The other shoe drops for Theravance

 After the failure of Theravance’s gut-selective Jak inhibitor izencitinib last month the company’s hopes hinged on getting a result with ampreloxetine in neurogenic orthostatic hypotension. Today the latter project was also revealed to be a dud, and the group has slashed its headcount and R&D efforts in response. Such an outcome was entirely predictable given unconvincing phase 1/2 ampreloxetine data, and a restructuring had also been foreseen by Leerink analysts. More surprisingly, Theravance does not seem to have learned its lesson: the group’s core assets now include the inhaled Jak inhibitor nezulcitinib, which is in development for acute lung injury despite recently failing a Covid-19 trial. More sensible, if unexciting, is a focus on the approved respiratory products Trelegy, on which Theravance receives royalties from Glaxosmithkline, and Yupelri, sold in partnership with Viatris. Theravance hopes that its streamlining will allow it to become “sustainably cash flow positive” by the second half of 2022, but many investors are not hanging around to find out. The company, already worth less than half of what it was at the start of the year, fell another 22% this morning.

The new-look Theravance
Project	Description	Setting	Trial details
Still in play
Nezulcitinib (TD-0903)	Lung-selective Jak inhibitor	Acute lung injury	Failed ph2 in Covid-19, development continues in acute lung injury
Unnamed	Dry-powder Jak inhibitors	Asthma	Preclinical
Out of favour
Ampreloxetine (TD-9855)	Norepinephrine reuptake inhibitor	Neurogenic orthostatic hypotension	Failed ph3 Sequoia; ph3 Redwood being closed out
Izencitinib (TD-1473)*	Gut-selective Jak inhibitor	Ulcerative colitis, Crohn's	Failed ph2b Rhea in UC; ph2 Dione in Crohn's reads out Q4'21/Q1'22
TD-8236	Lung-selective Jak inhibitor	Asthma	Failed in ph2a asthma allergen challenge trial; development "paused"
TD-5202*	Gut-selective Jak inhibitor	Coeliac disease	Ph1 in healthy volunteers completed; deprioritised
Inhaled ALK5i	Inhaled Alk5 inhibitor	Idiopathic pulmonary fibrosis	Ph1; presumed deprioritised
*Being developed in partnership with J&J. Source: Evaluate Pharma & clinicaltrials.gov. https://www.evaluate.com/vantage/articles/news/snippets/other-shoe-drops-theravance