Cognition Therapeutics’ Proof-of-Concept Phase 2 SHINE Trial Demonstrates Consistent Improvement in Cognitive Outcomes with Once-Daily Oral CT1812 in Mild-to-Moderate Alzheimer’s Patients
Cognition Therapeutics (NASDAQ: CGTX) reported positive results from its Phase 2 SHINE trial for CT1812, an oral treatment for mild-to-moderate Alzheimer's disease. The study showed:consistent cognitive improvement compared to placebo across all measures, with a ~40% mean improvement in cognitive outcomes. CT1812 demonstrated a favorable safety profile with mostly mild or moderate adverse events. Significant changes were observed in neurofilament light chain, a marker of neurodegeneration. The 100mg dose showed particularly promising results, informing future dose selection. These findings suggest that CT1812's amyloid oligomer antagonism mechanism may have potential as a monotherapy or in combination with approved drugs for Alzheimer's and related dementias.
Cognition Therapeutics (NASDAQ: CGTX) ha riportato risultati positivi dal suo trial di Fase 2 SHINE per il CT1812, un trattamento orale per l'Alzheimer da lieve a moderato. Lo studio ha mostrato:un miglioramento cognitivo costante rispetto al placebo in tutte le misure, con un ~40% di miglioramento medio nei risultati cognitivi. Il CT1812 ha dimostrato un profilo di sicurezza favorevole con principalmente eventi avversi di entità lieve o moderata. Cambiamenti significativi sono stati osservati nel neurofilamento light chain, un marcatore della neurodegenerazione. La dose da 100 mg ha mostrato risultati particolarmente promettenti, fornendo indicazioni per la selezione futura della dose. Questi risultati suggeriscono che il meccanismo di antagonismo degli oligomeri di amiloide del CT1812 potrebbe avere potenziale come monoterapia o in combinazione con farmaci approvati per l'Alzheimer e le demenze correlate.
Cognition Therapeutics (NASDAQ: CGTX) reportó resultados positivos de su ensayo de Fase 2 SHINE para el CT1812, un tratamiento oral para la enfermedad de Alzheimer de leve a moderada. El estudio mostró:mejoras cognitivas consistentes en comparación con el placebo en todas las medidas, con una mejora media del ~40% en los resultados cognitivos. El CT1812 demostró un perfil de seguridad favorable con eventos adversos mayormente leves o moderados. Se observaron cambios significativos en la cadena ligera de neurofilamento, un marcador de neurodegeneración. La dosis de 100 mg mostró resultados particularmente prometedores, lo que informa sobre la selección futura de dosis. Estos hallazgos sugieren que el mecanismo de antagonismo de oligómeros de amiloide del CT1812 podría tener potencial como monoterapia o en combinación con medicamentos aprobados para el Alzheimer y demencias relacionadas.
Cognition Therapeutics (NASDAQ: CGTX)는 CT1812에 대한 2상 SHINE 시험의 긍정적인 결과를 보고했습니다. CT1812는 경증에서 중등도 알츠하이머병을 위한 경구 치료제입니다. 이 연구는:플라시보와 비교하여 일관된 인지 개선을 보여주었으며, 인지 결과에서 약 ~40%의 평균 개선을 기록했습니다. CT1812는 대부분 경증 또는 중간 정도의 부작용으로 유리한 안전성 프로필을 보여주었습니다. 신경퇴행의 마커인 신경 필라멘트 경량 사슬의 유의미한 변화가 관찰되었습니다. 100mg 용량은 특히 유망한 결과를 보여 향후 용량 선택에 대한 정보를 제공했습니다. 이러한 발견은 CT1812의 아밀로이드 올리고머 길항제 메커니즘이 알츠하이머와 관련된 치매에 대해 단독 요법 또는 승인된 약물과의 조합으로서 잠재력이 있을 수 있음을 시사합니다.
