Cassava Sciences, Inc.SAVANASDAQ
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Operator: Ladies and gentlemen, welcome to Cassava Sciences Report for the Third Quarter 2024. At this time, all participants are in a listen-only mode. A question-and-answer session will follow the formal presentation. As a reminder, this audio webcast is being recorded. During this call and the question-and-answer session afterwards, representatives of Cassava Sciences may make what are known as forward-looking statements. A forward-looking statement is one that is not historical fact. Forward-looking statements are not guarantees, and they involve risks, uncertainties and assumptions. Such statements represent current expectations or beliefs concerning future events or future performance. Forward-looking statements are predictions only based upon information currently available to the company. Actual events or results could differ materially from those made in any forward-looking statement due to a number of factors, risks and uncertainties. Please refer to Cassava Sciences' recent filings with the SEC, including Forms 10-K and 10-Q for a description of the factors that could cause the events or results to differ materially from those made in forward-looking statements. Importantly, this conference call contains time-sensitive information that is accurate only as of the date of the live webcast, November 7, 2024. Except as required by law, the company undertakes no obligation to revise or update any forward-looking statements to reflect events or circumstances after the date of this webcast. It's now my pleasure to turn today's meeting over to Rick Barry, President and Chief Executive Officer. The floor is yours.
Rick Barry: Well, thank you, Noel, for the introduction. Good morning, everyone, and thank you for joining us. With me today is Chris Cook, our Swiss Army Knife and also our General Counsel, as well as Eric Schoen, who I think of as the Chancellor of the Exchequer, also known as our Chief Financial Officer. Dr. Jim Kupiec, our Chief Medical Officer and the star of the August investor call, will not be able to join us today. As you know, we announced the last patient/last visit of our first Phase 3 trial, RETHINK-ALZ, several weeks ago. Database cleanup is ongoing. This is a routine process that takes place at the end of every clinical trial. The purpose is to ensure the accuracy of all information in the database before it is locked and the statistical analysis begins. We expect to announce the top-line results of the trial before the end of this year. This is an exciting time for us. We remain optimistic that we will see promising data that could ultimately lead to a best-in-class treatment for Alzheimer's, but we will all see whether our optimism is warranted or misplaced before too long. There really isn't much more we can say about the trial until our data are unblinded and revealed to us by our biostatisticians at Pentara Corporation. We look forward to sharing our data with you. As a reminder, we expect to report our biomarker data from a subset of patients from the ReTHINK study at the same time as our cognition data. This will involve approximately 100 patients and provide plasma biomarker results for p-tau217, neurofilament Light Chain, otherwise known as NfL, glial fibrillary acidic protein, known as GFAP, and total-tau. I want you to be reassured about a couple of things. Given the scrutiny this company has been under, you can expect that we will measure twice and cut once before we report our results. We will be especially careful to be sure that what we report is accurate to the best of our ability. Also, we will report our data to you whether it is good, bad or ambiguous. Last week, a team of us from Cassava attended the Clinical Trials for Alzheimer's Disease, or CTAD, conference in Madrid. First, I have to tell you how impressed I am by our clinical team, which is headed by Dr. Kupiec. If you aren't aware, Jim is a highly-respected member of the Alzheimer's research community, having led Pfizer's neuroscience group for many years. And he has surrounded himself with a team of professionals who are cut from the same dedicated cloth. Jim and his team have assembled a virtual all-star team of private investigators for our Phase 3 program. I had the privilege to meet many of the principal investigators from our Phase 3 program as well as the people who ran the operation in their sites. Many of the investigators are considered the best in their business. These are the same investigators who were also involved, for example, in the successful trials for Eli Lilly's donanemab and Eisai's lecanemab. The many doctors I met decided to participate in our trials because they made their own assessment of simufilam, and they believe that based on its hypothesized mechanism of action, the drug had a reasonable chance of working. If the trials are successful, they know it would make a difference in the lives of their patients. These doctors live for innovation in Alzheimer's drug discovery and they want to be involved with something that could make a real difference. They know better than anyone that there is no sure thing in Alzheimer's, but they believe the drug needed to be studied. Additionally, I believe they chose to be involved because of the trust they have in Jim and his remarkable team. I am really proud to be associated with this team. And I'm truly grateful to these courageous doctors who have given simufilam the opportunity to demonstrate its potential by participating in our trials when it would have been so much easier to have just said no. We witnessed a lot of very interesting presentations at CTAD last week, but there