Brainstorm Cell Therapeutics Inc.

And welcome to the Brainstorm Cell Therapeutics Second Quarter 2023 Earnings Call. At this time, all participants are in a listen-only mode. As a reminder, this call is being recorded. And I would now like to introduce your host for today's call, Mr. Michael Wood of LifeSite Advisors. Mr. Wood, you may begin.

Good morning, and thank you for joining us this morning. Earlier today, Brainstorm issued a press release with its financial results for the second quarter of 2023, including a corporate update. Before passing it off to the company for prepared remarks, I'd like to remind listeners that this conference call will contain numerous statements, descriptions, forecasts, and projections regarding Brainstorm Cell Therapeutics and its potential future business operations and performance, statements regarding the market potential for the treatment of neurodegenerative diseases such as ALS, the sufficiency of the company's existing capital resources for continued operations in 2023 and beyond, the safety and clinical effectiveness of Neuron technology platform, clinical trials of Neuron, and related clinical development programs, and the company's ability to develop strategic collaborations and partnerships to support its business planning efforts. Forelooking statements are subject to numerous risks and uncertainties. many of which are beyond Brainstorm's control, including the risks and uncertainties described from time to time in the company's SEC filings. The company's results may differ materially from those projected on today's call, and the company undertakes no obligation to publicly update any forward-looking statements. Joining us on the call this morning will be Karin Leibowitz, President and CEO of Brainstorm, Dr. Stacey Lindberg, Co-Chief Executive Officer, and Ala Patlis, Interim Chief Financial Officer. In addition, Brainstorm's Executive VP and Chief Medical Officer, Dr. Kirk Taylor, is also on the call and will be available to answer questions during the Q&A session. So I'd like to turn the call now to Mr. Leibowitz. Please go ahead.

Thank you, Michael. Thank you all who have joined us to discuss our Q2 2023 financial results and recent progress. Our main priorities right now are to prepare for the forthcoming advisory committee for Neuron, our investigational therapy for the treatment of ALS, and to make sure the company is prepared to make Neuron available to patients. As announced in June, the FDA will convene a meeting of the Cellular Tissue and Gene Therapies Advisory Committee to review our BLA for Neuron on September 27. In addition, the BLA has been assigned a PDUFA action date of December 8, 2023. Neuron's regulatory process, as we have mentioned previously, will be the same as it is for any other investigational therapy that is subject of a filed BLA. The upcoming outcome will be guided by an agenda that includes detailed presentations by Brainstorm and the FDA, which will allow our team and the agency to discuss the clinical evidence supporting neurons' safety and efficacy as an ALS therapy. Other key stakeholders, including independent medical experts, statisticians, and patient advocates, will then have the opportunity to provide their own unique perspective on neurons' clinical data set as well as the unmet needs of people living with ALS. Members of the outcome will then have the opportunity to vote on the response to the question set forth by the FDA. The agency will take the results of this vote, or these votes, as well as the preceding discussions at the meeting, under advisement when coming to a decision on the BLA, which will be made by the December 8th PDUFA date. Given the strength of the clinical evidence we have generated on Neuron, we remain confident in our ability to achieve a successful outcome from the outcome and are preparing for success to ensure we can make Neuron available to patients as quickly as possible if approved later this year. Our team is focused on being fully prepared in advance of the upcoming outcome. These preparations began months ago and continue today as we work with our expert consultants to ensure we can present and respond to all questions that the FDA and ATCA members might raise. We are grateful to the FDA for its cooperation throughout the review process and recognize that the agency is taking our application very seriously. I'll now turn the call over to my colleague, Dr. Stacey Klimberg, for additional comments. Stacey?

