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

I am Stacy Lindborg. I'm Executive Vice President and Head of Global Clinical Research at BrainStorm Cell Therapeutics, and I'm pleased to be here today speaking to you on behalf of the company. I'd like to start by introducing you to BrainStorm's unique cell therapy product. It's an autologous product, which means that we use a patient's own cells to produce their product. As part of the manufacturing, cryopreservation allows us to create an off-the-shelf product for each patient as one harvest of bone marrow creates several years of therapy. From the point of harvesting bone marrow, the first treatment is available in 19 days, with subsequent treatments being available in 7 days. Attributes that contribute to the product being consistent and reliable include things like there are no animal proteins or antibiotics, genetic modifications or viral vectors used. Neuron is culture rescued, creating a product with a very high cell viability and consistent performance characteristics. And during the production of neuron, mesenchymal stem cells are expanded and induced to differentiate into MSC-NTF cells, which are optimized to secrete neurotrophic factors. And lastly, neuron is manufactured with cell potency criteria, and all of these contribute to the reliable and consistent nature of this product. From a platform perspective, we've been conducting clinical studies for 10 years with animal studies, and neurodegenerative disease animal models preceding this. And across these studies, we've observed consistent biology, in vitro and in vivo data. And we confirm the same neuroprotection, neurotrophic support and immunomodulatory effects from earlier trials in Phase II ALS population. Our knowledge of safety continues to grow across indications with more than 170 trial participants being treated to date. We're a publicly traded company that's capitalized on strengths of our R&D center in Israel by complementing the leadership team with experienced executives from pharmaceutical companies based in the U.S. and Europe. We've taken the best cell therapy, and we've applied this to neurodegenerative disease. This slide shows our growing development pipeline. And as you can see, we've leveraged our innovative cell-based platform and progressed clinical [indiscernible] across a set of neurodegenerative diseases. We're currently conducting clinical studies in 3 areas: ALS, progressive MS, and we'll soon be starting a trial in Alzheimer's disease. Our flagship program is in ALS, and the Phase II trial is fully enrolled with top line data expected to readout in the fourth quarter of 2020. And we're proud that this was able to continue as planned through the current pandemic, and we hope that we'll soon be bringing positive news for people suffering from this horrible disease. In parallel, we have a Phase II study going on in progressive MS with top line data also expected in Q4 this year. And our Alzheimer's study is scheduled to start before the end of 2020. As I've referenced earlier, we've been conducting ALS clinical research for more than 10 years. Our earlier trials have been published in JAMA Neurology and Neurology and are easily accessible if you'd like to learn more about the evidence generated in these trials. Prior to Phase III, we completed a rigorously conducted Phase II study that identified dosing, safety and an important efficacy signal, which I will now take you through, and then conclude with our Phase III trial design in primary end point. Our Phase II study was a double-blind trial with 3:1 randomization to neuron or MSC-NTF cells and placebo. 48 trial participants total were randomized and had a 12-week run-in period, which is important in a disease like ALS with -- that has such great heterogeneity in disease progression across patients. During this period, we had 4 collections of the ALS functional rating scale, which allows us to understand the rate of ALS decline for each participant prior to treatment. And this allows us more precision in our estimates of treatment, the treatment effect in the treated period. In this trial, participants received one treatment and then were followed for 24 to 26 weeks. And the study was primarily a safety and tolerability study, although we collected efficacy data and CSF biomarker data. Fast progressor criteria and clinical response criteria was also established a priority. We can see from the slide that a single dose of neuron slowed the rate of progression by improving the ALSFRS-R average rate of decline posttreatment compared to pretreatment. The difference on this slide between panel A and panel B are the trial participants included in the analysis. Panel A is all trial participants, and panel B are the subset of rapid progressors. And as it was noted on the previous slide, fast progressors were defined as trial participants with a greater than 2-point decrease in that 3-month lead-in period. So as we look to panel B, we can see there's a more pronounced treatment effect as measured by the change in the rate of ALS decline posttreatment to pretreatment in trial participants whose pretreatment ALS decline was more rapid. Another way of observing the treatment response is to leverage a clinical response criteria. A participant is labeled a responder if they have a 1.5 or greater points per month improvement in their ALSFRS-R slope posttreatment compared to pretreatment. We observe a treatment effect in the left panel, which, again, is reporting all trial participants enrolled in the trial. So we observe a larger treatment effect in all trial participants that were treated with neuron and a larger percentage of participants