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'''Cassava Sciences''' (symbol: '''SAVA''') is a [[pharmaceutical company]] based in Austin, Texas, USA. Its founder, Chief Executive Officer and President is Remi Barbier. Its drug candidate simufilam is in Phase 3 clinical trials for Alzheimer's disease. According to a Cassava Sciences press release, the first trial would enroll about 750 participants, and the second 1,000.<ref>{{Cite press release |date=December 23, 2021 |title=Cassava Sciences Launches Clinical Website to Support Phase 3 Studies of Oral Simufilam in Alzheimer's Disease |url=https://www.globenewswire.com/news-release/2021/12/23/2357426/8339/en/Cassava-Sciences-Launches-Clinical-Website-to-Support-Phase-3-Studies-of-Oral-Simufilam-in-Alzheimer-s-Disease.html |access-date=April 30, 2022 |website=GlobeNewswire News Room |publisher= Cassava Sciences, Inc. |language=en}}</ref> As of August 2022, over 400 people had enrolled in these trials.<ref>https://www.cassavasciences.com/news-releases/news-release-details/cassava-sciences-reports-second-quarter-financial-results-2022</ref>
'''Cassava Sciences''' (symbol: '''SAVA''') is a [[pharmaceutical company]] based in Austin, Texas, USA. Its founder, Chief Executive Officer and President is Remi Barbier. Its drug candidate [[simufilam]], an oral tablet, is in Phase 3 clinical trials for Alzheimer's disease. Phase 3 trials of Simufilam started in 2021.<ref>{{cite press release |title=Cassava Sciences Initiates a Second Phase 3 Study of Simufilam for the Treatment of Patients with Alzheimer's Disease {{!}} Cassava Sciences, Inc. |url=https://www.cassavasciences.com/news-releases/news-release-details/cassava-sciences-initiates-second-phase-3-study-simufilam |publisher= Cassava Sciences, Inc. |language=en |date= November 18, 2021}}</ref> According to a Cassava Sciences press release, the first trial would enroll about 750 participants, and the second 1,000.<ref>{{Cite press release |date=December 23, 2021 |title=Cassava Sciences Launches Clinical Website to Support Phase 3 Studies of Oral Simufilam in Alzheimer's Disease |url=https://www.globenewswire.com/news-release/2021/12/23/2357426/8339/en/Cassava-Sciences-Launches-Clinical-Website-to-Support-Phase-3-Studies-of-Oral-Simufilam-in-Alzheimer-s-Disease.html |access-date=April 30, 2022 |website=GlobeNewswire News Room |publisher= Cassava Sciences, Inc. |language=en}}</ref> As of August 2022, over 400 people had enrolled in these trials.<ref>https://www.cassavasciences.com/news-releases/news-release-details/cassava-sciences-reports-second-quarter-financial-results-2022</ref> The company is also developing a blood-based diagnostic for Alzheimer's disease called SavaDx.


