Ther­a­vance takes a gut punch as J&J-part­nered JAK drug flops key test in ul­cer­a­tive col­i­tis

When J&J signed a $100 mil­lion check away to biotech Ther­a­vance back in 2018, the drug gi­ant saw some promise in the com­pa­ny’s lead “pan-JAK” drug in in­flam­ma­to­ry bow­el dis­ease. A key tri­al check­point for that is now of­fi­cial­ly a dud — and the J&J deal may be dead in the wa­ter as well.

Ther­a­vance’s izenci­tinib, a “gut-se­lec­tive” JAK in­hibitor de­vel­oped for ul­cer­a­tive col­i­tis and Crohn’s dis­ease, failed a key Phase II test, giv­ing the com­pa­ny no choice but to slice R&D costs on that pro­gram and send in­vestors run­ning for the hills. A planned Phase III study in UC al­so won’t be hap­pen­ing, ex­ec­u­tives con­firmed on a Mon­day call with an­a­lysts.

In the eight-week in­duc­tion por­tion of the Phase II tri­al, izenci­tinib failed to show ben­e­fit over place­bo on the Mayo score im­prove­ment pri­ma­ry end­point or clin­i­cal re­mis­sion, a key sec­ondary end­point. The drug­mak­er not­ed “a small dose-de­pen­dent in­crease in clin­i­cal re­sponse” mea­sured by Mayo, but not enough to dri­ve sig­nif­i­cant ben­e­fit.

De­spite Ther­a­vance wait­ing on fol­low-up, 16-week da­ta in UC and a Phase II read­out in Crohn’s, in­vestors weren’t as­suaged. Shares in $TBPH were trad­ing down around 22% af­ter the bell.

Rick Win­ning­ham

The Crohn’s da­ta are due as ear­ly as Q4, of­fer­ing an­oth­er in­flec­tion point for the biotech. As it awaits those re­sults, Ther­a­vance will cut its R&D costs for the izenci­tinib pro­gram, sig­nal­ing its lack of be­lief in the drug’s com­mer­cial fu­ture.

“We had high ex­pec­ta­tions for the Phase 2b study af­ter eight weeks of treat­ment with izenci­tinib in ul­cer­a­tive col­i­tis giv­en the to­tal­i­ty and con­sis­ten­cy of the broad range of clin­i­cal, his­to­log­ic, and bio­mark­er da­ta we saw in the Phase 1b study with on­ly four weeks of treat­ment, al­beit in a small num­ber of pa­tients,” CEO Rick Win­ning­ham said in a state­ment. “We plan to an­a­lyze the da­ta to bet­ter un­der­stand the find­ings and the po­ten­tial for op­ti­miza­tion of a gut-se­lec­tive med­i­cine as a treat­ment for pa­tients with in­flam­ma­to­ry bow­el dis­eases.”

Ther­a­vance high­light­ed that all dos­es up to 200 mg were gen­er­al­ly well-tol­er­at­ed with 13 se­ri­ous side ef­fects re­port­ed but none re­lat­ed to izenci­tinib. That’s no small re­sult for a JAK in­hibitor, a drug class with a his­to­ry of dele­te­ri­ous side ef­fects, but not worth much with­out clin­i­cal ef­fi­ca­cy to show.

An­drew Hind­man

The tri­al fail­ure like­ly leaves Ther­a­vance’s de­vel­op­ment deal with Janssen for izenci­tinib (TD-1473) — and a $200 mil­lion opt-in mile­stone — in the wind. The part­ners signed that deal for $100 mil­lion cash back in 2018, with J&J jump­ing on board the biotech’s pipeline promise for tis­sue-se­lec­tive JAK drugs.

With that cash now like­ly not com­ing, Ther­a­vance is in the process of “flex­ing all as­pects of our cap­i­tal struc­ture to make sure we can keep the com­pa­ny ful­ly fund­ed,” CFO An­drew Hind­man said on the Mon­day call.

“We do have a num­ber of el­e­ments on­go­ing, and the im­pact to our guid­ance in 2021 is like­ly to be neg­li­gi­ble,” VP of de­vel­op­ment Richard Gra­ham added. “It’s re­al­ly about the di­rec­tion of the com­pa­ny in 2022 and be­yond where we’ll be do­ing a lot of work in­ter­nal­ly.”

The Big Phar­ma dis­card pile; Lay­offs all around while some biotechs bid farewell; New Roche CEO as­sem­bles top team; and more

Welcome back to Endpoints Weekly, your review of the week’s top biopharma headlines. Want this in your inbox every Saturday morning? Current Endpoints readers can visit their reader profile to add Endpoints Weekly. New to Endpoints? Sign up here.

With earnings seasons in full swing, we’ve listened in on all the calls so you don’t have to. But news is popping up from all corners, so make sure you check out our other updates, too.

