NASDAQ: CRVO

We believe we are a leader in the industry in developing a treatment for DLB, a disease with no approved therapies in the US or European Union, despite being the second most common progressive dementia. Neflamapimod is the only clinical drug candidate that, to our knowledge, has shown statistically significant improvements on clinical endpoints and a biomarker of neurodegeneration in both a Phase 2a and Phase 2b clinical trial. Differentiating our approach from potential competitors, we believe we are also the only company specifically targeting the treatment of DLB patients without AD co-pathology. While DLB patients with AD co-pathology generally have significant, irreversible neuronal loss, DLB without AD co-pathology is primarily a disease of functional deficits of synapses that we believe is more treatable. We believe if neflamapimod is given in the early stages of certain degenerative diseases of the brain like DLB without AD co-pathology, it may reverse synaptic dysfunction, improve neuron health and function, and slow further progression by delaying synaptic dysfunction and neuronal death. We believe this approach enhances the alignment of our development path with neflamapimod’s mechanism of action, reduces the heterogeneity of our target patient population, and provides the opportunity to demonstrate heightened clinical effect in shorter duration trials.

Our Pipeline

Set forth below is a table presenting our clinical pipeline:

Anticipated Milestones

Set forth below are our anticipated clinical development milestones during the next 12 months, subject to, among other things, available funding:

Anticipated Milestones

2Q26
Complete enrollment in Phase 2a clinical trial in nfvPPA

Mid-2026
Complete enrollment in Phase 2a RESTORE Trial in RAS

Mid-2026

Initial Phase 2a biomarker data in nfvPPA

2H26

Topline Phase 2a clinical data in RAS

2H26
Initial Phase 2a clinical data in nfvPPA

2H26

Initiation of planned Phase 3 trial in DLB

YE26

First patient dosed with neflamapimod in EXPERTS-ALS trial in ALS

1H27
Topline Phase 2a clinical and biomarker data in nfvPPA

Our Strategy

Our mission is to develop and commercialize innovative medicines that change the course of the disease in patients who suffer from age-related brain disorders.

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The key elements of our strategy are:

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Capitalize on neflamapimod’s unique properties and our differentiated approach to progress the development of neflamapimod for the treatment of age-related brain disorders with high unmet medical need. Our approach to treating neurodegenerative disorders is highly differentiated, focusing on reducing the impact of neuroinflammation in patients afflicted by diseases primarily of synaptic dysfunction who do not have significant, irreversible neuronal loss. We believe, if approved, the nature of neflamapimod’s mechanism of action, combined with the nature and prevalence of these diseases, could significantly improve patients’ quality of life and ability to function, reduce caregiver burden and systemic health care costs, and present a significant commercial opportunity in one or more indications.

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Advance clinical development of neflamapimod as a potential first-in-class treatment for DLB without AD co-pathology, including securing sufficient funding and initiating our planned Phase 3 trial in the second half of 2026, subject to available funding. During 2025, we announced 16-week and 32-week results from the Extension Phase of our RewinD-LB Trial in which neflamapimod demonstrated significant, durable effects on the trial’s primary endpoint (CDR-SB), a key biomarker of neurodegeneration in DLB (plasma GFAP), and secondary endpoints including ADCS-CGIC when target blood concentrations were achieved. These results were even more pronounced in the patient population to be enrolled in our planned Phase 3 trial, which will use more restrictive criteria to exclude patients with AD co-pathology. In November 2025, we announced alignment with the FDA on key aspects of our planned Phase 3 clinical trial of neflamapimod, and we plan to initiate that trial in the second half of 2026, subject to available funding.

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Advance clinical development of neflamapimod for other disease indications. Beyond DLB, neflamapimod’s mechanism of action provides opportunities for advancement in a range of additional neurologic disorders. During 2025, we initiated Phase 2a clinical trials in nfvPPA and RAS, from which we expect initial biomarker results and topline clinical results in mid-2026 and the second half of 2026, respectively, subject to available funding to continue operations. In addition, in February 2026, we announced that neflamapimod has been selected for inclusion in EXPERTS-ALS, a platform funded by the UK government and leading charities to facilitate rapid testing of potential treatments for ALS to identify promising drug candidates and potentially accelerate their path to regulatory approval. We believe neflamapimod's inclusion in the EXPERTS-ALS platform serves to further validate its mechanism of action and potential in neurodegenerative diseases. We also believe there is strong scientific basis for evaluating neflamapimod in these indications and that differences in the treatment setting and disease processes involved provide development opportunities that are both differentiated from and complementary to our DLB program.

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Explore strategic collaborations to maximize neflamapimod’s potential value, support its development, and expedite commercialization, if approved. We believe that strategic collaborations may provide opportunities to maximize neflamapimod’s potential value for our stockholders and we intend to explore potential strategic collaborations in parallel with our planned clinical development program for neflamapimod, which may include region- or indication-specific partnerships. In addition, if neflamapimod receives regulatory approval, we intend to be prepared to commercialize as soon as practicable in the market(s) where it is first approved, if at all, which we expect would be in North America and/or Europe. In the future, we may seek partners to seek approval and commercialize our products in other regions.

Neflamapimod in Dementia with Lewy Bodies

DLB Background

Significant Disease Burden & High Unmet Medical Need

DLB is the second most common progressive dementia after AD, representing approximately 10-20% of all dementia cases and affecting millions worldwide. The Lewy Body Dementia Association suggest there are more than 700,000 individuals with DLB in each of the US and the European Union, and neuropathology studies suggest true incidence may be significantly higher due to underdiagnosis in current practice. Despite this prevalence, there are currently no approved treatments specifically for DLB in the US or the European Union.

The disease is characterized by progressive dementia and fluctuating cognition (particularly deficits in attention), visual hallucination, motor dysfunction (disturbances in gait and balance), and sleep disturbances. While DLB afflicts fewer total patients than AD, it is arguably a more debilitating disease. With respect to life expectancy, in a large cohort of DLB and AD cases (251 DLB, 222 AD), after controlling for age at diagnosis, comorbidity, and antipsychotic prescribing, the average survival for DLB patients (<4 years) was nearly 50% was shorter than the average survival for AD patients (~7 years). The average time progression to severe dementia was also shorter by nearly two years in DLB and, even in the mild-to-moderate stages, the disease burden with respect to quality of life and caregiver burden is greater in DLB than in AD, with deficits occurring in both cognitive and motor function. For example, in a large prospective study, mild dementia patients with DLB were admitted to a nursing home after only a median of 1.8 years from presentation and diagnosis, nearly two years shorter than the 3.7-year median in the AD group. Patients with DLB are also more frequently admitted to general hospitals, are more prone to falls, and utilize inpatient care to a substantially higher degree than patients with AD and the general elderly population.

