An­oth­er pro­tein degra­da­tion biotech emerges, with the promise of a new ap­proach from an old hand

The mon­ey keeps pour­ing in for pro­tein degra­da­tion.

A field that six years ago had the fi­nan­cial equiv­a­lent of tum­ble­weed is now flush with cash. Last month, a pair of biotechs, now backed with big phar­ma and big biotech deals, land­ed a to­tal of $222 mil­lion in fund­ing on con­sec­u­tive days. And in Oc­to­ber, Plex­i­um launched out of San Diego with $28 mil­lion in Se­ries A fi­nanc­ing and a promise for a dif­fer­ent ap­proach to a bare­ly adult field.

The newest ad­di­tion comes out of Scot­land and a for­mer fel­low of the field’s god­fa­ther, Alessio Ciul­li. Ciul­li has for the last cou­ple years been help­ing in­cu­bate the com­pa­ny, known as Am­phista, in his lab at the Uni­ver­si­ty of Dundee, un­til last Oc­to­ber, when Am­phista moved to their own lab out­side Glas­gow. To­day they an­nounced a $7.5 mil­lion Se­ries A – with the promise of a larg­er Se­ries B lat­er this year – but they’re keep­ing the specifics of the tech­nol­o­gy close to the vest.

Nic­ki Thomp­son

“I can’t go in­to too much de­tail about ex­act­ly how we’re do­ing this,” CEO Nico­la Thomp­son told End­points News. “What I can say is that with our nov­el ap­proach and our nov­el bi­func­tion­al mol­e­cule and our de­grade-in­duc­er war­head, we’re in­de­pen­dent of the tra­di­tion­al ap­proach­es.”

Mean­ing that Am­phista works dif­fer­ent­ly — how­ev­er they de­fine dif­fer­ent­ly — than pro­tein degra­da­tion has so far, quite pos­si­bly by us­ing a few dif­fer­ent pro­teins.

In 2001, Craig Crews and Ray­mond De­shaies pub­lished a pa­per in the Pro­ceed­ings of the Na­tion­al Acad­e­my of the Sci­ences ex­plain­ing how you could use a mol­e­cule to take dis­ease-caus­ing pro­tein and ba­si­cal­ly shoot it di­rect­ly in­to the body’s garbage dis­pos­al sys­tem.

The mol­e­cule, called PRO­TAC or pro­te­ol­y­sis-tar­get­ing chimera, looks like a dumb­bell. On one side are atoms that bind to the pro­tein re­searchers want to re­move. On the oth­er side are atoms that bind to a pro­tein known as an E3 lig­ase. The E3 lig­ase sends the tar­get­ed pro­tein to a mol­e­c­u­lar shred­der. One of the ad­van­tages of such an ap­proach over tra­di­tion­al small mol­e­cules and an­ti­bod­ies is that it doesn’t re­quire an ac­tive site; you can use it to drug troves of the pre­vi­ous­ly in­ac­ces­si­ble pro­teins and the dis­eases they caused.

Pro­tac-1, as the pro­to­type was called, was too large to work as a drug in hu­mans. But in 2012, with fund­ing from Glax­o­SmithK­line, Crews, his grad stu­dent and a for­mer fel­low in his lab – Ciul­li – found a small mol­e­cule binder for an E3 lig­ase called von Hip­pel–Lin­dau dis­ease tu­mour sup­pres­sor, or sim­ply VHL. The next year Crews found­ed Arv­inas, which in 2019 be­came the first com­pa­ny to bring a pro­tein de­grad­er in­to the clin­ic, and a host of biotechs and large drug­mak­ers soon joined the game.

Alessio Ciul­li

These biotechs and phar­ma com­pa­nies, though, al­most ex­clu­sive­ly use VHL or one of three oth­er E3 lig­as­es, out of the hun­dreds that ex­ist in the hu­man body. A ma­jor goal of the field has been to ex­pand that short list of us­able lig­as­es, and with them, the po­ten­tial of pro­tein degra­da­tion as ther­a­py. That ap­pears to be where Ciul­li and Am­phista step in, al­though it’s un­clear.

“We’re in­de­pen­dent of the tra­di­tion­al E3 lig­as­es that are used com­mon­ly by the field,” Thomp­son, who pre­vi­ous­ly worked in drug dis­cov­ery and busi­ness de­vel­op­ment for Roche and GSK, said. “We don’t use those E3 lig­as­es.”

Asked if they used oth­er E3 lig­as­es, Thomp­son de­clined to com­ment.

The idea, Thomp­son said, is that us­ing their ap­proach they’ll be able to over­come some is­sues re­cent­ly seen with the cur­rent lig­as­es, cit­ing re­sis­tance mech­a­nisms.

The com­pa­ny will start in on­col­o­gy, with plans to an­nounce an ini­tial tar­get lat­er this year. Am­phista now con­sists of 10 em­ploy­ees, pri­mar­i­ly bi­ol­o­gists and chemists, work­ing out of a lab in BioC­i­ty just out­side of Glas­gow, al­though Thomp­son de­clined to an­swer if work was be­ing done at the lab amid the Covid-19 pan­dem­ic.

“We are hav­ing to think about work­ing dif­fer­ent­ly,” Thomp­son said. “At the mo­ment, I’m not see­ing a big im­pact on our over­ar­ch­ing time­lines.”

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.
Contact us about your next study.
Download our Frost & Sullivan APAC CRO Report here. 

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.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 124,200+ biopharma pros reading Endpoints daily — and it's free.

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.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 124,200+ biopharma pros reading Endpoints daily — and it's free.

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.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 124,200+ biopharma pros reading Endpoints daily — and it's free.

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.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 124,200+ biopharma pros reading Endpoints daily — and it's free.

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.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 124,200+ biopharma pros reading Endpoints daily — and it's free.

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.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 124,200+ biopharma pros reading Endpoints daily — and it's free.

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.”

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 124,200+ biopharma pros reading Endpoints daily — and it's free.

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.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 124,200+ biopharma pros reading Endpoints daily — and it's free.