(L-R) Samta Kundu (COO), Jake Becraft (CEO), Tasuku Kitada (head of R&D) [Strand Therapeutics]

A pair of for­mer MIT re­searchers think they've un­locked the next gen­er­a­tion of mR­NA us­ing syn­bio 'log­ic cir­cuit­s'

The time of mR­NA is in full swing as Mod­er­na and Pfiz­er/BioN­Tech have blown the doors off the field. But in drug de­vel­op­ers’ eyes, cur­rent-gen mR­NA vac­cines are just an ap­pe­tiz­er to the full course of ther­a­peu­tics fur­ther down the menu — at least that’s what two for­mer MIT re­searchers with syn­thet­ic bi­ol­o­gy roots are gam­bling on.

Strand Ther­a­peu­tics emerged from stealth Wednes­day with a $52 mil­lion Se­ries A to ad­vance its pipeline of pro­gram­ma­ble, self am­pli­fy­ing mR­NA ther­a­pies ini­tial­ly tar­get­ed at sol­id tu­mor im­muno-on­col­o­gy, the biotech said.

The team’s re­search stems from the work of CEO Jake Be­craft and head of R&D Tasuku Ki­ta­da at MIT’s Syn­thet­ic Bi­ol­o­gy Cen­ter and the Weiss Lab, where the pair met and fo­cused on ap­ply­ing syn­bio prin­ci­ples to mR­NA ther­a­peu­tic de­vel­op­ment. Along the way, their work formed Strand’s plat­form, which turns out long act­ing mR­NA ther­a­pies with greater speci­fici­ty and a wider ther­a­peu­tic in­dex than the cur­rent gen­er­a­tion of mR­NA vac­cines.

The biotech is us­ing self am­pli­fy­ing tech, which in­duces a sin­gle copy of the mR­NA drug to repli­cate it­self in vi­vo. That of­fers a much longer ther­a­peu­tic win­dow than cell ther­a­pies like the Covid-19 vac­cines from Mod­er­na and BioN­Tech, Be­craft told End­points News, which work on the scale of days rather than weeks.

But per­haps the biggest dif­fer­ence from its range of com­peti­tors is Strand’s use of “ge­net­i­cal­ly pro­gram­ma­ble log­ic cir­cuits,” which al­low its mR­NA drugs to en­ter a spe­cif­ic cel­lu­lar en­vi­ron­ment and turn pro­tein ex­pres­sion on or off de­pend­ing on a se­ries of bio­mark­ers. It’s a for­mu­la fa­mil­iar in syn­thet­ic bi­ol­o­gy: Use “sen­sors” to iden­ti­fy the tar­get en­vi­ron­ment, “log­ic process” or com­pute those sig­nals, and then ef­fect a tar­get out­put.

The com­pa­ny’s syn­bio plat­form serves a dual pur­pose of al­low­ing tight con­trol over RNA self-repli­ca­tion, en­sur­ing the ther­a­py is on­ly around in the cell as long as it needs to be.

“One of the ma­jor prob­lems with self repli­ca­tion mR­NA is that you ac­tu­al­ly need to con­trol their repli­ca­tion at a much tighter lev­el — and that’s ac­tu­al­ly what syn­thet­ic bi­ol­o­gy is re­al­ly per­fect for,” Be­craft said. “You go in­to the se­quence of the repli­ca­tion ma­chin­ery and you can make mod­i­fi­ca­tions to how it repli­cates and ac­tu­al­ly con­trol it.”

All that, ul­ti­mate­ly, means one drug could the­o­ret­i­cal­ly have an ef­fect on a range of dis­ease types — par­tic­u­lar­ly in a het­ero­ge­neous ther­a­peu­tic area such as can­cer. No sur­prise, then, that can­cer is ex­act­ly where Strand is aim­ing first.

