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. 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.’
Their Staying Power Lies in their Patient-Centricity
Decentralized clinical trials (DCTs) were traditionally utilized in an isolated fashion prior to the COVID-19 pandemic. To continue their research within the constraints of the pandemic, sponsors and clinical investigators pivoted to a decentralized model out of necessity. At the onset, regulatory agencies offered some guidance on the digital approaches that are acceptable to ensure DCT approaches are applied in a way that maintains patient safety, as well as data quality and integrity.
Patrick Collison, co-founder of Stripe, has become one of Silicon Valley’s biggest advocates for new forms of funding and conducting science (Matt Winkelmeyer/Getty Images for WIRED)
It’s big days for biology.
The pandemic has seen a series of very public scientific breakthroughs: mRNA vaccine, Covid antibodies, CRISPR as therapy. The minds behind these advancements have graced magazine covers and received prestigious awards.
But the last two years have also, far more quietly, seen a series of new experiments in how to fund the next generation of scientific breakthroughs.
Since March 2020, investors, academics, a significant number of Silicon Valley types, at least one Russian billionaire and two crypto billionaires and, most recently, a few West Coast universities have launched a series of grant programs, institutes, NGOs and companies hoping to change how life science research is done. Though unaffiliated and varying greatly in both size and form, they have broadly promised to evade bureaucracy and misaligned incentives and advance both basic and not-so-basic research in ways they say can’t be done in either conventional academia or profit-focused biotech.
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The FDA this week announced further changes to revamp its structure, this time with alterations to its Office of the Chief Scientist that were agreed to by HHS late last month.
The FDA’s OCS has decided to shift its technology transfer program from the Office of Regulatory Science and Innovation to the OCS Immediate Office to further enhance the effectiveness of the agency’s outside partnership programs.
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Jeff Albers and Kate Haviland (Brad Bahner Photography/PR Newswire)
After a busy 2021 brought Blueprint Medicines its fourth FDA approval, the company is kicking off the new year with plans to shake up its C-suite.
Jeff Albers, Blueprint’s CEO for the past eight years, will be stepping down April 4 and transitioning to the executive chairman position, the biotech announced Wednesday morning. He will be replaced by COO Kate Haviland, who moves into both the chief executive and president roles. Christina Rossi also nabs a promotion from chief commercial officer to COO.
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Rick Modi, Affinia Therapeutics CEO (Affinia)
Nine months after Affinia Therapeutics raised $110 million in a Series B, the biotech has set its eyes on the Nasdaq.
The MA-based preclinical gene therapy biotech, which got $60 million in startup capital from New Enterprise Associates, F-Prime and Atlas in 2019, filed an S-1 with the SEC on Tuesday, announcing initial plans to go public and penciling in a $100 million raise. Affinia plans to list under the ticker $AFTX.
Ray Tabibiazar, SalioGen CEO
Roughly 10 months ago, a fledgling biotech emerged from stealth with a modest Series A and a big promise looking to develop gene therapy 3.0. The promise inched closer to reality Wednesday as investors have now hopped on board thanks to a new, nine-figure round.
SalioGen Therapeutics closed its $115 million Series B, the company announced Wednesday morning, aiming to push forward its ‘gene coding’ platform and growing preclinical pipeline. The biotech, which focuses on activating dormant mammalian enzymes to edit genes in vivo, secured the new raise after fleshing out some of the technologies’ applications, CEO Ray Tabibiazar told Endpoints News.
For anyone who’s been following how the US government has been allocating and shipping supplies of its Covid-19 treatments over the past year, the news has shifted so many times that it can be difficult to keep track of what’s still being shipped and where.
More change is coming this week too, as HHS has now decided to re-start shipments of both Eli Lilly (bamlanivimab plus etesevimab) and Regeneron (casirivimab plus imdevimab) monoclonal antibody products after a short pause because neither product works against the new variant Omicron. Lilly’s combo also was halted last June due to the presence of other variants.
Kicking off 2022, hundreds of pharmaceuticals, including some blockbusters, saw their list prices rise by about 5% on average. But overall, net drug prices (cost after rebates) declined for the fourth year in a row, potentially complicating already stalled drug price reform efforts.
Among the drugs seeing new increases as of Jan. 1 are Gilead’s bevy of blockbuster HIV drugs.
Biktarvy, which pulled in more than $7 billion in worldwide sales in 2020, saw a 4.8% price increase in 2021, and now, another 5.6% increase in 2022, according to a new report from the nonprofit 46brooklyn Research.
All the big R&D trends are on display in this new list of drug approvals for 2021. Plus one.
Add up everything OK’d from CDER and CBER, and you have 60 new drug approvals for last year, topping the 59 in 2020. That’s a close second to the 64 OKs that came out of the FDA in 2018. The dark days of the early 2000s are a distant memory now, with a host of hungry upstarts promising to make their own entries one day as Big Pharmas double down on innovation.
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