Ladies and gentlemen, good morning. My name is Abby, and I will be your conference operator today. At this time, I would like to welcome everyone to the Athersys April business update call. Today's call is being recorded, and all lines have been placed on mute to prevent any background noise. Thank you, and I will now turn the conference over to Ellen Gurley, Corporate Communications and Investor Relations Manager. You may begin.
Good morning, and welcome to the Athersys April 2023 business update conference call. Please note that any remarks that management may make about future expectations, plans and prospects constitute forward-looking statements for purposes of the Safe Harbor provision under the Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by the forward-looking statements as a result of various factors, including those contained in our Forms 10-Q, 10-K, and other SEC filings. This conference call contains time-sensitive information that is accurate only as of the date of the live broadcast, April 20, 2023. Athersys undertakes no obligation to revise or update any forward-looking statements to reflect events or circumstances after the date of this conference call, except as required by law. I would like to now turn the call over to Daniel Camardo, Chief Executive Officer.
Dan, please go ahead.
Thank you, Ellen. Good morning, everyone, and thank you for joining us. I would like to begin by stating how much I have enjoyed speaking with many of the long-term shareholders over the past few weeks that continue to support Athersys and share in our mission of successfully developing MultiStem as a unique cell therapy for patients who suffer acute critical injuries and have very few therapeutic options. These business update calls support our commitment to ongoing transparency and keeping everyone informed of the progress we're making toward achieving this mission. On prior calls, we discussed how MultiStem for the treatment of ischemic stroke is our primary focus. Since our last update call in February, we have made some of the most meaningful progress yet with MASTERS-2, our ongoing Phase 3 clinical trial.
On today's call, I look forward to sharing my views on why the positive outcome of our recent Type B meeting with the FDA has the potential to be a significant value driver for Athersys. We will also review clinical progress in our other trials and cover business priorities and our financial strategy. On the call with me today is Dr. Robert Mays, Co-founder and Executive Vice President of Regenerative Medicine and Head of Neuroscience, who will speak on MultiStem's growing role in the evolving stroke treatment landscape. Also joining us during the Q&A portion of the call will be Maia Hansen, our Chief Operating Officer, and Kasey Rosado, our Interim Chief Financial Officer. In February, we announced that we were granted a Type B meeting with the FDA that occurred in late March, and I'm delighted to report that the meeting ended in a very positive way.
Going into the FDA meeting, our goal was to address uncertainty in the design of our MASTERS-2 trial by requesting protocol modifications that represented our observations and analysis from the recently completed TREASURE trial in Japan and our own Phase 2 MASTERS-1 trial. Our proposal also incorporated changes in the standard of care for stroke patients, specifically with the expanded use of mechanical reperfusion, and will more accurately recognize the full potential benefit of MultiStem treatment for patients with acute moderate to severe ischemic stroke over an extended observation period. I'd like to thank the FDA for their guidance, feedback, and timely response to our proposal. We recognize the importance of our RMAT, Fast Track, and Special Protocol Assessment designations that provide timely regulatory interactions and perspectives on trial design.
We are pleased that the FDA agrees with our opinions from our KOL panel that we conducted last November and our proposed clinical protocol modifications, despite the fact that we passed the halfway mark for patient enrollment in MASTERS-2, as communicated earlier this year. The most significant modification we are now preparing for is a change in the primary endpoint from mRS shift analysis at day 90 to mRS shift at day 365. This is consistent with continual improvements in patient outcomes that we have observed in both the TREASURE trial and the MASTERS-1 trial. Dr. Mays will speak in more detail about the biological basis for this continuing improvement shortly. mRS shift analysis at day 90 will remain in the protocol as a key secondary endpoint, along with other revised secondary endpoints that have been reprioritized to show clinical outcomes at a one-year period of time.
In the amended protocol, we also found the opportunity to broaden patient enrollment by removing eligibility caps on patients administered tPA or undergoing mechanical reperfusion to align with changes in ischemic stroke standard of care. Reperfusion caps were originally established to limit the number of patients who underwent reperfusion and experienced limited benefit in the trial to allow for a majority of naive patients or non-reperfused patients to be treated. This protocol appropriately reflects standard care back in 2018 and was primarily designed to show MultiStem's use on a standalone basis.
