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. 

Cell and Gene Con­tract Man­u­fac­tur­ers Must Em­brace Dig­i­ti­za­tion

The Cell and Gene Industry is growing at a staggering 30% CAGR and is estimated to reach $14B by 20251. A number of cell, gene and stem cell therapy sponsors currently have novel drug substances and products and many rely on Contract Development Manufacturing Organizations (CDMO) to produce them with adherence to stringent regulatory cGMP conditions. Cell and gene manufacturing for both autologous (one to one) and allogenic (one to many) treatments face difficult issues such as: a complex supply chain, variability on patient and cellular level, cell expansion count and a tight scheduling of lot disposition process. This complexity affects quality, compliance and accountability in the entire vein-to-vein process for critically ill patients.

Phase III read­outs spell dis­as­ter for Genen­tech’s lead IBD drug

Roche had big plans for etrolizumab. Eyeing a hyper-competitive IBD and Crohn’s market where they have not historically been a player, the company rolled out 8 different Phase III trials, testing the antibody for two different uses across a range of different patient groups.

On Monday, Roche released results for 4 of those studies, and they mark a decided setback for both the Swiss pharma and their biotech sub Genentech, potentially spelling an end to a drug they put over half-a-decade and millions of dollars behind.

Vi­da Ven­tures co-leads Dyne's $115M megaround for next-gen oli­go ther­a­pies aimed square­ly at mus­cles

Dyne Therapeutics started out last April with a modest $50 million to mine targeted muscle disease therapies from its in-house conjugate technology. The biotech has now convinced more investors that it’s got gems on its hands, closing $115 million in fresh financing to push its next-gen oligonucleotide drugs into the clinic.

Vida Ventures and Surveyor Capital led the round, joined by a group of other new backers including Wellington Management Company, Logos Capital and Franklin Templeton.

Eli Lil­ly teams with Pieris on HER2+ tu­mors; Op­di­vo + Yer­voy best chemo in mesothe­lioma

Despite the FDA putting a partial clinical hold on its lead program only a few weeks ago, Boston-based Pieris Pharmaceuticals is plowing forward with a new collaboration.

Pieris will work with Eli Lilly to further advance studies on PRS-343, a 4-1BB/HER2 bispecific for HER2-positive tumors, in combination with the latter’s ramucirumab and paclitaxel for the second-line treatment of patients with HER2-positive gastric cancer in a single-arm, Phase II study.

In­novent and Eli Lil­ly chal­lenge Mer­ck­'s mega-block­buster Keytru­da in non-small cell lung can­cer field

China-based Innovent Biologics and its multinational ally Eli Lilly shared Phase III evidence that their PD-1 inhibitor combo can delay the progression of nonsquamous non-small cell lung cancer.

But the drugmakers will face stiff competition in China from Merck’s Keytruda, the ruling PD-1 which is already approved to treat both squamous and nonsquamous NSCLC and boasts positive overall survival rates.

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DFC CEO Adam Boehler and Kodak CEO Jim Continenza (Kodak)

Covid-19 roundup: Cure­Vac beefs up its uni­corn IPO dreams as bil­lion­aire own­er takes this Covid-19 mR­NA play­er on a forced march to Nas­daq; Ko­dak's $765M deal is put on hold

When CureVac initially jotted down $100 million for its IPO raise a couple of weeks ago, it seemed small. The German mRNA player, after all, had jumped into a Covid-19 race that swelled the sails of Moderna and BioNTech by tens of billions. And after raising $640 million in a slate of deals, $100 million in a hot market like this seemed like a pittance in the bigger scheme of things.

Today, we got a look at a figure that probably comes closer to the game-changing number the top execs probably have in mind. Selling 15.3 million shares at the high end of their $14 to $16 range would net a $243 million bounty. Majority owner Dietmar Hopp is putting in another €100 million, bringing the total to around $350 million. And what are the chances they want to do even better than that?

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Eric Shaff (Seres)

UP­DAT­ED: Af­ter a 4-year so­journ, strug­gling mi­cro­bio­me pi­o­neer Seres claims a break­out PhI­II come­back. And shares re­spond in fren­zied spike

Almost exactly 4 years ago, Seres Therapeutics $MCRB experienced one of those soul-crunching failures that can raise big questions about a biotech’s future. Out front in their pursuit of a gut punch to C. difficile infection (CDI), the Phase II test was a flat failure, and investors wiped out a billion dollars of equity value that never returned in the years that followed.

Seres, though, pressed ahead, changing out CEOs a year ago — bidding Merck vet Roger Pomerantz farewell from the C suite — and pushing through a Phase III, hoping that amping up the dosage would make the key difference. And this morning, they unveiled a claim that they had aced the Phase III and positioned themselves for a run at a landmark FDA OK.

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Anap­tys­Bio's etokimab pro­vides more dis­ap­point­ing re­sults, rais­ing ques­tions about com­pound's fu­ture

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Gallia Levy, Spark CMO (Roche)

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Spark Therapeutics is getting a new CMO from their new owners.

The gene therapy company-turned-subsidiary has named Gallia Levy, who had been running rare blood disorders — including clinical development for their blockbuster-potential hemophilia antibody Hemlibra for Roche’s big biotech sub Genentech — to run medical affairs.

The appointment is a fitting one. Roche spent $4.8 billion to acquire Spark last year in large part to get their hands on their hemophilia gene therapy, SPK-8011, and expand the toe-hold Hemlibra gave them in an crowded hemophilia space.  It’s also a somewhat ironic appointment: The FTC held up the Spark acquistions for nearly a year, reportedly over concerns about the anti-trust implications of Roche owning both a top chronic treatment in Hemlibra and a top one-time treatment in Spark’s gene therapy.

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