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.

Op­ti­miz­ing Cell and Gene Ther­a­py De­vel­op­ment and Pro­duc­tion: How Tech­nol­o­gy Providers Like Corn­ing Life Sci­ences are Spurring In­no­va­tion

Remarkable advances in cell and gene therapy over the last decade offer unprecedented therapeutic promise and bring new hope for many patients facing diseases once thought incurable. However, for cell and gene therapies to reach their full potential, researchers, manufacturers, life science companies, and academics will need to work together to solve the significant challenges facing the industry.

Pfiz­er, Sarep­ta and two oth­ers sug­gest Duchenne drug safe­ty is­sues tied to "class ef­fect"

Since the first experimental Duchenne gene therapy programs came about, the space has proven rife with safety issues and patient deaths in clinical trials. Pfizer and three biotechs now think they’ve found a reason why.

The four companies suggested there may be a “class effect” causing the adverse events in Duchenne gene therapies, they wrote in a new study. They specifically highlighted how side effects in five patients across three trials, who all showed muscle weakness with cardiac involvement, were “strikingly similar.”

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 142,400+ biopharma pros reading Endpoints daily — and it's free.

Pre­sent­ing a live End­points News event: Man­ag­ing a biotech in tur­bu­lent times

Biotech is one of the smartest, best educated industries on the planet. PhDs abound. We’ve had a long enough track record to see a new generation of savvy, experienced execs coming together to run startups.

And in these times, they are being tested as never before.

Biotech is going through quite a rough patch right now. For 2 years, practically anyone with a decent resume and some half-baked ideas on biotech could start a company and get it funded. The pandemic made it easy in many ways to pull off an IPO, with traditional road shows shut down in exchange for a series of quick Zoom meetings. Generalist investors flocked as the numbers raised soared into the stratosphere.

Peter Marks (Greg Nash/Pool via AP)

Even FDA's Pe­ter Marks is wor­ried about the com­mer­cial vi­a­bil­i­ty of gene and cell ther­a­pies

When bluebird bio’s gene therapy to treat beta thalassemia won European approval in 2019, the nearly $2 million per patient price tag for the potential cure seemed like a surmountable hurdle.

Fast forward two years later, and bluebird has withdrawn Zynteglo, the beta thal drug, along with the rest of its gene therapy portfolio from Europe, which the company said is generally unwilling to pay a fair price for the treatment.

Martin Shkreli (Dennis Van Tine/MediaPunch/IPX)

In­fa­mous biotech ex­ec Mar­tin Shkre­li gets out of prison, hits the street

Martin Shkreli, the infamous biotech CEO who made headlines for his jeering assault on a legion of critics in and out of Congress, is back on the streets after 4 years inside a federal penitentiary.

Shkreli’s attorney put out a statement Wednesday afternoon saying that the “pharma bro” had been transferred to a halfway house in New York with a few more months to go under federal custody, slated to end September 14. Attorney Benjamin Brafman acknowledged the release and vowed that he and Shkreli are keeping quiet.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 142,400+ biopharma pros reading Endpoints daily — and it's free.

De­spite fed­er­al ef­forts to di­ver­si­fy clin­i­cal tri­als, progress re­mains 'stag­nan­t' — re­port

While calls to diversify clinical trials have grown louder in recent years — gaining support from federal agencies such as the FDA and NIH — progress has largely stalled, according to a new report from the National Academies of Sciences, Engineering and Medicine.

Swaths of patients in racial and ethnic minority groups, as well as LGBTQIA+, pregnant and older adult populations continue to be left out of clinical trials. While some advances have been made in the last 30 years — women now account for roughly half of clinical trial participants — growth in other areas remains stagnant, according to the report, which was mandated by Congress and sponsored by the NIH.

Paul Chaplin, Bavarian Nordic president and CEO

Bavar­i­an Nordic se­cures BAR­DA con­tract for small­pox vac­cine

It seems that smallpox vaccination production is weighing on the mind of the US government. And manufacturer Bavarian Nordic is the latest company to benefit.

Just a few days after Emergent, a company that has made government contracts its lifeblood, acquired the exclusive rights to Tembexa from Chimerix, with a $225 million cash payment and an expected BARDA contract, the agency has offered a contract for smallpox vaccine production.

Frank Pallone (D-NJ), House Energy and Commerce Committee chair (Kevin Dietsch/Pool via AP Images)

House com­mit­tee unan­i­mous­ly ad­vances FDA user fee leg­is­la­tion with ac­cel­er­at­ed ap­proval tweaks

The House Energy and Commerce Committee on Wednesday offered a rare show of bipartisan support for a bill that would provide the FDA with user fees for the next five years.

The committee voted 55-0 to advance the quinquennial user fee bill to the full House floor, which if approved, will allow the FDA to use biopharma funds to hire new reviewers, and hit new marks as outlined in the user fee deals that the FDA and biopharma companies forged over the past several years.

Lina Khan, FTC chair (Saul Loeb/Pool via AP)

New FTC com­mis­sion­er could turn the tide for an in­ves­ti­ga­tion in­to PBMs

The Senate last week voted along party lines, 51-50, with Vice President Kamala Harris casting the tie-breaker, to make President Biden appointee Alvaro Bedoya the deciding vote on a split 2-2 Federal Trade Commission.

The addition of Bedoya to the FTC could not only spell more trouble for biopharma M&A activity, as he may align with his Democrat partners to break the FTC ties, but it may also mean that FTC Chair Lina Khan has what she needs to move forward on a study around the pharma middlemen known as pharmacy benefit managers.