However, as mechanical reperfusion has become more commonly utilized and imaging technology has become more advanced, it presented potential issues with our patient enrollment timeline, and the outcome of the trial would not have adequately represented this evolving standard of care. The trial is now appropriately designed to demonstrate clinical efficacy of MultiStem as either adjunct therapy to reperfusion or as a standalone therapy when reperfusion is not appropriate. We confirmed this point with KOLs during our November panel discussion and believe this modification, along with the changing of the primary endpoint to day 365, if proven successful in the trial, will ultimately change the treatment paradigm for ischemic stroke.
We believe in allowing more reperfusion patients would be a better reflection of the likely use of MultiStem as a complement therapy based on MultiStem's different mechanism of action, while also allowing for MultiStem to be used on a standalone basis if a patient was not eligible for either mechanical reperfusion or tPA. This is a highly meaningful change in the way we are thinking about how MultiStem can be administered, given the unique mechanism of action, observed safety profile and significant unmet need. Early on, we recognized the influence reperfusion caps had on patient enrollment timelines and their increasing misalignment with the evolving stroke therapy landscape. Despite being encouraged by an increasing patient enrollment rate over the past year, we've been unable to offer a clear timeline to complete enrollment in the trial until reaching agreement with the FDA.
With caps now allowed to be removed and allowing some time to implement the FDA-approved protocol changes with individual clinical trial sites, we estimate that patient enrollment in MASTERS-2 will be complete by the Q2 of 2024, less than one year from now. Let me repeat that. Our timeline to complete enrollment in our Phase 3 MASTERS-2 trial is by Q2 of 2024, pending results from an interim analysis and provided we continue to obtain sufficient funding. Patient enrollment in MASTERS-2 has continued at a steady pace, and we have adequate supply of MultiStem clinical product in our possession to complete this 300 patient trial. In addition to heightened clinical site engagement, we've also screened 9 new trial sites that are in the process of being activated and will be able to begin enrolling patients soon.
We will continue to execute our accelerated enrollment plan to heighten awareness of these protocol changes, and we will keep you updated on our progress throughout the year. Lastly, our amended protocol allows us the opportunity to perform an interim analysis to determine appropriate powering of the trial. The FDA was in agreement with our plan to conduct an interim analysis for power, which will provide us an opportunity to ensure we're on the right track to achieve statistical significance with a new primary endpoint of mRS shift analysis at day 365 and confirm we have a sufficient number of patients enrolled in the trial. The interim analysis would also allow us to explore more attractive data-driven agreements with potential partners that may be interested in licensing on a global or regional basis and working with us to bring MultiStem to market.
Patients in the interim analysis would need to be enrolled for 365 days. The total number of patients would need to reach a desired statistical threshold, as discussed in the Type B meeting with the FDA. There is no penalty on P-value from this interim look, and we are not conducting the analysis for futility. Because patient enrollment increased so significantly over the past year, we're expecting this interim analysis can be completed in 2023, pending ongoing conversations with the FDA and contingent on our ability to obtain sufficient funding. To recap our progress in MASTERS-2. The change to a day 365 primary endpoint and mRS shift analysis reflects a more meaningful and consistent clinical outcome as observed in earlier completed trials.
By removing caps on reperfusion, the trial now more appropriately includes patients that are more representative of the evolving standard of care. Our enrollment timelines are now clear, and we remain focused on accelerating new patient enrollment to complete the trial. If proven successful, MultiStem has the potential to dramatically change the treatment paradigm for ischemic stroke patients and offer clinicians a unique therapeutic option that could be used with or without reperfusion. I'm gonna turn now to the topic of partnering. We continue to engage with interested companies on potential MultiStem licensing deals both on a global and regional level, as well as for our animal health IP and our SIFU technology. We remain steadfast in our interest to secure one or more attractive partners.
