In this interview, I’m talking with Rick Geoffrion, Founder, President, and CEO of Cyrano Therapeutics, about FLAVOR, a Phase II randomized, double-blind study of CYR-064 for chronic post-viral smell loss. We delve into how the team designed endpoints that matter to patients and regulators, the biology behind CYR-064, safeguards against placebo and spontaneous recovery, and practical considerations for recruitment, adherence, and future pivotal plans. The discussion also touches on a parallel Parkinson’s study exploring cross-disease signals, offering leadership insights on translating a novel sensory therapy from concept to potential approval.
Moe: In FLAVOR, how did we balance patient-reported outcomes with functional smell tests, given FDA preference for PROs and the novelty of these endpoints?
Rick: We faced a fundamental tension: how to make a subjective, lived experience measurable while satisfying regulators. We weighed patient-reported outcomes against validated functional olfactory tests, which exist, but risk bias because odor familiarity varies culturally. The FDA signals favored PROs in this nascent space, and we were among the first to propose a Phase II, randomized, double-blind design for chronic post-viral smell loss. We structured FLAVOR with safety as the primary endpoint to establish the safety profile and then we utilized PROs as the primary efficacy signal. We pre-specified thresholds that could serve to define a clinically meaningful improvement from the patient’s perspective, and potential shifts in the roadmap toward a pivotal trial. We also implemented monthly safety checks, standardized PRO instruments, and a robust data lock process to ensure interpretability across sites and over time.
Moe: CYR-064’s biology hinges on olfactory signaling under stress from viral injury. How did this mechanism influence inclusion criteria, and what did you drop to keep the trial feasible?
Rick: You’re right to tease apart the mechanism. CYR-064 isn’t a direct activator of olfactory receptor neurons; instead, it is believed to modulate the environment in which ORNs operate by sustaining cyclic AMP signaling, which can help ORNs fire after viral injury when sustentacular support is compromised. The virus attacks sustentacular cells, which typically fuel ORNs, leading to impaired signaling and potential neuron loss over time. By maintaining cyclic AMP, CYR-064 it is believed to support signaling despite a reduced energy state in the environment. This mechanistic framing influenced our acceptance criteria: we target patients with persistent post-viral smell loss rather than other etiologies, and we avoid introducing confounders that could obscure a sensorimotor readout. A clear “cutting room floor” item was intranasal medication use; we explicitly excluded participants on concomitant intranasal therapies to avoid confounding the nasal environment and potential drug interactions. This exclusion helps maintain a cleaner signal and cleaner interpretation of CYR-064’s effect on PROs and safety. In short, the biology informed a careful balance: select a population where the mechanism could plausibly help, and minimize factors that could muddy the readout.
In addition, we have aligned endpoints with this mechanism, focusing on patient-reported improvements in daily smell-related function and tolerability, with safety embedded in every step. A mechanistic framing supports interpretability: any PRO benefit is plausible given improved ORN signaling, and the safety profile is monitored alongside. The challenge is that biology is complex and multifactorial, so we designed a clean, mechanism-consistent study population and a tight nasal environment control to preserve the interpretability of the signal.
Moe: Placebo effects and spontaneous recovery are well documented in smell loss research. What safeguards did you build to separate true signal from background noise, and how do they reflect best practices in subjective sensory trials?
Rick: We anticipated natural history would complicate signal interpretation. To mitigate this, we required participants to have a loss of smell for at least six months before enrollment. The literature suggests that spontaneous recovery within the 6–24/30-month window is possible, but relatively modest, at around 15% of patients seeing some level of improvement but most likely not getting back to normal. By starting at six months and extending eligibility up to 30 months post-loss, we narrow the window where spontaneous improvement is most likely and reduce the risk that natural recovery masks a drug effect. This creates a built-in baseline against which a proper treatment signal can be detected, while acknowledging that some spontaneous improvement can still occur and that we’ll interpret PRO changes in light of this background. We also maintain safety oversight and standardized PRO measures to ensure comparability across sites and time. This principle aligns with best practices in subjective sensory trials where robust data hygiene is essential.
Beyond design, we emphasize adherence and monitoring to minimize noise. We predefine late-stage endpoints and plan predefined analyses that separate stable responders from early improvements that could reflect placebo effects or spontaneous recovery. We believe this approach facilitates a clearer attribution of observed changes to the intervention. It underscores the importance of rigorous endpoint specification and trial governance in a field where patient perception is a key factor in efficacy signals.
Moe: You mentioned a parallel Parkinson’s study. What cross-disease learnings could strengthen FLAVOR readouts, and how will you interpret any signals for future development?
