AD3 𝕏

The Consistency of the Positive Data from $sava Points to Phase 3 Success All this remarkable trial data reported here was reviewed by the DOJ and SEC and not flagged with any issues Phase 3 data coming ~December 15. TLDR: What are the CLINICAL results showing us? How are the patients doing on the drug? What are the people closest to the results saying? What sticks out to me is a quote from Remi Barbier “It's the consistency of data from the basic research to the animal data, to the CSF biomarkers, to the early cognition, to the open-label study. There's a consistent theme that, in my opinion, the world of Alzheimer's disease R&D has never seen before.” Every import data point I have reviewed points to the drug working. All of these show consistency of data aligning to make phase III very very likely to be positive (details below): 1. 5 - Phase 2 and Phase 3 trial site investigators speak of patients doing better on the drug 2. 8 Patients Stories of Dramatic #Alzheimers symptom reversals or stabilization with mild to severe disease states. Dropouts within historical norms despite nasty short seller attack and press. hmm? 3. Cassava Team and Board consistently VERY excited about the prospects of the drug. Talented professionals stuck through all of the investigations and short seller attacks 4. Suzanne Hendrix, a very experienced Alzheimer's biostatistician, spoke of open label cognition FAR outside historical placebo. 5. NONE OF THIS DATA WAS CALLED INTO QUESTION BY THE SEC OR DOJ. ALL OF THIS FALLS OUTSIDE OF THEIR CLAIMS. WE KNOW THEY REVIEWED EVERYTHING, SO IT ADDS MUCH MORE CREDENCE TO THE ACCURACY OF THE REPORTING OF THEIR OPEN LABEL STUDY RESULTS 1. Clinical Trial Sites Positive about the Drug - The team has extensive conversations with the clinical trial site investigators. James Kupiec, Chief Medical Officer, said "We have expanded the open-label trials in direct response to requests from our clinical research sites". I think he is hearing this from the sites, but he doesn't tell us. They cannot ask trial sites how the patients are doing, but the trial sites can tell them. When patients we know call their trial sites, this is what they say about their experience: “You should have heard the excitement in her voice! She said it is going to be so nice to finally have a safe option that helps people improve versus the MABS that don't really work and cause brain bleeds. “ The open label patient families I have spoken to talked directly to the trial sites as they were in the trial. The clinical trial sites are overwhelmingly positive about the drug. They are all very experienced with #alzheimers trials and some of them experienced tragic deaths caused by the MABs at their trial sites. Two phase 2 trial site investigators spoke out about the drug. Dr Gonzalex-Rojas ran Phase 1 & Phase 2 clinical trials for Simufilam for Cassava Sciences as an ACRP certified Principal Investigator. She treats hundreds of Alzheimer’s patients annually and ran 13 different Alzheimer’s drug trials. "After month two and 3, several of the patients that we have on the open labels, the husband, the wife of the son, the daughter, they're telling me that some patients are improving. For example, one of the patients that didn't remember much the names and the past important person or phone numbers and now he's showing better it's recall in these these activities. I have another patient of Cassava also that told me that the patient was get confused it took a shower or not and sometimes used to have like a wet underwear in the in the shower to make sure that she didn't take a shower again that day and the wife is telling me that this is not happening anymore that he kind of is able to tell that they if a patient took a shower or not" Here is her recording on YouTube from a Cassava Conference call youtube.com/watch?v=YmTS7_z9… Dr. Boris Nikolv - Research Physician and CEO of IMIC I have spoken to Boris a number of times. The short attack had a dramatic impact on their business, BUT the emerged very very successful and are doing great now. The FDA audited their site due to the short seller attack and passed with no actions required. When asked about patients on the study he said: “We see a lot of patients through these studies. We have seen improvements in many of the patients. Including descriptions of the patient by the caregiver. For example a patient caregiver that came to us the other week and told us that the patient started cooking again she used to burn every time that she cooked on the stove and now she can cook again small simple meals but she was not able to do that before and there is a lot of cases like that… a