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In sum, DLB often progresses quickly and severely impacts not only the daily lives of patients suffering from the disease but that of their caregivers. There are currently no approved treatments available for DLB in the US or European Union, so management of DLB focuses on transient relief of symptoms, including its cognitive manifestations and motor components via cholinesterase inhibitors and dopaminergic medications, respectively. Even with these treatments, the cognitive and functional impairments progress rapidly, caregiver burden remains high, and new options are needed for these patients. No prior approaches have been shown to clinically slow neuronal loss or prevent cognitive decline in DLB, and neflamapimod is one of only a handful of drug candidates that have demonstrated positive effects in a Phase 2 clinical trial.

Neflamapimod’s Mechanism of Action & Scientific Rationale

Our approach is based on an understanding of the mechanism by which neuroinflammation leads to the initiation and establishment of the neurodegenerative process in DLB. The process of neurodegeneration starts with dysfunction of synapses. Treating synaptic dysfunction has emerged as a major therapeutic objective to address progression of neurodegenerative diseases, particularly in the early stages prior to the onset of significant cell death. Importantly, in animal models, while neurodegeneration is irreversible, synaptic dysfunction has been observed to be reversible. In addition, even in animal models of rapidly progressive neurodegenerative disorders, interventions that reverse synaptic dysfunction both improve function and “arrest” the neurodegenerative process. Thus, therapeutic interventions that target synaptic dysfunction have the potential to both reverse and slow disease progression in the early stages of neurodegenerative dementias.

The basal forebrain – specifically, nerve cells producing the neurotransmitter acetylcholine known as cholinergic neurons – plays critical roles in controlling and optimizing a wide range of cognitive, motor, and visual tasks. Synaptic dysfunction in the BFC system is the primary pathogenic driver of disease expression and progression in DLB. In collaborative work we conducted with the New York University Langone Medical Center, and later published in the journal Nature Communications, we demonstrated that neflamapimod targets the specific molecular mechanisms underlying BFC dysfunction and degeneration, and may successfully reverse disease progression in the early stages of BFC dysfunction.

Neflamapimod was hypothesized to reduce Rab5 protein activity – a key therapeutic target in this pathogenic model for cholinergic degeneration in DLB – because of scientific literature showing that the immediate target of neflamapimod, p38α, is the major activator of Rab5. The protein Rab5 is a master regulator of endocytosis and endosomal trafficking. As shown in the figure below, cholinergic degeneration is believed to result from inflammation and various aggregated proteins that lead to aberrant activation of Rab5. This Rab5 activation leads to impaired retrograde axonal transport and a block in NGF signaling from the synapses at the ends of nerve fibers (or “axons”) back to cell body of cholinergic neurons in the basal forebrain. As NGF provides support for neuronal health, the resulting loss is then believed to lead to dysfunction, and, eventually, degeneration of cholinergic neurons – which, as noted above, plays a critical role in DLB disease expression – as these neurons’ very long fibers make them particularly vulnerable to this pathogenic process.

Molecular Mechanisms Underlying Cholinergic Neurodegeneration in DLB and Point of Intervention for Neflamapimod

Our Differentiated Approach: DLB Without AD Co-Pathology

Historically, a major challenge in developing effective drug treatments for chronic neurodegenerative diseases has been an inability to demonstrate clinically meaningful improvement in Phase 2 clinical trials of less than six-months in duration. Instead, due to a variety of factors including the nature of many such diseases, particularly AD, demonstrating effectiveness often depends on clinical trial durations of 12-18 months that enroll 1,000 or more participants. Further, prior Phase 2 clinical trial data – often utilizing a different primary endpoint than will be used in Phase 3, such as an indicative biomarker – may not provide as meaningful a predictor of these drug candidates' potential for a successful clinical outcome in Phase 3. Effectively requiring Phase 3 trials to see a clinical effect, late-stage clinical development in these indications is often associated with significant costs, time horizons, and clinical risk. Some incorrectly associate these same challenges with DLB drug development, in part due to the prominence of AD co-pathology in DLB patients.

In contrast, our DLB development program for neflamapimod is focused on the treatment of DLB without AD co-pathology, which we sometimes refer to as “pure DLB.” These patients comprise approximately 50% of all DLB patients, with hundreds of thousands of patients diagnosed in the US and millions worldwide. While DLB patients with AD co-pathology have significant, irreversible neuronal loss in the hippocampus, pure DLB is primarily a disease of reversible synaptic dysfunction in the BFC system. Relative to patients with AD co-pathology, these patients have limited neurodegeneration and neuronal loss in the cortical regions of the brain, particularly in the hippocampus. As those neurons are still alive, with successful pharmacological treatment, they can be rescued and the disease process reversed. Importantly, DLB remains a rapidly progressing disease, even in the absence of AD co-pathology, with families and caregivers often reporting seeing patients progress on a weekly or even daily basis.

The core of our differentiated approach sits at the intersection of these two features of pure DLB. The combination of less extensive neuronal loss and fixed clinical deficit, on the one hand, and rapid progression, on the other, provides the opportunity to demonstrate meaningful clinical effects compared to control in as soon as 16 weeks – as we have in our two Phase 2 trials described in more detail below – rather than the 52 weeks or more that is often required in AD trials. This approach was also central to our November 2025 alignment with the FDA on key aspects of our proposed Phase 3 clinical trial of neflamapimod for the treatment of DLB. With the FDA’s feedback, and subject to available funding, we plan to initiate a single Phase 3 clinical trial of 32 weeks duration in approximately 300 patients with DLB without AD co-pathology, utilizing the same primary endpoint (mean change in CDR-SB) as our recently completed Phase 2b trial.

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We believe that, in contrast to many late-stage trials in other neurodegenerative diseases like AD, this consistency in primary endpoint from Phase 2b has the potential to increase our probability of success in Phase 3, while the ability to demonstrate a clinically meaningful effect with fewer patients and on a shorter timeline allows us to execute towards that outcome with more capital efficiency.

AscenD-LB Trial: Our Phase 2a Trial in Dementia with Lewy Bodies

The AscenD-LB Trial was an exploratory, Phase 2a clinical trial designed to evaluate the effects of neflamapimod against a range of clinical endpoints. A total of 91 participants were enrolled between October 2019 and March 2020 and randomized to receive neflamapimod capsules at one of two doses (40mg6 BID or 40mg TID) or matching placebo capsules (randomized 1:1) for 16 weeks. In the primary analysis of the AscenD-LB Trial, which included all participants enrolled and evaluated for treatment effects, neflamapimod demonstrated improvement compared to placebo in dementia severity (assessed by CDR-SB, p=0.023 vs. placebo) and functional mobility (as assessed by the TUG test, p=0.044 vs. placebo). In additional analyses, at the higher dose (40mg TID), improvement on NTB was evident as compared to placebo (p=0.049). Encouraging positive trends on the ten-item Neuropsychiatric Inventory were also seen, particularly with respect to visual hallucinations. This primary analysis of the AscenD-LB Trial data showing neflamapimod significantly improved dementia severity and motor function was published in Nature Communications in September 2022.

