Brainstorm Cell Therapeutics Inc (BCLI) 2022 Q3 法說會逐字稿

Greetings, and welcome to the BrainStorm Cell Therapeutics third-quarter 2022 conference call. (Operator Instructions) As a reminder, this conference call is being recorded.

And now I would like to introduce your host for today's conference, Michael Wood of LifeSci Advisors. Mr. Wood, you may begin.

Good morning and thank you for joining us. Before we begin the call and opening remarks, we'd like to remind listeners that this conference call contains 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 and MS, the sufficiency of the company's existing capital resources for continuing operations in 2022 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 their business planning efforts.

Forward-looking 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 takes no obligation to publicly update any forward-looking statements.

Joining us on the call today will be Chaim Lebovits, President and CEO of BrainStorm; Dr. Stacy Lindborg, Executive Vice President and Chief Development Officer; Dr. Ralph Kern, President and Chief Medical Officer; and Alla Patlis, Interim Chief Financial Officer. In addition, Dr. David Setboun, Executive Vice President and Chief Operating Officer is also on the call and will be available to answer your questions during the Q&A session.

So now I'd like to turn the call over to Mr. Lebovits. Please go ahead.

Thanks, Michael, and thank you to everyone for joining us this morning. As is our usual practice, we'll follow our prepared remarks by addressing questions we received from investors in advance, as well as taking live questions from those of you listening on the call today.

The main topic I want to cover this morning is the FDA's issuance of a refusal to file letter for the NurOwn BLA submission. The letter we received from the FDA contained two topics that led to the issuance of the refusal to file letter. The first is clinical and statistics, and the second is CMC or chemistry, manufacturing, and controls.

On the first topic, clinical and statistics, the letter basically summarizes what was known prior to the filing, that the trial missed the primary endpoint. On the second topic, the letter itemizes CMC items that we expect to be able to fully remediate.

Returning to the first and arguably the most important topic in the letter. It is clear that the FDA still seeks substantial evidence defined by statistically significant result on the clinical outcomes measured by the primary endpoint. And anything short of this, in their view, is insufficient evidence for a filing. We obviously have a different view on the value of the evidence that has been generated from the Phase 3 trial. We continue to believe that the totality of evidence from the Phase 3 trial is sufficient to support an approval and represents a significant contribution to ALS therapy.

We also believe there needs to be urgency and flexibility in the review and approval of treatments for individuals with ALS who have no time to waste. ALS remains a uniformly fatal illness where death occurs typically within two to five years from diagnosis. The limited number of available treatments have only a modest impact on the disease progression.

We will pursue a Type A meeting to progress this application, and as part of this meeting, we will discuss with FDA a path to an FDA Advisory Committee meeting, an AdCom. We believe that it is more than reasonable to expect that the FDA will allow a fair hearing in an open and transparent setting as an FDA Advisory Committee meeting.

An AdCom provides an open and fair hearing in a public venue, which the FDA can frame their review of the evidence and all the other relevant stakeholders can also express their view. And also hear how medical experts, statisticians, patients and other members of the ALS community view our data. This forum will also allow patients, physicians, and the broader advocacy community to express their views relevant to an approval.

At this point, I will turn the call over to Dr. Stacy Lindborg, our Executive Vice President and Chief Development Officer for some additional comments and to provide a review of data shared through recent medical conference presentations. Stacy?

Thank you, Chaim. Let me begin by reiterating my support for the path forward that Chaim just outlined. We remain committed to people living with ALS, and we'll do everything within our power to allow due process for NurOwn because we continue to believe that the totality of evidence from the Phase 3 trial is sufficient to support an approval and represents a significant contribution to ALS therapy.

We will press forward in the regulatory process and take the steps necessary to move towards an Advisory Committee, and we are fortunate to have support from some of the most respected analysts, clinicians, and researchers, who have indicated to us that they are frustrated by the news of the FDA refusal to file our BLA.

As we shared in previous earnings calls, we continue to have scientific discussions around our data, and there is a growing belief that the totality of evidence for NurOwn suggests a signal of efficacy that should not be ignored. While the regulatory process remains the primary focus for the company, we continue to share new data on NurOwn with the medical community.

