Any statements on hyper growth must be prefaced by answers to the accusations on the petition
Presence of a Whistleblower
This one is obvious – there wasn’t any. The petitioner used the term once and that too in the title of the petition. It was merely a ploy to garner increased attention. They being short on the stock, this smells of manipulation and we hope the SEC investigates them for inducing hysteria.
Dr. Wang’s papers and experiments (western blots, tissue images, experiment concerns)
We don’t know the truth here and don’t want to speculate. As Dr. Bik suggests, the original high resolution images could help alleviate any concerns and if there were errors, Dr. Wang may be able to correct them.
Our concern with the experiments being fudged are low because we were able to find complementary research by a team at Yale as described in this paper. Here they were able to determine that targeting elevated levels of aberrant Filamin A with PTI-125 reduced seizure activity by over 60% in mice when compared to saline. They ran several experiments like treating neonatal mice with a genome type that cause seizures with PTI-125 and also treating mice that were already experiencing seizures for many weeks. Results were extremely positive in all their experiments.
One can also read about research on Filamin A and diseases caused by mutations of the protein
Joe Springer, a Seeking alpha contributor also listed a host of complementary research here. Here in this blog, we are working on an article that will attempt to explain the MoA of the drug. Please subscribe for an update.
After corrections to the poster data, measurements done with the plasma assay showed a significant correlation between Simufilam use and p-tau181 decline. This matches the strong correlation that was also seen in the OLE study between cognition and p-tau181 decline.
The number of patients being < 64 is not a concern as they clearly marked the criteria for p-tau181 evaluation in the posters methods section. We also posted earlier on why the poster data is not relevant to phase 3 studies.
Independence of the CUNY lab
This particular point is prone to the most speculation. Here are some details on the study.
The masking requirements are clearly specified. Those concerned with the rigor of following these guidelines can read documents from the FDA here and here. Also the following excerpt gives more information.
Cassava has also confirmed that they use independent bio-statisticians to analyze the data obtained from primary and secondary outcomes. In the phase 2b study they used axiom real time metrics.
Cassava also released a press statement after the reanalysis of phase2b samples. It can be observed below that the blinding was maintained even though there is some confusion on the difference between outside labs and the academic lab. It would be nice if Cassava clarifies this.
Concluding remarks on the petition
Our view is, the FDA verified all processes were followed correctly before granting SPA for phase 3 trials. We also think the petition will be dismissed in due course because of the obvious conflict of interest of the petitioners and the fact that safety concerns were never even raised (the primary purpose of a citizen petition).
One additional point to note is that in comparison with many other AD trials listed on clinicaltrials.gov, Cassava have been one of the few companies that has been diligent in updating the database with protocol data and results. They have invited the scientific community and investors to scrutinize those results. One must also note that many big bio pharmas tend to use their own affiliated labs and don’t even list them publicly.
Here is CEO Remi Barbier’s statement on the phase 3 trials,
Criticisms of the Open Label trial
Dr. Burns and her team of scientists have persistently reminded us that the OLE trial does not prove Simufilam is effective without confirmatory phase 3 studies and there will be risks. However the smart investor can see some positive signals from these trials. As discussed previously, the impressive cognition results at 9 months is in comparison with a placebo baseline from a meta analysis of over 20,000 patients with mild to moderate AD. Also it has been researched that the placebo effect for AD patients begins to decline after ~6 months. Even if placebo was in effect, showing improvements in cognition for 9 months, where decline is the norm is truly ground breaking. If we see these results repeat for the next 50 patients and at 12 months, one should really start to feel good even without the results of the p3 trials. Cassava have also initiated a double blind Cognition Maintenance Study with randomized placebo control that proceeds to extend the duration of patients getting treated with Simufilam in the OLE trial and we hope to see interim results from that study the first half of next year.
The Hyper-growth story
For a company that is being accused of misconduct and false claims, Cassava sure isn’t playing it slow and milking investor cash. Their cash spend is low, insiders haven’t sold, even bonus targets that were met weren’t awarded. All this to preserve cash for all the expensive trials they are running. They are also working hard and fast with the FDA to run multiple studies to collect as much data as possible for approval.
We fully believe Cassavas growth story can continue and don’t think anything has significantly changed except for the stock price becoming cheaper. We are buyers at these levels. Here are some of our predictions,
- Continued cognition improvements in a majority of the 50 patients in the OLE trial at 12 months with data being released by early October
- Phase3 trials begin recruiting mid september with large interest driven by word of mouth
- A potential partnership deal that may be delayed because of all the bad press
- Announcement of trials for new indications
- Data release from more patients on the current OLE trial.
- Break through therapy designation
Reason for caution
Our chief concern at this point is the extra scrutiny around the company and if there were any concerns from the FDA on how the blinding was maintained during pandemic times. We don’t have access to the end of phase 2 meeting minutes. However if Dr. Wang’s academic lab maintained blinding standards and there were no concerns raised by the FDA in those minutes then the concerns will shift to successful outcomes in the phase 3 trial.
We hope this article will switch you from the fear and uncertainty being propagated by short interests and instead look at the Cassava team in a new light. We hope the Cassava team are more diligent about how they present results and hope they use the extra scrutiny to make less errors while continuing to be transparent
Good luck to all!