With progress in laboratory testing techniques for blood biomarkers of neurodegeneration during and shortly following completion of the AscenD-LB Trial, additional pre-specified analyses of the AscenD-LB Trial data were conducted to evaluate the results specifically in DLB patients without AD co-pathology, as assessed by plasma ptau181. As shown in the table below, participants without evidence of AD co-pathology had an average higher treatment response (evaluated by Cohen’s d effect size) compared to the average response in the overall trial population, and demonstrated significant improvement in CDR-SB, cognitive tests of attention, the TUG test, and in a test of recognition memory (International Shopping List Test recognition index), with Cohen’s d treatment effect sizes indicating, in each case, clinical effects that are moderate-to-large in magnitude (> 0.7). By comparison, cholinesterase inhibitors – the current standard of care in DLB – have Cohen’s d effect size of approximately 0.3 in the treatment of both DLB and AD. Further, not only was the effect size with 40mg TID neflamapimod treatment comparatively larger, the effect demonstrated was on top of participant’s background therapies which, in many cases, included cholinesterase inhibitors.

RewinD-LB Trial: Our Phase 2b Trial in Dementia with Lewy Bodies

Trial Background and Design

Based on our successes and advances in Phase 2a, we designed our Phase 2b RewinD-LB Trial and, in January 2023, we were awarded a $21.0 million grant from the NIA, and an additional $0.3 million was awarded in August 2024, to fund the majority of the trial’s costs. The trial, subsequently initiated in mid-2023, evaluated neflamapimod in 159 participants with DLB and incorporated in its design several important things we learned from the AscenD-LB Trial and our other clinical evaluations of neflamapimod:

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Evaluating only a 40mg TID dosing regimen, as earlier clinical trials in DLB and AD demonstrated that achieving target plasma drug concentrations (which 40mg BID did not do in Phase 2a) was critical to maximizing neflamapimod’s effectiveness to date;

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Selecting CDR-SB, increasingly viewed as the gold standard for clinical evaluation of early AD and arguably even more well-suited to DLB’s symptomology, as it can detect effects on both cognitive and motor function, as the trial’s primary endpoint; and

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Partially enriching the trial’s patient population by excluding certain patients with AD co-pathology, as assessed by screening levels of plasma ptau181, a blood biomarker of AD co-pathology.

The RewinD-LB Trial included two distinct parts. The Randomized Phase was a double-blind, placebo-controlled evaluation of neflamapimod administered orally, 40mg TID, randomized with placebo on a one-to-one basis, with a primary analysis after 16 weeks of treatment. Each treatment group included approximately 80 participants diagnosed with DLB by consensus criteria (global CDR = 0.5 or 1.0). To enrich for patients without AD co-pathology, patients with significantly elevated plasma ptau181 at screening (≥ 27.2 pg/ml) were excluded. The second phase of the trial was a 32-week open-label treatment Extension Phase for participants completing the Randomized Phase. The failure of Batch A to achieve target drug concentrations and the pre-planned introduction of Batch B (which did) allowed us to amend the trial’s statistical analysis plan in February 2025 – prior to our analysis and announcement of 16-week Extension Phase results in March 2025 – to include a pre-specified analysis of Batch B versus Batch A after both 16- and 32-weeks of treatment during the Extension Phase. Further, although the Extension Phase was open-label, both participants and site personnel were unaware of which batch they were receiving, allowing a controlled comparison of an effective batch of neflamapimod (Batch B, which served as the active arm) against an ineffective batch (Batch A, which served as a control).

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The primary objective of the trial was to demonstrate that neflamapimod, compared with placebo or control, improved dementia severity, as assessed by mean change from baseline to Week 16 in CDR-SB. CDR-SB is designed to assess both cognition and function, and is obtained by clinicians rating the severity of symptoms across six domains – memory, orientation, judgment & problem solving, community affairs, home & hobbies, and personal care – after a semi-structured interview with the patient and a reliable informant (e.g., family member) on a 0–3 scale for each domain (total range 0-18, with a higher score indicating worse dementia). Secondary objectives included further evaluation of the safety and tolerability of neflamapimod and treatment effects on (1) global rating of treatment effect, assessed by the ADCS-CGIC, (2) motor function, as assessed by the TUG test, and (3) cognition, assessed by a DLB-specific cognitive test battery. Tertiary endpoints examined whether neflamapimod affects neuropsychiatric outcomes as assessed by the NPI-12, effect on fluctuations in cognition as assessed by the Dementia Cognitive Fluctuations Scale, impact on resting-state EEG (as well as alpha-reactivity evaluated by EEG) and in a sub-set of participants, basal forebrain atrophy assessed by structural MRI.

Randomized Phase Results

In December 2024, we announced topline results from the Randomized Phase of the RewinD-LB Trial. In the Randomized Phase, during which all participants received Batch A, no significant differences were observed between the neflamapimod and placebo treatment groups with respect to CDR-SB or any of the trial's secondary endpoint. However, average trough plasma drug concentrations with Batch A during the Randomized Phase were more than 20% lower than our target concentration level. As described further below under Alignment with FDA on Planned Phase 3 Trial – Pre-Phase 3 Manufacturing Improvements, we subsequently determined that the reduction was caused by an unknown, latent property of neflamapimod DS. We are implementing a manufacturing improvement that will address this issue ahead of our planned Phase 3 trial and going forward. However, particularly given the importance of achieving target drug concentrations to maximizing neflamapimod’s effectiveness described above, we believe this issue was a primary driver of our failure to see during the Randomized Phase the same positive results with saw with Batch B during the Extension Phase.

Extension Phase Results

Of the 159 participants randomized in the Randomized Phase, 152 completed the Randomized Phase and 149 entered the neflamapimod only Extension Phase. The chart below shows when the pre-planned introduction of Batch B to resupply the Extension Phase occurred for those 149 patients:

In March 2025, we announced that, in the first 16 weeks of the Extension Phase, treatment with Batch B – which, unlike Batch A, achieved target drug concentrations – demonstrated statistically significant improvement on CDR-SB, the trial’s primary outcome measure, and ADCS-CGIC, a key secondary outcome measure, in each case, compared to Batch A. In July 2025, we reported additional data from the Extension Phase showing significant, durable treatment effects out to 32 weeks, including a significant risk reduction in clinically significant worsening (≥ 1.5-point increase in CDR-SB) with Batch B neflamapimod treatment compared to control.

The final results of the RewinD-LB Trial were presented in December 2025 at the Clinical Trials in Alzheimer’s Disease (CTAD) conference. The key results included:

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Through the first 16 weeks of the Extension Phase, the change in CDR-SB was significantly lower in the Batch B group compared to the Batch A group (difference = -0.57, 95% CI: -0.98, -0.16; p=0.007).