Established in 1998 as Pain Therapeutics, the company moved its focus from [[opioid]]s to drug development for [[neurodegenerative diseases]] and changed its name.<ref name=NameChange>{{Cite press release |last=Schoen |first=Eric |date=March 27, 2019 |title=Pain Therapeutics Announces Name Change to Cassava Sciences, Inc. |url=https://www.globenewswire.com/news-release/2019/03/27/1773930/8339/en/Pain-Therapeutics-Announces-Name-Change-to-Cassava-Sciences-Inc.html |access-date=April 28, 2022 |website=[[GlobeNewswire]] |publisher= Cassava Sciences, Inc. |language=en}}</ref><ref name=Keefe2022>{{Cite magazine |last=Keefe |first=Patrick Radden |date=January 15, 2022 |title=Jordan Thomas's Army of Whistle-Blowers |url=https://www.newyorker.com/magazine/2022/01/24/jordan-thomas-army-of-whistle-blowers |access-date=April 29, 2022 |magazine=[[The New Yorker]] |language=en-US}}</ref> Cassava initially worked on three drugs: Oxytrex and Remoxy, which were pain drugs, and PTI-901, which aimed to treat irritable [[irritable bowel syndrome]].<ref name=Jacobs2005>{{Cite journal |last=Jacobs |first=Tom |date=2005 |title=No pain, no gain? |url=https://www.nature.com/articles/nbt0805-934 |journal=[[Nature Biotechnology]] |language=en |volume=23 |issue=8 |pages=934 |doi=10.1038/nbt0805-934|pmid=16082357 |s2cid=20266178 }}</ref> None of the drugs have been approved by the [[Food and Drug Administration]].
Established in 1998 as Pain Therapeutics, the company moved its focus from [[opioid]]s to drug development for [[neurodegenerative diseases]] and changed its name.<ref name=NameChange>{{Cite press release |last=Schoen |first=Eric |date=March 27, 2019 |title=Pain Therapeutics Announces Name Change to Cassava Sciences, Inc. |url=https://www.globenewswire.com/news-release/2019/03/27/1773930/8339/en/Pain-Therapeutics-Announces-Name-Change-to-Cassava-Sciences-Inc.html |access-date=April 28, 2022 |website=[[GlobeNewswire]] |publisher= Cassava Sciences, Inc. |language=en}}</ref><ref name=Keefe2022>{{Cite magazine |last=Keefe |first=Patrick Radden |date=January 15, 2022 |title=Jordan Thomas's Army of Whistle-Blowers |url=https://www.newyorker.com/magazine/2022/01/24/jordan-thomas-army-of-whistle-blowers |access-date=April 29, 2022 |magazine=[[The New Yorker]] |language=en-US}}</ref> Cassava initially worked on three drugs: Oxytrex and Remoxy, which were pain drugs, and PTI-901, which aimed to treat irritable [[irritable bowel syndrome]].<ref name=Jacobs2005>{{Cite journal |last=Jacobs |first=Tom |date=2005 |title=No pain, no gain? |url=https://www.nature.com/articles/nbt0805-934 |journal=[[Nature Biotechnology]] |language=en |volume=23 |issue=8 |pages=934 |doi=10.1038/nbt0805-934|pmid=16082357 |s2cid=20266178 }}</ref> None of the drugs have been approved by the [[Food and Drug Administration]].


Cassava is developing an [[Alzheimer's disease|Alzheimer's]] diagnostic SavaDx (originally known as PTI-125Dx), and [[simufilam]] (previously known as PTI-125 and sumifilam), an oral-tablet drug candidate for the treatment of Alzheimer's disease. Phase III trials of Simufilam started in 2021.<ref>{{cite press release |title=Cassava Sciences Initiates a Second Phase 3 Study of Simufilam for the Treatment of Patients with Alzheimer's Disease {{!}} Cassava Sciences, Inc. |url=https://www.cassavasciences.com/news-releases/news-release-details/cassava-sciences-initiates-second-phase-3-study-simufilam |publisher= Cassava Sciences, Inc. |language=en |date= November 18, 2021}}</ref> A Citizen Petition was filed to the U.S. [[Food and Drug Administration]] (FDA) in an attempt to suspend the clinical trial,<ref name= Piller2022/> but it was rejected as the FDA ruled the request fell out of the purview of the Citizen Petitions.<ref>{{cite web |title=The Show Will Go On for Cassava after FDA Denies Citizen Petition |url=https://www.biospace.com/article/fda-denies-citizen-petition-to-halt-phase-iii-studies-of-cassava-sciences-alzheimer-s-drug/ |website=BioSpace.com |date= February 11, 2022 |first= Alex |last= Keown}}</ref><ref>{{cite web |title=An FDA ruling on Cassava's Alzheimer's drug leaves bulls and bears waiting for more |url=https://www.statnews.com/2022/02/11/an-fda-ruling-on-cassavas-alzheimers-drug-leaves-bulls-and-bears-waiting-for-more/ |website=[[Stat (website)|STAT]] |date=February 11, 2022 |first=Adam |last= Feuerstein }}</ref>
A Citizen Petition was filed to the U.S. [[Food and Drug Administration]] (FDA) in an attempt to suspend the clinical trials,<ref name= Piller2022/> but it was rejected as the FDA ruled the request fell out of the purview of the Citizen Petitions.<ref>{{cite web |title=The Show Will Go On for Cassava after FDA Denies Citizen Petition |url=https://www.biospace.com/article/fda-denies-citizen-petition-to-halt-phase-iii-studies-of-cassava-sciences-alzheimer-s-drug/ |website=BioSpace.com |date= February 11, 2022 |first= Alex |last= Keown}}</ref><ref>{{cite web |title=An FDA ruling on Cassava's Alzheimer's drug leaves bulls and bears waiting for more |url=https://www.statnews.com/2022/02/11/an-fda-ruling-on-cassavas-alzheimers-drug-leaves-bulls-and-bears-waiting-for-more/ |website=[[Stat (website)|STAT]] |date=February 11, 2022 |first=Adam |last= Feuerstein }}</ref>


