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.”

Health­care Dis­par­i­ties and Sick­le Cell Dis­ease

In the complicated U.S. healthcare system, navigating a serious illness such as cancer or heart disease can be remarkably challenging for patients and caregivers. When that illness is classified as a rare disease, those challenges can become even more acute. And when that rare disease occurs in a population that experiences health disparities, such as people with sickle cell disease (SCD) who are primarily Black and Latino, challenges can become almost insurmountable.

Jacob Van Naarden (Eli Lilly)

Ex­clu­sives: Eli Lil­ly out to crash the megablock­buster PD-(L)1 par­ty with 'dis­rup­tive' pric­ing; re­veals can­cer biotech buy­out

It’s taken 7 years, but Eli Lilly is promising to finally start hammering the small and affluent PD-(L)1 club with a “disruptive” pricing strategy for their checkpoint therapy allied with China’s Innovent.

Lilly in-licensed global rights to sintilimab a year ago, building on the China alliance they have with Innovent. That cost the pharma giant $200 million in cash upfront, which they plan to capitalize on now with a long-awaited plan to bust up the high-price market in lung cancer and other cancers that have created a market worth tens of billions of dollars.

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David Meek, new Mirati CEO (Marlene Awaad/Bloomberg via Getty Images)

Fresh off Fer­Gene's melt­down, David Meek takes over at Mi­rati with lead KRAS drug rac­ing to an ap­proval

In the insular world of biotech, a spectacular failure can sometimes stay on any executive’s record for a long time. But for David Meek, the man at the helm of FerGene’s recent implosion, two questionable exits made way for what could be an excellent rebound.

Meek, most recently FerGene’s CEO and a past head at Ipsen, has become CEO at Mirati Therapeutics, taking the reins from founding CEO Charles Baum, who will step over into the role of president and head of R&D, according to a release.

Rafaèle Tordjman (Jeito Capital)

Con­ti­nu­ity and di­ver­si­ty: Rafaèle Tord­j­man's women-led VC firm tops out first fund at $630M

For a first-time fund, Jeito Capital talks a lot about continuity.

Rafaèle Tordjman had spotlighted that concept ever since she started building the firm in 2018, promising to go the extra mile(s) with biotech entrepreneurs while pushing them to reach patients faster.

Coincidentally, the lack of continuity was one of the sore spots listed in a report about the European healthcare sector published that same year by the European Investment Bank — whose fund is one of the LPs, alongside the American pension fund Teacher Retirement System of Texas and Singapore’s Temasek, to help Jeito close its first fund at $630 million (€534 million). As previously reported, Sanofi had chimed in €50 million, marking its first investment in a French life sciences fund.

FDA hands ac­cel­er­at­ed nod to Seagen, Gen­mab's so­lo ADC in cer­vi­cal can­cer, but com­bo stud­ies look even more promis­ing

Biopharma’s resident antibody-drug conjugate expert Seagen has scored a clutch of oncology approvals in recent years, finding gold in what are known as “third-gen” ADCs. Now, another of their partnered conjugates is ready for prime time.

The FDA on Monday handed an accelerated approval to Seagen and Genmab’s Tivdak (tisotumab vedotin-tftv, or “TV”) in second-line patients with recurrent or metastatic cervical cancer who previously progressed after chemotherapy rather than PD-(L)1 systemic therapy, the companies said in a release.

Dave Lennon, former president of Novartis Gene Therapies

Zol­gens­ma patent spat brews be­tween No­var­tis and Re­genxbio as top No­var­tis gene ther­a­py ex­ec de­parts

Regenxbio, a small licensor of gene therapy viral vectors spun out from the University of Pennsylvania, is now finding itself in the middle of some major league patent fights.

In addition to a patent suit with Sarepta Therapeutics from last September, Novartis, is now trying to push its smaller partner out of the way. The Swiss biopharma licensed Regenxbio’s AAV9 vector for its $2.1 million spinal muscular atrophy therapy Zolgensma.

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Time for round 2: Il­lu­mi­na-backed VC snags $325M for its next fund

Illumina Ventures closed off its second investment fund with a total commitment of $325 million, offering fresh fuel to back a slate of startups that have already included a smorgasbord of companies, covering everything from diagnostics to biotech drug development and genomics.

Fund II brings the total investment under Illumina Ventures’ oversight to $560 million, which has been focused on early-stage companies. And it has a transatlantic portfolio that includes SQZ, Twist and Encoded Therapeutics.

Volker Wagner (L) and Jeff Legos

As Bay­er, No­var­tis stack up their ra­dio­phar­ma­ceu­ti­cal da­ta at #ES­MO21, a key de­bate takes shape

Ten years ago, a small Norwegian biotech by the name of Algeta showed up at ESMO — then the European Multidisciplinary Cancer Conference 2011 — and declared that its Bayer-partnered targeted radionuclide therapy, radium-223 chloride, boosted the overall survival of castration-resistant prostate cancer patients with symptomatic bone metastases.

In a Phase III study dubbed ALSYMPCA, patients who were treated with radium-223 chloride lived a median of 14 months compared to 11.2 months. The FDA would stamp an approval on it based on those data two years later, after Bayer snapped up Algeta and christened the drug Xofigo.

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Raju Mohan, Ventyx Biosciences CEO

Months af­ter a mam­moth raise, Ven­tyx Bio­sciences dips back in­to ven­ture well

Several months after emerging from what CEO Raju Mohan called “quiet mode” with a mammoth $114 million raise, Ventyx Biosciences is now making its plans for the clinic loud and clear.

The California-based immune modulation player kicked the week off with a $51 million Series B, while also naming some key hires ahead of its big clinical push.

The CMO slot is going to Jörn Drappa, former CMO at Viela Bio before it was bought out by Horizon Therapeutics earlier this year. The AstraZeneca vet stayed on at Horizon for a while as executive VP of R&D before making the jump to Ventyx.