Cassava Sciences

Cassava Sciences

Company type	Public
Industry	Pharmaceutical
Predecessor	Pain Therapeutics, Inc.
Founded	May 1998 (1998-05)
Founder	Remi Barbier
Headquarters	Austin , United States
Key people	Richard J. (Rick) Barry (CEO), Claude Nicaise (Board Chairman)
Products	Simufilam (development halted), Oxytrex, Remoxy, PTI-901
Number of employees	25 (2021)

Cassava Sciences is a pharmaceutical firm based in Austin, Texas, United States. It developed simufilam (previously known as PTI-125), an oral medication candidate aimed at treating Alzheimer's disease. However, development was halted in November 2024 after phase III clinical trials failed to show therapeutic efficacy.

In June 2024, the United States Department of Justice charged Cassava advisor Hoau-Yan Wang with research fraud associated with simufilam. Within weeks, Remi Barbier, the company's founder, president, CEO, and chairman, stepped down along with Lindsay Burns, senior vice president for neuroscience and Wang’s co-author and spouse. Subsequently, in September 2024, the U.S. Securities and Exchange Commission (SEC) filed fraud allegations against Cassava Sciences, Barbier, Burns, and Wang. They consented to a settlement—without admitting fault—awaiting judicial approval that would impose fines of $40 million on Cassava, $175,000 on Barbier, $85,000 on Burns, and $50,000 on Wang.

Established in 1998 by Remi Barbier under the name Pain Therapeutics, Inc., the company adopted the Cassava Sciences name in 2019. Its early portfolio centered on pain management drugs such as Oxytrex and Remoxy, as well as PTI-901 for irritable bowel syndrome. Between 2013 and 2021, the company had no approved medications or revenue streams. Despite a workforce of only 25 employees, its stock was among the market's best performers in 2021 before declining amid doubts regarding simufilam’s research integrity.

Origins

Entrepreneur Remi Barbier founded the company in May 1998 as Pain Therapeutics, focusing on opioid-based treatments for chronic pain. Inspired by Stanley M. Crain’s research at the Albert Einstein College of Medicine around 1993, Barbier initiated the company in South San Francisco, California, backed by initial capital of $1 million.

Rebranding

Following four FDA rejections of its experimental pain medication Remoxy, the company shifted its strategic focus toward Alzheimer's therapies and diagnostics in August 2018. The rebranding to Cassava Sciences occurred in 2019.

Management

Remi Barbier held the roles of president, CEO, and chairman until his unexpected departure in July 2024. Richard J. (Rick) Barry was appointed executive chairman and subsequently CEO by September 2024; Claude Nicaise took over as board chairman. Barbier continued in a non-executive capacity until mid-September 2024.

Lindsay Burns resigned in 2024 after co-researcher Hoau-Yan Wang faced fraud charges; she was succeeded by Angélique Bordey in May 2025. Wang—a professor at CUNY and former advisory board member—was indicted in June 2024 for falsifying data connected to simufilam.

Other senior leaders as of July 2024 included James W. Kupiec as chief medical officer and Eric Schoen as chief financial officer. Kupiec announced his retirement in April 2025; Jack Moore replaced him as senior vice president of clinical development with a focus on simufilam’s application for tuberous sclerosis-associated epilepsy. Additional senior vice presidents comprise R. Christopher Cook (senior counsel), Michael Marsman (regulatory affairs), Michael Zamloot (technical operations), and George Thornton (technology).

In 2022, despite SEC filings listing prominent scientific advisers like Jeffrey Cummings and Steven Arnold, Barbier did not publicly disclose these consultants. According to Patrick Keefe’s report in The New Yorker, the company’s bonus scheme tied cash incentives exclusively to stock price performance across consecutive days rather than drug approval or clinical success. This structure could generate over $200 million in bonuses overall, with Barbier’s potential payout estimated at $108 million by The Wall Street Journal.

Financial

From 2013 through 2021, the company did not generate any revenue from product sales. Between 2015 and 2021, Cassava and its partners obtained more than $20 million in funding through NIH grants.

According to The Wall Street Journal, Cassava Sciences became the sixth-best performing stock in 2021, largely due to Simufilam’s perceived promise. This success pushed the company's valuation beyond $5 billion, with share prices reaching a high of $125. The rapid increase was partly fueled by enthusiasm on online forums, leading to its classification as a meme stock. Nevertheless, after an FDA petition in August 2021 questioned the validity of the company’s research, the stock price declined to $42. Following the indictment of founder Wang in June 2024, shares dropped sharply by 46% to approximately $10. Later, in November 2024, when Simufilam failed its Phase III clinical trials, Cassava’s stock plummeted by 84% in a single trading day, closing at $4.29.

