Brainstorm Cell Therapeutics Inc. (BCLI) Earnings Call Transcript & Summary

Greetings, and welcome to the BrainStorm Cell Therapeutics Conference Call. [Operator Instructions] As a reminder, this call is being recorded. And I would now like to introduce your host for today's call, Michael Wood of LifeSci Advisors. Mr. Wood, you may begin.

Good morning, and thank you for joining us. Earlier today BrainStorm issued a press release, announcing that the FDA will hold an Advisory Committee meeting to review the company's biologic license application for NurOwn in the treatment of ALS. This announcement will be the topic of today's call. Before passing it off to the company for prepared remarks, I would 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 disorders 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 the NurOwn, technology platform, clinical trials of NurOwn and related clinical development programs and the company's ability to develop strategic collaborations and partnerships to support its business planning efforts. Forward-looking statements are subject to numerous risks and uncertainties, many of which are beyond the company's control, including the risks and uncertainties described from time to time in the company's SEC filings. BrainStorm's results may differ materially from those projected on today's call, and the company takes -- undertakes no obligation to publicly update any forward-looking statements. Joining us on the call today will be Chaim Lebovits, President and CEO of BrainStorm; as well as Co-CEO, Dr. Stacy Lindborg. Following the prepared remarks, both speakers will be available to answer questions during the live Q&A session. I'd now like to turn the call over to Mr. Lebovits. Please go ahead.

Thank you, Michael, and thanks to all, who have joined us for this important company update. We are very pleased to announce today that we received notification last Wednesday from the U.S. Food and Drug Administration that it intends to hold an Advisory Committee meeting to discuss our BLA seeking NurOwn's approval for the treatment of ALS. We believe this is an extremely positive development, not only for BrainStorm but for the entire ALS community. Given the urgent need for novel therapies that can improve the lives of individuals living with this devastating disease. In addition, we believe an Advisory Committee meeting is the most prudent and appropriate next step for NurOwn's regulatory path, as there are several complex scientific and policy issues at end. Having NurOwn's full data set and the need for new ALS therapies discussed in the public forum offered by an ADCOM will allow for an open discussion that includes agency reviewers, BrainStorm's experts, clinical program investigators and all other relevant stakeholders in the ALS community. Each of these groups has its own expertise, experience and point of view to contribute, and it is critical that all voices be heard. Before I go on, I want to take the opportunity to thank the FDA for their collaboration throughout the process, that led them to this decision. The team of BrainStorm has been actively working with the agency for quite some time. In fact, this includes the time prior to and after our Type A meeting. We want to be transparent on what is accurate. So before we go further, let me walk you through a high-level overview of the time line leading to today's announcement. We had the Type A meeting in January 11, 2023, and received the minutes, 30 days later. During the Type A meeting, we and the FDA had a detailed discussion on our perspectives. We really appreciated the opportunity to make our case, which we feel is quite substantial and deserving of an outcome. The perspective shared by the FDA review team reflected what was already in the previously issued RTF letter, which is not surprising since there had not been any additional information shared between the refusal to file letter and the type A meeting. Conversations on the best pathways to resolve the outstanding questions that remained following the Type A meeting, continue the next day and for the following few weeks. During these discussions, BrainStorm was presented with multiple options to return the BLA to regulatory review, which included the regulatory procedure the File Over Protest. These discussions resulted in BrainStorm requesting FDA to file our BLA or Protest as this was the regulatory procedure that allowed us to reach an outcome in the shortest amount of time. Next, I would really like to apologize to those who follow BrainStorm for the longer-than-expected gap in our communication. I'm sure you will now understand that given the sensitivity of the regulatory process, we were not in a position to publicly comment on our interactions with the FDA until now, as we only received written confirmation of this outcome that was granted, last Wednesday. This development was the result of diligent work, both by BrainStorm employees and officials of the FDA, all of them consistently displayed professionalism and dedication to their mission and the ALS community. Looking forward, NurOwn's BLA is now under review. That's what matters. The process should be the same, as it would be for any other BLA that was submitted and accepted for filing by the FDA. There will be an outcome with an agenda and set of questions set out by the FDA, which allows experts at FDA and BrainStorm to frame the efficacy and safety of NurOwn and ALS, followed by an opportunity to hear from medical and statistical experts and members of the ALS community. Finally, the agency will render a decision on the BLA by a specified PDUFA date. We anticipate that we will have the date of the outcome soon when we receive the date, we'll also have 30 on the PDUFA date. Lastly, before handing the corner off to Stacy, I want to emphasize one point on our decision to utilize the File Over Protest pathway. As mentioned earlier, this pathway we offered the fastest path to an ADCOM and regulatory decision of the multiple options provided to us. Given the incredibly urgent needs of those living with ALS, we believe this was the only real option for BrainStorm. In addition, taking this path also enabled us to respond to matters identified by the FDA in its refusal to file letter through amendments to the existing BLA without having to withdraw and resubmit the application, which would have taken many months. So in other words, there was no downside utilizing the File Over Protest pathway, while any other pathway would have lengthened the time line to ADCOM and PDUFA date. I'll now turn the call over to Dr. Stacy Lindborg for further comments. Stacy?

