Scoop: Google’s GV spear­heads the Spot­light syn­di­cate — back­ing an up­start biotech aimed at ‘de­moc­ra­tiz­ing’ gene edit­ing

CRISPR had no soon­er start­ed to shake the very foun­da­tions of drug de­vel­op­ment be­fore its lim­i­ta­tions be­gan to loom large. Gene edit­ing could change the world — if on­ly you could get around the hur­dles that threat­ened to trip up every pro­gram.

Blake By­ers

So it’s on­ly nat­ur­al to see CRISPR 2.0 tak­ing shape be­fore the pi­o­neers can get the lead ther­a­pies through de­vel­op­ment. And who bet­ter than Google’s GV ven­ture arm to take the lead spot in a small syn­di­cate back­ing some sci­en­tists with their own unique twist on a so­lu­tion?

GV gen­er­al part­ner Blake By­ers took point on this one, join­ing with some in­di­vid­ual in­vestors who are stay­ing in the back­ground. They were all at­tract­ed by the idea that the small team at Spot­light Ther­a­peu­tics could by­pass the de­liv­ery is­sues em­bed­ded in every gene edit­ing pro­gram by us­ing pro­gram­ma­ble CRISPR ri­bonu­cle­o­pro­teins de­signed for in vi­vo cell-tar­get­ed de­liv­ery.

And now the Spot­light team is jump­ing in­to the in­dus­try spot­light with a $30 mil­lion launch round to go af­ter lead pro­grams in he­mo­glo­binopathies and im­muno-on­col­o­gy.

Right now, de­spite all the promise of CRISPR, the pi­o­neers are un­able to ad­dress spe­cif­ic cell types in vi­vo, says CEO Mary Haak-Frend­scho. This new ap­proach of­fers the op­por­tu­ni­ty “to re­al­ly open up, de­moc­ra­tize gene edit­ing.”

Mary Haak-Frend­scho

The tech used to­day de­pends a lot on us­ing an AAV or LNP to ex­press the ed­i­tor in the tar­get cell, says By­ers. Those have bet­ter up­take in liv­er cells, so that’s where the ear­ly play­ers have start­ed. And as we’ve seen at Sol­id and oth­er places, there are lin­ger­ing con­cerns about safe­ty and ef­fi­ca­cy.

Spot­light, he says, is tak­ing a dif­fer­ent, com­plete­ly non-vi­ral ap­proach. And it starts with a ques­tion.

“Why don’t we bind the RNP (ri­bonu­cle­o­pro­tein) ed­i­tor to oth­er things?” asks By­ers. “That could be oth­er pro­teins, let’s say an an­ti­body. Get an­ti­bod­ies to a tar­get on the cell sur­face, it’s in­ter­nal­ized at some rate, then hitch­hikes in­to the cell and from there ed­it the tar­get site in the genome.”

“There’s a lot of things you can latch your gene ed­i­tors to,” says By­ers. The goal is to ex­plore the space, search­ing for 5 to 10 port­fo­lio prod­ucts bound to dif­fer­ent hitch­hik­er mol­e­cules that you can use to get your ed­i­tor of choice in­to the ex­act cell type you want, with high speci­fici­ty and low cost of goods.

Alex Mar­son

In the process, you have to es­cape de­struc­tion by the lyso­some and go on to the nu­cle­o­some to do the edit­ing, so there’s plen­ty of de­bug­ging along the way to get it to work right.

Much of the in­spi­ra­tion for this work came from 3 key sci­en­tists who are ad­vis­ing the start­up.

Alex Mar­son and Patrick Hsu thought a lot of this out. Mar­son is at UC San Fran­cis­co and Hsu is now close by at UC Berke­ley. Ja­cob Corn at ETH Zürich rounds out the line­up of sci­en­tif­ic founders with pres­ti­gious re­sumes.

Patrick Hsu

The longterm plan is to stick with the non-vi­ral ap­proach and build a pipeline.

As A rounds go these days, $30 mil­lion isn’t a lot of mon­ey, par­tic­u­lar­ly when you’re talk­ing about a tech plat­form ap­proach like this. I point­ed that out to By­ers, who wasn’t feel­ing apolo­getic about the $30 mil­lion.

“How old school of us,” he re­spond­ed, adding that there are dif­fer­ent strate­gies for dif­fer­ent play­ers. Some should be laser fo­cused on prod­uct de­vel­op­ment. Be­sides, he adds, “small mounts of cap­i­tal are very fo­cus­ing for a com­pa­ny.”

Ja­cob Corn

The mon­ey “gets us to 2022,” says the CEO. At that point they ex­pect to have their first de­vel­op­ment can­di­date, with­in a year of the clin­ic for ei­ther or both their cho­sen in­di­ca­tions.

And then they can see about start­ing their own gene edit­ing rev­o­lu­tion.

Da­ta Lit­er­a­cy: The Foun­da­tion for Mod­ern Tri­al Ex­e­cu­tion

In 2016, the International Council for Harmonisation (ICH) updated their “Guidelines for Good Clinical Practice.” One key shift was a mandate to implement a risk-based quality management system throughout all stages of a clinical trial, and to take a systematic, prioritized, risk-based approach to clinical trial monitoring—on-site monitoring, remote monitoring, or any combination thereof.