The biotech is hop­ing to take its lead drug, which is fo­cused in the sol­id tu­mor I/O space in­to the clin­ic by 2022. The com­pound is the tar­get of a li­cens­ing pact with Chi­nese drug­mak­er BeiGene, which has pledged to cov­er some de­vel­op­ment and com­mer­cial­iza­tion costs in the re­gion. Can­cer is no easy area to jump head­first in­to, but it is a prof­itable one. Be­craft high­light­ed the field’s well-es­tab­lished bi­ol­o­gy as ripe with big tar­gets for Strand’s drugs.

“I think can­cer is a great first tar­get for things like the next gen­er­a­tion of RNA ther­a­peu­tics be­cause can­cer has a lot of known tar­gets and known bi­ol­o­gy for ther­a­peu­tic in­ter­ven­tion,” Be­craft said. “It just gives you a great start­ing point to de­vel­op a new plat­form. Can­cer kills peo­ple; we got­ta do some­thing.”

Be­craft said his com­pa­ny would look to sign sim­i­lar deals in the com­ing months, aim­ing to sign on “high­ly strate­gic” part­ners to ad­vance Strand’s pipeline and com­mer­cial op­por­tu­ni­ties.

It’s the first go-round as CEO for Be­craft, who made the jump straight from MIT as he worked to build Strand in stealth mode along­side Ki­ta­da start­ing in 2018. He said his first pri­or­i­ties are dri­ving the com­pa­ny’s lead pro­gram ahead while build­ing the pipeline and adding a strong team around him. The com­pa­ny is cur­rent­ly on a hir­ing spree with 25 on board and hopes to hit as many as 80 em­ploy­ees as it nears the clin­ic, Be­craft said.

The Se­ries A round was joined by a syn­di­cate of in­vestors in Red­mile Group, BeiGene and Cam­ford Cap­i­tal, as well as ex­ist­ing in­vestors Play­ground Glob­al and AN­RI.

Adap­tive De­sign Meth­ods Of­fer Rapid, Seam­less Tran­si­tion Be­tween Study Phas­es in Rare Can­cer Tri­als

Rare cancers account for 22 percent of cancer diagnoses worldwide, yet there is no universally accepted definition for a “rare” cancer. Moreover, with the evolution of genomics and associated changes in categorizing tumors, some common cancers are now characterized into groups of rare cancers, each with a unique implication for patient management and therapy.

Adaptive designs, which allow for prospectively planned modifications to study design based on accumulating data from subjects in the trial, can be used to optimize rare oncology trials (see Figure 1). Adaptive design studies may include multiple cohorts and multiple tumor types. In addition, numerous adaptation methods may be used in a single trial and may facilitate a more rapid, seamless transition between study phases.

Matt Gline (L) and Pete Salzmann

UP­DAT­ED: Roivant bumps stake in Im­muno­vant with a $200M deal. But with M&A off the ta­ble, shares crater

Roivant has worked out a deal to pick up a chunk of stock in its majority-owned sub Immunovant $IMVT, but the stock buy falls far short of its much-discussed thoughts about buying out all of the 43% of shares it doesn’t already own.

Roivant, which recently inked a SPAC move to the market at a $7 billion-plus valuation, has forged a deal to boost its ownership in Immunovant by 6.3 points, ending with 63.8% of the biotech’s stock following a $200 million injection. That cash will bolster Immunovant’s cash reserves, giving it a $600 million war chest to fund a slate of late-stage studies for its big drug: the anti-FcRn antibody IMVT-1401.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 113,300+ biopharma pros reading Endpoints daily — and it's free.

Sanofi preps a multi­bil­lion-dol­lar buy­out of an mR­NA pi­o­neer af­ter falling be­hind in the race for a Covid-19 jab — re­port

It looks like Sanofi CEO Paul Hudson is dead serious about his intention to vault directly into contention for the future of mRNA vaccines.

A year after paying Translate Bio a whopping $425 million in an upfront and equity payment to help guide the pharma giant to the promised land of mRNA vaccines for Covid-19, Sanofi is reportedly ready to close the deal with a buyout.

Translate’s stock $TBIO soared 78% after the market closed Monday. A spokesperson for Sanofi declined to comment on the report, telling Endpoints News that the company doesn’t comment on market rumors.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 113,300+ biopharma pros reading Endpoints daily — and it's free.

