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Friday, 04/08/2016 9:56:50 AM

Friday, April 08, 2016 9:56:50 AM

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From another board, science types please comment:

AGN, AVXL > Sosei deal marks Allergan’s return to business as usual

http://epvantage.com/Universal/View.aspx?type=Story&id=632030&isEPVantage=yes

Today’s Allergan deal focuses specifically on muscarinic agonists, including the muscarinic M1 agonists HTL9936 – Heptares’s lead asset – and HTL18318. Its initial focus is Alzheimer’s disease, Heptares’s chief executive, Malcolm Weir, told EP Vantage, and there is potential to go into additional CNS indications.

But he seemed to scotch the idea that the breakdown of Pfallergan had much to do with it, saying: “We’ve been talking to Allergan for months and months about this specific transaction.” Nevertheless, as yesterday’s 6% climb in the Nasdaq biotechnology index indicates, plenty of investors think that deals are back on the agenda now the two big pharma groups are set to go it alone.

It is possible that Allergan had looked at Heptares as regards the asset Teva licensed, too; shortly before the Teva deal Allergan had bought from Merck & Co two projects that also target calcitonin gene-related peptide.

Selectivity

As far as today’s tie-up goes, Allergan will clearly have studied the muscarinic space before settling on Heptares, which Mr Weir said had the most advanced project. Anavex’s phase II asset ANAVEX 2-73 is a muscarinic agonist, but also agonises the sigma-1 receptor, which Mr Weir said meant that it lacked HTL18318’s selectivity.

And selectivity is key to targeting Alzheimer’s with this approach. The rationale is based around the mechanism of Eisai’s Aricept, approved for palliative treatment of Alzheimer’s; this blocks breakdown of acetylcholine, and raised levels of this neurotransmitter stimulate muscarinic receptors, but activity at M2 and M3 receptors results in poor tolerability at high doses.

Mr Weir stressed that Heptares was able to design highly specific agonists of the M1 and M4 muscarinic receptor subtype. As another example he cited sabcomeline, a relatively non-selective muscarinic agonist ditched by GlaxoSmithKline owing to a poor risk/benefit balance.

Available phase I results for HTL9936 show initial evidence of target engagement, with no adverse events attributed to stimulating the M2 or M3 subtype. The data, announced in February, likely focused Allergan’s mind. “It’s poised to go into phase II later in the year,” said Mr Weir.

Like HTL9936, HTL18318 is specific for muscarinic M1 receptors; behind these is an M4-targeting project that could be in the clinic next year, he added, in addition to earlier-stage dual M1/M4 agonists.





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