There are two important recent presentations, one at the ALS ONE Research Symposium and another at the Annual NEALS meeting that I want to highlight. Both presentations contained new analyses from NurOwn's Phase 3 ALS trial. At ALS ONE, we presented data showing that NurOwn had a consistent effect on biomarkers, both in people with advanced ALS at baseline in the trial and those with less advanced disease, with no evidence of a floor effect in the biomarker data.

At the NEALS meeting, we had a poster on new sensitivity analyses that account for the floor effect in the ALS functional rating scale, revised ALS functional rating scale on the key endpoints from NurOwn's Phase 3 trial. Both of these datasets add to the robust body of evidence that we believe supports a clinically meaningful treatment for NurOwn and ALS.

Let me begin by speaking about a presentation I gave at the Fifth Annual ALS ONE Research Symposium that took place in October. As we've described before, seven CSF samples were collected in all participants in the Phase 3 trial. NurOwn was shown to decrease biomarkers associated with neuroinflammation and neurodegeneration and increase neuroprotective biomarkers over 20 weeks, demonstrating its multifaceted mechanism of action.

The new analyses that were shared at ALS ONE looks at the longitudinal trajectory of biomarkers for the subgroup of participants with baseline ALSFRS-R scores greater than 25 compared to those with a baseline scores less than or equal to 25, the latter group being those participants that were most likely to be impacted by the floor effect on the ALSFRS- R scale.

Consistent patterns were observed across biomarkers in both subgroups. Specifically, we observed decreases in pro-neuroinflammatory and neurodegenerative markers and increases in neuroprotective and anti-inflammatory markers in participants treated with NurOwn compared to placebo. These results indicate that NurOwn was having similar biological effects on trial participants, regardless of the level of disease progression at baseline.

This is important because while it was difficult to accurately assess the treatment effect of NurOwn in participants who had more advanced disease at baseline because of the limitations with the revised ALS functional rating scale, the biomarker data showed that murine was actually producing a biological effect in all trial participants.

Furthermore, prespecified statistical modeling designed to identify biomarkers that have the potential to predict a clinical response with NurOwn identified biomarkers that span the three key pathways of neurodegeneration, neuroinflammation and neuroprotection, and the model had good statistical properties.

I'd now like to move on to discuss the poster presented at the recent NEALS meeting, which featured the results of two post-hoc and sensitivity analysis methods, looking at the total score threshold and the item level threshold. These methods allow us to take orthogonal approaches to better understand the true effects of treatment with NurOwn observed in this Phase 3 trial compared to placebo by directly addressing the floor effect of the ALSFRS-R, which confounds the treatment estimate in the trial.

Results generated with each method show that after controlling for the impact of the ALSFRS-R floor effect, participants treated with NurOwn had a higher rate of clinical response and less function lost across 28 weeks compared to placebo. The treatment response observed in these sensitivity analyses are consistent with results from the prespecified subgroup from the trial, which was statistically significant at a p of 0.050 level in the secondary endpoint average chain from baseline to week 28.

This presentation was jointly delivered by myself and Dr. Merit Cudkowicz, Chief of Neurology at Massachusetts General Hospital; Julieanne Dorn, Professor of Neurology at Harvard Medical School and Director of the Sean Healey -- Sean M. Healey and AMG Center for ALS at the Massachusetts General Hospital.

To gather these data give us new insights into the NurOwn and Phase 3 data and provide evidence of NurOwn's clinically meaningful effects. We are pleased to be able to share them with the ALS community. We believe that the scientific vetting of our data will be important to an AdCom discussion and will enable better understanding of the evidence that's been generated.

I'll now turn the call over to our President and Chief Medical Officer, Dr. Ralph Kern.

Thank you, Stacy. There's one other important piece of recent news that we want to mention briefly today, which relates to publications of our Phase 2 trial of NurOwn in progressive MS. The study was featured in the Multiple Sclerosis Journal in September of this year and was also presented at the 38th Congress of the European Committee for Treatment and Research in Multiple Sclerosis, also known as ECTRIMS by Dr. Jeffrey Cohen, Hazel Prior Hostetler, Endowed Chair and Professor of Neurology at the Cleveland Clinic, Lerner College of Medicine and Director of Experimental Therapeutics Mellen Center for MS Treatment and Research.

