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.”

ZS Per­spec­tive: 3 Pre­dic­tions on the Fu­ture of Cell & Gene Ther­a­pies

The field of cell and gene therapies (C&GTs) has seen a renaissance, with first generation commercial therapies such as Kymriah, Yescarta, and Luxturna laying the groundwork for an incoming wave of potentially transformative C&GTs that aim to address diverse disease areas. With this renaissance comes several potential opportunities, of which we discuss three predictions below.

Allogenic Natural Killer (NK) Cells have the potential to displace current Cell Therapies in oncology if proven durable.

Despite being early in development, Allogenic NKs are proving to be an attractive new treatment paradigm in oncology. The question of durability of response with allogenic therapies is still an unknown. Fate Therapeutics’ recent phase 1 data for FT516 showed relatively quicker relapses vs already approved autologous CAR-Ts. However, other manufacturers, like Allogene for their allogenic CAR-T therapy ALLO-501A, are exploring novel lymphodepletion approaches to improve persistence of allogenic cells. Nevertheless, allogenic NKs demonstrate a strong value proposition relative to their T cell counterparts due to comparable response rates (so far) combined with the added advantage of a significantly safer AE profile. Specifically, little to no risk of graft versus host disease (GvHD), cytotoxic release syndrome (CRS), and neurotoxicity (NT) have been seen so far with allogenic NK cells (Fig. 1). In addition, being able to harness an allogenic cell source gives way to operational advantages as “off-the-shelf” products provide improved turnaround time (TAT), scalability, and potentially reduced cost. NKs are currently in development for a variety of overlapping hematological indications with chimeric antigen receptor T cells (CAR-Ts) today, and the question remains to what extent they will disrupt the current cell therapy landscape. Click for more details.

Graphic: Kathy Wong for Endpoints News

What kind of biotech start­up wins a $3B syn­di­cate, woos a gallery of mar­quee sci­en­tists and re­cruits GSK's Hal Bar­ron as CEO in a stun­ner? Let Rick Klaus­ner ex­plain

It started with a question about a lifetime’s dream on a walk with tech investor Yuri Milner.

At the beginning of the great pandemic, former NCI chief and inveterate biotech entrepreneur Rick Klausner and the Facebook billionaire would traipse Los Altos Hills in Silicon Valley Saturday mornings and talk about ideas.

Milner’s question on one of those mornings on foot: “What do you want to do?”

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Hal Barron, Endpoints UKBIO20 (Jeff Rumans)

'Al­tos was re­al­ly a once-in-a-life­time op­por­tu­ni­ty': Hal Bar­ron re­flects on his big move

By all accounts, Hal Barron had one of the best jobs in Big Pharma R&D. He made more than $11 million in 2020, once again reaping more than his boss, Emma Walmsley, who always championed him at every opportunity. And he oversaw a global R&D effort that struck a variety of big-dollar deals for oncology, neurodegeneration and more.

Sure, the critics never let up about what they saw as a rather uninspiring late-stage pipeline, where the rubber hits the road in the Big Pharma world’s hunt for the next big near-term blockbuster, but the in-house reviews were stellar. And Barron was firmly focused on bringing up the success rate in clinical trials, holding out for the big rewards of moving the dial from an average 10% success rate to 20%.

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Executive Director of the EMA Emer Cooke (AP Photo/Geert Vanden Wijngaert)

Eu­ro­pean Par­lia­ment signs off on strength­en­ing drug reg­u­la­tor's abil­i­ty to tack­le short­ages

The European Parliament on Thursday endorsed a plan to increase the powers of the European Medicines Agency, which will be better equipped to monitor and mitigate shortages of drugs and medical devices.

By a vote of 655 to 31, parliament signed off on a provisional agreement reached with the European Council from last October, in which the EMA will create two shortage steering groups (one for drugs, the other for devices), a new European Shortages Monitoring Platform to facilitate data collection and increase transparency, and on funding for the work of the steering groups, task force, working parties and expert panels that are to be established.

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FDA+ roundup: FDA's neu­ro­science deputy de­parts amid on­go­ing Aduhelm in­ves­ti­ga­tions; Califf on the ropes?

Amid increased scrutiny into the close ties between FDA and Biogen prior to the controversial accelerated approval of Aduhelm, the deputy director of the FDA’s office of neuroscience has called it quits after more than two decades at the agency.

Eric Bastings will now take over as VP of development strategy at Ionis Pharmaceuticals, the company said Wednesday, where he will provide senior clinical and regulatory leadership in support of Ionis’ pipeline.

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Sec­ondary patents prove to be key in biosim­i­lar block­ing strate­gies, re­searchers find

While the US biosimilars industry has generally been a disappointment since its inception, with FDA approving 33 biosimilars since 2015, just a fraction of those have immediately followed their approvals with launches. And more than a handful of biosimilars for two of the biggest blockbusters of all time — AbbVie’s Humira and Amgen’s Enbrel — remain approved by FDA but still have not launched because of legal settlements.

Hal Barron (GSK via YouTube)

GSK R&D chief Hal Bar­ron jumps ship to run a $3B biotech start­up, Tony Wood tapped to re­place him

In a stunning switch, GlaxoSmithKline put out word early Wednesday that R&D chief Hal Barron is exiting the company after 4 years — a relatively brief run for the man chosen by CEO Emma Walmsley in late 2017 to turn around the slow-footed pharma giant.

Barron is being replaced by Tony Wood, a close associate of Barron’s who’s taking one of the top jobs in Big Pharma R&D. He’ll be closer to home, though, for GSK. Barron has been running a UK and Philadelphia-based research organization from his perch in San Francisco.

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Chamath Palihapitiya and Pablo Legorreta

Bil­lion­aires Chamath Pal­i­hapi­tiya and Pablo Legor­re­ta hatch an $825M SPAC for cell ther­a­py biotech

Three years after Royalty Pharma chief Pablo Legorreta led a group of investors to buy up a pair of biotechs and create a new startup called ProKidney, the biotech is jumping straight into an $825 million public shell created by SPAC king and tech billionaire Chamath Palihapitiya.

ProKidney was founded 6 years ago but really got going at the beginning of 2019 with the $62 million acquisition of inRegen, which was working on an autologous — from the patient — cell therapy for kidney disease. After extracting kidney cells from patients, researchers expand the cells in the lab and then inject them back into patients, aiming to restore the kidneys of patients suffering from CKD.

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Troy Wilson, Kura CEO

FDA lifts par­tial hold on Ku­ra's Phase Ib AML pro­gram as biotech re­dou­bles mit­i­ga­tion ef­forts

Kura Oncology is clear to resume studies for its early-stage leukemia program after the FDA lifted a clinical hold Thursday afternoon.

Regulators had placed the hold on a Phase Ib study of KO-539, an experimental oral treatment for some genetic subsets of acute myeloid leukemia last November after a patient died while taking the drug. Kura expects to begin enrolling patients again imminently, CEO Troy Wilson told Endpoints News.