Spun out of George Church's lab, this biotech up­start is map­ping the AAV uni­verse for No­var­tis, Sarep­ta to gaze

In a few days, through a se­ries of video con­fer­ences, gene ther­a­py re­searchers around the world will be pre­sent­ing their lat­est find­ings at the vir­tu­al an­nu­al meet­ing of the Amer­i­can So­ci­ety of Gene & Cell Ther­a­py. Al­most every dis­cus­sion will fea­ture a top­ic that has been cen­tral to the ex­is­tence of the field but con­tin­ues to per­plex ex­perts as they seek to re­fine the modal­i­ty: the de­liv­ery of a gene to the tis­sue where it’s need­ed to fix dis­ease.

For the first time, a biotech up­start will be pub­licly out­lin­ing their take on the prob­lem — with an ar­ti­fi­cial in­tel­li­gence fla­vor that No­var­tis and Sarep­ta are gob­bling up.

Sea­soned at­ten­dees of AS­GCT would rec­og­nize the team be­hind Dyno Ther­a­peu­tics. Since Er­ic Kel­sic be­gan build­ing the plat­form in 2015 as a post­doc at George Church’s il­lus­tri­ous lab at Wyss In­sti­tute, he’s been mak­ing the rounds at sci­en­tif­ic meet­ings. At Har­vard, his group had demon­strat­ed how — by do­ing high through­put screen­ing on all cap­sid vari­ants of one par­tic­u­lar AAV serotype, mod­el­ing the space with ma­chine learn­ing, and fi­nal­ly build­ing a pro­file of each cap­sid that can be ranked by dif­fer­ent at­trib­ut­es — they could point to syn­thet­ic AAV cap­sid can­di­dates that are su­pe­ri­or to the hand­ful of nat­ur­al vari­ants cur­rent­ly in use.

Alan Crane

“This was by far the best ap­pli­ca­tion that I’d ever seen of AI in bi­ol­o­gy,” Alan Crane, an en­tre­pre­neur part­ner at Po­laris and Dyno’s ex­ec­u­tive chair­man, told End­points News. “It turns out po­ten­tial part­ners were see­ing it the same way, be­cause when Er­ic came to me back in mid-2018, he al­ready had this list of lit­er­al­ly dozens of com­pa­nies that have proac­tive­ly ap­proached him.”

Out of that pool Dyno had picked No­var­tis for a col­lab­o­ra­tion on eye dis­or­ders and Sarep­ta to team up on mus­cle dis­eases. Up­front pay­ments, sup­port, op­tion fees and mile­stones from these two deals could add up to $2 bil­lion, in­clud­ing $40 mil­lion from the re­search phase of the Sarep­ta deal.

Louise Rodi­no-Kla­pac

“We al­ways con­stant­ly try to make sure that we are ahead of the curve in terms of our tech­nol­o­gy and look­ing at next-gen­er­a­tion treat­ments,” Louise Rodi­no-Kla­pac, Sarep­ta’s head of gene ther­a­py, said. “So al­though we’re very hap­py with our cur­rent ap­proach and our cur­rent vec­tor, we’re think­ing about the fu­ture po­ten­tial tech­nolo­gies for oth­er mus­cu­lar dy­s­tro­phies.”

Cap­sids — the pro­tein shells that en­close ge­net­ic ma­te­r­i­al of a virus — is one of three core com­po­nents need­ed to form a gene ther­a­py, she ex­plained, along­side the trans­gene that’s miss­ing or de­fec­tive in a pa­tient, and a pro­mot­er that turns the gene on in the cell. And small tweaks to the cap­sid can trans­late to pro­found changes in the fi­nal prod­uct’s im­muno­genic­i­ty, man­u­fac­tura­bil­i­ty, ef­fi­cien­cy of de­liv­ery, speci­fici­ty to tar­get cells and pack­age size.

Er­ic Kel­sic

All of these met­rics are tak­en in­to con­sid­er­a­tion on Dyno’s Cap­sidMap plat­form, which takes “the most com­pre­hen­sive ap­proach to map­ping out the AAV uni­verse,” fill­ing the gaps in each galaxy and telling stars from pure void, Kel­sic said.

“We don’t want to im­prove one prop­er­ty but have oth­er things get worse,” a chal­lenge that oth­ers who have at­tempt­ed to solve the prob­lem have faced, he added.

With a new tech­nol­o­gy that promis­es to op­ti­mize vi­ral vec­tors for in­di­vid­ual ap­pli­ca­tions like that, Crane pre­dict­ed the com­pa­ny — which Po­laris seed­ed with a mod­est $9 mil­lion — might nev­er need ad­di­tion­al ven­ture funds.

While Dyno re­tains the op­tion to cre­ate its own ther­a­pies, ex­pect part­ner­ships (and there are more com­ing) to re­main at the cen­ter for a while.

