Feng Zhang, heavy­weight col­lab­o­ra­tors un­veil lat­est CRISPR up­start — a di­ag­nos­tic com­pa­ny

Im­age: David Walt, Todd Gol­ub, Rahul Dhan­da, Feng Zhang, Deb­o­rah Hung. SHER­LOCK


One of the more dra­mat­ic dy­nam­ics in the aca­d­e­m­ic CRISPR world in­volves the Broad In­sti­tute and the Uni­ver­si­ty of Cal­i­for­nia, where Feng Zhang and Jen­nifer Doud­na, two pi­o­neers of the field, have their labs re­spec­tive­ly. As the dust starts to set­tle on their patent dis­pute re­gard­ing ther­a­peu­tic us­es of the gene edit­ing tech, a new storm is brew­ing in the di­ag­nos­tic ap­pli­ca­tions of CRISPR.

Zhang and eight oth­er lead­ing ex­perts in CRISPR, syn­thet­ic bi­ol­o­gy, di­ag­nos­tics and in­fec­tious dis­eases have pulled back the cur­tain on Sher­lock Bio­sciences, a start­up aimed at pro­vid­ing “bet­ter, faster and more af­ford­able” ways to de­tect ge­net­ic sig­na­tures of dis­ease.

The com­pa­ny stands on two foun­da­tion­al tech­nolo­gies: SHER­LOCK, or Spe­cif­ic High-sen­si­tiv­i­ty En­zy­mat­ic Re­porter un­LOCK­ing, was de­vel­oped by Zhang and col­lab­o­ra­tors in­clud­ing co-founders Jonathan Gooten­berg and Omar Abu­dayyeh. Pair­ing CRISPR with the Cas13 en­zyme, the tech­nol­o­gy uti­lizes a guide RNA to find a ge­net­ic se­quence, where Cas13 not on­ly cuts the tar­get but be­gin shriv­el­ing oth­er RNA near­by, cre­at­ing a sig­nal that can then be pre­sent­ed in ob­serv­able forms — such as a line on a pa­per strip.

“Any one tech­nol­o­gy out there had some re­al­ly valu­able at­trib­ut­es in mol­e­c­u­lar di­ag­nos­tics but SHER­LOCK brought all of those to­geth­er,” Rahul Dhan­da, a co-founder and di­ag­nos­tics vet­er­an who took on the CEO role, told me. “It had speed, so you didn’t have to wait days for an in­fec­tious dis­ease re­sult; it had af­ford­abil­i­ty, which meant that you can do on­col­o­gy test­ing in a way that let every­body par­tic­i­pate in those re­sults; and it had sim­plic­i­ty, which means that you can reach peo­ple to do test­ing that couldn’t do it be­fore in de­cen­tral­ized set­tings.”

First in­vent­ed in 2017, an en­hanced ver­sion of SHER­LOCK was de­scribed in a pa­per pub­lished last Feb­ru­ary along­side an­oth­er ex­plain­ing DE­TEC­TR, a sim­i­lar tool that de­ploys Cas12 and a flu­o­res­cent mol­e­cule for de­tec­tion.

Doud­na of UC Berke­ley, who led the work on DE­TEC­TR, de­buted Mam­moth Bio­sciences short­ly there­after with a group of grad stu­dents, some of them from her lab. When we last heard from them, Mam­moth was work­ing with a $23 mil­lion round and back­ing from May­field, NFX, 8VC as well as Ap­ple’s Tim Cook and Grail found­ing CEO Jeff Hu­ber.


Im­age: Omar Abu­dayyeh, Jonathan Gooten­berg, Rahul Dhan­da, James Collins, Par­dis Sa­beti. SHER­LOCK

While com­par­isons with Mam­moth might be in­evitable, Dhan­da says he’s “very con­fi­dent” on the patent side and has faith in Sher­lock’s mul­ti-plat­form ap­proach to en­gi­neer­ing bi­ol­o­gy.

“Now I’ve been in the in­dus­try 20 years, I know how to nav­i­gate this field; it’s a nu­anced enough field that ex­pe­ri­ence mat­ters,” he added. “I would say that when I think about who we should be fo­cused on as com­pe­ti­tion, those are the large play­ers, the es­tab­lished mul­ti-bil­lion dol­lar di­ag­nos­tic com­pa­nies out there, and those are the com­pa­nies that we in­tend to build strong part­ner­ships with if we can find the right com­ple­ment to our goals and theirs.”

