Heart­burn: Iron­wood shares sink af­ter block­buster con­tender dis­ap­points on a key goal in PhI­Ib

Iron­wood Phar­ma­ceu­ti­cals $IR­WD CEO Pe­ter Hecht has some block­buster ex­pec­ta­tions for one of his top clin­i­cal can­di­dates. But he’s hav­ing a hard time con­vinc­ing an­a­lysts and in­vestors of that to­day af­ter rolling out a dis­ap­point­ing batch of top-line da­ta.

The biotech re­port­ed Thurs­day morn­ing that the high dose of its ex­per­i­men­tal drug — IW-3718 — for gas­troe­sophageal re­flux dis­ease (GERD) not con­trolled by avail­able meds hit the pri­ma­ry end­point on sig­nif­i­cant­ly re­duc­ing heart­burn sever­i­ty for pa­tients in a Phase IIb tri­al.

Pe­ter Hecht

Among pa­tients tak­ing a com­bi­na­tion of 1500 mg IW-3718 and a pro­ton pump in­hibitor like Nex­i­um, there was a 58% mean de­crease in heart­burn sever­i­ty. That’s high, but there was al­so a high re­sponse for the PPI-on­ly group, with a 46% drop. That 12-point sep­a­ra­tion was sta­tis­ti­cal­ly sig­nif­i­cant, says Iron­wood, with a p-val­ue of 0.04.

An­a­lysts, though, were dis­ap­prov­ing, not­ing they were look­ing for a 15-point or greater sep­a­ra­tion from the con­trol group — as guid­ed by the com­pa­ny. That is­sue came up quick­ly on the call this morn­ing as an­a­lysts weighed the short­fall. Ex­ecs called it a clear suc­cess, even with­out hit­ting that 15% mark. In ad­di­tion, the crew at Iron­wood al­so con­ced­ed that the 500 mg and 1000 mg dos­es were not suc­cess­ful against all end­points.

On an­oth­er key score, pa­tients treat­ed with IW-3718 1500 mg plus a PPI showed a mean de­crease of 55.4% from base­line in re­gur­gi­ta­tion fre­quen­cy com­pared to 37.9% in pa­tients treat­ed with a PPI alone.

Iron­wood shares slid 7% in ear­ly morn­ing trad­ing as in­vestors weighed in on the da­ta.

Ge­off Meacham at Bar­clays sum­ma­rized the dis­en­chant­ment with Iron­wood to­day, which has billed IW-3718 as a drug worth $2 bil­lion-plus per year in peak sales.

While the da­ta and val­i­da­tion of the pa­tient re­port­ed out­comes (PRO) in­stru­ment sup­port ad­vance­ment in­to the planned Phase III (an­tic­i­pat­ed start in 2H18), we think the clin­i­cal mean­ing­ful­ness of the 12-point re­duc­tion in heart­burn sever­i­ty will re­main a point of de­bate.  More­over, even though there are no treat­ment al­ter­na­tives or com­peti­tors in the re­frac­to­ry GERD cat­e­go­ry, we be­lieve that in­vestors will per­ceive IW-3718’s com­mer­cial po­ten­tial as some­what damp­ened giv­en the low­er than ex­pect­ed dif­fer­ence.  We see a 2020 launch as more like­ly now but al­so view the com­pa­ny’s >$2B peak US sales tar­get as po­ten­tial­ly am­bi­tious ab­sent more de­tailed da­ta.

David Nieren­garten at Wed­bush al­so didn’t care for the nasty sur­prise, not­ing that the Phase III now looks “long, ex­pen­sive and high-risk.”

Armed with the da­ta, Iron­wood says that they will now take the da­ta to the FDA and plan to set up a piv­otal pro­gram to get start­ed in the sec­ond half of 2018.

This drug is a key cat­a­lyst for Iron­wood, which sees this as a big ad­di­tion to its Linzess fran­chise.

“This is a re­al sci­en­tif­ic break­through,” Hecht told an­a­lysts Thurs­day morn­ing.

“The re­sults from this tri­al, demon­strat­ing en­cour­ag­ing im­prove­ments in heart­burn sever­i­ty and re­gur­gi­ta­tion, ap­pear to val­i­date our ap­proach of tar­get­ing bile acid re­flux in pa­tients with un­con­trolled GERD in ad­di­tion to sup­press­ing acid with PPIs,” said Mark Cur­rie, chief sci­en­tif­ic of­fi­cer at Iron­wood, in a state­ment. “These da­ta were con­sis­tent and ro­bust across key end­points, and re­in­force our be­lief that IW-3718 may lead to mean­ing­ful symp­tom re­lief for pa­tients with un­con­trolled GERD.”

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

Covid-19 roundup: As­traZeneca shoots for 2B dos­es of Ox­ford vac­cine — with $750M from CEPI, Gavi

Forget 1 billion. AstraZeneca is now promising to supply 2 billion doses of Oxford University’s Covid-19 vaccine around the world per year.

Three new partners are coming on board to help reach that goal, as well as a broader vision to ensure access for nations that have been largely left out of the bargaining table.

CEPI — the coalition that’s been doling out grants to support other vaccine projects — is providing $383 million to support manufacturing of 300 million doses, while Gavi the Vaccine Alliance will chip in $367 million and be in charge of the procurement and distribution, a spokesperson told Wall Street Journal. A separate licensing agreement directs the Serum Institute of India to produce 1 billion doses for low- and middle-income countries, with the first 400 million due before the end of the year.

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.

Michael Gladstone, partner at Atlas Venture

At­las rais­es new $400M fund amid spree of VC rais­es. Here’s what they’ll spend it on

You can add another few hundred million to the now Montana-sized reservoir of cash biotech VCs have raised since the WHO declared Covid-19 a pandemic.

Atlas Venture, the prominent Kendall Square incubator, has raised $400 million for its twelfth biotech fund, their first in 3 years. After a string of mammoth new raises from other major VCs in April and May, the total pot now stands between $5 billion and $6 billion, depending on how you slice it.

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UP­DAT­ED: Es­ti­mat­ing a US price tag of $5K per course, remde­sivir is set to make bil­lions for Gilead, says key an­a­lyst

Data on remdesivir — the first drug shown to benefit Covid-19 patients in a randomized, controlled trial setting — may be murky, but its maker Gilead could reap billions from the sales of the failed Ebola therapy, according to an estimate by a prominent Wall Street analyst. However, the forecast, which is based on a $5,000-per-course US price tag, triggered the ire of one top drug price expert.

FDA de­lays de­ci­sion on No­var­tis’ po­ten­tial block­buster MS drug, wip­ing away pri­or­i­ty re­view

So much for a speedy review.

In February, Novartis announced that an application for their much-touted multiple sclerosis drug ofatumumab had been accepted and, with the drug company cashing in on one of their priority review vouchers, the agency was due for a decision by June.

But with June less than 48 hours old, Novartis announced the agency has extended their review, pushing back the timeline for approval or rejection to September. The Swiss pharma filed the application in December, meaning their new schedule will be nearly in line with the standard 10-month window period had they not used the priority voucher.

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