Having these positive data published in a prestigious peer review journal, in addition to being presented at ECTRIMS is an important step in the evaluation of NurOwn's potential as an innovative therapy in progressive MS, a devastating neurological disease with limited therapeutic options. The study met the primary endpoint of safety and demonstrated improvements in tests of neurological function and cognition as well as important changes in CSF biomarkers that reflect NurOwn's mechanism of action on important MS disease pathways.

We believe the clinical and biomarker results that were featured in the manuscript provides strong rationale to continue the evaluation of NurOwn to potentially address the unmet clinical needs of these patients who have fewer therapeutic options. Furthermore, the biomarker results provide additional support for NurOwn's potential as a platform technology with broad applications in neurodegenerative diseases. We are currently collecting feedback from MS experts and regulators, which will inform our plans to advance NurOwn in progressive MS.

Before I turn the call over to Alla Patlis, who will review our financials, let me conclude my remarks by expressing our sincere gratitude to the FDA for offering to discuss the path forward for NurOwn in ALS through a Type A meeting, which, as my colleagues mentioned, could offer a path to an AdCom. We believe this is the best outcome for patients and caregivers with ALS.

I will now turn the call over to Alla Patlis, who will review our financials.

Thank you, Ralph. It is my pleasure now to discuss our financial results for the third quarter ended September 30, 2022. BrainStorm's cash, cash equivalents and short-term bank deposits were approximately $7.4 million as of the end of September, and this compares with approximately $22.1 million on December 31, 2021.

Our research and development expenditures net in the third quarter of 2022 were $3.8 million compared to $3.6 million for the comparable period in 2021. General and administrative expenses for the third quarter were $3.1 million compared with $1.7 million in the comparable period of 2021.

Net loss for the third quarter was $6.9 million or $0.19 per share as compared to a net loss of $5.3 million or $0.15 per share for the comparable period in 2021.

Back to you, Chaim.

Thank you, Alla. Michael Wood from LifeSci will now read questions we have received from investors. Michael?

Thanks, Chaim. I have first question here. Can you tell us in as much detail as possible but without jeopardizing your company to shareholders and the future approval of NurOwn why the FDA rejected the company's BLA? The ALS community needs as much information as you can provide so we can support you and respond respectfully to the FDA.

Thank you. I believe we've covered this question quite a lot of detail in our prepared remarks. Obviously, we don't think it will jeopardize the company by being transparent with the community as you have seen. However, I want to say I truly appreciate the way this question is framed specifically the wording around how you can respond respectfully to FDA on social media.

We believe that people living with ALS and ALS community deserve to hear an open professional debate and to have their voice heard, but it is critical that for any of you that decide to reach out to FDA or write comments in the social media, we urge you please be respectful. Vulgar language is not fair, nor helpful. I thought it was important to say in this call.

Thank you, Michael. The next question, please.

If you intend to refile the BLA, what additional information or data can you include that would influence the FDA to change their mind and accept the filing?

Stacy.

Yes. So as we've already stated, our next step will be to pursue a Type A meeting. This meeting allows a discussion of the best path forward, which could include two things: number one, additional data; number two, a possible agreement for submission and a request for an AdCom as stated in the prepared remarks.

Thank you.

Next question, what is the expected timing of the Type A meeting?

Stacy, for you, too.

Per the FDA regulations, we have 30 days from the receipt of the refusal to file letter to request a Type A meeting, and the FDA then should schedule this Type A. meeting, which should occur within 30 days of the receipt of our meeting request.

Thank you. As we move forward, can you comment on any potential learnings that you would apply from the process that preceded with Relyvrio's approval in ALS?

Thank you. Michael. Relyvrio, you mean in Amylyx. Ralph, please take this.

Yeah. Thanks for the question. One of the major learnings from Relyvrio's approval process is the importance of having an open and transparent discussion among regulators, clinicians, statisticians, and the broader ALS community. Recall that the FDA originally instructed Relyvrio's sponsor not to file on the basis of their single Phase 2 trial. After further consideration, this decision was reversed, leading to the Relyvrio NDA filing.

Then please recall that after this filing, the agency issued briefing documents for both AdComs, which contain quite negative views on Relyvrio data. At this first AdCom, the committee voted 6 to 4 against Relyvrio. This was then followed by continued discussion and analysis of data, eventually leading to a second AdCom where the agency again issued negative briefing documents.

