Maggie Cook, Renovacor

Biotech tar­get­ing rare heart mu­ta­tion with gene ther­a­py scores $11M in Se­ries A haul

While car­dio­vas­cu­lar dis­ease is the lead­ing cause of death glob­al­ly — it is can­cer that has ben­e­fit­ed most from strides in pre­ci­sion med­i­cine. Now that car­dio­vas­cu­lar-spe­cif­ic ge­net­ic mu­ta­tions are be­ing dis­cov­ered — they are prime tar­gets for ge­net­ic ther­a­py. A biotech­nol­o­gy com­pa­ny carved out of re­search con­duct­ed at Tem­ple Uni­ver­si­ty is fo­cus­ing on a mu­tant gene that is un­der­stood to cause a rare heart con­di­tion, which can even­tu­al­ly lead to a heart trans­plant or the use of im­plant­ed car­diac as­sist de­vices.

The con­di­tion, di­lat­ed car­diomy­opa­thy, af­fects more than 3 mil­lion pa­tients in the Unit­ed States — and in about 35,000 pa­tients, its eti­ol­o­gy can be traced to mu­ta­tions in the BAG3 gene. It is a dis­ease of the heart mus­cle, usu­al­ly start­ing in the heart’s main pump­ing cham­ber, the left ven­tri­cle. The ven­tri­cle stretch­es and di­lates, pre­clud­ing its abil­i­ty to pump blood ef­fi­cient­ly.

So far, pa­tients are typ­i­cal­ly treat­ed with a cock­tail of treat­ments in­clud­ing ACE in­hibitors, be­ta-block­ers, wa­ter pills and blood thin­ners. The com­pa­ny, chris­tened Ren­o­va­cor, is de­vel­op­ing a gene-ther­a­py de­signed to treat the BAG3 sub­pop­u­la­tion us­ing vi­ral vec­tor. In this pop­u­la­tion, the mu­ta­tion pre­vents the gene from func­tion­ing prop­er­ly — and the ther­a­py is en­gi­neered to re­place the gene to re­store func­tion.

“Gene ther­a­py is…com­ing in­to its own and be­com­ing a more a more prac­ti­cal modal­i­ty for ther­a­peu­tic in­ter­ven­tion. So as those things come to­geth­er I think…we’re on the cusp of car­dio­vas­cu­lar dis­ease mov­ing in­to a new phase where pre­ci­sion med­i­cine is go­ing to be­come one of the ap­proach­es we have,” chief Mag­gie Cook not­ed in an in­ter­view with End­points News.

Arthur Feld­man Tem­ple Uni­ver­si­ty

In some ways, car­diomy­opathies ap­pear to be more amenable to pre­ci­sion med­i­cine than can­cer — fail­ing hearts are thought to be gen­er­al­ly ho­moge­nous; many sig­nal­ing path­ways re­spon­si­ble for reg­u­lat­ing car­diac func­tion have been iden­ti­fied; mu­ta­tions in at least forty genes have been shown to cause fa­mil­ial di­lat­ed car­diomy­opa­thy, and the var­i­ous forms of heart mus­cle dis­ease have been well char­ac­ter­ized phe­no­typ­i­cal­ly, Ren­o­va­cor co-founder Arthur Feld­man wrote in a pa­per pub­lished in 2017.

“A prin­ci­pal dif­fer­ence be­tween the trans­la­tion­al sci­ences in HF (heart fail­ure) and in can­cer bi­ol­o­gy that might ex­plain in part the rel­a­tive lack of pre­ci­sion ther­a­py in the treat­ment of HF is that HF re­search has been dri­ven in large part by dis­cov­er­ies in in­ves­ti­ga­tion­al mod­els of HF, where­as drug dis­cov­ery in can­cer has been dri­ven by the elu­ci­da­tion of al­tered bi­ol­o­gy of hu­man tu­mors,” he not­ed.