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On ADCS-CGIC, which was administered at Week 8 of the Extension Phase, administration of Batch B led to an improved score (4.02 vs. 4.42 Batch A, p<0.05). In addition, in a within-participant analysis, mean ADCS-CGIC score was reduced in participants administered Batch B compared to placebo (4.00 vs. 4.44, p<0.05).

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Over the full course of the study, the risk of clinical progression (defined as ≥ 1.5 point increase in CDR-SB score) was reduced by over 50% with Batch B treatment, both vs. Batch A (hazard ratio=0.46 95%CI 0.30-0.69) and vs. placebo (hazard ratio=0.49, 95%CI 0.30-0.80) over 32 weeks of treatment.

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Participants treated with Batch B for all 32 weeks of the Extension Phase demonstrated a statistically significant reduction from baseline in plasma GFAP levels, a validated biomarker of neurodegenerative disease activity, with a median change of -16.0 pg/mL (Interquartile range -35, 6.7) in all participants (N=107; p<0.001 for change from baseline; p=0.014 vs. Batch A).

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Additional data from the Extension Phase presented at the 19th International Conference on Alzheimer’s and Parkinson’s Disease and Related Neurologic Disorders in April 2025 included that Batch B demonstrated improvements on endpoints measuring cognitive fluctuations and working memory.

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Both Batch B and Batch A demonstrated comparable tolerability profiles and no new safety signals were identified during the Extension Phase.

Alignment with FDA on Planned Phase 3 Trial

In November 2025, we announced alignment with the FDA on key aspects of our planned Phase 3 clinical trial of neflamapimod for the treatment of DLB. Based on FDA feedback, we plan to initiate a single, global, randomized, double-blind, placebo-controlled Phase 3 clinical trial evaluating the efficacy and safety of neflamapimod in approximately 300 participants with DLB by consensus clinical criteria in the second half of 2026, subject to available funding. The trial will exclude patients who have historical evidence of AD co-pathology by brain imaging scan or cerebrospinal fluid sampling. In addition, the trial will be further enriched for participants who do not have AD co-pathology by excluding patients with plasma ptau181 ≥ 21.0 pg/mL at screening. Participants will be randomized 1:1 to receive either oral neflamapimod or placebo for 32 weeks, followed by a neflamapimod only extension for 48 weeks. Worsening of global cognition and function as measured by change CDR-SB – the same primary endpoint as in our RewinD-LB Trial – will be the primary endpoint for the planned Phase 3 trial. Secondary endpoints will include the percentage of participants who have a greater than 1.5-point increase in CDR-SB and other well-established measures of cognitive and motor function. The trial will also include assessments of key biomarkers of the neurodegenerative process, such as GFAP, to further support regulatory review and clinical interpretation. CervoMed expects feedback from other global regulators in the coming months and to announce additional details regarding the planned Phase 3 trial design in early 2026 following these interactions.

As we did between Phase 2a and Phase 2b, we will incorporate several important things we learned from the RewinD-LB Trial into the design of our planned Phase 3 trial, which we believe will further increase the trial’s probability of success.

Pre-Phase 3 Manufacturing Improvements

Despite the disparity in performance, Batch A and Batch B were manufactured using the same manufacturing process. While there was no evidence of chemical degradation in our customary release or stability testing prior to the trial's initiation, we conducted additional evaluations of Batch A and Batch B in late 2024 and early 2025 to determine the reason for Batch A's failure to achieve target plasma drug concentrations. Our investigations identified a previously undiscovered mixture of polymorphic forms of neflamapimod’s DS. These polymorphic forms have different physical chemistry properties, including solubility, potentially with a time-dependent change in relative amounts of the individual forms. The Batch A capsules were more than three years out from their manufacture date at the time of administration during the RewinD-LB Trial – much older than Batch B and the drug product utilized in our past clinical trials at their respective time of use. We believe this time-dependent change accounted for the reduced performance of Batch A in the RewinD-LB trial, as well as the difference in performance between the two batches despite using the same DS and DP manufacturing processes.

To mitigate the potential for this reduction in performance over time, we identified the most stable polymorphic form, as well as a controlled manufacturing process to reliably manufacture DS that contains only (or predominantly) this stable form. In March 2025, we announced bioavailability data from a Phase 1 trial evaluating this stable crystal form of neflamapimod manufactured using the new, controlled manufacturing process. Following our evaluation of the results, we selected 50mg TID of the stable crystal form of neflamapimod as the dose and dosing regimen for our planned Phase 3 study in patients with DLB. While the PK profiles of 40mg of Batch B and 40mg of the stable crystal form of neflamapimod are largely overlapping, the dose will be increased to 50mg with the intent of ensuring the dosing regimen achieves the plasma drug concentrations observed with Batch B.

Enhanced Patient Enrichment Strategy

At the time RewinD-LB Trial was initiated in mid-2023, 27.2 pg/ml was estimated to be the optimal ptau181 cutoff for excluding patients with AD co-pathology from the trial, based on the limited data set available at that time. However, pre-specified analyses of the Extension Phase data, conducted in March 2025 and presented at the Alzheimer’s Association International Conference in July 2025, indicated that lower cutoff points (e.g., 25.2 pg/mL, 23.0 pg/mL, 21.0 pg/mL) led to progressively greater treatment effect size for CDR-SB and ADSC-CGIC in the RewinD-LB Trial, with the greatest effect size at 21.0 pg/mL. This finding was confirmed in a large (N=1298), third-party validation study published in June 2025, indicating that a ptau181 cutoff of 21.0 pg/mL was the high sensitivity cutoff for identifying AD pathology in AD and non-AD dementia (including DLB) by CSF criteria. This means the RewinD-LB Trial was only partially enriched for patients without AD co-pathology, as patients with screening ptau181 between 21.0 pg/mL and 27.2 pg/mL were enrolled in the trial. Based on recent scientific literature, we estimate that between 60-65% of those enrolled in the RewinD-LB Trial using the 27.2 pg/mL cutoff were patients without AD co-pathology, while reducing that cutoff to 21 pg/mL would increase that enrichment rate to approximately 80-90% of the patients.

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Accordingly, our planned Phase 3 clinical trial in DLB will be further enriched for patients who do not have AD co-pathology by excluding patients with plasma ptau181 greater than 21.0 pg/mL at screening. In our pre-specified analysis of this cohort in the RewinD-LB Trial, effectively representing our target patient population in Phase 3, we observed even more pronounced clinical effects, including:

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In secondary analyses of data from the RewinD-LB Trial, for both change in CDR-SB and ADCS-CGIC, the magnitude of the effect was greater in the subset of patients without AD co-pathology defined by the lower 21.0 pg/mL screening ptau181 cutoff. Specifically, in a within-participant comparison to placebo among participants who received placebo during Randomized Phase and Batch B during the Extension Phase, Batch B treatment improved change in CDR-SB by 1.12 points (p=0.004 vs. placebo) and the ADCS-CGIC score by 0.82 points (p=0.004 vs. placebo).

