CVN766

Psychiatric & CNS-controlled metabolic disorders

Designed to be a highly selective oral antagonist of the orexin 1 receptor (Ox1R)

Designed to be a highly selective oral antagonist of the orexin-1 receptor (Ox1R)

Orexin, a neuropeptide that is dysregulated in many psychiatric conditions, binds both Ox1R and orexin-2 receptors (Ox2R). Ox1R is primarily involved in regulating both the reward and stress pathways, whereas Ox2R is associated with wakefulness and arousal.

Despite differences in functionality, both receptors are structurally similar, which results in the challenge of selectively binding Ox1R over Ox2R. Previous attempts by others in the industry to selectively antagonize Ox1R have been complicated by unwanted effects from Ox2R antagonism, such as somnolence.

CVN766 has shown over 1,000-times more selectivity to Ox1R over the Ox2R in vitro, which may potentially mitigate the off-target risk of somnolence observed in competitor compounds.

orexin-1 and 2 recpetor comparison
Orexin-1 Receptor
Orexin-2 Receptor

Localized on the locus coeruleus controlling noradrenergic neurotransmission and the reward pathways of the ventral tegmental area / nucleus accumbens.
Key brain structures involved in regulating mood, motivation, addictions (including food), and behavior.Dysfunctional in psychiatric disorders, such as schizophrenia, addictions and anxiety.

Preferentially localized in the histaminergic tuberomamillary nucleus.
Controls arousal and wakefulness.Ox2R modulators targeted for sleep indications (e.g., suvorexant).

Phase 1 SAD/MAD Study

CVN766 Adverse events on the SAD study

Most commonly reported TEAEs with 2 or more subjects receiving active drug.
1TEAEs considered related to treatment. All others were unrelated to treatment.
2Ten healthy volunteers including the same two individuals receiving placebo in both the 45 mg fasted and 45 mg fed groups in the SAD portion.

CVN766 was generally well-tolerated with no adverse event (AE)-related discontinuations.

The majority of treatment emergent adverse events (TEAEs) were mild, and there were no reported serious or severe AEs.

Notably, only one subject dosed in the single ascending dose (SAD) portion reported mild somnolence as a TEAE; no somnolence was reported with repeat dosing in the multiple ascending dose (MAD) portion

The lack of somnolence is a key potential differentiator of CVN766 as daytime sleepiness is a major side effect of less selective Ox1R antagonists.

PK results for CVN766 demonstrated favorable characteristics, including a dose proportional increase in AUC and Cmax after multiple days of dosing with no observed food effect, along with robust CNS exposure.

Psychiatric & CNS-Controlled Metabolic Disorders

We plan to initiate a Phase 2 clinical trial with CVN766 in adult patients with binge eating disorder. We also intend to initiate a Phase 2 clinical trial to evaluate CVN766 in adult patients with schizophrenia. Given Ox1R is known to orchestrate numerous complex behaviors including anxiety, reward-seeking behaviors, and impulse control, we may pursue further indications, such as panic-related disorders and addictions.