I thought I'd put together all the broad reports back from the AGM in one post. As can be seen it does seem some things like RETT slipped away, perhaps the focus being on AD/PD/Schizo rest of year? Also Schizo not moving as fast as indicated at AGM. However other aspects such as Sabbagh becoming more prominent clearly did turn out correct.
1st perspective - (stjernerogvann on stocktwits) - "notes from today's ASM:
1. Paper due before MAA
2. MAA should come before end of SEP but could slide to YE
3. Cohort 1 referred to low dose Part A group in 3-71 schizophrenia trial - high dose cohort also accrued and dosed now. Part B coming up. Possible completion by YE.
4. PD and Rett trial should start this year.
5. Autophagy is key component of MOA (Sigmar1 promotes autophagy, the recycling of underperforming or unhealthy cells)
6. They have not met with FDA since end of P2/p3 - plan to do so when they have OLE data/analysis and can show the same data that MAA has seen
adding more color:
1. CM said we should assume by YE for MAA filing...but CM also suggested that was a CYA date. FWIW, 07SEP2024 should be around the date of filing if we follow the regulatory timeline breadcrumbs.
2. CM said the paper that will be released will make us happy. Great data across the board (endpoints, biomarkers, MRI) and we will be happy with the dose dependency, too.
3. OLE info will be a key component to the filings.
4. There is a Rett conference this week and something should be announced there (probably regarding new trial.)
5. The new Rett trial will be 2x as large as the last trial, will have a larger % of placebo patients, and the inclusion/exclusion criteria will be slightly modified based on lessons-learned.
- When MAA is filed then maybe we get a slight PPS increase but I don't think we will see real appreciate (to 15+) until late next year.
- CM said execution is the key to share price increase. In the meeting, at least one share holder complained about share price and this was CM's answer. He is right: only material developments will move the PPS substantially and there are only 2 material developments on the horizon over the next 18 months that could manifest - 1) EMA approval, and 2) Schizophrenia trial results."
2nd perspective - (William Munny):
"1. As to the peer reviewed paper, he did say it would very likely be published before the MAA is submitted (although he did take care to say that they were completely independent events.)
2. My understanding of what he said (and it was slipped in quickly) was that the MAA wouldn't be submitted before September. This is no surprise given what I have been saying about the submission request for rapporteur assignment. It was apparently made before the February 7th submission deadline, and at that point the EMA was therefore being told that it was projected to be filed between late August and early September. They have had the opportunity to amend the filing date since then. What he did specifically say in the presentation is what he has said publicly before, "It will definitely be filed this year."
3. As to Schizophrenia, yes, he did say they were beyond the first cohort and I also understood that the second cohort was being dosed now. That does mean that Part B should be coming up fairly soon after that data is analyzed. In answer to my question Missling said that it was quite possible that the study could be finished before the end of the year.
4. In answer to another trial question he did reiterate what he said on the last call - i.e., that the PD trial would start this year. As to Rett, he suggested that we would hear more about their plans at the Rett conference where they are presenting (this week?).
5. He did make some more remarks on autophagy as a key component of the MOA. (Personally, I believe as the story of our drug comes out, this autophagy angle will provide a good bit of extra sizzle.)
6. Yes, he did say that they have had no formal meetings with the FDA since the end of the AD trial (although it wouldn't surprise me if there had been some back channel communications). As he has said before, he plans to go to them when he has the OLE data/analysis and after he has filed the MAA. He did also say that the doesn't believe there is a need to wait on filing before the new FDA guidance on AD is fully approved and in the Federal Register. He showed a fair bit of confidence by saying that under the new guidance "the study should be fully approvable."
BTW, in regard to the full data set (in the peer reviewed paper, I presume), Missling said that we would be pleased to see the data "broken out by every arm of the study...all measures." He also threw out - in an apparent jab at Annovis (and others) - that the study participants were "all confirmed Alzheimer's patients."
3rd perspective: Hi, I got permission from a friends take to release his notes. Cheers:
"They are calling themselves a regulatory stage CNS company.