Ren­o­va­cor is ex­pect­ed to be ready for ear­ly-stage stud­ies with­in three years — for now, it is putting to­geth­er an ap­pli­ca­tion to take the drug in­to the clin­ic. On Wednes­day, it un­veiled an $11 mil­lion Se­ries A round of fi­nanc­ing co-led by No­var­tis Ven­ture Fund, Broad­view Ven­tures, and BioAd­vance, and in­clud­ed the par­tic­i­pa­tion of New Leaf Ven­ture Part­ners and Inno­gest Cap­i­tal.

Ex­ist­ing rare dis­ease gene ther­a­pies — while con­sid­ered rev­o­lu­tion­ary in terms of po­ten­cy — threat­en to wreak hav­oc on the US health­care sys­tem with their mil­lion-dol­lar price tags. For pre­clin­i­cal Ren­o­va­cor, it is too ear­ly to dis­cuss pric­ing.

How­ev­er, the dis­ease the com­pa­ny is tar­get­ing car­ries a heavy bur­den of hos­pi­tal­iza­tion and mor­bid­i­ty.  “The dis­ease comes on in their ear­ly 40s, and these are oth­er­wise healthy young adults, so they can live with the dis­ease, and have a huge cost of care over time, then progress to meet­ing heart trans­plant, or im­plant­ed car­diac as­sist de­vices. So…based on dif­fer­ent method­olo­gies that you could con­sid­er the over­all mar­ket op­por­tu­ni­ty…is an at­trac­tive one in many dif­fer­ent pric­ing mod­els,” Cook said.

“I think there will al­ways be… car­dio­vas­cu­lar dis­ease that’s due to lifestyle choic­es. And that can’t al­ways nec­es­sar­i­ly be parsed out ge­net­i­cal­ly…some of that lifestyle in­ter­ven­tion will al­ways be nec­es­sary,” she added. “How­ev­er, there are prob­a­bly groups like the one we’ve iden­ti­fied, where a ge­net­ic cause is the pri­ma­ry cause of dis­ease and we can ap­proach that with a more pre­cise ther­a­py.”

The start­up is not rul­ing out a part­ner­ship in the fu­ture. “You can cer­tain­ly see it (the ther­a­py) fit­ting in­to the port­fo­lio of a larg­er com­pa­ny,” Cook said.

In May, the head of the Cen­ter for Hu­man Ge­net­ic Re­search at Mass­a­chu­setts Gen­er­al Hos­pi­tal and the Broad’s Car­dio­vas­cu­lar Dis­ease Ini­tia­tive, Sekar Kathire­san, set up his own shop to tweak genes, such as APOC3 or ANGPTL3, which car­ry mu­ta­tions that can rapid­ly clear triglyc­eride-rich lipopro­teins — which raise in­di­vid­u­als’ risk of heart at­tack — from cir­cu­la­tion.

Brian Kaspar. AveXis via Twitter

AveX­is sci­en­tif­ic founder fires back at No­var­tis CEO Vas Narasimhan, 'cat­e­gor­i­cal­ly de­nies any wrong­do­ing'

Brian Kaspar’s head was among the first to roll at Novartis after company execs became aware of the fact that manipulated data had been included in its application for Zolgensma, now the world’s most expensive therapy.

But in his first public response, the scientific founder at AveXis — acquired by Novartis for $8.7 billion — is firing back. And he says that not only was he not involved in any wrongdoing, he’s ready to defend his name as needed.

I reached out to Brian Kaspar after Novartis put out word that he and his brother Allen had been axed in mid-May, two months after the company became aware of the allegations related to manipulated data. His response came back through his attorneys.

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Novartis CEO Vas Narasimhan [via Bloomberg/Getty]

I’m not per­fect: No­var­tis chief Vas Narasimhan al­most apol­o­gizes in the wake of a new cri­sis

Vas Narasimhan has warily stepped up with what might pass as something close to a borderline apology for the latest scandal to engulf Novartis.

