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.”

Ven­ture Cap­i­tal as a Strate­gic Part­ner: Fu­el­ing In­no­va­tion be­yond Fi­nance

The average level of investment required for a biotech start-up to succeed is increasing every year, elevating the pressure even further on venture capital to make smart financial investments. Financial investment alone, however, does not always guarantee that exciting innovations can be transformed into real businesses that make a meaningful difference to patients.

Beyond just capital

At Astellas Venture Management (AVM) – a wholly-owned venture capital organization within Astellas, headquartered in the San Francisco Bay Area – capital is just one of the ingredients we offer to add value to our biotechnology investments and partnerships. We generally take a strategic investor approach for companies in our invested portfolio, providing access to expertise, technology and/or resources in addition to the injection of finance. An equity investment from AVM can include access to Astellas’ research and development (R&D) capabilities and expertise, and a global network of partner academic institutions and biotechnology companies, to help advance and accelerate the start-up’s innovation.

UP­DAT­ED: Ver­tex joins Mer­ck, Pfiz­er — re­vamp­ing multi­bil­lion-dol­lar tri­al strat­e­gy as biotech R&D crum­bles

You can add Pfizer, Merck and — as we found out Friday morning — Vertex to the growing list of pharma giants hitting the pause button on a range of clinical trials. But not everyone in R&D is getting a red light.

Vertex says that it’s doing its best to keep working its pipeline strategy, coming up with a plan “to enable virtual clinic visits and home delivery of study drug to ensure study continuity and medical monitoring, and to facilitate study procedures.”

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Covid-19 roundup: In­ter­cept, blue­bird and a grow­ing list of biotechs feel the pain as pan­dem­ic man­gles FDA, R&D sched­ules

Around 100 staffers at Boston area hospitals have now tested positive for Covid-19, spotlighting the growing risk that the pandemic will sideline many of the most essential workers in healthcare as caseloads peak in the US and around the globe. With more than 3,400 deaths, Spain has become the latest country to surpass the official death count attributed to the new coronavirus in China, where the outbreak originated. As of Thursday morning, confirmed global cases had crossed 470,000 and the death count eclipsed 21,000.

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Af­ter crit­ics lam­bast­ed Gilead for grab­bing the FDA's spe­cial rare drug sta­tus on remde­sivir, they're giv­ing it back

Two days after Gilead won orphan drug status for remdesivir as a potential treatment for Covid-19, they’re handing it back.

The company was slammed from several sides after Gilead reported that the FDA had come through with the special status, which comes with 7 years of market exclusivity, the waiver of FDA fees and some tax credits as well. Typically, everyone who can get orphan status lands it without much of a fuss, but Democratic presidential candidate Bernie Sanders, Public Citizen and other consumer groups were outraged.

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Mod­er­na CEO Stéphane Ban­cel out­lines a short path for emer­gency use of a coro­n­avirus vac­cine

NIAID director Anthony Fauci has left no doubts that it takes 12 to 18 months to get a new vaccine tested and in commercial use, in the best of circumstances. But in times of a global emergency — like these — maybe there’s another, faster route to follow.

In an SEC filing on Tuesday, Moderna $MRNA staked out a record-setting pathway to getting their mRNA vaccine into the frontline of the healthcare response as early as this fall. The SEC filing notes that CEO Stéphane Bancel told Goldman Sachs that an emergency use approval could allow the vaccine to go to healthcare workers and certain individuals in a matter of months — presumably provided the NIH sees the safety and efficacy data they would need from the Phase I.

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As share buy­backs come un­der scruti­ny, what's in store for the bio­phar­ma in­dus­try?

Stock buybacks are not to be permitted for companies that will be bailed out in the coronavirus stimulus package, Congressional leaders have signaled. To what degree the biopharma industry has relied on buybacks for earnings growth in recent years, and if the trend continues, are the big questions as scrutiny into the practice heightens and balance sheets weaken with the coronavirus pandemic wreaking havoc on global economies.

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A Sin­ga­pore VC rais­es $200M for a new round, but will Covid-19 pre­vent it from rais­ing the rest?

A top Singaporean biotech venture fund is nearly halfway toward its largest ever fund, but in a sign of what could be in store for VCs amid a global economic freeze, said they could face headwinds raising the other half.

Vickers Venture Partners has secured $200 million out of a targeted $500 million for its 6th fund, first announced in early 2018. They’ve given themselves 13 months to complete the financing, Vickers founder Finian Tan told Deal Street Asia, but the financial frost settling amid the Covid-19 pandemic could slow efforts.

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Strug­gling Unum ex­ecs are ready to con­sid­er a sale, merg­er or any deal that comes its way

Unum $UMRX is working its way through a survival plan of sorts.

After getting hit with a trio of FDA holds in its brief public history and triggering its second pivot to a new lead drug program while laying off 60% of the staff, the troubled penny stock biotech Unum Therapeutics has hatched new plans to secure financial backing while lining up a go-forward strategy for the company.

First, Lincoln Park Capital Fund has agreed to buy up to $25 million of the long-suffering stock, as Unum directs. And the executive team — led by CEO Chuck Wilson — has put everything on the table for consideration: a sale, acquisition, merger, licensing deal, you name it. The ACTR707 program, meanwhile, is being formally wrapped up — their second failed lead program.

Caught in a Covid-19 mael­strom, Eli Lil­ly locks down clin­i­cal tri­als as multi­bil­lion-dol­lar R&D ops de­rail

The Covid-19 pandemic has derailed Eli Lilly’s $6 billion R&D operations.

The pharma giant reported Monday morning that it has decided to hit the brakes on most new study starts and pause enrollment for most ongoing studies. Lilly adds that it is continuing dosing for ongoing studies, “but with study-by-study consideration.”

The pandemic has severely disrupted healthcare systems around the globe, says Lilly, making it difficult or impossible to conduct studies at many research sites. And there’s no timeline for when it expects to get back on track.

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