Back to the Top


Name: CT1812
Synonyms: Elayta
Therapy Type: Small Molecule (timeline)
Target Type: Amyloid-Related (timeline)
Condition(s): Alzheimer's Disease
U.S. FDA Status: Alzheimer's Disease (Phase 2)
Company: Cognition Therapeutics Inc.


CT1812 is a small-molecule antagonist of the sigma2 receptor. It binds to the progesterone receptor membrane component 1 subunit of the receptor complex. The rationale behind this therapeutic approach is that ligands for the sigma2/PGRMC1 receptor are negative allosteric regulators that reduce the affinity of oligomeric Aβ for its receptor, and thus interfere with Aβ-induced synaptic toxicity.

CT1812 grew out of screening programs at Cognition Therapeutics. Company scientists have reported that compounds in this series not only block binding of a range of different Aβ species to neuronal receptors but also displace it when applied after Aβ has bound (Dec 2014 conference news).

CT1812 is a chemically optimized derivative of small molecules selected for their ability to reverse the synaptotoxicity of soluble Aβ oligomers on cultured neurons (Rishton et al., 2021). Similar compounds in the series have been reported to enter the brain, occupy up to 80 percent of sigma2/PGRMC1 receptors, and restore behavioral deficits in APP transgenic mice (Izzo et al., 2014Izzo et al., 2014). In preclinical work, CT1812 facilitated brain clearance of Aβ oligomers and improved cognitive behaviors in transgenic mouse models of Alzheimer’s disease. The compound also displaced Aβ oligomers from human postmortem AD brain tissue (Izzo et al., 2021).


From September 2015 to May 2016, Cognition Therapeutics ran a Phase 1 trial in 80 healthy volunteers aged 18 to 75 in Melbourne, Australia; target enrollment was originally listed as 114. Single-ascending-dose administration was followed by multiple ascending doses given once daily for two weeks. The dose range in this trial spanned 10 to 650 mg; if this would not generate data to set a maximum tolerated dose, doses up to 1,350 mg were to be tried. Outcome measures included safety, tolerability, plasma pharmacokinetics, and CSF CT1812 concentration. At the 2016 and 2017 AAIC conferences, company scientists reported that single doses up to 1,120 mg were given, as were multiple doses of up to 840 mg in young and up to 560 mg in elderly volunteers. The drug was reported to be well-tolerated, with suitable pharmacokinetics, sufficient brain penetrance and target exposure, and minimal drug-drug interactions affecting cytochrome P450 activity (Catalano et al., 2016). Results have been published (Grundman et al., 2019). Another Phase 1 trial in 2016 assessed drug-drug interactions in 16 healthy volunteers.

From September 2016 to August 2017, Cognition Therapeutics ran a Phase 1/2 trial at four sites in Australia, enrolling 19 participants with mild to moderate Alzheimer's disease supported by a recent MRI. It compared a four-week course of 90, 280, or 560 mg of CT1812 to placebo, taken once daily, on safety and tolerability parameters. At the subsequent CTAD conference, Elayta was reported to have been generally safe and well-tolerated, though there were four cases of lymphocytopenia. Exploratory measures such as ADAS-Cog14, verbal or category fluency tests recorded no difference between groups, but exploratory biomarker analyses yielded possible signals of synapse protection (Dec 2017 conference news). Later, investigators reported that CT1812 increased Aβ oligomers in CSF, suggesting CT1812 promoted oligomer clearance from the brain (2019 AAIC meeting abstract). According to published data, the Aβ oligomer concentration in CSF rose after treatment, while the concentration of synaptic proteins neurogranin and synaptotagmin fell, compared to placebo. CSF Aβ40 or 42 monomers, neurofilament light chain, SNAP-25, total Tau, and p-Tau181 were unchanged (Izzo et al., 2021).