Thank you, Haim. We are looking forward to the outcome in September and cannot overstate the importance of this meeting in Neuron's regulatory path, given the scientific and policy issues that need to be understood. The FDA has rightly shown a willingness to apply regulatory flexibility when evaluating investigational ALS therapies over the last year, and we look forward to having Neuron's full dataset discussed in the context of the need for new ALS therapies in the public forum offered by NADCOM. As we move towards the FDA's decision, we continue to have full confidence in our data and believe that a comprehensive analysis of our results strongly supports Neuron's clinical efficacy and safety. We remain committed to the scientific and regulatory process, which includes continuing research to confirm the results of the Neuron clinical program. We also remain committed to ongoing learning about the safety and the clinical effectiveness of neurons. For this reason, we have assembled a steering committee to gather input on goals and the core design elements of a confirmatory trial. We look forward to providing an update prior to the outcome. We continue to be active with the ALS community at scientific conferences. We delivered an important presentation featuring new biomarker data at the recent 2023 Gordon Research Conference for ALS and Related Motor Neurone Diseases. As we described previously, during the neuroinvasor trial, we collected CSF fluid from all trial participants and examined biomarkers spanning three pathways important to ALS pathology, neuroinflammation, neurodegeneration, and neuroprotection. This study is the most robust DSS biomarker study conducted in people living with ALS. And the new data presented at the Gordon Conference features analysis of a biomarker known as neurofilament light, in addition to more broadly providing evidence of the importance of using baseline disease characteristics in the analysis of biomarker data, which I'll provide the rationale for. I believe we all appreciate how heterogeneous ALS is as a disease. Because of this, it is common practice to include ALS disease characteristics as covariates in the analysis of clinical data, which we also did in our phase three trial. The goal is to include information that could influence an individual's prognosis in addition to therapy so that you're drawing appropriate conclusions relative to the treatment effects in a trial. When we decided to include these as covariates in our biomarker analyses, We drew on the ALS literature and the final guidance released in 2023 by the FDA on adjusting for covariates in randomized clinical trials for drugs and biologic products. Towards the goal of exploring the importance of ALS disease characteristics in our biomarker data from phase three, we employed five disease covariates that were pre-specified and used in the primary efficacy model in the trial. These covariates, which include baseline ALS-FRS-R score, the baseline rate of decline, use of Riluzole, fight of ALS disease onset, and time since symptom onset to treatment, are well supported in the literature. As highlighted in our poster presentation, all five disease covariates, in addition to biomarker data, had a significant impact on clinical outcomes. Therefore, the analysis of biomarker data can reflect the treatment effect more accurately when accounting for the baseline heterogeneity of participants. Including these covariates in the analysis across all biomarkers simply adds precision to the results. In the poster, we highlighted the longitudinal trajectory of four biomarkers, including neurofilament light, as examples of the improvements observed in biomarkers following treatment with neurons. compared to placebo across all participants in the trial. Neurofilament Lite has been getting a lot of attention in the scientific community and with drug developers, as evidenced by the exponential growth in publications in recent years. In neuro-treated participants, we observed an 11% decrease from baseline to week 20 in neurofilament Lite, with a change of around 1% with placebo. and a significant treatment difference of a P less than 0.05. The other biomarkers highlighted in the poster also showed significant treatment differences with decreases in pro-inflammatory biomarker MCP1 and large increases in neuroprotective biomarkers VEGF and GALECTIN1. I also presented two other results in the poster. First, neurofilament light baseline levels appear to be prognostic of ALS disease progression. This means that participants with higher baseline neurofilament light values had greater decline from baseline to week 28, as measured by the ALS FRSR. This finding confirms results seen in other ALS trials, which is promising for the field. The last analysis we presented was motivated by the literature and has been used in the review and approval of products by the FDA in diseases such as pulmonary arterial hypertension and triple-class refractory multiple myeloma, in addition to ALS through the review of Traversin. And while Neuron's mechanism of action is very different from Traversin's, as we have a broad, multimodal mechanism of action simultaneously targeting biological deficiencies associated with ALS, We felt these analyses were important to conduct and understand the insights derived into our data based on the relationship between neurofilament light and clinical outcomes. The analysis used an approach called causal inference, sometimes referred to as outcomes regression, and it allows us to explore the relationship between the change in neurofilament light and the change in ALS or FFR due to neuron alone. by adjusting the observed outcome with the change we would have expected due to the natural progression of the disease. The analysis presented confirmed that neuron-driven reductions in neurofilament light are associated with less decline in the ALS-F-RASAR from baseline to week 28. Taken together, data from the literature and the neuron phase three trials, support the hypothesis that treatment-driven reductions in neurofilament light are reasonably likely to be associated with clinical benefit in ALS. We believe these results are timely given the regulatory precedent that was set in ALS this year. In April, the FDA granted accelerated approval to Biogen and Ionis' drug to a person to treat a genetic form of ALS known as SOD1 ALS, which represents approximately 2% of ALS patients. The approval decision was based, in part, on Teverson's ability to lower plasma levels of neurofilament light, establishing the view that reductions in neurofilament light are reasonably likely to be associated with clinical benefit in ALS. Specifically, when the adcom that reviewed Teverson was asked Whether the available evidence supported the reduction in plasma neurofilament concentration was reasonably likely to predict clinical benefit, the committee voted unanimously nine to zero. This is the first time an ALS drug was approved by the FDA based on biomarker data. I'll now turn the call back to Haim for some additional comments.

