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.

Mi­no­ryx and Sper­o­genix ink an ex­clu­sive li­cense agree­ment to de­vel­op and com­mer­cial­ize lerigli­ta­zone in Chi­na

September 23, 2020 – Hong Kong, Beijing, Shanghai (China) and Mataró, Barcelona (Spain)  

Minoryx will receive an upfront and milestone payments of up to $78 million, as well as double digit royalties on annual net sales 

Sperogenix will receive exclusive rights to develop and commercialize leriglitazone for the treatment of X-linked adrenoleukodystrophy (X-ALD), a rare life-threatening neurological condition

Isaac Veinbergs, Libra CEO

With $29M in Se­ries A, Boehringer-backed Li­bra looks to tack­le neu­rode­gen­er­a­tion through cel­lu­lar clean­ing

Can the natural process by which cells clean out toxic proteins be harnessed to create potential treatments for neurodegenerative disorders?

That’s the question Libra Therapeutics will be trying to answer, as the new biotech officially launched Wednesday morning with $29 million in Series A financing. The company has three preclinical programs at the ready, with its lead candidate targeting ALS and frontotemporal dementia. But CEO Isaac Veinbergs said he hopes to develop therapies for a wide range of diseases, including Parkinson’s, Alzheimer’s and Huntington’s.

Vas Narasimhan (AP Images)

UP­DAT­ED: Still held down by clin­i­cal hold, No­var­tis' Zol­gens­ma falls fur­ther be­hind Bio­gen and Roche as FDA asks for a new piv­otal study

Last October, the FDA slowed down Novartis’ quest to extend its gene therapy to older spinal muscular atrophy patients by slapping a partial hold on intrathecal administration. Almost a year later, the hold is still there, and regulators are adding another hurdle required for regulatory submission: a new pivotal confirmatory study.

The new requirement — which departs significantly from Novartis’ prior expectations — will likely stretch the path to registration beyond 2021, when analysts were expecting a BLA submission. That could mean more time for Biogen to reap Spinraza revenues and Roche to ramp up sales of Evrysdi in the absence of a rival.

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Scoop: ARCH’s Bob Nelsen is back­ing an mR­NA up­start that promis­es to up­end the en­tire man­u­fac­tur­ing side of the glob­al busi­ness

For the past 2 years, serial entrepreneur Igor Khandros relied on a small network of friends and close insiders to supply the first millions he needed to fund a secretive project to master a new approach to manufacturing mRNA therapies.

Right now, he says, he has a working “GMP-in-a-box” prototype for a new company he’s building — after launching 3 public companies — which plans to spread this contained, precise manufacturing tech around the world with a set of partners. He’s raised $60 million, recruited some prominent experts. And not coincidentally, he’s going semi-public with this just as a small group of pioneers appears to be on the threshold of ushering in the world’s first mRNA vaccines to fight a worldwide pandemic.

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Gene Wang, Immetas co-founder and CEO (file photo)

Im­metas Ther­a­peu­tics nabs $11M Se­ries A to nar­row their bis­pe­cif­ic work tar­get­ing in­flam­ma­tion in age-re­lat­ed dis­eases

How does a biotech celebrate its two-year anniversary? For Immetas Therapeutics, it’s with an $11 million Series A round and a game plan to fight age-related disease.

Co-founders Gene Wang and David Sinclair came together years ago around the idea that inflammation is the ultimate process driving age-related illnesses, including cancer. The duo launched Immetas in 2018 and packed the staff with industry experts. Wang, who says he’s always had an entrepreneurial spirit, has held lead roles at Novartis, GSK, Bristol Myers Squibb and Merck. He’s worked on blockbuster drugs like Humira, Gardasil, Varubi and Zolinza. And now, he’s channeling that spirit as CEO.

FDA commissioner Stephen Hahn at the White House (AP Images)

Un­der fire, FDA to is­sue stricter guid­ance for Covid-19 vac­cine EUA this week — re­port

The FDA has been insisting for months that a Covid-19 vaccine had to be at least 50% effective – a measure of transparency meant to shore public trust in the agency and in a vaccine that had been brought forward at record speed and record political pressure. But now, with concerns of a Trump-driven authorization arriving before the election, the agency may be raising the bar.

The FDA is set to release new guidance that would raise safety and efficacy requirements for a vaccine EUA above earlier guidance and above the criteria used for convalescent plasma or hydroxychloroquine, The Washington Post reported. Experts say this significantly lowers the odds of an approval before the election on November 3, which Trump has promised despite vocal concerns from public health officials, and could help shore up public trust in the agency and any eventual vaccine.

Secretary of health and human services Alex Azar speaking in the Rose Garden at the White House (Photo: AFP)

Trump’s HHS claims ab­solute au­thor­i­ty over the FDA, clear­ing path to a vac­cine EUA

The top career staff at the FDA has vowed not to let politics overrule science when looking at vaccine data this fall. But Alex Azar, who happens to be their boss’s boss, apparently won’t even give them a chance to stand in the way.

In a new memorandum issued Tuesday last week, the HHS chief stripped the FDA and other health agencies under his purview of their rule making ability, asserting all such power “is reserved to the Secretary.” Sheila Kaplan of the New York Times first obtained and reported the details of the September 15 bulletin.

Patrick Enright, Longitude co-founder (Longitude)

As its biotechs hit the pan­dem­ic ex­it, Lon­gi­tude rais­es $585M for new neu­ro, can­cer, ag­ing and or­phan-fo­cused fund

The years have been kind to Longitude Capital. This year, too.

A 2006 spinout of Pequot Capital, its founders started their new firm just four years before the parent company would go under amid insider trading allegations. Their first life sciences fund raised $325 million amid the financial crisis, they added a second for $385 million and then in, 2016, a third for $525 million. In the last few months, the pandemic biotech IPO boom netted several high-value exits from those funds, as Checkmate, Vaxcyte, Inozyme and Poseida all went public.

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Samit Hirawat (Bristol Myers Squibb)

Af­ter bruis­ing re­jec­tion, blue­bird and Bris­tol My­ers Squibb land ide-cel pri­or­i­ty re­view. But will it mat­ter for the CVR?

With the clock all but up, the FDA accepted and handed priority review to Bristol Myers Squibb and bluebird bio’s BCMA CAR-T, keeping a narrow window open for Celgene investors to still cash in on the $9 CVR from the $63 billion Celgene merger.

The acceptance comes five months after the two companies weres slammed with a surprise refuse-to-file that threatened to foreclose the CVR entirely. Today’s acceptance sets the FDA decision date for March 27, 2021 – or precisely 4 days before the CVR deadline of March 31. Given the breakthrough designation and strong pivotal data — 81.5% response rate, 35.2% complete response rate — priority review was largely expected.

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