CervoMed Announces Presentation at AAIC 2024 on Plasma Biomarker Data That Are Consistent with Neflamapimod Impacting the Underlying Disease Process in Patients with Dementia with Lewy bodies (DLB)

Rhea-AI Summary

CervoMed Inc. (NASDAQ: CRVO) presented plasma biomarker data from the AscenD-LB Phase 2a trial of neflamapimod in patients with dementia with Lewy bodies (DLB) at the Alzheimer's Association International Conference® 2024. Key findings include:

1. Baseline plasma glial fibrillary acidic protein (GFAP) levels correlated with dementia severity in DLB patients.

2. Neflamapimod treatment significantly reduced plasma GFAP levels in early-stage DLB patients without Alzheimer's disease co-pathology.

3. In early-stage DLB patients, GFAP reduction was associated with improved clinical outcomes.

These results suggest neflamapimod's potential to address the underlying disease process in early-stage DLB. CervoMed's ongoing RewinD-LB Phase 2b trial is optimized based on these findings, with topline data expected in December 2024.

Positive

• Neflamapimod treatment led to significant reduction in plasma GFAP levels compared to placebo in early-stage DLB patients
• Reduction in GFAP levels was associated with improvement in clinical outcomes (CDR-SB scores) in early-stage DLB patients
• Results suggest neflamapimod's potential to address the underlying disease process in early-stage DLB
• RewinD-LB Phase 2b trial is fully enrolled and optimized based on AscenD-LB Phase 2a findings
• Topline data from RewinD-LB Phase 2b trial expected in December 2024

Negative

• No significant reduction in GFAP levels observed in advanced DLB patients with AD-related co-pathology

Insights

Medical Research Analyst

As a Medical Research Analyst, I find the presentation of plasma biomarker data from the AscenD-LB Phase 2a trial of neflamapimod in patients with dementia with Lewy bodies (DLB) to be highly significant. The correlation between plasma glial fibrillary acidic protein (GFAP) levels and dementia severity, as measured by the Clinical Dementia Rating Sum of Boxes (CDR-SB), is a important finding. This suggests that GFAP could serve as a valuable biomarker for DLB progression.

The study's results indicating that neflamapimod treatment led to a significant reduction in plasma GFAP levels compared to placebo, particularly in early-stage DLB patients, is promising. The mean 10.6 pg/mL reduction in GFAP levels with neflamapimod treatment versus a 14.1 pg/mL increase in the placebo group (p=0.04) in early-stage DLB patients is especially noteworthy. This suggests that neflamapimod may have the potential to slow or even reverse some aspects of disease progression in DLB.

Furthermore, the correlation between GFAP reduction and improvement in CDR-SB scores in neflamapimod-treated patients (r=0.54, p=0.04) provides additional evidence of the drug's potential efficacy. This link between a measurable biomarker and clinical outcomes is important for demonstrating the drug's impact on the underlying disease process.

The data from the Mayo Clinic and the European Dementia with Lewy Bodies consortium further support the use of plasma GFAP as a biomarker for DLB. The elevation of GFAP in prodromal DLB patients and its association with cognitive decline rate, independent of amyloid status, strengthen its potential as a DLB-specific biomarker.

These findings collectively suggest that neflamapimod could be a promising treatment for DLB, particularly in its early stages. The ongoing RewinD-LB Phase 2b trial, optimized based on these insights, will be important in confirming these results and potentially paving the way for a new treatment option in this challenging neurodegenerative disorder.

Neuroscience Expert

The presentation of plasma biomarker data from the AscenD-LB Phase 2a trial offers intriguing insights into the potential of neflamapimod as a treatment for dementia with Lewy bodies (DLB). As a Neuroscience Expert, I'm particularly interested in the role of glial fibrillary acidic protein (GFAP) as a biomarker and its implications for understanding DLB pathology.

The strong correlation between baseline plasma GFAP levels and CDR-SB scores suggests that GFAP could be a reliable indicator of disease severity in DLB. This is significant because it provides a quantifiable measure that could be used to track disease progression and treatment efficacy.

