Feng Zhang (Susan Walsh/AP Images)

Feng Zhang’s qui­et spin­out snares $215M in a race for the next big CRISPR com­pa­ny

Af­ter Sig­ilon Ther­a­peu­tics’ $126 mil­lion IPO last De­cem­ber, COO De­vyn Smith start­ed get­ting calls. Job of­fers, most­ly, for this biotech or that, none that quite hit.

Then a re­cruiter reached out about an open­ing at a spin­out from Feng Zhang’s MIT CRISPR lab that, de­spite a flashy launch, had gone large­ly qui­et for three years. The com­pa­ny, Ar­bor Biotech­nolo­gies, was ready to en­ter a new phase and need­ed a new leader with ex­pe­ri­ence bring­ing drugs in­to hu­man tri­als. Smith, a for­mer Pfiz­er ex­ec­u­tive re­mem­ber­ing the press re­leas­es around Ar­bor’s launch, said yes.

De­vyn Smith

Near­ly a year lat­er, Ar­bor is qui­et no longer. Four months af­ter Smith of­fi­cial­ly joined as CEO, the biotech an­nounced a $1.2 bil­lion deal with Ver­tex to help the big biotech de­vel­op to en­gi­neer pan­creas cells that can be trans­plant­ed in­to a di­a­betes pa­tient with­out trig­ger­ing an im­mune re­sponse, among oth­er cell ther­a­pies.

And on Tues­day, the com­pa­ny an­nounced new a bit of cash: $215 mil­lion in Se­ries B fund­ing — more than 13 times the Se­ries A — led by Temasek, Al­ly Bridge Group, and TCG Crossover.

The Steph Cur­ry-sized deal will bankroll Ar­bor’s tran­si­tion from a biotech fo­cused sole­ly on min­ing the mi­cro­bial world for new CRISPR-based gene edit­ing tools to a biotech that tries to turn these new tools in­to med­i­cines.

In do­ing so, it joins a small flur­ry of biotechs claim­ing they can ex­pand gene edit­ing’s reach by re­ly­ing on new­ly dis­cov­ered DNA-cut­ting en­zymes: not just the No­bel-win­ning Cas9, but al­so Cas12, Cas13, CasX, CasΦ and a long list of more ob­scure ge­net­ic blades.

These com­pa­nies tout ei­ther their ex­cep­tion­al abil­i­ty to en­gi­neer en­zymes (Scribe), or their ex­cep­tion­al abil­i­ty to sift for new en­zymes among large data­bas­es of bac­te­r­i­al genomes (Metageno­mi), or both (Ar­bor). Of­ten, they make du­el­ing claims in the press. Mam­moth, in an­nounc­ing a $195 mil­lion round to fi­nance its own ex­pan­sion in­to ther­a­pies, claimed to have “the largest tool­box of nov­el Cas en­zymes.” Ar­bor on Tues­day said it had “the most ex­ten­sive tool­box of pro­pri­etary ge­nom­ic ed­i­tors in the in­dus­try.”

None of these com­pa­nies are yet near the clin­ic, but larg­er drug­mak­ers are watch­ing close­ly. De­spite a long-run­ning col­lab­o­ra­tion with CRISPR Ther­a­peu­tics, Ver­tex struck deals the past year with both Mam­moth and Ar­bor to find en­zymes that fit the new ther­a­pies they’re de­vel­op­ing. Mod­er­na turned to Metageno­mi for the mR­NA be­he­moth’s first for­ay in­to gene edit­ing, dis­ap­point­ing in­vestors who hoped Mod­er­na would strike a larg­er deal with one of the orig­i­nal CRISPR com­pa­nies.

Smith notes Ar­bor, found­ed in 2016, has been work­ing on new en­zymes longer than its ri­vals. He has spent much of his first year at the com­pa­ny help­ing craft a strat­e­gy to move those en­zymes in­to the clin­ic.

The com­pa­ny will start in the liv­er, he said. It’s eas­i­er to de­liv­er CRISPR there than any part of the body, as In­tel­lia did with lipid nanopar­ti­cles ear­li­er this year. But In­tel­lia on­ly knocked out a sin­gle gene. Smith said Ar­bor will try to use new and more ver­sa­tile en­zymes to do what he called “knock­out-plus”: ei­ther knock­ing out a gene and in­sert­ing a new one, or knock­ing out mul­ti­ple genes.

“It al­lows us to re­al­ly see how we dif­fer­en­ti­ate from some of the sim­ple knock­down ap­proach­es the Cas9 folks are tak­ing,” Smith said. It “demon­strates the util­i­ty and func­tion­al­i­ty of our ed­i­tors.”

In­sert­ing genes has proven one of the biggest hur­dles in CRISPR gene edit­ing, be­cause it re­lies on hu­man cells’ own in­tri­cate and dif­fi­cult-to-ma­nip­u­late DNA re­pair mech­a­nisms. Con­verse­ly, re­searchers fear that mak­ing mul­ti­ple cuts to the genome at once, at least with cur­rent ed­i­tors, can lead to off-tar­get ef­fects and oth­er forms of DNA dam­age.