[[Reuters]] reported on July 27, 2022, that a criminal investigation of Cassava Sciences had been started by the [[United States Department of Justice]] (DOJ) over research results related to the experimental Alzheimer's drug.<ref name="TaylorSpectorJuly27">{{cite news |last1=Taylor |first1=Marisa |last2=Spector |first2=Mike |date=July 27, 2022 |title=Exclusive: Cassava Sciences faces U.S. criminal probe tied to Alzheimer's drug, sources say |publisher=Reuters |url=https://www.reuters.com/business/healthcare-pharmaceuticals/exclusive-cassava-sciences-faces-us-criminal-probe-tied-alzheimers-drug-sources-2022-07-27/ |access-date=July 31, 2022}}</ref> ''[[The Wall Street Journal]]'' stated that the [[U.S. Securities and Exchange Commission]] (SEC) and the U.S. [[National Institutes of Health]] (NIH) are also investigating whether Cassava manipulated data.<ref name= Michaels/>
[[Reuters]] reported on July 27, 2022, that a criminal investigation of Cassava Sciences had been started by the [[United States Department of Justice]] (DOJ) over research results related to the experimental Alzheimer's drug.<ref name="TaylorSpectorJuly27">{{cite news |last1=Taylor |first1=Marisa |last2=Spector |first2=Mike |date=July 27, 2022 |title=Exclusive: Cassava Sciences faces U.S. criminal probe tied to Alzheimer's drug, sources say |publisher=Reuters |url=https://www.reuters.com/business/healthcare-pharmaceuticals/exclusive-cassava-sciences-faces-us-criminal-probe-tied-alzheimers-drug-sources-2022-07-27/ |access-date=July 31, 2022}}</ref> The company responded to this article by stating it had already disclosed this request for information by certain government agencies in the fall of 2021.<ref>https://www.cassavasciences.com/news-releases/news-release-details/cassava-sciences-responds-media-reports</ref> ''[[The Wall Street Journal]]'' stated on November 17, that the [[U.S. Securities and Exchange Commission]] (SEC) and the U.S. [[National Institutes of Health]] (NIH) were also investigating allegations of manipulated data.<ref name= Michaels/>


== History ==
== History ==

Revision as of 22:48, 15 August 2022

Cassava Sciences, Inc.
FormerlyPain Therapeutics, Inc.
Company typePublic
IndustryPharmaceuticals
Founded1998; 26 years ago (1998) in South San Francisco, CA, US
FounderRemi Barbier
HeadquartersAustin, Texas, US
Key people
  • Lindsay Burns (Senior Vice President, Neuroscience)
  • Nadav Friedmann (Chief Medical Officer)
  • James W. Kupiec (Chief Clinical Development Officer)
Products
Websitewww.cassavasciences.com

