Foveal LLP Independent Investment Research Foveal Research

CNTA/4502/ALKS: Differentiation challenges for CNTA ORX750 orexin agonist vs Takeda in NT1&2, despite clean phase 1

October 14, 2025

Ahead of CNTA’s ORX750 phase 2 data and after the recent publication of Takeda’s orexin agonist oveporexton (TAK-861) two phase 3 trials, interest in competitor orexin agonists from CNTA and ALKS in both narcolepsy type I (NT1), as well as related narcolepsy type II (NT2) and hyper insomnia, have come back into focus. We undertake an in-depth analysis of the current orexin agonist efficacy and safety data to make a like-for-like comparison of oveporexton with Centessa’s very early-phase I ORX750 data and ALKS 2680's recent phase 2 data. We highlight several difficulties for CNTA in demonstrating differentiation from Takeda’s TAK861, besides being once a day, as a likely second to market in NT1, as well as unclear prospects in the naïve NT2 market.

 

Questions addressed include:

• What are the prospects for Takeda’s phase 3 program in NT1?

• How differentiated would a follow-on ORX750 entering the NT1 market approximately 2 years later be?

• NT2: What can be concluded from the published NT2 data from TAK-861 on the prospects of ORX750 in NT2?

• Toxicity: Are visual disturbances a class effect?

• How manageable are the urinary frequency symptoms?

• How manageable are the insomnia side effects inherent in the mechanism of action?

• What is the likely toxicity profile for ORX750?

• Will a once-a-day formulation of similar efficacy from CNTA be enough to take a significant share from a likely established TAK-861?

• Any differences in cognition and nighttime symptoms between TAK-861 & ORX750?