Ram Aiyar, Korro CEO

Can RNA edit­ing take At­las start­up where Ver­tex could­n't go? Ko­r­ro lands $116M to find out

As the CEO of RNA edit­ing start­up Ko­r­ro Bio, Ram Ai­yar of­ten gets the same ques­tion.

“I get al­ways asked, you know, if you can fix DNA, why both­er with RNA?” he told End­points News. “And it’s like ask­ing, which child do you pre­fer — your old­er one or your younger one?”

But in­vestors are ap­pre­ci­at­ing the dif­fer­ence. More than a year af­ter clos­ing its Se­ries A just shy of the megaround mark, Ko­r­ro Bio is back in the spot­light with $116 mil­lion in fresh cash and a lead can­di­date — tar­get­ing al­pha-1 an­tit­rypsin de­fi­cien­cy, or AATD.

Where­as gene edit­ing on the DNA lev­el promis­es a one-and-done ap­proach to ge­net­ic dis­or­ders com­pared to the tra­di­tion­al ap­proach of block­ing prob­lem­at­ic pro­teins, RNA edit­ing oc­cu­pies a space some­where in be­tween: a tran­sient yet pre­cise fix that gets to the root of a dis­ease.

And un­like the oth­er RNA modal­i­ties, from an­ti­sense oligonu­cleotides to RNA in­ter­fer­ence, Ko­r­ro is not in­ter­est­ed in knock­ing down pro­duc­tion of path­o­gen­ic pro­teins.

Nes­san Berming­ham

In­spired by a nat­ur­al mech­a­nism in squid and oc­to­pus, the biotech’s sci­en­tists use oligonu­cleotide guides to re­cruit an en­doge­nous en­zyme known as ADAR to a spe­cif­ic RNA site where they want to con­vert an A to a G — the kind of change that can make a world of dif­fer­ence for dis­or­ders like Rett syn­drome, co-founder and chair­man Nes­san Berming­ham pre­vi­ous­ly not­ed.

“All the tar­gets that we look at, we’re look­ing at it from a gain of func­tion stand­point,” Ai­yar said. “So ei­ther in­creas­ing the half life of a pro­tein, or up­reg­u­lat­ing the pro­tein, or re­pair­ing the pro­tein that is at a low lev­el, is re­al­ly go­ing to be the fo­cus. It’s a modal­i­ty that on­ly small mol­e­cules cur­rent­ly re­al­ly play in, but they haven’t been able to do that suc­cess­ful­ly be­cause they’re not high­ly spe­cif­ic.”

Ai­yar be­lieves those unique char­ac­ter­is­tics would al­low Ko­r­ro to tar­get preva­lent in­di­ca­tions, set­ting them apart from peers like Shape Ther­a­peu­tics, which he notes is fo­cus­ing on per­ma­nent edit­ing. And AATD, with some­where be­tween 100,000 and 150,000 pa­tients, is just one of them.

First brought on­to the broad­er biotech stage by Ver­tex, AATD is marked by mis­fold­ed pro­teins that go from the liv­er to the lung. Ver­tex tried to fix it by bind­ing to the pro­tein in a way that it be­lieves is re­spon­si­ble for the mis­fold­ing, but culled its ini­tial small mol­e­cule can­di­dates af­ter de­cid­ing they’re un­like­ly to show clin­i­cal ben­e­fit.

“It’s a very, very dif­fer­en­ti­at­ed pro­gram rel­a­tive to small mol­e­cule cor­rec­tors be­cause they’re just sit­ting in the pock­et and try­ing to pre­vent the mis­fold­ing, where­as we are fix­ing the amino acid se­quence on the RNA side to en­sure prop­er fold­ing,” Ai­yar said.

De­liv­ery, he reck­ons, will be the main chal­lenge here. But since Ko­r­ro is work­ing with mech­a­nisms like GalNAc and LNPs, Ai­yar notes that “we are stand­ing on shoul­ders of gi­ants” like Al­ny­lam and Io­n­is.