achieving the clinical response versus placebo at all time periods. In panel B, again, we observe a more pronounced treatment effect in the subgroup of rapid progressors with some points reaching statistical significance compared to placebo. When we look at our biomarker data, we observe a few important things. The cells are delivering their cargo and are secreting increased levels of neurotrophic factors, while changes of pre and posttreatment for placebo-treated participants have changed. You can see this -- the blue in the slide represents pretreatment and green represents posttreatment. If we look at inflammation and inflammatory markers, we also see a significant reduction in these, as illustrated by MCP-1, which is an inflammatory mediator. And again, there's a reduction of MCP-1, in fact, and as you can see on this graph, by 40% in neuron-treated participants, and there's no change in placebo-treated patients. The treatment difference is significant in this analysis. And for both the neurotrophic factors as well as inflammatory markers, I don't have the time to walk you through more data, but we see similar movements in all of the markers that we collected. And I also can't take you through additional biomarker data, but I do want to remind you that -- of the consistency of the read-through in the effect that we've observed in neuron in not only being -- delivering a neuroprotective effect, increased neurotrophic support and immunomodulatory effects in neuron. This really does create a foundation to launch our clinical research of this technology platform -- the cell-based technology platform to many different neurodegenerative diseases. So I'd like to round out my time by taking you through the Phase III trial design and then illustrating the primary end point. So what can you expect from this Phase III trial design? The features are -- there are a lot of features that are very similar to our Phase II trial design. You can see the 12-week run-in period, the length of treatment of 28 weeks, also very similar, and a continued emphasis on biomarker data, of course, along with clinical end points. We are collecting 7 CSF samples in all trial participants across the study. The main differences, which you'll observe -- in this trial, we're choosing to focus on fast progressors as well as the number of treatments that are given across this treatment period has increased. In Phase III, we have 3 treatments that are given 2 months apart. And in Phase II, we only have one treatment. Our primary end point is a responder analysis that is assessing the rate of decline posttreatment compared to pretreatment, similar to the analysis that I've already shown you from Phase II. And for our secondary end points, we have outlined a set of key end points, which have been outlined in our SEP and have the appropriate control of type I error rate. These end points include looking at change in the ALSFRS-R from baseline, the combined analysis of function and survival, which is often called CAFS. We'll analyze additional end points such as slow vital capacity, [ track-free ] survival as well as overall survival in addition to the CSF biomarkers. And of course, safety remains paramount in all of our trials. So I'd like to leave you with an illustration of our primary end point, which I hope helps you understand the importance of this measure and the insights that we can glean from it. This graph illustrates 2 individual trial participants and their ALSFRS-R scores over time. The placebo patient illustrated on this slide is in red and is at the top. And you can see the red triangles highlight the rate of decline, the actual data points pretreatment as well as the line that is fitted. And you can see the rate of decline or the slope pretreatment for this trial participant was negative 1.16, which is slightly over the 1 point per month loss on the ALSFRS-R, which is the median progression rate estimated in the literature across the ALS population. Posttreatment, you can see for this participant is really quite similar to their pretreatment rate of decline. Again, you can see the individual data points, the circles that are on the plot, and the estimate of the rate of decline or slope, which is negative 1.45. Comparing the pretreatment slope and the posttreatment slope, there's a difference of negative 0.29 and -- compared to the criteria is clearly not a responder. The graph at the bottom of the slide and with the blue dots and lines represent a neuron-treated participant. And you can see from the pretreatment period that this participant had a rate of decline or a slope of negative 2.11 pretreatment. The dotted line is very important on this graph because it actually highlights the expected trajectory for this individual from their pretreatment rate of decline have they not actually received treatment. The blue dots highlight the ALSFRS-R scores at each of the time point measured. And then you can see that the posttreatment rate of decline or slope is estimated to be negative 0.21. So we see a stabilization of ALS decline in points per month in this individual with the difference between the posttreatment slope and the pretreatment slope of 1.89. So clearly larger than the 1.25 criteria defined in Phase III as a responder, therefore, making this participant's trajectory a responder -- a clinical response. Then to complete the analysis for the primary end point, the response data is analyzed using a statistical model with important disease covariates, which are well-established in the literature. So I'd like to thank you for your attention, and we look forward to sharing results with you from our trials as they complete in the near future.