“What I’ve ob­served in the in­dus­try — not on­ly in gene ther­a­py but in all ar­eas — is as com­pa­nies start to move in­to pipelines, they usu­al­ly have to leave the plat­form be­hind,” Crane said.

Much work is to be done. Dyno cur­rent­ly has ca­pac­i­ty to screen hun­dreds of thou­sands to mil­lions of cap­sids and test them both in vit­ro and in vi­vo, but the plan is to scale up the in­fra­struc­ture even fur­ther — both on the ex­per­i­men­tal and the com­pu­ta­tion­al fronts. The head­count is dou­bling from rough­ly 20 while all the ma­chine learn­ing gets moved on­to the cloud.

A can­di­date won’t emerge any time soon, and even when it does ma­te­ri­al­ize it would have to go through rig­or­ous safe­ty test­ing at the part­ners’ own R&D op­er­a­tions — a process that could take an­oth­er one or two years. Still, Kel­sic sees it as the quick­est way to bring their work to pa­tients even while they fig­ure new things out.

“Es­pe­cial­ly when we’re think­ing about tech­nol­o­gy, some­thing George and I talked a lot about when we start­ed this project, it still feels re­al­ly ear­ly days for gene ther­a­py,” he said. “There’s so much po­ten­tial.”

Elizabeth Nabel speaks at a news conference, Oct. 7, 2019 (Elise Amendola/AP Images)

Brigham and Wom­en's pres­i­dent Eliz­a­beth Nabel fol­lows Mon­cef Slaoui off Mod­er­na's board

Amid recent scrutiny on how Moderna’s top executives have been cashing out their increasingly valuable shares, the biotech is parting ways with a board member who’s also heading a hospital where its Covid-19 vaccine is being tested.

Elizabeth Nabel — the president of Brigham and Women’s Hospital — has followed in Moncef Slaoui’s footsteps in resigning from Moderna’s board of directors. She took the role in 2015, two years before the Operation Warp Speed leader did; and as with Slaoui and MIT professor Robert Langer, her term was due to expire in 2021.

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Tony Coles, Cerevel Therapeutics CEO

Adding $445M, Tony Coles and his big Pfiz­er neu­ro spin­out hitch a ride to Wall Street on Per­cep­tive’s SPAC

Two years ago, after Pfizer abruptly shut down its entire neuroscience division, Bain Capital bet $350 million that those assets were still worth something and packaged them into a new biotech: Cerevel Therapeutics. A year later, they got seasoned executive Tony Coles, who had recently jumped back into the C-suite of another neuroscience startup, to run the company.

Now Coles is steering Cerevel public, in what he says is the largest ever transaction of its kind. Cerevel has agreed to merge with Perceptive Advisors’ specialty acquisition company ARYA II. Between the roughly $125 million Perceptive raised through ARYA and an additional investment of $320 million Bain Capital, Perceptive and — yes, really — Pfizer, among others, Cerevel will now move forward with an added $445 million in its coffers.

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Roche de­clares a PhI­II fail­ure for Covid-19 as the IL-6 re­pur­pos­ing the­o­ry bites the dust

Another big IL-6 drug has failed to move the needle for Covid-19 patients, leaving that particular field of repurposed drug R&D on the ropes for the pandemic.

This morning it was Roche’s turn to outline a Phase III failure for Actemra, adding compelling data that have now all but extinguished the theory that an IL-6 drug could significantly help the most severely afflicted patients. That comes just weeks after Regeneron and Sanofi hit the red light on their trial for Kevzara after getting back-to-back readouts that made Roche’s trial a long shot at best.

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Sanofi and GSK say they're near a vac­cine deal with EU hours af­ter fi­nal­iz­ing Warp Speed con­tract

On the heels of landing the largest Warp Speed contract to date, Sanofi and GlaxoSmithKline continued to make moves Friday afternoon.

The two companies announced they are in advanced discussions with the EU to supply up to 300 million doses of their Covid-19 vaccine candidate, coming just a few hours after securing their $2.1 billion deal with the US. Should the agreement be finalized, all EU member states will have the option to purchase the vaccine.

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Sandy Macrae, Sangamo CEO

No­var­tis turns to Sang­amo with a $795M-plus deal aimed at us­ing zinc fin­ger tech for the neu­ro pipeline

When Novartis recruited Ricardo Dolmetsch from Stanford to lead its neuroscience group, great emphasis was placed on decoding genomics and the brain circuitry to find new breakthroughs for the beleaguered field. Seven years and a failed Fragile X therapy later, he has a new tool to go after some of these targets his team has unearthed.

In a new collaboration, Novartis is paying Sangamo Therapeutics $75 million upfront to leverage zinc finger protein transcription factors in the regulation of three genes ties to autism — a core focus of Dolmetsch’s academic research days — intellectual disability and other neurodevelopmental disorders. Another $720 million in milestones are on the table, alongside a pledge to reimburse all of Sangamo’s research work.

