Sarah Cole, Takeda Ventures partner

Al­most a decade af­ter iden­ti­fy­ing a new class of RNA, a group of sci­en­tists sparks in­ter­est from Take­da Ven­tures

Over the last sev­er­al years, sci­en­tists have turned their at­ten­tion to long non­cod­ing RNAs (lncR­NAs) — a mys­te­ri­ous class of nat­u­ral­ly oc­cur­ring mol­e­cules that don’t code for pro­teins, but ful­fill im­por­tant reg­u­la­to­ry func­tions in the cell. Ste­fano Gustin­ci­ch and his team iden­ti­fied a new class of them back in 2012, and now the sci­en­tists have pulled in seed fund­ing to see if the mol­e­cules can go where cur­rent ther­a­peu­tics can’t.

Ste­fano Gustin­ci­ch

Gustin­ci­ch, a pro­fes­sor at the Is­ti­tu­to Ital­iano di Tec­nolo­gia in Genoa, Italy, helped iden­ti­fy what he calls SINE­UPs: a type of lncR­NA that has the abil­i­ty to specif­i­cal­ly el­e­vate pro­tein trans­la­tion. His lab pub­lished a pa­per on the mol­e­cules in Na­ture back in 2012, in which they said the da­ta re­vealed “an­oth­er lay­er of gene ex­pres­sion con­trol at the post-tran­scrip­tion­al lev­el.”

Since then, Gustin­ci­ch has been in close col­lab­o­ra­tion with Piero Carn­in­ci and his team at the Riken Cen­ter for In­te­gra­tive Med­ical Sci­ences in Yoko­hama, Japan. The sci­en­tists be­lieve their dis­cov­ery can lead to high-speci­fici­ty ther­a­peu­tics for any tar­get in which mR­NA is present, which even­tu­al­ly piqued the in­ter­est of Take­da Ven­tures part­ner Sarah Cole. On Wednes­day, they un­veiled a $12.8 mil­lion (£9.1 mil­lion) seed round to launch Tran­sine Ther­a­peu­tics.

“The SINE­UP gives the abil­i­ty to tar­get a nat­u­ral­ly ex­pressed mol­e­cule in the cell, and in a very sen­si­tive way boosts the ex­pres­sion of that par­tic­u­lar tar­get,” said Cole, who’s now VP of R&D.

SINE­UPs have two main com­po­nents, Cole said. First, you’ve got a bind­ing do­main that binds to mR­NA. To in­crease ex­pres­sion, the mol­e­cule needs the ac­tiv­i­ty of an em­bed­ded in­vert­ed SINEB2 se­quence — hence the name.

“What’s par­tic­u­lar­ly in­ter­est­ing about the SINE­UP tech­nol­o­gy is the fact that it boosts pro­tein trans­la­tion in the cell,” she said. “But where­as oth­er tech­niques and oth­er ther­a­peu­tic av­enues such as pro­tein re­place­ment ther­a­py or gene ther­a­py may well lead the cell to over­ex­press a lot of your tar­get pro­tein, which can be prob­lem­at­ic, SINE­UPs are ac­tu­al­ly ex­ert­ing a mod­est ef­fect on pro­tein trans­la­tion.”

Cole says SINE­UPs can es­sen­tial­ly re­store pro­tein ex­pres­sion back to nor­mal lev­els, get­ting at the “root cause” of ge­net­ic dis­eases caused by such de­fi­cien­cies. Tran­sine al­so be­lieves SINE­UPs could be used to mod­u­late pro­teins that have reg­u­la­to­ry ef­fects. And be­cause they’re small in size, SINE­UPs can be de­liv­ered in a va­ri­ety of dif­fer­ent ways — in­clud­ing as naked oligonu­cleotides, or via vi­ral vec­tors.

“If you’ve got a sig­nif­i­cant neu­rode­gen­er­a­tive dis­ease, we would ac­tu­al­ly be able to al­so of­fer a ther­a­py that could ac­tu­al­ly tar­get a reg­u­la­to­ry pro­tein that could have a very strong im­pact on cell health,” Cole said.

To start, Tran­sine is ze­ro­ing in on CNS dis­eases and oph­thal­mol­o­gy. While Cole said she couldn’t share which spe­cif­ic in­di­ca­tions the com­pa­ny will pur­sue first, the com­pa­ny’s oth­er ma­jor in­vestor of­fers a big hint: the De­men­tia Dis­cov­ery Fund.

“Long non-cod­ing RNAs are emerg­ing as key cel­lu­lar reg­u­la­tors which could be ex­ploit­ed as new ther­a­peu­tic ap­proach­es for mul­ti­ple in­di­ca­tions,” Gustin­ci­ch said in a state­ment. “Tran­sine SINE­UPs be­long to this fam­i­ly and can be en­gi­neered to tar­get al­most any pro­tein with ex­quis­ite speci­fici­ty.”

The com­pa­ny is in the process of on­board­ing a CEO, who will for­mal­ly join in Ju­ly.

Un­pack­ing the Aduhelm de­ci­sion, Ver­tex's half full glass, a $525M J&J breakup, 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.

By now you have surely read about the FDA’s controversial approval of Biogen’s Alzheimer’s drug and all its reverberations. But I’d still recommend checking out the meaty recap below to make sure you didn’t miss all the angles that the Endpoints team has covered. If you’d rather look ahead, look no further than our three-day virtual panels next week at BIO, where we will discuss what the new normal means for every part of the industry.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 109,100+ biopharma pros reading Endpoints daily — and it's free.