Thank you, Stacey. Our second main priority, as I mentioned earlier, is to ensure commercial preparedness and execute on the various activities that we need to complete in order to make Neuron available to patients if approved. These include activities across manufacturing, commercial, and medical affairs to engage with the physicians who treat ALS and also early discussions with payers In terms of how Neuron would actually be delivered to ALS patients, the first step is to collect bone marrow from the patients, and this is then shipped to our manufacturing facility, where the MSCs would undergo a series of steps to create the therapeutic product. We're currently in discussions to be able to sign contracts with centers of excellence across the United States so that they will be set up to collect bone marrow from patients and we can initiate a manufacturing process for each person's personalized treatment. We'll begin with eight to 10 centers and then move to broader engagement with more centers. As we have outlined before, we're in the process of a targeted capability build to expand our team in preparation for anticipated growth. We want to be able to move quickly So if we're successful in achieving approval for Neuron, we will have the infrastructure in place and the wait for patients and families to gain access will be as short as possible. We've made a number of hires and management changes so far in 2023. At the beginning of the year, Dr. Stacey Lindbergh was promoted to co-CEO. Then early in the second quarter, we appointed Dr. Kirk Taylor, as Executive Vice President and Chief Medical Officer. Kirk will lead the global medical affairs function and launch activities, including planned product launches, post-approval commercialization efforts, and deepening relationships with the medical community. More recently, in July, we appointed Dr. Bob Dagger as Executive Vice President and Chief Development Officer, Bob will be responsible for the portfolio strategy and advancement of clinical development plans towards regulatory approval, including the expansion of Neuron into new diseases and the translation of preclinical research into first in human trials. He brings approximately 20 years of industry expertise in the development and approval of treatments for challenging neurological and rare diseases. He began his career at GSK, and has served in leadership positions of science and medicine at companies such as Sanofi Genzyme and LabCorp Covance. Finally, we also made an important addition to our board with the appointment of Nir Noor as a board member and the chairman of the audit committee and member of the governance nomination and compensation committee. Nir brings over 20 years of global work experience as a CFO and senior finance leader, He has a broad background that includes large pharma and biotech and has overseen organizations with up to $2.5 billion in sales and $1 billion in annual spend. We are excited to expand our team with these and other talented individuals, and I know they share our vision and excitement around Neuron's prospects. This expanded team is fully focused to prepare Brainstorm for the exciting future ahead. I'll now turn the call over to Alaa to discuss our financials. Alaa.

Thank you, Chaim. Cash, cash equivalents and short-term bank deposits were approximately $0.75 million as of the end of June 2023, compared to approximately $3 million as of the end of December 2022. In July, In 2023, subsequent to the end of the quarter, the company raised net proceeds of approximately $7 million in a registered direct offering. Research and development expenses for the three months ended June 30, 2023 and 2022 were approximately $2.8 million and $5.1 million, respectively. General and administrative expenses for the three months ended June 30, 2023 and 2022 were approximately $2.7 million and $2.5 million, respectively. Net loss for the three months ended June 30, 2023, was approximately $5.3 million, or $0.13 per share, as compared to a net loss of approximately $7 million, or $0.19 per share, for the three months ended June 30, 2022. I'll turn it back to Chaim. Chaim?

Thank you, Ola. I'll ask Michael Wood from LifeSci to read the questions we have received from investors. Michael?

Thanks, Kyle. The first question, is the submitted BLA for Neuron specifically seeking full approval or accelerated approval?

The BLA filed is seeking full approval. Thank you.

Thanks. And does the BLA include data collected from patients that have been treated under the Expanded Access Program and from the Israeli HE pathway?

Yes, that is correct. Data from both programs were included in the BLA.

Do you still intend to publish your biomarker manuscript?

