Trevor Martin (Mammoth)

Eye­ing in-vi­vo edit­ing, Mam­moth li­cens­es Jen­nifer Doud­na’s new CRISPR en­zyme

Last month, Jen­nifer Doud­na re­vealed in Sci­ence a new, “hy­per-com­pact” CRISPR en­zyme that was half the size of tra­di­tion­al CRISPR en­zymes and could, she sus­pect­ed, of­fer a new, more ver­sa­tile tool for gene edit­ing.

Now, the Uni­ver­si­ty of Cal­i­for­nia-Berke­ley has li­censed that en­zyme, known as Casφ, ex­clu­sive­ly to a biotech start­up she and two for­mer stu­dents set up three years ago: Mam­moth Bio­sciences. It’s the sec­ond new CRISPR pro­tein Mam­moth has li­censed from Doud­na’s lab, af­ter they li­censed Cas14 in 2019.

“Cas9 is like a stan­dard sized sys­tem, Casφ is like a mi­cro-sized sized sys­tem, you could say,” CEO and co-founder Trevor Mar­tin told End­points News. “It has huge ad­van­tages in terms of de­liv­ery. There’s ini­tial kind of ev­i­dence in the pa­per that’s su­per-ex­cit­ing around flex­i­bil­i­ty and tar­get­ing.”

Mam­moth has been pri­mar­i­ly known as a di­ag­nos­tic com­pa­ny, most no­tably de­vel­op­ing a CRISPR di­ag­nos­tic for Covid-19 that has been au­tho­rized by the FDA and which Mam­moth and GSK are try­ing to turn in­to a rapid, point-of-care test. But the com­pa­ny, Mar­tin notes, has spent much of the last three years on ba­sic bi­ol­o­gy, de­vel­op­ing new CRISPR sys­tems that can of­fer ad­van­tages not on­ly for test­ing but al­so for ther­a­peu­tics and gene edit­ing.

In that ef­fort, they’re joined by aca­d­e­m­ic labs at Berke­ley and MIT and biotechs such as Ar­bor, which de­vel­oped a new en­zyme called Cas13d and has a “search en­gine” plat­form to find oth­er pro­teins.  Doud­na and for­mer stu­dent and In­no­v­a­tive Ge­nomics In­sti­tute en­tre­pre­neur­ial fel­low Ben­jamin Oakes are al­so launch­ing Scribe Ther­a­peu­tics around a new en­zyme they call CasX.

Casφ’s small stature, Mar­tin said, could make it a good fit for de­liv­er­ing in-vi­vo. One of the more dif­fi­cult ap­pli­ca­tions for CRISPR, sci­en­tists on­ly just did for the first time in a pa­tient this year. Casφ’s size should make that eas­i­er, by let­ting you fit a sys­tem in­to the AAV vec­tors com­mon­ly used for gene ther­a­py. It could al­so be used for what Mar­tin calls “CRISPR-plus” — tech­nolo­gies like base-edit­ing or oth­er ap­pli­ca­tions that might re­quire com­bin­ing mul­ti­ple CRISPR sys­tems in­to a sin­gle fu­sion.

For those, he said, you want com­po­nents “as small as pos­si­ble, so you have room to fit all this oth­er ma­chin­ery.”

Mar­tin not­ed in par­tic­u­lar that Casφ doesn’t re­quire some of the ex­tra RNA oth­er CRISPR sys­tems do to hit their tar­gets; it can func­tion as its own hom­ing mech­a­nism.

“Many of these prop­er­ties are go­ing to be tru­ly crit­i­cal for re­al­iz­ing the po­ten­tial of CRISPR,” he said.

Cor­rec­tion: An ear­li­er ver­sion in­cor­rect­ly at­trib­uted the in­ven­tion of CasX. It came out of Doud­na’s lab.

Secretary of health and human services Alex Azar speaking in the Rose Garden at the White House (Photo: AFP)

Trump’s HHS claims ab­solute au­thor­i­ty over the FDA, clear­ing path to a vac­cine EUA

The top career staff at the FDA has vowed not to let politics overrule science when looking at vaccine data this fall. But Alex Azar, who happens to be their boss’s boss, apparently won’t even give them a chance to stand in the way.

In a new memorandum issued Tuesday last week, the HHS chief stripped the FDA and other health agencies under his purview of their rule making ability, asserting all such power “is reserved to the Secretary.” Sheila Kaplan of the New York Times first obtained and reported the details of the September 15 bulletin.

Samit Hirawat (Bristol Myers Squibb)

Af­ter bruis­ing re­jec­tion, blue­bird and Bris­tol My­ers Squibb land ide-cel pri­or­i­ty re­view. But will it mat­ter for the CVR?

With the clock all but up, the FDA accepted and handed priority review to Bristol Myers Squibb and bluebird bio’s BCMA CAR-T, keeping a narrow window open for Celgene investors to still cash in on the $9 CVR from the $63 billion Celgene merger.