Cassava Sciences (symbol: SAVA) is a pharmaceutical company based in Austin, Texas, USA. Its founder, Chief Executive Officer and President is Remi Barbier. Its drug candidate simufilam, an oral tablet, is in Phase 3 clinical trials for Alzheimer's disease. Phase 3 trials of Simufilam started in 2021.[1] According to a Cassava Sciences press release, the first trial would enroll about 750 participants, and the second 1,000.[2] As of August 2022, over 400 people had enrolled in these trials.[3] The company is also developing a blood-based diagnostic for Alzheimer's disease called SavaDx.

Established in 1998 as Pain Therapeutics, the company moved its focus from opioids to drug development for neurodegenerative diseases and changed its name.[4][5] Cassava initially worked on three drugs: Oxytrex and Remoxy, which were pain drugs, and PTI-901, which aimed to treat irritable irritable bowel syndrome.[6] None of the drugs have been approved by the Food and Drug Administration.

A Citizen Petition was filed to the U.S. Food and Drug Administration (FDA) in an attempt to suspend the clinical trials,[7] but it was rejected as the FDA ruled the request fell out of the purview of the Citizen Petitions.[8][9]

Reuters reported on July 27, 2022, that a criminal investigation of Cassava Sciences had been started by the United States Department of Justice (DOJ) over research results related to the experimental Alzheimer's drug.[10] The company responded to this article by stating it had already disclosed this request for information by certain government agencies in the fall of 2021.[11] The Wall Street Journal stated on November 17, that the U.S. Securities and Exchange Commission (SEC) and the U.S. National Institutes of Health (NIH) were also investigating allegations of manipulated data.[12]

History

Cassava Sciences was founded by Remi Barbier in May 1998 as Pain Therapeutics.[13][14] Barbier first heard of the research led by Stanley M. Crain at the Albert Einstein College of Medicine in New York City around 1993.[15] Crain invited Barbier to his lab and explained the potential pharmaceutical and financial benefits.[15] In 1998, Barbier started Pain Therapeutics in South San Francisco, CA,[16] with an initial investment of one million dollars.[15]

The company started with three drug candidates: Oxytrex, Remoxy and PTI-901 (modified naltrexone for irritable bowel syndrome).[6] Oxytrex was a mixture of oxycodone, a generic opioid, combined with naltrexone that aimed to enhance analgesia while reducing opioid tolerance and withdrawal symptoms.[16] Its Phase III trial was underpowered due to high dropout rates, causing the share value of the company to recede by 19% the next day.[17] Remoxy was a twice-daily oxycodone. Clinical trials for Remoxy in 2006 were successful.[16] The FDA declined to approve Remoxy, culminating in the final rejection in 2018 after an FDA advisory meeting raised concerns about its potential risk of abuse.[18] Barbier accused the FDA of "math errors, material mistakes and misrepresentations", which the agency denied.[18] The FDA rejection led to a 36% loss in Cassava's share value.[19]

In 2019, the company changed its name to Cassava Sciences, Inc., with the stock ticker SAVA, stating in a press release that the name better reflected "the Company's strategic focus on drug development for neurodegenerative diseases".[4]

In August 2020, the World Health Organization,[20] and the United States Adopted Names (USAN) assigned the chemical name simufilam to the company's experimental drug (previously called PTI-125). The company reported in 2020 that initial biomarker analysis of CSF samples from its Phase 2b clinical trials failed due to high variability visible in the placebo group that should not change dramatically over one month.[5] However, analysis of backup CSF samples showed improvements, replicating results of the Phase 2a clinical trial.[21]