Staffing

As of November 2021, Cassava’s workforce consisted of 25 employees.

Research candidates

By 2021, Cassava had yet to secure approval for any pharmaceutical products.

FLNA hypothesis

Cassava’s scientific focus is on the protein Filamin A (FLNA), which they propose becomes structurally altered in individuals with Alzheimer's disease, contributing to amyloid accumulation. Research papers co-authored by founder Wang and Burns claim that correcting FLNA’s conformation could impede disease progression. However, independent researchers have expressed doubts since all supporting data originates exclusively from Wang’s laboratory. Notably, Wang and Burns have prior joint work investigating FLNA’s involvement in opioid receptor signaling.

Oxytrex, Remoxy and PTI-901

The company initially pursued development of three opioid-based drug candidates: Oxytrex (a combination of oxycodone and naltrexone), Remoxy (a reformulated oxycodone), and PTI-901 (low-dose naltrexone intended for irritable bowel syndrome).

Oxytrex was designed to deliver pain relief while minimizing opioid tolerance and withdrawal by combining oxycodone with naltrexone; however, it failed to meet endpoints in phase III clinical trials.

Remoxy, formulated as a twice-daily gel version of oxycodone with abuse-deterrent properties, was repeatedly rejected by the FDA. The agency ultimately denied approval in 2018 due to concerns over potential misuse. Additionally, the FDA reprimanded Cassava Sciences for marketing an unapproved drug—a claim disputed by the company which accused the FDA of errors.

Alzheimer's disease

In August 2020, Cassava rebranded its investigational Alzheimer's treatment PTI-125 as simufilam, aiming to restore aberrant FLNA protein structure within the brain. Open-label trials commenced in March 2020. Early phase IIb biomarker data showed no significant improvements; however, subsequent analyses conducted by an external laboratory—later identified as Wang’s lab at CUNY—reported positive biomarker and cognitive outcomes.

Phase III trials began in late 2021 with plans to enroll approximately 1,750 participants across two studies. Enrollment slowed by early 2022 amid ongoing controversies surrounding the drug. Development of simufilam was halted in November 2024 after phase III results failed to demonstrate clinical efficacy; it remained Cassava’s only drug candidate undergoing clinical evaluation.

Allegations of research fraud

In June 2024, founder Wang was indicted by the United States Department of Justice (DOJ) on charges of fraud involving falsification of data connected to $16 million in NIH grant applications related to simufilam. Reuters reported in July 2024 that investigations were also underway by both the DOJ and U.S. Securities and Exchange Commission (SEC) into two senior executives at Cassava. Subsequently, Barbier and Burns resigned abruptly in July 2024.

In September, the SEC filed charges against Cassava Sciences along with Barbier and Burns for making "misleading statements" about a phase two clinical trial concerning their Alzheimer's drug; Wang was accused of "manipulating trial results". Reuters highlighted that the company failed to disclose complete patient data demonstrating "no measurable cognitive improvement" and concealed Wang’s involvement and vested interests regarding the drug’s success. The allegations included violations of federal securities laws related to antifraud provisions and reporting requirements. Cassava Sciences agreed to pay a civil penalty of $40 million; Barbier and Burns were fined $175,000 and $85,000 respectively and accepted bans from serving as officers or directors for three and five years. The settlement is pending approval from a U.S. District Court.

The journal Science reported that CUNY determined Wang committed "egregious" scientific misconduct. The SEC alleged Wang had access to unblinded patient fluid samples during the trial while Burns "negligently failed to fully disclose" excluding data from roughly 40% of participants after treatment assignments became known. Furthermore, according to SEC documents, Cassava raised over $260 million from investors following the phase two announcement despite data indicating no improvement in episodic memory among Alzheimer's patients.

Citizen petition submitted to the FDA

In August 2021, the Food and Drug Administration (FDA) received a citizen petition filed by two whistleblowers accusing Cassava Science of unreliable research and possible data manipulation in its preclinical studies for an investigational drug. The petition, lodged by attorney Jordan A. Thomas from Labaton Sucharow, urged the FDA to suspend clinical trials until audits could verify Cassava's scientific assertions and clinical biomarker data. Cassava Sciences dismissed these claims as "outlandish," asserting that the FDA’s process was being exploited. Following the petition’s release, Cassava’s stock value plummeted by 55%.