Anthony Sun, Zentalis and Zentera CEO (Zentalis)

With clin­i­cal tri­als lined up for Zen­tal­is drugs, Chi­na's Zen­tera sets its sights on more deal­mak­ing and an IPO

As Zentalis geared up for an AACR presentation of early data on its WEE1 inhibitor earlier this year, its Chinese joint venture Zentera wasn’t idle, either.

Zentera, which has headquarters in Shanghai, had already nabbed clearance to start clinical trials in China for three of the parent company’s drugs. In May — just a month after Zentalis touted three “exceptional responses” out of 55 patients for their shared lead drug, ZN-c3 — it got a fourth CTA approval.

Thomas Soloway, T-knife CEO

What hap­pens when you give a mouse a hu­man self-anti­gen? In­vestors bet $110M to find out

T-knife Therapeutics launched last August on a mission to isolate T cell receptors not from human donors, but from mice. Now, with a new CEO and a candidate bound for the clinic, the Versant-backed company is reloading with a fresh $110 million.

“What we are trying to do for the field of TCR therapy and solid tumor therapy is very analogous to what the murine platforms have done in antibody development,” CEO Thomas Soloway told Endpoints News. 

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 113,300+ biopharma pros reading Endpoints daily — and it's free.

UP­DAT­ED: Watch out Glax­o­SmithK­line: As­traZeneca's once-failed lu­pus drug is now ap­proved

Capping a roller coaster journey, AstraZeneca has steered its lupus drug anifrolumab across the finish line.

Saphnelo, as the antibody will be marketed, is the only treatment that’s been approved for systemic lupus erythematosus since GlaxoSmithKline’s Benlysta clinched an OK in 2011. The British drugmaker notes it’s also the first to target the type I interferon receptor.

Mirroring the population that the drug was tested on in late-stage trials, regulators sanctioned it for patients with moderate to severe cases who are already receiving standard therapy — setting up a launch planned for the end of August, according to Ruud Dobber, who’s in charge of AstraZeneca’s biopharmaceuticals business unit.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 113,300+ biopharma pros reading Endpoints daily — and it's free.

Not all mR­NA vac­cines are cre­at­ed equal. Does it mat­ter?; Neu­ro is back; Pri­vate M&A af­fair; 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.

As part of our broader and deeper drive, Endpoints has been pairing webinars with our special reports to cover more angles on a given topic. In conjunction with Max Gelman’s neuroscience feature, Kyle Blankenship moderated an insightful panel to discuss where the field is headed. You can register to watch it on demand here.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 113,300+ biopharma pros reading Endpoints daily — and it's free.

Bris­tol My­ers pulls lym­phoma in­di­ca­tion for Is­to­dax af­ter con­fir­ma­to­ry tri­al falls flat

Amid an industrywide review of cancer drugs with accelerated approval, Bristol Myers Squibb had to make the tough call last month to yank an approval for leading I/O drug Opdivo after flopping a confirmatory study. Now, a second Bristol Myers drug is on the chopping block.

Bristol Myers has pulled aging HDAC inhibitor Istodax’s indication in peripheral T cell lymphoma after a Phase III confirmatory study for the drug flopped on its progression-free survival endpoint, the drugmaker said Monday.

Rick Pazdur (via AACR)

FDA's on­col­o­gy head Rick Paz­dur de­fends the ac­cel­er­at­ed ap­proval path­way, claim­ing it is 'un­der at­tack'

The FDA is sounding the alarm over its accelerated approval pathway as backlash continues over the recent nod in favor of Biogen’s Alzheimer’s drug Aduhelm, and an ODAC meeting on six such approvals that could potentially be pulled from the market — two of which already have.

“Do you think accelerated approval is under attack? I do,” Rick Pazdur, head of FDA’s Oncology Center of Excellence, said at a Friends of Cancer Research webinar on Thursday.

Endpoints Premium

Premium subscription required

Unlock this article along with other benefits by subscribing to one of our paid plans.