In April 2018, a Phase 1/2 study started enrolling 23 people whose mild to moderate AD was confirmed by amyloid PET or CSF testing. Conducted at Yale University School of Medicine and dubbed COG0105 or SPARC, this trial compared a six-month course of 100 or 300 mg of Elayta to placebo. A six-month, double-blind extension was later added. The primary outcome was originally listed as cognition as assessed by the Alzheimer's Disease Clinical Study Activities of Daily Living (ADCS-ADL), but was changed in September 2018 to safety. The trial used the investigational PET tracer UCB-J, which binds to the synaptic vesicle glycoprotein 2A, in an attempt to monitor synapse density before and after treatment (see company press release; Jul 2016 news). Midway through the study, synaptic density was added as co-primary. The trial finished in October 2020, and results are posted on At the 2022 AAIC, the company disclosed that treatment had not altered synaptic density, measured by SV2a PET, compared to baseline. CSF proteomics analysis revealed a reduction in the inflammatory marker YKL-40. Other CSF proteins related to synaptic biology and amyloid were reportedly normalized after treatment (company presentation).

In May 2018, a Phase 1b target engagement study at the University of Pennsylvania began enrolling 18 people whose mild to moderate AD was to be confirmed by amyloid PET. Called COG0104 or SNAP, the study was to compare single injections of 90, 280, or 560 mg of Elayta to placebo for their ability to displace Aβ oligomers and clear them into the CSF. This was assessed by an Aβ oligomer assay on CSF samples collected hourly for 24 hours after treatment. This study ended in February 2019, with only three participants enrolled. According to published results, the investigators had difficulty recruiting because of the study's requirement for a 28-hour spinal catherization and the lack of an optional open-label extension. Of the three participants, two received 560 mg CT1812, one placebo. CSF Aβ oligomers increased by 2.5- and 5-fold over baseline in the treated patients, and did not change in the one who received placebo. Concentrations of monomeric Aβ stayed the same in all three. One patient who had higher blood levels of CT1812, also had higher CSF Aβ oligomer concentrations.

A similar pilot trial in Sweden was to measure CSF Aβ oligomers after a single 100 mg dose in 16 people with mild to moderate AD, followed by six months of open-label daily dosing. The trial was to assess drug effects on CSF biomarkers of Aβ, tau, and synaptic function after six months. In November 2020, this trial was stopped early.

In October 2018, a Phase 2 multicenter safety study called SHINE or COG0201 began enrolling 24 people with mild to moderate AD as confirmed by amyloid PET for a six-month course of 100 or 300 mg of CT1812, or placebo. The primary outcome is the number of adverse events. The company later increased the study size to 144, and added cognitive endpoints. The trial, at 36 sites in the U.S., Europe, and Australia, is expected to finish in July 2024. At the 2020 Alzheimer’s Association International Conference, the company reported positive trends for cognitive endpoints in the first 24 people who completed six months of treatment (Aug 2020 conference news).

In July 2020, a pilot study started in Amsterdam to assess synaptic effects of CT1812 using quantitative electroencephalography. Sixteen participants with mild to moderate Alzheimer’s disease receive 300 mg Elayta and placebo for 29 days each, in a crossover design. Outcomes include EEG, cognitive and functional measures, CSF biomarkers, and safety. Completion was slated for March 2023.

In January 2022, the company conducted an eight-patient study of the absorption, metabolism, and secretion of a single oral dose of [14C]-CT1812. In March, they conducted a pharmacokinetic study in 35 older healthy volunteers, evaluating 150 mg once or twice a day, and 300 mg once a day.

In June 2022, a Phase 2 trial called SHIMMER began assessing CT1812 in 120 people with mild to moderate dementia with Lewy bodies. At 30 centers in the U.S., this six-month study is comparing 100 or 300 mg of CT1812 to placebo on primary outcomes of safety and tolerability. Secondary outcomes include measures of cognition, sleepiness, clinical change, daily function, movement, and neuropsychiatric symptoms. Completion is planned for April 2024.

In September 2022, the company registered a Phase 2 trial called START. It will compare 18 months of 100 or 300 mg CT1812 to placebo in 540 people with mild cognitive impairment or mild dementia due to Alzheimer’s. The primary outcome is change in CDR-SB, with planned secondaries of the ADAS-Cog13, ADCS-Activities of Daily Living, CSF biomarkers of Aβ, tau, neurofilament light chain, neurogranin, and synaptotagmin, as well as volumetric MRI. The Alzheimer’s Clinical Trial Consortium is running the trial, with funding from the National Institute on Aging (press release). Recruitment is to start in December, completion is expected in summer 2026. After awaiting FDA clearance, the trial is set to begin in June 2023, and run until summer 2026.

