CEO Lex Rovner (64x Bio)

George Church backs a start­up so­lu­tion to the mas­sive gene ther­a­py man­u­fac­tur­ing bot­tle­neck

George Church and his grad­u­ate stu­dents have spent the last decade seed­ing star­tups on the ra­zor’s edge be­tween bi­ol­o­gy and sci­ence fic­tion: gene ther­a­py to pre­vent ag­ing, CRISPRed pigs that can be used to har­vest or­gans for trans­plant, and home kits to test your poop for healthy or un­healthy bac­te­ria. (OK, maybe they’re not all on that ra­zor’s edge.)

But now a new spin­out from the De­part­ment of Ge­net­ics’ sec­ond floor is tack­ling a far hum­bler prob­lem — one that ma­jor com­pa­ny af­ter ma­jor com­pa­ny has stum­bled over as they tried to get cures for rare dis­eases and oth­er gene ther­a­pies in­to the clin­ic and past reg­u­la­tors: How the hell do you build these?

There’s a lot hap­pen­ing for new ther­a­pies but not enough at­ten­tion around this prob­lem,” Lex Rovn­er, who was a post-doc at Church’s lab from 2015 to 2018, told End­points News. “And if we don’t fig­ure out how to fix this, many of these ther­a­pies won’t even reach pa­tients.”

This week, with Church and a cou­ple oth­er promi­nent sci­en­tists as co-founders, Rovn­er launched 64x Bio to tack­le one key part of the man­u­fac­tur­ing bot­tle­neck. They won’t be look­ing to retro­fit plants or build gene ther­a­py fac­to­ries, as Big Phar­ma and big biotech are now spend­ing bil­lions to do. In­stead, with $4.5 mil­lion in seed cash, they will try to en­gi­neer the in­di­vid­ual cells that churn out a crit­i­cal com­po­nent of the ther­a­pies.

George Church

The goal is to build cells that are fine-tuned to do noth­ing but spit out the vi­ral vec­tors that re­searchers and drug de­vel­op­ers use to shut­tle gene ther­a­pies in­to the body. Dif­fer­ent vec­tors have dif­fer­ent de­mands; 64x Bio will look to make ef­fi­cient cel­lu­lar fac­to­ries for each.

“While a few gen­er­al ways to in­crease vec­tor pro­duc­tion may ex­ist, each unique vec­tor serotype and pay­load pos­es a spe­cif­ic chal­lenge,” Church said in an emailed state­ment. “Our plat­form en­ables us to fine tune cus­tom so­lu­tions for these dis­tinct com­bi­na­tions that are par­tic­u­lar­ly hard to over­come.”

Be­fore join­ing Church’s lab, Rovn­er did her grad­u­ate work at Yale, where she stud­ied how to en­gi­neer bac­te­ria to pro­duce new kinds of pro­tein for drugs or oth­er pur­pos­es. And af­ter leav­ing Church’s lab in 2018, she ini­tial­ly set out to build a man­u­fac­tur­ing start­up with a broad fo­cus.

Yet as she spoke with hun­dreds of biotech ex­ec­u­tives on LinkedIn and in cof­fee shops around Cam­bridge, the same is­sue kept pop­ping up: They liked their gene ther­a­py tech­nol­o­gy in the lab but they didn’t know how to scale it up.

“Every­one kept say­ing the same thing,” Rovn­er said. “We ba­si­cal­ly re­al­ized there’s this huge prob­lem.”

The is­sue would soon make head­lines in in­dus­try pub­li­ca­tions: blue­bird de­lay­ing the launch of Zyn­te­glo, No­var­tis de­lay­ing the launch of Zol­gens­ma in the EU, Ax­o­vant de­lay­ing the start of their Parkin­son’s tri­al.

Part of the prob­lem, Rovn­er said, is that gene ther­a­pies are de­liv­ered on vi­ral vec­tors. You can build these vec­tors in mam­malian cell lines by feed­ing them a small cir­cu­lar strand of DNA called a plas­mid. The prob­lem is that mam­malian cells have, over bil­lions of years, evolved tools and de­fens­es pre­cise­ly to avoid mak­ing virus­es. (Lest the mam­mal they live in die of in­fec­tion).