Sher­lock now has $35 mil­lion in the bank — half of it in the form of a grant from the Open Phil­an­thropy Pro­ject, which al­so pro­vid­ed an ad­di­tion­al in­vest­ment. As it ex­plores ap­pli­ca­tions in in­fec­tious dis­eases, pre­ci­sion on­col­o­gy and food in­spec­tion, it is on the look­out for “se­lec­tive part­ner­ing” while ad­vanc­ing de­vel­op­ment pro­grams and de­sign­ing new as­says on its own, the com­pa­ny said. So far, that has in­volved every­thing from phar­ma­ceu­ti­cal com­pa­nies look­ing for com­pan­ion di­ag­nos­tics to an­timi­cro­bial de­vel­op­ers seek­ing help with clin­i­cal tri­als to con­sumer health play­ers in search of at-home test­ing. Agri­cul­ture and bio­process test­ing are among the pos­si­bil­i­ties, too.

Dhan­da is still rais­ing cash for Sher­lock’s Se­ries A, which will al­so help fund the sec­ond plat­form in Sher­lock’s ar­se­nal: IN­SPEC­TR (IN­ter­nal Splint-Pair­ing Ex­pres­sion Cas­sette Trans­la­tion Re­ac­tion). James Collins at the Wyss In­sti­tute was cred­it­ed for the tech, which com­pris­es two halves of a cod­ing re­gion that fuse to cre­ate a sig­nalling pro­tein when the tar­get is present, ba­si­cal­ly repli­cat­ing how a cell would gen­er­ate a pro­tein.

In the com­ing year, Dhan­da is al­so plan­ning to hire 6 to 10 peo­ple to ramp up the R&D work cur­rent­ly han­dled by 10 staffers.

Oth­er co-founders in­clude Todd Gol­ub, Deb­o­rah Hung, Par­dis Sa­beti and David Walt — il­lus­tri­ous aca­d­e­mics who make up a team “like none oth­er.”

De­vel­op­ment of the Next Gen­er­a­tion NKG2D CAR T-cell Man­u­fac­tur­ing Process

Celyad’s view on developing and delivering a CAR T-cell therapy with multi-tumor specificity combined with cell manufacturing success
Overview
Transitioning potential therapeutic assets from academia into the commercial environment is an exercise that is largely underappreciated by stakeholders, except for drug developers themselves. The promise of preclinical or early clinical results drives enthusiasm, but the pragmatic delivery of a therapy outside of small, local testing is most often a major challenge for drug developers especially, including among other things, the manufacturing challenges that surround the production of just-in-time and personalized autologous cell therapy products.

Paul Hudson. Sanofi

New Sanofi CEO Hud­son adds next-gen can­cer drug tech to the R&D quest, buy­ing Syn­thorx for $2.5B

When Paul Hudson lays out his R&D vision for Sanofi tomorrow, he will have a new slate of interleukin therapies and a synthetic biology platform to boast about.

The French pharma giant announced early Monday that it is snagging San Diego biotech Synthorx in a $2.5 billion deal. That marks an affordable bolt-on for Sanofi but a considerable return for Synthorx backers, including Avalon, RA Capital and OrbiMed: At $68 per share, the price represents a 172% premium to Friday’s closing.

Synthorx’s take on alternative IL-2 drugs for both cancer and autoimmune disorders — enabled by a synthetic DNA base pair pioneered by Scripps professor Floyd Romesberg — “fits perfectly” with the kind of innovation that he wants at Sanofi, Hudson said.

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Roche faces an­oth­er de­lay in strug­gle to nav­i­gate Spark deal past reg­u­la­tors — but this one is very short

Roche today issued the latest in a long string of delays of its $4.3 billion buyout of Philadelphia-based Spark Therapeutics. The delay comes as little surprise — it is their 10th in as many months — as their most recent delay was scheduled to expire before a key regulatory deadline.

But it is notable for its length: 6 days.

Previous extensions had moved the goalposts by about 3 weeks to a month, with the latest on November 22 expiring tomorrow. The new delay sets a deadline for next Monday, December 16, the same day by which the UK Competition and Markets Authority has to give its initial ruling on the deal. And they already reportedly have lined up an OK from the FTC staff – although that’s only one level of a multi-step process.

