French biotech In­ven­ti­va's lead drug stum­bles in sys­temic scle­ro­sis study, ahead of NASH read­out

France’s In­ven­ti­va (Eu­ronext: $IVA) has suf­fered its first big set­back fol­low­ing its pub­lic list­ing in 2017. The com­pa­ny’s lead ex­per­i­men­tal drug, lan­i­fi­bra­nor, failed a mid-stage tri­al in pa­tients with a form of sys­temic scle­ro­sis (SSc) — a rare, chron­ic life-threat­en­ing dis­or­der in which the im­mune sys­tem at­tacks its own or­gans and is char­ac­ter­ized by a buildup of scar tis­sue — prompt­ing the Daix-based drug de­vel­op­er to aban­don the pro­gram for the in­di­ca­tion.

The Phase IIb tri­al eval­u­at­ed two dos­es of lan­i­fi­bra­nor (800 mg, 1200 mg) against a place­bo in 145 pa­tients with dif­fuse cu­ta­neous sys­temic scle­ro­sis, which ac­count for rough­ly 35% of the SSc pop­u­la­tion. Pa­tients were giv­en lan­i­fi­bra­nor in ei­ther two dos­es of 400mg per day or two dos­es of 600mg per day over 48 weeks in ad­di­tion to stan­dard of care, which typ­i­cal­ly in­clud­ed im­muno­sup­pres­sive ther­a­py.

Com­pared to the place­bo, nei­ther dose of the drug in­duced a sta­tis­ti­cal­ly sig­nif­i­cant change in the mod­i­fied Rod­nan Skin Score — a scale mea­sur­ing the evo­lu­tion of skin fi­bro­sis, which is cor­re­lat­ed with in­ter­nal scar­ring — miss­ing the main goal of the study. None of the sec­ondary end­points, in­clud­ing changes in pul­monary func­tion mea­sured via forced vi­tal ca­pac­i­ty and over­all pro­gres­sion of the dis­ease, were met, In­ven­ti­va said on Mon­day.

There are no ap­proved ther­a­pies for SSc, a dis­ease that dis­pro­por­tion­ate­ly af­fects women. Ac­cord­ing to an­a­lysts at H.C. Wain­wright, the dif­fuse cu­ta­neous form of the dis­ease trans­lates to an ad­dress­able mar­ket of about 23,500 pa­tients in the Eu­rope and 31,500 in the Unit­ed States.

Lan­i­fi­bra­nor is an oral small mol­e­cule de­signed to spark an­tifi­brot­ic, an­ti-in­flam­ma­to­ry changes by spurring three iso­forms — α, δ and γ — of PPAR (per­ox­i­some pro­lif­er­a­tor-ac­ti­vat­ed re­cep­tor), which are nu­clear re­cep­tor pro­teins that reg­u­late gene ex­pres­sion. There are oth­er PPAR ag­o­nists on the mar­ket (in­clud­ing di­a­betes drug pi­ogli­ta­zone) and in de­vel­op­ment (ex­per­i­men­tal NASH drugs such as Gen­fit’s elafi­bra­nor and CymaBay’s se­ladel­par) that tar­get on­ly one or two PPAR iso­forms for ac­ti­va­tion, but lan­i­fi­bra­nor is a pan-PPAR ag­o­nist like bezafi­brate, which In­ter­cept ac­quired last month to de­vel­op in com­bi­na­tion with its NASH con­tender obeti­cholic acid.

In­ven­ti­va is al­so test­ing lan­i­fi­bra­nor for NASH — a fat­ty liv­er dis­ease af­fect­ing mil­lions that has no ap­proved ther­a­pies — which has thus cap­ti­vat­ed a pletho­ra of drug de­vel­op­ers, in­clud­ing Gilead $GILD, In­ter­cept $ICPT and Gen­fit (Eu­ronext: $GN­FT). In­ven­ti­va’s Phase IIb tri­al for lan­i­fi­bra­nor in NASH pa­tients is ex­pect­ed to read­out in the first half of 2020.

In a note ear­li­er this month, H.C. Wain­wright an­a­lysts sug­gest­ed that pos­i­tive SSc da­ta would bode well for In­ven­ti­va’s NASH pro­gram: “(Grow­ing) clin­i­cal ev­i­dence points to a mech­a­nis­tic link be­tween fi­brot­ic NASH and cer­tain in­flam­ma­to­ry skin con­di­tions, like pso­ri­a­sis…  an­oth­er an­ti-fi­brot­ic agent in de­vel­op­ment for NASH, Galectin Ther­a­peu­tics’ GR-MD-02, has sep­a­rate­ly re­port­ed sig­nif­i­cant im­prove­ment in pa­tients across both plaque pso­ri­a­sis and cir­rhot­ic NASH.”

Last year, In­ven­ti­va raised raised about $44 mil­lion from a group of ven­ture back­ers, in­clud­ing Paris-based Sofinno­va, af­ter go­ing pub­lic in 2017 in a $51 mil­lion IPO. The com­pa­ny, which has pro­grams part­nered with Ab­b­Vie and Boehringer In­gel­heim, was spun out of Ab­bott in 2012.

BiTE® Plat­form and the Evo­lu­tion To­ward Off-The-Shelf Im­muno-On­col­o­gy Ap­proach­es

Despite rapid advances in the field of immuno-oncology that have transformed the cancer treatment landscape, many cancer patients are still left behind.1,2 Not every person has access to innovative therapies designed specifically to treat his or her disease. Many currently available immuno-oncology-based approaches and chemotherapies have brought long-term benefits to some patients — but many patients still need other therapeutic options.3

Is a pow­er­house Mer­ck team prepar­ing to leap past Roche — and leave Gilead and Bris­tol My­ers be­hind — in the race to TIG­IT dom­i­na­tion?

