) to be run mainly in the United States."

Commercial • New P3 trial • Acute Respiratory Distress Syndrome

Decision Regarding Policy to File for Conditional and Time-Limited Approval of Ischemic Stroke Treatment in Japan and Development Strategy Overview (Healios Press Release) - "HEALIOS K.K...has conducted a placebo-controlled, double-blind Phase II/III clinical study (TREASURE study) in Japan to evaluate the efficacy and safety of HLCM051 (invimestrocel)...We have been in ongoing discussions with regulatory authorities regarding the direction of data collection and our application strategy...In line with the plan for this project, we hereby announce that we have decided on a policy to target a conditional and time-limited approval application...for acute ischemic stroke in Japan...With respect to the development and regulatory filing strategy for our acute ischemic stroke treatment, we do not intend to conduct an additional Phase 3 trial; instead, the efficacy of the product will be evaluated through Post-Marketing Studies...By presenting this rational and feasible Post-Marketing Study design, we believe that the path toward filing for conditional and time-limited approval—and ultimately full approval—for ischemic stroke has become clear."

Japan filing • Trial status • Ischemic stroke

Healios to Submit Application for Allogeneic Cell Therapy for ARDS Aiming for Conditional and Time-Limited Approval [Google translation] (Nikkei) - "On April 9, 2025, Healios held an R&D briefing on allogeneic bone marrow-derived mesenchymal stem cells (development code: HLCM051) for acute respiratory distress syndrome (ARDS). The company plans to apply for approval of HLCM051 for ARDS in Japan in fiscal year 2025, aiming to obtain conditional and time-limited approval. In parallel, the company will also begin global Phase 3 clinical trials, mainly in the United States, as a verification test for full approval in Japan."

Japan filing • New P3 trial • Acute Respiratory Distress Syndrome

Clinical efficacy of invimestrocel for acute respiratory distress syndrome caused by pneumonia: Comparison with historical data using propensity score analysis. (PubMed, Regen Ther) - "The addition of invimestrocel to the standard treatment for pneumonia-induced ARDS may result in early withdrawal from the ventilator and lower mortality. However, further randomized, blinded, and placebo-controlled studies without or addressing multiplicity are required to confirm these findings."

Journal • Acute Respiratory Distress Syndrome • Infectious Disease • Pneumonia • Pulmonary Disease • Respiratory Diseases

Publication of peer-reviewed paper on the ONEBRIDGE clinical trial for acute respiratory distress syndrome (ARDS) in Japan [Google translation] (Healios Press Release) - P2 | N=35 | ONE-BRIDGE (NCT03807804) | Sponsor: Healios K.K. | "As announced in 'Status of Conditional and Time-Limited Approval Applications for ARDS Treatment Drugs in Japan' (announced on January 15, 2025), based on the positive results of the Phase 2 trial (ONE-BRIDGE trial) already completed in Japan and the Phase 2 trial (MUST-ARDS trial) conducted in the US and the UK, and on the premise of conducting a global Phase 3 trial (REVIVE-ARDS trial) mainly in the US as a verification trial, we are proceeding with preparations for the conditional and time-limited approval application for ARDS treatment drug HLCM051 in Japan...clinical data to be submitted for this application has been published in Regenerative Therapy....The results showed that the number of days during the 28 days after administration that patients were free of ventilators was extended by 8.1 days (average), and the mortality rate 180 days after administration was reduced by approximately 33.7%..."