Even­tide As­set Man­age­ment led the Se­ries B, with par­tic­i­pa­tion from new in­vestors Fi­deli­ty Man­age­ment & Re­search Com­pa­ny, In­vus, Point72, Veri­tion Fund Man­age­ment, Monashee In­vest­ment Man­age­ment, Six­ty De­gree Cap­i­tal and an ad­di­tion­al health­care spe­cial­ist fund. All ex­ist­ing in­vestors joined, bring­ing to the syn­di­cate At­las Ven­ture, NEA, Wu Cap­i­tal, Qim­ing Ven­ture Part­ners USA, Sur­vey­or Cap­i­tal (a Citadel com­pa­ny), Cor­morant As­set Man­age­ment, MP Health­care Ven­ture Man­age­ment and Alexan­dria Ven­ture In­vest­ments.

Hav­ing grown the team from 27 to 59 in just around eight months, Ai­yar ex­pects the fund­ing to fu­el a con­tin­ued hir­ing dri­ve so Ko­r­ro has enough staffers to con­struct a siz­able pipeline. They’re de­vel­op­ing a CNS pro­gram to bal­ance out the lead liv­er in­di­ca­tion, with oth­er chron­ic in­di­ca­tions in mind, be­fore get­ting in­to the clin­ic, ide­al­ly in the next 18 months.

“The bi­ol­o­gy here is very nov­el,” he said. “I think it’s go­ing to be hard for peo­ple to dab­ble rather than, you know, take a very con­cert­ed ef­fort in terms of clin­i­cal de­vel­op­ment, be­cause the last thing you want to do is get to the clin­ic with a com­pound that looks good and then fall off the cliff very fast.”

Achiev­ing Dig­i­tal Trans­for­ma­tion: Un­lock­ing Cost Re­duc­tion, Clin­i­cal Ex­cel­lence & Pre­ci­sion Ther­a­peu­tics Man­u­fac­tur­ing

In the dynamic landscape of pharmaceutical and biotech industries, L7 Informatics is leading the charge in transforming traditional operations through digital innovation. With a firm focus on cost reduction, clinical improvements, reducing tech-transfer times, L7 Informatics is revolutionizing the way companies research, develop, and manufacture while also prioritizing the well-being of patients and providers thereby paving the way for a future where patients receive better treatments at lower costs.

End­points 20(+2) un­der 40, 2023; Bio­phar­ma's high­est-paid CEOs; N-of-1 CRISPR sto­ry goes on af­ter tragedy; and more

Welcome back to Endpoints Weekly, your review of the week’s top biopharma headlines. Want this in your inbox every Saturday morning? Current Endpoints readers can visit their reader profile to add Endpoints Weekly. New to Endpoints? Sign up here.

We will be off Monday in observance of Memorial Day — and when we get back, it will be a straight march to ASCO, BIO and more. Enjoy the (long) weekend!

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 170,200+ biopharma pros reading Endpoints daily — and it's free.

Rich Horgan (R) with his late brother, Terry

Rich Hor­gan spear­head­ed a gene ther­a­py for his broth­er. The tri­al end­ed in tragedy, but the work con­tin­ues for more pa­tients

Rich Horgan’s quest to create a custom gene therapy for his brother, Terry, ended in tragedy. But Horgan doesn’t believe it’s the end of the story.

Terry, a 27-year-old patient with Duchenne muscular dystrophy, died last October just eight days after receiving the therapy in a clinical trial in which he was the only participant. The case raised questions about the safety of certain gene therapies and what would happen to other drug programs under a nonprofit that Horgan created, called Cure Rare Disease.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 170,200+ biopharma pros reading Endpoints daily — and it's free.

Athena Countouriotis, Avenzo Therapeutics CEO (website via Nasdaq)

Ex-Turn­ing Point ex­ecs plan to have their next bet, Aven­zo, on the Nas­daq next sum­mer

The crew at Turning Point Therapeutics is back together for a new biotech that wants to acquire early-stage oncology small molecules, including antibody drug conjugates, and potentially form partnerships with China-based drug developers for ex-China rights as it eyes a speedy leap onto the Nasdaq around this time next year, CEO Athena Countouriotis told Endpoints News.