lot.” Here is his interview on YouTube youtube.com/live/a6ejKofWui0… Reread my tweets about the clinical sites for more: nitter.gq/MattNachtrab/status/18… The Patients I have spoken to or emailed all of these patient families except 8. Their stories bring in obvious evidence that they were or are in the studies. Patient 1 Refocus ~Nov 2022 - May 2024 : 16 MMSE to 20 MMSE Patient 2 Refocus ~Nov 2022 - May 2024 : 17 MMSE to 24 MMSE Patient 3 Rethink ~Aug 2022 - Aug 2023: 27 MMSE to 24 MMSE Rethink OLE ~Aug 2023- April 2023: 24 MMSE to 27 MMSE Patient 4 Rethink ~May 2022 - May 2023: Unknown Rethink OLE ~May 2023 - May 2024 Showed improved cognitive behavior and less anger and anxiety Patient 5 Phase 2 OLE Aug 2020 - Aug 2022 Falling down (moderate MMSE 16-18) to stable. Unable to read lab results (he is/was a very successful Dr.) to giving detailed diet recommendations. Small drop in observed behaviors during withdrawal study Phase 2 OLE - extended again Aug 2022 - July 2024 Still not falling. Playing poker with friends This is the patient family we are doing a documentary on Patient 6 Phase 2 OLE Aug 2020 - Aug 2022 Stayed at home. Lost personality. Very agitated. Moderate AD ~16 to ~24. Got social out with friends. Regained personality Phase 2 OLE - extended again Aug 2022 - July 2024 Still going strong. No changes Patient 7 14 MMSE still stable after 10 months on treatment in REFOCUS OLE - Historical placebo would decline 2.5 MMSE or 5 ADAS-cog11 over similar timeframe She was in $sava simufilam Phase 3 Refocus - Diagnosed 2016 with Alzheimer's Blinded Refocus 18 Months July 2022 - Jan 2024 : 17-18 MMSE at start declined to 14 Refocus 12 Month OLE Jan 2024 - July 2024: On the medicine for 6 months maintained at 14 after dropping 1.3 MMSE points every six months while blinded . Husband believes she was on placebo, but stabilized. He believes there is a treatment effect on the open label. UPDATE Oct 2024 "She is doing well. She is still showing no signs of agitation and I believe is stable. We are at the clinic next Tuesday. Thanks for asking, generally very optimistic…." For reverence a 14 MMSE normally would decline about 5 ADAS-cog11 or 2.5 MMSE points over this period. Untreated over a 10 month period you would see disease progression on key AD symptoms. These estimates are from the ITO study of placebo populations. This patient is the first I have seen evidence of stabilization of a low Moderate AD (I called her severe last update but a 14 is not severe, but it is below the entry criteria for the drug) patient from simufilam. It aligns with my theory that some of the Phase 2 readout volatility was the later Phase 2 trial sites screened poorly and allowed patients with co-pathologies. Hence, the milds are more representative of treatment effects from simufilam because they are much less likely to have co-pathologies. Particularly the 87 that made it all the way through the 24 mark on the OLE. Patient 8 I do not have much detailed information on, but from a credible source they said there is another remarkable patient story from a clinical trial site. I am not 100% sure that this patient does not overlap with the other 7 or from a site that is different from the other 5. I have found that stories I hear through the grapevine have overlap. The first 7, I directly interacted with their families and know their real identity. I have had no patients that reached out to me saying the drug is dangerous or that they are not doing well. The drug clearly did not work on some patients based on the clinical data... just haven't heard from anyone in that state. AAIC Individual Patient Scatter Plot 2021 August A chart of the 50 patients at 9 months from AAIC in August of 2021 sheds light that the story of the patients above align with the broader patients in the open label. The patient stories that I have heard seem to point to some moderate patients are the super responders. This chart aligns with that theory as it would be very surprising to see a mild improvement to a perfect score. It is more likely that moderates are the ones that improved 7-14 points on ADAS-Cog11 at 9 months. The average ADAS-Cog11 baseline score for mild's was 15 and the moderates were 25.7. Again, this was reviewed by the SEC and not mentioned by their reports. To me, this validates a full detailed review of this data by the SEC showed it was reported accurately. AAIC 2021 slide deck - acrobat.adobe.com/id/urn:aai… The Team 1. Rick Barry said "suffice to say, we are believers" in the drug. 2. Remi Barbier "It's the consistency of data from the basic research to the animal data, to the CSF biomarkers, to the early cognition, to the open-label