De­nali grabs an­oth­er megaround while ink­ing a flur­ry of neu­rode­gen­er­a­tion R&D pacts


South San Fran­cis­co-based up­start De­nali Ther­a­peu­tics has been busy. A lit­tle more than a year af­ter mak­ing a splash with its $217 mil­lion start­up round de­signed to fund a new breed of neu­rode­gen­er­a­tion drug de­vel­op­er, the biotech is back with an­oth­er megaround fi­nanc­ing and a string of deals topped by a move in­to the clin­ic for its lead drug.

De­nali is go­ing big, ear­ly on. The sec­ond chap­ter in De­nali’s sto­ry starts with a $130 mil­lion Se­ries B, bring­ing its to­tal close to $350 mil­lion. And it’s lin­ing up a Phase I study for a small mol­e­cule RIP1 in­hibitor tar­get­ing glial dys­func­tion, where De­nali hopes to start es­tab­lish­ing a track record for suc­cess against ALS and Alzheimer’s.

Start­ing from scratch, the team at De­nali — large­ly ex-Genen­tech staffers who have struck out on their own — has set out to build a com­pa­ny that they be­lieve can suc­ceed af­ter many of the gi­ants in the in­dus­try have paid heav­i­ly for more than a decade of fail­ure.

“We’ve looked at part­ner­ing as a means to build­ing the port­fo­lio,” Chief Op­er­at­ing Of­fi­cer Alex Schuth tells me, high­light­ing a first set that in­cludes two fo­cused on con­quer­ing the blood-brain bar­ri­er, which has thrown a host of ear­li­er drugs off tar­get. Here they are, in se­quence:

  • De­nali has ac­quired San Diego-based In­cro Phar­ma­ceu­ti­cals, a vir­tu­al, sin­gle-as­set af­fair that de­liv­ers a RIP1 drug out of Har­vard. And just days ago the biotech filed a tri­al ap­pli­ca­tion with Eu­ro­pean of­fi­cials with plans to start hu­man test­ing, con­cen­trat­ing on a ki­nase that reg­u­lates in­flam­ma­to­ry sig­nal­ing.

  • They struck a deal with their al­ma mater Genen­tech to de­vel­op and com­mer­cial­ize LRRK2 in­hibitors for the treat­ment of Parkin­son’s dis­ease.

  • There’s an­oth­er pact with Wash­ing­ton Uni­ver­si­ty School of Med­i­cine in St. Louis for the de­vel­op­ment and com­mer­cial­iza­tion of an­ti­bod­ies tar­get­ing ApoE, a big tar­get for Alzheimer’s.

  • Cam­bridge, UK-based F-star, mean­while, is bring­ing its bis­pe­cif­ic an­ti­body de­vel­op­ment ex­per­tise to the ta­ble, as De­nali looks to break through the blood-brain bar­ri­er. That deal in­cludes an op­tion to buy out a new­ly formed group for $450 mil­lion, with an ear­ly-stage trig­ger on the de­ci­sion.

  • Seat­tle-based Blaze Bio­science, mean­while, is work­ing on some ther­a­peu­tics that F-star’s bis­pecifics can hus­tle across the BBB.

There’s more. Deals have been signed with the ALS Ther­a­py De­vel­op­ment In­sti­tute (ALS TDI), Ap­tu­it, Evotec, Mass­a­chu­setts Gen­er­al Hos­pi­tal, The Michael J. Fox Foun­da­tion, Pa­tients­LikeMe and the Uni­ver­si­ty of Cal­i­for­nia San Diego School of Med­i­cine.

The staff at De­nali, mean­while, has swelled to 80, says CEO Ryan Watts, who adds that that num­ber will con­tin­ue to grow as the biotech signs up with more col­lab­o­ra­tors and builds its first 10 pro­grams for the clin­ic.

Chief Med­ical Of­fi­cer Ca­r­ole Ho says she’s been re­view­ing hun­dreds of pa­pers and some 80 failed stud­ies in this field to prep for the com­ing de­vel­op­ment work, look­ing to avoid the same pit­falls.

“This may sounds like Drug 101,” she says, but De­nali’s suc­cess af­ter so many fail­ures will get down to its abil­i­ty to en­gage the tar­get, with the right kind of bio­mark­ers in place to track their suc­cess. De­vel­op­ing bio­mark­ers ear­ly, she adds, is crit­i­cal. And the bi­ol­o­gy of these dis­eases is be­com­ing more clear through the rapid ad­vance of ge­net­ics re­search.

