Leslie Williams, hC Bioscience CEO

With a new start­up, ARCH and Take­da wade in­to grow­ing search for a Swiss Army knife RNA drug

ARCH and Take­da are step­ping — if not quite leap­ing — in­to one of the hottest new ar­eas in RNA drug de­vel­op­ment: tR­NA.

On Wednes­day the promi­nent VC firm and the Japan­ese phar­ma, along with tech-ori­ent­ed 8VC, an­nounced a $24 mil­lion in­vest­ment in hC Bio­science, a new start­up that will try to use this once-over­looked cor­ner of ge­net­ic ma­chin­ery to de­vel­op treat­ments for rare dis­eases and can­cer.

The promise of tR­NA, or trans­fer RNA, rests in its Swiss Army knife ver­sa­til­i­ty. Un­like with oth­er forms of ge­net­ic med­i­cine, such as mR­NA or gene ther­a­py, where each can­di­date has to be cus­tom cod­ed and de­signed for each new dis­ease or pa­tient pop­u­la­tion, a sin­gle tR­NA drug could in the­o­ry be used in­ter­change­ably across nu­mer­ous dis­or­ders.

For now, that’s most­ly spec­u­la­tive. No tR­NA drugs are in the clin­ic. But it’s fea­si­ble and po­ten­tial­ly im­pact­ful enough to at­tract a wave of in­ter­est from promi­nent firms. hC Bio­science joins All­tr­na, launched by Flag­ship in No­vem­ber with a $50 mil­lion Se­ries A, and Re­Code Ther­a­peu­tics, which has raised $160 mil­lion since 2020. Well-heeled RNA edit­ing out­fit Shape Ther­a­peu­tics al­so has tR­NA pro­grams and Zo­genix has teamed with a tiny start­up called Tevard Bio­sciences on tR­NAs for one rare form of epilep­sy.

hC Bio­science comes out of work from Christo­pher Ah­ern’s lab at the Uni­ver­si­ty of Iowa, the same group that li­censed tech to Tevard. In 2019, Ah­ern and post­doc John Lueck — now a co-founder and a pro­fes­sor at the Uni­ver­si­ty of Rochester — out­lined a method to iden­ti­fy hun­dreds of po­ten­tial­ly ther­a­peu­tic tR­NAs.

Christo­pher Ah­ern

It’s co-found­ed and led by Leslie Williams, a long­time biotech ex­ec­u­tive who last ran Im­mu­sanT, an ARCH-backed celi­ac dis­ease biotech that qui­et­ly van­ished af­ter a Phase II tri­al failed in 2019.

tR­NAs serve a spe­cif­ic func­tion in the cell. To pro­duce a pro­tein, DNA tran­scribes a gene in­to mR­NA and mR­NA car­ries the in­struc­tions to the ri­bo­some, a cell’s pro­tein-pro­duc­ing fac­tor. There, it hits a lan­guage bar­ri­er.

Both mR­NA and DNA are writ­ten in nu­cleotides. But pro­teins are made up of amino acids, an en­tire­ly dif­fer­ent class of chem­i­cal struc­tures.

tR­NA’s job is to trans­late be­tween the two. It folds in­to a spindly 3D struc­ture in the ri­bo­some. For every three let­ters of mR­NA (rough­ly), a strand of tR­NA reach­es and grabs the cor­re­spond­ing amino acid, build­ing up the pro­tein piece by piece.

hC Bio­science and the oth­er new star­tups hope to in­ter­vene in a key step where that trans­la­tion process can go awry. Not every three let­ters codes for an amino acid. Some of these triplets, al­so known as a codon, tell the ri­bo­some to start mak­ing the pro­tein in the first place, or to stop be­cause the pro­tein is com­plete.

A sig­nif­i­cant num­ber of ge­net­ic dis­or­ders — around 10% to 15% by some es­ti­mates, in­clud­ing forms of cys­tic fi­bro­sis and mus­cu­lar dy­s­tro­phy — oc­cur be­cause a ge­net­ic mu­ta­tion has put a “stop” codon in the wrong place. tR­NA doesn’t nat­u­ral­ly bind to stop codons. So when a stop codon ap­pears in the wrong place, the mi­ni-fac­to­ry may think its done and send the pro­tein off un­formed and in­ef­fec­tive.

Each new tR­NA com­pa­ny is en­gi­neer­ing tR­NA strands that can bind to the stop codon. Ide­al­ly, in a pa­tient, it would step in at that pro­duc­tion step, strap the right amino acid on and al­low the full-length and ful­ly func­tion­al pro­tein to be com­plet­ed.

And be­cause pa­tients with dif­fer­ent ge­net­ic dis­eases share the same stop codons — just place in dif­fer­ent genes and dif­fer­ent places in those genes — one drug could work for many dif­fer­ent con­di­tions.

Of course, a lot can go wrong too. The ther­a­peu­tic tR­NA could in the­o­ry dis­rupt the pro­duc­tion of oth­er pro­teins in a pa­tient, plac­ing an amino acid where a stop codon re­al­ly did be­long. And there’s the biggest ques­tion with every ge­net­ic med­i­cine: How do you de­liv­er it? En­gi­neered virus­es called AAVs and the lipid nanopar­ti­cles com­mon­ly used to de­liv­er mR­NA are the two clear op­tions, but both come with draw­backs.

And there are al­ready signs that, in some dis­or­ders, oth­er tech­nolo­gies may have ad­van­tages. Re­Code launched with both mR­NA-based and tR­NA-based ther­a­pies for cys­tic fi­bro­sis, but it said in the fall it will pri­or­i­tize the mR­NA ap­proach af­ter find­ing bet­ter re­sults.