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Ludwig Hantson, Alexion CEO

UP­DAT­ED: The lead drug in Alex­ion’s $930M buy­out deal last fall just flopped — adding in­jury to an­a­lysts’ M&A in­sults

When Alexion $ALXN put down $930 million in cash last fall to buy Achillion, the biotech’s top execs were particularly proud of 2 clinical-stage assets, with a spotlight on the lead drug danicopan (ACH-4471) in Phase II. That drug, along with a companion therapy in Phase I, fit right in their R&D wheelhouse, noted CEO Ludwig Hantson.

But now the lead drug, redubbed ALXN2040, is being washed out and repositioned after failing 2 Phase II trials for C3 Glomerulopathy.

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Robert Nelsen (Illustration by Emma Kumer for Endpoints News)

Af­ter Big Phar­ma aban­doned in­fec­tious dis­eases, 5 biotech con­trar­i­ans de­cid­ed to go all in. Then Covid-19 changed every­thing

Bob Nelsen had been quietly wondering how to eradicate viruses for years, before one day in 2015, he welcomed a pair of immunologists into the ARCH Venture Partners offices on the 34th floor of Seattle’s Wells Fargo Building.

Louis Picker and Klaus Früh, professors at Oregon Health & Science University, had by then spent 5 years running around the country in search of funding for their startup, TomegaVax, and Früh, at least, was nearing wit’s end. The Gates Foundation was interested but told them they needed other investors. Investors told them to come back with more data, pharmaceutical executives said they’re in the wrong game — too little money to be made fighting infectious disease. Still, a well-connected board member named Bob More landed them a meeting with the coveted venture capitalist, and so, in a narrow conference room overlooking the Puget Sound, Picker prepared to again explain the idea he had spent 15 years on: re-engineering a benign microbe into the first vaccines for HIV and better ones for hepatitis and tuberculosis.

“This lightbulb went on his head,” Picker recalled in a recent interview. “Most of them just didn’t get it. And Bob’s hit.”

By that point, Nelsen was more than just a venture capitalist. Scraggly and greying but no less opinionated at 52, he was mobbed at biotech conferences, having earned a reputation for crass wisdom and uncanny foresight, for making big bets on big ideas that changed medicine. Those ideas included DNA sequencing, which he first cut a check for in the 90s, and leveraging the immune system to tackle cancer. He earned millions making billion-dollar companies.

Yet for years he had harbored an almost singular obsession: “I hate viruses,” he told Forbes in 2016. He told me he was “pissed off” at them. The obsession drove him to his first biotech investment in 1993, for an inhalable flu vaccine approved a decade later and still in use. And it drove him to invest in CAR-T as a potential cure for HIV, years before it proved a wildly effective treatment for some cancers.

Now, listening to Picker talk about T cells and antibodies and the curious biology of cytomegalovirus, Nelsen began wondering if it was time for another bet. Picker’s technology was not only promising, he reasoned, it could be the basis of a company that changed how researchers approached viruses. Instead of trying to come up with an antidote for every pathogen, you could do what cancer researchers had learned to do, and harness the immune system to do the work for you.

This wasn’t a popular opinion at the time. “It’s like the least trendy idea in the world,” Nelsen told me. “People would say, ‘Why the hell are you going into infectious disease?’”

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Roche/Genen­tech dou­bles down on tau, fronting $120M cash to al­ly on a 2-pronged strat­e­gy to fight Alzheimer’s

After butting up against repeated failures on the amyloid beta side of the R&D strategy for fighting Alzheimer’s, Roche is once again turning to the runner-up target that has been getting an increased focus in the hopes of finding something — anything — that can slow the progress of this disease.

The terms of the deal include $120 million upfront for UCB, plus potential development and sales milestones, cost reimbursement and royalties totaling nearly $2 billion. UCB will fund and conduct a proof-of-concept study in Alzheimer’s, and with the results in hand, Genentech, a Roche subsidiary, can either return the rights to UCB or push ahead in a drive to the market.

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President Trump speaks during an event to sign executive orders on lowering drug prices, July 24, 2020 (Alex Brandon/AP Images)

Trump’s ‘rad­i­cal’, ‘hor­ri­ble’ ex­ec­u­tive or­ders on drug pric­ing earn a C-suite back­lash this week — with one threat to do more over­seas

Once the pandemic erupted in the US, Big Pharma enjoyed a brief period of detente — if not actually warm relations — with the Trump administration.

After years of criticizing high drug prices and threatening legislation that would curb the industry’s pricing freedom, the president warmly encouraged the industry’s commitment to a pell mell race to new vaccines and drugs to fight Covid-19 — often at speeds that would have been considered impossible back in January. And it raised the possibility that biopharma could finally find a way to achieve some kind of popularity after years of public toxicity.

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