RIP1, ApoE and LRRK2 have nev­er re­al­ly been test­ed be­fore, adds the CEO, giv­ing De­nali a “much bet­ter start­ing point.”

The deal with F-star starts small, but could wind up in the big leagues. De­nali is pay­ing $6 mil­lion to get a new op­er­a­tion dubbed F-star Gam­ma off the ground, F-star CEO John Hau­rum tells me. De­nali will al­so fund the re­search work, head­ing to a cross­roads where De­nali can ei­ther pick up an op­tion to buy the op­er­a­tion for $450 mil­lion or ink a li­cens­ing pact for the rights to its bis­pecifics. The op­tion de­ci­sion falls ahead of Phase I, says Hau­rum, and if the biotech choos­es to go the li­cens­ing route, the mile­stones could add up to more than $1 bil­lion.

This isn’t the first of these kinds of deals for F-star, which has col­lab­o­ra­tions un­der­way with Bris­tol-My­ers Squibb and Ab­b­Vie. Hau­rum’s been im­pressed with the De­nali crew, which came to him af­ter de­cid­ing that F-star’s abil­i­ty to cre­ate both bis­pe­cif­ic as well as bi­va­lent an­ti­bod­ies gave it the best shot at hit­ting the tar­gets lined up once they get through the blood-brain bar­ri­er — a ma­jor ob­sta­cle in neu­rode­gen­er­a­tive re­search work.

“They bring as­pects of the Genen­tech cul­ture that every­one has re­spect­ed for years,” says Hau­rum.

Bail­lie Gif­ford, a UK-based mu­tu­al fund, led the round, with all of De­nali’s orig­i­nal in­vestors com­ing back in along with some un­named in­sti­tu­tion­al in­vestors. The found­ing in­vestors in­clude ARCH Ven­ture Part­ners, F-Prime Bio­sciences, Flag­ship Ven­tures and the Alas­ka Per­ma­nent Fund.

The in­ten­tion here is to get the right syn­di­cate to­geth­er to back a com­pa­ny that has years of ex­pen­sive re­search work ahead be­fore it can es­tab­lish a clear proof-of-con­cept case that its on the right track, says CFO Steve Krognes.

So is an IPO in sight? De­nali’s ex­ec­u­tive team will on­ly say that it has plen­ty of re­sources at this stage, and more than enough of time to con­sid­er all the ways to con­tin­ue to fund the work, whether that means more mon­ey from the syn­di­cate, an IPO at some point, or a part­ner­ship or two with a ma­jor al­ly that could al­so sup­port their work.

The way they’re go­ing, De­nali may take every­thing on the ta­ble.

Australia’s Avance Clinical: no IND required and a 43.5% rebate on clinical spend for CGT biotechs

No IND Re­quired for Cell and Gene Ther­a­py Stud­ies with Aus­tralia’s Ac­cred­it­ed CRO Avance Clin­i­cal

Avance Clinical is the specialist Australian CRO, with CGT accreditation, for international biotechs that leverages Australia’s supportive clinical trials environment which includes no IND requirement plus a 43.5% Government incentive rebate on clinical spend.

Learn more about Avance ClinicReady here.
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The cell and gene therapies (CGT) sector offers unprecedented opportunities for patient disease management across virtually all therapeutic areas. However, finding the right accredited clinical teams to take a therapy through to the clinic and manage the regulatory process can be a major challenge for biotechs with a CGT product.

Ursula von der Leyen, President of the European Commission

Omi­cron: Re­searchers scram­ble as new coro­n­avirus mu­ta­tion takes flight around the globe — Pfiz­er/BioN­Tech, Mod­er­na vow swift re­sponse

As Americans were waking up for their Black Friday rituals, they were greeted with the news that a new mutation of the Covid-19 virus has appeared and been sequenced — after it caught an international flight to Hong Kong. And two of the leading Covid-19 vaccine developers promised delivery of a new vaccine “within 100 days” if necessary while a third spelled out its 3-prong strategy hours later.

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Thanks­giv­ing edi­tion: Top 15 End­points sto­ries of 2021; Can you name that vac­cine?; Mer­ck­'s Covid an­tivi­ral dis­ap­points; FDA nom­i­nee's in­dus­try ties; 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.

Happy Thanksgiving to all those who are celebrating it — although, if we are being honest, this week’s abbreviated edition is really for those who are not. Wherever you’re tuning in from, we appreciate your support, hope you find this recap helpful and we wish you a wonderful weekend.

