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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:
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What are the prospects for Takeda’s phase 3 program in NT1?
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How differentiated would a follow-on ORX750 entering the NT1 market approximately 2 years later be?
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NT2: What can be concluded from the published NT2 data from TAK-861 on the prospects of ORX750 in NT2?
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Toxicity: Are visual disturbances a class effect?
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How manageable are the urinary frequency symptoms?
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How manageable are the insomnia side effects inherent in the mechanism of action?
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What is the likely toxicity profile for ORX750?
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Will a once-a-day formulation of similar efficacy from CNTA be enough to take a significant share from a likely established TAK-861?
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Any differences in cognition and nighttime symptoms between TAK-861 & ORX750?
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Dr Amit Roy, Founding Partner
Dr Roy has been serving the Hedge Fund and Mutual Fund community for 20 years with bold, contrarian research, founding Foveal LLP in 2014.
After graduating from the University of Cambridge and gaining Membership of the Royal College of Surgeons, he became one of the youngest Cardio-Thoracic surgeons in the U.K. He developed a unique insight into the drivers of drug safety and pharmaceutical risk assessment during his years in R&D at Roche Pharmaceuticals, while gaining an MBA from London Business School. Amit was a Managing Director at Nomura and head of European Healthcare Equity Research since 2008, having joined from Citigroup. He has delivered a consistent, strong track record of predicting the outcomes of key catalysts and value drivers in the biotech & pharma sectors for over 20 years, yielding persistent alpha for his clients.
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