The acceptance comes five months after the two companies weres slammed with a surprise refuse-to-file that threatened to foreclose the CVR entirely. Today’s acceptance sets the FDA decision date for March 27, 2021 – or precisely 4 days before the CVR deadline of March 31. Given the breakthrough designation and strong pivotal data — 81.5% response rate, 35.2% complete response rate — priority review was largely expected.

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Anthony Coyle (Repertoire)

Flag­ship's merged biotech Reper­toire nets ex-Pfiz­er CSO An­tho­ny Coyle as R&D chief

Flagship is building a big-name C-suite at its new, $220 million merged biotech.

Repertoire Immune Medicines, which already boasts former Bioverativ chief John Cox as its CEO, announced yesterday that Anthony Coyle, the former Pfizer CSO and the founding CEO of Pandion, will join as their head of R&D.

“As we progress clinical trials for our multi-clonal T cell candidates in immuno-oncology, Tony’s deep expertise in cellular immunology and novel therapeutic development will help us achieve our vision of creating a new class of transformative medicines for patients,” Cox said in a statement.

#ES­MO20: Push­ing in­to front­line, Mer­ck and Bris­tol My­ers duke it out with new slate of GI can­cer da­ta

Having worked in parallel for years to move their respective PD-1 inhibitors up to the first-line treatment of gastrointestinal cancers, Merck and Bristol Myers Squibb finally have the data at ESMO for a showdown.

Comparing KEYNOTE-590 and CheckMate-649, of course, comes with the usual caveats. But a side-by-side look at the overall survival numbers also offer some perspective on a new frontier for the reigning checkpoint rivals, both of whom are claiming to have achieved a first.

UP­DAT­ED: Two wild weeks for Grail end in $8B Il­lu­mi­na buy­out

Grail’s whirlwind two weeks have ended in the wealthy arms of its former founder and benefactors.

Illumina has shelled out $8 billion to reacquire the closely-watched liquid biopsy startup they spun out just 5 years ago and sold off much of its shares just 3 years ago. The deal comes nearly two weeks after the well-heeled startup filed for a potentially massive IPO — one that was disrupted just a week later when Bloomberg reported that Illumina was in talks to buy their former spinout for up to $8 billion.

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Roche vaults to the front of the NL­RP3 clin­i­cal race, pay­ing $448M up­front to bag In­fla­zome

Roche is going all in on NLRP3.

The pharma giant is putting down $448 million (€380 million) upfront to snatch Novartis-backed Inflazome, which makes it a clinical player in the space overnight.

Dublin and Cambridge, UK-based Inflazome is the second NLRP3-focused biotech Roche has acquired in less than two years, and although no numbers were disclosed in the Jecure buyout, this is almost certainly a much larger deal.

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President Donald Trump (via AP Images)

Signs of an 'Oc­to­ber Vac­cine Sur­prise' alarm ca­reer sci­en­tists. HHS con­tin­ues to claim Azar “will de­fer com­plete­ly to the FDA"

President Donald Trump, who seems intent on announcing a Covid-19 vaccine before Election Day, could legally authorize a vaccine over the objections of experts, officials at the FDA and even vaccine manufacturers, who have pledged not to release any vaccine unless it’s proved safe and effective.

In podcasts, public forums, social media and medical journals, a growing number of prominent health leaders say they fear that Trump — who has repeatedly signaled his desire for the swift approval of a vaccine and his displeasure with perceived delays at the FDA — will take matters into his own hands, running roughshod over the usual regulatory process.

Can a mag­net­ic cell ther­a­py re­place corneal trans­plan­ta­tion? As eight-year jour­ney leads to the clin­ic, two broth­ers un­veil bold vi­sion

Jeff Goldberg was getting acquainted with a brand new way to do corneal transplants when an even newer, even bolder idea hit him.

It was almost 10 years ago, and Goldberg was in his first faculty position at Bascom Palmer Eye Institute at the University of Miami. Scientists had developed a new way to do cornea transplants where instead of sewing a whole donor cornea — a decades-old practice — they were just engrafting the inner layer of cells.

News brief­ing: Tiny Vac­cinex's drug flops in PhII Hunt­ing­ton's tri­al, stock craters; Siol­ta nabs $30M Se­ries B to de­vel­op mi­cro­bio­me drug

Siolta Therapeutics, a microbiome company targeting allergic diseases, raked in a $30 million Series B to develop its lead candidate, STMC-103H. The drug, which has been FDA fast-tracked, is headed for proof-of-concept trials, according to the company. Its various indications include allergic asthma, food allergies, atopic dermatitis, allergic rhinitis, and allergy prevention.

The news comes just after the California-based biotech added a prominent biopharma veteran as an advisor: 20-year Gilead CEO John Martin. The biotech also gained Richard Shames as CMO, who came by way of Protagonist Therapeutics.