Cognition Therapeutics (NASDAQ: CGTX) a rapporté des résultats positifs de son essai de Phase 2 SHINE pour le CT1812, un traitement oral pour la maladie d'Alzheimer légère à modérée. L'étude a montré:une amélioration cognitive cohérente par rapport au placebo sur toutes les mesures, avec une amélioration moyenne d'environ 40% des résultats cognitifs. Le CT1812 a démontré un profil de sécurité favorable avec principalement des événements indésirables légers ou modérés. Des changements significatifs ont été observés dans la chaîne légère des neurofilaments, un marqueur de neurodégénérescence. La dose de 100 mg a montré des résultats particulièrement prometteurs, informant la sélection future des doses. Ces résultats suggèrent que le mécanisme d'antagonisme des oligomères d'amyloïde du CT1812 pourrait avoir un potentiel en tant que monothérapie ou en combinaison avec des médicaments approuvés pour l'Alzheimer et les démences connexes.
Cognition Therapeutics (NASDAQ: CGTX) berichtete über positive Ergebnisse aus der Phase-2-Studie SHINE für CT1812, eine orale Behandlung für leichte bis mittelschwere Alzheimer-Krankheit. Die Studie zeigte:konstante kognitive Verbesserungen im Vergleich zum Placebo über alle Messungen hinweg, mit einer ~40% durchschnittlichen Verbesserung der kognitiven Ergebnisse. CT1812 wies ein günstiges Sicherheitsprofil auf, mit überwiegend milden oder moderaten Nebenwirkungen. Bedeutende Veränderungen wurden in der neurofilamentären leichten Kette beobachtet, einem Marker für Neurodegeneration. Die Dosis von 100 mg zeigte besonders vielversprechende Ergebnisse und informierte über künftige Dosisentscheidungen. Diese Ergebnisse deuten darauf hin, dass der Antagonismus von Amyloid-Oligomeren von CT1812 potenziell als Monotherapie oder in Kombination mit zugelassenen Medikamenten für Alzheimer und verwandte Demenzen eingesetzt werden könnte.
- CT1812 showed ~40% mean improvement in cognitive measures vs placebo
- Consistent positive changes across cognitive and functional measures
- Favorable safety profile with most treatment-related adverse events mild or moderate
- Significant changes in neurofilament light chain, a marker of neurodegeneration
- 100mg dose showed particularly promising results for future development
- Potential for CT1812 as a monotherapy or in combination with approved drugs
- CT1812 did not achieve statistical significance on the first of the ordered secondary efficacy endpoints
- Nine patients experienced treatment-emergent LFT increases at the 300mg dose
- Three patients experienced treatment-emergent SAEs in the 300mg group
Insights
The Phase 2 SHINE trial results for Cognition Therapeutics' CT1812 in mild-to-moderate Alzheimer's disease (AD) patients are intriguing, albeit with some caveats. The ~40% mean improvement in cognitive measures compared to placebo is noteworthy, especially given the oral administration and favorable safety profile.
Key points to consider:
- The consistent trend in cognitive improvement across multiple measures (ADAS-Cog 11, ADAS-Cog 13, cognitive composite, MMSE) strengthens the validity of the findings.
- The 100mg dose appears to have the most promising efficacy-to-safety ratio, with improvements comparable to approved antibodies but with easier administration.
- The significant changes in neurofilament light chain (NfL) at the 300mg dose support CT1812's potential as a synaptoprotective agent.
- However, the study did not achieve statistical significance on the first of the ordered secondary efficacy endpoints, which is a limitation.
The amyloid oligomer antagonism mechanism represents a novel approach in AD treatment. If further validated, it could potentially complement existing therapies or serve as a standalone option. The upcoming SHIMMER trial results in Lewy body dementia and the ongoing START trial in early-stage AD will be important in establishing CT1812's broader efficacy profile across neurodegenerative disorders.
From a financial perspective, these results could significantly impact Cognition Therapeutics' market position and valuation. Key financial implications include:
- Potential market expansion: If CT1812 proves effective, it could tap into the lucrative Alzheimer's market, estimated to be worth
$5.6 billion globally in 2023 and growing. - Cost-effectiveness: As an oral drug, CT1812 could offer a more cost-effective alternative to injectable antibodies, potentially leading to higher market penetration and revenue.
- R&D efficiency: The
$170 million in grants from NIH, NIA, ADDF and MJFF have significantly defrayed R&D costs, improving the company's financial position. - Pipeline value: Positive results in AD could increase investor confidence in Cognition's broader neurodegenerative disease pipeline, potentially boosting the company's valuation.
