Dan Siegwart (UT Southwestern)

Cou­pling mR­NA with tR­NA and new de­liv­ery tech, MPM and Or­biMed help birth new $80M biotech in­to a slowed down world

Part­ners at MPM and Or­biMed were hop­ing David Lock­hart could help them with due dili­gence when they brought him and his team at Tran­scrip­Tx in to look at a tiny up­start spun out of the Uni­ver­si­ty of Texas South­west­ern Med­ical Cen­ter in Dal­las. Dubbed Re­Code Ther­a­peu­tics, it was de­vel­op­ing a lipid nanopar­ti­cle (LNP) de­liv­ery plat­form for var­i­ous ge­net­ic med­i­cines, with a lead pro­gram in cys­tic fi­bro­sis backed by the CF Foun­da­tion.

But Lock­hart, the for­mer CSO of Am­i­cus Ther­a­peu­tics and a one-time biotech en­tre­pre­neur, saw an im­me­di­ate match with the mR­NA and res­pi­ra­to­ry dis­ease work that Tran­scrip­Tx was do­ing. Since his com­pa­ny was al­so look­ing to raise mon­ey, wouldn’t it make sense to merge the two?

So in­stead of two Se­ries B rounds, MPM and Or­biMed have now put their mon­ey be­hind a brand new biotech that’s tak­ing the Re­Code name and $80 mil­lion in Se­ries A cash to hus­tle to­ward the clin­ic and get se­ri­ous about BD — al­beit at a slight­ly slow­er pace amid a pan­dem­ic.

“We closed the merg­er and the fi­nanc­ing on March 6,” Lock­hart told End­points News. “Even though in some ways that wasn’t very long ago, the world was kind of in a dif­fer­ent place even three weeks ago.”

Colt Ven­tures co-led the round with Or­biMed, with par­tic­i­pa­tion from Vi­da Ven­tures, Hunt Tech­nol­o­gy Ven­tures and Os­age Uni­ver­si­ty Part­ners.

The aca­d­e­m­ic labs at UT South­west­ern, where founders Dan Sieg­wart and Philip Thomas are based, have been shut down. With most of the staff work­ing from home, the CEO of­ten finds him­self work­ing in an emp­ty of­fice in Men­lo Park by him­self. Re­Code doesn’t plan to pull the trig­ger on any new hires in the next few weeks.

What they are do­ing, though, is lay­ing the ground­work so that they have every­thing lined up to go at full speed once they can, from pre­clin­i­cal ex­per­i­ments to job can­di­dates. The sci­en­tists who are tend­ing to cru­cial cell lines are al­so still at work while keep­ing their dis­tance, which is rel­a­tive­ly easy with a team of 12 in Cal­i­for­nia and just 3 in Texas.

The orig­i­nal lead pro­gram at Tran­scrip­Tx was de­signed to treat the rare ge­net­ic dis­or­der pri­ma­ry cil­iary dysk­i­ne­sia (PCD) us­ing an mR­NA drug de­liv­ered by an LNP li­censed ear­li­er. While Re­Code is mov­ing for­ward with it, the team will al­so test oth­er can­di­dates us­ing the pro­pri­etary plat­form in par­al­lel. If the re­sults pan out, Re­Code will like­ly swap it out, Lock­hart said.

Not on­ly is the class of LNPs in­vent­ed by Sieg­wart — who stud­ied un­der MIT whiz Robert Langer — eas­i­er to make and ver­sa­tile in the pay­load they can car­ry, they can al­so be de­liv­ered sys­tem­at­i­cal­ly then dis­trib­uted to dif­fer­ent tis­sue types.

Philip Thomas

There are no ap­proved treat­ments for PCD, and as with CF be­fore Ver­tex’s ther­a­pies came along, pa­tients can die of res­pi­ra­to­ry fail­ure in their 30s or 40s even on the best sup­port­ive care. And sev­er­al ge­net­ic mu­ta­tions are known to cause the dis­ease.

