Samir Ounzain, Haya CEO

A new RNA start­up looks to reimag­ine heart treat­ments, with eyes set on En­tresto

When Samir Oun­z­ian left Lon­don a decade ago to study a lit­tle-un­der­stood branch of the genome at a Swiss lab, he wasn’t sure what he would find. Known as long-non-cod­ing RNA, these sec­tions were trans­lat­ed in­to loop­ing rings of RNA — hence the name — but didn’t ac­tu­al­ly trans­late in­to pro­teins, and no one was quite sure how many there were or pre­cise­ly what they were do­ing.

“We didn’t ex­pect any­thing at the time,” Oun­z­ian told End­points News, “be­cause we didn’t re­al­ly un­der­stand how fre­quent they were in the genome.”

Over the years, though, Oun­zain and his col­lab­o­ra­tors found these strands ex­pressed every­where, in­clud­ing in one area they found par­tic­u­lar­ly promis­ing: the heart. In 2017, they showed in Sci­ence Trans­la­tion Med­i­cine that one such loop, called Wis­per, con­trols fi­bro­sis — scar­ring — in the heart af­ter in­jury, and set about find­ing a way to drug it.

On Tues­day, the com­pa­ny Oun­zain built around the ap­proach, Haya Ther­a­peu­tics, an­nounced $20 mil­lion in seed fund­ing led by Broad­view Ven­tures, a car­dio­vas­cu­lar-fo­cused VC. They’ll use the pro­ceeds to try to push an an­ti­sense ther­a­py to neu­tral­ize Wis­per strands in­to the clin­ic in 2 to 3 years, while al­so iden­ti­fy­ing oth­er long-cod­ing RNAs to drug through­out the body.

Long-non-cod­ing RNAs are im­por­tant, re­searchers now be­lieve, in part be­cause they gov­ern how the same genes are ex­pressed in dif­fer­ent tis­sues, in­clud­ing how those genes re­spond to the en­vi­ron­ment. In the heart, Wis­per turns on fi­bro­sis in re­sponse to some type of trig­ger. Evo­lu­tion­ary, that was like­ly an ad­van­tage, help­ing pro­tect the tis­sue from in­jury, Oun­zain said. But now peo­ple are ex­posed to all sorts of dam­age — di­a­betes, high blood pres­sure, clogged ar­ter­ies — that fi­bro­sis on­ly wors­ens.

“These new stress­es of our species make the heart think it’s con­stant­ly stressed, and then the fi­bro­sis just con­tin­ues over time,” he said.

Al­though a se­ries of heart fail­ure drugs have hit the mar­ket over the last decade, most no­tably No­var­tis’s En­tresto and Mer­ck’s Verqu­vo, but none di­rect­ly treat fi­bro­sis. By shut­ting down Wis­per, Oun­zain be­lieves they can not on­ly stop fi­bro­sis but re­verse ex­ist­ing dam­age; scar tis­sue in the heart turns over quick­ly, he said, so if you stop the scar­ring process, even­tu­al­ly the tis­sue will re­store it­self.

They plan to first test the ther­a­py in a rare form of heart fail­ure called non-ob­struc­tive hy­per­trophic car­diomy­opa­thy, where fi­bro­sis lev­els are linked to symp­tom sever­i­ty. If they get proof-of-con­cept there, they’ll move to heart fail­ure with pre­served ejec­tion frac­tion — a com­mon con­di­tion in­volv­ing scar­ring in the heart and where there are so few op­tions, the FDA ap­proved En­tresto for it, de­spite a failed piv­otal tri­al.

Oun­zain, though, doesn’t want Haya thought of as a heart com­pa­ny. They can do much more go­ing af­ter long-cod­ing RNAs, he said.

“We be­lieve this par­a­digm is more than the heart,” he said. “And we ac­tu­al­ly think it could be a very pow­er­ful par­a­digm for the fu­ture of an­ti-fi­brot­ic drug de­vel­op­ment.”

In­side Track: Be­hind the Scenes of a Ma­jor Biotech SPAC

Dr. David Hung and Michelle Doig are no strangers to the SPAC phenomenon. As Founder and CEO of Nuvation Bio, a biotech company tackling some of the greatest unmet needs in oncology, Dr. Hung recently took the company public in one of this year’s biggest SPAC related deals. And as Partner at Omega Funds, Doig not only led and syndicated Nuvation Bio’s Series A, but is now also President of the newly formed, Omega-sponsored, Omega Alpha SPAC (Nasdaq: OMEG; oversubscribed $138m IPO priced January 6, 2021).

Aus­tralian spin­out eyes the clin­ic with a pro­phy­lac­tic nasal spray for Covid-19

Whether patients are immunocompromised or just don’t like needles, one fledgling Australian biotech says it has an alternative to Covid-19 vaccines that doesn’t involve a jab in the arm — and on Tuesday, it pulled in a fresh round of funding to take it into the clinic.

ENA Respiratory, which spun out of ENA Therapeutics last year, has pulled in nearly $24.7 million (AU $30 million) to advance its nasal spray for respiratory viral infections, the company said Tuesday.