Thank you, Chaim. Let me start by reiterating that securing an ADCOM has been central to our strategy because we have a robust and intricate data set that we believe supports approval and will benefit by a deep and thoughtful discussion. This is why, we are thrilled to have the FDA's commitment to hold an ADCOM to review the full body of clinical evidence. I would note that 2 other ALS treatments, Relyvrio and Tofersen, both have had the benefit of an ADCOM review and are examples of how powerful these meetings can be, especially when dealing with a disease with a clear impressing need for new treatments. Relyvrio was approved after being the subject of 2 Advisory Committees last year and in last week's ADCOM to discuss Tofersen, the expert serving on the advisory panel voted unanimously that biomarker evidence supports accelerated approval of the drug. Note that in its Phase III trial, Tofersen did not meet statistical significance on the primary endpoint, looking at the combined analysis of function and survival. Rather, a potential accelerated approval would be supported by favorable trends, post-hoc analyses and biomarker data. We see these recent developments as a major positive for individuals living with ALS, as they underscore a commitment amongst the community for regulatory flexibility when evaluating investigational therapies for this horrific disease. As we move towards our ADCOM, we have the utmost confidence in our team, which has long been preparing for this meeting, essentially starting from the moment we filed the BLA -- we also have full confidence in our data and believe that a comprehensive analysis of our results strongly supports NurOwn's clinically meaningful effectiveness. To summarize some key findings from NurOwn Phase III trial, let me start by acknowledging that it missed its primary endpoint. It's believed that this was influenced and was very likely driven by participants who entered the trial with advanced ALS, who fell victim to the floor effect of the ALS Functional Rating Scale, which is a scale used to quantify disease progression in mini trials, including NurOwn. A floor effect is observed when scale items reach 0 and ongoing progression cannot be measured on the attributes crude. The rate of the ALS Functional Rating Scale decline appears to slow and plateau in many participants despite further deterioration in these same participants. This phenomenon needs to be addressed to gain accurate treatment estimates from the trial. Clinically meaningful preservation of function was observed with NurOwn on primary and secondary endpoints in the trial across analyses that accounted for the floor effect. The treatment effect observed provides important quality of life for persons living with ALS and their loved ones. Specifically, this was observed in a prespecified subgroup with less advanced ALS for the primary and secondary endpoints, as specified in the protocol and analysis plan. In this subgroup, which was defined by a baseline ALS Functional Rating Scale score of 35 and above, -- there was a larger treatment effect across all endpoints with NurOwn compared to placebo with a statistically significant difference observed on a key endpoint, the change from baseline in the ALSFRS-R to week 28 with a p-value of 0.05. This was actually published and can be found on our website with a link to the primary manuscript from the trial and that primarily which included an update to the manuscript published shortly after it was in print. Furthermore, a post-hoc sensitivity analysis of participants across baseline thresholds on the ALSFRS-R above 26 which includes thresholds all the way up to the prespecified threshold of 35, all highlights that NurOwn treated participants retain on average, at least 2 points of function, which is more -- 2 points more than compared to placebo. A difference that was statistically significant with a p-value of less than or equal to 0.05 across all participants with baseline scores above 26. This represents the majority of the clinical trial data and is also summarized in the manuscript in [ muscle and nerve ]. In addition, numerous post hoc sensitivity analyses focused on assessing the treatment effect in participants not impacted by the floor effect of the scale at baseline, including new analyses presented last week at the Annual Muscular Dystrophy Association meeting in Dallas, Texas. These analyses showed higher and statistically significant response rate in NurOwn versus placebo in the primary endpoint. With 41% of participants clinically responding that were treated with NurOwn compared to 23% response on placebo, a p-value that was 0.035. In addition, there were statistically and significantly less disease progression on the endpoint average change from baseline in the ALSFRS-R to week 28, with a difference of 2.31 points preserved with NurOwn treated participants compared to placebo and a p-value 0.04. The presentation that was given at MDA is in the Events and Presentations section of our website. And then finally, we are all encouraged and further encouraged by the strong and consistent changes observed in the biomarker data, which is in all trial participants. This includes those that had advanced ALS. Results showed post-treatment reductions in markers of neuroinflammation and neurodegeneration and in addition, elevations in markers of neuroprotection. All these pathways are externally important to ALS. These results align with NurOwn's mechanism of action. And additionally, 3 biomarkers were identified as being predictive of clinical response, using prespecified modeling designed to identify the importance of biomarker changes in the context of clinical outcomes observed in the trial. These biomarkers include neurofilament light, latency associated peptide or LAP and Galectin 1, which are markers of neurodegeneration, neuroinflammation and neuroprotection, respectively. Biomarker results have presented at a variety of scientific meetings, including in January of this year, the California ALS Research Summit, which is also on our website in the Events and Presentations section. Importantly, the various findings, I've just discussed, represent only a sample of the body of clinical evidence supporting NurOwn's effectiveness, that will be discussed at the upcoming ADCOM. I'll now turn the call back to Chaim for closing remarks.