Roche caused quite a stir at ASCO with its first look at some positive — but not so impressive — data for their combination of Tecentriq with their anti-TIGIT drug tiragolumab. But some analysts believe that Merck is positioned to make a bid — soon — for the lead in the race to a second-wave combo immuno-oncology approach with its own ambitious early-stage program tied to a dominant Keytruda.

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President Donald Trump (left) and Moncef Slaoui, head of Operation Warp Speed (Alex Brandon, AP Images)

UP­DAT­ED: White House names fi­nal­ists for Op­er­a­tion Warp Speed — with 5 ex­pect­ed names and one no­table omis­sion

A month after word first broke of the Trump Administration’s plan to rapidly accelerate the development and production of a Covid-19 vaccine, the White House has selected the five vaccine candidates they consider most likely to succeed, The New York Times reported.

Most of the names in the plan, known as Operation Warp Speed, will come as little surprise to those who have watched the last four months of vaccine developments: Moderna, which was the first vaccine to reach humans and is now the furthest along of any US effort; J&J, which has not gone into trials but received around $500 million in funding from BARDA earlier this year; the joint AstraZeneca-Oxford venture which was granted $1.2 billion from BARDA two weeks ago; Pfizer, which has been working with the mRNA biotech BioNTech; and Merck, which just entered the race and expects to put their two vaccine candidates into humans later this year.

Leen Kawas, Athira CEO (Athira)

Can a small biotech suc­cess­ful­ly tack­le an Ever­est climb like Alzheimer’s? Athi­ra has $85M and some in­flu­en­tial back­ers ready to give it a shot

There haven’t been a lot of big venture rounds for biotech companies looking to run a Phase II study in Alzheimer’s.

The field has been a disaster over the past decade. Amyloid didn’t pan out as a target — going down in a litany of Phase III failures — and is now making its last stand at Biogen. Tau is a comer, but when you look around and all you see is destruction, the idea of backing a startup trying to find complex cocktails to swing the course of this devilishly complicated memory-wasting disease would daunt the pluckiest investors.

GSK presents case to ex­pand use of its lu­pus drug in pa­tients with kid­ney dis­ease, but the field is evolv­ing. How long will the mo­nop­oly last?

In 2011, GlaxoSmithKline’s Benlysta became the first biologic to win approval for lupus patients. Nine years on, the British drugmaker has unveiled detailed positive results from a study testing the drug in lupus patients with associated kidney disease — a post-marketing requirement from the initial FDA approval.

Lupus is a drug developer’s nightmare. In the last six decades, there has been just one FDA approval (Benlysta), with the field resembling a graveyard in recent years with a string of failures including UCB and Biogen’s late-stage flop, as well as defeats in Xencor and Sanofi’s programs. One of the main reasons the success has eluded researchers is because lupus, akin to cancer, is not just one disease — it really is a disease of many diseases, noted Al Roy, executive director of Lupus Clinical Investigators Network, an initiative of New York-based Lupus Research Alliance that claims it is the world’s leading private funder of lupus research, in an interview.

Gilead bol­sters its case for block­buster hope­ful fil­go­tinib as FDA pon­ders its de­ci­sion

Before remdesivir soaked up the spotlight amid the coronavirus crisis, Gilead’s filgotinib was the star experimental drug tapped to rake in billions competing with other JAK inhibitors made by rivals including AbbVie and Eli Lilly.

Now, long term data on the drug — discovered by Gilead’s partners at Galapagos and posted as part of a virtual medical conference — have solidified the durability and safety of filgotinib in patients with rheumatoid arthritis, spanning data from three late-stage trials. An FDA decision on the drug is expected this year.

Bris­tol-My­ers is clean­ing up the post-Cel­gene merg­er pipeline, and they’re sweep­ing out an ex­per­i­men­tal check­point in the process

Back during the lead up to the $74 billion buyout of Celgene, the big biotech’s leadership did a little housecleaning with a major pact it had forged with Jounce. Out went the $2.6 billion deal and a collaboration on ICOS and PD-1.

Celgene, though, also added a $530 million deal — $50 million up front — to get the worldwide rights to JTX-8064, a drug that targets the LILRB2 receptor on macrophages.

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Covid-19 roundup: Mod­er­na read­ies to en­ter PhI­II in Ju­ly, As­traZeneca not far be­hind; EU ready to ne­go­ti­ate vac­cine ac­cess with $2.7B fund

Moderna may soon add another first to the Covid-19 vaccine race.

In March, the mRNA biotech was the first company to put a Covid-19 vaccine into humans. Next month, they may become the first company to put their vaccine into the large, late-stage trials that are needed to prove whether the vaccine is effective.

In an interview with JAMA editor Howard Bauchner, NIAID chief Anthony Fauci said that a 30,000-person, Phase III trial for Moderna’s vaccine could start in July. The news comes a week after Moderna began a Phase II study that will enroll several hundred people.

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New safe­ty da­ta ex­pose po­ten­tial weak­ness as Pfiz­er's abroc­i­tinib takes on Dupix­ent in eczema

Last September, when Pfizer celebrated positive data from a second Phase III study of abrocitinib, many watchers applauded the efficacy but were still waiting to see whether the JAK1 inhibitor is “safe enough to be a formidable competitor to Dupixent,” the clear leader in the atopic dermatitis field. The full slate of safety data are now out and, according to one analyst, the answer is: probably not.