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A 75% reduction in the risk of clinically meaningful progression (≥ 1.5-point increase in CDR-SB) over up to 32 weeks of treatment with Batch B treatment compared to placebo.

Other Ongoing DLB Trials

In August 2024, we initiated a Phase 2a trial in Strasbourg, France, to evaluate a twice daily regimen (80mg BID) of neflamapimod in 26 patients with DLB with MCI (MoCA score ≥ 18 during screening). Unlike our RewinD-LB Trial, the patient population in the Strasbourg trial was not enriched for patients without AD co-pathology. Rather, the primary objective of the trial is to obtain additional safety and PK data on a dosing regimen not previously evaluated in any of our clinical trials (80mg BID) that, among other things, may provide additional dosing flexibility in future trials. On an exploratory basis, we will also collect data on basal forebrain atrophy, as measured by MRI, and a broad range of clinical endpoints.

In the first quarter of 2025, all patients completed dosing in the trial and, based on the topline data, the primary objectives around safety and PK were achieved. Neflamapimod was well tolerated with no new safety signals being identified. The mean Ctrough, defined as 12-hour post last dose plasma drug concentrations, demonstrated a dose-proportionate increase. One participant discontinued early due to Grade 3 elevations in ALT and AST, but there was no observed increase in bilirubin levels, values normalized after treatment discontinuation, and concomitant medications known to affect liver enzymes were considered to have been a contributory factor. We plan to present clinical endpoint and brain MRI results from the trial at a future medical conference.

Neflamapimod’s Potential in Additional Indications

Frontotemporal Disorders // Primary Progressive Aphasia

FTDs are a category of neurodegenerative disorders characterized by progressive deterioration in behavior, personality, and language abilities, typically affecting individuals between the ages of 40 and 65 including an estimated tens of thousands of individuals in the US alone. Unlike AD, which primarily targets memory, FTD primarily affects the frontal and temporal lobes of the brain, leading to changes in social conduct, emotional regulation, and decision-making. There are several subtypes of FTD, including the behavioral variant FTD, the most common subtype (approximately half the patients with FTD) and PPA, each presenting with distinct symptom profiles. PPA, a subtype of FTD itself, has three main variants: nonfluent/agrammatic variant PPA, semantic variant PPA, and logopenic variant PPA, though the latter is not considered an FTD subtype. The prevalence of these PPA subtypes varies, with approximately 40% of PPA patients being nonfluent/agrammatic variant PPA, 40% being semantic variant PPA, and 20% being logopenic variant PPA. As the disease progresses, individuals with FTD may require increasing levels of care and support, with management focusing on alleviating symptoms and maximizing function.

The rationale for potentially evaluating neflamapimod as a treatment for FTD is based on the effects of p38α on axonal transport and tau pathologies, as well as atrophy of the BFC system being a driver of disease and the mechanisms that neflamapimod targets being operative in FTD. Additionally, when assessed by MRI, the volume of the basal forebrain is reduced, relative to age-matched healthy control, most prominently in patients who have “tauopathies” (i.e., patients at autopsy who have tau pathology, rather than TDP-43 pathology). Moreover, in March 2024, at the AD/PD 2024 scientific conference in Lisbon, Portugal, academic collaborators from University College London presented data that showed that p38 MAPK inhibitors generally, and neflamapimod specifically, enhanced axonal transport in a transgenic mouse model of FTD (rg4510 transgenic harboring P301L mutation). Based in part on these nonclinical results, in November 2024, the FDA granted neflamapimod Orphan Drug Designation for the treatment of frontotemporal dementia.

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To best align with the scientific rationale described above, we have chosen to evaluate neflamapimod in nfvPPA because more than 90% of patients with this subtype of FTD at autopsy have tau pathology, rather than TDP-43 pathology. In 2025, we initiated our Phase 2a trial evaluating neflamapimod in up to 25 participants with nfvPPA. Participants in the trial will receive six months of open label treatment with neflamapimod, followed by a three month blinded (randomized 1:1 placebo or continued neflamapimod) washout period. The primary objective is to evaluate the safety and tolerability of neflamapimod in this patient population. In addition, treatment effects on a range of clinical measures of aphasia and plasma neurodegeneration biomarkers, including GFAP and NfL, will be evaluated. We expect to report initial plasma biomarker from the trial in mid-2026, subject to available funding.

Acute Indication: Recovery after Ischemic Stroke

A treatment to improve recovery from stroke remains a significant unmet medical need. Every year, more than 795,000 people in the US suffer a stroke, and approximately 610,000 of these are first or new strokes. About 87% of all strokes are ischemic strokes, in which blood flow to the brain is blocked. During the last 10 years, the medical and scientific communities have gained a better understanding of the mechanisms underlying neuronal recovery following a stroke. The major translational opportunity for therapeutics that target recovery after stroke is the time window in which intervention must be initiated. Rather than just the first few hours after the stroke, the window for therapeutics that could improve recovery is days and even weeks after an acute stroke. From a drug development perspective, waiting to initiate therapy until 48 hours after the stroke allows inclusion of a homogenous patient population as the diagnosis and extent of the stroke can be definitively established by that time in most patients. As a result, a POC study in stroke recovery is in the range 50-100 patients per treatment arm, compared to 500+ per treatment arm in neuroprotection trials.

We believe the therapeutic benefit of targeting neuroinflammation-induced synaptic dysfunction is not limited to chronic neurodegenerative diseases. A drug that improves synaptic function could also be considered for evaluation of the potential to improve brain function after acute neurological injury. The scientific rationale for evaluating neflamapimod to promote recovery after stroke is that the BFC system plays a critical role in recovery after ischemic stroke, particularly motor function recovery. The BFC system is suppressed by residual inflammation in the weeks and months after the acute stroke event. Neflamapimod, through the same mechanisms operating in DLB, would be expected to reverse the suppression of BFC function, leading to improved recovery of motor function. Supporting that concept is our nonclinical data with neflamapimod demonstrating significant improvement in neurological recovery vs. vehicle treatment, and TUG results from the AscenD-LB clinical trial where positive effects of neflamapimod on basal forebrain mediated control of movement were observed in the clinic.

In a nonclinical study of neflamapimod that evaluated effects on recovery after stroke, which has been published in a peer-reviewed scientific journal, transient ischemia of sufficient duration was induced in rats such that significant neurologic disability developed without mortality, and the neurologic disability did not substantially reverse during follow-up without therapy. These rats were then treated with either vehicle or one of two different doses of neflamapimod. The three groups in the study were: vehicle control (n =18), 1.5 mg/kg neflamapimod (n = 21) and 4.5 mg/kg neflamapimod (n = 21). Six weeks of neflamapimod treatment, starting at 48-hours after stroke, led to substantial improvement on multiple parameters of neurologic function compared to vehicle controls (p<0.001 for each of global neurologic scores; motor and sensory specific tests).