Thank you so much, Stacy. Before we start the Q&A session, I would like to again, thank our employees and those at the FDA for their work moving NurOwn through the regulatory process. Our commitment to improving the lives of those living with ALS is unwavering, and we really look forward to our upcoming outcome. We'll now open the call for questions. Jenny?

Certainly, the floor is now open for questions. [Operator Instructions] Your first question is coming from David Bautz of Zacks Small-Cap Research.

Congrats Chaim, Stacy on the news today. So my first question is, what is the actual filing date then that the FDA considers for the BLA? And,, I ask because I'm trying to figure out when the most likely date will be for the PDUFA?

Yes. Very good question, David. And the FDA and the notification said that they will be advising us very soon on the date. They've been working on this quite a while, to get the data to you or undertaking to put up an outcome. And also you may know that office of tissue is now no more the FDA now launched the new office and the same people working everything there. So we've got to give them a few more, I don't know, days or week, I don't want to say then, they will quote what I said. But we understand that we'll get that data very soon, but the FDA wanted us to be able to communicate to patients.

Okay. Is there any additional data that the company has yet to disclose? Or that might be disclosed before the ADCOM is going to take place?

Well, we definitely are working on a biomarker manuscript. But, I'll let Stacy fill in that question in more detail.

Yes, David. Thanks for the question. So, large trials like our Phase III trial contains a huge amount of data, as we continue to meet with neurologists in the community and have really great discussions with insightful questions. We will continue to analyze our trial, and to gain new insights. So we will continue to uncover new perspectives. And as you -- as we just referenced, we presented recent results at the Muscular Dystrophy Association.

Okay. And just a quick follow-up. Is data from, say, the hospital exemption program, is that going to be included as well in the ADCOM discussion?

Stacy.

Yes, I'm happy to take that. So, that is a compassionate use program that was started and remains ongoing. It was not like a clinical trial in the sense of collecting data in a rigorous fashion. So, it is unlikely to be the focus of discussion and an ADCOM.

Okay. And then my last question is about the floor effect, which you guys have discussed a lot and clearly, it had an impact on the trial results. I'm just curious, how the FDA feels about the floor effect. Are they aware of it? Are they -- do they understand the impact that it can have on trials like yours?

S Stacy go for it.

Yes. I think that will become clear at the Advisory Committee meeting. We've presented, as clearly as we can. And I think very objectively, when you take data points on the gold standard scale, the ALS Functional Rating Scale that goes back to 0 at baseline. It's pretty objective to say that we can't measure ongoing decline on these items. And as you have an accumulation of this, it creates a problem. The FDA certainly has seen this data clearly and has not disagreed with the statements we've made, but I think the Advisory Committee will bring for all of us, the more comprehensive review of the evidence and the extent, that we feel supports NurOwn, as a product.

[Operator Instructions] Okay, appears we have no further questions in the queue. I will now hand back over to any closing remarks.

Let's wait a minute, sometimes people complain that we run away from questions. Let's see, if there's going to be other questions. Sometimes the queue doesn't work in a computer or want solved the patient. Let's wait a minute. Please, if you can give again the instructions how people can queue for a question.

[Operator Instructions]

Okay. Jenn, -- no one is asking. Do you see the majority of people listen again from the Internet, and they don't have how to ask, right? Yes. So yes, I'll thank everyone for being on this call here today. We're looking forward for additional updates, when we get it from the FDA on the actual date. Thank you very, very much for being with us here this morning.

Thank you, everybody. This does conclude today's conference call.

I do have a question. We can take it.

Okay. We have a question from Richard Robbins, who's a private investor.

I just have a question about what were the other pathways to an ADCOM that the FDA presented to you.

We didn't get -- Richard, what was other what...

On the pathways, you mentioned that there were alternate pathways...

Okay. Yes, definitely. -- sure, sure. 100%. So just to express one of them, and we won't go into a lot of detail, we want to respect the process. But we were able, for example, to withdraw and resubmit including the amendment, but that would take for a longer time. Filing Over Protest, we gain that the date that we filed is taking into consideration towards the PDUFA date. So, the first 2 months until we got the RTF letter, that's already counted. And then when re-filed, it goes back to that -- it adds on to the first month. Versus to, for example, to withdraw and resubmit that can take months until that happens, and then it starts from again from 0 to date. So this is just one example. But thank you for that question.

Thank you...

Okay. And just to remind everybody that the 2022 year-end earnings call will be taking place on March 30.

Thank you very much, Jenny. Have a wonderful day.

Thank you, everyone. You can disconnect your phone lines, and have a wonderful day. Thank you for your participation.