Centessa Pharmaceuticals executives will be breathing a sigh of relief as its stock price recovered after a drop caused by the release of Phase IIa data on its experimental sleep disorder therapy.
After an initial 25% fall from a 4 November close of $23.74 to a 5 November open of $17.79, the company’s stock has seemingly settled, opening at $22.18 on 6 November.
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This came amid data readouts from the Phase IIa CRYSTAL-1 trial (NCT06752668) of ORX750, an orexin receptor type 2 (OXR2) agonist, in narcolepsy and idiopathic hypersomnia, and a Phase I trial (NCT07082829) of ORX142, also an OXR2 agonist, in healthy volunteers.
In the narcolepsy type 1 (NT1) cohort of the CRYSTAL-1 trial, patients in both dose groups (1mg and 1.5mg) of ORX750 saw statistically significant, clinically meaningful and dose-dependent improvements in mean sleep latency on the maintenance of wakefulness test (MWT).
In the 1.5mg cohort there was a more than 20-minute change in mean sleep latency at week two, with half the patients achieving more than 30 minutes in mean sleep latency on the MWT.
There was also a statistically significant, clinically meaningful and dose-dependent improvement in the Epworth sleepiness scale (ESS) in both doses, with the 1.5mg cohort achieving a mean ESS total score of 5.1 with ORX750 compared to a mean ESS total score of 18.7 with placebo after two weeks. This was down from a mean ESS total score of 19.6 at baseline.
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By GlobalDataIn the narcolepsy type 2 (NT2) cohort, dosed with 2mg and 4mg ORX750, a statistically significant, clinically meaningful and dose-dependent change in MWT was seen, with a more than 10-minute change seen in the 4mg cohort after two weeks compared to placebo. The ESS score was again statistically significant, with the 4mg cohort achieving a score of 8.1 with ORX750 compared to 15.9 in the placebo cohort.
In the idiopathic hypersomnia (IH) cohort, ORX750 achieved statistically significant and clinically meaningful improvements on multiple efficacy measures including mean sleep latency on the MWT.
Based on this data, Centessa is looking into activating registrational studies of the drug, which are due to initiate in Q1 2026. If successful, GlobalData predicts a 2028 approval for the candidate, with a 2031 sales forecast of $875m.
GlobalData is the parent company of Clinical Trials Arena.
With ORX-142, the candidate’s Phase I display was associated with a rapid onset of action, differentiated pharmacokinetics, and was observed to be generally well-tolerated. In healthy patients who were classed as “acutely sleep-deprived”, there were statistically significant and dose-dependent improvements on the MWT, paving the way for future investigation.
While the Phase IIa data is seemingly positive, it does not put the company in a stronger position than rivals Takeda and Alkermes.
Takeda’s OXR2 agonist oveporexton (TAK-861) has already shown success in two Phase III studies, teeing it up for review by global regulators. GlobalData predicts approval for Takeda’s candidate in 2026, with a 2031 sales forecast of $1.33bn.
Alkermes is also racing ahead with alixorexton, which is due to move into Phase III trials in early 2026. GlobalData predicts a 2028 approval for Alkermes’ OX2R, with a sales forecast of $778m in 2031.
In 2020, Jazz Pharmaceuticals’ Xywav (calcium, magnesium, potassium, and sodium oxybates) was approved by the FDA and was the first approved new treatment option indicated for both cataplexy and excessive daytime sleepiness in people living with narcolepsy in more than 15 years.
Treatment options for NT1 include trying to manage a regular sleeping pattern, as well as therapies, including stimulants such as Provigil (modafinil), Nuvigil (armodafinil), and Ritalin (methylphenidate) to promote wakefulness. Patients may also receive solriamfetol or pitolisant.
Editors note: Indications have been added to the individual treatment cohorts and data on IH has been added.