Oh, absolutely. The biomarker data is a compelling part of our evidence, which provides strong support of the clinical data. And we can confirm the paper is under review at a highly regarded journal. The senior authors are Dr. Bob Brown and Dr. Meret Sitkowitz, and the paper includes other leading researchers and scientists.

Thanks. So the next question relates to the Gordon Conference. Why did you only recently decide to look at baseline characteristics of patients and make this presentation at Gordon? And did the results change substantially once you counted the baseline characteristics? And then having listened to Stacey's discussion this morning, I have an additional question I'm going to add, and that is we're intrigued by the word precision that Stacey used in her prepared remarks. Can you please explain what this means?

Stacey, I'll have you answer this question.

Okay. So, to the first question, why adjust for baseline characteristics now? Basically, this is an example of emerging science. If you look at the public documents from Terfercin's ADCOM, you'll see that the FDA did a lot of work exploring the importance of disease covariates, including all of the baseline disease covariates that we pre-specified in our efficacy analyses that I actually spoke about in my prepared remarks. And they did this as they were analyzing Terfercin data. Also, as I referenced earlier, the FDA issued a final guidance on adjusting for covariates in randomized clinical trials, which was very timely and provided important perspective. In fact, when we reviewed the guidance, which focused on prognostic baseline covariates, what stood out to us was that sponsors should prospectively specify covariate adjusted analyses Therefore, we thought it logical to use the covariates specified in our phase three statistical analysis plan. The guideline also noted that covariate adjustment was acceptable even if baseline covariates were strongly associated with each other. So this guidance, combined with the importance the FDA placed on these covariates into person's review led us to explore the importance of these covariates in our data. As a side note, in analyses that we ran, We also used the model that FDA used with two-person data. And in the cases where this was done, the significant effect held across our data, so it's quite robust. Michael, if I understood the question at the end, you wanted to know what I meant by the word precision. Let me first recall the statement I made earlier. So I referenced that in the analysis of our biomarker data, we can reflect the treatment effect more accurately when we account for baseline heterogeneity of patients. So in other words, by adding these characteristics, which really help identify ways that the disease is variable across patients, it brings precision to the estimate of treatment. So here, when I use this word precision, what I mean is that the model with disease covariates included in it, and these covariates can influence the rate of disease progression this will have a better ability to capture variability observed in the data. And the significance of these covariates tells us that this is the right way to analyze the data. Otherwise, you're ignoring important information in the analysis. The last part of the question was how the results compared across the model that had baseline covariates versus the model that did not. The biomarker results from the model from both models actually are very similar, with no conclusions changing substantially for any biomarker. There were two biomarkers that were already trending towards a significant treatment effect. One was neurofilament light, the other was neuroprotective biomarker HGS. And accounting for these disease characteristics resulted in the p-value dropping just below the conventional level of 0.05. But even for these two biomarkers, the overall pattern in the treatment effect as well as the percent change from baseline in both arms is very similar to the results of the model that didn't adjust for the terms. The estimate of the treatment effect just had more precision because it could take into account important information that also influenced clinical outcomes in addition to treatment.

Thanks, Stacey. Next question. Do you intend to proceed with a confirmatory clinical trial?

Yes, we have definite plans to proceed with the confirmatory trial. It's for months now that we have been meeting with a steering committee of leading clinicians and statisticians. We intend to share more after we get input from the FDA. In this regard, I would like to really share that we're thankful for the California Institution for Regenerative Medicine, CIRM, that reached out to us and they asked us that they would be interested that we submit an application for such a trial. Thank you.

Is there a reason that you're granted a different adcom from the adcom that oversaw the Amalix and Biogen drugs? Do you think this is a good or bad sign that you're being reviewed in a different adcom?

Yeah. So the designation of the advisory committee that advises FDA for an application under review is determined by the specific center of the FDA center that the application is filed with. Relivirio and Calceti were both submitted as new drug applications, NDA, to CDER, or the Center for Drug Evaluation and Research, while Neuron, being a biological product, a stem cell product, was submitted as a biologic license application to CBIR, or the Center for Biologics Evaluation and Research. Each center has multiple outcomes. For example, CBER has four. Neuron will be reviewed by CBER's Cellular Tissue and Gene Therapies Advisory Committee. If anyone is interested to look in deeper to this, there's a document called the Intercenter Agreement between the CDER and the CBER, assigned to each center jurisdiction for regulation of drug and biological products and combination of drugs and biological products. and it describes those product characteristics or medical indications that will require a collaborative review effort by the two centers.