After selling Turning Point to Bristol Myers Squibb, announced at the onset of last year’s ASCO confab, she and colleague Mohammad Hirmand founded Avenzo Therapeutics. The CEO and CMO already have approximately $200 million in seed and Series A financing from five big-name investors to evaluate which drugs to bring into its pipeline. That includes SR One, OrbiMed, Foresite Capital, Citadel’s Surveyor Capital and Lilly Asia Ventures. Bidding wars for assets have led Avenzo to miss out on some deals in recent months, but the biotech has three active term sheets and hopes to bring in its first asset in the third quarter, Countouriotis said in a Friday morning interview.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 170,200+ biopharma pros reading Endpoints daily — and it's free.

Bio­phar­ma's 20 high­est-paid CEOs of 2022, each bring­ing in $20M+ pay­days

Even in a down year for much of the biopharma market, 20 CEOs brought in pay packages valued at more than $20 million, an Endpoints News analysis found.

Endpoints collected data on more than 350 CEO compensation packages, covering a wide range of pharma, biotech, and life sciences companies. All told, the 20 largest earners made over $725 million in 2022 — an average package of $36.4 million. Three brought in paydays over $50 million, and one CEO broke the $100 million mark.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 170,200+ biopharma pros reading Endpoints daily — and it's free.

Douglas Love, Annexon CEO

An­nex­on’s GA drug miss­es on pri­ma­ry goal but win on vi­su­al acu­ity will be fo­cus of planned late-stage tri­al

Annexon’s complement inhibitor didn’t prove better than sham at reducing lesion growth in a leading cause of blindness, but the biotech still plans to move forward on the back of secondary endpoints showing visual acuity preservation, which will “certainly” be the primary goal in a late-stage trial to be discussed shortly with the FDA, CEO Douglas Love told Endpoints News. 

The California biotech’s ANX007 was not statistically significant compared to pooled sham, the comparator, at 12 months in patients with geographic atrophy, per a Wednesday presentation. In every-month dosing, the GA lesion area changed about 6.2% from baseline (p=0.526) and 1.3% (p=0.896) in the every-other-month group. In a March note, Jefferies analyst Suji Jeong said a reduction of 20% to 30% would be “encouraging.”

Endpoints Premium

Premium subscription required

Unlock this article along with other benefits by subscribing to one of our paid plans.

The 20(+2) un­der 40: Your guide to the next gen­er­a­tion of biotech lead­ers

This year’s list of 20 biotech leaders under the age of 40 includes a huge range of ambitions. Some of our honorees are planning to create the next big drug giant. Others are pushing the bounds of AI. One is working to revolutionize TB testing. All are compelling talents who are still young in age, but already far along in achievement.

And, as in years past, we went over. The 20 are actually 22 because of two double profiles that reflect how important teamwork is in the industry. As one of our honorees, Joe Illingworth of DJS Antibodies, told me in our interview, “It takes a village to raise a biotech.”

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 170,200+ biopharma pros reading Endpoints daily — and it's free.

FDA ap­proves Lex­i­con’s heart-fail­ure drug af­ter de­feat in di­a­betes

The FDA on Friday approved Lexicon’s heart failure drug sotagliflozin following a string of setbacks for the pharma company, including an FDA rejection in diabetes and the loss of a development deal with Sanofi.

The dual SGLT1 and SGLT2 inhibitor will be marketed as Inpefa and is a once-daily tablet. It’s been approved to reduce the risk of cardiovascular death and heart failure-related hospitalization or urgent visits in adults with heart failure or type 2 diabetes mellitus, chronic kidney disease, and other cardiovascular risk factors. The label spans the range of left ventricular ejection fraction, including preserved ejection fraction and reduced ejection fraction, as well as patients with or without diabetes, Lexicon said Friday.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 170,200+ biopharma pros reading Endpoints daily — and it's free.

Eu­ro­pean Com­mis­sion to re­ceive few­er Pfiz­er-BioN­Tech vac­cine dos­es un­der amend­ed con­tract

The European Commission has made a few changes to its vaccine contract with Pfizer and BioNTech, reducing the dose volume while extending the delivery timeline to cope with “evolving public health needs.”

The Commission previously struck a contract in May 2021 for 900 million doses, with the option to purchase another 900 million. Of those, 450 million were expected to be delivered in 2023, though an amendment now calls for fewer doses. While neither the Commission nor Pfizer and BioNTech have revealed an exact amount, an unnamed source told Reuters that the amendment reduces the remaining expected doses by about a third.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 170,200+ biopharma pros reading Endpoints daily — and it's free.