KalVis­ta's di­a­bet­ic mac­u­lar ede­ma da­ta falls short — will Mer­ck walk away?

Merck’s 2017 bet on KalVista Pharmaceuticals may have soured, after the UK/US-based biotech’s lead drug failed a mid-stage study in patients with diabetic macular edema (DME).

Two doses of the intravitreal injection, KVD001, were tested against a placebo in a 129-patient trial. Patients who continued to experience significant inflammation and diminished visual acuity, despite anti-VEGF therapy, were recruited to the trial. Typically patients with DME — the most frequent cause of vision loss related to diabetes — are treated with anti-VEGF therapies such as Regeneron’s flagship Eylea or Roche’s Avastin and Lucentis.

Roger Perlmutter, Merck

#ASH19: Here’s why Mer­ck is pay­ing $2.7B to­day to grab Ar­Qule and its next-gen BTK drug, lin­ing up Eli Lil­ly ri­val­ry

Just a few months after making a splash at the European Hematology Association scientific confab with an early snapshot of positive data for their BTK inhibitor ARQ 531, ArQule has won a $2.7 billion buyout deal from Merck.

Merck is scooping up a next-gen BTK drug — which is making a splash at ASH today — from ArQule in an M&A pact set at $20 a share $ARQL. That’s more than twice Friday’s $9.66 close. And Merck R&D chief Roger Perlmutter heralded a deal that nets “multiple clinical-stage oral kinase inhibitors.”

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Ob­sE­va makes case for best-in-class hor­mone sup­pres­sive ther­a­py in pos­i­tive uter­ine fi­broid study

About a month after the Swiss biotech disclosed a failed late-stage study in its IVF program, ObsEva on Monday unveiled positive pivotal data on its experimental treatment for heavy menstrual bleeding triggered by uterine fibroids.

ObsEva in-licensed the drug, linzagolix, from Japan’s Kissei Pharmaceutical in 2015. Two doses of the drug (100 mg and 200 mg) were tested against a placebo in the 535-patient Phase III study, dubbed PRIMROSE 2, in patients who were both on and off hormonal add-back therapy (ABT).

Samit Hirawat. Bristol-Myers Squibb

Bris­tol-My­ers is mak­ing a bee-line to the FDA with pos­i­tive liso-cel da­ta — but is it too late in the CAR-T game?

Bristol-Myers Squibb came to ASH this past weekend with a variety of messages on the new cancer drugs they had acquired in the big Celgene buyout, including liso-cel, the lead CAR-T program picked up in the $9 billion Juno acquisition. And one of the most important was that they had the pivotal efficacy and safety data needed to snag an approval from the FDA next year, with the BLA on track for a filing this month.

J&J team shows off 'break­through' BC­MA CAR-T da­ta, and that could cause a big headache at blue­bird and Bris­tol-My­ers

Just hours after J&J’s oncology team bragged about scoring a breakthrough therapy designation for their BCMA CAR-T drug, they pulled the wraps off of the multiple myeloma data for JNJ-4528 that impressed the FDA. And it’s easy to see why they may well be on a short path to a landmark approval — which may well be making the rival team at bluebird/Bristol-Myers more than a little nervous.

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Jake Van Naarden, Josh Bilenker, Nisha Nanda (Credit: Loxo, Aisling Capital)

Josh Bilenker and his Loxo crew are tak­ing the reins on on­col­o­gy R&D at Eli Lil­ly, culling the weak and map­ping a new path

Josh Bilenker, Jake Van Naarden and Nisha Nanda came out of Eli Lilly’s $8 billion Loxo Oncology buyout with a bundle of cash and plenty of choices on what they could do next. Start a new company, go public. Live on the beach in 5-star luxury. Contemplate the stars — in their own observatory.

So what are they doing?

They formed a new executive team that is taking over the management of Eli Lilly’s hundreds-strong oncology R&D group — essentially using Loxo as a base for a bold new experiment in Big Pharma R&D in an attempt to create a true biotech environment with the deep pockets of a top-15 industry player. They’ve recruited David Hyman from Memorial Sloan Kettering to join the team as chief medical officer. And the mandate includes culling out the oncology pipeline, highlighting their star prospects and going after new programs wherever they can find the best prospects.

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