The whistleblowers were later revealed to be neuroscientist David S. Bredt and cardiologist Geoffrey Pitt, both affiliated with Weill Cornell Medical College. Bredt, who is also an executive partner at a firm investing in Alzheimer’s biotech, criticized the research for conflicting with established biological and pharmacological principles. The Wall Street Journal uncovered that Cassava’s statement about an “independent lab” reexamining simufilam’s efficacy was misleading; the laboratory was actually operated by Wang, a longtime compensated consultant for Cassava. Bredt and Pitt identified suspicious irregularities in Western blot images and nondisclosure of reanalysis data, raising concerns regarding participant safety in ongoing trials. They took short positions on Cassava shares anticipating a decline; estimates suggest short sellers profited approximately $100 million during the August downturn.

In February 2022, the FDA rejected the petition, deeming it inappropriate for citizen petitions and choosing not to intervene. Subsequently, in July 2022, Vanderbilt neuroscientist Matthew Schrag, identified as another whistleblower, reported discrepancies in 34 publications linked to scientists associated with Cassava. Schrag received $18,000 for conducting extensive image analyses. Following SEC charges announced in September 2024, Schrag advocated for halting ongoing clinical trials due to evidence indicating data falsification.

An FDA inspection report from September 2022 obtained through FOIA disclosed numerous issues that cast doubt on the credibility of Wang’s and Cassava’s claims regarding simufilam’s effectiveness.

On November 3, 2022, Cassava Sciences initiated a defamation lawsuit against Quintessential Capital Management LLC, Bredt, Pitt, and other short sellers, accusing them of orchestrating a coordinated smear campaign containing over 1,000 false statements. The case was dismissed in March 2024 because most statements were considered protected opinions or part of scientific discourse; remaining defamatory allegations lacked sufficient proof of actual malice. After refiling in April 2024, Cassava withdrew the lawsuit in August following Wang’s indictment on charges related to submitting false data to the NIH.

Additional investigations

In July 2022, Reuters reported that the Department of Justice had launched a criminal investigation into Cassava Sciences. Prior to this, in 2021, The Wall Street Journal had noted ongoing probes by the SEC, NIH, and CUNY concerning accusations of data manipulation tied to the company’s Alzheimer’s treatment.

By October 2023, CUNY disclosed its inability to access Wang’s original datasets, hindering verification or dismissal of image manipulation allegations; shortly thereafter, the inquiry was suspended due to concerns over confidentiality and maintaining procedural integrity. Despite these investigations, Cassava Sciences has consistently denied any misconduct.

Following Wang’s indictment in June 2024, Cassava issued a statement clarifying that Wang’s involvement was limited to early-stage development and that he had no role in Phase 3 clinical trials of simufilam. Attorney Kate Moss emphasized in July 2022 that Cassava Sciences has never faced criminal charges nor engaged in unlawful activities.

Cassava has actively collaborated with authorities throughout these inquiries, reportedly providing nearly 100,000 pages of documentation to various agencies and inviting CUNY to conduct reviews of its research activities.

Additional Issues Raised

An April 2022 article in the New York Times brought to light doubts among researchers about Cassava’s assertions, pointing out flawed research designs, unclear methodologies, and results that seemed unlikely. Robert Howard, a psychiatry professor at University College London, criticized the absence of placebo groups and the limited participant numbers, describing the conclusions as "implausible." Similarly, Elisabeth Bik, an expert in image analysis, along with Nobel Prize winner Thomas C. Südhof, challenged both the data authenticity and the scientific soundness of Cassava’s reported outcomes.

Investigations by Academic Journals

Several scientific journals have revisited publications associated with Cassava’s studies. The Journal of Neuroscience issued a correction for a 2012 simufilam-related article but subsequently released an expression of concern while awaiting results from a CUNY investigation. Neurobiology of Aging identified mistakes in a 2017 study, prompting both a correction and an expression of concern as they await further findings. In contrast, The Journal of Prevention of Alzheimer’s Disease decided not to take action after reviewing a 2020 paper concerning simufilam.

PLOS One withdrew five papers authored by Wang on FLNA binding due to unresolved questions about data integrity; these included fundamental research pivotal to Cassava’s drug development efforts. The retraction notices cited anomalies such as splice artifacts and recurring pixel patterns in images that compromised the trustworthiness of the data.

A 2005 article in Neuroscience, co-written by Burns and Wang, received an expression of concern regarding image-related problems, with the journal continuing to observe developments from the ongoing CUNY inquiry.

Cassava advisors Wang and Arnold collaborated on a significant 2012 publication in the Journal of Clinical Investigation that proposed simufilam’s mechanism through reducing insulin resistance. Although concerns about reproducibility and whistleblower claims—some linked to investors holding short positions on Cassava—were investigated by the journal, no evidence was found to support these allegations.

These persistent journal reviews combined with external criticisms affect Cassava Sciences’ scientific reputation, which is vital for its business model, competitive standing, and investor trust in its leading Alzheimer's treatment development program.