However, investors should note that further clinical trials are needed and the path to FDA approval remains long and uncertain. The company's ability to finance these trials and potential commercialization will be crucial. The stock may see increased volatility as the market digests these results and anticipates future trial outcomes.
These results position CT1812 as a potentially disruptive player in the Alzheimer's treatment landscape. The oral administration and favorable safety profile could give it a significant competitive advantage over existing antibody treatments like Aduhelm and Leqembi, which require infusions or injections.
Key industry implications:
- Paradigm shift: If successful, CT1812 could shift treatment paradigms towards earlier intervention in AD, given its ease of administration and safety profile.
- Combination potential: The distinct mechanism of action opens possibilities for combination therapies, potentially creating new partnership opportunities in the industry.
- Market dynamics: An effective oral treatment could reshape market dynamics, potentially pressuring current leaders to innovate or partner.
- Regulatory landscape: Success of CT1812 might influence regulatory approaches, potentially setting new standards for cognitive improvement in AD trials.
However, it's important to remember that many promising AD drugs have faltered in later-stage trials. The industry will be watching the upcoming trials closely, particularly for replication of these cognitive benefits and further safety data. The potential impact on Cognition Therapeutics and the broader AD treatment landscape is significant, but cautious optimism is warranted given the historically challenging nature of AD drug development.
- CT1812 Treatment Showed ~
- Consistent Positive Changes Across Cognitive and Functional Measures -
- Favorable Safety Profile with Most Treatment-Related Adverse Events Mild or Moderate -
- Significant Changes in Neurofilament Light Chain, a Marker of Neurodegeneration -
- Investor Webcast to be Conducted at 8:30a.m. ET to Review Findings -
PURCHASE, N.Y., July 29, 2024 (GLOBE NEWSWIRE) -- Cognition Therapeutics, Inc. (the “Company” or “Cognition”) (NASDAQ: CGTX), a clinical stage company developing drugs that treat neurodegenerative disorders, today reported that participants in the proof-of-concept Phase 2 ‘SHINE’ study (NCT03507790) who were treated with CT1812 for six months showed a consistent trend in cognitive improvement compared to placebo across all cognitive measures including ADAS-Cog 11, ADAS-Cog 13, cognitive composite and MMSE. In addition, there were signals of improvement in functional measures (ADCS-ADL and ADCS-CGIC). Details of these clinical and biomarker findings are reported in posters at the Alzheimer’s Association’s International Conference on July 29, 2024 in Philadelphia, PA.
“The SHINE trial showed that after 182 days of treatment, CT1812 demonstrated evidence of clinical improvements on cognition coupled with a favorable safety and tolerability profile, particularly in the 100mg dose cohort. These findings will inform dose selection and provide a foundation for advancing to the next stage of clinical development,” stated Lisa Ricciardi, president and CEO of Cognition Therapeutics. “We believe these results provide evidence that amyloid oligomer antagonism – a new and distinct mechanism for therapeutic intervention – may have a role as a monotherapy or in a combination with approved drugs for the treatment of AD and related dementias. In terms of percent improvement on evaluated cognitive measures, our results are comparable in magnitude to what was achieved with currently approved antibodies, with great ease of administration as a once daily dose, and less patient burden.”
SHINE enrolled 153 adults with mild-to-moderate (MMSE 18-26) Alzheimer's disease who were randomized evenly (1:1:1) to one of two oral daily doses of CT1812 (100mg or 300mg) or placebo. P-values less than 0.05 were observed on ADAS-Cog 11 and MMSE at Day 98, the midpoint of the study. Through the course of the study, participants in the placebo arm worsened approximately 2.70 points as measured by ADAS-Cog 11 on Day 182. In contrast, CT1812-treated participants declined by an average of 1.66 points, a
“A key objective of this trial was to provide evidence of cognitive benefit potential with CT1812 treatment, which we accomplished,” added Anthony Caggiano, Cognition’s CMO and head of R&D. “We are pleased about the consistent cognitive effect and signals of functional benefit across the entire study. We intend to utilize these findings to enable us to design and power future clinical trials to advance the development of CT1812 in Alzheimer’s disease. We believe that the data supports the advancement of a 100mg dose of CT1812 in additional clinical trials in a mild-to-moderate patient population.”
