David Liu (Rose Lincoln/Harvard Staff Photographer)

Out of CRISPR pi­o­neer David Li­u's lab comes a small mol­e­cule play tar­get­ing ex­osites — and it's raised a mod­est $25M to push to­ward clin­ic

David Liu may be best known as a CRISPR trail­blaz­er be­hind Ed­i­tas Med­i­cine, Beam Ther­a­peu­tics and Prime Med­i­cine. But more than six years ago, he worked with a stu­dent from his Har­vard lab and then-col­league Alan Saghatelian on a much dif­fer­ent project: de­vel­op­ing a small mol­e­cule in­hibitor of in­sulin-de­grad­ing en­zymes.

Alan Saghatelian

For close to six decades, sci­en­tists had the­o­rized that block­ing the en­zyme can sal­vage enough in­sulin to treat Type 2 di­a­betes. The prob­lem is that IDE, de­spite its name, doesn’t just de­grade in­sulin; it al­so gets rid of glucagon, which is some­thing you ac­tu­al­ly don’t want a lot of for a di­a­bet­ic pa­tient. Tra­di­tion­al drug dis­cov­ery meth­ods couldn’t solve the need to shut down one ac­tiv­i­ty while leav­ing the oth­er alone.

The so­lu­tion Liu and Saghatelian’s team found was on the en­zyme it­self.

Rather than drug­ging the ac­tive site, they re­al­ized that they could hit the ex­osite — a far away site where in­sulin ac­tu­al­ly comes to dock — and achieve the se­lec­tive in­hi­bi­tion.

Juan Pablo Ma­ianti

The stu­dent, Juan Pablo Ma­ianti, stayed with Liu at the Broad for a post­doc to de­vel­op the idea be­fore co-found­ing and be­com­ing em­ploy­ee No. 1 at Exo Ther­a­peu­tics. A seed round and two years lat­er, the Cam­bridge, MA-based biotech is push­ing ahead on four pre­clin­i­cal pro­grams with $25 mil­lion in Se­ries A cash from New­path Part­ners, No­var­tis Ven­ture Fund, CRV and 6 Di­men­sions Cap­i­tal.

What the 2014 pa­per es­tab­lished is now just one of four pil­lars at Exo, said CEO Michael Bruce, name­ly the abil­i­ty to dis­cov­er an ex­osite on an en­zyme. Un­like al­losteric sites — the bind­ing of which can in­di­rect­ly im­pact the ac­tive site — ex­osites are typ­i­cal­ly in­volved in some func­tion of the pro­tein, open­ing up a more spe­cif­ic way to deal with pleiotrop­ic en­zymes.

Michael Bruce

“I read some­where that 672 en­zymes make up the en­tire drug in­dus­try, the mul­ti-tril­lion dol­lar drug in­dus­try,” Bruce, who came on board in Feb­ru­ary, told End­points News, “but there are some­thing like 10,000 en­zymes that are thought to have a role in hu­man dis­ease.”

Ma­ianti and the eight oth­er staffers who joined him al­so built a plat­form that can make the en­zymes or en­zyme com­plex­es for them to ex­per­i­ment with; brought in DNA-en­cod­ed li­braries to start a screen­ing ef­fort; and nailed down the ini­tial tar­gets in on­col­o­gy and in­flam­ma­tion.

Down the road, though, Bruce sees the com­pa­ny ap­ply­ing its tech to neu­ro­science, car­dio­vas­cu­lar and meta­bol­ic, plus a range of dis­eases.

They will all be draw­ing from a whole new in­fra­struc­ture that Exo has con­struct­ed from scratch — one that, while rem­i­nis­cent of what he’s ex­pe­ri­enced dur­ing his years at Pfiz­er, doesn’t feel any less cut­ting-edge than the CRISPR and mi­cro­bio­me tech he’s seen over sev­er­al stints at biotech star­tups.

“To me there’s this con­flu­ence of tech­nolo­gies start­ing with cryo-EM go­ing to mol­e­c­u­lar mod­el­ing go­ing to DNA-en­cod­ed li­braries go­ing to pro­tein syn­the­sis — all of these things I think now al­low us to re­al­ly ex­plore some of these en­zymes and en­zyme com­plex­es in new ways,” he said.

Bruce ex­pects to steer Exo’s first drugs in­to the clin­ic in the next cou­ple of years, at which point he al­so en­vi­sions ex­osite con­fer­ences start­ing to be a thing as the sci­ence de­vel­ops.

At least a trio of re­spect­ed sci­en­tists are sim­i­lar­ly con­vinced it would. Stu­art Schreiber of the Broad, Ben Cra­vatt at Scripps and Ben Ebert of Dana-Far­ber have all joined Liu and Saghatelian (who’s now at Salk) on the sci­en­tif­ic ad­vi­so­ry board as Exo plans to dou­ble its size.

