Ness Bermingham (file photo)

What uni­fies Hunt­ing­ton's, spin­ocere­bel­lar atax­ia and my­oton­ic dy­s­tro­phy? Ness Berming­ham's new start­up looks to drug that

Ness Berming­ham’s lat­est ven­ture brings throw­backs to some of his ear­li­est work in bio­phar­ma. Part of his PhD work at Im­pe­r­i­al Col­lege Lon­don re­volved around triplet re­peat dis­or­ders, a group of 40 or so ge­net­ic dis­eases char­ac­ter­ized by the rep­e­ti­tion and ex­pan­sion of spe­cif­ic trin­u­cleotide se­quences. Dur­ing his ear­ly years at At­las Ven­ture — way be­fore he be­came known as a co-founder of pi­o­neer­ing CRISPR play­er In­tel­lia — he helped cre­ate a biotech, Prest­wick Phar­ma­ceu­ti­cals, that cre­at­ed a Hunt­ing­ton’s drug dubbed tetra­benazine.

Back then — and un­til very re­cent­ly — even though Hunt­ing­ton’s and oth­er dis­eases such as spin­ocere­bel­lar atax­ia and my­oton­ic dy­s­tro­phy fell un­der the same um­brel­la, they were con­strued as sep­a­rate af­flic­tions. A po­ten­tial­ly uni­fy­ing the­o­ry, as it turned out, lay in one ques­tion: Why don’t pa­tients born with the same re­peats al­ways be­gin to see symp­toms at the same age?

“For quite some time peo­ple had known that there are these ge­net­ic mod­i­fiers that re­al­ly seem to pro­found­ly im­pact these dis­eases and the on­set and pro­gres­sion of these dis­eases,” Berming­ham told End­points News.

Triplet Ther­a­peu­tics, which is do­ing the rounds to­day with $59 mil­lion in launch cash from At­las, MPM Cap­i­tal and Pfiz­er Ven­tures, be­lieves the key to that mech­a­nism is the DNA dam­age re­sponse path­way.

Iri­na An­toni­je­vic

The DNA dam­age re­sponse path­way, or DDR, is a cru­cial way for cells to re­pair ge­net­ic ma­te­r­i­al. But in pa­tients with re­peat ex­pan­sion dis­or­ders, when their DDR ma­chine goes in to fix the kinks dur­ing DNA repli­ca­tion, they al­so in­sert mul­ti­ple re­peat­ing se­quences — in turn blow­ing up the size of the DNA so much that it’s more prone to dam­age, cre­at­ing a snow­ball ef­fect, ac­cord­ing to Berming­ham.

Out of about 100 genes in­volved in the DDR path­way, Triplet has iden­ti­fied a cou­ple key dri­vers that they can tar­get to stop the in­ser­tion of re­peats, there­by hold­ing the dis­ease at bay.

Bri­an Bet­ten­court

That has al­lowed to shift their think­ing from a dis­ease stand­point to a tis­sue stand­point, Berming­ham said, and the first tis­sue they will go af­ter is the brain: Hunt­ing­ton’s, mul­ti­ple sub­types of spin­ocere­bel­lar atax­ia, den­ta­torubral–pal­li­doluysian at­ro­phy, my­oton­ic dy­s­tro­phy, and so on.

“As you move from tis­sue to tis­sue, it opens up dif­fer­ent drugs of dif­fer­ent for­mu­la­tions that hit the same tar­get,” he said.

Un­like at Ko­r­ro Bio, the RNA edit­ing out­fit Berming­ham has re­cent­ly un­veiled as ex­ec­u­tive chair­man, Triplet is not look­ing to new tools. Rather, the goal is to home in on a “fun­da­men­tal dri­ver” of dis­ease up­stream of what ri­vals like Roche/Io­n­is and Wave are knock­ing out in Hunt­ing­ton’s.

David Mor­risey

The can­di­dates they are now test­ing in non-hu­man pri­mates for CNS dis­or­ders are an­ti­sense oligonu­cleotides, but for oth­er tis­sues such as mus­cles, the eye or even the kid­ney, they al­so plan to use small in­ter­fer­ing RNA. These tools were cho­sen as they pro­vide more spe­cif­ic tar­get­ing and less safe­ty is­sues than, say, small mol­e­cules, Berming­ham said.

The CEO added that us­ing ASO and siR­NA has al­lowed his team of 29 to move quick­ly, ready to en­ter the clin­ic with­in two years — the run­way that the Se­ries A (al­so fea­tur­ing In­vus, Part­ners In­no­va­tion Fund and Alexan­dria Ven­ture In­vest­ments) is pro­vid­ing. In the process he’s look­ing to grow the com­pa­ny to some­where be­tween 45 to 60.

