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.

How pre­pared is bio­phar­ma for the cy­ber dooms­day?

One of the largest cyberattacks in history happened on a Friday, Eric Perakslis distinctly remembers.

Perakslis, who was head of Takeda’s R&D Data Sciences Institute and visiting faculty at Harvard Medical School at the time, had spent that morning completing a review on cybersecurity for the British Medical Journal. Moments after he turned it in, he heard back from the editor: “Have you heard what’s going on right now?”

Endpoints Premium

Premium subscription required

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

Pearl Huang, Dunad Therapeutics CEO (Ken Richardson, PR Newswire)

Long­time biotech leader Pearl Huang takes the reins as CEO of No­var­tis-backed up­start

It has only been a few months since Pearl Huang exited the top seat at Cygnal Therapeutics, but now she’s back at the helm of another biotech.

After taking a few months off — passing an exam in that time to get her captain’s license from the US Coast Guard — she’s been named CEO of Dunad Therapeutics, a biotech focused on developing a small molecule covalent therapies that was founded in 2020. Huang told Endpoints News that two factors attracted her to going back to the c-suite: the company’s technology and its co-founders.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 144,400+ biopharma pros reading Endpoints daily — and it's free.

Scoop: Boehringer qui­et­ly shut­ters a PhII for one of its top drugs — now un­der re­view

Boehringer Ingelheim has quietly shut down a small Phase II study for one of its lead drugs.

The private pharma player confirmed to Endpoints News that it had shuttered a study testing spesolimab as a therapy for Crohn’s patients suffering from bowel obstructions.

A spokesperson for the company tells Endpoints:

Taking into consideration the current therapeutic landscape and ongoing clinical development programs, Boehringer Ingelheim decided to discontinue our program in Crohn’s disease. It is important to note that this decision is not based on any safety findings in the clinical trials.

Endpoints Premium

Premium subscription required

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

Ben Zimmer, Priovant CEO

Roivant un­veils lat­est spin­out as Pfiz­er en­trusts JAK1/TYK2 to Pri­o­vant

In November, Pfizer disclosed it’s spun out the Phase II dual JAK1/TYK2 inhibitor to a startup formed in collaboration with an unnamed, experienced partner.

We now know who the partner is. And as Pfizer and Roivant officially take the wraps off Priovant Therapeutics, the companies reveal that they have started two registrational trials of the drug, brepocitinib, as part of a broader plan to develop a big, first-in-class franchise spanning multiple orphan and specialty autoimmune diseases.

Matt Gline, Roivant CEO (John Sciulli/Getty Images for GLG)

Roivant chops sick­le cell gene ther­a­py, der­ma­tol­ogy drugs to fo­cus on 'high­er val­ue pro­ject­s'

Roivant is sweeping a suite of drugs, including a gene therapy for sickle cell disease already in the clinic, out of its pipeline.

Six programs from four of its “vants” are being wound down as part of “a company-wide cost optimization and pipeline reprioritization initiative to reduce our expected operating expenses and prioritize our capital resources.”

When reached by Endpoints News, a spokesperson said, “We don’t anticipate a material reduction in headcount but we will likely reassign some folks to higher value projects as part of winding down specific programs.”

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 144,400+ biopharma pros reading Endpoints daily — and it's free.

Laurence Reid, Decibel CEO

Still in pre­clin­i­cal test­ing for ear gene ther­a­pies, Deci­bel touts small snap­shot of chemo-in­duced hear­ing loss drug

Though Decibel Therapeutics has largely pivoted toward gene therapies for the inner ear, its lead clinical candidate simply aims to protect cancer patients from chemotherapy-induced hearing loss. On Tuesday, the biotech presented its first efficacy data for the program, and execs like what they see.

Decibel reported interim results from a Phase Ib study showing the experimental drug, dubbed DB-020, largely protected a small group of patients from losing their hearing. Researchers used a particularly unique study design, administering the compound in one of each patients’ ears before they received cisplatin chemotherapy and placebo in the other.

Alex­ion puts €65M for­ward to strength­en its po­si­tion on the Emer­ald Isle

Ireland has been on a roll in 2022, with several large pharma companies announcing multimillion-euro projects. Now AstraZeneca’s rare disease outfit Alexion is looking to get in on the action.

Alexion on Friday announced a €65 million ($68.8 million) investment in new and enhanced capabilities across two sites in the country, including at College Park in the Dublin suburb of Blanchardstown and the Monksland Industrial Park in the central Irish town of Athlone, according to the Industrial Development Agency of Ireland.

Members of the G7 from left to right: Prime Minister of Italy Mario Draghi, European Commission President Ursula von der Leyen, President Joe Biden, German Chancellor Olaf Scholz, British Prime Minister Boris Johnson, Canadian Prime Minister Justin Trudeau, Prime Minister of Japan Fumio Kishida, French President Emmanuel Macron and European Council President Charles Michel (AP Photo/Susan Walsh)

Biden and G7 na­tions of­fer funds for vac­cine and med­ical prod­uct man­u­fac­tur­ing project in Sene­gal

Amidst recently broader vaccine manufacturing initiatives from the EU and European companies, the G7 summit in the mountains of Bavaria has brought about some positive news for closing vaccine and medical product manufacturing gaps around the globe.

According to a statement from the White House, the G7 leaders have formally launched the partnership for global infrastructure, PGII. The effort will aim to mobilize hundreds of billions of dollars to deliver infrastructure projects in several sectors including the medical and pharmaceutical manufacturing space.

State bat­tles over mifepri­s­tone ac­cess could tie the FDA to any post-Roe cross­roads

As more than a dozen states are now readying so-called “trigger” laws to kick into effect immediate abortion bans following the overturning of Roe v. Wade on Friday, these laws, in the works for more than a decade in some states, will likely kick off even more legal battles as states seek to restrict the use of prescription drug-based abortions.

Since Friday’s SCOTUS opinion to overturn Americans’ constitutional right to an abortion after almost 50 years, reproductive rights lawyers at Planned Parenthood and other organizations have already challenged these trigger laws in Utah and Louisiana. According to the Guttmacher Institute, other states with trigger laws that could take effect include Arkansas, Idaho, Kentucky, Mississippi, Missouri, North Dakota, Oklahoma, South Dakota, Tennessee, Texas, and Wyoming.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 144,400+ biopharma pros reading Endpoints daily — and it's free.