are a few that I want to focus on. You may recall that in our last call, Jim Kupiec spoke of what he calls the biomarker revolution in Alzheimer's disease. There has been an explosion of innovation in plasma and cerebrospinal fluid biomarkers over the last several years. We now find ourselves at a point where commercially available plasma biomarker tests are demonstrating an extremely high correlation with amyloid-beta positivity in the brain as measured by CSF or PET scans. Neuroscientists believe that the presence of amyloid-beta is one of the key hallmarks of Alzheimer's. Research indicates that a patient with amyloid-beta and clinical symptoms has Alzheimer's or, if asymptomatic, is clearly at a high risk of developing the disease. One CTAD presentation reported data from biomarker assays developed by companies such as Eli Lilly, Fujirebio, and C2N Diagnostics. All three showed positive predictive values, that is the probability that a person has the disease given a positive test result of over 90%. I think you'll agree that sure beats a post-mortem analysis. Why am I bringing this up? Because these types of tools have the power to change the way medicine is practiced, specifically with respect to the Alzheimer's patient journey. You may recall last quarter that I mentioned that Cassava is planning for success. I specifically told you we were significantly expanding our manufacturing capabilities, including ramping up our active pharmaceutical ingredient production. Those activities are being informed by a commercial plan that we've been developing with the help of an experienced industry consultant. I'd like to share with you some of the things that we're thinking about and just beginning to map out. Before I do that, however, you need to understand that I'm not about to give you forecasts. We do not know how the trials will read out, and I'm not trying to hint that we know we're going to be successful. We do not. I'm just describing our vision of the potential opportunity, how we could focus on commercial efforts on that opportunity and what the market could look like. We all know that up until recently, physicians have had very few tools to diagnose and treat people with Alzheimer's. Cholinesterase inhibitors are still widely prescribed even though they are not disease modifying. Some doctors are prescribing the recently approved monoclonal antibody-based drugs from Lilly and Eisai. Although these new drugs have demonstrated disease-modifying capabilities, they have their own well-known limitations. The primary care physician is typically the first to diagnose or suspect Alzheimer's. To date, these doctors have had few options at hand to help their patients. In fact, research tells us that 85% of patients get their initial diagnosis from the PCP, but quite often, diagnosis is delayed until a patient is in the moderate and advanced stages of the disease due to many factors, including diagnostic uncertainty. Some PCPs don't feel adequately trained to determine a definitive diagnosis. Doctors also struggle with time constraints, stigma and fear of causing the patient emotional distress, especially when treatment options are so limited. We envision a world where that PCP does have a treatment option that is superior to cholinesterase inhibitors and doesn't come with the challenges posed by the new monoclonal antibody-based drugs. If that option is twice a day, more oral medication with an excellent safety profile, the PCP would be in a much better position to treat his or her patient. Now, couple that treatment with a readily-available, cost-effective and accurate plasma biomarker diagnostic assay and PCPs can actually diagnose and treat their patients. Reimagine the number of moments we can [preserve] (ph) if we can accelerate the point at which treatment is initiated by preparing PCPs for this revolutionary opportunity. If we can realize our vision, the doctor could have high confidence in making a diagnosis and then prescribe a drug that is convenient, safe and effective. What does the market look like? We know there is approximately 7 million patients currently diagnosed with Alzheimer's disease in the United States, but we also know that the disease is underdiagnosed. We know that half the diagnosed Alzheimer's patients are considered to be mild. Our research tells us that 1.2 million Alzheimer's patients are diagnosed in the US each year, but only about 55% of Alzheimer's patients are treated with a prescription drug approved for the disease. I want you to reimagine Alzheimer's disease treatment possibilities should simufilam's approval become a reality. Simufilam is potentially a first-of-a-kind, disease-modifying, specialty-like treatment that could be prescribed by a PCP. This is the scenario for which we are planning if our Phase 3 trials are successful. Even if simufilam is successful, it may still take more time than we would prefer before physicians become comfortable using biomarkers like p-tau217 to diagnose their patients. We understand that it will take brilliant execution on our part even if simufilam shows the kind of results we would all like to see. We are up for the challenge. And if the past few months have proven anything about us, it is that this team doesn't shy away from challenging situations. We lean in and we work our way through them. Our North Star is to be on the front lines of transforming the way this disease is diagnosed and treated so that the patients can experience the moments they deserve with their loved ones. Well, thank you for indulging the vision that motivates all of us at Cassava. I'd now like to turn the call over to Eric Schoen, who will provide you with the financial update. Eric?