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Raymond Stevens, Structure Therapeutics CEO

Be­hind Fri­day's $161M IPO: A star sci­en­tist, GPCR drug dis­cov­ery and a plan to chal­lenge phar­ma in di­a­betes

What does it take to pull off a $161 million biotech IPO these days?

In Structure Therapeutics’ case, it means having a star scientist co-founder paired with the computational drug discovery company Schrödinger, $198 million in private funding from blue-chip investors, almost six years of research work on G protein-coupled receptors and a slate of oral, small-molecule drugs, with an eye on the huge and growing diabetes and weight-loss market.

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Ma­gen­ta halts stem cell work and may sell it­self fol­low­ing pa­tient death, clin­i­cal hold

Magenta Therapeutics said it is halting work on its stem cell transplant drug pipeline and may sell itself, a week after the company reported the death of a patient in an early stage trial of its antibody-drug conjugate.

The Cambridge, MA-based company said it will conduct a “review of strategic alternatives,” and that could include an “acquisition, merger, business combination, or other transaction.”

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Sen. Ron Wyden (D-OR) (Francis Chung/E&E News/Politico via AP Images)

In­fla­tion re­bates in­com­ing: Wyden calls on CMS to move quick­ly as No­var­tis CEO pledges re­ver­sal

Senate Finance Chair Ron Wyden (D-OR) this week sent a letter to the head of the Centers for Medicare & Medicaid Services seeking an update on how and when new inflation-linked rebates will take effect for drugs that see major price spikes.

The newly signed Inflation Reduction Act requires manufacturers to pay a rebate to Medicare when they increase drug prices faster than the rate of inflation.

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Trodelvy notch­es a win in most com­mon form of breast can­cer

Following a promise last year to go “big and fast in breast cancer,” Gilead has secured a win for Trodelvy in the most common form.

The drug was approved to treat HR-positive, HER2-negative breast cancer patients who’ve already received endocrine-based therapy and at least two other systemic therapies for metastatic cancer, Gilead announced on Friday.

Trodelvy won its first indication in metastatic triple-negative breast cancer back in 2020, and has since added urothelial cancer to the list. HR-positive HER2-negative breast cancer accounts for roughly 70% of new breast cancer cases worldwide per year, according to senior VP of oncology clinical development Bill Grossman, and many patients develop resistance to endocrine-based therapies or worsen on chemotherapy.

Sanofi scraps PhI­II tri­al for Prin­cip­ia drug af­ter re­view­ing com­pe­ti­tion

Months after the FDA placed Phase III trials of Sanofi’s BTK inhibitor on hold, the company is winding down one of the studies.

Sanofi reported in its Q4 earnings that the URSA study “was discontinued after careful evaluation of the emerging competitive treatment landscape in” myasthenia gravis, a rare disease that causes muscle weakness.

The Phase III, placebo-controlled trial was testing tolebrutinib in patients with the moderate-to-severe form of the disease. It started in late 2021, according to records on clinicaltrials.gov, and was originally designed to recruit 154 participants who were receiving the standard of care.

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Af­ter 13 years, Ramy Mah­moud steps in­to CEO seat at Opti­nose; Ru­pert Vessey set to ex­it Bris­tol My­ers in Ju­ly

After 13 years as president and COO at Optinose, Ramy Mahmoud has stepped into a new role as its CEO. He is taking the place of Peter Miller, who stepped down earlier this week, though Miller is still staying with the company as a consultant.

In 2010, the two business partners joined Optinose to take it in a new direction, transforming it from a delivery platform to product company. They previously worked together at Johnson & Johnson, when Miller was president at Janssen and Mahmoud headed medical affairs. Miller said after he learned about Optinose, “I did what I always do, which is find people smarter than me to talk with about the idea. And the first person I called was Ramy … and I said, ‘Hey, Ramy, what do you think of this technology?’”

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How to use ex­ter­nal con­trols: FDA spells out think­ing in new draft guid­ance

The use of real-world evidence to inform the FDA’s decision-making continues apace, with the agency releasing new draft guidance yesterday on how sponsors can compare outcomes of trial participants receiving a test treatment with outcomes in a group of people external to the trial.

The practice of externally controlled trials is common, particularly in oncology or other difficult areas where it’s not ethical or feasible to use internal controls.

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The Big Phar­ma axe: Mer­ck cuts chikun­gun­ya vax, Bris­tol My­ers drops Cy­tomX-part­nered pro­gram, and more

As fourth quarter earnings come in, Big Pharmas are disclosing changes to their pipelines during their investor calls, and sometimes more quietly in presentation appendices.

Merck dropped its chikungunya vaccine candidate, which completed a Phase II study. Merck acquired the vaccine through its purchase of Themis Bioscience in 2020. In developing a vaccine for chikungunya, a mosquito-borne virus, Valneva is the frontrunner, as it submitted its vaccine to the FDA at the end of December.

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