study. There's a consistent theme that, in my opinion, the world of Alzheimer's disease R&D has never seen before. " Being Patient Interview with Remi youtu.be/z8ipamyLuuQ?si=lrnU… 3. Suzanne Hendrix - She is one of the foremost experts in Alzheimer’s disease endpoint analysis. She has EXTENSIVE experience and knowledge of what is normal for placebo’s in AD. She analyzed the open label results against other AD Placebo’s with patients with similar baseline demographics with Mild-to-Moderate. She said "The treatment effect with simufilam from the open label study so essentially what this is showing is that the pattern of decline that was seen in the mild to moderate treatment arm was a lot less decline than you would normally see with a placebo group of similar populations so whichever placebo group you used there was quite a bit more decline than was seen in that active arm in the open label” This is the chart that she is referring to: Then they analyzed just the mild patients. Alzheimer’s studies now are mostly done on early to mild patients. This patient group is where simufilam really clearly separates from the studies with similar baseline characteristics. She said “The active simufilam group [confidence interval] barely overlaps with the mildest of the placebo arms from those mild and early AD studies” Note, the one it overlapped with was EARLY AD, so there was no overlap with the mild studies of about 15,000 mild placebo patients She goes on to say “Patients with mild AD, simufilam stabled ADAS-Cog11 scores scores over 18 months and based on the comparison to the historic data you can tell that that's pretty unusual to have that much stabilization over that long of a time period” Finally, here is her analyzing the 18 month data with mild patients. She says: “Again, the decline that we’re saying is substantially less than you would normally expect based on comparison to these historical control arms.” This 18 month data is incredibly powerful because the longer you go, the placebo research says, it is more likely that the data is showing separation from the typical placebo. And as you can see, for the mild patients, the 18 month data further separates from the historical placebo’s. These studies are EARLY AD compared to mild. Early AD declines slower than Mild AD. Here is her full YouTube video from CTAD 2023 is here: youtube.com/watch?v=q1Z6NeqP… Here is her presentation: acrobat.adobe.com/id/urn:aai… Finally, the 24 month readout, No Decline in Cognition Scores in Patients with Mild Alzheimer's Disease Who Received Simufilam Continuously For 24 Months. This is even further outside historical norms. This was 87 patients for two years. The open label study was performed in the US at 17 different US sites that are experienced with ADAS-Cog evaluations and Alzheimer’s studies. The screening procedure was similar to other AD screening that these sites were used to performing. PR covering the 24 month results: cassavasciences.com/news-rel… Clinical Trials link for the study: clinicaltrials.gov/study/NCT… (@MartinShkreli, These comments from Suzanne were relevant to the comments you made about placebo’s. There are two purposes to placebo’s… 1) To make it so the patient does not know whether treatment is administered, so they are less likely to “invent” symptom remediation. In AD this stops showing in 1 year. See research below. 2) To align patient populations to similar baseline characteristics. In AD, historically placebo performance has wildly varied and given false hope to early trials. Great performing placebos have also caused drugs with promise to fail. It is actually more statistically reliable to compare an AD trial to a large number of AD placebos than to run one yourself. It does require you to do enough patients for at least 12 months to compare to other studies. Here are two references to historical placebo analysis that I use to understand typical placebo performance: ITO - 2013 Placebo Study - acrobat.adobe.com/id/urn:aai… Here are two articles from data analyzed by Lon Schneider alzforum.org/news/conference… alzforum.org/news/conference… I unblocked you because of the short sellers you seem to come with some good faith to the discussion. Lots of off the wall comments with no evidence, but some recognition of some facts or low likelihood events like trial pauses. FYI, patients I talked to are hyper aware of all the bad press Cassava gets and are frustrated and fearful the drug will be taken from them. They say the SEC, DOJ and press are violently mischaracterizing the situation and they are benefiting from the drug. Adam and the others are not protecting patients. They are harming them. -Matt )