Matthew Porteus (Credit: Timothy Archibald for Stanford Children's)

Ver­sant teams up with Stan­ford gene edit­ing ex­perts on a $45M next-gen play — mar­ry­ing CRISPR and AAV to fix sick­le cell

When a re­searchers talk about gene edit­ing, they’re usu­al­ly think­ing about sev­er­al steps. First you need to ze­ro in on the de­fec­tive gene; then, de­pend­ing on the need, you’d want to knock out, re­place or in­sert ge­net­ic ma­te­r­i­al.

CRISPR/Cas9 tech­nolo­gies have trans­formed the field by mak­ing a break­through for the first prob­lem. In­duc­ing dou­ble-strand­ed DNA breaks, or achiev­ing sin­gle-let­ter changes as base edit­ing al­lows, have promis­ing ap­pli­ca­tions in mul­ti­ple dis­eases that are start­ing to get test­ed in hu­mans.

Jer­el Davis

But Ver­sant Ven­tures, one of the pi­o­neer­ing in­vestors in the space, still sees a gap. And they’re team­ing up with a group of promi­nent Stan­ford re­searchers — plus a sea­soned biotech ex­ec — to fill it.

“Achiev­ing high-ef­fi­cien­cy tar­get­ed gene in­te­gra­tion has been a crit­i­cal ob­jec­tive of gene edit­ing for more than 15 years, but on­ly now is this tech­no­log­i­cal­ly pos­si­ble,” Jer­el Davis, Ver­sant’s Van­cou­ver-based man­ag­ing di­rec­tor, said.

Graphite Bio has $45 mil­lion to start things off, but the mon­ey mat­ters lit­tle when com­pared to the rich brain bank it’s draw­ing from.

Matthew Por­teus, an aca­d­e­m­ic founder of CRISPR Ther­a­peu­tics, is lend­ing the tech plat­form to cre­ate this next-gen play along­side gene ther­a­py ex­pert Maria Grazia Ron­car­o­lo.

Draw­ing from re­search work led by Dan­ny De­v­er while a post­doc at Por­teus’ lab, Graphite’s big promise is to in­crease in­te­gra­tion ef­fi­cien­cy from less than 1% to greater than 50% “across di­verse ge­net­ic le­sions in a wide range of cell types.”

Daniel De­v­er

Specif­i­cal­ly, De­v­er and Por­teus showed that they could cor­rect the sick­le β glo­bin gene in pa­tient-de­rived hematopoi­et­ic stem cells ex vi­vo by com­bin­ing Cas9 ri­bonu­cle­o­pro­teins with a donor mol­e­cule that serves as a tem­plate, de­liv­ered in re­com­bi­nant ade­no-as­so­ci­at­ed vi­ral vec­tors of serotype 6 (rAAV6).

That could make for a much more scal­able re­place­ment for trans­plants, they wrote in a 2017 pa­per de­scrib­ing mouse stud­ies.

“No­tably, we de­vise an en­rich­ment par­a­digm to pu­ri­fy a pop­u­la­tion of HSPCs with >90% tar­get­ed in­te­gra­tion,” they wrote. “We al­so show ef­fi­cient cor­rec­tion of the SCD-caus­ing E6V mu­ta­tion in pa­tient-de­rived HSPCs that af­ter dif­fer­en­ti­a­tion in­to ery­thro­cytes, ex­press adult β-glo­bin (HbA) mR­NA, con­firm­ing in­tact tran­scrip­tion­al reg­u­la­tion of edit­ed HBB al­le­les.”

Josh Lehrer

Chief ex­ec­u­tive Josh Lehrer is lead­ing the charge to start Phase I for this pro­gram in ear­ly 2021, bring­ing all the sick­le cell knowl­edge and ex­pe­ri­ence from a six-year run as Glob­al Blood Ther­a­peu­tics, most re­cent­ly as CMO. More pre­clin­i­cal ther­a­pies are in the works for un­named se­ri­ous dis­eases. Sam­sara Bio­Cap­i­tal is join­ing Ver­sant for the launch round and send­ing Abe Bas­san to the board, which al­so fea­tures Davis and Car­lo Riz­zu­to from Ver­sant.

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.

President Donald Trump (via AP Images)

Signs of an 'Oc­to­ber Vac­cine Sur­prise' alarm ca­reer sci­en­tists

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.

#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.

Is­raeli biotech rais­es $57M to go where cur­rent BRAF in­hibitors can't, with back­ing from No­var­tis, SR One

For the blockbuster potential of Novartis’ Tafinlar and Pfizer’s Braftovi, all the BRAF inhibitors on the market so far only target V600 mutations — which accounts for roughly 50% of patients.

Israeli biotech Novellus now has $57 million to develop a drug that they say can help the other 50% who have everything else.

The Series C will fund a Phase II trial for PLX-8394, a “paradox breaker” that could block RAF without activating MAPK signaling. In a Phase I trial, a patient with a BRAF fusion saw their tumor go away after taking the drug, allowing Novellus to hit the ground running.

Jonathan Rigby, Immune Regulation group CEO

Im­mune Reg­u­la­tion, tak­ing two clin­i­cal pro­grams to 're­set' the im­mune sys­tem, nets $53M+ Se­ries B

A little under two years after a company rebranding, Immune Regulation is taking an even bigger step toward advancing its goals.

Formerly known as Peptinnovate, the British biotech announced a $53.4 million Series B early Monday morning, helping to further advance two clinical programs in rheumatoid arthritis and asthma. Though those are the two initial indications the company is focusing on, CEO Jonathan Rigby told Endpoints News he hopes the candidates can be applied to a broad swath of autoimmune disorders.

Frank Zhang (AP Images)

Rocked by cus­toms in­ves­ti­ga­tion, Leg­end's CFO takes over as CEO Frank Zhang placed un­der house ar­rest

When Frank Zhang stepped down from GenScript — the contract research group he’s run for 18 years — to take up the CEO post at its CAR-T focused spinout Legend Biotech, he assured analysts that he was in for the long haul.

Just 49 days later, though, he’s been forced to hand back the title.

In a dramatic turn of events, Legend disclosed that Zhang is under house arrest in China as part of a customs investigation involving GenScript. While he remains the chairman, CFO Ying Huang has been tapped to double as interim CEO.

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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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Anthony Fauci (AP Images)

A press of­fi­cer at An­tho­ny Fau­ci’s NI­AID was un­masked as a hard-right Covid troll. He just re­tired to­day

William B Crews had been a public affairs specialist at the NIH’s National Institute of Allergy and Infectious Diseases.

That ended today when he informed the agency of his decision to retire, after he was identified as the managing editor at RedState, a prominent Trump loyalist website.

Crews’ RedState duties are performed under the alias streiff. While enjoying the benefits of pseudonymity, he disparaged and worked against NIAID with an incendiary level of rhetoric in the midst of a pandemic.