While we are continuing to analyze the exploratory CSF biomarker program data, the study showed favorable changes in neurofilament light chain (NfL), which is a marker of neurodegenerative disease. These changes were significant at the 300mg dose. We believe this finding supports the understanding of the potential role of CT1812 as a synaptoprotective agent. Other CSF biomarkers not approaching significance include neurogranin, synaptotagmin, SNAP25, pTau, total Tau and GFAP.
The SHINE study achieved its primary objective and demonstrated a favorable safety and tolerability profile, consistent with previous clinical experience. Overall, the percentage of participants experiencing any adverse event (AE) was similar between the pooled CT1812 treatment arms (
In the placebo arm,
At the 300mg dose, nine patients experienced treatment-emergent LFT increases (greater than 3xULN), which subsided after cessation of drug without evidence of serious liver injury. There were no LFT elevations observed in the 100mg dose.
“We are optimistic about the SHINE results and are looking ahead to the results of our SHIMMER trial in mild-to-moderate Lewy body dementia, which is anticipated to read out later this year,” stated Lisa Ricciardi, president and CEO of Cognition Therapeutics. “In addition, we are studying patients with early stage Alzheimer’s disease in our START trial of 540 patients. Another Phase 2 proof-of-concept trial in dry AMD is currently enrolling patients. Cognition is committed to advancing the field of research to provide clinical options for patients with neurodegenerative disease, and we could not have done this without the grant support of over
| AAIC Presentation details | |
| Title: | Clinical Efficacy Results from COG0201: a Randomized, Double-Blind, Placebo-Controlled Phase 2 Study to Evaluate the Safety and Efficacy of CT1812 in Adults with Mild-to-Moderate Alzheimer’s Disease |
| Authors: | Vijverberg EGB, Catalano S, Hamby ME, Grundman M, Iaci J, Devins T, Caggiano AO |
| Date/Time: | July 29, 2024: 8:30 a.m. - 4:15 p.m. Eastern Time |
| Location: | Pennsylvania Convention Center, Philadelphia, PA |
This and Cognition’s other AAIC posters will be available on the Company’s Publication webpage in accordance with the conference’s embargo policy.
Webcast Information
Company management will be joined by an investigator in the SHINE study, Everard (Jort) Vijverberg, MD, PhD of the Alzheimer Center Amsterdam and Neuroscience Amsterdam, who will present an overview of the results. In addition, Martin J. Sadowski, MD, PhD, DSci of New York University School of Medicine will participate as an Alzheimer’s industry expert. A live question and answer session will follow formal presentations. Interested parties may register from the event listing on the Cognition Therapeutics Investor Relations webpage under News & Events or directly by visiting https://lifescievents.com/event/cognition/.
About the SHINE Study
The SHINE study is a double-blind, placebo-controlled Phase 2 clinical trial which enrolled 153 adult patients with mild-to-moderate Alzheimer’s disease. Based on the study design, SHINE was powered to detect a 3-point change in ADAS-Cog 11. The primary endpoint was safety and tolerability and the key secondary endpoint cognitive measure was ADAS-Cog 11. Participants were evenly randomized to receive either placebo or one of two doses of CT1812 (100 mg or 300 mg), which was taken orally daily for six months. The SHINE study was supported by two grant awards from the National Institute on Aging of the National Institutes of Health (NIH) totaling approximately
About CT1812
CT1812 is an experimental orally delivered small molecule oligomer antagonist that penetrates the blood-brain barrier and binds selectively to the sigma-2 (σ-2) receptor complex. Preclinical and clinical data demonstrated that this binding resulted in the displacement of toxic Aβ oligomers. The σ-2 receptor complex is involved in the regulation of key cellular processes such as membrane trafficking and autophagy that are damaged by toxic interaction with Aβ oligomers, oxidative stress and other stressors. This damage to sensitive synapses can progress to a loss of synaptic function, which manifests as cognitive impairment and Alzheimer’s disease progression.
Participants are currently being recruited in the SHIMMER study (NCT05225415) of CT1812 in adults with dementia with Lewy bodies; the START study (NCT05531656) of CT1812 in adults with early Alzheimer’s disease; and the MAGNIFY study (NCT05893537) in adults with geographic atrophy (GA) secondary to dry age-related macular degeneration.
