The expanding world of RNA therapies

Research into RNA interference, a Nobel Prize-winning technique to mute disease-causing gene mutations, has gained momentum in recent years. Since 2018, six medicines based on the technology have won approval to treat a variety of rare diseases, as well as high cholesterol. Dozens more are in clinical testing.

Yet the field's best-known companies, led by Alnylam Pharmaceuticals, have only taken RNAi so far. Their drugs are still largely focused on disease targets in the liver, limiting RNAi’s reach compared to other types of medicines. The technology’s maturation has also come at a time of fast progress for genetic medicines, like those built from CRISPR, that promise longer-lasting benefits.

A new group of startups, though, believes RNAi is ready to take another big leap forward. Backed by experienced and high-powered investors, they say the necessary technical advances have been made to significantly expand use of the technology.

Two, City Therapeutics and Judo Bio, debuted in October 2024 with more than $100 million in funding. Two others, Switch Therapeutics and Aro Biotherapeutics, raised sizable private financings in 2024 as well.

“There’s an opportunity to create a whole new generation of RNAi therapeutics,” said John Maraganore, the former CEO of Alnylam, who serves as City’s executive chair and advises Judo.

Excitement over RNAi’s potential dates back to the 1990s, when scientists Andrew Fire and Craig Mello discovered a way to use tiny, synthetic RNA strands to “silence” a gene. The concept caught on in scientific labs around the world and birthed a group of biotech companies including Alnylam, Arrowhead Pharmaceuticals and Dicerna Pharmaceuticals.

But it took two decades for RNAi research to yield an approved drug, as developers wrestled with how to safely and effectively deliver the therapies into cells. Along the way, large pharmaceutical companies like Novartis, Roche and Merck & Co. first embraced and then later retreated from the field.

Alnylam persevered with the help of partnerships and by focusing on the liver, using fatty spheres and sugar molecules to deliver its medicines. A string of drug approvals followed, starting with Onpattro in 2018, and turned Alnylam into one of biotech’s most valuable companies.

New techniques for delivering RNAi drugs to other tissues are now creating opportunities to broaden the technology’s use. "A lot of times, investments are driven by past successes," said Dee Datta, CEO of Switch Therapeutics.

In 2023, Alnylam revealed early evidence it could get an RNAi drug into the brain. Arrowhead, after an earlier setback, might have found a way to send RNAi therapies into the lungs, a tough target for nucleic acid therapies. Dyne Therapeutics and Avidity Biosciences have shown they may be able to use antibodies to deliver different RNA medicines — antisense oligonucleotides — into muscles.

“With all these new data points, I think people are saying, ‘Oh, wow, there's a new opportunity that’s emerging out there,’” Maraganore said.

City is one example. It’s developing synthetic RNAs meant to be smaller and more potent than their predecessors, as well as targeting molecules that can get RNAi therapies to more tissue types.

Judo, meanwhile, is "in the mold" of Alnylam, just with a focus on the kidney, said Jeff Goater, a venture partner at The Column Group and a Judo investor. The startup is making drugs that use a special ligand to send RNA payloads to specific types of kidney cells.

Goater's firm invested in Judo about a year after Atlas Venture incubated the startup in 2022. It co-led Judo’s seed financing as well as the company’s Series A. He said hearing Judo’s core concept was "one of those ‘aha’ moments."

The startup was built from "pieces of knowledge that were all available," Goater said. "It's almost like you whack yourself on the head and say, 'Oh, I wish I thought of that.’”

Switch, which debuted with $52 million in 2023, has a different twist on RNAi. It’s attaching compact sensors to RNAs so they only activate in certain cell types. The company is using the approach to target CNS disorders.

Another startup, Aro, is conjugating proteins it calls Centyrins to RNAi drugs and other oligonucleotides. It raised about $42 million in 2023 and has a medicine for Pompe disease in human testing.

Datta, the CEO of Switch, said the investment in new RNAi companies shows investors know they’re “just scratching the surface” of what the technology can do.

Alnylam’s work has "mostly addressed" the scientific risk involved, allowing new companies to experiment with what's next, Datta said.