Then Ar­bor will try to ed­it the cen­tral ner­vous sys­tem. That’s “an area where we feel there’s re­al­ly an op­por­tu­ni­ty to dif­fer­en­ti­ate sig­nif­i­cant­ly and be first in class in that space,” Smith said.

Al­though com­pa­nies, in­clud­ing Ar­bor, are de­vel­op­ing al­ter­na­tive de­liv­ery tech­nolo­gies, putting CRISPR in the cen­tral ner­vous sys­tem re­quires strap­ping it in­to an ade­no-as­so­ci­at­ed virus, the harm­less virus com­mon­ly used across gene ther­a­py.

Most CRISPR sys­tems are too big to fit in­side these virus­es, so small­er ed­i­tors could of­fer a sig­nif­i­cant ad­van­tage.

CRISPR sys­tems can al­so on­ly ed­it parts of the genome that hap­pen to be near a ge­net­ic land­ing strip called a PAM site, lim­it­ing the num­ber of genes and dis­eases you can tar­get. Smith said the com­pa­ny de­vel­oped ed­i­tors that can hit a broad­er range of tar­gets.

The goal is to file for FDA clear­ance for Ar­bor’s first tri­al by the end of 2023. In the mean­time, they’ll con­tin­ue ex­pand­ing, spend­ing the com­pa­ny’s new­found galleons on dou­bling their staff from around 60 em­ploy­ees to around 120.

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.

David Baker working with a student on their protein design (Jason Mast)

Sci­en­tists are fi­nal­ly learn­ing how to de­sign pro­teins from scratch. Drug de­vel­op­ment may nev­er be the same

SEATTLE — It’s a cloudy Thursday afternoon in mid-July and David Baker is reclining into the futon in his corner office at the University of Washington, arms splayed out like a daytime talk show host as he coaches another one of his postdocs through the slings and arrows of scientific celebrity.

“Be jealous of your time,” he says, before plotting ways of sneaking her out of Zooms. “It’s this horrible cost to science that you’re tied up in some stupid meeting.”

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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.

Patty Murray, D-WA (Graeme Sloan/Sipa USA)(Sipa via AP Images)

Sen­ate user fee reau­tho­riza­tion bill omits ac­cel­er­at­ed ap­proval re­forms, shows wide gaps with House ver­sion

The Senate health committee on Tuesday released its first version of the bill to reauthorize all the different FDA user fees. But unlike the House version, there are only a few controversial items in the Senate’s version, which does not address either accelerated approval reforms or clinical trial diversity (as the House did).

While it’s still relatively early in the process of finalizing this legislation (the ultimate statutory deadline is the end of September), the House and Senate, at least initially, appear to be starting off in different corners on what should be included.

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Clay Siegall (Photo by Dimitrios Kambouris/Getty Images for Gabrielle's Angel Foundation)

UP­DAT­ED: Clay Sie­gall re­signs from Seagen amid in­ves­ti­ga­tion in­to do­mes­tic vi­o­lence claims

A week after Seagen revealed that longtime CEO Clay Siegall was on leave due to an allegation of domestic violence, he has resigned.

Since that shocking revelation, more details about the claims have emerged into the public eye. As Endpoints News reported, Siegall was arrested on April 23. A police report about that night and a subsequent temporary restraining order described a pattern of abusive behavior against his wife and a physical altercation that left her with multiple bruises. Siegall denied the claims.

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Warren Buffett, Berkshire Hathaway CEO

Berk­shire Hath­away pulls out of Ab­b­Vie, Bris­tol My­ers Squibb in­vest­ments

It looks like Warren Buffett is sticking to ice cream and railroads for the moment.

The billionaire CEO of Berkshire Hathaway backed out of two major holdings in the pharma industry, Forexlive first reported, including a $410 million investment in AbbVie and a $324.4 million stake in Bristol Myers Squibb.

The move comes after Berkshire abandoned its Teva shares just last quarter, Bloomberg reported.

Long-ex­pect­ed UK lay­offs im­mi­nent for No­var­tis fol­low­ing sale

Nearly a year ago, more than 200 workers at Novartis’ Grimsby, UK, facility were able to hang on to their jobs after the pharma closed a Switzerland site as a part of its workforce restructuring plan. Now, it looks like those employees’ time is up, as the site has been sold, Grimsby Telegraph reported today.

The manufacturing site has been sold to Humber Industrials, a subsidiary of International Process Plants. None of the current staff members will be working with the new owners, however.

FDA lob­bies Con­gress over rare dis­ease court rul­ing with wide im­pli­ca­tions

Usually reserved for making decisions on drug applications or enforcing what Congress stipulates, the FDA is now dipping its toe into the wild world of congressional politics as it attempts to fix a major court decision that could have a chilling effect on rare disease R&D.

The case in question from last October saw a US appeals court overturn a prior FDA court win, saying that the agency never should’ve approved a rare disease drug because a previously approved but more expensive drug with the same active ingredient has orphan drug exclusivity barring such an approval.