The company is also planning a Phase 2 study testing CT1812 for age-related macular degeneration (press release).

For all trials of this compound, see and EU Clinical Trials Register.

Clinical Trial Timeline

  • Phase 1/2
  • Phase 2
  • Study completed / Planned end date
  • Planned end date unavailable
  • Study aborted
Sponsor Clinical Trial 2014 2015 2016 2017 2018 2019 2020 2021 2022 2023 2024 2025 2026 2027 2028 2029 2030 2031 2032 2033
Cognition Therapeutics Inc. NCT02907567
Cognition Therapeutics Inc. NCT03493282
Cognition Therapeutics Inc. NCT03507790

Last Updated: 30 May 2023


No Available Comments

Make a Comment

To make a comment you must login or register.


News Citations

  1. Elusive or Not, Aβ Oligomers Are in BioPharma Crosshairs
  2. Next Up for Human Brain Imaging: Synaptic Density?
  3. At AAIC, Hints of Target Engagement for Some Drug Candidates
  4. Meet Sigma2, a New Aβ Receptor?

Paper Citations

  1. . A Two-Part, Double-Blind, Placebo-Controlled, Phase 1 Study of the Safety and Pharmacokinetics of Single and Multiple Ascending Doses of Ct1812 in Healthy Volunteers. Alzheimer's & Dementia, July 2016, Volume 12, Issue 7S, Part 24, pp1183-4. Alzheimers Dement.
  2. . A phase 1 clinical trial of the sigma-2 receptor complex allosteric antagonist CT1812, a novel therapeutic candidate for Alzheimer's disease. Alzheimers Dement (N Y). 2019;5:20-26. Epub 2019 Jan 23 PubMed.
  3. . Clinical biomarker evidence for target engagement, reduction of synaptic damage and disease modification in Alzheimer’s patients treated with CT1812, poster abstract. Alzheimer's & Dementia, July 2019 Alzheimer's & Dementia
  4. . Preclinical and clinical biomarker studies of CT1812: A novel approach to Alzheimer's disease modification. Alzheimers Dement. 2021 Feb 8; PubMed.
  5. . Discovery of Investigational Drug CT1812, an Antagonist of the Sigma-2 Receptor Complex for Alzheimer's Disease. ACS Med Chem Lett. 2021 Sep 9;12(9):1389-1395. Epub 2021 Aug 9 PubMed.
  6. . Alzheimer's therapeutics targeting amyloid beta 1-42 oligomers I: Abeta 42 oligomer binding to specific neuronal receptors is displaced by drug candidates that improve cognitive deficits. PLoS One. 2014;9(11):e111898. Epub 2014 Nov 12 PubMed.
  7. . Alzheimer's therapeutics targeting amyloid beta 1-42 oligomers II: Sigma-2/PGRMC1 receptors mediate Abeta 42 oligomer binding and synaptotoxicity. PLoS One. 2014;9(11):e111899. Epub 2014 Nov 12 PubMed.

External Citations

  1. company press release
  3. company presentation
  4. press release
  5. press release
  8. EU Clinical Trials Register.

Further Reading


  1. . Alzheimer's protection effect of A673T mutation may be driven by lower Aβ oligomer binding affinity. J Neurochem. 2021 May;157(4):1316-1330. Epub 2020 Oct 25 PubMed.
  2. . Sigma-2 receptor antagonists rescue neuronal dysfunction induced by Parkinson's patient brain-derived α-synuclein. J Neurosci Res. 2021 Apr;99(4):1161-1176. Epub 2021 Jan 22 PubMed.
  3. . Targeting Sigma Receptors for the Treatment of Neurodegenerative and Neurodevelopmental Disorders. CNS Drugs. 2023 May;37(5):399-440. Epub 2023 May 11 PubMed.
  4. . The Allosteric Antagonist of the Sigma-2 Receptors-Elayta (CT1812) as a Therapeutic Candidate for Mild to Moderate Alzheimer's Disease: A Scoping Systematic Review. Life (Basel). 2022 Dec 20;13(1) PubMed.