All in on IL-11, Fra­zier un­veils lat­est start­up with dual fo­cus on fi­bro­sis and can­cer

In late 2017, a team of Sin­ga­pore­an sci­en­tists pub­lished a Na­ture pa­per high­light­ing what they call a “ground­break­ing” and “out­stand­ing” new tar­get for fi­bro­sis. In­ter­leukin-11, a cy­tokine down­stream of the well-known TGFβ1 path­way, had been over­looked but ac­tu­al­ly plays an even more cen­tral role in the fi­brot­ic process, they wrote.

“The dis­cov­ery that IL11 is a crit­i­cal fi­brot­ic fac­tor is the type of break­through that the sci­en­tists and phar­ma­ceu­ti­cal com­pa­nies have been search­ing for,” Stu­art Cook, a se­nior au­thor and the di­rec­tor of the Na­tion­al Heart Re­search In­sti­tute Sin­ga­pore, said then.

Cook and Se­bas­t­ian Schäfer, a co-au­thor, had found­ed a biotech named En­le­ofen that would go on to score a ma­jor al­liance with Boehringer In­gel­heim. Now, Fra­zier Health­care is de­but­ing its own ef­fort to drug the tar­get — aim­ing not just at var­i­ous types of fi­bro­sis but al­so can­cer.

Mark Bar­rett

With Mark Bar­rett, Sanofi Gen­zyme vet and now Fra­zier en­tre­pre­neur-in-res­i­dence, at the helm, Lassen Ther­a­peu­tics has $31 mil­lion to find out which in­di­ca­tions they’d like to start with and reach IND next year.

The Na­ture pa­per had piqued their in­ter­est in IL-11, Bar­rett told End­points News, just as he and co-founder David King were search­ing for a new con­cept that would play to King’s ex­per­tise in an­ti­body dis­cov­ery and de­vel­op­ment.

“We be­lieved that there’s such a great pro­lif­er­a­tion of re­al­ly high-qual­i­ty and high-ca­pa­bil­i­ty an­ti­body gen­er­a­tion tech­nolo­gies avail­able that a biotech com­pa­ny to­day can be high­ly suc­cess­ful lever­ag­ing those tech­nolo­gies for the right ap­pli­ca­tions,” he said.

King, who had had a com­pa­ny cre­ation ex­er­cise with Fra­zier at Anap­tys­Bio, brought over a few sci­en­tists to the found­ing team and built it out to a group of 10 based out of San Diego. Bar­rett re­mains in Boston, where he’s been based for the past decade — not that it had made a dif­fer­ence for the last few months as his West Coast col­leagues found them­selves chat­ting with him and one an­oth­er over video calls amid a statewide shut­down.

David King

They be­gan by scour­ing the patent lit­er­a­ture on IL-11 block­ade and dis­cov­ered an IP es­tate that CSL had cre­at­ed around a suite of an­ti­bod­ies hit­ting the IL-11 re­cep­tor. The Aus­tralian phar­ma gi­ant had done some work with them in COPD and asth­ma but it was, af­ter all, not a great fit for their core plas­ma and vac­cines busi­ness.

“They had worked on the pro­gram but had kind of parked it at the stage where it need­ed more fo­cus and in­vest­ment,” Bar­rett said. “We hap­pened to come in at just the right mo­ment” last year to li­cense it all.

Through the deal CSL be­came an eq­ui­ty hold­er in Lassen along­side Fra­zier (with its lat­est, $617 mil­lion fund), Al­ta Part­ners and Long­wood Fund. An­drew Nash, the SVP of re­search at CSL, is al­so join­ing the biotech’s sci­en­tif­ic ad­vi­so­ry board.

Bar­rett has been around long enough to re­mem­ber that IL-11 does have a past in on­col­o­gy. Cam­bridge, MA-based Ge­net­ics In­sti­tute had ush­ered a re­com­bi­nant IL-11 to the mar­ket as a sup­port ther­a­peu­tic to chemother­a­py be­fore get­ting ac­quired by Wyeth, which in time rolled up in­to Pfiz­er.

“But the fur­ther bi­ol­o­gy in terms of its role in fi­bro­sis or can­cer just wasn’t well enough un­der­stood, I guess, for peo­ple to be suc­cess­ful to de­vel­op block­ing ther­a­peu­tics like IL-6, al­though IL-11 and IL-6 are in the same fam­i­ly of cy­tokines,” he said. “It’s just one of those things; bi­ol­o­gy is hard. Fig­ur­ing out the right ap­pli­ca­tion takes time — decades, some­times.”

Lassen now has its foot on the gas ped­al, look­ing to ac­cel­er­ate the R&D work by part­ner­ing with both aca­d­e­m­ic in­ves­ti­ga­tors and Fu­ji­film Diosynth, which will man­u­fac­ture clin­i­cal-grade ma­te­r­i­al for them once they de­cide on the fi­brot­ic con­text and or­gan sys­tem to tar­get first.

There’s plen­ty of room for both Boehringer and Lassen to bring forth new treat­ments in the broad space, Bar­rett added, es­pe­cial­ly as “we may di­verge in the way we fo­cus.”

Ryan Watts, Denali CEO

De­nali slips as a snap­shot of ear­ly da­ta rais­es some trou­bling ques­tions on its pi­o­neer­ing blood-brain bar­ri­er neu­ro work

Denali Therapeutics had drummed up considerable hype for their blood-brain barrier technology since launching over six years ago, hype that’s only intensified in the last 14 months following the publications of a pair of papers last spring and proof of concept data earlier this year. On Sunday, the South San Francisco-based biotech gave the biopharma world the next look at in-human data for its lead candidate in Hunter syndrome.