However, at the second AdCom, senior FDA officials opined that the AdCom members should consider the unmet need for people living with ALS. And as FDA guidelines allow to vote based on the afforded regulatory flexibility to consider when sufficient evidence may suffice, ultimately, the committee voted 7 to 2 in favor of Relyvrio, which then subsequently went on to gain FDA approval.

Looking back at these events you can see just how powerful and critically important for patients the AdCom process can be. It provides an open forum for the public to hear opinions from professionals on both sides of the debate around data. Moreover, we've seen that this debate can ultimately prove to be persuasive with the agency and lead to patients gaining access to new therapies.

We, therefore, remain fully committed to NurOwn's advancements. And we feel strongly that having an opportunity to have our BLA filed so that we can discuss our data in the context of an AdCom is the best interest of the ALS community.

Thank you. Next question, would you consider running an additional clinical trial to convince the FDA of NurOwn's clinical effectiveness?

Stacy, please take this.

Thanks for the question. As stated in the prepared remarks, we believe that for diseases such as ALS, which are uniformly fatal with limited treatment options, that individuals should have the chance to gain broad access to therapies that suggest a clinically important treatment effect. Even if clinical trial results are less than absolute, we believe NurOwn fits this criterion. Having said that, part of our Type A meeting will be to discuss with FDA a possible confirmatory trial.

Thank you.

But with the FDA having refused to file the BLA, is it possible for an AdCom meeting to take place?

Stacy, please take this.

Absolutely. There are processes in place at the FDA that can allow for a sponsor's application to go from a refusal to file letter So all that ultimately being filed with an advisory committee meeting to follow. And not only that, there are examples with precedent of this. However, to be clear, our next step will be to request and participate in a Type A meeting with the FDA. And as part of this meeting to discuss all of these issues, we will listen to the feedback from FDA and seek insights that allow us to chart the best path forward.

Thank you. Given this news from the FDA, will BrainStorm now consider first pursuing approvals in other countries?

Ralph?

Yes. Thank you for the question. As we previously stated, we continue to evaluate opportunities for filings in other countries and jurisdictions. But for now our primary focus is with the FDA.

Thanks. And next question, what happened with the biomarker data from the Phase 3 study? You've spoken about a peer-reviewed manuscript for this in the past.

Stacy?

Great question. The biomarker data from this study is an important part of the body of evidence from the Phase 3 trial. Biomarker data, as you know, from this trial has been presented at numerous scientific meetings, all of which can be found in the Events and Presentations section of our company's website.

However, we are actively working with leading biomarker experts on a comprehensive manuscript that reports on all biomarkers collected. An early draft of the manuscript exists and getting the manuscript under review in a prestigious peer-reviewed journal is one of the highest priorities for BrainStorm.

I want to take the opportunity while we're discussing the biomarker data to thank three important partners for their support of our biomarker study, the ALS Association, I AM ALS, and the California Institute of Regenerative Medicine. Each of these partners believed in NurOwn, believed in the importance of developing ALS biomarkers, and invested funds to generate the rich biomarker data that we now have from our Phase 3 trial.

Thank you.

So the next question is from an ALS patient family member. This is the time to be perfectly honest with your shareholders and ALS patients, if you wanted to fight for NurOwn. For some strange reason, I'm still waiting -- willing to do that, Chaim, even though my son, Andrew, who completed the Phase 3 at the Mayo Clinic, had died waiting October 3, 2022. I don't want any other mother to have to watch her child die. Be honest with us, please. This is crucial.

I guess I have to take this one. It's addressed to me. It is heartbreaking to hear this question. I regret to share that we received heartbreaking emails like this all too frequently. I think this question took courage to share. So thanks.

Please know that we use these unimaginable events to propel us forward. These stories, each of which represent loved ones gone far too soon are the reason we won't give up. Hearing that your son was in our Phase 3 trial, I want to let you know how grateful we are to you and your son for participating in our Phase 3 trial, for hoping to generate evidence that we can take forward to the FDA and to the community with the goal of helping others.

We want you to know that we are always honest with our statements. There are times when we have to be silent to allow due process. Today is not one of those times. Today, we have shared openly with investors and with all others listening, as you have heard. Thank you for not giving up. Thank you for your fight on behalf of other mothers and family members. Thank you.

The next question is regarding the expanded access program. What is the status of the EAP and were the EAP data is submitted to the FDA?

Stacy?