But he couldn’t quite get there.

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FDA to Sarep­ta: Your wide­ly an­tic­i­pat­ed fol­lowup to Ex­ondys 51 is not get­ting an ac­cel­er­at­ed OK for Duchenne MD

In one of the least anticipated moves of the year, the FDA has rejected Sarepta’s application for an accelerated approval of its Duchenne MD drug golodirsen after fretting over safety issues.

In a statement that arrived after the bell on Monday, Sarepta explained the CRL, saying:

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Levi Garraway. Broad Institute via Youtube

Roche raids Eli Lil­ly for its next chief med­ical of­fi­cer as San­dra Horn­ing plans to step down

We found out Monday morning where Levi Garraway was headed after he left Eli Lilly as head of oncology R&D a few days ago. Roche named Garraway as their new chief medical officer, replacing Sandra Horning, who they say is retiring from the company.

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Af­ter a posse of Wall Street an­a­lysts pre­dict a like­ly new win for Sarep­ta, we're down to the wire on a crit­i­cal FDA de­ci­sion

As Bloomberg notes, most of the Wall Street analysts that cover Sarepta $SRPT are an upbeat bunch, ready to cheer on the team when it comes to their Duchenne MD drugs, or offer explanations when an odd setback occurs — as happened recently with a safety signal that was ‘erroneously’ reported last week.

Ritu Baral Cowen
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UP­DAT­ED: No­var­tis spin­off Nabri­va fi­nal­ly scores its first an­tibi­ot­ic ap­proval

In May, Nabriva Therapeutics suffered a setback after the FDA rejected its antibiotic for complicated urinary tract infections — the Novartis spinoff has now had some better luck with the US agency, which on Monday approved its other drug for community-acquired bacterial pneumonia.

The drug, lefamulin, has been developed as an intravenous and oral formulation and been tested in two late-stage clinical trials. The semi-synthetic compound, whose dosing can be switched between the two formulations, is engineered to inhibit the synthesis of bacterial protein by binding to a part of the bacterial ribosome.

Saqib Islam. CheckRare via YouTube

Spring­Works seeks $115M to push Pfiz­er drugs across fin­ish line while Sat­suma sells mi­graine play in $86M IPO

SpringWorks and Satsuma — both biotech spinouts that have closed B rounds in April — are loading up with IPO cash to boost their respective late-stage plans.

Bain-backed SpringWorks is the better-known company of the two, and it’s gunning for a larger windfall of $115 million to add to $228 million from previous financings. In the process, the Stamford, CT-based team is also drawing the curtains on the partnerships it has in mind for the pair of assets it had initially licensed from Pfizer.

Mi­nor­i­ty racial groups con­tin­ue to be dis­mal­ly rep­re­sent­ed in can­cer tri­als — study

Data reveal that different racial and ethnic groups — by nature and/or nurture — can respond differently in terms of pharmacokinetics, efficacy, or safety to therapeutics, but this disparity is not necessarily accounted for in clinical trials. A fresh analysis of the last decade of US cancer drug approvals suggests the trend continues, cementing previous research that suggests oncology trials are woefully under-representative of the racial makeup of the real world.

Van­da shares slide af­ter FDA spurns their big end­point and re­jects a pitch on jet lag re­lief

Back in the spring of last year, Vanda Pharmaceuticals $VNDA served up a hot stew of mixed data for a slate of endpoints related to what they called clear evidence that their melatonin sleep drug Hetlioz (tasimelteon) could help millions of travelers suffering from jet lag.

Never mind that they couldn’t get a planned 90 people in the study, settling for 25 instead; Vanda CEO Mihael H. Polymeropoulos said they were building on a body of data to prove it would help jet-lagged patients looking for added sleep benefits. And that, they added, would be worth a major upgrade from the agency as they sought to tackle a big market.