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Why is On­col­o­gy Drug De­vel­op­ment Re­search Late to the Dig­i­tal Bio­mark­ers Game?

During the recent Annual ASCO Meeting, thousands of cancer researchers and clinicians from across the globe joined together virtually to present and discuss the latest findings and breakthroughs in cancer research and care. There were more than 5000+ scientific abstracts presented during this event, yet only a handful involved the use of motion-tracking wearables to collect digital measures relating to activity, sleep, mobility, functional status, and/or quality of life. Although these results were a bit disappointing, they should come as no surprise to those of us in the wearable technology field.

J&J’s Rem­i­cade — the poster child for how to block biosim­i­lars — fi­nal­ly set­tles Pfiz­er suit

Biosimilars have proven time and again (although mostly in Europe) that competition works to bring down the cost of a once-pricey biologic, and can even expand its use.

J&J’s Remicade, however, has always proven to be an outlier.

Back in 2016, Pfizer won FDA approval for its infliximab biosimilar, known as Inflectra, but when the launch foundered, the company sued J&J, claiming that the company’s plan to block biosimilar competition worked incredibly well. Pfizer even went on to win FDA approval for a second infliximab biosimilar in 2017, known as Ixifi, but decided to never launch it.

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An­oth­er one bites the dust: Bris­tol My­ers Squibb pulls 'dan­gling' ac­cel­er­at­ed ap­proval for Op­di­vo in liv­er can­cer

Bristol Myers Squibb has agreed to pull a second-line liver cancer indication for its blockbuster Opdivo as a monotherapy, becoming the second PD-(L)1 indication to bite the dust after the FDA’s oncology adcomm reviewed six “dangling” accelerated approvals in April.

The outside experts voted against two of the six indications discussed at the meeting, including Opdivo as a monotherapy for hepatocellular carcinoma (HCC) patients who have previously been treated with sorafenib, and Merck’s Keytruda as a third-line treatment for stomach cancer. The adcomm voted 5 to 4 not to maintain Opdivo’s indication, after it failed to show clinical benefit in a confirmatory trial.

Pascal Soriot, AstraZeneca CEO (Raphael Lafargue/Abaca/Sipa via AP Images)

Covid-19 roundup: Fau­ci warns that US is head­ed in wrong di­rec­tion, rec­om­mends boost­er; As­traZeneca-Pfiz­er com­bo proves ef­fec­tive in South Ko­rea

A combination of unvaccinated Americans and the Delta variant has led a frustrated NIAID director Anthony Fauci to say the US is headed in the wrong direction, he said on CNN’s show “State of the Union.”

Booster shots may be required for those with suppressed immune systems and public health officials are considering a mask recommendation for those who are already vaccinated, the Associated Press reported. More than 163 million people are vaccinated, but that number is less than half of the US population. And 57% of those who are eligible for the vaccine have been inoculated.

Seth Lederman, Tonix Pharmaceuticals CEO

Small, strug­gling biotech winds up with a 3X los­er as an­oth­er PhI­II of its lead drug col­laps­es

Little Tonix Pharmaceuticals has run into another brick wall as its lead drug — a reformulated muscle relaxant originally approved 44 years ago — has failed another Phase III study, sending shares back into penny stock territory.

Three years after going down in their first Phase III trial of TNX-102 SL (cyclobenzaprine HCl sublingual tablets) for symptoms of PTSD, the biotech — which had been encouraged by a breakthrough designation at the FDA — reported late Friday the drug also failed its second late-stage challenge for pain associated with fibromyalgia. Outside data monitors recommended the Phase III trial be halted for futility after deciding interim data made it unlikely the drug would pass muster.

Hervé Hoppenot, Incyte CEO (Jeff Rumans for Endpoints News)

FDA un­sur­pris­ing­ly brings down the ham­mer on In­cyte's PD-1 — draw­ing a line for fu­ture ac­cel­er­at­ed ap­provals

It appears the PD-(L)1 honeymoon is finally over.

Incyte $INCY revealed late Friday the FDA has slammed its PD-1 retifanlimab — which was under priority review for locally advanced or metastatic squamous cell carcinoma of the anal canal — with a complete response letter, demanding “additional data” to show clinical benefit.

On one hand, the rejection should come as no surprise: Regulators spelled out the problems they saw with Incyte’s data package in no uncertain terms, raising concerns about the low response rates, lack of diversity and dearth of safety data in the single-arm trial. During the ensuing adcomm, the FDA’s cancer czar, Richard Pazdur, suggested the whole episode underscores the need to “reassess” how drugs get approved under the accelerated approval pathway without randomized studies.

No­var­tis reshuf­fles its wild cards; Tough sell for Bio­gen? Googling pro­teins; Ken Fra­zier's new gig; 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.

If you enjoy the People section in this report, you may also want to check out Peer Review, my colleagues Alex Hoffman and Kathy Wong’s comprehensive compilation of comings and goings in biopharma.

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In­side Bio­gen's scram­ble to sell Aduhelm: Pro­ject 'Javelin' and pres­sure to ID as many pa­tients as pos­si­ble

In anticipation of Aduhelm’s approval for Alzheimer’s in June, Biogen employees were directed to identify and guarantee treatment centers would administer the drug through a program called “Javelin,” a senior Biogen employee told Endpoints News.

The program identified about 800 centers for use, he said, and Biogen now pays for the use of bioassays to identify beta amyloid in potential patients having undergone a lumbar puncture procedure, the employee said — and one center preparing to administer the drug confirmed its participation in the bioassay program.

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