(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.

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.

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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Raymond Stevens, ShouTi Pharma CEO

A new Schrödinger-backed start­up emerges from the sci­en­tist who mapped the first hu­man GPCR

One of the most popular targets in drug development, representing about a third of existing drugs, are G-protein coupled receptors — the tiny but integral membrane proteins responsible for recognizing things like light, taste, smell, hormones and pain.

But due to challenges in mapping their structure, the protein family remains largely unexplored.

A slate of companies has emerged over the last few years to change that. If one can figure out the structure of these elusive membrane receptors, it might be possible to create small molecule drugs that overcome the limitations of, say, biologic and peptide therapies. That promise is what gets serial entrepreneur Raymond Stevens out of bed in the morning.

Man­u­fac­tur­ing woes for No­vavax’s Covid jab bad­ly dis­rupt plans for roll­out to the poor — re­port

Production problems at a Novavax facility in Maryland have led to delays in the Covax vaccine sharing program. Now, a shortage of 1 billion doses is expected, as the supplier tries to navigate producing a shot up to regulators’ standards, Politico reported Tuesday.

The company has run into trouble with the purity of the vaccine. Novavax has had trouble proving it can produce a shot consistently up to standards, and it has caused significant delays in the rollout to low- and middle-income countries. This follows several delays at Novavax that has put the executive crew on the defensive.

Sur­geons suc­cess­ful­ly at­tach pig kid­ney to a hu­man for the first time, us­ing tech from Unit­ed's Re­vivi­cor

In a first, researchers reportedly successfully transplanted a pig kidney into a human without triggering an immediate immune response this week. And the technology came from the biotech United Therapeutics.

Surgeons spent three days attaching the kidney to the patient’s blood vessels, but when all was said and done, the kidney appeared to be functioning normally in early testing, Reuters and the New York Times were among those to report. The kidney came from a genetically altered pig developed through United’s Revivicor unit.

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Michel Vounatsos, Biogen CEO (Credit: World Economic Forum/Valeriano Di Domenico)

Up­dat­ed: Bio­gen sells just $300K worth of Aduhelm in Q3, as ques­tions on long-term vi­a­bil­i­ty re­main

Barely anyone is accessing Biogen’s controversial Alzheimer’s treatment, with the company reporting just $0.3 million in Aduhelm sales in the third quarter. Although investors will be looking to the longer term, when CMS may decide to cover the drug and open the floodgates for more reimbursement, use of the drug is currently stalled.

Since June, when the FDA first signed off on the drug under its accelerated pathway, Biogen said Wednesday that it’s sold a total of $2 million worth of Aduhelm. That’s a far cry from the peak Wall Street sales estimate of about $9 billion in annual sales.

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With hun­dreds of mil­lions spent on failed ac­cel­er­at­ed ap­provals, re­searchers call for faster FDA with­drawals

Between 2017 and 2019, Medicare spent more than $220 million on cancer drugs for which the indications were either voluntarily pulled by their applicants or FDA’s oncology adcomm had recommended their withdrawal.

That kind of massive spending on cancer drugs lacking overall survival benefit is wasteful and risks harming people’s health, a research letter published in JAMA Internal Medicine on Monday said. The researchers from Harvard and the London School of Economics called on the FDA to move faster in both requiring timely postmarketing trials and accelerating the speed in pulling these dangling approvals when the confirmatory studies fail.

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Bill Gates at the Global Investment Summit in London, Oct. 19, 2021 (Leon Neal/Pool via AP Images)

Gates Foun­da­tion pledges $120M to ramp up gener­ic sup­ply of Mer­ck­'s Covid-19 pill while ac­tivists blast Pfiz­er's dis­pro­por­tion­ate pow­er

Merck’s molnupiravir may not be officially authorized anywhere in the world yet, but who will get access to it has shaped up to be a huge issue. The Bill & Melinda Gates Foundation is now stepping up to ensure lower-income countries won’t be left behind — and calling on others to follow its lead.

The oral antiviral pill, which was shown to dramatically cut the risk of severe Covid-19 disease and death in a Phase III study, is the latest rallying symbol in the battle against not just the coronavirus but the inequality it’s exposed.