The original expanded access program was designed to provide three treatments with NurOwn, and all given two months apart. During the conduct of the program, we were approached by the FDA and requested to consider expanding the program to include a second period. We agreed to their request and amended the protocol to include one additional period with three additional treatments two months apart, which is a total of six treatments across the entire expanded access program.

Regarding the status, the first period of the EAP is complete, and the second period is ongoing. And since the EAP was ongoing at the time of the BLA filing, we submitted a summary of EAP data available prior to the filing of our BLA with the FDA.

Thank you.

The next is a financial question. How do you plan to fund the company going forward?

Yes. The $1 billion question. We have an ATM of $100 million that we can tap into opportunistically. In addition, quite a few of our major shareholders are considering supporting the company at this time. They felt it might be a good time to even out their investments while supporting the company's potential pathway to approval. [Wilson] talks with institutional investors that might see this as an opportunity to get in the ground floor closer to potential pivotal milestones such as an AdCom and a possible approval.

The best strategy for financial means where the main focus of the company is, and that is to arrive at an agreement with the FDA to allow an AdCom. Once we have it figured this out, our burn rate will be, in my belief, a nonissue. Thank you.

And just one last question from a list of submitted questions. Can you comment please on BrainStorm's and exosome technology?

Sure. Ralph, please take that.

Yes, Thank you for that question. Our preclinical program of acute and fibrotic respiratory indications is actively ongoing with more positive results from an in vivo study in an LPS-induced acute lung injury model treated with aerosolized exosomes. We observed statistically significant higher blood oxygen saturation in treated mice compared to controls.

Furthermore, we have initiated an exploratory program to screen for inflammatory indications in which the exosome immunomodulatory effects point to potential clinical benefit. Additionally, in line with our view of exosomes as a platform technology for targeted delivery of therapeutic molecules, we have initiated a program to bind targeting moieties and load the exosomes with bioactive molecules.

Finally, we have delineated the roadmap for SMP Exosome for GMP Exosome manufacturing and are in active discussions with leading clinicians for planning first clinical trials in inflammatory lung conditions.

Thank you. Holly, could you open for questions?

(Operator Instructions) David Bautz, Zacks Small Cap

Hey. Good morning, everybody. Chaim, I'm curious if you could give just a little bit more information about the CMC issues that the FDA brought up. And perhaps, importantly, how costly, if they will be costly, will those changes need to be?

Yeah. Thank you very much, David. So the CMC issues are more trivial issues. It's not really costly. It's asking much on questions about some validation and some others. Some are already in the BLA, and we have to point out where it is. Some are we anticipated. Most of the questions we would see them as review questions. We don't see outside of the clinical comment any red flag.

Okay. That's good to hear. And then I guess this question is for Stacy. Stacy, you've talked about the floor effect, and I guess some data that you presented you guys were accounting for that. I was wondering if you could just talk a little bit about more what actually is the floor effect and why it needs to be accounted for in the trial.

Yeah, David, that's a great question. And it has been part of the presentations that we've given to really be very clear with what we mean by the spring floor effect. So what we observed in participants that are starting at baseline, we've chosen to focus on the threshold of 25 and below, which really represents a set of trial participants who haven't been in other late-phased trials.

What's experienced with these if we see a pronounced rate of ALSFRS-R items that start at the score of zero. So individual items and scale items go from zero to four. You start at zero, you cannot measure ongoing disease progression. So when this happens, the scale is not able to quantify or to measure any disease progression, certainly in those questions as well as across the multiple other items that, in some patients, started at zeros.

So the overall effect is that the participants are declining. This is a uniformly fatal illness. We know that disease progression continues, but the scale is not able to quantify it. So it misrepresents certainly with the primary endpoint, which when you have a change in the rate of decline, if labeled a treatment response on the primary endpoint, it actually misrepresented the data as a clinical response when it is simply an inability to measure disease progression.

So it's a critical thing. It's something that we can actually very objectively quantify, and it's something that does need to be controlled for, and to be able to see the endpoints that were prespecified, how they are influenced once we control for that data. And in fact, see that the treatment effect is as we expected with the powering of the trial. It's very consistent with the powering of the trial, and it's very consistent across (technical difficulty) all of these that we do control -- control those data with different methods.

Okay, great. That's actually really helpful. Thanks for taking the questions this morning.

Well, thank you, David.

[Myra Klingenberg], private investor.

Yes, can you hear me?