Has the mo­ment fi­nal­ly ar­rived for val­ue-based health­care?

RBC Capital Markets’ Healthcare Technology Analyst, Sean Dodge, spotlights a new breed of tech-enabled providers who are rapidly transforming the way clinicians deliver healthcare, and explores the key question: can this accelerating revolution overturn the US healthcare system?

Key points

Tech-enabled healthcare providers are poised to help the US transition to value, not volume, as the basis for reward.
The move to value-based care has policy momentum, but is risky and complex for clinicians.
Outsourced tech specialists are emerging to provide the required expertise, while healthcare and tech are also converging through M&A.
Value-based care remains in its early stages, but the transition is accelerating and represents a huge addressable market.

Lat­est on ul­tra-rare dis­ease ap­proval; Pos­i­tive, if mixed, signs for Bio­gen's ALS drug; Clay Sie­gall finds a new job; 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.

Over the last four years, we’ve honored 80 women whose extraordinary accomplishments have changed the game in biopharma R&D. You can now nominate someone to be highlighted in this year’s special report. Details are here.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 163,600+ biopharma pros reading Endpoints daily — and it's free.

FDA spells out how can­cer drug de­vel­op­ers can use one tri­al for both ac­cel­er­at­ed and full ap­provals

The FDA’s Oncology Center of Excellence has been a bright spot within the agency in terms of speeding new treatments to patients. That flexibility was on full display this morning as FDA released new draft guidance spelling out exactly how oncology drug developers can fulfill both the accelerated and full approval’s requirements with just a single randomized controlled trial.

While Congress recently passed legislation that will allow FDA to require confirmatory trials to be recruiting and ongoing prior to granting an accelerated approval, the agency is now making clear that the initial trial used to win the AA, if designed appropriately, can also serve as the trial for converting the accelerated approval into a full approval.

Clay Siegall, Morphimmune CEO

Up­dat­ed: Ex-Seagen chief Clay Sie­gall emerges as CEO of pri­vate biotech

Clay Siegall will be back in the CEO seat, taking the helm of a private startup working on targeted cancer therapies.

It’s been almost a year since Siegall resigned from Seagen, the biotech he co-founded and led for more than 20 years, in the wake of domestic violence allegations by his then-wife. His eventual successor, David Epstein, sold the company to Pfizer in a $43 billion deal unveiled last week.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 163,600+ biopharma pros reading Endpoints daily — and it's free.

FDA ad­vi­sors unan­i­mous­ly rec­om­mend ac­cel­er­at­ed ap­proval for Bio­gen's ALS drug

A panel of outside advisors to the FDA unanimously recommended that the agency grant accelerated approval to Biogen’s ALS drug tofersen despite the drug failing the primary goal of its Phase III study, an endorsement that could pave a path forward for the treatment.

By a 9-0 vote, members of the Peripheral and Central Nervous System Drugs Advisory Committee said there was sufficient evidence that tofersen’s effect on a certain protein associated with ALS is reasonably likely to predict a benefit for patients. But panelists stopped short of advocating for a full approval, voting 3-5 against (with one abstention) and largely citing the failed pivotal study.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 163,600+ biopharma pros reading Endpoints daily — and it's free.

No­vo Nordisk oral semaglu­tide tri­al shows re­duc­tion in blood sug­ar, plus weight loss

Novo Nordisk is testing higher levels of its oral version of its GLP-1, semaglutide, and its type 2 diabetes trial results released today show reductions in blood sugar as well as weight loss.

In the Phase IIIb trial, Novo compared its oral semaglutide in 25 mg and 50 mg doses with the 14 mg version that’s currently the maximum approved dose. The trial looked at how the doses compared when added to a stable dose of one to three oral antidiabetic medicines in people with type 2 diabetes who were in need of an intensified treatment.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 163,600+ biopharma pros reading Endpoints daily — and it's free.

Ly­me vac­cine test com­ple­tion is pushed back by a year as Pfiz­er, Val­ne­va say they'll ad­just tri­al

Valneva and Pfizer have adjusted the end date for the Phase III study of their investigational Lyme disease vaccine, pushing it back by a year after issues at a contract researcher led to thousands of US patients being dropped from the test.

In a March 20 update to clinicaltrials.gov, Valneva and Pfizer moved the primary completion date on the trial, called VALOR, from the end of 2024 to the end of 2025.

Endpoints Premium

Premium subscription required

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

Stuart Peltz, former PTC Therapeutics CEO

Stu­art Peltz re­signs as PTC Ther­a­peu­tics CEO af­ter 25 years

Stuart Peltz, the longtime CEO of PTC Therapeutics who’s led the rare disease drug developer since its founding 25 years ago, is stepping down.

Succeeding him in the top job is Matthew Klein, who joined PTC in 2019 and was promoted to chief operating officer in 2022. In a call with analysts, he said the CEO transition has been planned for “quite some time” — in fact, as part of it, he gave the company’s presentation at the JP Morgan healthcare conference earlier this year.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 163,600+ biopharma pros reading Endpoints daily — and it's free.

Bet­ter Ther­a­peu­tics cuts 35% of staff while await­ing dig­i­tal ther­a­peu­tic ap­proval

Digital therapeutics company Better Therapeutics announced on Thursday that it’s cutting 35% of its staff as it awaits FDA clearance for its first product.

The company, which launched eight years ago, is one of a growing group of companies seeking a digital alternative to traditional medicine. The space saw a record $7.5 billion in investments in 2021, according to Chris Dokomajilar at DealForma, with uses spanning ADHD, PTSD and other indications. However, private insurers have been slow to hop on board.