Cyclerion Therapeutics, Inc. - Pre Recorded Special Call

2025-09-24 12:53:50 ET

Cyclerion Therapeutics, Inc. - Pre Recorded Special Call

Company Participants

Regina Graul - CEO, President & Director

Presentation

Regina Graul
CEO, President & Director ...

Good morning, everyone. Yesterday, we announced Cyclerion's transformational relaunch as a neuropsychiatric company, supported by an MIT licensing agreement that secures foundational intellectual property. A copy of this release and presentation to accompany this call are available on the Investor Relations section of our website at ir.cyclerion.com. I am Regina Graul, Chief Executive Officer of Cyclerion Therapeutics. Thank you for joining us for the Cyclerion overview. Today, we'll share our strategy for building a new era in neuropsychiatric therapies, highlight the opportunities ahead and walk through our clinical and corporate road map.

Before we get started, I would like to remind everyone that certain matters discussed in this presentation are forward-looking statements. We may, in some cases, use terms such as potential, may, expects, plans, could, opportunity or other words that convey uncertainty of future events or outcomes to identify these forward-looking statements. These statements involve risks, uncertainties and other factors that may cause actual results, performance or achievements to be materially different from the information expressed or implied by these forward-looking statements. We caution you that these statements are based on a combination of facts and factors currently known by us and our projections of the future about which we cannot be certain.

Forward-looking statements in this presentation include, but are not limited to, statements about our ability to develop product candidates and the timing of related milestones, creation of shareholder value, adoption of our product candidates once commercialized and expected addressable market size. We cannot assure you that the forward-looking statements in this presentation will prove to be accurate. Actual performance and results may differ materially from those projected or suggested in the forward-looking statements due to a variety of risk factors and uncertainties. These are included under the heading of Risk Factors in our annual report on Form 10-K filed with the SEC on March 4, 2025, as well as other risks and uncertainties, which may be described in any subsequent quarterly report on Form 10-Q filed by the company and other reports the company files with the Securities and Exchange Commission.

Cyclerion is relaunching as a neuropsychiatric-focused company. This is not simply a continuation of our past. It's a strategic reset built on a strong foundation and clear growth strategy. At our core, we are a publicly traded company with a start-up mentality. We are lean, we are nimble, and we are focused. Our approach centers on the opportunity for patient impact and shareholder value creation, driven by a team with world-class expertise in neuropsychiatry and the biopharmaceutical industry. We intend to advance programs with discipline moving through well-defined derisked inflection points.

Equally important is our pipeline focus. We are developing tech-enabled therapies designed to optimize patient outcomes, targeting large neuropsychiatric markets with urgent unmet need. These are potentially novel, improved or first-in-class therapies backed by validated modes of action and designed for a rapid path to proof-of-concept. Together, this foundation and pipeline strategy define our relaunch, positioning Cyclerion to lead the next era in neuropsychiatric treatment.

Our collective vision is guided by a highly experienced Board and network of advisers with leadership experience from early research through late-stage commercialization. From seasoned biotech executives to global leaders in psychiatry, anesthesiology, regulatory affairs and commercialization, Cyclerion is supported by expertise that enables both scientific rigor and business discipline, all areas of direct relevance to advancing our pipeline. I would also like to highlight the news in yesterday's press release. We just announced that we have acquired the foundational intellectual property that was developed at MIT, IP that will help define and protect Cyclerion's leadership position in the field. I have great enthusiasm for the future prospects of our company and the impact we can deliver to patients.

We intend to use our foundational platform to pioneer a first-in-class option for anesthetic-based therapy in neuropsychiatry. Our lead indication is treatment-resistant depression, a severe condition affecting approximately 3 million patients in the U.S. alone. With few effective options, this patient population represents one of the highest unmet needs in psychiatry. We are advancing a proprietary tech-enabled delivery system designed to personalize therapies through bio feedback. Our approach harnesses well-characterized anesthetics with extensive safety data and a proven clinical history.