There are ge­net­ic mu­ta­tions that can turn off some of the in­ter­nal de­fens­es and un­leash a cell’s abil­i­ty to pro­duce virus, but they’re rare and hard to find. Oth­er plat­forms, Rovn­er said, try to find these mu­ta­tions by us­ing CRISPR to knock out genes in dif­fer­ent cells and then screen­ing each of them in­di­vid­u­al­ly, a process that can re­quire hun­dreds of thou­sands of dif­fer­ent 100-well plates, with each well con­tain­ing a dif­fer­ent group of mu­tant cells.

“It’s just not prac­ti­cal, and so these plat­forms nev­er find the cells,” Rovn­er said.

64x Bio will try to find them by build­ing a li­brary of mil­lions of mu­tant mam­malian cells and then us­ing a mol­e­c­u­lar “bar­cod­ing” tech­nique to screen those cells in a sin­gle pool. The tech­nique, Rovn­er said, lets them trace how much vec­tor any giv­en cell pro­duces, al­low­ing re­searchers to quick­ly iden­ti­fy su­per-pro­duc­ing cells and their mu­ta­tions.

The tech­nol­o­gy was de­vel­oped par­tial­ly in-house but draws from IP at Har­vard and the Wyss In­sti­tute. Har­vard’s Pam Sil­ver and Wyss’s Jef­frey Way are co-founders.

The com­pa­ny is now based in So­Ma in San Fran­cis­co. With the seed cash from Fifty Years, Refac­tor and First Round Cap­i­tal, Rovn­er is re­cruit­ing and look­ing to raise a Se­ries A soon. They’re in talks with phar­ma and biotech part­ners, while they try to val­i­date the first pre­clin­i­cal and clin­i­cal ap­pli­ca­tions.

Gene ther­a­py is one fo­cus, but Rovn­er said the plat­form works for any­thing that in­volves vi­ral vec­tor, in­clud­ing vac­cines and on­colyt­ic virus­es. You just have to find the right mu­ta­tion.

“It’s the rare cell you’re look­ing for,” she said.

Tar­get­ing a Po­ten­tial Vul­ner­a­bil­i­ty of Cer­tain Can­cers with DNA Dam­age Re­sponse

Every individual’s DNA is unique, and because of this, every patient responds differently to disease and treatment. It is astonishing how four tiny building blocks of our DNA – A, T, C, G – dictate our health, disease, and how we age.

The tricky thing about DNA is that it is constantly exposed to damage by sources such as ultraviolet light, certain chemicals, toxins, and even natural biochemical processes inside our cells.¹ If ignored, DNA damage will accumulate in replicating cells, giving rise to mutations that can lead to premature aging, cancer, and other diseases.

Roivant par­lays a $450M chunk of eq­ui­ty in biotech buy­out, grab­bing a com­pu­ta­tion­al group to dri­ve dis­cov­ery work

New Roivant CEO Matt Gline has crafted an all-equity upfront deal to buy out a Boston-based biotech that has been toiling for several years now at building a supercomputing-based computational platform to design new drugs. And he’s adding it to the Erector set of science operations that are being built up to support their network of biotech subsidiaries with an eye to growing the pipeline in a play to create a new kind of pharma company.

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Fol­low biotechs go­ing pub­lic with the End­points News IPO Track­er

The Endpoints News team is continuing to track IPO filings for 2021, and we’ve designed a new tracker page for the effort.

Check it out here: Biopharma IPOs 2021 from Endpoints News

You’ll be able to find all the biotechs that have filed and priced so far this year, sortable by quarter and listed by newest first. As of the time of publishing on Feb. 25, there have already been 16 biotechs debuting on Nasdaq so far this year, with an additional four having filed their S-1 paperwork.

Ken Frazier, Merck CEO (Bess Adler/Bloomberg via Getty Images)

UP­DAT­ED: Mer­ck takes a swing at the IL-2 puz­zle­box with a $1.85B play for buzzy Pan­dion and its au­toim­mune hope­fuls

When Roger Perlmutter bid farewell to Merck late last year, the drugmaker perhaps best known now for sales giant Keytruda signaled its intent to take a swing at early-stage novelty with the appointment of discovery head Dean Li. Now, Merck is signing a decent-sized check to bring an IL-2 moonshot into the fold.