“PCD alone is a pipeline that will be big­ger than the Gen­zyme pipeline that made Gen­zyme what it was,” Lock­hart said, cit­ing the rare dis­ease gi­ant that Am­i­cus was of­ten com­pared to.

In CF, Ver­tex has made dra­mat­ic break­throughs with its ar­se­nal of drugs tar­get­ing mu­tant CFTR pro­teins, cov­er­ing 90% of pa­tients. Re­Code’s goal is to catch the oth­er 10%: those with a non­sense mu­ta­tion that pre­vents a full length pro­tein from be­ing pro­duced in the first place. With the LNP tech, its ther­a­py ush­ers in a piece of trans­fer RNA — a bridge be­tween mes­sen­ger RNA and pro­tein syn­the­sis — to the pre­ma­ture stop codon and al­ters the cell ma­chin­ery, coax­ing it to make a func­tion­al ver­sion of CFTR.

PTC Ther­a­peu­tics has tak­en a sim­i­lar read-through ap­proach with its small mol­e­cule drug, but while ataluren has demon­strat­ed (con­tro­ver­sial) ef­fect in Duchenne mus­cu­lar dy­s­tro­phy, it failed in CF.

“They’re ac­tu­al­ly sort of sis­ter dis­eases in some ways,” he added. “The same doc­tors that treat PCD treat peo­ple with CF.”

Be­yond these ini­tial pro­grams, for which clin­i­cal tri­als are still ex­pect­ed in 2021, there’s plen­ty of room for li­cens­ing and col­lab­o­ra­tions. It was a key top­ic for the new board of di­rec­tors, now com­pris­ing Or­biMed’s Pe­ter Thomp­son, MPM’s Ed Hur­witz, Vi­da Ven­tures’ He­len Kim, R.A. Ses­sion from Bridge­Bio and Michael Tor­res, Re­Code founder and new VP of R&D.

“We had our first board meet­ing with the new board just on Fri­day,” Lock­hart said. “Every­one was in a room by them­selves talk­ing in­to a phone.”

At the In­flec­tion Point for the Next Gen­er­a­tion of Can­cer Im­munother­a­py

While oncology researchers have long pursued the potential of cellular immunotherapies for the treatment of cancer, it was unclear whether these therapies would ever reach patients due to the complexity of manufacturing and costs of development. Fortunately, the recent successful development and regulatory approval of chimeric antigen receptor-engineered T (CAR-T) cells have demonstrated the significant benefit of these therapies to patients.

Stéphane Bancel, Moderna CEO

'This is not go­ing to be good': Mod­er­na CEO Ban­cel warns of a 'ma­te­r­i­al drop' in vac­cine ef­fi­ca­cy as Omi­cron spreads

Even as public health officials remain guarded about their comments on the likelihood Omicron will escape the reach of the currently approved Covid-19 vaccines, there’s growing scientific consensus that we’re facing a variant that threatens to overwhelm the vaccine barricades that have been erected.

Stéphane Bancel, the CEO of Moderna, one of the leading mRNA players whose quick vault into the markets with a highly effective vaccine created an instant multibillion-dollar market, added his voice to the rising chorus early Tuesday. According to Bancel, there will be a significant drop in efficacy when the average immune system is confronted by Omicron. The only question now is: How much?

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Philip Dormitzer, new GSK global head of vaccines R&D

Glax­o­SmithK­line poach­es Pfiz­er's vi­ral vac­cines lead in rush to cap­i­tal­ize on fu­ture of mR­NA

GlaxoSmithKline has appointed Philip Dormitzer, formerly chief scientific officer of Pfizer’s viral vaccines unit, as its newest global head of vaccines R&D, looking to leverage one of the leading minds behind Pfizer and BioNTech’s RNA collaboration that led to Covid-19 jab Comirnaty, the British drug giant said Tuesday.

Dormitzer had been with Pfizer for a little more than six years, joining up after a seven-year stint with Novartis, where he reached the role of US head of research and head of global virology for the company’s vaccines and diagnostics unit.

