Cassava Sciences Responds to Allegations

Rhea-AI Summary

Cassava Sciences (Nasdaq: SAVA), a biotech firm focused on Alzheimer's disease, issued a response to recent online claims about its scientific integrity, labeling them as false and misleading. The company asserts that its biomarker data was independently generated and stands firm in the credibility of its research. Key clarifications include the accurate increase of plasma p-tau levels in a patient, the legitimacy of Western blot techniques, and FDA agreement on Phase 3 study protocols for simufilam. Cassava emphasizes the importance of distinguishing fact from fiction to uphold stakeholder trust.

Positive

• Cassava Sciences defends the validity of its scientific data against recent allegations.
• Independent verification of plasma p-tau data enhances credibility.
• Agreement with the FDA on Special Protocol Assessments for Phase 3 studies affirms regulatory alignment.

Negative

• None.

AUSTIN, Texas, Aug. 25, 2021 (GLOBE NEWSWIRE) -- Cassava Sciences, Inc. (Nasdaq: SAVA), a biotechnology company focused on Alzheimer’s disease, today issued a response to claims that were posted on-line yesterday after market hours. Cassava Sciences believes the claims made in this post regarding scientific integrity are false and misleading. The Company stands behind its science, its scientists and its scientific collaborators, and is responding to ensure the facts are known and respected.

“As a science company, we champion facts that can be evaluated and verified,” said Remi Barbier, President & CEO. “This helps people make informed choices. It is important for stakeholders to separate fact from fiction, which is why we wish to address allegations head-on.”   

Fiction: Biomarker data is generated by Cassava Sciences or its science collaborators and therefore are falsified.
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 Association International Conference¹.

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 August 18, 2021, is evidence of wrongdoing.
Fact: Five days after the Citizen’s Petition, Cassava Sciences announced it had reached an agreement with FDA on Special Protocol Assessments (SPA) for its Phase 3 studies of simufilam for the treatment of Alzheimer’s disease. The SPAs underscore alignment with FDA on key scientific, clinical and regulatory requirements of the Company’s Phase 3 program of simufilam in Alzheimer’s disease.³ Furthermore, a Citizen’s Petition allows any party to raise safety/efficacy concerns with drugs the FDA is considering for approval, which is not the case for Cassava Sciences’ simufilam.⁴

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. Cassava Sciences is not aware of an industry-wide ‘expiration date’ on human post-mortem brain tissue that is properly collected, processed and stored.

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.
Fact: Cassava Sciences agrees. This nicely describes the mechanism of action for simufilam.

About Cassava Sciences, Inc.
Cassava Sciences’ mission is to discover and develop innovations for chronic, neurodegenerative conditions. Over the past 10 years, Cassava Sciences has combined state-of-the-art technology with new insights in neurobiology to develop novel solutions for Alzheimer’s disease. For more information, please visit: https://www.CassavaSciences.com.

For More Information Contact:
Eric Schoen, Chief Financial Officer
eschoen@CassavaSciences.com, or (512) 501-2450

^{________________________________
1} Lynn A. Brunelle, Quanterix Corp, is co-author, “SavaDx, a Novel Plasma Biomarker to Detect Alzheimer’s Disease, Confirms Mechanism of Action of Simufilam”, poster presentation, AAIC July 2021
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 July 2021
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 December 31, 2020 and future reports to be filed with the SEC. The foregoing sets forth many, but not all, of the factors that could cause actual results to differ from expectations in any forward-looking statement. In light of these risks, uncertainties and assumptions, the forward-looking statements and events discussed in this news release are inherently uncertain and may not occur, and actual results could differ materially and adversely from those anticipated or implied in the forward-looking statements. Accordingly, you should not rely upon forward-looking statements as predictions of future events. Except as required by law, we disclaim any intention or responsibility for updating or revising any forward-looking statements contained in this news release.

For further information regarding these and other risks related to our business, investors should consult our filings with the SEC, which are available on the SEC's website at www.sec.gov.

FAQ

What is Cassava Sciences' response to allegations regarding its scientific integrity?

Cassava Sciences has labeled the recent allegations as false and misleading, asserting the validity of its scientific data.

What does Cassava Sciences say about the plasma p-tau data?

The company clarified that plasma p-tau data showing an increase was independently generated, correcting misinformation about the extent of this increase.

How does Cassava Sciences support its claims about Western blot analysis?

Cassava states that Western blot analysis is a standard lab technique and defends its usage in their research against claims of manipulation.

What is the significance of the FDA's agreement on Special Protocol Assessments?

The agreement underscores the FDA's alignment with Cassava on key scientific and regulatory requirements for its Phase 3 program of simufilam.