Yes.

Yes. I just want to state that my son, Matthew, was in the Phase 3 trial and he received EAP 1 and EAP 2. He and his wife and the rest of us in the family have never doubted that NurOwn helped him stabilize and improve for periods of time. I think an AdCom is absolutely necessary. We continue to fight every day for NurOwn. We thank BrainStorm for your continued work and to not -- and for not abandoning ALS. We are here to support the process. Thank you.

Well, I guess it's not a question, and thank you very much for your comments. Appreciate that.

[Kylan Morris], private investor.

Good morning, everybody. And my name is Kylan Morris. My mom was in the BrainStorm trial as well as EAP. I just wanted to first thank you all for your help and my family getting to keep I'm for an extra couple of years. We have no doubt along with, as (inaudible) said, this helped my mom. We believe in the following and also -- her breathing improved. We, unfortunately, lost my mom two months ago, that was August 28.

So my question here, because my mom was certainly at the tail end of this disease. Her ALSFRS-R was well below 25 when entering the EAPs. I just wanted to go over the biomarkers once more. And can you confirm that my BrainStorm found changes in all biomarkers even for people at mom's ALSFRS-R score.

Chaim, would you like me to take that?

Please, Stacy, yes. I was on mute.

Yes. Thank you for the quick question, Kylan. And yes, I am able to confirm your understanding is exactly right. And it was a very important finding for us to be able to present in the scientific literature that we see consistent patterns in our biomarkers with NurOwn treated persistent levels of inflammation decreasing, levels of no protection increasing, end levels of neurodegeneration increasing.

These were seen consistently in participants that were in the lower end of the scale, similar to where your mother into the trial as well as participants that had higher values. It was very, very consistent patterns across the biomarker data.

Awesome. I do have one more question. Were there any difference in biomarkers seen with people with higher scores up, I guess, above 35 versus those below and 25 like my mom?

I think it's similar question to what you asked before and maybe what I'll add in. So when we uncover that, we don't see differences in the baseline values in the -- across the biomarkers, across -- not only these important pathways, but really across every biomarker that we collected. Then it becomes very powerful because we're able to present the biomarker data in total. So all participants.

So as you look at the presentations we've given, you'll see that these are all trial participants, and we believe that's the best way to represent the data. What's also very important in our data and I shared this in the prepared remarks -- but when we look at connecting biomarker data with the clinical data, this was a prespecified analysis, which is very important. We had a separate statistical analysis plan that was submitted to the FDA to govern our analyses of the biomarker data and really the importance of the biomarker data relative to the clinical outcomes.

And when we look at NurOwn treated participants, and we look at the biomarker data, we find through an appropriate and powerful statistical model that there are three key biomarkers that explain or are predictive of the clinical outcomes observed in the trial. So what that means is these changes in these biomarkers are important and they're relevant to the clinical outcome.

Thank you, Stacy. I appreciate it. And again, thank you to you all. Truly, I believe that you gave us years extra with my mom. So thank you.

Sure. Thank you.

[Dialo Wilkerson].

Hi. Thanks for taking my question, if there is from a chance to maybe narrow the scope of the application to support the ALSFRS patients with the score of at least 26 and above. It seems like your data supports that strongly. And if there's any and if there is any breakdown in your application to the FDA, I was just asking if that was part of it or was it just a full request for approval no matter what the point score was for patients.

Yeah. Thank you for your question, but legal counsel would advise us not to go into such detail today. As you can imagine, we're still there for our Type A meeting. We'll share when it won't be an issue for us to share. Any additional question you might have. Hello? I guess we lost him. Okay, operator?

[Paula Smith].

Thank you.

Hi. My name is Paula Smith. My son, Josh, is 33 years old and he was in the NurOwn trial and both EAPs. First of all, as a mother, I just want to say how grateful I am to the BrainStorm team, as I believe that my son, Josh is still here today because of the NurOwn. Josh was diagnosed in March of 2019. And today, he's still walking, talking, eating, breathing, and still able to take family vacations.

Well, he was in the trial and in the EAP, every time that he received the NurOwn, it halted his progression significantly and his spiculations stopped. When he wasn't receiving it, he declined. We're now worried that EAP is over and that his loss of function is so ominous.