Eric Schoen: Thanks, Rick. Let's start with our cash and cash equivalents. We ended the September quarter with $149 million in cash. That balance is expected to be sufficient for operations through the conclusion of both ongoing Phase 3 trials and into calendar 2026. Separate from the $149 million of cash is $40 million of restricted cash that is a new and temporary line on our balance sheet. That bucket is being held in an escrow account for the sole purpose of satisfying the monetary penalty as part of our settlement with the Securities and Exchange Commission that we announced in September. That settlement is still subject to approval by the US District Court after which the escrow account will be released to the SEC. We don't anticipate any issues with court approval. On the spending side of the equation, net cash used in operations during the nine months ended September 30 was $55.7 million, or roughly $18.5 million each quarter. Net cash used in operations for the second half of 2024 is expected to be between $80 million and $90 million. This is consistent with our previous guidance. That estimate includes the $40 million settlement I just referenced. Considering this spending level, we believe we will end the year with between $117 million to $127 million in cash. That is the same amount as guided to in our last quarterly call; no change. Now, on to our profit and loss for the quarter. Our net loss was $27.9 million, or $0.58 per share, in Q3 compared to a net loss of $25.7 million, or $0.61 per share, for the same period in 2023. Research and development expenses for Q3 were $17.7 million. This compared to $23.6 million for the same period last year. R&D expenses are naturally decreasing as more and more patients complete the Phase 3 studies and rollover into the lower-cost open-label study. General and administrative expense for Q3 were $12.9 million compared to $4.3 million for the same quarter last year. The significant increase was due primarily to higher legal-related expenses, which were partially offset by insurance recoveries, increased compensation costs, including severance costs, as well as an increase in stock-based compensation expense due to new awards granted in late 2023 and 2024. Now, I'll turn it back to Rick.
Rick Barry: Thank you, Eric. Okay, operator, could you please open the line for questions?
Operator: Thank you. At this time, we'll be conducting a question-and-answer session. [Operator Instructions] Our first question comes from Vernon Bernardino from H.C. Wainwright. Please go ahead.
Vernon Bernardino: Hi, good morning, and thanks for taking my question. Congratulations on the progress. Looking forward to those top-line results. The only question I really had is something that has been developed and I was just wondering if I could get an update on status. And that is the status of SavaDx. One thing that would be important for simufilam's success would be the biomarker diagnostic results as you mentioned. Obviously, p-tau is something that can be used for a biomarker. But I was wondering if you could give us an update on SavaDx.
Rick Barry: Sure. Thanks, Vernon.
Vernon Bernardino: Hi, Rick.
Rick Barry: In a world where the diagnostic tools are becoming so good, particularly as p-tau217, we wonder where SavaDx is going to fit into that. That doesn't mean we're not going to pursue it. We will, but we're a small company with limited resources and there are other ways that we could spend our money such as looking at additional indications for simufilam. And so, there's a lot to think about once we have results, how do we want to allocate our capital? Do we want to put it into a diagnostic that may be an improvement over some of the diagnostics that are out there? Or do we want to pursue other indications? That's the best answer I can give you.
Vernon Bernardino: Perfect. And as a follow-up, I was just wondering, again, what kind of detail will you be providing in the top-line results before year-end as far as biomarkers are concerned?