Japan filing • P2 data • Acute Respiratory Distress Syndrome

MultiStem® for Treatment of Trauma Induced Multiple Organ Failure/Systemic Inflammatory Response Syndrome (clinicaltrials.gov) - P2 | N=156 | Recruiting | Sponsor: Athersys, Inc | Trial completion date: Aug 2023 ➔ Dec 2025 | Trial primary completion date: Sep 2022 ➔ Dec 2025

Trial completion date • Trial primary completion date • Immunology • Inflammation • Mood Disorders • Systemic Inflammatory Response Syndrome

Treatment Evaluation of Acute Stroke for Using in Regenerative Cell Elements (clinicaltrials.gov) - P2/3 | N=206 | Completed | Sponsor: Healios K.K. | Active, not recruiting ➔ Completed

Trial completion • Cardiovascular • Ischemic stroke

ONE-BRIDGE: Efficacy and Safety Study of HLCM051(MultiStem®) for Pneumonic Acute Respiratory Distress Syndrome (clinicaltrials.gov) - P2 | N=35 | Completed | Sponsor: Healios K.K. | Active, not recruiting ➔ Completed

Trial completion • Acute Respiratory Distress Syndrome • Inflammation • Pneumonia • Pulmonary Disease • Respiratory Diseases

Allogeneic Stem Cell Therapy for Acute Ischemic Stroke: The Phase 2/3 TREASURE Randomized Clinical Trial. (PubMed, JAMA Neurol) - P2/3 | "Further research is needed to determine whether MultiStem therapy for ischemic stroke has a beneficial effect in patients who meet specific criteria, as indicated by the exploratory analyses in this study. ClinicalTrials.gov Identifier: NCT02961504."

Clinical • Journal • P2/3 data • Cardiovascular • Ischemic stroke

Clinical efficacy and safety of multipotent adult progenitor cells (invimestrocel) for acute respiratory distress syndrome (ARDS) caused by pneumonia: a randomized, open-label, standard therapy-controlled, phase 2 multicenter study (ONE-BRIDGE). (PubMed, Stem Cell Res Ther) - P2 | "In Japanese patients with ARDS caused by pneumonia, invimestrocel plus standard treatment resulted in no significant difference in the number of VFDs but may result in improved survival compared with standard treatment. Invimestrocel was well tolerated."

Clinical • Journal • P2 data • Acute Respiratory Distress Syndrome • Infectious Disease • Pneumonia • Pulmonary Disease • Respiratory Diseases

Athersys Announces Successful Type B Meeting with the FDA (Businesswire) - "Athersys...announced planned amendments to its MASTERS-2 clinical trial protocol following a Type B meeting with the U.S. Food & Drug Administration (FDA). Held on March 21, 2023, the meeting addressed Athersys’ proposed modifications that seek to establish primary and secondary endpoints that it believes best reflect the full potential benefit of MultiStem treatment for patients with acute, moderate-to-severe ischemic stroke as well as the evolving standard of care."

FDA event • CNS Disorders • Immunology • Ischemic stroke

Athersys Expands IP Protection with First New Patent for SIFU Technology (Businesswire) - "Athersys...announced today that the United States Patent and Trademark Office has granted the Company a new patent for its novel cryogenic storage system, the Secure Integrated Freezer Unit (SIFU®). This U.S. Patent No. 11,566,834, titled “Apparatus and Method for Cryostorage and Manipulation of a Plurality of Container Units,” adds to the Company’s existing IP portfolio and is an important milestone."

Patent • Graft versus Host Disease • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

Athersys Granted Clinical Type B Meeting with FDA for MASTERS-2 Clinical Trial Protocol Discussion (Businesswire) - "Athersys...announced today that the Company has been granted a clinical Type B meeting with the U.S. Food & Drug Administration (FDA)....In the Type B meeting with the FDA, scheduled for late March, the Company intends to discuss proposed modifications to the ongoing pivotal Phase 3 MASTERS-2 clinical trial, which is under special protocol assessment (SPA) agreement....During the upcoming Type B meeting, the Company will bring forward proposed modifications to the MASTERS-2 trial...The Company will be hosting a business update call later this morning, February 14th at 11:00 a.m. ET, during which more details will be provided."