Company performance

As of November 2021, Cassava had 25 employees. The Wall Street Journal wrote that, due to the promise of its experimental Alzheimer's drug, Cassava Sciences stock became the sixth-best stock of 2021, driving the company's value to over $US5 billion, with the stock price reaching $125 per share, before falling to $42 after a petition was filed with the FDA in August 2021, questioning the company's research. It also reported that the company produced no product revenues between 2013 and 2021.[12]

Simufilam and allegations of research fraud

Citizen petition to the FDA

In August 2021, the Food and Drug Administration (FDA) received a citizen petition alleging concerns about unreliable research and potential data manipulation in Cassava Science's preclinical research for simufilam.[5][7] Submitted by Jordan A. Thomas of the law firm Labaton Sucharow in New York City, the letter requested that the FDA halt the clinical trials until the issues could be resolved.[22]

Cassava Sciences publicly maintained that the research data were genuine, leading Barbier to announce that, "as a science company, we champion facts that can be evaluated and verified."[22] Both Cassava and Quanterix stated that some biomarker data from the Phase II trial was generated by Quanterix Corporation, appropriately conducted blind to treatment group: "Quanterix or its employees did not interpret the test results or prepare the data charts presented by Cassava."[23][24]

According to Charles Piller, writing in Science, Barbier would not specify who were the company's 2022 scientific advisers.[7][a] Piller identified Vanderbilt University neuroscientist Matthew Schrag as the whistleblower who examined images and reported irregularities to the NIH.[7]

In November 2021, The Wall Street Journal stated that the whistleblower who filed a complaint to the FDA was neuroscientist David Bredt.[12][28] Bredt had noticed Cassava Sciences when its stock share increased in early 2021 following early positive trial results for simufilam. He was concerned with the methodology in the clinical trial, which was an open-label trial and not blinded. (The Phase 2b trial was blinded). After examining the preclinical research papers, he remarked that "they were making statements that were incompatible with biology and with pharmacology", and said that if the research was in fact legitimate, it should "win five Nobel Prizes". Joining with Geoffrey Pitt, his childhood friend and a cardiologist and a professor at Weill Cornell Medical College, they approached Thomas.[5] Bredt and Pitt had shorted shares of Cassava Sciences, expecting the price of its stock (one of the best performing stocks of 2021) to drop once problems with the research were revealed.[12] After the stock's precipitous drop caused by the petition, it was revealed that they were short sellers.[29]

In February 2022, Patrizia Cavazzoni, Director of the Center for Drug Evaluation and Research, rejected the petition on the ground that requests to halt trials were not appropriate for a citizen petition and the requested actions would require public disclosure of research materials which FDA is obligated to keep confidential and because the petitioners did not bring their own evidence but requested FDA to investigate. The letter concluded: "Please note that your Petitions are being denied solely on the grounds that your requests are not the appropriate subject of a citizen petition. This response does not represent a decision by the Agency to take or refrain from taking any action relating to the subject matter of your Petitions."[30]

Other concerns raised

The New York Times wrote in April 2022 that "many scientists have been deeply skeptical of the company's claims, asserting that Cassava's studies were flawed, its methods opaque and its results improbable"; Lawrence Sterling Honig, professor of neurology at Columbia University Irving Medical Center, noted: "But in fact, all the evidence seems to be from this [Wang's] lab."[31] Robert Howard, professor of psychiatry at the University College London, remarked on the lack of placebo and small sample size (50 subjects; however as of August 2022, similar data were released on 100 subjects) that making such research conclusion "at the very least is implausible".[31] Elisabeth Bik, image-manipulation consultant, agreed to the citizen petition and alleged data errors and inconsistencies in the publications, identifying many irregularities consistent with instances of copy and paste across different experiments.[12] Thomas C. Südhof, Nobel laureate neuroscientist at Stanford University, also commented: "The overall conclusions with regard to Alzheimer's disease make no sense to me whatsoever... [The findings of Cassava Sciences] are not in the mainstream of the field, and to me they seem implausible and contrived."[31]