Rick Barry: So, on the biomarkers, we will be measuring p-tau217, NfL, GFAP, total-tau, and I think that's it. So, just remember, I talked about this, in the second trial, we have a lot more. There's more patients, there's some CSF analysis and there's also imaging analysis.
Vernon Bernardino: And can you remind us the time points at which these in the Phase 3 are being measured?
Rick Barry: From baseline to last visit.
Vernon Bernardino: Baseline and last visit only?
Rick Barry: I believe so. I mean, I could get back to you. There might have been an interim analysis -- not analysis, there might have been an interim draw, but I have it in my head that it was the baseline and finish.
Vernon Bernardino: Great. Thanks for taking my question. Looking forward to the results, as I mentioned.
Rick Barry: Okay. We are too. Thanks.
Operator: Thank you. Next question comes from Elemer Piros from Rodman. Please go ahead.
Elemer Piros: Yes. Good morning. What I'd like to verify, Rick, is that the statistical analysis plan has been locked down with the FDA. And maybe a part of that question is, you're talking about the ADAS-Cog and the ADL as co-primary endpoints. Would both of those or either of those would have to hit for success? And obviously, there is a different statistical treatment of either of those or both of those scenarios. If you could elaborate, please?
Rick Barry: Sure. Thanks, Elemer, and thanks for the question. There's been this, I don't know, misunderstanding about the SAP. And just to make it clear, so we submitted a statistical analysis plan to the FDA and you submit this to get their comments. And they gave us some comments, which are relatively minor. Now, we would be not very clever if we didn't take their comments into account and incorporate them in our plan. But we took their comments, we went back to Pentara, and put their comments in, had Pentara make some changes. And then, the important thing is that you have to sign the SAP before you lock your database. And we've done that. As far as the endpoints of the trial, we have two primary endpoints, as you know. It's ADAS-Cog12 and its activities of daily living. And our SPA with FDA says we have to hit on both in order to call the trial successful. And there'll be -- there are secondary endpoints, et cetera, but they matter a lot less than hitting the primaries.
Elemer Piros: And Rick, the integrated endpoint of [indiscernible], is that out of the picture or is that relegated to as a secondary endpoint?
Rick Barry: Yeah, good question. It's a secondary endpoint.
Elemer Piros: Okay. Now, is there a preset analysis of mild patients only? And if you have to go to that sort of analysis, how does the statistics work there?
Rick Barry: There is. We are expecting to have an analysis of mild patients as well as moderate, and then the combined. So, I think, as you know, 70% of the -- roughly 70% of the patients were mild in this trial, the rest were moderates.
Elemer Piros: Okay. And just one clarification of the phospho-tau measurement. I think the enrollment criteria was using phospho-tau181. And you mentioned that you'll provide analysis of phospho-tau217 as how it may change due to treatment. If you could help us understand whether I'm correct in assuming that? And what's the significance of one versus the other? Has the field evolved into looking at phospho-tau217 as more prominent biomarker?
Rick Barry: Yeah, you got it, Elemer. It's when we started the trial, I think the scientific community with respect to Alzheimer's lean towards the p-tau181 as a better biomarker, but here we are three-plus years later, and I can tell you being at the conference last week, yeah, people still talk a bit about 181. It's a pretty good tool, but 217 is what everybody in Alzheimer's is focused on right now. So, I don't know, I think we're measuring 181 at the end of the trial as well. So -- but it's not -- I don't think it's going to be that important of a biomarker.
Elemer Piros: And maybe one last question. As you look through or work through the data cleanup, roughly what proportion of the total data you have been able to clean and set up for the analysis plan at this stage?
Rick Barry: And I can't blame you for answering -- for asking the question. It's a great one. We don't want to go there.
Elemer Piros: So, it's still by year-end?
Rick Barry: By year-end, definitely.
Elemer Piros: Okay. Looking forward to it. Thank you very much, Rick.
Rick Barry: Thank you. Thanks for the questions.
Operator: Thanks. Our next question comes from [Matthew Nachtrab] (ph). Please go ahead.
