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.”

Fangliang Zhang, AP Images

UP­DAT­ED: Leg­end fetch­es $424 mil­lion, emerges as biggest win­ner yet in pan­dem­ic IPO boom as shares soar

Amid a flurry of splashy pandemic IPOs, a J&J-partnered Chinese biotech has emerged with one of the largest public raises in biotech history.

Legend Biotech, the Nanjing-based CAR-T developer, has raised $424 million on NASDAQ. The biotech had originally filed for a still-hefty $350 million, based on a range of $18-$20, but managed to fetch $23 per share, allowing them to well-eclipse the massive raises from companies like Allogene, Juno, Galapagos, though they’ll still fall a few dollars short of Moderna’s record-setting $600 million raise from 2018.

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As it hap­pened: A bid­ding war for an an­tibi­ot­ic mak­er in a mar­ket that has rav­aged its peers

In a bewildering twist to the long-suffering market for antibiotics — there has actually been a bidding war for an antibiotic company: Tetraphase.

It all started back in March, when the maker of Xerava (an FDA approved therapy for complicated intra-abdominal infections) said it had received an offer from AcelRx for an all-stock deal valued at $14.4 million.

The offer was well-timed. Xerava was approved in 2018, four years after Tetraphase posted its first batch of pivotal trial data, and sales were nowhere near where they needed to be in order for the company to keep its head above water.

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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Por­tion of Neil Wood­ford’s re­main­ing in­vest­ments, in­clud­ing Nanopore, sold off for $284 mil­lion

It’s been precisely one year and one day since Neil Woodford froze his once-vaunted fund, and while a global pandemic has recently shielded him from the torrent of headlines, the fallout continues.

Today, the California-based patent licensing firm Acacia Research acquired the fund’s shares for 19 healthcare and biotech companies for $284 million.  Those companies include shares for public and private companies and count some of Woodford’s most prominent bio-bets, such as Theravance Biopharma, Oxford Nanopore and Mereo Biopharma, according to Sky News, which first reported the sale. It won’t include shares for BenevelontAI, the machine learning biotech once valued at $2 billion.

Drug man­u­fac­tur­ing gi­ant Lon­za taps Roche/phar­ma ‘rein­ven­tion’ vet as its new CEO

Lonza chairman Albert Baehny took his time headhunting a new CEO for the company, making it absolutely clear he wanted a Big Pharma or biotech CEO with a good long track record in the business for the top spot. In the end, he went with the gold standard, turning to Roche’s ranks to recruit Pierre-Alain Ruffieux for the job.

Ruffieux, a member of the pharma leadership team at Roche, spent close to 5 years at the company. But like a small army of manufacturing execs, he gained much of his experience at the other Big Pharma in Basel, remaining at Novartis for 12 years before expanding his horizons.

Covid-19 roundup: Ab­b­Vie jumps in­to Covid-19 an­ti­body hunt; As­traZeneca shoots for 2B dos­es of Ox­ford vac­cine — with $750M from CEPI, Gavi

Another Big Pharma is entering the Covid-19 antibody hunt.

AbbVie has announced a collaboration with the Netherlands’ Utrecht University and Erasmus Medical Center and the Chinese-Dutch biotech Harbour Biomed to develop a neutralizing antibody that can treat Covid-19. The antibody, called 47D11, was discovered by AbbVie’s three partners, and AbbVie will support early preclinical work, while preparing for later preclinical and clinical development. Researchers described the antibody in Nature Communications last month.

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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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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