According to The New York Times, Cassava had initially reported that a reanalysis of simufilam's effectiveness was done by "an outside lab," which was later revealed to be the lab of Wang.[31] Wang was known to be a long-time advisor and collaborator, who can receive bonuses based on the company's performance.[12] However, simufilam's effect on plasma biomarker p-tau181 was also seen from a sample analysis conducted by the independent laboratory Quanterix Corporation, who also conducted sample analysis blind to treatment group.[32]

Journal investigations

Following the public controversies, The Journal of Neuroscience reassessed the 2012 paper that described simufilam binding to FLNA.[12] The journal published a correction along with the original images in December 2021 remarking that the "error does not affect the conclusions of the article".[12][33] After further data concerns were brought to the attention of the journal, it issued an expression of concern stating: "These and other concerns are currently under investigation by the academic authorities at the City University of New York (CUNY). JNeurosci will await the outcome of that investigation before taking further action."[34]

Neuroscience investigated an allegation of image manipulation in a 2005 paper and found no evidence of data manipulation.[35]

PLOS One re-examined all the Burns and Wang's research papers in March 2020 and found "similarities in background pixels" in the Western blot data. Five of Wang's papers were retracted, two of which were co-authored with Burns[36] that include the original papers on the discovery of FLNA binding as it relates to opioid receptor signaling. Three papers are on prenatal cocaine. The FLNA retraction notices both mention image irregularities, "vertical irregularities suggestive of splice lines".[37][38] Retraction notices stated: "The data and comments provided did not resolve the concerns about the integrity and reliability of data presented in this article. In light of these issues, the PLOS ONE Editors retract this article."[39][40]

The journal Neurobiology of Aging found "no compelling evidence of data manipulation intended to misrepresent the results", but issued an expression of concern on the 2017 paper,[41] saying they identified multiple errors. The journal concluded: "The authors have requested a corrigendum to correct these issues. However, Neurobiology of Aging is aware of an ongoing inquiry of these and other concerns by the sponsoring institution, the City University of New York (CUNY), and will make a final decision as to appropriate corrective action once that inquiry has been concluded."[42]

DOJ, NIH, SEC investigations

The Wall Street Journal stated in November 2021 that the U.S. Securities and Exchange Commission (SEC) and the U.S. National Institutes of Health (NIH) are also investigating whether Cassava manipulated data. Cassava and its collaborators were awarded NIH grants of $20 million between 2015 and 2021.[12]

Reuters reported on July 27, 2022, that a criminal investigation of Cassava Sciences had been started by the United States Department of Justice over research results related to the experimental Alzheimer's drug. Two anonymous sources told Reuters that the investigation involved criminal charges over allegations that the company had "manipulated research results".[10]

According to Reuters, Cassava "neither confirmed nor denied" the DOJ probe, but Kate Moss, attorney, replied via email: "To be clear: Cassava Sciences vehemently denies any and all allegations of wrongdoing" and "has never been charged with a crime, and for good reason – Cassava Sciences has never engaged in criminal conduct."[10]

Notes

  1. ^ The company's SEC Form 10-K filings from 2021 state that Scientific Advisory Board members included Jeffrey Cummings, Steven Arnold, Barbara Sahakian, Trevor Robbins, and Hoau-Yan Wang.[25][26][27]

