Good morning and welcome to the Cassava Sciences conference call. At this time, all attendees are in a listen-only mode. I'd now like to turn the call over to Eric Schoen, Chief Financial Officer of Cassava Sciences. Please go ahead, Eric.
Thank you, Tara. Good morning, everyone, and thank you for joining us today. This morning, Cassava issued a press release regarding the phase III results for the RETHINK ALZ study. Please note that certain information discussed on the call today is forward-looking. Forward-looking statements are based on current expectations and assumptions and require caution. Actual results could differ materially from those stated or implied by these forward-looking statements due to risks and uncertainties associated with the company's business. These forward-looking statements are qualified by the cautionary statements contained in Cassava's press release issued today and the company's SEC filings, including the annual report on Form 10-K for the year ended December 31, 2023, and subsequent filings. This conference call also contains time-sensitive information that is accurate only as of the date of this live broadcast, November 25, 2024.
Cassava undertakes no obligation to revise or update any forward-looking statements to reflect events or circumstances after the date of this conference call. With me on today's call are Cassava's President and CEO, Rick Barry, and Cassava's Chief Medical Officer, Dr. Jim Kupiec. Because the Rethink ALZ data are so new to us, there are still a tremendous amount that we don't know. That is why we are not taking questions after our remarks today. Now, I would like to hand the call over to Rick Barry. Rick.
Thank you, Eric, and good morning, everyone. Earlier today, we released the top-line results from our Phase III Alzheimer's disease study called RETHINK ALZ. As outlined in our press release, the study failed to meet each of its pre-specified co-primary endpoints as well as its secondary endpoints and exploratory plasma biomarker endpoints. When I joined the management team of Cassava, I told our investors, our trial investigators, our patients, and their loved ones that we would be transparent with our communications as we move forward. We said that we would be forthcoming with our data and release it, whether it was good, bad, or indifferent. We are living up to that commitment today, although this is by no means the news we were hoping for. We took careful measures to enroll patients with mild to moderate Alzheimer's.
Despite that, the loss of cognition in the placebo group was less pronounced than was previously reported in other placebo-controlled studies in AD. We're working to understand this better. The results are disappointing for patients and their families who are living with this disease and physicians who've been looking for novel treatment options. A result like this has implications on our second phase III trial, REFOCUS ALZ. We have made the difficult decision to discontinue REFOCUS ALZ given the nature of today's results. Complete 52-week dataset will be available from the study along with a large portion of 76-week data. We intend to report detailed analyses of both studies in the future. We will also be discontinuing the open-label extension study. We have a special gratitude for the patients and their families and caregivers who participated in our clinical program for AD.
We are also immensely grateful to our employees, study investigators, and site coordinators, as well as our other partners for their commitment to this program. I'm now going to ask Dr. Jim Kupiec, our Chief Medical Officer, to share what we have learned from our data. Jim?
Thanks, Rick. Next, I will take you through a few slides related to the study and its results. On this slide, you can see a summary of the study design. It's a very high-level summary of much of the detail that's provided on ClinicalTrials.gov. The study is conducted in two segments, a screening period and a treatment period, and what you see on the slide is, on the left-hand side, some of the key inclusion criteria. This first segment was 60 days in length in which we screened patients to determine whether or not they could be enrolled in the study. In this segment, subjects had to meet the protocol-specified inclusion criteria and not meet the exclusion criteria. This ensured that they had mild to moderate dementia due to Alzheimer's disease.
Once they were enrolled in the study, they were randomized to either simufilam or placebo, as you can see in the second box. There's a one-to-one randomization, so 50% were on the active drug and 50% were on placebo. With regards to endpoints, at the end of the study, our independent biostatisticians analyzed the data based on a pre-specified analytical plan. The co-primary endpoints were the ADAS-Cog12 and the ADCS-ADL. The ADAS-Cog12 is a 12-item cognitive subscale of the Alzheimer's Disease Assessment Scale. The other scale, which looks at activities of daily living, is a functional assessment of patients, and this was created by the Alzheimer's Disease Cooperative Study. The co-primary endpoints were the change in cognition and function from baseline to the end of the double-blind period at week 52. As you can see from the chart, we also had other secondary endpoints and exploratory plasma biomarkers.
On this slide, I've summarized the baseline characteristics of the study participants. Participants had a mean age of about 74 years, and about 55% of subjects were women. When study enrollment was completed, about 60%-62% of subjects had mild dementia defined by a Mini-Mental State Exam, or MMSE, in the range of 21-27, while the rest of the study participants had moderate dementia. The two co-primary endpoints were analyzed using the Intent to Treat population dataset. For the cognitive assessment using the ADAS-Cog12, patients randomized to simufilam showed a 0.39-point reduction in their overall mean score. Although this change is moving in the direction of improvement, it did not reach statistical significance with a P-value of 0.43. For the assessment of functional ability using the ADCS-ADL scale, patients randomized to simufilam showed a 0.51-point increase in their overall mean score.
Again, although this change is moving in the direction of improvement, it did not reach statistical significance with a P-value of 0.40. Not shown here, top-line analysis of the mild and moderate subgroups likewise did not demonstrate statistical significance at week 52 for either the ADAS-Cog12 or the ADLs. This chart summarizes the adverse events. Adverse events were fairly well-balanced and slightly more common in the simufilam group, 71% in simufilam-treated patients, and 68% for patients receiving placebo. This chart shows the most frequent adverse events observed in more than 4% of patients. In general, there is a balance of adverse events between the two groups, except for dizziness, which is noted on this slide, 5.3% versus 0.3%. Therefore, based on all the safety data from the RETHINK ALZ study, we believe that simufilam continues to demonstrate an overall favorable safety profile. Now, I'll hand the call back to Rick.
Rick?
Thank you, Jim. To recap, today we announced that the top-line results from the phase III RETHINK ALZ study of simufilam in mild to moderate AD did not meet the co-primary, secondary, or exploratory biomarker endpoints. Simufilam continued to demonstrate an overall favorable safety profile. We took careful measures to enroll patients with mild to moderate AD. Despite that, the loss of cognition in the placebo group was less pronounced than was previously reported in other placebo-controlled studies in AD. The results are disappointing for our patients and their families who are living with this disease and physicians who have been looking for novel treatment options. Cassava will continue to review all of the data and evaluate next steps. We plan to share the detailed results at a future medical meeting.
We are most thankful, of course, to the patients, their loved ones, and the investigators who participated in this trial and worked so hard with the hope of finding a new treatment for this deadly disease. Also, we are extremely grateful to our employees. Our clinical team has worked for more than three years on this program. Many of the Cassava team members are here because they've personally witnessed the devastation of Alzheimer's in their own families. We remain focused on the interests of Cassava shareholders and are committed to enhancing shareholder value. Cassava is well-capitalized with approximately $149 million in cash and cash equivalents as of the end of third quarter 2024. We hope the information we have gathered can ultimately be used to benefit ongoing research in AD with the aim of making a difference for Alzheimer's patients and their loved ones.
Thank you for joining our call today. Operator, that concludes our prepared remarks.
Thank you, everyone, for joining today. This concludes today's conference call. You may now disconnect.