Cyrano’s CYR-064 Improves Smell Loss in Phase 2 Trial

Cyrano Therapeutics has reported positive results from its Phase 2 FLAVOR trial (NCT06019000), evaluating CYR-064, an investigational intranasal theophylline spray for persistent post-viral hyposmia, or reduced sense of smell following a viral infection.

Presented at the 72nd Annual Meeting of the American Rhinologic Society (ARS) in Los Angeles, the findings showed that the trial met its primary safety endpoint. In patients younger than 60 years, high-dose CYR-064 also improved two patient-reported measures of smell function compared with placebo at Week 24.

The results support further investigation of a pharmacological approach to persistent post-viral smell loss. However, the publicly reported efficacy findings are limited to a specific age and dose subgroup.

FLAVOR Trial Met Its Primary Safety Endpoint

FLAVOR was a randomized, double-blind, placebo-controlled Phase 2 study conducted at 14 US clinical sites. It enrolled 151 patients whose hyposmia had persisted for at least six months and evaluated treatment over 24 weeks.

Participants received one of two CYR-064 dose levels or placebo, administered twice daily. Safety was the primary endpoint, while efficacy was assessed through prespecified secondary endpoints.

Cyrano reported the following safety findings:

• Treatment-related serious adverse events: None reported among the 151 participants.
• Overall adverse events: Rates were comparable between CYR-064 and placebo.
• Serious adverse events: Overall rates were also comparable between treatment groups.

These findings support continued evaluation of the formulation’s tolerability over the study period. They do not establish its long-term safety or exclude less common adverse effects.

High-Dose CYR-064 Improved Two Patient-Reported Measures

Patients younger than 60 years represented approximately 66% of trial enrollment. In this subgroup, high-dose CYR-064 produced statistically significant improvements over placebo on two patient-reported measures at Week 24.

The trial used two scales to assess changes in perceived smell function:

• Visual Rating Scale (VRS): A 0–3 scale used to rate the severity of smell loss, with higher scores indicating greater impairment.
• Numerical Rating Scale (NRS-11): An 11-point scale ranging from 0 to 10 that patients use to rate their smell function.

Key efficacy results at Week 24

• VRS: Mean improvement of 0.72 points with high-dose CYR-064 versus 0.12 points with placebo (p=0.002).
• NRS-11: Mean improvement of 2.08 points versus 0.68 points with placebo (p=0.029).

Cyrano also reported clinically meaningful improvements among patients receiving the high dose:

• VRS: 58% experienced a clinically meaningful improvement, averaging 1.3 points.
• NRS-11: 69% improved, with an average improvement of 3.2 points.

According to the sponsor, improvements in the high-dose group continued through Week 24, while the placebo group plateaued earlier. The company also reported that both measures were assessed for reliability and content validity with support from an external specialist firm.

However, these are patient-reported outcomes. The public announcement does not provide corresponding results from objective olfactory testing, such as standardized smell-identification assessments.

Severe Baseline Smell Loss Shows a Larger Response

A further signal emerged among patients younger than 60 years who had severe smell loss at baseline, defined as a VRS score of 3.

Reported results in this subgroup

• Mean VRS improvement: 1.10 points with high-dose CYR-064 versus 0.30 points with placebo (p=0.005).
• Clinically meaningful improvement: 82.4% of high-dose patients versus 31.3% of placebo recipients.

The magnitude of this difference warrants further investigation, particularly in patients with more pronounced baseline impairment.

However, the announcement does not specify the subgroup size or establish whether this analysis was prespecified. These results should therefore be treated as a subgroup finding rather than evidence of a confirmed treatment advantage across all patients with severe hyposmia.

Clinical Interpretation and Phase 3 Outlook

CYR-064 uses an intranasal formulation of theophylline, a phosphodiesterase inhibitor, with a targeted delivery system designed to enhance olfactory neuron excitability. The approach aims to improve local drug delivery to the olfactory region.

Whether it provides a clinically meaningful advantage over oral theophylline or existing non-drug management strategies has not been established by the reported findings.

The principal limitation is that the publicly disclosed efficacy results focus on patients younger than 60 years receiving the high dose. Cyrano has not reported corresponding full-population results, lower-dose outcomes or efficacy findings for patients aged 60 years and older in its announcement.

The release also does not clarify whether the age subgroup was prespecified or whether statistical adjustments were made for multiple comparisons. These details matter because statistically significant secondary-endpoint findings do not, by themselves, establish efficacy across the intended treatment population.

Cyrano has said it is preparing to advance CYR-064 into Phase 3 development. The next trial will need to confirm the treatment effect across relevant patient groups, establish the appropriate dose and assess whether improvements are clinically meaningful and durable.

References

Study of CYR-064 Versus Placebo in Patients, ClinicalTrials.gov ID NCT06019000

Cyrano Therapeutics Announces Presentation of Positive Phase 2 FLAVOR Data Demonstrating Statistically Significant Improvement in Smell Function with CYR-064 in Patients with Post-Viral Smell Loss, Cyrano Therapeutics, 16 October 2026