Merck will shell out roughly $1.85 billion for Pandion Pharmaceuticals, a biotech hoping to gin up regulatory T cells (Tregs) to treat a range of autoimmune disorders, the drugmaker said Thursday.

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CEO Fred Aslan (Artiva)

NK cell ther­a­py play­er Arti­va makes some more noise, pulling in $120M Se­ries B less than a month af­ter Mer­ck deal

Not even one month after Big Pharma took notice of Artiva when Merck signed a collaboration worth nearly $2 billion in milestones, the off-the-shelf NK cell biotech already has its next big fundraise.

Artiva returns from the venture well Friday with a $120 million Series B round, money they will use to get their first program into the clinic and to file INDs for another two candidates. The raise marks the latest development in a rapidly expanding footprint for Artiva, which, in addition to the Merck deal last month, has now raised almost $200 million since its Series A last June.

With dust set­tled on ac­tivist at­tack, Lau­rence Coop­er leaves Zio­pharm to a new board

Laurence Cooper has done his part.

In the five years since he left a tenured position at Houston’s MD Anderson Cancer Center to become CEO of Boston-based Ziopharm, he’s steered the small-cap immunotherapy player through patient deaths in trials, clinical holds, short attacks and, most recently, an activist attack on the board.

So when the company has “fantastic news” like an IND clearance for a TCR T cell therapy program, he’s ready to pass on the baton.

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Doug Ingram (file photo)

Why not? Sarep­ta’s third Duchenne MD drug sails to ac­cel­er­at­ed ap­proval

Sarepta may be running into some trouble with its next-gen gene therapy approach to Duchenne muscular dystrophy. But when it comes to antisense oligonucleotides, the well-trodden regulatory path is still leading straight to an accelerated approval for casimersen, now christened Amondys 45.

We just have to wait until 2024 to find out if it works.

Amondys 45’s approval was unceremonious, compared to its two older siblings. There was no controversy within the FDA over approving a drug based on a biomarker rather than clinical benefit, setting up a powerful precedent that still haunts acting FDA commissioner Janet Woodcock as biotech insiders weighed her potential permanent appointment; no drama like the FDA issuing a stunning rejection only to reverse its decision and hand out an OK four months later, which got more complicated after the scathing complete response letter was published; no anxious tea leaf reading or heated arguments from drug developers and patient advocates who were tired of having corticosteroids as their loved ones’ only (sometimes expensive) option.

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Steve Cutler, Icon CEO (Icon)

In the biggest CRO takeover in years, Icon doles out $12B for PRA Health Sci­ences to fo­cus on de­cen­tral­ized clin­i­cal work

Contract research M&A had a healthy run in recent years before recently petering out. But with the market ripe for a big buyout and the Covid-19 pandemic emphasizing the importance of decentralized trials, Wednesday saw a tectonic shift in the CRO world.

Icon, the Dublin-based CRO, will acquire PRA Health Sciences for $12 billion in a move that will shake up the highest rungs of a fragmented market. The merger would combine the 5th- and 6th-largest CROs by 2020 revenue, according to Icon, and the merger will set the newco up to be the second-largest global CRO behind only IQVIA.

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J&J ad­comm live blog: Com­mit­tee votes 22-0 to rec­om­mend an FDA OK for the J&J vac­cine, set­ting up 3rd US Covid-19 jab

The US could have a third authorized Covid-19 vaccine within hours.

The FDA’s advisory committee voted unanimously — 22-0 — to recommend the agency issue an emergency use authorization for J&J’s vaccine. If they follow the precedent of the Pfizer and Moderna vaccine,  the FDA will likely authorize the vaccine by Saturday, immediately adding a few million doses to the US supply and adding a 100 million by June. An authorization would give the world its first single-dose vaccine, a major weapon in the effort to vaccinate the world and bring the virus to heel, particularly in rural and developing areas.