I have two questions today. During the EAP, my son's pulmonologist documented a 41% improvement and he's breathing function -- his breathing was at 64%. And it went to 105%. I know that the EAP sites weren't collecting this data because of COVID. Several others in the EAP program have also improved in their breathing. My question is how can we ensure that BrainStorm includes this information in the submission to the FDA to show that NurOwn is working?

Listen, these questions from on patient families, members calling us, we are not prepared for this in an investor call, but we really appreciate it, number one. But as you can imagine, we cannot comment about patient data. I'm sure we collect everything professionally through our CRO and only that data we are able to submit.

I know you EAP patients find their own ways to perhaps submit maybe through a doctor in the centers and they can share with us our CRO perhaps. We don't -- we cannot have direct contact with patients, as you know. Again, it's very warming to hear from one hand. On the other hand, you know restrained we are, regulatory-wise, to discuss any patients.

I just want to thank you, of course, and your son for being part of this and it's really warming to hear what you're saying. But I hope you understand that we cannot really comment to these comments.

I just feel like if it's the data that they're looking for, we have it. We have it proven by the trial, the EAP, and then our outside directors. Our outside directors can't believe the change in my son. I mean, if you're looking for the information, we have the information. That's all I'm saying.

Okay. We will pursue all leads that we can professionally offline. We thank you for approaching us on this.

Okay. Thank you.

And I'll say again how happy I am here. We are all probably hear -- to hear how the families benefiting, you feel benefiting from NurOwn.

Yes.

The patient and it's very warming to hear that. But we cannot comment outside of that, as you can understand.

Okay. Thank you.

We'll take one more follow-up question, I believe, and we are getting close to 9:00. So, operator?

[Daniel Walker].

Yes, good morning. Daniel Walker with [Nest industries]. Chaim, can you maybe just talk a little bit about this Refusal to File letter? I guess it seemed like in some of your previous comments that you are working very closely with the FDA. You spoke very highly of your work that you're doing with the FDA. How much of a surprise was this Refusal to File? I mean, again, you had indicated they were working with great urgency and partnering very closely with you. Can you just opine on that a little bit?

Yeah. Thank you. So as you know, we share that with the public when we announced the intention to file. So we had long ago taking the decision we have to file the BLA. That's the only way to get through to an AdCom meeting. So we filed the BLA. We were hoping it would be accepted for review and will be offered an outcome. But the -- definitely the letter that we got from the FDA, it wasn't what we expected.

But the good news is that the Type A meeting allow us an AdCom request from the FDA. So like it's a bump in the road, and that's a big bump in the road. But I think we're still on the right track to proceed. And I believe that FDA respect the due process here. We respect their view. It's a different view than our view. We have huge support from leading key opinion leaders and some of the patient community.

And we think, as we said on the call, you heard that the AdCom is the right venue to be able to have the debate like you've seen other products in ALS. But we're only approved because they got -- some got more than one AdCom. So I think we should get a chance at one AdCom and we want to win at the first AdCom. That's our plan and we have to prepare for that. So that's where we are, I think, that the FDA has no reason not to allow an AdCom. Thanks for that question.

Great. Thank you so much. And Chaim, maybe just to kind of follow that up. I guess Merit, the doctor at Mass General said that you made -- had there been different understanding of the flexibility between or what might be considered flexibility between at SEDAR at Cyber. Can you comment on that?

Well, listen, Dr. Cudkowicz, she speaks for herself. I don't have to explain her statements. She's one of the leading doctors in the United States for ALS. She's Chief of Neurology at Harvard. She understands (inaudible) better than we do even. What I could share with you is that our view is similar to many rare disease experts' opinion that in such rare diseases as ALS, where there are very few treatment options, if at all to offer, the FDA should -- must be more concerned with a false negative rather than the concern of a false positive.

And we hope to see that. I think we have seen some flexibility in a previous approval for these reasons. We've heard doctors hearing and that they accepted it. And we hope -- we're very hopeful that we are on the same track to that approval. So thank you for this question.

Thank you so much, Chaim.

Yes. Operator, I think that brings our call to a conclusion today.

Do you have any closing comments, Chaim?

I just gave us the closing comments. But thank you very much, Holly. This was very well done and look forward for our upcoming calls with additional better news. Thank you very, very much.

Thank you. Ladies and gentlemen, this does conclude today's event. You may disconnect your phone lines at this time and have a wonderful day. Thank you for your participation.