Alex Mok, Mantra Bio CEO and co-founder

Co­di­ak gets a com­peti­tor, as Mantra Bio leaves stealth and en­ters grow­ing ex­o­some space

Alex Mok had been try­ing to build mi­ni-or­gans in a lab for years, when he start­ed read­ing about re­search in­to a form of cel­lu­lar postal ser­vice called ex­o­somes.

Sci­en­tists were be­gin­ning to see how these minute en­velopes car­ried mes­sages be­tween cells, help­ing them form tis­sue or, when things go wrong, cause dis­ease. Mok start­ed im­mers­ing him­self in­to the field too late to change the com­pa­ny, called Cel­lA­SIC, which he co-found­ed af­ter leav­ing UC Berke­ley. It was still good enough to sell it to Mer­ck KgAA, but he be­gan won­der­ing about the pos­si­bil­i­ties.

“Right un­der our noses there was this mas­sive com­mu­ni­ca­tion chan­nel that we had just not been study­ing,” Mok told End­points News. “If we had known that and start­ed work­ing and study­ing that, maybe we would’ve had bet­ter organoids, we would’ve been able to solve a lot of tech­ni­cal chal­lenges.”

So Mok launched a new com­pa­ny: Mantra Bio. Found­ed in 2016, it is now emerg­ing from stealth mode with $25 mil­lion in Se­ries A fund­ing led by 8VC and Viking Glob­al In­vestors. Mantra joins a se­ries of oth­er com­pa­nies — most promi­nent­ly Co­di­ak Bio­sciences — who are try­ing to un­der­stand this nat­ur­al mes­sag­ing sys­tem and copy it to build stealthy couri­ers that can slide drugs in­to hard-to-reach places and shut­tle gene ther­a­pies past the body’s nat­ur­al de­fens­es.

“I know the term ‘plat­form of biotech’ gets used a lot,” 8VC in­vestor and Mantra board mem­ber Fran­cis­co Gimenez told End­points. “But it is tru­ly a plat­form by which we could con­ceive of de­liv­ery of all sorts of ther­a­peu­tic agents.”

Still, Gimenez ac­knowl­edges, there are a lot of chal­lenges left to solve. Ex­o­somes, al­so known as ex­tra­cel­lu­lar vesi­cles, are tiny lipid sacs, around a thou­sandth the size of a cell, that con­tain mi­cro-strands of RNA or oth­er bi­o­log­i­cal car­go and shut­tle them around the body, to dif­fer­ent cells and or­gans. They are found in all life, and they have evolved to car­ry those RNA mes­sages through­out the body with­out at­tract­ing at­ten­tion from the im­mune sys­tem.

That makes them an ide­al drug de­liv­ery mech­a­nism. Co­di­ak’s first pro­gram was an ex­o­some to tar­get KRAS, an onco­gene that has been no­to­ri­ous­ly hard to hit be­cause the pro­teins lack a nat­ur­al groove for a small mol­e­cule. More re­cent­ly, they’ve signed up with Sarep­ta to de­vel­op the first mul­ti­ple-dose gene ther­a­py; tra­di­tion­al­ly gene ther­a­py has been sin­gle-dose in part be­cause im­mune sys­tems evolve de­fens­es against the vec­tor used to de­liv­er it.

Yet ex­o­somes are com­pli­cat­ed — “very, very com­pli­cat­ed,” Mok said.

On top of just the lipid sac it­self, there are al­so nu­mer­ous pro­teins on top of them that are re­quired to si­lence the im­mune sys­tem and nu­mer­ous pro­teins that are in­volved in as­sur­ing the vesi­cle docks and en­ters its tar­get cells. “We’re talk­ing about su­per, su­per small hun­dred-nanome­ter vesi­cles where na­ture just ba­si­cal­ly evolved it to be the best drug de­liv­ery ve­hi­cle there is,” he said.

It’s no sur­prise, then, that no ex­o­some drugs have en­tered the clin­ic so far, or that Co­di­ak strug­gled to de­vel­op its KRAS pro­gram and ul­ti­mate­ly put it on the back­burn­er. Gimenez said he’s been watch­ing the field for years, from the time when re­searchers were ex­cit­ed about the po­ten­tial but lacked the tools to even look at in­di­vid­ual ex­o­somes.

“It’s been kind of a pain in the ass to ac­tu­al­ly get it work­ing,” he said, re­fer­ring to the over­all field.

Mantra Bio hopes to solve some of these prob­lems by us­ing a com­pu­ta­tion­al plat­form to first find tar­gets and de­sign ex­o­somes and then build­ing a set of them in the lab. So far they have in the tens of ex­o­somes, Mok said, but they hope to soon es­ca­late to over 100. They’ve al­so in­vest­ed ear­ly in the man­u­fac­tur­ing tech­nol­o­gy to pre­vent some of the bot­tle­necks that have held up oth­er re­searchers.

For now, the com­pa­ny is keep­ing its par­tic­u­lar po­ten­tial close to the vest, but they plan on fil­ing an IND by 2022 or 2023. Mok al­so said they could part­ner with oth­er biotechs, such as Mod­er­na or Al­ny­lam, in help­ing de­liv­er their RNA drugs.

“We’re cer­tain­ly re­al­ly ex­cit­ed about gene ther­a­py and rare dis­eases and the un­drug­gable space,” he said.

Up­date: The first quote in the sto­ry con­tained a mistype. It has since been up­dat­ed. 

Eli Lilly CEO David Ricks (Evan Vucci/AP Images)

A P val­ue of 0.38? NE­JM re­sults raise new ques­tions for Eli Lil­ly's vaunt­ed Covid an­ti­body

Generally, a P value of 0.38 means your drug failed and by a fair margin. Depending on the company, the compound and the trial, it might mean the end of the program. It could trigger layoffs.