In the past, Alnylam crowded out early competitors by acquiring much of the intellectual property covering RNAi. That likely made it difficult for other startups to form and raise funding, according to Maraganore.

But when a company gets as large as Alnylam is now, it’s hard to dedicate many millions of dollars “on some new frontier.” That’s what is “unique” about startups, Maraganore said.

“It's hard to imagine that Alnylam would spend $135 million on a new twist on RNAi or $100 million on kidney delivery,” he said. “They couldn’t.”

The biotechnology careers of John Maraganore and Clive Meanwell have brought them into collaboration time and time again.

As the respective founders of Alnylam Pharmaceuticals and The Medicines Company, the two previously partnered on the drug that would ultimately become Leqvio, which was later bought in a $10 billion acquisition of Medicines Co. by Novartis. And before Alnylam, Maraganore had led development at Biogen of Angiomax, which was later licensed to Meanwell’s company.

Now, the two have partnered to launch and run Corsera Health, which aims to make a preventive medicine for cardiovascular disease as well as an artificial intelligence tool to identify who could benefit from earlier heart intervention. 

Corsera’s target are younger people who are not “willing to wait 40 years to see whether they have a heart attack,” Meanwell said. “They're saying, ‘What can I find that will help me?’”

Corsera’s lead drug, an RNA interference therapeutic now in preclinical testing, is designed to be a once-yearly injection that blocks two targets known to drive cardiovascular disease: PCSK9 and angiotensinogen. The company expects to begin clinical testing by the end of 2025.

There are two antibody drugs that reduce LDL, or “bad,” cholesterol by binding to and blocking PCSK9, while Leqvio accomplishes the same goal by using RNA interference to reduce PCSK9 production. Currently, all three drugs are approved to treat people who have high cholesterol or, in the case of the two antibodies, to reduce cardiovascular risk in people with established heart disease.

Corsera aims to develop its medicine as a preventive treatment. It’s betting there will be demand from people who want to lower their lifetime risk of heart disease. Even there, though, it could have competition from Amgen’s PCSK9-targeting antibody, which is in advanced testing for primary prevention as well.

Maraganore and Meanwell argue an annual treatment could appeal to payers as well as patients, boosting treatment adherence and reducing barriers to access.

“We’re willing to trade off a little bit on maximal effect in order to get the benefit of that low disutility that enables adoption,” Maraganore said.

In its launch statement, Corsera said it intends to develop its medicine for “population-scale reach,” with “pricing that enables broad accessibility.”

Since leaving Alnylam in 2021, Maraganore has helped launch other biotech companies specializing in RNA interference. In 2024, he founded City Therapeutics, and he sits on the advisory board for another, Judo Bio.

Meanwell, after selling Medicines Co. to Novartis, helped launch obesity drug developer Metsera, which earlier in 2025 priced an initial public offering and presented promising Phase 1 data for its amylin-targeting shot.

The two will serve as co-CEOs of Corsera. 

Corsera is also developing an AI tool it calls Klotho Health, named after the Greek fate who, in mythology, controlled the threads of human life. Corsera’s name, meanwhile, is rooted in the Latin word for heart.

The company has raised more than $50 million since its formation in 2023, backed only by the founders and insiders. Maraganore and Meanwell said they decided it would be “efficient” if they worked on the company in stealth without tapping traditional venture capital firms.

“When you have a really novel idea, you have to have proof of concept before you can bring the professionals in,” Meanwell said. “Otherwise they tell you, ‘Come back when you when you've got something.’ We really think we've got something now.”

To many scientists and doctors, messenger RNA vaccines are an incredible feat of modern medicine. But to top health leaders in the Trump administration, shots made with the technology pose more risks than they do benefits.

In August, Secretary Robert F. Kennedy Jr. directed the Department of Health and Human Services to cancel some $500 million in contracts for research and development of mRNA vaccines, which are credited with helping control the COVID-19 pandemic.

The controversial move is a U-turn from the first Trump Administration, which created “Operation Warp Speed” to develop, manufacture and distribute COVID vaccines in record time, and in the process gave mRNA technology a starring role.

