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. 

Pi­o­neer­ing Click Chem­istry in Hu­mans

Reimagining cancer treatments

Cancer is a leading cause of death worldwide, accounting for nearly 10 million deaths in 2020, which is nearly one in six deaths. Recently, we have seen incredible advances in novel cancer therapies such as immune checkpoint inhibitors, cell therapies, and antibody-drug conjugates that have revamped cancer care and improved survival rates for patients.

Despite this significant progress in therapeutic targeting, why are we still seeing such a high mortality rate? The reason is that promising therapies are often limited by their therapeutic index, which is a measure of the effective dose of a drug, relative to its safety. If we could broaden the therapeutic indices of currently available medicines, it would revolutionize cancer treatments. We are still on the quest to find the ultimate cancer medicine – highly effective in several cancer types, safe, and precisely targeted to the tumor site.

Ivan Cheung, Eisai US chairman and CEO

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One of the most-watched Alzheimer’s therapies in the clinic, lecanemab met the study’s primary goal on the CDR-SB — Clinical Dementia Rating-Sum of Boxes — giving the biotech the confidence to ask for full approval in the US, EU and Japan by next March 31. The experimental drug reduced clinical decline on the scale by 27% compared to placebo at 18 months, the companies said Tuesday night Eastern time and Wednesday morning in Japan.

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The pharma giant on Wednesday provided an update on what it called a “large-scale, sophisticated counterfeiting conspiracy,” accusing two new defendants of “leading and orchestrating” a scheme to sell hundreds of millions of dollars in illegitimate drugs posing as meds such as Biktarvy and Descovy.

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Silicon Valley Bank’s Nooman Haque and I are once again jumping back into the thick of it with a slate of virtual and live events on October 12. I’ll get the ball rolling with a virtual fireside chat with Novo Nordisk R&D chief Marcus Schindler, covering their pipeline plans and BD work.

Vlad Coric, Biohaven CEO (Photo Credit: Andrew Venditti)

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Thursday morning, Biohaven announced that its drug verdiperstat failed its arm of an ALS platform trial led by Massachusetts General Hospital. According to a press release, the drug did not meet its primary endpoint — improvement on an ALS functional status test — or any key secondary endpoints at 24 weeks. The trial had enrolled 167 patients, giving them either verdiperstat or placebo twice a day.

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Work taking place in the clean rooms at Vor (Credit: Vor)

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Vor Biopharma has started manufacturing operations at an in-house facility at its HQ in Cambridge, MA after beginning construction last summer.

According to the biotech, the facility aims to develop Vor’s hematopoietic stem cells (eHSCs) and CAR-T therapies for patients with blood cancers. The site will initially manufacture a clinical supply of its candidate VCAR33allo to support its IND, which is slated to be submitted in the first half of next year. It also plans to transfer the production of VOR33 to the facility. Vor is getting to work quickly as engineering runs for VCAR33allo has started this week.

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The biotech has yet to complete confirmatory trials for those first three conditional nods. The filing for its fourth Duchenne muscular dystrophy treatment, disclosed Thursday, is not a surprise. Sarepta said in late-July it would do so after releasing positive results for the Roche-partnered gene therapy.

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Of the total doses, $5.1 million worth of oral antivirals called Tpoxx (tecovirimat) will be delivered this year, with the US Department of Defense having the option of buying the rest at a later point.

The new contract follows an earlier one in which the government had purchased $7.4 million worth of Tpoxx from the company.

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Simcere and Almirall announced Thursday that the two companies had reached a deal for Simcere’s IL-2 mutant fusion protein drug candidate, called SIM0278. According to a statement, Almirall gets an exclusive right to develop and commercialize the drug candidate in all indications and markets outside of China, Hong Kong, Taiwan and Macau.

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