Cassava Sciences Responds to Allegations
“As a science company, we champion facts that can be evaluated and verified,” said
Fiction: Biomarker data is generated by
Fact: Cassava Sciences’ plasma p-tau data from Alzheimer’s patients was generated by Quanterix Corp., an independent company, and presented at the recent Alzheimer’s
Fiction: Plasma p-tau for one individual Alzheimer’s patient increased by 235%, which was not shown in the scatterplot.
Fact: This patient’s plasma p-tau increased by 38%, not 235%, as shown in a scatterplot.2
Fiction: Tissue staining showing Abeta42 inside neurons shows treatment effects.
Fact: Yes, Abeta42 is indeed inside neurons prior to plaque formation.
Fiction: The author’s Citizen Petition to FDA dated
Fact: Five days after the Citizen’s Petition,
Fiction: Extensive use of Western blot analysis is foundational to Cassava Sciences’ research and therefore suspicious.
Fact: Western blot analysis is foundational to the biotechnology industry5. Western blotting is a standard lab technique used world-wide to detect a protein of interest.
Fiction: Cassava Sciences’ Western blots data appear overexposed and highly processed, evidence of image manipulation.
Fact: High quality bands are supposed to look sharp6. Smudged bands can be evidence of inexperience, depending on levels of protein in the band.
Fiction: Western blots data are identical, more evidence of image manipulation.
Fact: The Western blots bands shown in the allegation are control bands. Control bands are supposed to be highly similar (since they show equal amounts of protein between lanes). Bands show clear differences when expanded. In addition, image manipulation of control bands makes no sense since these would not change the end data.
Fiction: “Halo” effects in certain bands indicate fraud.
Fact: A “Halo” effects in certain bands is a direct result of very dense dark loading control bands.7
Fiction: Unusual looking bands on Western blots were pieced together from multiple sources.
Fact: Proteins can and do stick to the side of a lane and migrate that way, resulting in ‘candy-wrapper’ appearance or other fictional images.
Fiction: Femtomolar binding affinity is unusual and suspicious.
Fact: Femtomolar binding affinity is a fundamental property of simufilam and may account for its relative potency and safety.
Fiction: Post-mortem brain tissue that is dead for a decade is unreliable.
Fact: Because of the inaccessibility of the human brain and its unavailability for biopsy, translational medicine can rely on post-mortem tissue8. In our case, human brain tissue was collected within 6 hours of death, flash-frozen and stored at -80 Centigrade. This is a standard procedure for pathologists. Such tissue processing is also used in cancer and other fields.
Fiction: Isoelectric focusing gels should not have crisp bands, which is evidence of fraud.
Fact: Quality isoelectric focusing gels often do have crisp bands9.
Fiction: Changes in the Y-maze test for transgenic mice could be interpreted as a decline in cognition.
Fact: A panel of independent, peer-reviewers believe these changes represent an improvement, along with significant improvements in two other behavior tests.
Fiction: High-affinity binding of naloxone for filamin A is suspicious.
Fact: Naloxone binds the same site on filamin A. Of course, it will have high-affinity binding.
Fiction: Isoelectric focusing experiments indicate 100% of filamin A is in altered conformation in Alzheimer’s disease and is largely restored to correct conformation by simufilam.
Cassava Sciences’ mission is to discover and develop innovations for chronic, neurodegenerative conditions. Over the past 10 years,
For More Information Contact:
eschoen@CassavaSciences.com, or (512) 501-2450
2 Please see Figures 5 & 4, “SavaDx, a Novel Plasma Biomarker to Detect Alzheimer’s Disease, Confirms Mechanism of Action of Simufilam”, poster presentation, AAIC
3 Please visit: https://www.fda.gov/regulatory-information/search-fda-guidance-documents/special-protocol-assessment-guidance-industry
4 Please see: “FIVE ACTIONS TO STOP CITIZEN PETITION ABUSE”, Columbia Law Review, https://columbialawreview.org/content/five-actions-to-stop-citizen-petition-abuse-2/
5 Please see: https://www.thermofisher.com/us/en/home/life-science/protein-biology/protein-biology-learning-center/protein-biology-resource-library/pierce-protein-methods/overview-western-blotting.html
6 Please see: “10 Tips for Successful Westerns”, https://www.enzolifesciences.com/science-center/technotes/2015/may/10-tips-for-successful-westerns/
7 Please see, “Western Blot Doctor – Protein Band Appearance Problems” from BioRad. https://www.bio-rad.com/en-us/applications-technologies/western-blot-doctor-153-mdash-protein-band-appearance-problems?ID=MIW4Q8C4S
8 Please see, “Human Postmortem Tissue: What Quality Markers Matter?”, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1995236/
9 Please see: https://en.wikipedia.org/wiki/Isoelectric_focusing
Cautionary Note Regarding Forward-Looking Statements:
Drug development involves a high degree of risk, and historically only a small number of research and development programs result in commercialization of a product. Clinical results from our earlier-stage clinical trials may not be indicative of full results or results from later-stage or larger scale clinical trials and do not ensure regulatory approval. You should not place undue reliance on these statements or any scientific data we present or publish. Such statements are based largely on our current expectations and projections about future events.
Such statements speak only as of the date of this news release and are subject to a number of risks, uncertainties and assumptions, including, but not limited to, those risks relating to the ability to conduct or complete clinical studies on expected timelines, to demonstrate the specificity, safety, efficacy or potential health benefits of our product candidates, the severity and duration of health care precautions given the COVID-19 pandemic, any unanticipated impacts of the pandemic on our business operations, and including those described in the section entitled “Risk Factors” in our Annual Report on Form 10-K for the year ended
For further information regarding these and other risks related to our business, investors should consult our filings with the
Source: Cassava Sciences, Inc.