References

  1. ^ "Cassava Sciences Initiates a Second Phase 3 Study of Simufilam for the Treatment of Patients with Alzheimer's Disease | Cassava Sciences, Inc" (Press release). Cassava Sciences, Inc. November 18, 2021.
  2. ^ "Cassava Sciences Launches Clinical Website to Support Phase 3 Studies of Oral Simufilam in Alzheimer's Disease". GlobeNewswire News Room (Press release). Cassava Sciences, Inc. December 23, 2021. Retrieved April 30, 2022.
  3. ^ https://www.cassavasciences.com/news-releases/news-release-details/cassava-sciences-reports-second-quarter-financial-results-2022
  4. ^ a b Schoen, Eric (March 27, 2019). "Pain Therapeutics Announces Name Change to Cassava Sciences, Inc". GlobeNewswire (Press release). Cassava Sciences, Inc. Retrieved April 28, 2022.
  5. ^ a b c d Keefe, Patrick Radden (January 15, 2022). "Jordan Thomas's Army of Whistle-Blowers". The New Yorker. Retrieved April 29, 2022.
  6. ^ a b Jacobs, Tom (2005). "No pain, no gain?". Nature Biotechnology. 23 (8): 934. doi:10.1038/nbt0805-934. PMID 16082357. S2CID 20266178.
  7. ^ a b c d Piller C (July 21, 2022). "Blots on a field?". Science. 377 (6604): 358–363. doi:10.1126/science.add9993. PMID 35862524. S2CID 250953611. Archived from the original on July 21, 2022.
  8. ^ Keown, Alex (February 11, 2022). "The Show Will Go On for Cassava after FDA Denies Citizen Petition". BioSpace.com.
  9. ^ Feuerstein, Adam (February 11, 2022). "An FDA ruling on Cassava's Alzheimer's drug leaves bulls and bears waiting for more". STAT.
  10. ^ a b c Taylor, Marisa; Spector, Mike (July 27, 2022). "Exclusive: Cassava Sciences faces U.S. criminal probe tied to Alzheimer's drug, sources say". Reuters. Retrieved July 31, 2022.
  11. ^ https://www.cassavasciences.com/news-releases/news-release-details/cassava-sciences-responds-media-reports
  12. ^ a b c d e f g h i Michaels, Dave; Walker, Joseph (November 17, 2021). "SEC Investigating Cassava Sciences, Developer of Experimental Alzheimer's Drug". Wall Street Journal. ISSN 0099-9660. Retrieved April 29, 2022.
  13. ^ "Pain Therapeutics, Inc. – Cruelty Free Investing". crueltyfreeinvesting.org. Retrieved May 7, 2022.
  14. ^ "SAVA – Cassava Sciences Inc Company Profile". CNN Business. Retrieved May 7, 2022.
  15. ^ a b c Wolfson, Wendy (2005). "Janus-Faced Drugs: The Double-Edged Synthetic Opiate Trade". Chemistry & Biology. 12 (10): 1055–1056. doi:10.1016/j.chembiol.2005.10.003. PMID 16242645.
  16. ^ a b c Sturgeon, Christopher (June 15, 2006). "Pain Therapeutics Takes Different Path". GEN – Genetic Engineering and Biotechnology News. Retrieved April 29, 2022.
  17. ^ "Pain Therapeutics slumps as Oxytrex fails Phase III trial". PharmaTimes. PharmaTimes. November 23, 2005. Retrieved April 29, 2022.
  18. ^ a b "A 'disoriented' Pain Therapeutics flips out after FDA rejects appeal on Remoxy". Endpoints News. Retrieved June 15, 2022.
  19. ^ Mishra, Manas; Shyam, Ashwin (August 6, 2018). "FDA declines to approve Pain Therapeutics' opioid drug, shares plunge". Reuters. Retrieved April 28, 2022.
  20. ^ "USAN Modifies Lead Drug Candidate's Chemical Name to 'Simufilam'". GlobeNewswire News Room (Press release). Cassava Sciences, Inc. November 27, 2020. Retrieved May 3, 2022.
  21. ^ https://pubmed.ncbi.nlm.nih.gov/32920628/