The strategy is supported by 3 independent proof-of-concept trials that demonstrated encouraging signals in treatment-resistant depression. Importantly, our therapy is designed to be delivered in a familiar setting by providers who already manage these medications and patients while addressing limitations of existing treatments. With this foundation, the program is Phase II ready, and we expect to initiate our proof-of-concept study by the end of 2026.

Yesterday, as a next step in bringing this important therapy to patients, we announced that we've entered into a licensing agreement with MIT to secure foundational intellectual property for the platform. Beyond treatment-resistant depression, we believe our platform offers expansion potential into other neuropsychiatric diseases, which we continue to investigate. We also retain the optionality to add strategically relevant therapies that enhance the platform. And we continue to monetize our legacy assets, which we believe can provide non-dilutive capital to further drive pipeline development.

Now let's step back to look at the treatment-resistant depression market. Out of the 21 million adults in the U.S. living with major depressive disorder, roughly 14% progressed to treatment-resistant depression. That's about 3 million patients. These 14% of patients account for half of the $40 billion economic burden of depression. They face two to tenfold higher incidence of suicide or suicide attempts and a 23% higher all-cause mortality rate compared to patients with major depression. This is not just a clinical crisis, but also a massive cost burden for health care systems, employers and families, there was a need for better options and that need is urgent. Unfortunately, today's treatments for treatment-resistant depression are limited and often unsatisfactory. Electroconvulsive therapy remains a standard intervention but carries both acute and chronic safety risks, including memory loss and is further limited by the significant social stigma associated with the procedure.

Recently approved medicines such as Spravato provide another option, but they come with box safety warnings and the potential for misuse. Brain stimulation devices like rTMS can be helpful for some, but the results are inconsistent and the treatment schedules can be burdensome. This leaves many patients cycling through therapies with limited benefit and concomitant safety risks before escalating to highly invasive interventions. That's where Cyclerion can come in, offering the potential for a safe, effective and scalable alternative. Our approach is designed to intervene and provide durable relief without the stigma, safety concerns or logistical burdens of today's therapies and to fill that critical gap between standard antidepressants and invasive procedures.

Our solution is a personalized tech-enabled therapy that uses well-known generic anesthetics with extensive safety databases, medicines that anesthesiologists are deeply familiar with from decades of routine use in surgical and procedural settings. What makes our approach novel is not only the drugs themselves in depression, but also the way they are delivered. Through continuous EEG monitoring and proprietary algorithmic controller, our system is designed to allow precise titration to specific brain states linked to antidepressant benefit. We believe this biofeedback-driven model could enable truly individualized treatment tailored to each patient's brain activity in real time. The result is a therapy that's potentially safe, highly efficacious, scalable and efficient. Patients may benefit from rapid durable relief without the burden of current TRD treatments.

Providers would gain a familiar framework to administer care and hospitals would be able to integrate this into their existing infrastructure. Our therapeutic candidate is designed to be a preferred option across the treatment landscape. For patients, it could offer the potential for a safe, effective and well-tolerated treatment with a rapid return to normal activities. For providers, our therapy offers the potential for a low treatment burden delivered within a familiar procedural framework and the ability to administer care without the common side effects of available options such as cognitive impairment, social stigma and disassociation.

For hospitals, we believe the model is highly attractive, the potential for reimbursement for the procedure, device and medicines, all while fitting neatly into an established procedural framework within the PACU setting. Taken together, we believe this is a solution that could be the preferred treatment for TRD and has the potential to benefit all stakeholders, patients, providers and health systems, paving the way for broad adoption and impact, filling the gap between inadequate standard interventions and invasive last resort procedures.

