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.”

2023 Spot­light on the Fu­ture of Drug De­vel­op­ment for Small and Mid-Sized Biotechs

In the context of today’s global economic environment, there is an increasing need to work smarter, faster and leaner across all facets of the life sciences industry.  This is particularly true for small and mid-sized biotech companies, many of which are facing declining valuations and competing for increasingly limited funding to propel their science forward.  It is important to recognize that within this framework, many of these smaller companies already find themselves resource-challenged to design and manage clinical studies themselves because they don’t have large teams or in-house experts in navigating the various aspects of the drug development journey. This can be particularly challenging for the most complex and difficult to treat diseases where no previous pathway exists and patients are urgently awaiting breakthroughs.

Christian Itin, Autolus CEO (UKBIO19)

Au­to­lus tips its hand, bags $220M as CAR-T show­down with Gilead looms

The first batch of pivotal data on Autolus Therapeutics’ CAR-T is in, and execs are ready to plot a path to market.

With an overall remission rate of 70% at the interim analysis featuring 50 patients, the results set the stage for a BLA filing by the end of 2023, said CEO Christian Itin.

Perhaps more importantly — given that Autolus’ drug, obe-cel, is going after an indication that Gilead’s Tecartus is already approved for — the biotech highlighted “encouraging safety data” in the trial, with a low percentage of patients experiencing severe immune responses.

Dipal Doshi, Entrada Therapeutics CEO

Ver­tex just found the next big ‘trans­for­ma­tive’ thing for the pipeline — at a biotech just down the street

Back in the summer of 2019, when I was covering Vertex’s executive chairman Jeff Leiden’s plans for the pipeline, I picked up on a distinct focus on myotonic dystrophy Type I, or DM1 — one of what Leiden called “two diseases (with DMD) we’re interested in and we continue to look for those assets.”

Today, Leiden’s successor at the helm of Vertex, CEO Reshma Kewalramani, is plunking down $250 million in cash to go the extra mile on DM1. The lion’s share of that is for the upfront, with a small reserve for equity in a deal that lines Vertex up with a neighbor in Seaport that has been rather quietly going at both of Vertex’s early disease targets with preclinical assets.

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WIB22: Am­ber Salz­man had few op­tions when her son was di­ag­nosed with a rare ge­net­ic dis­ease. So she cre­at­ed a bet­ter one

This profile is part of Endpoints News’ 2022 special report about Women in Biopharma R&D. You can read the full report here.

Amber Salzman’s life changed on a cold, damp day in Paris over tiny plastic cups of lukewarm tea.

She was meeting with Patrick Aubourg, a French neurologist studying adrenoleukodystrophy, or ALD, a rare genetic condition that causes rapid neurological decline in young boys. It’s a sinister disease that often leads to disability or death within just a few years. Salzman’s nephew was diagnosed at just 6 or 7 years old, and died at the age of 12.

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Ahead of ad­comm, FDA rais­es un­cer­tain­ties on ben­e­fit-risk pro­file of Cy­to­ki­net­ic­s' po­ten­tial heart drug

The FDA’s Cardiovascular and Renal Drugs Advisory Committee will meet next Tuesday to discuss whether Cytokinetics’ potential heart drug can safely reduce the risk of cardiovascular death and heart failure in patients with symptomatic chronic heart failure with reduced ejection fraction.

The drug, known as omecamtiv mecarbil and in development for more than 15 years, has seen mixed results, with a first Phase III readout from November 2020 hitting the primary endpoint of reducing the odds of hospitalization or other urgent care for heart failure by 8%. But it also missed a key secondary endpoint analysts had pegged as key to breaking into the market.

Stephen Squinto, Gennao Bio chairman

Scoop: Stephen Squin­to’s Yale spin­out is rais­ing a Se­ries B for ge­net­ic med­i­cines

The nucleic acid therapeutics at Stephen Squinto’s Yale-originated biotech are en route to a $40 million R&D payday.

After a Series A of that size in the spring of 2021, Hopewell, NJ-based Gennao Bio is closing on a round of the same amount, Endpoints News has learned. A Series B is in the works, according to an investor’s post on LinkedIn and as confirmed by a spokesperson. An SEC filing on Thursday outlines $15 million in equity sold thus far in the round.

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Nashville-based CD­MO nets a $65M Se­ries B to ex­pand fa­cil­i­ty and ca­pa­bil­i­ties

Another $65 million is music to the ears of the team at August Bioservices, a contract manufacturer in Nashville.

The company announced the Series B round last week, which will fund equipment in a new building expected to open in 2023, according to CEO Jenn Adams. It was led by Oak HC/FT, the same firm that led August’s Series A round in July 2020.

August Bioservices, a producer of materials such as prefilled syringes, IV bags and vials, was formed back in 2020 after the acquisition of PMI BioPharma Solutions, also based in Nashville. Adams said the goal was to build a business that could “address the scarcity of supply relative to sterile injectable manufacturing based in the US” and provide a broad range of manufacturing services.

Ab­b­Vie slapped with age dis­crim­i­na­tion law­suit, fol­low­ing oth­er phar­mas

Add AbbVie to the list of pharma companies currently facing age discrimination allegations.

Pennsylvania resident Thomas Hesch filed suit against AbbVie on Wednesday, accusing the company of passing him over for promotions in favor of younger candidates.

Despite 30 years of pharma experience, “Hesch has consistently seen younger, less qualified employees promoted over him,” the complaint states.

Rami Elghandour, Arcellx CEO

Up­dat­ed: Gilead, Ar­cel­lx team up on an­ti-BC­MA CAR-T as biotech touts a 100% re­sponse rate at #ASH22

Gilead and Kite are plunking down big cash to get into the anti-BCMA CAR-T game.

The pair will shell out $225 million in cash upfront and $100 million in equity to Arcellx, Kite announced Friday morning, to develop the biotech’s lead CAR-T program together. Kite will handle commercialization and co-development with Arcellx, and profits in the US will be split 50-50.

Concurrent with the deal, Arcellx revealed its latest cut of data for the program known as CART-ddBCMA, ahead of a full presentation at this weekend’s ASH conference — a 100% response rate among patients getting the therapy. Investors jumped at the dual announcements, sending Arcellx shares $ACLX up more than 25% in Friday’s morning session.

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