For Eli Lilly, though, it was part of the key endpoint on a trial that landed them a $1.2 billion deal with the US government to supply up to nearly 1 million Covid-19 antibodies.

So what does one make of that? Was the endpoint not so important, as Lilly maintains? Or did the US government promise a princely sum for a pedestrian drug?

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No­var­tis buys a new gene ther­a­py for vi­sion loss, and this is one pre­clin­i­cal ven­ture that did­n't come cheap

Cyrus Mozayeni got excited when he began to explore the academic work of Ehud Isacoff and John G. Flannery at UC Berkeley.

Together, they were engaged in finding a gene therapy approach to pan-genotypic vision restoration in patients with photoreceptor-based blindness, potentially restoring the vision of a broad group of patients. And they did it by using a vector to deliver the genetic sequence for light sensing proteins.

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Noubar Afeyan, Flagship founder and CEO (Victor Boyko/Getty Images)

UP­DAT­ED: Flag­ship launch­es Sen­da Bio­sciences with $88M in back­ing, look­ing to pi­o­neer the field of 'In­ter­sys­tems Bi­ol­o­gy'

Flagship Pioneering has a fresh company out this week, one that aims to lay the groundwork for a whole new discipline.

Senda Biosciences launched Wednesday with $88 million in Flagship cash. The goal? Gain insights into the molecular connections between people and coevolved nonhuman species like plants and bacteria, paving the way for “Intersystems Biology.”

Guillaume Pfefer has been tapped to run the show, a 25-year biotech veteran who comes from GSK after leading the development of the company’s shingles vaccine.

Daphne Koller, Getty

Bris­tol My­er­s' Richard Har­g­reaves pays $70M to launch a neu­rode­gen­er­a­tion al­liance with a star play­er in the ma­chine learn­ing world

Bristol Myers Squibb is turning to one of the star upstarts in the machine learning world to go back to the drawing board and come up with the disease models needed to find drugs that can work against two of the toughest targets in the neuro world.

Daphne Koller’s well-funded insitro is getting $70 million in cash and near-term milestones to use their machine learning platform to create induced pluripotent stem cell-derived disease models for ALS and frontotemporal dementia.

Eli Lilly CEO David Ricks at the Rose Garden, May 26, 2020 (Evan Vucci/AP Images)

Eli Lil­ly lines up a block­buster deal for Covid-19 an­ti­body, right af­ter it failed a NI­AID tri­al

Two days after Eli Lilly conceded that its antibody bamlanivimab was a flop in hospitalized Covid-19 patients, the US government is preparing to make it a blockbuster.

The pharma giant reported early Wednesday that it struck a deal to supply the feds with 300,000 vials of the drug at a cost of $375 million — once it gets an EUA stamp from the FDA. And once that 2-month supply deal is done, the government has an option on another 650,000 doses on the same terms — which could potentially add another $812 million.

Q32 Bio grabs $60M to kick off hu­man stud­ies for next-gen com­ple­ment drugs — with some Covid-19 tweaks along the way

For a company that launched in the early months of the pandemic, Q32 Bio had its fair share of run-ins with the new normals under Covid-19.

The original plan, for instance, was to conduct first-in-human studies of the IL-7 receptor antibody it licensed from Bristol Myers Squibb in the Netherlands. But they realized shortly after that while the country was beginning to open up clinical trials, there were additional restrictions on drugs that tampered with immunological mechanisms.

Konstantin Poukalov

Per­cep­tive re­cruits A-list in­vestors to back its in-house Chi­na start­up with a mam­moth $310M raise

It took two years for Perceptive Advisors to conceive and boot up LianBio, its big bet on a new kind of in-licensing model for China, seeding it with enough cash to set up two anchoring deals with MyoKardia and BridgeBio. The result was a startup that was all ready to go, reaping $310 million just a little over two months after official launch.

Homegrown Chinese biotechs — many of them boasting of US ties and execs with overseas credentials — have been raking in mega-venture rounds in 2020, both from influential local backers and overseas VC firms that have been loading up new cash. As with IPOs, the deal flow might be slower but the amounts are often more staggering. LianBio’s latest round, unusually, is branded both a Series A and crossover.

Ar­cus and As­traZeneca part­ner on a high stakes an­ti-TIG­IT/PD-L1 PhI­II can­cer study, look­ing to im­prove on a stan­dard of care

For AstraZeneca, the PACIFIC trial in Stage III non-small cell lung cancer remains one of the big triumphs for AstraZeneca’s oncology R&D group. It not only made their PD-L1 Imfinzi a franchise player with a solid advance in a large niche of the lung cancer market, the study — which continues to offer data on the long-range efficacy of their drug — also helped salve the vicious sting of the failure of the CTLA-4 combo in the MYSTIC study.

Jude Samulski, Marianne De Backer

Bay­er buys a biotech ‘race horse’ with a $4B deal — $2B in cash — aimed at go­ing big in­to gene ther­a­py

In the latest sign that Big Pharma wants a leading place in the push to develop a new generation of cell and gene therapies, Bayer is stepping up today with a $2 billion cash deal to buy out one of the fast-moving pioneers in the field, while adding up to $2 billion more in milestones if the new pharma subsidiary can deliver the goods.

As part of a continuing series of deals engineered by Bayer BD chief Marianne De Backer, the pharma player has snapped up Asklepios, more commonly referred to in more casual fashion as AskBio. And they are paying top dollar for a Research Triangle Park-based company that raised $225 million a little more than a year ago to back the brainchild of Jude Samulski, the gene therapy pioneer out of the University of North Carolina Gene Therapy Center.

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