Based upon these data and hypotheses, we initiated our ongoing RESTORE Trial, a Phase 2 placebo-controlled trial evaluating neflamapimod in up to 90 participants recovering from a moderate to moderately-severe anterior circulation ischemic stroke, in the second quarter of 2025. Patients will be enrolled between 3 and 7 days after the onset of their qualifying stroke event, and randomized 1:1 to placebo or neflamapimod for 12 weeks. The primary objective of the study is to evaluate effects of neflamapimod on recovery of motor function. The major outcome measures include change from baseline to week 12 in the Fugl-Meyer Assessment of Motor Recovery after Stroke (FMMS), Timed Up and Go (TUG) test and the National Institutes of Health Stroke Scale (NIHSS) motor score. We anticipate completing enrollment at the end of the second quarter of 2026 and expect to report topline data in the second half of 2026, subject to available funding.

Amyotrophic Lateral Sclerosis (ALS)

ALS is a progressive neurodegenerative disease that affects nerve cells in the brain and spinal cord that control voluntary muscle movement and breathing. Over the course of the disease, people lose the ability to move, sometimes also to speak, and eventually, to breathe. There are no approved therapies that stop or reverse the progression of ALS. Approximately 168,000 people worldwide live with ALS, with an estimated 90-95% of cases occurring without a family history of the condition.

In ALS, p38α is aberrantly activated and plays a key role in impairing axonal transport—a fundamental physiologic defect in the disease. Restoring axonal transport through p38α inhibition has been demonstrated both in vitro and in vivo, including in the SOD1 transgenic mouse model. More recently, independent nonclinical studies have further validated p38α as a disease-relevant, convergent target in ALS and, we believe, demonstrated the potential of neflamapimod. For example, recent third-party research related to both TDP-43 pathology and C9ORF72-associated ribotoxic stress response have independently concluded that p38α inhibitors may find important applications in ALS.

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In February 2026, we announced that neflamapimod has been selected for inclusion in EXPERTS-ALS, a platform that facilitates rapid testing of potential ALS to identify promising drug candidates and potentially accelerate their path to regulatory approval. Funded by the United Kingdom National Institute for Health and Care Research and leading motor neuron disease charities and sponsored by Sheffield Teaching Hospitals NHS Foundation Trust, EXPERTS-ALS assesses potential therapies through a randomized, multicenter, open-label, multi-arm trial that evaluates investigational medicines through the measurement of the blood biomarker NfL. NfL levels are significantly elevated in ALS patients due to accelerated neuroaxonal damage and correlate with the rate of disability progression and survival. Neflamapimod will be initially evaluated in approximately 35 participants with ALS for 18-24 weeks to determine its impact on NfL levels, with the potential for further evaluation in up to a total of 80 patients. Secondary and exploratory endpoints include several clinical and survival measures. We anticipate the first patient will be dosed with neflamapimod in EXPERTS-ALS trial in the fourth quarter of 2026, subject to available funding.

Additional Neflamapimod Development Background

Toxicology

A full chronic repeated dose toxicology program has been completed in rodents (rats) and non-rodents (dogs). In the rodent species, in the six-month chronic toxicology study, no human relevant findings were evident at dose levels that provided plasma neflamapimod drug concentration levels approximately ten-fold higher than those achieved in the CNS disease clinical trials. In shorter-term studies, the primary target organ was the liver, with findings commencing at plasma drug concentration levels 20-fold higher than the CNS clinical trial exposures. In the non-rodent species, in 9- and 12-month toxicology studies, dose dependent findings were evident beginning at plasma neflamapimod drug concentrations more than ten-fold higher than achieved with the doses utilized in our ongoing and anticipated clinical trials. The CNS findings indicated potential damage to axons, or nerve fibers, primarily in the spinal cord. p38α and p38β have been reported to have a role in transport of proteins in axons, and therefore we believe these toxicity findings are related to the inhibition of both p38α and p38β at the very high doses administered in the non-rodent studies. The plasma drug concentrations associated with doses we are using in our clinical trials in the US are at least ten-fold lower than the no adverse effect level for these effects.

Regulatory Status

We submitted an IND application to the FDA in February 2015. The FDA cleared our application in March 2015, and the IND remains open and active. In addition, the FDA granted neflamapimod Fast Track Designation for the treatment of DLB in October 2019 and Orphan Drug Designation for the treatment of frontotemporal dementia in November 2024.

Following a review of the long-term animal toxicology studies discussed above, the FDA placed a partial clinical hold on our first Phase 2a Trial in mild AD (Study 303) in August 2015, limiting administration of neflamapimod to doses that lead to plasma drug levels which provide at least a 10-fold safety margin to the plasma drug levels in animals to the no adverse effect level in long-term animal toxicity studies . At the present time, based on agreements with the FDA and on our current understanding of plasma drug levels achieved with neflamapimod in humans, this partial clinical hold effectively limits our clinical dosing in the US in patients with a weight of greater than or equal to 50kg (110 pounds) to the plasma drug concentrations associated with doses we are using in our ongoing and anticipated clinical trials.

In Europe, clinical trial applications in support of our clinical trials have been reviewed and approved in each of the Netherlands, United Kingdom, Czech Republic and Denmark. In addition, the Agence Nationale de Sécurité du Médicament et des Produits de Santé (the French national regulatory authority) has reviewed and approved a clinical trial application for an investigator-initiated study of neflamapimod in Toulouse, France. Our ongoing Phase 2a trial in Strasbourg, France, which is not subject to the FDA’s partial clinical hold, is evaluating an 80mg BID dosing regimen in participants with mild-to-moderate DLB.

Clinical Safety Results

Neflamapimod’s safety and tolerability profile has been extensively evaluated and is well understood. Specifically, long-term toxicology studies of neflamapimod have been completed and the drug has been administered to over 550 participants to date, including over 350 participants in Phase 2 clinical trials in CNS disorders. We also have several ongoing and planned clinical trials to further evaluate the safety, tolerability and PK profile of neflamapimod, including doses higher than the 40mg TID dose evaluated in our recent RewinD-LB Trial.