FDA event • CNS Disorders • Ischemic stroke

Athersys to Participate in Advanced Therapies Week and Allogeneic Cell Therapies Summit Europe in January (Businesswire) - “Athersys, Inc…announced today their participation in two January conferences, Advanced Therapies Week presented by Phacilitate from January 17-20, 2023 in Miami, FL and the 2^nd Allogeneic Cell Therapies Summit Europe from January 30-February 1, 2023 in London, UK.”

Clinical • CNS Disorders

"$ATHX Athersys Provides MultiStem Clinical Update https://t.co/cMlEgGLZsH" (@stock_titan)

Clinical

RESULTS OF THE TREATMENT EVALUATION OF ACUTE STROKE USING REGENERATIVE CELLS (TREASURE) CLINICAL TRIAL (WSC 2022) - "Post-hoc analysis of the MASTERS-1 exploratory trial indicated potential benefits of early treatment with bone marrow-derived, allogenic, clinical-grade multipotent adult progenitor cells (MultiStem®, HLCM051)... Data analysis is ongoing. Key results will be presented at the World Stroke Congress 2022."

Clinical • Late-breaking abstract • Cardiovascular • Ischemic stroke

"Well then it shouldn't be difficult at all to attract a big pharma partnership willing to invest in MultiStem for #stroke in the U.S. and take in a substantial upfront payment." (@WallStreetTitan)

Licensing / partnership • Cardiovascular

"Not in US or Europe, but in Japan, Healios/Athersys are poised for approval for Multistem cell therapy to treat ARDS." (@Athersyss)

Acute Respiratory Distress Syndrome

"$ATHX Athersys to Host a Virtual Presentation on Its MultiStem® Programs https://t.co/FpLWLMEM0x" (@stock_titan)

Treatment Evaluation of Acute Stroke for Using in Regenerative Cell Elements (clinicaltrials.gov) - P2/3; N=220; Active, not recruiting; Sponsor: Healios K.K.; Recruiting ➔ Active, not recruiting; Trial completion date: Dec 2022 ➔ Mar 2023; Trial primary completion date: Mar 2021 ➔ Jun 2021

Clinical • Enrollment closed • Trial completion date • Trial primary completion date • Cardiovascular • Ischemic stroke • MRI

"$ATHX stroke study on @fox32news in Chicago today #MultiStem" (@davidschull)

Cardiovascular

A Phase 2 Trial of AMI MultiStem® Therapy in Subjects With Non-ST Elevation Acute Myocardial Infarction (clinicaltrials.gov) - P2; N=34; Terminated; Sponsor: Athersys, Inc; N=90 ➔ 34

Enrollment change • Cardiovascular • Myocardial Infarction • MRI

MultiStem Administration for COVID-19 Induced ARDS (MACoVIA) (clinicaltrials.gov) - P2/3; N=400; Recruiting; Sponsor: Athersys, Inc; Trial completion date: Aug 2022 ➔ Dec 2023; Trial primary completion date: Sep 2021 ➔ Jan 2023

Clinical • Trial completion date • Trial primary completion date • Acute Respiratory Distress Syndrome • Infectious Disease • Novel Coronavirus Disease • Pulmonary Disease • Respiratory Diseases

MASTERS-2: MultiStem® Administration for Stroke Treatment and Enhanced Recovery Study (clinicaltrials.gov) - P3; N=300; Recruiting; Sponsor: Athersys, Inc; Trial completion date: Dec 2022 ➔ Jun 2023; Trial primary completion date: Mar 2022 ➔ Sep 2022

Trial completion date • Trial primary completion date • Cardiovascular • Ischemic stroke

ONE-BRIDGE: Efficacy and Safety Study of HLCM051(MultiStem®) for Pneumonic Acute Respiratory Distress Syndrome (clinicaltrials.gov) - P2; N=35; Active, not recruiting; Sponsor: Healios K.K.; Recruiting ➔ Active, not recruiting

Enrollment closed • Acute Respiratory Distress Syndrome • Pneumonia • Respiratory Diseases