Astra bake-off cooks up a new inhaled Jak

 Astrazeneca today disclosed that it has canned AZD0449, an inhaled Jak in development for asthma – but the group has not given up on this mechanism, and is instead now prioritising a similarly acting project, AZD4604. Astra’s head of biopharmaceuticals R&D, Mene Pangalos, said there had been a “bake-off” between these two assets, and that AZD4604 had won out on measures including lung distribution and toxicology. The inhaled Jak pipeline is looking sparser than it once was, with Roche discontinuing RG6151 and Theravance “pausing” development of TD-8236. The latter group is still in the game with nezulcitinib, but it is unclear how much it can invest in this asset after two clinical disasters last year led to a cost-cutting drive. Nezulcitinib has already failed in Covid, but Theravance thinks it still has potential in acute lung injury and fibrotic disease; however, trials here have yet to begin. This leaves the private company Kinaset as Astrazeneca’s main competitor, with early results on its contender, KN-002, due soon. Kinaset says a pan-Jak strategy is required for inhaled assets, while with AZD4604 Astrazeneca is sticking to a selective approach.

Selected inhaled Jak inhibitors in development
Project	Company	Mechanism	Indication(s)	Trial details/note
Nezulcitinib (TD-0903)	Theravance	Jak 1-3 & Tyk2 inhibitor	Acute lung injury, fibrotic disease	Failed ph2 in Covid-19
KN-002	Kinaset (ex Vectura)	Jak 1-3 & Tyk2 inhibitor	Asthma	Ph1 in healthy volunteers & pts, topline results due early 2022
AZD4604	Astrazeneca	Jak 1 inhibitor	Asthma	Ph1 in healthy volunteers, ends Sep 2022
Unnamed	Theravance	"Pan-Jak inhibitor"	Asthma	Preclinical; plans to progress to clinic via strategic partnership
Fallen by the wayside
AZD0449	Astrazeneca/Rigel	Jak 1 inhibitor	Asthma	Removed from ph1 2022
RG6151 (GCD-0214)	Roche	Jak 1 inhibitor	Asthma	Removed from ph1 Apr 2021
TD-8236	Theravance	Jak 1-3 & Tyk2 inhibitor	Asthma	Failed ph2 lung allergen challenge study in mild asthma; programmed "paused"
Source: Evaluate Pharma, clinicaltrials.gov & company presentations. https://www.evaluate.com/vantage/articles/news/corporate-strategy-snippets/astra-bake-cooks-new-inhaled-jak