(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.

ZS Per­spec­tive: 3 Pre­dic­tions on the Fu­ture of Cell & Gene Ther­a­pies

The field of cell and gene therapies (C&GTs) has seen a renaissance, with first generation commercial therapies such as Kymriah, Yescarta, and Luxturna laying the groundwork for an incoming wave of potentially transformative C&GTs that aim to address diverse disease areas. With this renaissance comes several potential opportunities, of which we discuss three predictions below.

Allogenic Natural Killer (NK) Cells have the potential to displace current Cell Therapies in oncology if proven durable.

Despite being early in development, Allogenic NKs are proving to be an attractive new treatment paradigm in oncology. The question of durability of response with allogenic therapies is still an unknown. Fate Therapeutics’ recent phase 1 data for FT516 showed relatively quicker relapses vs already approved autologous CAR-Ts. However, other manufacturers, like Allogene for their allogenic CAR-T therapy ALLO-501A, are exploring novel lymphodepletion approaches to improve persistence of allogenic cells. Nevertheless, allogenic NKs demonstrate a strong value proposition relative to their T cell counterparts due to comparable response rates (so far) combined with the added advantage of a significantly safer AE profile. Specifically, little to no risk of graft versus host disease (GvHD), cytotoxic release syndrome (CRS), and neurotoxicity (NT) have been seen so far with allogenic NK cells (Fig. 1). In addition, being able to harness an allogenic cell source gives way to operational advantages as “off-the-shelf” products provide improved turnaround time (TAT), scalability, and potentially reduced cost. NKs are currently in development for a variety of overlapping hematological indications with chimeric antigen receptor T cells (CAR-Ts) today, and the question remains to what extent they will disrupt the current cell therapy landscape. Click for more details.

Hal Barron, Endpoints UKBIO20 (Jeff Rumans)

'Al­tos was re­al­ly a once-in-a-life­time op­por­tu­ni­ty': Hal Bar­ron re­flects on his big move

By all accounts, Hal Barron had one of the best jobs in Big Pharma R&D. He made more than $11 million in 2020, once again reaping more than his boss, Emma Walmsley, who always championed him at every opportunity. And he oversaw a global R&D effort that struck a variety of big-dollar deals for oncology, neurodegeneration and more.

Sure, the critics never let up about what they saw as a rather uninspiring late-stage pipeline, where the rubber hits the road in the Big Pharma world’s hunt for the next big near-term blockbuster, but the in-house reviews were stellar. And Barron was firmly focused on bringing up the success rate in clinical trials, holding out for the big rewards of moving the dial from an average 10% success rate to 20%.

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Executive Director of the EMA Emer Cooke (AP Photo/Geert Vanden Wijngaert)

Eu­ro­pean Par­lia­ment signs off on strength­en­ing drug reg­u­la­tor's abil­i­ty to tack­le short­ages

The European Parliament on Thursday endorsed a plan to increase the powers of the European Medicines Agency, which will be better equipped to monitor and mitigate shortages of drugs and medical devices.

By a vote of 655 to 31, parliament signed off on a provisional agreement reached with the European Council from last October, in which the EMA will create two shortage steering groups (one for drugs, the other for devices), a new European Shortages Monitoring Platform to facilitate data collection and increase transparency, and on funding for the work of the steering groups, task force, working parties and expert panels that are to be established.

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Kenneth Galbraith, incoming Zymeworks CEO

Zymeworks re­places half its C-suite, aims to lay off 25% of to­tal work­force as new CEO takes over

New Zymeworks CEO Kenneth Galbraith is aiming to hit the ground running when his tenure officially begins next month, but he’ll be doing so with a much different looking team.

In a lengthy press release outlining the biotech’s 2022 goals, Galbraith said Zymeworks will be laying off at least 25% of its staff over the course of the year. Half of its C-suite will also be replaced immediately as Galbraith looks to remake the company in his image after Ali Tehrani, Zymeworks’ founder and CEO since 2003, stepped down two weeks ago.

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Crit­ics push back on Alzheimer’s As­so­ci­a­tion ad blitz to get Medicare to change its Aduhelm rul­ing: 'Dead wrong'

The latest Alzheimer’s Association advertising campaign encourages people to fight.

Not against the disease or for more research or treatments, but against the Centers for Medicare and Medicaid Services. More specifically, CMS’ recent reimbursement decision to only pay for Biogen and Eisai’s controversial Alzheimer’s drug Aduhelm for patients in clinical trials.

With CMS’ preliminary decision now in a 30-day comment period, patient advocates’ goal is to convince CMS to reverse its decision with a marketing blitz and public pressure.

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Dan O'Day, Gilead CEO (Jim Watson/AFP via Getty Images)

Fail­ing to con­firm clin­i­cal ben­e­fit, Gilead pulls 2 ac­cel­er­at­ed ap­proval in­di­ca­tions for can­cer drug

Gilead recently decided to pull two indications for its cancer drug Zydelig — in relapsed follicular B-cell non-Hodgkin lymphoma (FL) and relapsed small lymphocytic leukemia (SLL) — after failing to complete the confirmatory trials required as part of the accelerated approvals from 2014.

“As the treatment landscape for FL and SLL has evolved, enrollment into the confirmatory study has been an ongoing challenge,” Gilead said in a statement, noting it formally notified the FDA of its decision to voluntarily withdraw these indications.

Richard Pazdur (via AACR)

Time lim­its on ac­cel­er­at­ed ap­provals? FDA's on­col­o­gy chief Rick Paz­dur eyes po­ten­tial re­forms via in­ter­na­tion­al ap­proach­es

The spotlight on the accelerated approval pathway continues to shine bright, with the FDA’s top oncology official writing in an opinion that the pathway may be strengthened with bits and pieces of what other regulators in Europe and elsewhere have done with their expedited approval pathways, such as adding expiration dates for these faster approvals to ensure they confirm clinical benefit in a timely manner.

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Covid-19 roundup: HHS may strug­gle to ab­sorb Op­er­a­tion Warp Speed; Eu­rope has no plans for a fourth vac­cine dose

Operation Warp Speed, perhaps the greatest achievement of the former Trump administration, promptly delivered Covid-19 vaccine supplies nationwide when they became available, thanks to collaborations between HHS and the Department of Defense, while helping to fund and aid the manufacture of billions of doses.

But since the Biden administration took over a year ago, acting FDA commissioner Janet Woodcock transitioned out of her role as the therapeutics lead in Warp Speed, which has been converted into a new operation without the fancy name (now known as the “HHS-DOD COVID-19 Countermeasures Acceleration Group”), and as of the start of 2022, the Department of Defense is no longer helping HHS on the program.

Flori­da man con­vict­ed of fal­si­fy­ing clin­i­cal tri­al re­sults sen­tenced to over 2 years in prison

A Florida man who falsified medical records in connection to clinical trials was sentenced to 30 months in prison in federal court Thursday.

Daniel Tejeda, 35, of Clewiston, was also ordered to pay $2.1 million in restitution. Tejeda was a project manager and study manager for the CRO Tellus Clinical Research, and made it appear that subjects were participating in trials when they weren’t. Two other research workers from Florida were sentenced in the same case in August for 46 and 30 months, respectively.