While we have had multiple engagements with potential partners, one of the hurdles we encountered was the uncertainty over proposed changes to the MASTERS-2 trial and the lack of clarity of when we would complete the trial. Now that we clearly understand our path forward, we're optimistic that we'll have a better opportunity to complete a partnership that creates value for shareholders and recognizes the significant potential of MultiStem. Our current partner, Healios in Japan, continues to advance MultiStem in both acute respiratory distress syndrome and ischemic stroke. We believe our relationship with Healios is productive and continues to strengthen as we work through regulatory and financial challenges together. Last quarter, Healios received PMDA regulatory approval for a Phase 3 ARDS trial with a trial size of approximately 80 patients based on their orphan designation.
We're working closely with Healios and PMDA to determine which clinical product they will use in the ARDS trial, and we have adequate doses of both the 2D and 3D bioreactor product produced to support their needs. In stroke, we are evaluating the possibility of having Healios join MASTERS-2 and participating in discussions with PMDA on the use of MASTERS-2 data to support an application for approval in Japan. These talks include discussing registration in Japan using TREASURE trial data in addition to the MASTERS-2 data. As a reminder, Healios has a Sakigake designation for ischemic stroke, which allows them to take an accelerated regulatory pathway. On the manufacturing front, we announced last year that we provided Healios the license to manufacture MultiStem for use in Japan. This came as a result of our decision to suspend work with our CDMO following the TREASURE trial results.
We've been working with Healios on a tech transfer agreement and determining the appropriate next steps for investing in a suitable commercial manufacturing process for their needs in Japan. It's no secret that at times our relationship with Healios has been challenging, going back before my time. We consider Healios to be a valued partner that shares the same interests we do in bringing MultiStem to market and helping patients that suffer from these difficult and often debilitating or terminal diseases. Our existing agreements with Healios represent future milestones and royalties that, if commercially successful, could provide significant capital. It's important to me that we work together, and we will continue to do so. As a final topic, I'll touch on our financial position. We communicated previously that we'll be thoughtful in our approach and pursue non-dilutive opportunities as our first priority.
Should we pivot to a public capital raise, we're looking to attract institutional investors with a long-term view that recognize Athersys' value and understand what we're working towards and strengthen our investor base. We were successful with this strategy in August and November, attracting institutional funds despite difficult market conditions and our ongoing restructuring. The transaction we announced this week was with a few of the same institutional healthcare investors that had participated in the November transaction and the same single investor from the August transaction. The cash raised in this recent transaction extends our runway further while we continue to advance conversations with potential partners and seek non-dilutive capital. We plan to continue meeting with targeted institutional investors to raise awareness of the potential with MultiStem and communicate a clear timeline to complete enrollment in MASTERS-2, as well as review other upcoming milestones.
This strategy also includes attracting more analyst coverage and building on the recently announced initiation of coverage by Alliance Global Partners back in March. Last year, we began a restructuring with the goal of significantly reducing our operating expenses and prioritizing resources to support MASTERS-2 and business development. We have successfully reduced expenses down to less than $2.5 million per month. We continue to look for ways to reduce costs further. In addition, we remain engaged with our CDMO in determining a path forward to pay off outstanding debts, which represent over 80% of our accounts payable. They have been very supportive partners. As soon as an agreement is reached, we will provide an update. I would now like to turn the call over to Dr. Willie Mays, who will provide an update on our clinical programs. Willie ?
Thanks, Dan, good day, everyone. Historically, ischemic stroke has been extremely challenging to treat due to the limited window of time to administer the approved therapies or due to the location of the blockage in the brain. Approximately 60%-70% of stroke patients fail to meet the criteria for tPA or mechanical thrombectomy use, only approximately 40% of those treated experience meaningful benefit from these reperfusion therapies. Our MASTERS-2 trial is designed to provide MultiStem administration to all patients, regardless of whether they were treated with or without either therapy or both, because MultiStem's mechanism of action reduces the negative aspects of inflammation initiated by the acute injury and subsequently promotes healing by modulating the immune system.