Thanks. The next question relates to clinical manufacturing controls, or CMC. Have you been able to submit amendments to address the CMC items identified by the FDA in their initial RTF letter? And if so, or if not, do you anticipate any impact on the PDUCA data?

So, yeah, definitely. As we have shared, and I'll confirm this again, the FDA has allowed us to submit amendments, and we have submitted those amendments. Sure. Thank you.

And have you been having any conversations directly with the FDA while the PLA has been under review?

Yes. As is typical for a PLA under review, we have regularly occurring interactions with the FDA, We received quite a few requests for information, which we have responded to in a timely fashion. We also were able to share presentations in addition to other interactions.

You reported that around 25% of patients in your Phase III study had a baseline value below 25, and in these patients, further decline could not be measured because the items reached zero. You refer to this as the floor effect. Can you please expand on this floor effect, and do you have any buyer market data for these participants?

Thank you. Stacey, please.

Sure. I want to start by just reflecting on the fact that the ALS FFR remains the best outcome measure that we have today. But like any bounded scale, it has limitations. And in the group of participants asked about in this question who were in the bottom half of the scale, There was a high rate of participants with allosuppressor items, specifically in the fine and gross motor subdomain, that started at zero, with approximately 40% starting at zero across all six items. The rate of zero values, especially on the fine and gross motor, is problematic to measuring a treatment effect in a trial because it's expected that the fine and gross motor domains account for about 70% of decline observed in trials. This therefore confounds the ability to show a treatment effect, as the ALS FFR can't measure for the decline once items reach zero. So the question about biomarker data in these participants, we have looked at biomarker data in these participants. In fact, at the Gordon Conference, we reported first that we observed significant improvements on ALS biomarkers with Neuron versus placebo in all trial participants, and this was important. across the three important pathways that I referenced in my opening remarks, neuroinflammation, neurodegeneration, and neuroprotection. We, in fact, see very similar treatment patterns in participants with baseline scores 25 and below in ALS or PSR. And what this suggests is that neuron is biologically active in the overall population that was studied in the trial, which includes participants with advanced ALICE disease where the scale, the ALICE-EPRASAR scale, demonstrated measurement challenges.

Thanks, Stacy. Next question relates to your clinical pipeline. Brainstorm has said that it's working on the use of its product for other indications. Investors have been hearing about this now for years. Please provide some specificity with respect to what working on it means.

Oh, thank you. I'll ask Dr. Kirk-Taylor to take this question, please.

Great, Kaim. Thank you. Sure. Well, we completed a Phase II study evaluating Neuron as a treatment for progressive MS and announced positive results in 2021. We have worked with neurologists and statisticians with deep expertise in MS to design the next trial and have a solid protocol concept prepared that builds on the completed Phase II-A study. We've also prepared a protocol concept designed to study the impact of Neuron in Alzheimer's disease. in the context of the unmet need that remains with the approval of treatments that remove amyloid plaque, consulting with leading experts, and that's, you know, Neuron and Alzheimer's disease. The scientific question addressed here is, though, in patients where amyloid plaque has been removed, could Neuron increase cognitive function above baseline levels? That's the question. Neuron's mechanism of action supports our view that it may have broad applications in neurodegenerative disease, however, I'm sorry. However, like many of our peers in biotech industry, we need to prioritize resources and focus those programs that potentially benefit patients in the near term and create value for our stakeholders. At this point, we're focused primarily on the ALS program and getting approval in that indication. We intend to move forward with other programs as resources allow. Thank you. Thank you.

I have one final question. Did Brainstorm finalize on the follow-on offering with Maxim for $7.5 million?

Yeah. In addition to the PR on this matter, as is common practice, we did publish an 8K. Just to provide some more color on this, we will continue to explore the best ways for finance. We'll have multiple options to finance going forward. And the company will be quite opportunistic to utilize the most favorable opportunities that comes our way at the time of need.

Michael?

That's the final question.

Thank you so much. Jenny, would you open for any additional questions?