Patients are peeling off of Trofinetide, and patients on Blarcamesine, through compassionate care schemes, are continuing on the drug. FDA gave them feedback on RETT to run another phase 3 trial because it would be unfair to Acadia (Trofinetide) who had a drug approved on a successful phase 3 trial if drug was approved despite missing statistical significance on endpoints. They are at a RETT conference concurrent with the ASM, to present a new trial (12 week), in which they will enroll 2x patients (~150) on a 1:1 ratio.
Saw a picture of the pill. It’s a clear capsule with branding on the coating.
They have not met with fda on Alzheimer’s because of the missed ADL, but now with the new draft guidance and bio-markers, and black box warning and failure of MAB uptake, feel much more confident to talk with them. When asked if European approval would be first and FDA second, he answered not necessarily because though they started with EMA, FDA is much quicker.
When asked about long-term efficacy, he said they have good data and RWE of AD patients on drug for 146 weeks. They have not seen any of the ATTENTION data on the OLE. When asked if FDA will accept aBeta as a biomarker using blood plasma, he said many companies have now adopted this method. On brain atrophy data, he used the following language (attenuated, stopped, delayed). He did not give any ground on timeline for EMA submission or peer review, but held to by ‘end of year’ though he conceded this was playing it safe, which I interpret as meaning it may happen earlier. We saw some new slides, one in which they do a much better job illustrating their drug vs the MAB’s, comparing their downstream approach to the upstream approach of activating the sigma-1 receptor, emphasizing Autophagy. In my opinion, focusing on Autophagy, is smart because it gets lots of headlines in health news as it relates to intermittent fasting and other trending health fads regarding cell health.
They have completed part A of Schizophrenia trial which was a dosing study and have now started part B. When asked about delays with PD/PDD, he answered strongly that major advances were being made in PD biomarkers, and testing doesn’t just come off the shelf at ‘Amazon’ as he put it, they are being developed, and thus they are waiting because they feel they can run a more effective trial with them. He used the 2b/3 AD trial as an example, suggesting at the time they initiated that trial, the biomarkers they were testing for were not at all common then, but are now common in most AD trials. His comments seem to be pointing toward the new alpha-synuclein biomarker discovered by the Michael J Fox foundation last year.
In a question asked about partnering versus buyout, he first responded by saying that a buyout is an extreme form of partnership and at the other end of the spectrum was doing everything themselves. He indicated he was open to all options, with the criteria that it would be whatever was in the best long term interest of shareholders."
4th perspective comment -
"Regarding MMA filing Missling specifically stated that the 2-73 manufacturing has been solidified with a leading contractor that meets rigorous standards. He did say that this was a key component of the filing. He left the door open as to distribution via a partnership that would be most meaningful for share holders. He was very optimistic about 3-71 schizo trial. He was very confident that it's efficacy was superior to Karuna, which was recently acquired by BMY...Retts...acknowledged short comings of recent trial and went on to mention that feedback indicated people were waning with the ACAD therapy, which is the only thing available. He acknowledged that there was a prior communication issue and went on to say there would be better timely updates as to trial status. Other positive mention was that their lead SAB, Dr Marwan, who is world renown expert, would be more visible at future presentations. During a sidebar convo Miss told a few of us that AVXL has initiated a rigorous Educational Webinar campaign to Neuro groups to better get the word out. I got the impression that he realizes nobody really knows about AVXL and they need to be more proactive
On peer review...He specifically stated that it would appear in one of six major ALZ publications, indicating it had teeth. My impression was that he expected very soon, although vague."
stjernerogvann commenting on this - "I don't know if he said "one of six"...one of the iHub guys there was opining to CM that it had to be one of the super high impact journal (like JAMA) and CM was nonplussed. He basically just said he doesn't know/can't say which one but it will be an Alzheimers/Neurology-focused journal. FWIW, I didn't get the impression it would be this month or next because CM seemed to think no decisions had been made yet by editors and that editors should be expected to continue to move slowly."
AI