Brain regions communicate with one another through rhythmic electrical activity called oscillatory brain waves. In healthy individuals, these oscillations are well coordinated, allowing for proper regulation of mood, thought and behavior. In TRD, these rhythms become disrupted. The communication between key regions of the brain, including those responsible for emotion, motivation and cognition is dysregulated. And this breakdown is believed to underlie the persistent symptoms patients experience such as hopelessness, rumination, difficulty regulating emotion and anxiety. Research has shown that carefully controlled sedation can restore synchronized communication between brain regions, essentially resetting the neural circuits that have become dysfunctional in TRD. This is a scientific basis for Cyclerion's therapeutic candidate.

By using specific anesthetics and leveraging a tech-enabled delivery system to achieve these precise brain states, we believe we can unlock a safe, reproducible and individualized approach to treating depression. Importantly, this concept has already been supported by 3 independent clinical studies, providing a strong foundation for our development program. The use of anesthetics for TRD is supported by compelling early phase clinical evidence. Across 3 studies, propfol has demonstrated consistent antidepressant effects with favorable safety profiles. The rapid onset of benefit in all studies was observed within 1 to 2 weeks with durability lasting 3 to 6 months. All 3 studies used anesthesiologist controlled dosing with EEG guidance, optimizing to sedation with or without burst suppression. These results provide strong rationale for our development program.

Let's look at the clinical evidence supporting our approach, starting from left to right. On the left, a pilot study in 10 patients with moderate to severe TRD tested 10 infusions over 3 weeks. The results were striking, 60% of patients responded and 50% achieved remission. Importantly, 4 of the 5 remitters sustained remission for at least 3 months with 2 of the 4 sustained remission in the sixth month and potentially longer. In the middle, a larger randomized controlled trial of 24 patients compared different dosing strategies. At the higher dose, which targeted EEG suppression, half the patients responded and 42% achieved remission. At the lower dose, the results were minimal, but when those patients crossed over to the higher dose, response and remission rates matched the higher dose group. This reinforces the importance of reaching the right brain state to unlock antidepressant benefit.

Finally, on the right, in a study of 15 geriatric patients, 2 carefully controlled infusions that enhanced slow-wave sleep produced a 67% response rate. What's particularly compelling is that the symptom improvement was not random. It was correlated with the amount of slow wave activity achieved during treatment. In other words, patients who reached higher levels of slow wave activity experienced greater reduction in depressive symptoms. Taken together, these 3 independent studies in younger, older and mixed TRD populations consistently showed rapid onset, meaningful response and remission rates and durability over periods of months. This convergence of evidence forms a strong foundation for Cyclerion's development program.

We are now advancing toward a Phase II randomized double-blind proof-of-concept study. The trial will include 2 parts: Part A focused on safety and pharmacodynamics and Part B focused on safety and efficacy. Patients will be randomized across either 2 specific general anesthesia states, one deeper and the other a sham control arm. Treatment is expected to be delivered 3 times per week for 3 weeks, with follow-up extending up to 6 months to assess durability. We expect to initiate this trial in 2026 with initial data readouts in 2027. Our near-term milestones are clear. By year-end 2025, we expect to confirm our proof-of-concept trial design, complete our pre-IND with the FDA and finalize a working prototype of the device. In 2026, we aim to secure FDA IND clearance and initiate our Phase II proof-of-concept trial. Safety and pharmacodynamic data will follow leading into safety efficacy data in 2027. By 2028, we plan to have full Phase II data and to meet with the FDA to align on advancing into pivotal trials.

In closing, Cyclerion is transformationally relaunching as a new company dedicated to neuropsychiatry. Our lead focus is treatment-resistant depression where the unmet need is greatest. And from this foundation, we see the potential to expand into other serious neuropsychiatric disorders. We are operating with the discipline of a public company and the agility of a start-up, lean, focused and guided by world-class expertise. This relaunch is about more than just one program. It's about building a class of therapies designed to reshape the treatment landscape in mental health. Our goal is clear: to deliver meaningful impact for patients while creating significant sustainable value for our shareholders.

Thank you for your attention and support, and we look forward to updating you as Cyclerion continues this exciting new chapter.

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