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. 

Biotech Half­time Re­port: Af­ter a bumpy year, is biotech ready to re­bound?

The biotech sector has come down firmly from the highs of February as negative sentiment takes hold. The sector had a major boost of optimism from the success of the COVID-19 vaccines, making investors keenly aware of the potential of biopharma R&D engines. But from early this year, clinical trial, regulatory and access setbacks have reminded investors of the sector’s inherent risks.

RBC Capital Markets recently surveyed investors to take the temperature of the market, a mix of specialists/generalists and long-only/ long-short investment strategies. Heading into the second half of the year, investors mostly see the sector as undervalued (49%), a large change from the first half of the year when only 20% rated it as undervalued. Around 41% of investors now believe that biotech will underperform the S&P500 in the second half of 2021. Despite that view, 54% plan to maintain their position in the market and 41% still plan to increase their holdings.

So — that pig-to-hu­man trans­plant; Po­ten­tial di­a­betes cure reach­es pa­tient; Ac­cused MIT sci­en­tist lash­es back; and more

Welcome back to Endpoints Weekly, your review of the week’s top biopharma headlines. Want this in your inbox every Saturday morning? Current Endpoints readers can visit their reader profile to add Endpoints Weekly. New to Endpoints? Sign up here.

We’re incredibly excited to welcome Beth Bulik, seasoned pharma marketing reporter, to the team. You can find much of her work in our new Marketing channel — and in her weekly newsletter, Endpoints PharmaRx, which will launch in early November. Add it to your subscriptions here.

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NYU surgeon transplants an engineered pig kidney into the outside of a brain-dead patient (Joe Carrotta/NYU Langone Health)

No, sci­en­tists are not any clos­er to pig-to-hu­man trans­plants than they were last week

Steve Holtzman was awoken by a 1 a.m. call from a doctor at Duke University asking if he could put some pigs on a plane and fly them from Ohio to North Carolina that day. A motorcyclist had gotten into a horrific crash, the doctor explained. He believed the pigs’ livers, sutured onto the patient’s skin like an external filter, might be able to tide the young man over until a donor liver became available.

UP­DAT­ED: Agenus calls out FDA for play­ing fa­vorites with Mer­ck, pulls cer­vi­cal can­cer BLA at agen­cy's re­quest

While criticizing the FDA for what may be some favoritism towards Merck, Agenus on Friday officially pulled its accelerated BLA for its anti-PD-1 inhibitor balstilimab as a potential second-line treatment for cervical cancer because of the recent full approval for Merck’s Keytruda in the same indication.

The company said the BLA, which was due for an FDA decision by Dec. 16, was withdrawn “when the window for accelerated approval of balstilimab closed,” thanks to the conversion of Keytruda’s accelerated approval to a full approval four months prior to its PDUFA date.

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How to col­lect and sub­mit RWD to win ap­proval for a new drug in­di­ca­tion: FDA spells it out in a long-await­ed guid­ance

Real-world data are messy. There can be differences in the standards used to collect different types of data, differences in terminologies and curation strategies, and even in the way data are exchanged.

While acknowledging this somewhat controlled chaos, the FDA is now explaining how biopharma companies can submit study data derived from real-world data (RWD) sources in applicable regulatory submissions, including new drug indications.

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David Livingston (Credit: Michael Sazel for CeMM)

Renowned Dana-Far­ber sci­en­tist, men­tor and bio­phar­ma ad­vi­sor David Liv­ingston has died

David Livingston, the Dana-Farber/Harvard Med scientist who helped shine a light on some of the key molecular drivers of breast and ovarian cancer, died unexpectedly last Sunday.

One of the senior leaders at Dana-Farber during his nearly half century of work there, Livingston was credited with shedding light on the genes that regulate cell growth, with insights into inherited BRCA1 and BRCA2 mutations that helped lay the scientific foundation for targeted therapies and earlier detection that have transformed the field.

No­vo CEO Lars Fruer­gaard Jør­gensen on R&D risk, the deal strat­e­gy and tar­gets for gen­der di­ver­si­ty


I kicked off our European R&D summit last week with a conversation involving Novo Nordisk CEO Lars Fruergaard Jørgensen. Novo is aiming to launch a new era of obesity management with a new approval for semaglutide. And Jørgensen had a lot to say about what comes next in R&D, how they manage risk and gender diversity targets at the trendsetting European pharma giant.

John Carroll: I’m here with Lars Jørgensen, the CEO of Novo Nordisk. Lars, it’s been a really interesting year so far with Novo Nordisk, right? You’ve projected a new era of growing sales. You’ve been able to expand on the GLP-1 franchise that was already well established in diabetes now going into obesity. And I think a tremendous number of people are really interested in how that’s working out. You have forecast a growing amount of sales. We don’t know specifically how that might play out. I know a lot of the analysts have different ideas, how those numbers might play out, but that we are in fact embarking on a new era for Novo Nordisk in terms of what the company’s capable of doing and what it’s able to do and what it wants to do. And I wanted to start off by asking you about obesity in particular. Semaglutide has been approved in the United States for obesity. It’s an area of R&D that’s been very troubled for decades. There have been weight loss drugs that have come along. They’ve attracted a lot of attention, but they haven’t actually ever gained traction in the market. My first question is what’s different this time about obesity? What is different about this drug and why do you expect it to work now whereas previous drugs haven’t?

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David Lockhart, ReCode Therapeutics CEO

Pfiz­er throws its weight be­hind LNP play­er eye­ing mR­NA treat­ments for CF, PCD

David Lockhart did not see the meteoric rise of messenger RNA and lipid nanoparticles coming.

Thanks to the worldwide fight against Covid-19, mRNA — the genetic code that can be engineered to turn the body into a mini protein factory — and LNPs, those tiny bubbles of fat carrying those instructions, have found their way into hundreds of millions of people. Within the biotech world, pioneers like Alnylam and Intellia have demonstrated just how versatile LNPs can be as a delivery vehicle for anything from siRNA to CRISPR/Cas9.

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Ep­i­darex, Sofinno­va dou­ble down on a par­al­lel take on 3rd-gen CAR-T — aim­ing straight at ovar­i­an can­cer

When John Maher treated the first head and neck cancer patient at Guy’s Hospital in London with his pan-ErbB CAR-T back in 2015, he was among a small club of researchers convinced they had an answer to the challenges that had kept those engineered T cells — wildly successful in hematological cancers — either too dangerous or out of reach for patients with solid tumors.

The field has blossomed since then, with a proliferation of technologies that promise to address any number of challenges identified as unique to solid tumors. And Maher himself has rethought his approach and come up with a new CAR-T platform to generate the next slate of candidates.