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.

Hal Barron and Rick Klausner (GSK, Lyell)

Ex­clu­sive: GSK’s Hal Bar­ron al­lies with Rick Klaus­ner’s $600M cell ther­a­py start­up, look­ing to break new ground blitz­ing sol­id tu­mors

LONDON — Chances are, you’ve heard little or nothing about Rick Klausner’s startup Lyell. But that ends now.

Klausner, the former head of the National Cancer Institute, former executive director for global health at the Gates Foundation, co-founder at Juno and one of the leaders in the booming cell therapy field, has brought together one of the most prominent teams of scientists tackling cell therapy 2.0 — highlighted by a quest to bridge a daunting tech gap that separates some profound advances in blood cancers with solid tumors. And today he’s officially adding Hal Barron and GlaxoSmithKline as a major league collaborator which is pitching in a large portion of the $600 million he’s raised in the past year to make that vision a reality.

“We’ve being staying stealth,” Klausner tells me, then adding with a chuckle: “and going back to stealth after this.”

“Cell therapy has a lot of challenges,” notes Barron, the R&D chief at GSK, ticking off the resistance put up by solid tumors to cell therapies, the vein-to-vein time involved in taking immune cells out of patients, engineering them to attack cancer cells, and getting them back in, and more. “Over the years Rick and I talked about how it would be wonderful to take that on as a mission.”

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First place fin­ish: Eli Lil­ly just moved to fran­chise leader with their sec­ond mi­graine drug OK in 1 year

In a rare twist for Eli Lilly’s historically slow-moving R&D group, the pharma giant has seized bragging rights to a first-in-class new drug approval. And all signs point to an aggressive marketing followup as they look to outclass some major franchise rivals hobbled by internal dissension.

The FDA came through with an OK for lasmiditan on Friday evening, branding it as Reyvow and lining it up — once a substance classification comes through from the DEA — for a major market release. The oral drug binds to 5-HT1F receptors and is designed to stop an acute migraine after it starts. That makes it a complementary therapy to their CGRP drug Emgality, which has a statistically significant impact on preventing attacks.

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Allogene HQ Open House on September 17, 2019 in South San Francisco. (Jeff Rumans, Endpoints News)

The next 10 years: Where is biotech head­ed?

The last 10 years have seen a revolution in drug development. Timelines have shortened, particularly in oncology. Regulators have opened up. Investment has skyrocketed. China became a player. Biotechs have multiplied as gene and cell therapy has exploded — offering major new advances in the way diseases are treated, and sometimes cured.

So where are we headed from here? I journeyed out to San Francisco in September to discuss the answer to that question at Allogene’s open house. If the last 10 years have been an eye-opener, what does the next decade hold in store?

Patrick Mahaffy, Getty Images

Court green-lights Clo­vis case af­ter de­tail­ing ev­i­dence the board ‘ig­nored red flags’ on false safe­ty and ef­fi­ca­cy da­ta

Clovis investors have cleared a major hurdle in their long-running case against the board of directors, with a Delaware court making a rare finding that they had a strong enough case against the board to proceed with the action.

In a detailed ruling at the beginning of the month that’s been getting careful scrutiny at firms specializing in biotech and corporate governance, the Delaware Court of Chancery found that the attorneys for the investors had made a careful case that the board — a collection of experts that includes high-profile biotech entrepreneurs, a Harvard professor and well-known investigator as well as Clovis CEO Patrick Mahaffy — repeatedly ignored obvious warnings that Mahaffy’s executive crew was touting inflated, unconfirmed data for their big drug Roci. Serious safety issues were also reportedly overlooked while the company continued a fundraising campaign that brought in more than a half-billion dollars. And that leaves the board open to claims related to their role in the fiasco.

The bottom line:

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Bill Gates backs Gink­go Biowork­s' $350M raise to fu­el the buzzy syn­thet­ic bi­ol­o­gy 'rev­o­lu­tion'

If you want to understand Ginkgo Bioworks, the name should suffice: Bioworks, a spin off “ironworks,” that old industrial linchpin devoted to leveraging scale as a wellspring for vast new industries capable of remaking society. Ginkgo wants to be the ironworks for the revolution it’s heralded with as much fanfare as they can, playing off of one of the buzziest technologies in biotech.

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UCB bags a ri­val to Soliris in $2.1B buy­out deal — but will an in­creas­ing­ly vig­i­lant FTC sign off?

UCB is buying out Ra Pharma $RARX, announcing an acquisition deal that rings up at $48 a share, or $2.1 billion net of cash, and puts them toe-to-toe with Alexion on a clinical showdown.

Ra shares closed at $22.70 on Wednesday.

There’s a small pipeline in play at Ra, but UCB is going for the lead drug — a C5 inhibitor called zilucoplan in Phase III for myasthenia gravis (MG) looking to play rival to Alexion’s Soliris. Soliris has the market advantage, though, with a much earlier approval in MG in late 2017 that UCB feels confident in challenging.

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A new play­er is tak­ing the field in a push for a he­mo­phil­ia A gene ther­a­py, and it’s a big one

BioMarin, the execs at Spark (and buyer-to-be Roche) as well as the Sangamo/Pfizer team have a new rival striding onto the hemophilia block. And it’s a big one.

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Stuck with a PhI­II gene ther­a­py fail­ure at 96 weeks, Gen­Sight prefers the up­beat as­sess­ment

Two years after treatment, the best thing that GenSight Biologics $SIGHT can say about their gene therapy for vision-destroying cases of Leber Hereditary Optic Neuropathy is that it’s just a bit better than a placebo — just maybe because one treatment can cover both eyes.

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George Scangos / Credit: Cornell University

ARCH, Soft­Bank-backed Vir Biotech­nol­o­gy un­der­whelms with $143 mil­lion IPO

George Scangos went back to Wall Street, and came back 700 million pennies short.

Scangos’ vaunted startup Vir Biotechnology raised $143 million in an IPO they hoped would earn $150 million. Shares were priced at $20, the low-end of the $20-$22 target.

Launched with backing from ARCH Venture’s Robert Nelsen, Masayoshi Son’s SoftBank Vision Fund, and the Bill & Melinda Gates Foundation, the infectious disease startup was one of a new wave of well-resourced biotechs that emerged with deep enough coffers to pursue a full R&D line rather than slowly build their case by picking off a single lead program.