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.

Amarin CEO John Thero discussing the company's plans for Vascepa, August 2019 — via Bloomberg

Amarin wins a block­buster ap­proval from the FDA. Now every­one can shift fo­cus to the patent

For all those people who could never quite believe that Amarin $AMRN would get an expanded label with blockbuster implications, the stress and anxiety on display right up to the last minute on Twitter can now end. But new, pressing questions will immediately surface now that the OK has come through.

On Friday afternoon, the FDA stamped its landmark approval on the industrial strength fish oil for reducing cardio risks for a large and well defined population of patients. The approval doesn’t give Amarin everything it wants in expanding its use, losing out on the primary prevention group, but it goes a long way to doing what the company needed to make a major splash. The approval was cited for patients with “elevated triglyceride levels (a type of fat in the blood) of 150 milligrams per deciliter or higher. Patients must also have either established cardiovascular disease or diabetes and two or more additional risk factors for cardiovascular disease.”

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Sarep­ta was stunned by the re­jec­tion of Vyondys 53. Now it's stun­ning every­one with a sur­prise ac­cel­er­at­ed ap­proval

Sarepta has a friend in the FDA after all. Four months after the agency determined that it would be wrong to give Sarepta an accelerated approval for their Duchenne MD drug golodirsen, regulators have executed a stunning about face and offered the biotech a quick green light in any case.

It was the agency that first put out the news late Thursday, announcing that Duchenne MD patients with a mutation amenable to exon 53 skipping will now have their first targeted treatment: Vyondys 53, or golodirsen. Having secured the OK via a dispute resolution mechanism, the biotech said the new drug has been priced on par with their only other marketed drug, Exondys 51 — which for an average patient costs about $300,000 per year, but since pricing is based on weight, that sticker price can even cross $1 million.

Sarepta shares $SRPT surged 23% after-market to $124.

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Paul Hudson, Getty Images

UP­DAT­ED: Sanofi CEO Hud­son lays out new R&D fo­cus — chop­ping di­a­betes, car­dio and slash­ing $2B-plus costs in sur­gi­cal dis­sec­tion

Earlier on Monday, new Sanofi CEO Paul Hudson baited the hook on his upcoming strategy presentation Tuesday with a tell-tale deal to buy Synthorx for $2.5 billion. That fits squarely with hints that he’s pointing the company to a bigger future in oncology, which also squares with a major industry tilt.

In a big reveal later in the day, though, Hudson offered a slate of stunners on his plans to surgically dissect and reassemble the portfoloio, saying that the company is dropping cardio and diabetes research — which covers two of its biggest franchise arenas. Sanofi missed the boat on developing new diabetes drugs, and now it’s pulling out entirely. As part of the pullback, it’s dropping efpeglenatide, their once-weekly GLP-1 injection for diabetes.

“To be out of cardiovascular and diabetes is not easy for a company like ours with an incredibly proud history,” Hudson said on a call with reporters, according to the Wall Street Journal. “As tough a choice as that is, we’re making that choice.”

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Paul Biondi (File photo)

Paul Biondi's track record at Bris­tol-My­ers cov­ered bil­lions in deals of every shape and size. Here's the com­plete break­down

Paul Biondi was never afraid to bet big during his stint as business development chief at Bristol-Myers Squibb. And while the gambles didn’t all pay out, by any means, his roster of pacts illustrates the broad ambitions the pharma giant has had over the last 5 years — capped by the $74 billion Celgene buyout.

On Thursday, we learned that Biondi had exited the company. And Chris Dokomajilar at DealForma came up with the complete breakdown on every buyout, licensing pact and product purchase Bristol-Myers forged during his tenure in charge of the BD team at one of the busiest companies in biopharma.

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Arie Belldegrun (Photo: Jeff Rumans for Endpoints News)

Ju­ry finds Gilead li­able for $585M and big roy­al­ties in Kite CAR-T patent case

A Kite deal that’s already become a burden on Gilead’s back just got heavier as a California jury has ruled Gilead must pay Bristol-Myers Squibb and Sloan Kettering $585 million plus a 27.6% royalty for patent infringement committed by its subsidiary. The ruling is almost certain to be appealed.

Kite Pharma — founded by Arie Belldegrun, now focused on a next-gen CAR-T company — has been facing a lawsuit since the day its first CAR–T therapy won approval in October, 2017. Juno Therapeutics and Sloan Kettering filed a complaint saying Kite had copied its technology. Gilead acquired Kite in June of that year for $11.9 billion.  Juno was acquired the following year by Celgene for $9 billion, before Celgene was acquired by Bristol-Myers Squibb in 2019.

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FDA ex­pert pan­el unan­i­mous­ly rec­om­mends ap­proval for Hori­zon Ther­a­peu­tics eye drug

An FDA advisory committee noted with concern a small safety database but unanimously endorsed a Horizon Therapeutics drug for a rare eye autoimmune disease that can blind patients: teprotumumab for thyroid eye disease (TED).

“It was a pretty easy vote,” said Erica Brittain, an NIH biostatistician and one of the 12 panelists on FDA’s Dermatologic and Ophthalmic Drugs Advisory Committee.

Paul Biondi (File photo)

Bris­tol-My­er­s' strat­e­gy, BD chief Paul Bion­di ex­it­ed the com­pa­ny — just ahead of the $74B Cel­gene deal close

Paul Biondi, who orchestrated billions of dollars in deals for Bristol-Myers Squibb over the 5 years he’s run their business development team, has exited the company. Biondi left last month, according to a company spokesperson, in pursuit of another — unspecified — external opportunity.

After 17 years with Bristol-Myers Squibb, Paul Biondi, Head of Strategy and Business Development, decided to leave the company to pursue an external opportunity. The company wishes him well in his new endeavors. Bristol-Myers Squibb  is actively searching for Paul’s successor, and will make an announcement, as appropriate.

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Arie Belldegrun at UKBIO 2019. Shai Dolev for Endpoints News

Kite Phar­ma's ex-CEO con­tra­dicts founder as CAR-T patent tri­al heats up, with con­flict­ing val­u­a­tions

Two days after Kite Pharma founder Arie Belldegrun told a federal courtroom that a meeting he had with a Memorial Sloan Kettering executive wasn’t about licensing their immunotherapy patent, Kite’s ex-CEO Aya Jakobovits said it was.

The admission came Tuesday during cross-examination in a patent infringement case that features two of the biggest cancer biotechs and some of the most well-known names in American medicine.

Jakobovits initially said she was not in attendance, didn’t know it was going to happen and didn’t know what took place, according to Law360. But then the plaintiff’s lawyer handed her a document – whose contents were not publicly revealed – and asked again if she learned after-the-fact that the meeting involved a potential patent license.

“Yes,” Jakobovits eventually said.

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On the heels of promis­ing MCL da­ta, Kite hus­tles its 2nd CAR-T to the FDA as the next big race in the field draws to the fin­ish line

Three days after Gilead’s Kite subsidiary showed off stellar data on their number 2 CAR-T KTE-X19 at ASH, the executive team has pivoted straight to the FDA with a BLA filing and a shot at a near-term approval.

In a small, 74-patient Phase II trial reported out at the beginning of the week, investigators tracked a 93% response rate with two out of three mantle cell lymphoma patients experiencing a complete response.

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