Someit Sidhu, JATT

An­oth­er life sci­ences SPAC has popped up from a small biotech CEO with the help of Take­da, No­var­tis vet­er­ans

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

The SPAC train has slowed down since the extraordinarily high levels from late 2020 into early this year, but Tuesday saw the filing of a new blank-check company targeting the life sciences industry.

Jatt Acquisition submitted its SEC paperwork Tuesday, penciling in an estimated raise of $120 million as it sets its sights on a reverse merger partner. The SPAC is run by Someit Sidhu, a co-founder of Pathios Therapeutics, as well as CEO of Akaza Bioscience and Izana Bioscience. Sidhu will control about 97% of the blank-check company’s shares, per the S-1.

Janet Woodcock, acting FDA commissioner (Al Drago/Bloomberg via Getty Images)

New Alzheimer's drug ap­proval fall­out: Pub­lic Cit­i­zen seeks re­moval of FDA's Wood­cock, Cavaz­zoni and Dunn

As Capitol Hill begins to wake up to the financial and scientific mess behind the FDA’s approval of Biogen’s new controversial Alzheimer’s drug Aduhelm, nonprofit watchdog Public Citizen is now calling for the top three FDA officials who are responsible to be removed from their positions.

In a letter to HHS Secretary Xavier Becerra on Wednesday, the group highlighted the “litany of flaws” in the FDA’s approval of the new drug, including the “unprecedented, inappropriately close” collaboration between the FDA and Biogen in the analysis of key trial data, basing approval on an unvalidated surrogate endpoint, not following the advice of its expert advisory committee (3 members of which have since resigned), and the wide label that the agency granted.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 109,500+ biopharma pros reading Endpoints daily — and it's free.

CEO Harith Rajagopalan (Fractyl)

Af­ter a decade in the type 2 di­a­betes game, Fractyl Lab­o­ra­to­ries recharges with a fresh $100M and a new name

Harith Rajagopalan compared the way type 2 diabetes is managed to sticking your fingers in a dam that’s leaking from a number of places.

You can take drugs to lower your blood sugar, cholesterol, or blood pressure, but you’re not addressing what he says is the core issue — the metabolic abnormality that causes the disease.

“We’re so busy plugging the holes in the dam, we don’t have time to see that the whole infrastructure is at risk,” he said. “That infrastructure is a full-body systemic metabolic abnormality called metabolic syndrome, that we’re ignoring while we’re so busy trying to treat all of the individual symptoms of the condition.”

Michel Sade­lain puts his name and new cell en­gi­neer­ing tech be­hind 'ag­nos­tic' CAR-T start­up chas­ing epi­ge­net­ic anti­gens

It felt natural for Alain Maiore and Sebastian Amigorena to bring in Michel Sadelain as a co-founder of Mnemo Therapeutics. A CAR-T pioneer, Sadelain had been involved as an advisor since the early days — enthusiastic about Amigorena’s work in a genetic knockout that could enhance T cell memory and a new class of potential targets he’s discovered — and could introduce some well-known technologies to the toolbox. So they got the initial cash from Sofinnova Partners to plant roots in Paris and New York in early 2019; within a few months, they began to see more clearly just what the antigen discovery platform might unlock.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 109,500+ biopharma pros reading Endpoints daily — and it's free.

In a first, Re­gen­eron's an­ti­body cock­tail re­duces deaths for a sub­group of hos­pi­tal­ized Covid-19 pa­tients

Scientists have come up with the first evidence that Regeneron’s antibody cocktail, which has so far only been authorized for the outpatient setting, may reduce deaths of hospitalized Covid-19 patients — albeit only a subset.

The combination of casirivimab and imdevimab is the subject of the latest data cut from RECOVERY, the large-scale UK-based trial testing a variety of potential treatments. In total, 9,785 patients hospitalized with Covid-19 were enrolled in this arm of the study and were randomly assigned to receive either usual care plus the intravenous combo or usual care alone.

Barry Greene, Sage CEO

UP­DAT­ED: Sage's sec­ond chance at de­pres­sion hits the PhI­II pri­ma­ry, but ques­tions re­main over dura­bil­i­ty, side ef­fects

Looking to make a comeback after a big Phase III flop, Sage Therapeutics revealed data they believe could change the entire depression treatment landscape, given the vast array of failures in the field. But some results are spooking investors, sending Sage $SAGE shares down early Tuesday.

First, the primary: Sage and Biogen reported Phase III data for once-daily zuranolone Tuesday morning, saying the experimental drug hit its primary endpoint by spurring a statistically significant change from baseline in the 17-item Hamilton Rating Scale for Depression total score. After 15 days, patients in the drug arm saw an average change of -14.1 points, compared to -12.3 on placebo.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 109,500+ biopharma pros reading Endpoints daily — and it's free.

Bio­gen sig­nals a big PhI­II fail­ure as the lead gene ther­a­py in their $800M Night­star buy­out goes down in flames

That $800 million buyout of Nightstar has turned into a bust for Biogen as the lead therapy in the deal failed a pivotal study, signaling a severe setback for the biotech’s ambitions in gene therapies.

The big biotech put out the word after the market closed on Monday that the gene therapy they picked up in the deal for a degenerative blindness called choroideremia failed the Phase III study, just a month after their #2 drug in the deal also flopped in a mid-stage study.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 109,500+ biopharma pros reading Endpoints daily — and it's free.