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What were End­points read­ers tun­ing in­to this year? Here’s a look at our 15 most pop­u­lar re­ports of the year (so far)

At the beginning of this year, I laid out a basic objective for Endpoints News as we headed to our 5th anniversary. We’ve long been doing a fine job covering the breaking news in R&D — if I do say so myself — but we needed to expand our horizons on industry coverage, increase the staff and go much, much deeper when the stories demanded it.

In a phrase: broader and deeper.

It’s safe to say, based on our daily web traffic, that you all seemed to like this idea. We’ve doubled the staff — thanks to a growing group of paid subscribers — ramped up the daily report and now publish a regular slate of in-depth articles. And traffic — those clicks you always read about — have gone up in volume too. Monthly sessions are up 43%, to close to 1.5 million. Unique readers are up 63%, to 874,480 in October, after setting a record of close to a million the month before. Page views are running at 3 million-plus a month. And the overall number of subscribers has surged to 124,000.

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Troy Wilson, Kura CEO

UP­DAT­ED: FDA hits the red light on an ear­ly-stage AML study af­ter a pa­tient dies

The FDA has slapped a clinical hold on the early-stage program for one of Kura Oncology’s cancer drugs following a patient’s death in a clinical trial.

The biotech $KURA reported early Wednesday that the Phase Ib study of KO-539 for acute myeloid leukemia would be halted, suspending enrollment, while researchers and the FDA probed the death. Patients already on the drug can continue taking it.

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Mar­ket­ingRx roundup: Am­gen, Lil­ly, Bio­haven mi­graine brand re­call low, study says; No­var­tis looks to re­make drug launch mod­el

Forget the migraine marketing brand wars. When it comes to patients, many can’t even name one despite substantial advertising efforts, according to a new study from Phreesia that concludes CGRP migraine drugmakers still need to work on brand recognition.

Almost half (47%) of the patients Phreesia surveyed couldn’t name one preventative migraine brand. The best performer was Topamax, a small molecule anticonvulsant that’s been around since 2004, which 26% of migraine patients could recall. Among the new CGRP brand names recognized, Amgen’s Aimovig ranked highest with 8% recall, while Eli Lilly’s Emgality and Biohaven’s Nurtec tied at 7% and Teva’s Ajovy was remembered by 3% of patients.

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Emma Walmsley, GlaxoSmithKline CEO (Fang Zhe/Xinhua/Alamy Live News)

Glax­o­SmithK­line places a risky bet on Ar­row­head­'s RNA drug in the fail­ure-strewn NASH field

As activist investors champ at the bit for change at drug giant GlaxoSmithKline, the pharma giant has turned over many rocks to find an R&D success to present to its detractors. In NASH, a field strewn with failures, GSK hopes a new license deal can churn out a much-needed winner.

GSK will pay $120 million in upfront cash and $910 million in downstream milestones to develop and sell ARO-HSD, Arrowhead Pharmaceuticals’ RNA interference drug targeting fatty liver disease nonalcoholic steatohepatitis (NASH), the companies said Monday.

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Name that vac­cine: From Comir­naty to Spike­vax to Nu­vax­ovid, Covid-19 shot­s' brand names re­main lit­tle-known

Most people know if they’re “Team Pfizer” or “Team Moderna,” but few know if they got the Comirnaty or Spikevax Covid-19 vaccine. Those are the brand names of Pfizer and Moderna vaccines, respectively, however they have yet to take hold with consumers, media or even medical professionals.

And there are others. Covid vaccine brand names also include AstraZeneca’s Vaxzevria, Novavax’s Nuvaxovid, and Sanofi and GlaxoSmithKline’s Vidprevtyn. J&J’s Janssen-developed Covid vaccine is the lone major holdout and is still yet to be named, if ever. In EMA filings approving its conditional use, the brand name is listed simply as “Covid-19 Vaccine Janssen.”

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Joan Perelló, Sanifit CEO

Joan Perel­ló set out 17 years ago to de­vel­op a drug. And to­day he's be­ing re­ward­ed with a $424M biotech buy­out

Joan Perelló beat all the odds with his little Spanish biotech startup Sanifit.

Working on the far perimeter of the big US/European drug development scene, he took a drug born out of his PhD work and got enough seed cash to get started. That’s one near miracle. In the second near miracle he gathered a previously unheard of venture raise in Spain — helping build an industry ecosystem from scratch — to pursue a successful search for solid human data for his drug, SNF472. And while gathering a virtual team of developers from Europe and the US, the CEO/co-founder steered it into the late-stage arena.

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