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In the RewinD-LB Trial, adverse events were similar to the safety profile seen in all other trials and are shown in the table below:

Overview of Treatment-emergent Adverse Events (TEAEs) (≥5%) During the Randomized Phase (Safety Set) in Phase 2b RewinD-LB Study EIP21-NFD-504

System Organ Class

Preferred Term

Neflamapimod (40 mg

TID) (N=79) n (%)

Placebo (N=80) n (%)

Any TEAE

58 (73.4)

59 (73.8)

Fall

12 (15.2)

15 (18.8)

COVID-19

8 (10.1)

3 (3.8)

Diarrhea

6 (7.6)

3 (3.8)

Urinary tract infection

5 (6.3)

6 (7.5)

URTI

5 (6.3)

4 (5.0)

Headache

5 (6.3)

10 (12.5)

Fatigue

5 (6.3)

6 (7.5)

Dizziness

4 (5.1)

3 (3.8)

Confusional state

4 (5.1)

1 (1.3)

Alanine aminotransferase increased

4 (5.1)

1 (1.3)

Back pain

4 (5.1)

1 (1.3)

Hallucination

2 (2.5)

5 (6.3)

In the Extension Phase of the RewinD-LB Trial, the profile remained similar with the following events reported by more than 5% of participants: fall, UTI, COVID-19, hallucination and diarrhea. In our previously completed clinical trials, the most commonly reported non-serious TEAEs included were headache, respiratory infection, diarrhea, fall, and somnolence all mild to moderate in severity. Headache, diarrhea, and somnolence appear to have the strongest association with neflamapimod treatment.

As of November 11, 2025, in clinical trials evaluating neflamapimod in patients with AD and DLB, there have been 44 SAEs reported in 273 participants treated with neflamapimod. The events of cerebral hemorrhage, syncope, pneumothorax, subcutaneous emphysema, and rib fracture were considered possibly related to neflamapimod by the trials’ investigator(s).

P38 MAPK inhibitors as a class have been associated liver enzyme elevations including transient, asymptomatic liver enzyme (transaminase) elevations without signs otherwise of hepatotoxicity (e.g., no elevation in bilirubin). ALT and AST and other liver function tests are routinely monitored in participants in neflamapimod clinical studies. Across the neflamapimod clinical development program, liver function testing elevations have been observed, primarily involving asymptomatic increases in ALT and AST. Most events were mild to moderate in severity, transient, and reversible upon dose interruption or discontinuation. No cases consistent with Hy’s Law were identified. Overall, the hepatic safety profile of neflamapimod supports continued clinical development with appropriate monitoring.

Among approximately 350 participants exposed to neflamapimod across the most recent clinical trials in AD, HD, DLB, recovery after stroke, and PPA, ALT or AST elevations >3× ULN were reported in 2 % of subjects. Elevations >5× ULN occurred in 0.2%, and elevations >10× ULN were uncommon (<1%). Increases in total bilirubin were infrequent and generally not temporally associated with transaminase elevations. In the RewinD-LB Trial, one of 80 (1.3%) participants treated with neflamapimod discontinued because of liver enzyme elevation during the Randomized Phase but the event was determined to be reversible and not associated with bilirubin elevation. During the trial's Extension Phase, none of the 149 neflamapimod recipients discontinued for liver enzyme elevation.

Nonclinical Studies

Ts2 Transgenic Mice

Nearly all individuals who have Down Syndrome, characterized by trisomic chromosome 21, develop AD by their fourth decade of life, and have typical AD pathology when autopsied at death. This may be explained by chromosome 21 containing the gene for amyloid-precursor-protein, which is the gene linked to familial or genetic EOAD in humans. The Ts2 transgenic mouse model of Down Syndrome utilizes mice that are partially trisomic at chromosome 16, which is the mouse equivalent of chromosome 21. Along with developmental behavioral abnormalities, Ts2 mice develop typical early onset dementia pathology, including endosomal abnormalities and cholinergic neurodegeneration in the BFC system. Accordingly, Ts2 mice provide an ideal opportunity to evaluate the effects of drug treatment on BFC dysfunction and degeneration.

In a nonclinical study, wild-type mice, referred to as either wild-type or 2N, and Ts2 mice were treated over 28 days with either control or neflamapimod. Treatment was initiated at 6-7 months of age, representing a time point at which endosomal pathology and cholinergic neuronal loss is developing. To assess for effects on cholinergic neurodegeneration, ChAT+ neurons were quantitated in the region of the forebrain that is enriched for cholinergic neurons, which is known as the MSN.

At the end of treatment, consistent with current scientific literature, the number of cholinergic neurons in the MSN region was significantly decreased in control-treated TS2 mice compared to control-treated wild-type mice (p<0.001). This effect was reversed with neflamapimod treatment, with the number cholinergic neurons in the MSN increased in neflamapimod-treated Ts2 mice compared to vehicle-treated Ts2 mice, such that the number of ChAT+ neurons were similar to those seen in wild-type mice (p<0.001). Neflamapimod treatment also normalized Rab5 activity and phosphorylated (i.e., activated) p38 MAP kinase and its downstream substrates.

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Neflamapimod restored numbers of cholinergic neurons in basal forebrain (i.e., reversed disease progression) in Ts2 transgenic mouse.

Cholinergic neurons, as assessed by staining positive for ChAT+ neurons in the MSN of the basal forebrain, in wild-type treated with vehicle or Ts2 transgenic mice after treatment for four weeks with either vehicle or neflamapimod.

The finding of reversal of disease progression is consistent with studies in the scientific literature that suggest that “loss” of cholinergic neurons in the BFC system is not due to cell death. Rather, the “degeneration” and loss of such BFC neurons appears to be due to a loss of cholinergic phenotype and functional properties, and neuronal shrinkage. In animal studies, all of this disease progression can be reversed, evidenced by the increased number of cholinergic neurons. This is not a regenerative effect, however. Rather, we believe it reflects that treatment with neflamapimod is restoring the function of diseased neurons, allowing them to express ChAT. There is also evidence from studies in early AD, that cholinergic phenotype loss, rather than frank neuronal death and loss, occurs in the basal forebrain of humans as well. We believe this is consistent with the results obtained from the MRI evaluation of neflamapimod-treated patients with AD discussed above in whom an increase in the volume of BFC neurons was observed in the NbM.

Aged Rat Model

To obtain nonclinical proof-of-principle and confirm the role of p38α in the development of synaptic dysfunction, we tested neflamapimod in a rat model of age-related cognitive decline. When evaluated in the Morris-Water-Maze test of spatial learning, rats show cognitive deficits starting at 20 to 22 months of age, which is equivalent to approximately 60 years of age in humans. Of note, because the deficits in Morris-Water-Maze performance can be fully reversed by implanting healthy cholinergic neurons in the basal forebrain, those deficits are believed to be due to BFC dysfunction and degeneration.

The results of these nonclinical studies showed that treatment with neflamapimod fully reversed the learning deficits in the Morris-Water-Maze test in 20- to 22-month-old rats. Specifically, the performance of aged rats on the last day of testing (day 17) showed that animals treated with neflamapimod at the optimal dose performed significantly better than control–treated aged rats (p=0.007 for latency; p=0.01 for distance). Further, the performance of neflamapimod-treated aged rats was similar to that of young rats (i.e., cognitive deficits were fully reversed).