Unidentified Analyst: Thanks for bringing me on the call. So, the vision that you're laying out around the primary care physician is very exciting. I think like all investors and humans are excited about that vision. What I wanted to talk about is, as I've studied the Phase 2 and placebo results of hundreds of AD studies, I believe that hopefully we'll repeat that in Phase 3 and show significant improvement for ADAS-Cog12, but I'm also considering a scenario of Phase 3 results showing that mild significantly improved, but an underperformance of moderate and potentially resulting in the population missing statistical significance. I have two questions kind of related to that. First is, how are you thinking the company would navigate a subset of patients performing great with the FDA and taking the drug to market, if it's the mild-only that are significant? And then, the second question I have is, many families are reaching out to me asking when they'll get access to the drug in the US and around the world. And if the drug does perform, what are your -- what's your upper-level thoughts on when you think the drug could hit the market in the US and around the world?
Rick Barry: Very good questions, Matt. So, with respect to the potential results, and we're all speculating, but -- well, I guess, the overarching thing is we don't want to rely on subgroup analysis. However, if we showed statistical significance in mild patients and for some reason we miss our primary endpoints because of the moderates, we would have an interesting choice to make with respect to our ReFOCUS trial, because we would have the capability to go back to -- we'd have the capability to revise our statistical analysis plan and resubmit to FDA to make the second trial, put more of the alpha on the milds. That would be a really big decision to do it. So, with respect to subgroups, I've spoken to a few investors about this, what we won't do is we're not going to pick out some niche group that seem to perform really well based on the drug and then try to convince investors that we're going to take that one over the goal line. That's just not a winning argument. But if you do have 70% of your trial with statistical significance and showing great results in milds, but it's the moderates that have killed your primary endpoint, that's a different story, and we'd have to go and talk to the agency about that. So, I wouldn't think that, that situation is hopeless, but it's all going to depend on the data and how the agency responds to it. The second question about when will it be available, really a good one. We're kind of thinking, in all likelihood, it would be late summer, early fall would be an optimistic -- I'm sorry, late summer, early fall of 2026, not next year. Eric, just -- the heart attack that he was just about to have is becoming...
Eric Schoen: Let's do it.
Rick Barry: But there's a lot that depends on that. And -- but I think that's a realistic target to get to market. You could make some really aggressive assumptions that I don't think I would necessarily make to get maybe a few months off that, but that's probably the right ballpark.
Unidentified Analyst: I'd like another question, if you don't mind. Can you elaborate a little bit on what other indications you guys think there is the most potential impact from simulfilam and how you might prioritize which indications you would pursue after you get past this Phase 3 for Alzheimer's?
Rick Barry: Well, I don't want to go into too much detail. I mean, there's a lot of theoreticals where we have some scientific work that was done in the past, but we got to think about how we're going to allocate the resources and the probability of success. There is one indication that I think most people who know the company pretty well are aware of and that is there was a study done by a professor at Yale which was really a pretty fascinating study where she took our drug and built an animal model based upon Tuberous Sclerosis, the childhood epilepsy part of it. And she's absolutely convinced that the drug would work in that indication. That would be an indication that would not require enormous trials, huge resources. You get an answer pretty quickly. I don't want to say that we're doing that, but that would be kind of a logical place for us to go next. We have some things that we got to work out, but we're working on them.
Unidentified Analyst: I know the resources are strapped, but is this something that you guys are able to do some initial groundwork on now or in the recent past, like on these different indications? Just kind of get the process started?
Rick Barry: Well, we can with the one I was just talking about. The other is no. It's more theoretical.
Unidentified Analyst: Okay. Thank you very much.
Rick Barry: Okay. Thank you, Matt.
Operator: Thank you. This was the last question. I will now turn back to Rick Barry for closing remarks. Please go ahead.
Rick Barry: Thanks. Well, we really appreciate you joining the call today. We do, to repeat, expect to announce our top-line Phase 3 results before the end of 2024 and we really look forward to sharing them when they're available. Thanks so much for listening.
Operator: This does now conclude today's conference. You may now disconnect your lines at this time. Thank you for participation. Goodbye.