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.

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.

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.