MultiStem's mechanism of action is independent of reperfusion status, it provides a potential additional treatment benefit for patients who are not eligible for thrombectomy and may be added as a therapeutic option for patients who undergo reperfusion therapies and do not experience a meaningful recovery as measured by a change in the National Institutes of Health Stroke Scale score. As Dan touched on earlier when discussing the removal of reperfusion caps, MASTERS-2 is now designed to allow for the use of thrombolytics like tPA within 4 and a half hours of stroke onset or mechanical reperfusion up to 8 hours following observation periods to monitor changes in the patient's NIHSS score.
Should the change in that score be less than or equal to 3 points, the patient can be enrolled in MASTERS-2 to receive either the cells or placebo. There are no changes to the time of administration of MultiStem or placebo in the trial, and remains 18 to 36 hours post onset of ischemic stroke symptoms. In addition, based on what we have learned from the MASTERS-1 and TREASURE trials, we will also be evaluating multiple biomarkers from the blood and via spleen and brain imaging techniques to continue to better understand the mechanisms through which we believe MultiStem provides therapeutic benefit. I want to restate again, MultiStem is a novel treatment paradigm for rebalancing the immune system after acute severe inflammatory crises independent of reperfusion success. Let me quickly turn to an overview of our other clinical programs in ARDS and trauma.
We previously reported our engagement with the Biomedical Advanced Research and Development Authority, or BARDA, through a request for information process to explore the use of MultiStem for the treatment of ARDS in a Phase 2 clinical protocol. BARDA subsequently released an RFP to fund three candidate therapies. We successfully submitted a proposal for this request. We have an ample clinical supply of MultiStem bioreactor manufactured products available for this trial. We expect to learn more about the outcome of our submission by early Q3 of this year. Finally, our MATRICS-1 trial for treating trauma patients successfully completed DSMB review of cohort one, which used the 2D cell product, and cohort two using the 3D bioreactor product.
We are now working closely with our colleagues and collaborators at UTHealth Houston and Memorial Hermann Hospital to update the FDA with cohort one and cohort two data in support of moving into cohort three, which will be 140 patients receiving either the 3D manufactured cell product or placebo. We expect to have a decision on timing to initiate cohort three enrollment by late Q2 of this year. I'll now turn the call back to Dan for closing remarks and to start the Q&A. Dan?
Thanks, Willie. Before we start the question and answer portion of the call, I would like to provide a quick overview of expectations, milestones, and goals we are actively working toward in the next few months. We expect to know when an interim analysis on MASTERS-2 could be conducted based on further conversations with the FDA and statisticians. We expect to hear from BARDA regarding our proposed ARDS trial in early Q3. We expect to learn if the MATRICS-1 Phase 2 trauma trial is advancing to cohort 3. We expect to have greater clarity on the timing and next steps with Healios ARDS trial in Japan. We expect to learn if Healios will be participating in the MASTERS-2 trial, and if so, what that participation requires.
We will continue to advance conversations with potential MultiStem licensing partners on a global and regional level. We will also advance conversations with animal health and potential SIFU partners. Finally, we expect to reach an agreement with our CDMO on our outstanding accounts payable balance. Clearly we have a lot of exciting milestones ahead of us, and we will continue to remain laser focused on our execution. With that, I'll conclude today's prepared remarks and turn the QA portion of the call over to Ellen Gurley.
Thank you, Dan. For this portion of the call, I'm going to summarize several questions and common themes that we received via email and then allow Dan the opportunity to answer each. Starting with question one. Can Dan assure investors that obtaining additional and sufficient working capital to fund costs associated with operations and clinical trial advancement can be achieved in a shareholder friendly manner?
Thanks, Ellen, and thanks for that question. That's been our goal since we initiated restructuring of our business last June. I understand that continued dilution of shareholders is not ideal, and we knew that more capital was going to be needed to fund operations after the termination of the equity line with Aspire, which is why we began to engage with traditional institutional investors and really began conversations with potential licensing partners. Remember, the agreement with Aspire was in place for 14 years and provided the company significant capital and resulted in dilution over that period of time. Last year we initiated outreach to several potential licensing partners, some of whom had engaged with in the past and others that we thought would be attracted to Athersys based on their star established market presence and interest in cell therapy, as well as breadth of capabilities.