The differential effects of neflamapimod on GFAP levels in early-stage versus advanced DLB patients are noteworthy. In early-stage patients, the drug led to a mean reduction of 10.6 pg/mL in GFAP levels, compared to an increase in the placebo group. This suggests that neflamapimod may be most effective in the early stages of the disease, potentially slowing or halting progression.

The association between GFAP reduction and improvement in CDR-SB scores in neflamapimod-treated patients is particularly exciting. This link between a molecular marker and clinical outcomes provides strong evidence that the drug is affecting the underlying disease process, not just symptoms.

The data from the Mayo Clinic showing elevated GFAP levels in prodromal DLB patients, even before significant cortical atrophy, is fascinating. It suggests that GFAP elevation may reflect early cholinergic degeneration in the basal forebrain, a key driver of DLB progression. This aligns with the European Dementia with Lewy Bodies consortium data showing GFAP's association with cognitive decline rate, independent of amyloid status.

These findings collectively suggest that GFAP could be a valuable biomarker for early diagnosis and monitoring of DLB and that neflamapimod's effects on GFAP levels may translate to meaningful clinical benefits. The upcoming results from the RewinD-LB Phase 2b trial will be important in confirming these promising early findings and potentially revolutionizing our approach to treating DLB.

- Baseline data from the AscenD-LB Phase 2a trial in DLB demonstrated that plasma glial fibrillary acidic protein (GFAP) was highly correlated to scores on the CDR-SB; plasma GFAP shown to increase with neurodegenerative progression in DLB –

- AscenD-LB Phase 2a results demonstrated neflamapimod treatment led to significant reduction compared to placebo in plasma GFAP levels in patients with DLB and the effects of neflamapimod on plasma GFAP were associated with improvement in CDR-SB -

BOSTON, July 29, 2024 (GLOBE NEWSWIRE) -- CervoMed Inc. (NASDAQ: CRVO), a clinical stage company focused on developing treatments for age-related neurologic disorders, today announced that plasma biomarker data from the AscenD-LB Phase 2a trial of neflamapimod in patients with dementia with Lewy bodies (DLB), was featured in a poster presentation at the Alzheimer's Association International Conference^® (AAIC), being held in Philadelphia from July 28-August 1, 2024.

“Recent developments in the field support the use of plasma GFAP to evaluate the therapeutic effects on DLB-specific disease processes, and baseline data from AscenD-LB, our Phase 2a trial, further validate the utility of this biomarker,” said John Alam, MD, Chief Executive Officer of CervoMed. “We observed a clear association between plasma GFAP and dementia severity in patients with DLB. Additionally, growing data highlights the effects of neflamapimod on GFAP—particularly its association with the positive effects on clinical outcomes —and underscore the potential to address the underlying disease process in early-stage DLB. With these critical learnings from the AscenD-LB Phase 2a trial, we believe our fully enrolled RewinD-LB Phase 2b trial is optimized for success and we remain on track to report topline data in December 2024.”

The ePoster (91713) is accessible on the conference portal, and additional details are provided below. A PDF copy of the GFAP poster presentation will be available on the “Presentations and Publications” section of the CervoMed website.

• Title: Neflamapimod treatment reduces plasma glial fibrillary acidic protein GFAP levels in patients with dementia with Lewy bodies (DLB) who do not have co-existing AD co-pathology
• Authors: John Alam, Marleen Koel-Simmelink, Jennifer Conway, Inge Verberk, Charlotte Teunissen; CervoMed Inc (JA and JC) and Amsterdam Medical Center (MKS, IV, CT)

Key Takeaways from the presentation: The effects of neflamapimod on plasma GFAP were evaluated in both the overall and early-stage DLB patient population, and the treatment effects of GFAP correlated to clinical outcomes:

• Baseline (BL) plasma GFAP level was highly correlated to the baseline Clinical Dementia Rating Sum of Boxes (CDR-SB) score and was significantly higher in patients with AD Co-Pathology (BL ptau181 ≥ 2.2 pg/mL) compared to patients without AD co-pathology (baseline ptau181 < 2.2 pg/mL). Plasma GFAP was significantly elevated in both groups compared to levels in healthy controls in the literature.
• In early-stage DLB patients (i.e., patients with pre-treatment plasma ptau181 below the cutoff for AD-related co-pathology), there was a mean 14.1 pg/mL increase in the placebo treatment group (N=13) vs. mean 10.6 pg/mL reduction with neflamapimod treatment (N=15; p=0.04 for the difference). In patients with advanced DLB (i.e., patients with pre-treatment plasma ptau181 above the cutoff for AD-related co-pathology), there was a mean 6.0 pg/mL decrease in the placebo group (N=14) vs. mean 14.0 pg/mL reduction with neflamapimod treatment (N=15; the difference was not significant).
• In the early-stage DLB patient population, in participants treated with neflamapimod there was a significant correlation (r=0.54, p=0.04) between the effects of GFAP and clinical outcomes assessed by change from baseline to week 16 in CDR-SB, with increased GFAP being associated with worsening CDR-SB, while reduction in GFAP was associated with improvement on CDR-SB. The correlation was not seen in placebo-recipients (r=0.31, p=NS).  
  

Recent developments in the field support the use of plasma GFAP as a biomarker of the underlying disease process in DLB:

• Data from the Mayo Clinic (Diaz-Galvan et al, 2024) show that in patients with prodromal DLB plasma GFAP is elevated relative to healthy controls, while plasma neurofilament light chain and plasma ptau181 are not. As patients at this stage have cholinergic degeneration in the basal forebrain without significant cortical atrophy (Kantarci et al, 2022), GFAP elevation in this context appears to reflect the disease in the basal forebrain cholinergic system that is the primary driver of disease expression and progression in early-stage DLB (Okkels et al, 2024).
  
• Data from the European Dementia with Lewy Bodies consortium (Bolsewig et al, 2024), show that in patients with DLB, plasma GFAP is associated with rate of cognitive decline, but not with CSF amyloid status, suggesting that GFAP elevation has potential to evaluate DLB-specific disease processes.
  

About the RewinD-LB Phase 2b Study in Dementia with Lewy Bodies
CervoMed’s ongoing Phase 2b study, RewinD-LB, is a randomized, 16-week, double-blind, placebo-controlled clinical trial evaluating oral neflamapimod (40mg TID) in up to 160 patients with very mild or mild dementia due to DLB. Patients completing the 16-week placebo-controlled study period will be able to continue in the study while receiving open label neflamapimod treatment for an additional 32 weeks. Patients with Alzheimer’s Disease-related co-pathology, assessed by a blood biomarker (plasma ptau181), will be excluded. The primary endpoint in the study is change in the Clinical Dementia Rating Sum of Boxes, and secondary endpoints include the Timed Up and Go test, a cognitive test battery, and the Clinician’s Global Impression of Change. The RewinD-LB study is funded by a $21.0 million grant from the National Institutes of Health’s National Institute on Aging, which will be disbursed over the course of the study as costs are incurred. The study includes 43 sites (32 in the United States, eight in the United Kingdom, and three in the Netherlands). More information on the RewinD-LB study, is available at clinicaltrials.gov. The study completed enrollment in June 2024 and topline primary efficacy results are expected in December 2024.