Cur­rent­ly help­ing Berming­ham run the op­er­a­tions are some sea­soned ex­ecs in the space: Iri­na An­toni­je­vic, SVP of de­vel­op­ment, pre­vi­ous­ly led trans­la­tion­al med­i­cine and ear­ly de­vel­op­ment at Wave; Bri­an Bet­ten­court, SVP of com­pu­ta­tion­al bi­ol­o­gy & sta­tis­tics, spe­cial­ized in mod­el­ing and de­sign of oligonu­cleotide and mR­NA at Trans­late Bio; David Mor­ris­sey, SVP of tech­nol­o­gy, and Pe­ter Blalek, head of trans­la­tion­al sci­ences, are both old col­leagues from In­tel­lia; Head of phar­ma­col­o­gy Pei Ge led the Hunt­ing­ton’s pro­gram at Al­ny­lam be­fore mov­ing to Iron­wood; Er­ic Sul­li­van, CFO, was for­mer­ly of Gem­i­ni Ther­a­peu­tics and blue­bird bio; and Jef­frey Ce­rio, gen­er­al coun­sel, has served at Mod­er­na.

Shinichi­ro Fuse of MPM and Las­z­lo Kiss of Pfiz­er Ven­tures are join­ing the board, chaired by At­las part­ner Jean-François Formela, along­side Dou­glas Kerr, chief de­vel­op­ment of­fi­cer at Gen­er­a­tion Bio. Then there’s the sci­en­tif­ic ad­vi­so­ry board com­pris­ing three aca­d­e­m­ic ex­perts, in­clud­ing Vanes­sa Wheel­er at Mass­a­chu­setts Gen­er­al Hos­pi­tal, who hap­pened to be a PhD mate of Berming­ham’s.

Ramp­ing up would mean spend­ing the ma­jor­i­ty of his time with Triplet at the new Kendall Square of­fices they are mov­ing in­to in Jan­u­ary, slight­ly de­tached from At­las — which he re­joined as ven­ture part­ner less than two years ago in the wake of his ex­it from the helm of In­tel­lia.

“It’s my in­tent to stay here and see this com­pa­ny through,” he said. “I’m trained as a hu­man ge­neti­cist orig­i­nal­ly, and then fur­ther spe­cial­ized down to mol­e­c­u­lar bi­ol­o­gy. So this is ab­solute­ly in my sweet spot.”

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

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.

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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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.

Pfiz­er’s Doug Gior­dano has $500M — and some ad­vice — to of­fer a cer­tain breed of 'break­through' biotech

So let’s say you’re running a cutting-edge, clinical-stage biotech, probably public, but not necessarily so, which could see some big advantages teaming up with some marquee researchers, picking up say $50 million to $75 million dollars in a non-threatening minority equity investment that could take you to the next level.

Doug Giordano might have some thoughts on how that could work out.

The SVP of business development at the pharma giant has helped forge a new fund called the Pfizer Breakthrough Growth Initiative. And he has $500 million of Pfizer’s money to put behind 7 to 10 — or so — biotech stocks that fit that general description.

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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.

Covid-19 roundup: Mod­er­na read­ies to en­ter PhI­II in Ju­ly, As­traZeneca not far be­hind; EU ready to ne­go­ti­ate vac­cine ac­cess with $2.7B fund

Moderna may soon add another first to the Covid-19 vaccine race.

In March, the mRNA biotech was the first company to put a Covid-19 vaccine into humans. Next month, they may become the first company to put their vaccine into the large, late-stage trials that are needed to prove whether the vaccine is effective.

In an interview with JAMA editor Howard Bauchner, NIAID chief Anthony Fauci said that a 30,000-person, Phase III trial for Moderna’s vaccine could start in July. The news comes a week after Moderna began a Phase II study that will enroll several hundred people.

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José Basel­ga finds promise in new class of RNA-mod­i­fy­ing can­cer tar­gets, lock­ing in 3 pre­clin­i­cal pro­grams with $55M

Having dived early into some of the RNA breakthroughs of the last decades — betting on Moderna’s mRNA tech and teaming up with Silence on the siRNA front — AstraZeneca is jumping into a new arena: going after proteins that modify RNA.

Their partner of choice is Accent Therapeutics, which is receiving $55 million in upfront payment to steer a selected preclinical program through to the end of Phase I. After AstraZeneca takes over, the Lexington, MA-based startup has the option to co-develop and co-commercialize in the US — and collect up to $1.1 billion in milestones in the long run. The deal also covers two other potential drug candidates.

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Joseph Kim, Inovio CEO (Andrew Harnik, AP Images)

Caught in a stand­off with its con­tract man­u­fac­tur­er over Covid-19 vac­cine, In­ovio files suit in an at­tempt to break free while ri­vals race ahead

Inovio was one of the first vaccine developers to snag attention for a jab that their execs said promised to end the Covid-19 pandemic. Using their own unique DNA tech, CEO Joseph Kim said it took just 3 hours to work it out.

But while rivals are racing to the finish line with ambitious plans to make vast quantities of their vaccines with billions of dollars of deals, Inovio is still stuck at the starting line on manufacturing.