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.”

Inside FDA HQ (File photo)

The FDA just ap­proved the third Duchenne MD drug. And reg­u­la­tors still don’t know if any of them work

Last year Sarepta hit center stage with the FDA’s controversial reversal of its CRL for the company’s second Duchenne muscular dystrophy drug — after the biotech was ambushed by agency insiders ready to reject a second pitch based on the same disease biomarker used for the first approval for eteplirsen, without actual data on the efficacy of the drug.

On Wednesday the FDA approved the third Duchenne MD drug, based on the same biomarker. And regulators were ready to act yet again despite the lack of efficacy data.

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Franz-Werner Haas, CureVac CEO

UP­DAT­ED: On the heels of a snap $1B raise, Cure­Vac out­lines plans to seek emer­gency OK for their Covid-19 vac­cine in a mat­ter of months

CureVac is going from being one of the quietest players in the race to develop a new vaccine to fight the worst public health crisis in a century to a challenger for the multibillion-dollar market that awaits the first vaccines to make it over the finish line. Typically low-key at a time of brash comments and incredibly ambitious development timelines from the leaders, CureVac now is jumping straight into the spotlight.

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Cell and Gene Con­tract Man­u­fac­tur­ers Must Em­brace Dig­i­ti­za­tion

The Cell and Gene Industry is growing at a staggering 30% CAGR and is estimated to reach $14B by 20251. A number of cell, gene and stem cell therapy sponsors currently have novel drug substances and products and many rely on Contract Development Manufacturing Organizations (CDMO) to produce them with adherence to stringent regulatory cGMP conditions. Cell and gene manufacturing for both autologous (one to one) and allogenic (one to many) treatments face difficult issues such as: a complex supply chain, variability on patient and cellular level, cell expansion count and a tight scheduling of lot disposition process. This complexity affects quality, compliance and accountability in the entire vein-to-vein process for critically ill patients.

US gov­ern­ment re­port­ed­ly be­gins prepar­ing for Covid-19 chal­lenge tri­als. Are they eth­i­cal?

Controversial human challenge trials for potential Covid-19 vaccines reportedly have a new booster — the US government.

Scientists working for the government have begun manufacturing a strain of the novel coronavirus that could be used in such studies, Reuters reported Friday morning. The trials would enroll healthy volunteers to be vaccinated and then intentionally infected with a weakened coronavirus.

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Charlie Silver (Mission Bio)

'We want to be every­where.' Mis­sion Bio rais­es $70M be­hind re­sis­tance-hunt­ing se­quenc­ing plat­form

Charlie Silver wants to look really, really closely at a lot of your cells. And he just got a lot of money to do so.

Silver’s startup, Mission Bio, raised $70 million in a Series C round Thursday led by Novo Holdings. The money, which brings Mission Bio to $120 million raised since its 2012 founding, will be used to advance the single-cell sequencing platform they built to detect early response or resistance to new cancer therapies.

Trevor Martin (Mammoth)

Eye­ing in-vi­vo edit­ing, Mam­moth li­cens­es Jen­nifer Doud­na’s new CRISPR en­zyme

Last month, Jennifer Doudna revealed in Science a new, “hyper-compact” CRISPR enzyme that was half the size of traditional CRISPR enzymes and could, she suspected, offer a new, more versatile tool for gene editing.

Now, the University of California-Berkeley has licensed that enzyme, known as Casφ, exclusively to a biotech startup she and two former students set up three years ago: Mammoth Biosciences. It’s the second new CRISPR protein Mammoth has licensed from Doudna’s lab, after they licensed Cas14 in 2019.

Clockwise from left: Canaccord Genuity principal Michelle Gilson, Canaccord Genuity CSO Brian Mueller and BioMarin CSO Hank Fuchs (Canaccord Genuity webcast)

Bio­Marin CSO diss­es ri­vals for the he­mo­phil­ia A gene ther­a­py crown: Way be­hind, fac­ing big re­cruit­ment chal­lenges and at best a .6 on the gen-one scale

The leader in the race to a hemophilia A gene therapy does not like to be compared unfavorably to the competition. And when their top execs do the comparing, don’t look for any modesty — BioMarin, they say, owns the lead.

As Factor VIII expression wanes over time, quite a few analysts have raised questions about the kind of future BioMarin’s gene therapy — a supposed once-and-done treatment — faces if it stops working. But just 7 days away from their PDUFA date, with high odds of success, the top execs clearly feel that they are way out front, while promising their rivals will discover there’s a tough slog ahead trying to pursue trials where large numbers of patients are ineligible for new therapies.

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Sanofi vet Kather­ine Bowdish named CEO of PIC Ther­a­peu­tics; As the world Terns: Liv­er dis­ease biotech makes ex­ec­u­tive changes

PIC Therapeutics hasn’t raised much money, yet. But the fledgling biotech has attracted a high-profile player to the helm.

The Boston-based biotech has handed the reins to Katherine Bowdish as its president and CEO. Bowdish will also join the board of directors of PIC. Bowdish joins from Sanofi where she served as VP and head of R&D strategy, as well as helping launch and lead Sanofi Sunrise, a venture investment and partnering vehicle at Sanofi. Before that, Bowdish held several exec roles at Permeon Biologics, Anaphore, Alexion Pharmaceuticals and Prolifaron (acquired by Alexion).

Stéphane Bancel speaks to President Donald Trump at the White House meeting on March 2 (AP Images)

UP­DAT­ED: Mod­er­na of­fers steep dis­count in US sup­ply deal — but still takes the crown with close to $2.5B in vac­cine con­tracts

The US pre-order for Moderna’s Covid-19 vaccine is in.

Operation Warp Speed is reserving $1.525 billion for 100 million doses of Moderna’s Phase III mRNA candidate, rounding out to about $15 per dose — including $300 million in incentive payments for timely delivery. Given that Moderna has a two-dose regimen, it’s good for vaccinating 50 million people. The US government also has the option to purchase another 400 million doses for a total of $6.6 billion, or $16.5 per dose.

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