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.

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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Bahija Jallal, Immunocore

Buried in Im­muno­core's IPO fil­ings? A kick­back scheme from a now for­mer em­ploy­ee

Immunocore spent much of 2019 dealing with the fallout of the Neil Woodford scandal, as the former star investor’s fall crashed the biotech’s valuation out of unicorn range. Now it turns out that the company spent 2020 dealing with another internal scandal.

The longtime UK biotech darling disclosed in their IPO filing last week that they had fallen victim to an alleged kickback scheme involving one of their employees. After a whistleblower came forward, they said in their F-1, they spent the summer and spring investigating, finding fraud on the part of an employee and two outside vendors.

Can strug­gling Iterum turn the cor­ner to an an­tibi­ot­ic suc­cess sto­ry? They will know in six months

More than five years after Corey Fishman and Michael Dunne dusted sulopenem off Pfizer’s shelves — the second castoff antibiotic they’ve brought out of the pharma giant — and founded Iterum Therapeutics around that single drug, they have lined up a quick shot at approval with priority review from the FDA.

The decision, six months from now, will mark a make-or-break moment for a struggling biotech that has just enough cash to keep the lights on until the third quarter.

IPO track­er: 2021 gets start­ed with a flur­ry of new of­fer­ings

A global pandemic couldn’t slow down what turned out to be a record year for biotech IPOs. With the calendar turning toward 2021, the Endpoints News team is prepped to track each new filing this year, and the outcome. We’re off to another hot start at least.

Below, you’ll find the companies that have filed to go public, in addition to those that have already priced. Through the first two business weeks of January, there have already been 9 biotechs that have filed or priced, and the number is only expected to grow. We’ll keep the tracker updated as it does.

Matt Gline (L) and Vivek Ramaswamy

Scoop: Vivek Ra­maswamy is hand­ing the CEO job to a top lieu­tenant at Roivant — but he’s not ex­act­ly leav­ing the biotech scene

Over the past 7 years since founding Roivant, Vivek Ramaswamy has been a constant blur of biotech building motion.

He launched his first biotech with an Alzheimer’s drug he picked up cheap, and watched the experiment implode in one of the highest profile pivotal disasters seen in the last decade. But it didn’t slow the 30-something exec down; if anything, he hit the accelerator. Ramaswamy blazed global paths and went on to raise billions to spur the creation of a large lineup of little Vants promising big things at a fast pace. He sold off a section of the Vant brigade to Sumitomo Dainippon for $3 billion. And more recently the relentless dealmaker has been building a computational discovery arm to add an AI-driven approach to kicking up new programs and companies, supplementing the in-licensing drive while pursuing advances that have created more than 700 jobs at Roivant, with $2 billion in reserves.

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Ron Cooper, Albireo CEO

Al­bireo just ad­vanced down to the 10-yard line at the FDA. And Ron Coop­er’s team is get­ting prepped for the next big play

When Albireo Pharma’s board $ALBO moved to bring in Ron Cooper as the CEO more than 5 years ago, the development-stage company went with an experienced commercial player who had a big-time position on his resume after running Bristol Myers’ commercial ops in Europe.

Now, after successfully navigating a pivotal study, putting them in a foot race with a rival toward an FDA OK, Cooper is getting a boost from regulators on the last drive back to an arena he understands completely.

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David Southwell (L) and Christoph Westphal

Har­vard spin­out kicks off 2021 with a crossover round and sights set on the clin­ic

Several months after striking an alliance with Novartis, TCR therapy-focused TScan Therapeutics has reeled in a crossover round that should hold it over for the next two years as it eyes a public debut.

The Christoph Westphal portfolio company had been arranging the crossover for the last few months, CEO David Southwell said. Just before Christmas, they nailed down what he called a “really blue-chip” syndicate of four new investors, including BlackRock, RA Capital Management and two undisclosed funds. They closed on the $100 million Series C just over a week ago, and waited until Monday morning to announce it.

Stéphane Bancel, Moderna CEO (Steven Ferdman/Getty Images)

Covid-19 roundup: Mod­er­na dou­bles down on Covid-19 with new boost­er tri­als; Aus­tralia plans do­mes­tic pro­duc­tion of As­traZeneca vac­cine amid dis­tri­b­u­tion lag

As Merck bows out of the global race to develop vaccines for Covid-19, Moderna is doubling down to make sure they can quell new variants that have recently emerged and quickly spread.

The Cambridge, MA-based biotech put out word on Monday that in vivo studies indicate their mRNA vaccine works well enough against two strains first detected in the UK and South Africa. But with a six-fold reduction in neutralizing titers observed against the latter strain, the company is launching a new study of a booster version to make sure it can do the job.

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