About Cognition Therapeutics, Inc.
Cognition Therapeutics, Inc. is a clinical-stage biopharmaceutical company engaged in the discovery and development of innovative, small molecule therapeutics targeting age-related degenerative disorders of the central nervous system and retina. We are currently investigating our lead candidate CT1812 in clinical programs in Alzheimer’s disease, dementia with Lewy bodies (DLB) and dry age-related macular degeneration (dry AMD). We believe CT1812 and our pipeline of σ-2 receptor modulators can regulate pathways that are impaired in these diseases. We believe that targeting the σ-2 receptor with CT1812 represents a mechanism functionally distinct from other current approaches in clinical development for the treatment of degenerative diseases. More about Cognition Therapeutics and its pipeline can be found at https://cogrx.com
Forward Looking Statements
This press release contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. All statements contained in this press release, other than statements of historical facts or statements that relate to present facts or current conditions, including but not limited to, statements regarding our product candidates, including CT1812, and any expected or implied benefits or results, including that initial clinical results observed with respect to CT1812 will be replicated in later trials and our clinical development plans, including statements regarding our clinical studies of CT1812 and any analyses of the results therefrom, are forward-looking statements. These statements, including statements relating to the timing and expected results of our clinical trials, involve known and unknown risks, uncertainties and other important factors that may cause our actual results, performance, or achievements to be materially different from any future results, performance, or achievements expressed or implied by the forward-looking statements. In some cases, you can identify forward-looking statements by terms such as “may,” might,” “will,” “should,” “expect,” “plan,” “aim,” “seek,” “anticipate,” “could,” “intend,” “target,” “project,” “contemplate,” “believe,” “estimate,” “predict,” “forecast,” “potential” or “continue” or the negative of these terms or other similar expressions. We have based these forward-looking statements largely on our current expectations and projections about future events and financial trends that we believe may affect our business, financial condition, and results of operations. These forward-looking statements speak only as of the date of this press release and are subject to a number of risks, uncertainties and assumptions, some of which cannot be predicted or quantified and some of which are beyond our control. Factors that may cause actual results to differ materially from current expectations include, but are not limited to: our ability to successfully advance our current and future product candidates through development activities, preclinical studies and clinical trials and costs related thereto; uncertainties inherent in the results of preliminary data, pre-clinical studies and earlier-stage clinical trials being predictive of the results of early or later-stage clinical trials; the timing, scope and likelihood of regulatory filings and approvals, including regulatory approval of our product candidates; competition; our ability to secure new (and retain existing) grant funding; our ability to grow and manage growth, maintain relationships with suppliers and retain our management and key employees; changes in applicable laws or regulations; the possibility that the we may be adversely affected by other economic, business or competitive factors, including ongoing economic uncertainty; our estimates of expenses and profitability; the evolution of the markets in which we compete; our ability to implement our strategic initiatives and continue to innovate our existing products; our ability to defend our intellectual property; impacts of ongoing global and regional conflicts; the impact of the COVID-19 pandemic on our business, supply chain and labor force; and the risks and uncertainties described more fully in the “Risk Factors” section of our annual and quarterly reports filed with the Securities & Exchange Commission and are available at www.sec.gov. These risks are not exhaustive and we face both known and unknown risks. You should not rely on these forward-looking statements as predictions of future events. The events and circumstances reflected in our forward-looking statements may not be achieved or occur, and actual results could differ materially from those projected in the forward-looking statements. Moreover, we operate in a dynamic industry and economy. New risk factors and uncertainties may emerge from time to time, and it is not possible for management to predict all risk factors and uncertainties that we may face. Except as required by applicable law, we do not plan to publicly update or revise any forward-looking statements contained herein, whether as a result of any new information, future events, changed circumstances or otherwise.
| Contact Information: Cognition Therapeutics, Inc. info@cogrx.com | Casey McDonald (media) Tiberend Strategic Advisors, Inc. cmcdonald@tiberend.com | Mike Moyer (investors) LifeSci Advisors mmoyer@lifesciadvisors.com |
FAQ
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