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.

Covid-19 roundup: Eu­rope pur­chas­es 80M dos­es of Mod­er­na's vac­cine; CO­V­AXX se­cures $2.8B in emerg­ing mar­ket pre-or­ders

With the announcement of its vaccine efficacy data last week, Moderna is starting to line up customers for its Covid-19 mRNA jabs.

The Massachusetts-based biotech announced Wednesday it has agreed to sell an initial round of 80 million doses to the European Commission, with the option to double the amount to 160 million. Once the member states rubber stamp the approval, the deal will be finalized.

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Pascal Soriot (AP Images)

UP­DAT­ED: As­traZeneca, Ox­ford on the de­fen­sive as skep­tics dis­miss 70% av­er­age ef­fi­ca­cy for Covid-19 vac­cine

On the third straight Monday that the world wakes up to positive vaccine news, AstraZeneca and Oxford are declaring a new Phase III milestone in the fight against the pandemic. Not everyone is convinced they will play a big part, though.

With an average efficacy of 70%, the headline number struck analysts as less impressive than the 95% and 94.5% protection that Pfizer/BioNTech and Moderna have boasted in the past two weeks, respectively. But the British partners say they have several other bright spots going for their candidate. One of the two dosing regimens tested in Phase III showed a better profile, bringing efficacy up to 90%; the adenovirus vector-based vaccine requires minimal refrigeration, which may mean easier distribution; and AstraZeneca has pledged to sell it at a fraction of the price that the other two vaccine developers are charging.

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Jason Kelly, Ginkgo Bioworks CEO (Kyle Grillot/Bloomberg via Getty Images)

Af­ter Ko­dak de­ba­cle, US lends $1.1B to a syn­thet­ic bi­ol­o­gy com­pa­ny and their big Covid-19, mR­NA plans

In mid-August, as Kodak’s $765 million government-backed push into drug manufacturing slowly fell apart in national headlines, Ginkgo Bioworks CEO Jason Kelly got a message from his company’s government liaison: HHS wanted to know if they, too, might want a loan.

The government’s decision to lend Kodak three quarters of a billion dollars raised eyebrows because Kodak had never made drugs before. But Ginkgo, while not a manufacturing company, had spent the last decade refining new ways to produce materials inside cells and building automated facilities across Boston.

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Vivek Ramaswamy (Jeff Rumans/JPM 2020)

Urovan­t's lead drug dis­ap­points in mid-stage study as first big FDA de­ci­sion looms

Just as Urovant gets ready for its first big FDA decision on vibegron, the drug has flopped in what would’ve been a follow-on indication.

In a Phase IIa trial involving women with abdominal pain due to irritable bowel syndrome, vibegron failed to meet the bar on improving “average worst abdominal pain” over 12 weeks, compared to placebo, among IBS-D patients.

There were actually slightly more responders in the placebo group than in the drug arm, with only 40.9% of those randomized to vigebron achieving at least a 30% decrease in “worst abdominal pain” in the past 24 hours. The trial enrolled 222 women but only 189 completed the study.

Bob Nelsen (Photo by Michael Kovac/Getty Images)

Bob Nelsen rais­es $800M and re­cruits a star-stud­ded board to build the 'Fox­con­n' of biotech

Bob Nelsen spent his pandemic spring in his Seattle home, talking on the phone with Luciana Borio, the scientist who used to run pandemic preparedness on the National Security Council, and fuming with her about the dire state of American manufacturing.

Companies were rushing to develop vaccines and antibodies for the new virus, but even if they succeeded, there was no immediate supply chain or infrastructure to mass-produce them in a way that could make a dent in the outbreak.

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Bahija Jallal (file photo)

TCR pi­o­neer Im­muno­core scores a first with a land­mark PhI­II snap­shot on over­all sur­vival for a rare melanoma

Bahija Jallal’s crew at TCR pioneer Immunocore says they have nailed down a promising set of pivotal data for their lead drug in a frontline setting for a solid tumor. And they are framing this early interim readout as the convincing snapshot they need to prove that their platform can deliver on a string of breakthrough therapies now in the clinic or planned for it.

In advance of the Monday announcement, Jallal and R&D chief David Berman took some time to walk me through the first round of Phase III data for their lead TCR designed to treat rare, frontline cases of metastatic uveal melanoma that come with a grim set of survival expectations.

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Feng Tian, Ambrx CEO (Ambrx)

Af­ter 5 qui­et years, a for­mer Scripps spin­out rais­es $200M and an­nounces plans to try again at an IPO

The first time San Diego biotech Ambrx tried to go public in 2014, they failed and the company’s board switched to a radically different strategy: They sold themselves for an undisclosed amount to a syndicate of Chinese investors and pharma companies.

Now, after 5 quiet years, that syndicate has raised a mountain of cash and indicated they’ll soon make another bid to go public.

Earlier this month, Ambrx raised $200 million in what they billed as a crossover round financed by Fidelity, BlackRock, Cormorant Asset Management, HBM Healthcare Investments, Invus, Adage Capital Partners and Suvretta Capital Management. It’s the largest amount they’ve ever raised and, according to Crunchbase figures, more than doubles the total amount of VC capital collected since their launch 17 years ago.

FDA hands Liq­uidia and Re­vance a CRL and de­fer­ral, re­spec­tive­ly, as Covid-19 cre­ates in­spec­tion chal­lenge

Two biotechs said they got turned away by the FDA on Wednesday, in part due to pandemic-related travel restrictions.

North Carolina-based Liquidia Technologies was handed a CRL for its lead pulmonary arterial hypertension drug, citing the need for more CMC data and on-site pre-approval inspections, which the FDA hasn’t been able to conduct due to travel restrictions. The agency also deferred its decision on Revance Therapeutics’ BLA for its frown line treatment, because it needs to inspect the company’s northern California manufacturing facility. The action, Revance emphasized, was not a CRL.

News brief­ing: FDA re­quests new tri­al for Reata's Friedre­ich's atax­ia pro­gram; J&J's Trem­fya picks up ex­pand­ed la­bel in Eu­rope

Three months after Reata Pharmaceuticals suggested its Friedreich’s ataxia program omaveloxolone could be delayed, the company revealed that is indeed going to be the case.

Reata $RETA shares took a nosedive Wednesday after the biotech revealed that the FDA said supplemental data for its pivotal trial did not strengthen the case for approval. As a result, the drug is likely to need another study before the FDA takes up the case.