Rick: Cyrano is simply supplying clinical material for a separate Investigator Initiated Study that was proposed by Dr. David Silvers at Gardens Neurology in Palm Beach County Florida. Parkinson’s patients commonly experience smell loss years before motor symptoms, and the pathophysiology may involve dopaminergic signaling with a different olfactory dynamic. The investigator-initiated study uses the same high-dose level from the FLAVOR Trial to explore whether CYR-064 can yield a signal in a different disease milieu and follows those patients to observe early responses through 6 months. A positive signal in Parkinson’s could strengthen the rationale for broader use and justify an additional development program; however, the two programs address distinct pathophysiologies. Cross-disease exploration can reveal signals or timing that prompt a tailored plan, but readouts would be disease-specific. If the PD data show promise, we’ll use that to inform a future investigational strategy rather than assuming a direct read-across to post-viral smell loss. The learnings from PD help us anticipate differences in patient journeys, the timing of interventions, and the need for disease-tailored endpoints, data capture, and safety monitoring.
Moe: Adherence is a challenge with intranasal therapies. What behaviors have you observed in participants, and would you consider using digital tools or decentralized approaches to enhance engagement?
Rick: Adherence is a common challenge in long-term intranasal trials. We anticipated dropouts and built a six-month horizon as the maximum where adherence remains realistically sustainable, given twice-daily sprays and monthly visits. If a participant experiences no apparent benefit or is on a placebo, they may discontinue earlier. We accepted that reality and designed the study to preserve a robust signal within that six-month window. The plan for FLAVOR included clear expectations for participants, proactive follow-up, and a digital strategy that hinged upon daily reminders and questions issued both daily and weekly via each patients’ personal device with remote adherence tracking. That said, the six-month frame and follow-up cadence do create room for future decentralized tools: telemedicine check-ins and further optimized digital reminders could sustain engagement, especially for those in non-urban areas or with competing obligations. Looking forward, integrating optimized digital adherence strategies could become a core element of a pivotal program, enabling real-time engagement signals, early problem detection, and smoother data collection across diverse patient populations.
Moe: If FLAVOR is successful, how would you rethink the pivotal program—endpoints, recruitment, and site strategy—to accelerate late-stage success?
Rick: Recruitment has shown the power—and limits—of social media. Clinically, many ENT patients use intranasal therapies, which can create potential confounders that we must exclude. We are prioritizing high-density population centers where social media can reach large, eligible pools within a reasonable travel radius. Urban hubs, such as New York, Chicago, Los Angeles, and Houston, are focal points, while we will also include rural sites to address access and represent real-world diversity. If FLAVOR proves efficacious, the pivotal program would refine endpoints to align with regulatory expectations, potentially using adaptive site strategies to optimize performance. Data monitoring would be rigorous to preserve quality at scale, and we’d explore confirmatory PROs that maintain clinical relevance. The broader aim is speed without sacrificing interpretability, leveraging a scalable recruitment model that preserves patient diversity and trial integrity.
Moe: What is the most compelling potential impact if FLAVOR succeeds, and how would that reshape how the industry treats senses like smell and taste in pharmacology?
Rick: If successful, FLAVOR would mark the first pharmaceutical intervention for loss of sense of smell. Since smell is closely tied to taste, we believe restoring olfactory function might dramatically improve flavor perception and overall quality of life. This would not only provide a meaningful therapy for millions but also reshape the industry’s approach to sensory endpoints—nudging drug developers to invest in nasal-brain signaling pathways and patient-centered outcomes. It could catalyze broader investments in therapies for sensory dysfunctions that have historically been underrepresented, encouraging disease-specific endpoints, regulatory-aligned strategies, and real-world data capture to demonstrate meaningful benefits in daily life. The potential impact extends beyond a single indication and may well signal a paradigm shift in how we value and measure senses within the field of pharmacology.
Moe: Any final thoughts on leadership lessons or industry implications from FLAVOR for teams pursuing sensory therapies?
Rick: The core leadership takeaway is to couple patient-centric endpoints with rigorous design and regulatory awareness from day one. We’re navigating a space where regulators are still learning to evaluate drug candidates with evolving science, so flexibility and pre-specified decision rules are crucial, as is collegial communication with the regulators informed by the data.. Building cross-functional teams, including clinical science, regulatory, data management, and digital engagement, helps ensure that endpoints are meaningful, feasible, and scalable. The Parkinson’s exploration demonstrates the value of cross-disease exploration to inform risk-benefit and development pacing without assuming direct read-across. Finally, the recruitment and adherence lessons remind us that modern trials demand adaptive strategies—leveraging social networks for reach, but also planning for remote, decentralized elements that support participants and data integrity as we scale. If we remain patient-centered, data-driven, and regulator-aware, sensory therapies could become a more prominent and credible part of pharmacology’s future.
Moe Alsumidaie is Chief Editor of The Clinical Trial Vanguard. Moe holds decades of experience in the clinical trials industry. Moe also serves as Head of Research at CliniBiz and Chief Data Scientist at Annex Clinical Corporation.