What does a clear ma­jor­i­ty of the bio­phar­ma in­dus­try think of the FDA ap­proval of ad­u­canum­ab? 'Hor­ri­fy­ing' 'Dan­ger­ous' 'Con­fus­ing' 'Dis­as­ter'

Over the years, we’ve become used to seeing a consensus emerge early in our industry polls at Endpoints News. And when we took the pulse of drug hunters on the heels of a controversial FDA approval for aducanumab this week, it became immediately apparent that the vast majority of our readers — heavily concentrated among biopharma staffers and execs — were incensed by what they had just witnessed.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 109,100+ biopharma pros reading Endpoints daily — and it's free.

Aaron Kesselheim (Scott Eisen/AP Images for AIDS Healthcare Foundation)

Har­vard’s Aaron Kessel­heim re­signs from ex­pert pan­el in wake of ad­u­canum­ab OK, blast­ing FDA for ‘worst drug ap­proval de­ci­sion in re­cent U.S. his­to­ry'

A third member of the FDA’s Peripheral and Central Nervous System Drugs Advisory Committee has resigned in the wake of Biogen’s controversial Aduhelm approval, slamming the agency as he left and further deepening the controversy surrounding the decision.

Harvard University professor Aaron Kesselheim quit in protest Thursday afternoon, calling the Aduhelm OK “probably the worst drug approval decision in recent U.S. history.” Kesselheim follows both Joel Perlmutter, a neurologist from Washington University in St. Louis, and David Knopman, a neurologist from the Mayo Clinic, out the door.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 109,100+ biopharma pros reading Endpoints daily — and it's free.

David Knopman (Mayo Clinic via YouTube)

A sec­ond ad­comm mem­ber aban­dons his post in af­ter­math of con­tro­ver­sial ad­u­canum­ab de­ci­sion

As the fallout from the FDA’s approval of Alzheimer’s med aducanumab grows, a second member of the adcomm overseeing that drug’s review has walked away. But even with two experts now having resigned from that committee in protest, is there enough broad-level outrage to prevent another aducanumab from getting approved?

The FDA on Wednesday lost another member of its Peripheral and Central Nervous System Drugs Advisory Committee as Mayo Clinic neurologist David Knopman hit the exit over the agency’s decision to approve Biogen’s Alzheimer’s drug Aduhelm despite the committee’s near-unanimous vote against it.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 109,100+ biopharma pros reading Endpoints daily — and it's free.

FDA au­tho­rizes about 10M J&J vac­cine dos­es, trash­es 60M more from trou­bled Emer­gent plant

The FDA on Friday released about 10 million doses of J&J’s vaccine for use, and disposed of another 60 million doses that were manufactured at the now-shuttered Emergent BioSolutions facility in Baltimore where cross-contamination occurred.

The agency said it’s not yet ready to allow the Emergent plant to be included in the J&J EUA, but that may occur soon. FDA came to the decision to authorize some of the doses after reviewing facility records and quality testing results.

The IPO 4-1-1: Four fil­ings, a pric­ing and a with­draw­al head­line this week's Nas­daq ac­tion as raise ap­proach­es $7.5B

Editor’s note: Interested in following biopharma’s fast-paced IPO market? You can bookmark our IPO Tracker here.

Another week, another horde of biotechs is doing the Nasdaq dance.

This week saw four companies file their SEC paperwork ahead of expected debuts, another hit Nasdaq on Friday and a sixth formally withdrew its bid to go public. Aerovate Therapeutics, Ocean Biomedical and Acumen Pharmaceuticals all penciled in initial raises of $100 million, while Dermata Therapeutics is estimating a modest $18 million raise.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 109,100+ biopharma pros reading Endpoints daily — and it's free.

Keiichi Fukuda, Heartseed CEO

Fresh off $598M deal with No­vo Nordisk, a Japan­ese stem cell com­pa­ny is on its way to the clin­ic with a dif­fer­ent ap­proach to treat­ing heart fail­ure

A common approach to treating heart failure with induced pluripotent stem cells involves grafting sheets of cells onto the surface of the heart to improve vascularization and blood flow. It’s the easiest method of transplantation — but you run the risk of not making an electrical connection with the heart and the cells not synchronizing with the patient’s heart muscle.

So what if you could inject spherical clusters of heart cells directly into the heart muscle wall? For Heartseed, that’s now the $37 million question.

Janet Woodcock, acting FDA commissioner, at Thursday's Senate Appropriations hearing (Bill Clark/CQ Roll Call via AP Images)

Sen­a­tors lam­bast new Alzheimer’s drug’s price but give Janet Wood­cock a free pass on the ap­proval de­ci­sion

Senate Finance Democrats took aim at Biogen’s pricey new Alzheimer’s drug on Thursday, but members on both sides of the aisle at a separate appropriations hearing didn’t question acting FDA commissioner Janet Woodcock on the approval.

“I was appalled that Biogen priced their Alzheimer’s drug approved by the FDA at $56,000 per year — I’m not going to debate whether this is effective or not, but it’s double the household median income for Michiganders over the age of 65,” Sen. Debbie Stabenow (D-MI) said at the finance hearing.

Reshma Kewalramani, Vertex CEO (BIO via YouTube)

UP­DAT­ED: Ver­tex strikes out on its lat­est big shot at a rare ge­net­ic dis­ease. But they're go­ing to keep on swing­ing

It’s been several months since Vertex culled one of its small molecules for alpha-1 antitrypsin deficiency (AATD), taking a big hit after evidence of liver damage surfaced in a key Phase II trial. Now we learned that the company has whiffed on its second shot, and there’s nothing left in the clinic to treat the rare genetic disease — but that won’t stop it from trying.

Despite avoiding the safety issues that plagued the last candidate, Vertex $VRTX is taking the axe to VX-864 after Phase II results revealed the magnitude of the drug’s response is “unlikely to translate into substantial clinical benefit.” As a result of the news, the company’s stock fell 12.5% after hours.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 109,100+ biopharma pros reading Endpoints daily — and it's free.