Vertex Agreement

In August 2012, we entered into the Vertex Agreement, which granted us an option to acquire an exclusive worldwide license to develop and commercialize neflamapimod for the diagnosis, treatment and prevention of AD and other neurodegenerative diseases. This decision was made, in part, based on our team’s previous direct experience with this compound, our understanding of its profile, and emerging science around p38α in the brain. In August 2014, we exercised that option to acquire the license to neflamapimod.

The Vertex Agreement sets forth certain milestone events and the related payments we would be obligated to make to Vertex if and when such events occur. Each milestone payment is payable only once for each distinct licensed product, upon the first occurrence of the applicable milestone event. The first expected milestone events concern the filing of an NDA with the FDA for marketing approval of neflamapimod in the US and/or a similar filing for a non-US major market. The Vertex Agreement also provides that we will make royalty payments to Vertex in the event aggregate net sales for a commercialized licensed product meet specified thresholds. Such royalties will be on a sliding scale of percentages of net sales in the low- to mid-teens, depending on the amount of net sales in the applicable years. We are also obligated to make a one-time milestone payment to Vertex upon net sales reaching a certain specified amount in any 12-month period. The Vertex Agreement states that royalties will be reduced by 50% during any portion of the royalty term when there is no valid claim of an issued patent within specified patent rights covering the licensed product. We also have the right to deduct, on a country by country basis, from royalties otherwise payable to Vertex under the terms of the Vertex Agreement, 50% of all royalties, upfront fees, milestones and other payments paid by us or any of our affiliates or sublicensees to third parties under licenses that are necessary for the development, manufacture, sale or use of a licensed product, provided that in no event will the royalty payable to Vertex be reduced to less than 50% of the rates specified in the Vertex Agreement, subject to certain adjustments specified therein. In the aggregate, our potential milestone payment obligations, all of which relate to development milestones, under the Vertex Agreement are up to $117.0 million. To date, we have made an aggregate of $100,000 in payments to Vertex. In connection with our obligations under the Vertex Agreement, there is no minimum annual expenditure requirement. Our diligence obligations under the Vertex Agreement have included the making of annual expenditures in connection with the development of neflamapimod, completion of multiple Phase 2 clinical trials of neflamapimod, and our ongoing development efforts.

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The Vertex Agreement provides that we may sublicense the rights granted to us by Vertex, in whole or in part, to a third party (through multiple levels of sublicensing) (i) who is providing services to us in connection with the manufacture or development of the licensed product, solely for the purpose of providing such services, or (ii) with the prior written consent of Vertex, which shall not be unreasonably withheld.

The license term under the Vertex Agreement is deemed to have commenced on August 21, 2014, and continues until the expiration of the royalty term, unless sooner terminated in accordance with the terms of the Vertex Agreement. The royalty term commences on the first commercial sale of a licensed product and ends upon the later of (i) the date of expiration, unenforceability or invalidation of the last valid claim of certain specified underlying patent rights, or (ii) ten years after the date of such first commercial sale. Upon the expiration of the royalty term, the license will convert to a perpetual, fully paid-up non-royalty bearing license with the same scope.

The Vertex Agreement may be terminated by us for any reason upon 90 days’ prior written notice to Vertex if such termination occurs before receipt of the first marketing approval of a licensed product, and otherwise upon twelve months’ prior written notice to Vertex. Either party may terminate the Vertex Agreement if the other party is in material breach of its obligations thereunder, following a 60-day notice and cure period, or if the other party files for bankruptcy, reorganization, liquidation, receivership, or an assignment of a substantial portion of assets to creditors. The Vertex Agreement also provides that in the event we materially breach any of certain specified diligence obligations as to a specific major market, Vertex’s sole remedy for such breach, following the applicable notice and cure period, will be to terminate the license as to such specific major market country.

EIP200 – Novel Co-Crystal of Neflamapimod

We have an issued patent in the US, expiring in 2038, for novel co-crystals of neflamapimod with identified, specific, Generally Recognized as Safe compounds that have the potential to improve the solubility and other physical properties of neflamapimod. The development of one of these co-crystals as a product would be supported by composition of matter protection afforded by this patent, providing additional patent protection if we developed such a co-crystal product ourselves, the opportunity to license such a product to another pharmaceutical company while retaining the rights to neflamapimod and other potential benefits. The ability to develop one or more of these co-crystal products requires a fuller evaluation of the potential manufacturing processes than has been performed to date.

However, we believe these novel co-crystals of neflamapimod may provide additional optionality to multiple aspects of our development strategy, including related the partnering and/or commercialization of neflamapimod across the multiple indications in which it has demonstrated potential.

Sales and Marketing

We do not currently have any infrastructure for the sales, marketing, or distribution of an approved DP. In order to market and successfully commercialize neflamapimod or any other future product candidate, to the extent it or they are approved, we must either develop these capabilities internally or make arrangements with third parties to perform these services. We may also collaborate with global or regional strategic partners that have experience in these fields. There are significant expenses and risks involved in establishing our own sales, marketing and distribution functions, including our ability to hire, retain and appropriately incentivize qualified individuals, generate sufficient sales leads, provide adequate training to sales and marketing personnel, and effectively manage a geographically dispersed sales and marketing team. Alternatively, to the extent that we depend on third parties for such services, any revenues we receive will depend upon the efforts of those third parties, and there can be no assurance that such efforts will be successful.

Manufacturing

We do not own or operate manufacturing facilities, nor do we have plans to develop our own manufacturing operations in the foreseeable future. Our lead product candidate, neflamapimod, is a small molecule drug that is manufactured using commercially available technologies.

Our DS is manufactured at established commercial CMOs that are approved for and manufactures DS both for investigational use and marketed products. We have used the same manufacturer for our neflamapimod DS in all our clinical trials prior to 2026 but have recently begun working with a second DS CMO to, in part, diversify our prior sole supplier risk. We anticipate utilizing these or similar CMOs for the manufacture of DS to be used in future clinical trials, as well as potentially for commercial use if neflamapimod is approved. However, supplies of our neflamapimod DS could be interrupted from time to time, and we cannot be certain that alternative supplies could be obtained within a reasonable timeframe, at an acceptable cost, or at all.

We also currently rely on a third-party CMO (different than those for DS) for the manufacture of our neflamapimod DP. We have used the same manufacturer for our neflamapimod DP in all our clinical trials to date but have recently begun working with a second DP CMO to, in part, diversify our prior sole supplier risk. If neflamapimod is ultimately approved for commercial sale, we expect to continue to rely on third-party contractors for manufacturing the DP. Although we may do so prior to any commercial launch, we have not yet entered into long-term agreements for the commercial supply of either drug substance or DP with our current manufacturing providers, or with any alternate manufacturers.

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For a further description of our planned pre-Phase 3 manufacturing improvements and certain risks related to our manufacturing, see “Alignment with FDA on Planned Phase 3 Trial – Pre-Phase 3 Manufacturing Improvements,” “