The atopic der­mati­tis mar­ket is crowd­ed. Dupix­ent, from Re­gen­eron and Sanofi, may be king of the ar­se­nal of ther­a­pies to com­bat eczema — but var­i­ous drug­mak­ers big and small are out to usurp its throne. Pfiz­er on Fri­day made its pitch, with a sec­ond slate of pos­i­tive late-stage da­ta on its ex­per­i­men­tal drug, abroc­i­tinib.

Abroc­i­tinib be­longs to a class of drugs called Janus ki­nase (JAK) in­hibitors — which have been plagued with safe­ty con­cerns. Named af­ter the two-faced Ro­man God Janus, the fam­i­ly con­sists of four en­zymes: JAK1, JAK2, JAK3 and TYK2, which are as­so­ci­at­ed with cy­tokine re­cep­tors on the sur­face of cells and form part of a path­way in­volved in in­flam­ma­to­ry and im­mune re­spons­es.

Abroc­i­tinib, a JAK1 in­hibitor, is thought to mod­u­late mul­ti­ple cy­tokines in­volved in the patho­phys­i­ol­o­gy of eczema in­clud­ing in­ter­leukin (IL)-4, IL-13, IL-31, and in­ter­fer­on gam­ma. On Fri­day, the US drug­mak­er said it had met goals of the 391-pa­tient JADE MONO-2 study, which test­ed two dos­es (100mg and 200mg once dai­ly) of the drug against a place­bo.

Con­sis­tent with the JADE MONO-1 tri­al, da­ta from this study showed that by week 12 the per­cent­age of pa­tients achiev­ing each co-pri­ma­ry ef­fi­ca­cy end­point, as well as each key sec­ondary end­point, with ei­ther dose of abroc­i­tinib was sta­tis­ti­cal­ly sig­nif­i­cant­ly high­er than place­bo. In ad­di­tion, a sta­tis­ti­cal­ly sig­nif­i­cant num­ber of pa­tients achieved a re­duc­tion in pru­ri­tus (se­vere itch­ing) by week 2, as mea­sured by a four-point or larg­er re­duc­tion in itch sever­i­ty mea­sured with the pru­ri­tus nu­mer­i­cal rat­ing scale (NRS).

De­tailed da­ta from JADE MONO-1 are ex­pect­ed at a Madrid con­fer­ence in Oc­to­ber, Pfiz­er $PFE said, adding that re­sults from a tri­al test­ing abroc­i­tinib against an ac­tive con­trol should read­out in spring 2020.

There are var­i­ous JAK in­hibitors on the mar­ket ap­proved for a range of im­mune-me­di­at­ed dis­eases. Pfiz­er al­ready has a JAK1/JAK3 in­hibitor — Xel­janz — in its port­fo­lio, al­though its use has been blight­ed by reg­u­la­to­ry re­stric­tions af­ter the high­er dose of the block­buster drug was found to be as­so­ci­at­ed with the risk of blood clots and death.

Eli Lil­ly’s $LLY JAK1/JAK2 Olu­mi­ant, mean­while, was ini­tial­ly re­ject­ed by the US agency due to safe­ty con­cerns — on­ly to even­tu­al­ly se­cure ap­proval for the low­er dose. Lil­ly’s part­ner, In­cyte $IN­CY, elect­ed to walk away from co-fund­ing the drug’s de­vel­op­ment as fears about the ben­e­fit-risk pro­file of the class of drugs ac­cu­mu­lat­ed. Last month Ab­b­Vie’s $AB­BV JAK1 upadac­i­tinib was cleared by the FDA for rheuma­toid arthri­tis with a black box warn­ing, a fea­ture an­a­lysts ex­pect will be in­cor­po­rat­ed in­to the la­bel of Gilead’s $GILD Gala­pa­gos-part­nered fil­go­tinib, should it se­cure ap­proval.

In terms of atopic der­mati­tis specif­i­cal­ly, Re­gen­eron $REGN and Sanofi’s $SNY Dupix­ent (chem­i­cal­ly known as dupilum­ab) was the first bi­o­log­ic to win ap­proval for the con­di­tion in 2017, and is now the de-fac­to leader in the mar­ket. It is en­gi­neered to in­hib­it the sig­nal­ing of IL-4 and IL-13 — two pro­teins that like­ly play a key role in the in­flam­ma­tion that un­der­lies eczema and a host of al­ler­gic dis­eases.

“While dupilum­ab (dupi) has set an ex­treme­ly high bar in AD, the evolv­ing com­pet­i­tive land­scape has not been quite as strong yet. Re­cent de­vel­op­ments serve as im­por­tant re­minders that the ‘crowd­ed’ AD land­scape may not look quite as con­gest­ed once the dust starts to set­tle and the win­ners cre­ate sep­a­ra­tion from the rest of the pack,” SVB Leerink an­a­lysts wrote in a note in June.

In Pfiz­er’s JADE MONO-2 study, abroc­i­tinib’s safe­ty pro­file was less than straight­for­ward. The fre­quen­cy of treat­ment-emer­gent ad­verse events was high­er in treat­ment arms ver­sus place­bo, and one pa­tient with co-ex­ist­ing car­dio­vas­cu­lar risk fac­tors died three weeks fol­low­ing the study from un­known eti­ol­o­gy — al­though the drug­mak­er said the event was not re­lat­ed to abroc­i­tinib.

“While we ex­pect ef­fi­ca­cy for abroc­i­tinib to be po­ten­tial­ly com­pa­ra­ble to Re­gen­eron’s Dupix­ent, many ques­tions re­main whether abroc­i­tinib is safe enough to be a for­mi­da­ble com­peti­tor to Dupix­ent,” Cred­it Su­isse’s Evan Seiger­man wrote in a note. “We ex­pect in­ten­si­fy­ing com­pe­ti­tion in AD over the next few years from nov­el JAK in­hibitors (abroc­i­tinib, Ab­b­Vie’s upadac­i­tinib) and nov­el bi­o­log­ics (name­ly tar­get­ing IL-13 and 33).”

So­cial im­age: AP

The average level of investment required for a biotech start-up to succeed is increasing every year, elevating the pressure even further on venture capital to make smart financial investments. Financial investment alone, however, does not always guarantee that exciting innovations can be transformed into real businesses that make a meaningful difference to patients.

Beyond just capital

At Astellas Venture Management (AVM) – a wholly-owned venture capital organization within Astellas, headquartered in the San Francisco Bay Area – capital is just one of the ingredients we offer to add value to our biotechnology investments and partnerships. We generally take a strategic investor approach for companies in our invested portfolio, providing access to expertise, technology and/or resources in addition to the injection of finance. An equity investment from AVM can include access to Astellas’ research and development (R&D) capabilities and expertise, and a global network of partner academic institutions and biotechnology companies, to help advance and accelerate the start-up’s innovation.

Unum $UMRX is working its way through a survival plan of sorts.

After getting hit with a trio of FDA holds in its brief public history and triggering its second pivot to a new lead drug program while laying off 60% of the staff, the troubled penny stock biotech Unum Therapeutics has hatched new plans to secure financial backing while lining up a go-forward strategy for the company.

First, Lincoln Park Capital Fund has agreed to buy up to $25 million of the long-suffering stock, as Unum directs. And the executive team — led by CEO Chuck Wilson — has put everything on the table for consideration: a sale, acquisition, merger, licensing deal, you name it. The ACTR707 program, meanwhile, is being formally wrapped up — their second failed lead program.