No problem. At this time, we are opening the floor for questions. If you would like to ask a question, please press star 1 on your phone keypad now. A confirmation tone will indicate that your line is in the queue. You may press star 2 if you would like to remove your question from the queue. For any participants using speaker equipment, it may be necessary to pick up your handset before you press the star keys. Please hold a moment whilst we poll for questions.

Thank you.

Your first question is coming from Jason McCarthy of Maxim Group. Jason, your line is live.

Hi, all. Thanks for taking the questions. Really looking forward to that adcom in September. And about that adcom, do you expect, based on your covariant analysis of the five covariants and what you've shown around NFL, particularly in that presentation in July, do you expect the same questions that Biogen had gotten, where there was the vote on NFL 9-0, but there was differences in the voting, 3 yes, 5 no, on the full approval, I guess requiring a confirmatory study. Do you expect a similar set of questions?

Thank you very much, Stacy.

Hi, Jason. It's great to... hear from you um you know my my thinking about that is this is a different outcome it's a different fda center um different application very different mechanism of action i think what each of the drug programs was presenting is their evidence also is quite different so we both bring interesting insights into neurofilament light and the association with the ability to actually mention and show that reductions in neurofilament light results in an association with the improved clinical outcomes is a strength. But I've learned over the course of my career to not assume anything with regard to the regulators. We'll actually get the questions very close to the time of the adcom, and I think the questions that were asked were relevant, but we'll know for certain what our questions are right before the adcom.

During that adcom, as part of the presentation, we made more of a point on the safety aspects of Neuron, given that it is an autologous cell therapy, it's not genetically manipulated, and that it is a far safer approach, apparently, than other drugs for ALS, including the Biogen drug.

Stacy?

Yeah. So, we will present the full set of data, efficacy and safety. And, Jason, we share your confidence in the safety of Neuron. not only in the data we've generated, but as a result of the way that our product is made. And we will provide a compelling overview of all data at our presentation.

And just lastly, a brief question on the potential commercialization plan. From a, I know it's early, but from a pricing perspective to Ferrison price at around, $14,000 or so just north of that for treatment, but it's about $200,000 all told for a year. Is that a similar pricing strategy that you could expect for a cell therapy? And just from a launch perspective, Chaim, you had mentioned getting possibly eight, 10 centers initially for bone marrow collection. How large of a sales force would you need to complete your initial commercialization plan?

Yeah, so thank you very much. You know, many of these questions, it's premature for us to answer for regulatory reasons, as you know. But I like the assumptions you're laying out. And I think what will be very important is to find the centers of excellence doing not only the bone marrow respirations, but the interfecal injections, which some of these, like soraptor treatments and topazin treatments really helps out, that more and more centers have that expertise. And that's what we'll be focusing on And probably we'll start with the centers of the trial, which already have a lot of experience with our product. But we're also talking to many other geographical centers to make sure that patients from other geographies have a center close nearby to where they are. Just to comment to a previous question you asked and Stacey answered a little bit, is of course we believe that our clinical data set, even though the primary endpoint did not hit statistical significance, we think that the body of evidence we bring forward, we are able to show statistically significant results once we're able to show and dive more deeper into the data set, which you spent a lot of time, and I don't want to repeat it for you. But therefore, I think that the question will be more focused on clinical, why the biomarker data gives strong support to what we see in the clinical, as it covers even for the part of the score where we think it's not sensitive in the more advanced patients. But when you're able to eliminate advanced patients, we see both in the primary and secondary endpoints statistical significant results. Of course, we're not going to lay it out here. That's what we're going to do at the outcome. But thank you very much for those questions, Jason.

Hi, I'm Stacy. Thank you. Sure.

Thank you very much. Just a reminder, if you have any questions, please press star 1 on your phone keypad now. Okay, we don't appear to have any further questions in the queue. I can hand back over for closing comments.

Thank you. I really appreciate that. It looks like Stacy did a wonderful job laying out the plan, and there's no additional questions. So we had a long call this morning, so let's give back the time to everyone listening. We want to thank you again for listening in in mid-August to have so many investors listen again. It shows the importance. to our investors of our plan forward. And we really thank you for listening again today. Thank you very much, Jenny. Back to you.

Thank you, Chaim. This does conclude today's conference call. You may disconnect your phone lines at this time and have a wonderful day. Thank you for your participation.