These conversations have been productive to this point, once we decided to approach the FDA about changing the primary endpoint and other modifications to the MASTERS-2 trial, it became uncertain as to the status and timing of when we'd actually complete enrollment of the trial. We have clarity on MASTERS-2 and the potential to conduct an interim analysis is important, as well as several other near-term opportunities in front of us that we believe will support our efforts to raise capital we need to accomplish our goals. We've come a long way in a very short period of time under some challenging circumstances, we still have more work to do. Our path forward with MultiStem and MASTERS-2 in particular is now clear, we'll remain focused on execution.
Thank you, Dan. Moving on to question two. Is there an update on partnering discussions for MultiStem, SIFU or the ReGenesys Animal Health IP?
Sure. Thanks, Ellen, and thanks for that question. We continue to make meaningful progress with potential partners on both global and regional level, as I mentioned, and we're active in conversations. Now, I can't go into detail until a potential partnership is obviously secured. We remain committed to finding a partner that aligns with our mission of bringing MultiStem to market and pursuing a deal that's in the best interest of our shareholders. We're in talks with multiple parties to license or sell SIFU technology, which is a great example of an innovative asset with significant potential that exists within the company beyond MultiStem that we are now treating differently to realize its full potential and value. At this point, we'll keep you updated as we make progress.
Thank you. Moving on to question three. How are you managing your cash burn rate? Will additional financings to required?
Thanks, Ellen. Thank you for that question. While I can't comment on our cash balance today, I can say that we've been very prudent and responsible with managing our cash in order to provide as much runway as possible while we execute on our business plan. To date, we've reduced expenses from approximately $7 million to $8 million a month last year in growing to down to less than $2.5 million per month and continuing to decrease. We fully realize that additional funds are required to bring MultiStem to market, and we remain focused on our primary goal of completing the MASTERS-2 trial and achieving other value-creating business and strategic objectives. We also continue to engage with vendors, including our CDMO, to reach a settlement on outstanding obligations and preserve our relationship for the long term.
Thank you, Dan. Question four states, what is your status on risk of delisting from Nasdaq?
Thank you for that question. We received a notice from Nasdaq last Thursday, April 13th, regarding the deadline to satisfy non-compliance with the $35 million market cap requirements. We subsequently filed a request to appeal and notified Nasdaq on Friday, April 14th. The next step is to meet with an appeals panel to request a 180-day extension, and a date has already been scheduled for this virtual meeting in late May. During the appeals process, we will remain actively traded on Nasdaq.
Thank you, Dan. The last question is, in addition to ischemic stroke, ARDS, and trauma, are you having conversations to potentially license MultiStem for other indications?
Thanks, Dan. Thank you for that question. Yes, this is something we've been open to and exploring, although identifying a partner for ischemic stroke has been our first priority. A few of our neurological indications are IND ready and we feel would be attractive for potential partnerships, as well as other areas addressing inflammation such as transplantation and graft-versus-host disease. There's also the potential use of MultiStem in chronic conditions, including multiple sclerosis and Parkinson's disease based on the depth of pre-clinical research that has already been conducted.
Thank you, Dan. That was our final question for today. Thank you to everybody that emailed in questions. If you have any additional questions following this call, please send an email to ir@athersys.com.
Thanks, Ellen. I'd like to personally thank everyone who submitted questions and continues to support our efforts. In closing, I'd also like to thank our long-term shareholders that have been on this journey with us for some time, and I recognize it's been a volatile trip to this point. I'd also like to thank our newer shareholders who understand where we are today as a company and see the same exciting potential that we do in bringing MultiStem to market and what that could ultimately mean for patients. Thank you again for joining us on today's call, and we look forward to updating you again on our progress in a few months.
Ladies and gentlemen, this concludes today's conference call. Thank you for your participation. You may now disconnect.