Pfiz­er's big block­buster Xel­janz flunks its post-mar­ket­ing safe­ty study, re­new­ing harsh ques­tions for JAK class

When the FDA approved Pfizer’s JAK inhibitor Xeljanz for rheumatoid arthritis in 2012, they slapped on a black box warning for a laundry list of adverse events and required the New York drugmaker to run a long-term safety study.

That study has since become a consistent headache for Pfizer and their blockbuster molecule. Last year, Pfizer dropped the entire high dose cohort after an independent monitoring board found more patients died in that group than in the low dose arm or a control arm of patients who received one of two TNF inhibitors, Enbrel or Humira.

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Covid-19 roundup: EU and As­traZeneca trade blows over slow­downs; Un­usu­al unions pop up to test an­ti­bod­ies, vac­cines

After coming under fire for manufacturing delays last week, AstraZeneca’s feud with the European Union has spilled into the open.

The bloc accused the pharma giant on Wednesday of pulling out of a meeting to discuss cuts to its vaccine supplies, the AP reported. AstraZeneca denied the reports, saying it still planned on attending the discussion.

Early Wednesday, an EU Commission spokeswoman said that “the representative of AstraZeneca had announced this morning, had informed us this morning that their participation is not confirmed, is not happening.” But an AstraZeneca spokesperson later called the reports “not accurate.”

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Adeno-associated virus-1 illustration; the use of AAVs resurrected the gene therapy field, but companies are now testing the limits of a 20-year-old technology (File photo, Shutterstock)

Af­ter 3 deaths rock the field, gene ther­a­py re­searchers con­tem­plate AAV's fu­ture

Nicole Paulk was scrolling through her phone in bed early one morning in June when an email from a colleague jolted her awake. It was an article: Two patients in an Audentes gene therapy trial had died, grinding the study to a halt.

Paulk, who runs a gene therapy lab at the University of California, San Francisco, had planned to spend the day listening to talks at the American Association for Cancer Research annual meeting, which was taking place that week. Instead, she skipped the conference, canceled every work call on her calendar and began phoning colleagues across academia and industry, trying to figure out what happened and why. All the while, a single name hung in the back of her head.

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Pascal Soriot, AP

As­traZeneca CEO Pas­cal So­ri­ot sev­ers an un­usu­al board con­nec­tion, steer­ing clear of con­flicts while re­tain­ing im­por­tant al­liances

CSL Behring chief Paul Perreault scored an unusual coup last summer when he added AstraZeneca CEO Pascal Soriot to the board, via Zoom. It’s rare, to say the least, to see a Big Pharma CEO take any board post in an industry where interests can simultaneously connect and collide on multiple levels of operations.

The tie set the stage for an important manufacturing connection. The Australian pharma giant agreed to supply the country with 10s of millions of AstraZeneca’s Covid-19 vaccine, once it passes regulatory muster.

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Yanay Ofran (L) and Anat Binur (Ukko)

Leaps by Bay­er backs a pro­tein en­gi­neer­ing start­up tak­ing on Aim­mune — and Nestlé — in peanut al­ler­gy

Little capsules of peanut powder drove Nestlé’s $2.6 billion buyout of Aimmune. Now, with $40 million in new funding, a fledgling biotech is promising to bring a more sophisticated version of that protein therapy that can go much, much further.

Ukko’s goal is two-pronged — with the initial products spanning therapeutic and food — but it’s grounded in the same protein engineering platform, co-founder and CEO Anat Binur told Endpoints News.

As tar­get­ed ther­a­pies get ever more pre­cise, Deer­field un­veils $50M bet on an Har­vard pro­fes­sor's chem­istry in­sights

Behind the seemingly simple concept of targeted cancer therapies is the drug developer’s headache that the target is always changing. Each generation of kinase inhibitors may be ostensibly hitting the same oncogene, but in addition to blocking the wildtype oncogene, they must now also address the mutations that have developed along the way, spurring resistance to current drugs.

The more those target kinases evolve, too, the more they could resemble off-target kinases you don’t want to bind. So each iteration requires more selectivity — sometimes down to differences of a few atoms.

Vincent Sandanayaka (file photo)

UP­DAT­ED: Ex-MD An­der­son chief De­Pin­ho is help­ing launch an­oth­er biotech — and he's stick­ing with fa­mil­iar ground

Years after co-founding SINE-focused Karyopharm and stirring up controversy at MD Anderson, Ronald DePinho is helping uncloak a new biotech targeting solute carrier transporter proteins — and Karyopharm’s former head of chemistry is leading the charge.

Nirogy Therapeutics emerged from stealth mode on Tuesday with a $16.5 million Series A round and plans to hit the clinic by 2022. The financing should be enough to carry the startup’s lead program, a small molecule lactate transport inhibitor, through Phase I, CEO Vincent Sandanayaka said.

Mer­ck scraps Covid-19 vac­cine pro­grams af­ter they fail to mea­sure up on ef­fi­ca­cy in an­oth­er ma­jor set­back in the glob­al fight

After turning up late to the vaccine development game in the global fight against Covid-19, Merck is now making a quick exit.

The pharma giant is reporting this morning that it’s decided to drop development of 2 vaccines — V590 and V591 — after taking a look at Phase I data that simply don’t measure up to either the natural immune response seen in people exposed to the virus or the vaccines already on or near the market.

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