UPDATE: Astellas's European Screen Yields Ogeda

April 03, 2017 UPDATE: Astellas’s European screen yields Ogeda

Jacob Plieth

Japanese companies’ desire to grow in the west is a well-known biopharma phenomenon. But Astellas’s move yesterday to buy Ogeda – a private Belgian group formerly known as Euroscreen – seems more driven by a wish to own a particular asset than by expansion plans.

Ogeda’s lead product is a neurokinin-3 receptor antagonist called fezolinetant, one of just a handful of industry assets with this mechanism. The up-front fee of €500m ($533m) looks rich, but the takeout was clearly triggered by recent unveiling of phase II data in menopausal symptoms, and these must have focused attention in Astellas’s C-suite.

The phase II data, announced in January, showed fezolinetant to reduce the frequency and severity of menopausal hot flashes versus placebo, with statistical significance, in 80 women suffering from menopause- related vasomotor symptoms. At that point Ogeda said it would develop the project as a breakthrough treatment for hot flashes, aiming to start a larger phase IIb study later this year.

Subsidiary

The takeout by Astellas means that this will no longer be necessary, with Ogeda and all its assets becoming a subsidiary of the Japanese group, and an additional €300m coming Ogeda’s sellers’ way if future milestones are met.

It is not yet clear how Ogeda, which was founded as Euroscreen in 1994, will be run under the Astellas umbrella. If the template is Heptares, the private UK neuroscience company bought by Sosei in 2015, then the current management team can expect a lot of autonomy and an arm’s-length relationship with its new parent.

Ogeda’s focus is on therapeutics against G protein-coupled receptors (GPCRs), which have numerous biological applications, though fezolinetant is its only clinical asset. Fezolinetant’s target is the GPCR neutokinin-3 receptor, which was earlier thought to have utility in central nervous system disorders.

However, early leads faltered in clinical development, including Sanofi’s osanetant and Glaxosmithkline’s talnetant for schizophrenia. EvaluatePharma data suggest that beyond fezolinetant there is only one other clinical-stage agent acting solely on neurokinin-3 – Millendo Therapeutics’ MLE4901, in phase II for polycystic ovarian syndrome.

This is also a potential indication for fezolinetant, while Millendo cites menopausal hot flashes as an additional use for MLE4901. Millendo comprises the women’s health business that was spun out of Astrazeneca a year ago, and coincidentally reported publication in The Lancet of hot flash data the day after Ogeda's takeout.

These investigator-initiated phase II results showed MLE4901 to reduce total weekly hot flashes by 73% at the end of four weeks' treatment, versus a 28% reduction with placebo (p<0.0001), in 28 patients with menopause-related vasomotor symptoms.

Neurokinin-3 antagonists in clinical development (all phase II)

Project Company Pharmacology class Trial ID

MLE4901 Millendo Therapeutics Neurokinin-3 antagonist NCT02865915

Fezolinetant Ogeda (Astellas) Neurokinin-3 antagonist None

NT-814 Nerre Therapeutics Neurokinin-1 & neurokinin-3 antagonist NCT02865538

Source: EvaluatePharma

Nerre Therapeutics, a private UK company, has a number of early-stage neurokinin antagonists in development. NT-814, which it says has dual activity against neurokinin-1 as well as 3, is in phase II studies for post-menopausal vasomotor symptoms as well as in opiate use disorder.

The relevance of neurokinin-3 in women’s health is thought to result from the modulatory role the receptors play on the kisspeptin-neurokinin B-dynorphin network, which Nerre says controls the body’s heat-dissipating thermoregulatory centre and the hypothalamic-pituitary-gonadotrophin axis that regulates sex hormone release.

It is not clear why Astellas passed on Nerre and Millendo before settling on Ogeda, though clearly price and breadth of each portfolio will have played a part. Likewise it will be interesting to see if any earlier neurokinin-3 assets are dusted off and repurposed for women’s health.

This story was updated to reflect publication of Millendo's data in The Lancet.

To contact the writer of this story email Jacob Plieth in London at [email protected] or follow @JacobPlieth on Twitter