Forward-Looking Statements
This press release includes express and implied forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, regarding the intentions, plans, beliefs, expectations or forecasts for the future of CervoMed Inc. (the Company), including, but not limited to, the therapeutic potential of neflamapimod, the anticipated timing and achievement of clinical and development milestones, including the completion and achievement of primary endpoints of the RewinD-LB Phase 2b clinical trial and the Company’s announcement of topline data therefrom, any other expected or implied benefits or results, including that any initial clinical results observed with respect to neflamapimod in the RewinD-LB Trial will be replicated in later trials, and the Company’s clinical development plans. Terms such as “believes,” “estimates,” “anticipates,” “expects,” “plans,” “aims,” “seeks,” “intends,” “may,” “might,” “could,” “might,” “will,” “should,” “approximately,” “potential,” “target,” “project,” “contemplate,” “predict,” “forecast,” “continue,” or other words that convey uncertainty of future events or outcomes (including the negative of these terms) may identify these forward-looking statements. Although there is believed to be reasonable basis for each forward-looking statement contained herein, forward-looking statements by their nature involve risks and uncertainties, known and unknown, many of which are beyond the Company’s control and, as a result, actual results could differ materially from those expressed or implied in any forward-looking statement. Particular risks and uncertainties include, among other things, those related to: the Company’s available cash resources and the availability of additional funds on acceptable terms; the results of the Company’s clinical trials, including RewinD-LB; the likelihood and timing of any regulatory approval of neflamapimod or the nature of any feedback the Company may receive from the U.S. Food and Drug Administration; the ability to implement business plans, forecasts, and other expectations in the future; general economic, political, business, industry, and market conditions, inflationary pressures, and geopolitical conflicts; and the other factors discussed under the heading “Risk Factors” in the Company’s Annual Report on Form 10-K for the year ended December 31, 2023 filed with the U.S. Securities and Exchange Commission (SEC) on March 29, 2024, and other filings that the Company may file from time to time with the SEC. Any forward-looking statements in this press release speak only as of the date hereof (or such earlier date as may be identified). The Company does not undertake any obligation to update such forward-looking statements to reflect events or circumstances after the date of this press release, except to the extent required by law.

References:

Bolsewig, K., A. van Unnik, E. R. Blujdea, et al, and European-Dementia With Lewy Bodies (2024). "Association of Plasma Amyloid, P-Tau, GFAP, and NfL With CSF, Clinical, and Cognitive Features in Patients With Dementia With Lewy Bodies." Neurology (2024) 102): e209418

Diaz-Galvan, P., S. A. Przybelski, A. Algeciras-Schimnich, et al. "Plasma biomarkers of Alzheimer's disease in the continuum of dementia with Lewy bodies." Alzheimers Dement (2024) 20:2485-2496

Kantarci, K., Z. Nedelska, Q. Chen, M. et al. "Longitudinal atrophy in prodromal dementia with Lewy bodies points to cholinergic degeneration." Brain Communications (2022) 4:fcac013

Okkels, N., M. J. Grothe, J. P. Taylor, et al. "Cholinergic changes in Lewy body disease: implications for presentation, progression and subtypes." Brain (2024) 147:2308-2324.

Investor Contact:
PJ Kelleher
LifeSci Advisors
Investors@cervomed.com
617-430-7579

FAQ

What were the key findings of CervoMed's AscenD-LB Phase 2a trial for neflamapimod in DLB patients?

The key findings were: 1) Baseline plasma GFAP levels correlated with dementia severity, 2) Neflamapimod treatment significantly reduced plasma GFAP levels in early-stage DLB patients without AD co-pathology, and 3) GFAP reduction was associated with improved clinical outcomes in early-stage DLB patients.

When is CervoMed (CRVO) expected to report topline data from the RewinD-LB Phase 2b trial?

CervoMed (CRVO) is expected to report topline data from the RewinD-LB Phase 2b trial in December 2024.

How did neflamapimod affect plasma GFAP levels in early-stage DLB patients in the AscenD-LB trial?

In early-stage DLB patients without AD co-pathology, neflamapimod treatment led to a mean 10.6 pg/mL reduction in plasma GFAP levels, compared to a mean 14.1 pg/mL increase in the placebo group.

What is the significance of plasma GFAP as a biomarker in DLB according to recent studies?

Recent studies support the use of plasma GFAP as a biomarker of the underlying disease process in DLB. It is elevated in prodromal DLB patients and associated with cognitive decline, potentially reflecting disease progression in the basal forebrain cholinergic system.