  22. ^ a b McKenzie, Heather (August 27, 2021). "UPDATED: Cassava Sciences Responds to Allegations that Data is Manipulated and "Defies Logic"". BioSpace. Retrieved April 28, 2022.
  23. ^ "Quanterix Releases Statement". Quanterix (Press release). August 27, 2021. Retrieved April 29, 2022.
  24. ^ "Quanterix Releases Statement". www.businesswire.com (Press release). Quanteris. August 27, 2021. Retrieved April 29, 2022.
  25. ^ "United States Securities and Exchange Commission Form 10-K, Cassava Sciences, Inc". Cassava Sciences, Inc. March 23, 2021. Retrieved July 31, 2022.
  26. ^ "United States Securities and Exchange Commission Form 10-K, Cassava Sciences, Inc". Cassava Sciences, Inc. February 28, 2022. Retrieved July 31, 2022.
  27. ^ "Scientific Advisory Board". Cassava Sciences. March 5, 2021. Archived from the original on March 5, 2021. Retrieved July 31, 2022.{{cite web}}: CS1 maint: bot: original URL status unknown (link)
  28. ^ Rockoff, Jonathan D. (March 3, 2011). "J&J Poaches Lilly's Neurological Research Chief". Wall Street Journal. ISSN 0099-9660. Retrieved April 29, 2022.
  29. ^ Jaeger, Jaclyn (March 2, 2022). "The Cassava Sciences saga: Short sellers, 'gaming' the FDA, and the damaging ripple effects". Compliance Week. Retrieved July 31, 2022.
  30. ^ Cavazzoni, P. (February 9, 2022). "Response Letter from FDA CDER to Labaton Sucharow". www.regulations.gov. Retrieved April 29, 2022.
  31. ^ a b c d Mandavilli, Apoorva (April 18, 2022). "Scientists Question Data Behind an Experimental Alzheimer's Drug". The New York Times. ISSN 0362-4331. Retrieved April 28, 2022.
  32. ^ https://www.cassavasciences.com/news-releases/news-release-details/cassava-sciences-releases-statement-regarding-plasma-p-tau
  33. ^ "Erratum: Wang et al., "Reducing Amyloid-Related Alzheimer's Disease Pathogenesis by a Small Molecule Targeting Filamin A"". The Journal of Neuroscience. 41 (50): 10405. December 15, 2021. doi:10.1523/JNEUROSCI.2154-21.2021. ISSN 0270-6474. PMC 8672690. PMID 34759033.
  34. ^ "Expression of Concern: Wang et al., "Reducing Amyloid-Related Alzheimer's Disease Pathogenesis by a Small Molecule Targeting Filamin A"". Journal of Neuroscience. 42 (3): 529. January 19, 2022. doi:10.1523/JNEUROSCI.2306-21.2021. ISSN 0270-6474. PMC 8802929. PMID 34921050.
  35. ^ https://www.cassavasciences.com/news-releases/news-release-details/science-journal-finds-no-evidence-support-claims-data
  36. ^ Akst, Jef (March 31, 2022). "PLOS ONE Pulls Five Papers Tied to Alzheimer's Drug Controversy". The Scientist. Retrieved April 28, 2022.
  37. ^ "Retraction: Naloxone's Pentapeptide Binding Site on Filamin A Blocks Mu Opioid Receptor–Gs Coupling and CREB Activation of Acute Morphine". PLOS ONE. 17 (3): e0266629. March 30, 2022. doi:10.1371/journal.pone.0266629. PMC 8967007. PMID 35353864.
  38. ^ "Retraction: High-Affinity Naloxone Binding to Filamin A Prevents Mu Opioid Receptor–Gs Coupling Underlying Opioid Tolerance and Dependence". PLOS ONE. 17 (3): e0266627. March 30, 2022. doi:10.1371/journal.pone.0266627. PMC 8967022. PMID 35353861.
  39. ^ PLOS ONE Editorial Board (March 30, 2022). "Retraction: High-Affinity Naloxone Binding to Filamin A Prevents Mu Opioid Receptor–Gs Coupling Underlying Opioid Tolerance and Dependence". PLOS ONE. 17 (3): e0266627. doi:10.1371/journal.pone.0266627. ISSN 1932-6203. PMC 8967022. PMID 35353861.
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