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In­tro­duc­ing End­points Stu­dio, a new way to ad­ver­tise with End­points-craft­ed brand­ing cam­paigns

Since our start in 2016, Endpoints has grown fast while executing our mission to cover biopharma’s most critical developments for industry pros worldwide. As readership has grown, our advertising business has too. Endpoints advertising partners support the mission and engage their desired audiences through announcements on our email and web platforms, brand recognition in our event coverage and sponsorships of Endpoints daily and weekly reports.

With on­ly burns to show in gene ther­a­py, Astel­las inks deal with AAV spe­cial­ist Dyno in push for a bet­ter cap­sid

On the hunt for a better AAV capsid for gene therapy, Eric Kelsic’s Dyno Therapeutics has set itself apart with its focus on machine learning to help speed discovery. Now, Japanese drugmaker Astellas — fresh off a slate of gene therapy burns — is taking a bet on Dyno as it looks to the future.

Astellas and Dyno will work together as part of an R&D pact to develop next-gen AAV vectors for gene therapy using Dyno’s CapsidMap platform directed at skeletal and cardiac muscle, the companies said Wednesday. Under the terms of the deal, Dyno will design AAV capsids for gene therapy, while Astellas will be responsible for conducting preclinical, clinical and commercialization activities for gene therapy product candidates using the capsids.

As first Omi­cron case in US crops up, re­searchers won­der: which an­ti­bod­ies, vac­cines will hold up?

As Covid-19 drug and vaccine developers race to figure out which of their products might be hampered by the new variant, the CDC on Wednesday afternoon announced the first confirmed case of the Omicron variant (B.1.1.529) in the US, found in San Francisco.

The unidentified individual was a traveler who returned from South Africa on Nov. 22, 2021, was fully vaccinated, and had mild symptoms that the CDC described as improving. All close contacts have been contacted and have tested negative, the centers said.

Mod­er­na los­es lat­est bat­tle in key vac­cine de­liv­ery patent fight as fed­er­al ap­peal falls flat

The US Court of Appeals for the Federal Circuit on Wednesday rejected Moderna’s attempt to overturn key patents related to the delivery vehicle for its Covid-19 vaccine after the biotech sought to preempt a potentially risky infringement lawsuit.

For years, Moderna has been battling a tiny Pennsylvania biotech known as Arbutus over patents for a technology required to deliver its mRNA drugs and vaccines, known as lipid nanoparticles or LNP. Moderna is concerned there’s a substantial risk that Arbutus will assert the ’069 patent in an infringement suit targeting Moderna’s Covid-19 vaccine, particularly as Arbutus has boasted of its patent protection and refused to grant a covenant not to sue Moderna.

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Lan Huang, BeyondSpring CEO

Months af­ter shock­ing in­vestors with lung can­cer win, Be­yond­Spring's lead drug hits road­block at the FDA

BeyondSpring shocked investors in early August after its once-marginal lead drug suddenly showed a lot of promise in a common form of lung cancer. With hopes high, the FDA has now slammed the door on that drug in another indication — does that spell bad news for BeyondSpring’s Cinderella story?

The FDA issued BeyondSpring a complete response letter for its plinabulin in combination with granulocyte colony-stimulating factor (G-CSF) for the prevention of chemotherapy-induced neutropenia, effectively shutting down the drug’s immediate chances at a marketing approval, the biotech said Wednesday.

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What's fair? New ICER re­port shows pay­ers gen­er­al­ly en­sur­ing fair ac­cess to drugs

The nonprofit Institute for Clinical and Economic Review on Wednesday released a new report highlighting the ways in which payers are generally ensuring fair access to prescription drugs, even when based on a set of criteria set by the nonprofit.

While noting the lack of transparency hindered the report’s results, ICER said that the “great majority” of payer policies in the formularies evaluated are structured in a way to support many key elements of how ICER defines “fair access.”