“To go from the identification of a pathogen to the development of an efficacious vaccine within the period of nine months — never happened in human history, and it was only made possible because of mRNA,” Jeff Coller, a professor of RNA biology and therapeutics at Johns Hopkins University, said in an interview with BioPharma Dive.

“It's absolutely perplexing as to why President Trump would allow Robert Kennedy to undermine his legacy in creating these life-saving therapeutics that literally saved millions of lives,” Coller added.

Scientists worry Kennedy’s actions, which have followed other major changes in U.S. vaccine policy, might leave American medicine lagging behind China and other countries that once sought access to the same technology. Moreover, mRNA has shown promise as a drugmaking platform in other fields besides infectious disease, most notably in cancer.

Moving away from mRNA vaccines to embrace older technologies could delay the U.S. government’s response in future pandemics, too.

“If we go back and use the technologies [Kennedy] is proposing should be used for vaccinations, we would be five, six years into a pandemic with millions of lives lost before we even had a vaccine that might be able to work,” said Coller. “So this is a critical national security issue.”

Long a prominent critic of vaccines, Kennedy has questioned mRNA shots since the early days of the pandemic. In ordering the cancellation of HHS contracts, he claimed mRNA vaccines “fail to protect effectively against upper respiratory infections like COVID and flu,” despite the success of the COVID vaccines developed by Moderna and partners Pfizer and BioNTech. Their safety and efficacy was initially proven in large, placebo-controlled studies, and then by the experience of the tens of millions of people who received them around the world.

While they are associated with some side effects, including, in rare instances, potentially concerning heart inflammation, most people have mild or no adverse reactions. COVID can cause heart inflammation as well.

“The goal of this vaccine is to keep you out of the hospital, keep you out of the intensive care unit, and keep you out of the morgue,” said Paul Offit, a vaccine expert and professor of pediatrics at the Children’s Hospital of Philadelphia, in an interview with BioPharma Dive. “That's the goal. [Kennedy] doesn't understand that, or he does understand that and he's just saying what he says to scare people.”

HHS provided a list of data it says demonstrates the harms caused by mRNA vaccines. The studies appear cherry-picked to support that conclusion, however, and were compiled by individuals who have criticized the U.S.’s pandemic response.

National Institutes of Health Director Jay Bhattacharya, who in October 2020 co-wrote a proposal to end COVID isolation policies, claimed the administration defunded mRNA research because of public distrust of the technology. The NIH has also deprioritized some COVID research.

“COVID-19 is probably the most politically charged disease of the last 50 years or more, and there are people who have very strong feelings about how the disease was treated, epidemiologically, at the societal level, that has almost nothing to do with the potential of mRNA,” said Jonathan Kagan, co-founder of mRNA drug developer Corner Therapeutics and professor at Harvard Medical School, in an interview with BioPharma Dive.

“It just happens to be that the only FDA-approved drugs on the market today that use mRNA are COVID-19 drugs,” Kagan added.

Messenger RNA, a nucleic acid that cells use to translate genetic code into proteins, provides an easily adaptable foundation for medicines. That flexibility means scientists can respond more quickly in response to viral outbreaks, such as with avian influenza, than they can with traditional types of vaccines, which typically take longer to design and produce. It has aided Moderna and Pfizer in updating their COVID boosters yearly.

“Bird flu may never become a pandemic, but if it does, this kind of technology allows you to respond much more quickly than a traditional technology like whole-killed viral vaccine,” said Offit.

Kagan, of Corner Therapeutics, sees investment in mRNA as essential to U.S. science leadership, similar to how the federal government’s support of research in nuclear energy and physics helped the U.S. win the Cold War.

“It appears that our federal government does not realize that we're in the middle of another arms race — it's an arms race for biomedicine,” Kagan added.

Recent studies have shown mRNA medicines’ promise against several cancers, including those of the pancreas, colon and brain. Targeting cancer is now a focus for Moderna, as sales of its COVID vaccine have evaporated and the Food and Drug Administration has narrowed COVID vaccine approvals.

Moderna was one of the companies affected by HHS’ contract cancellations. The company did not respond when reached out to by BioPharma Dive.

Others affected by HHS’ cuts, including Sanofi, CSL Seqirus, Gritstone Bio and Emory University, did not reply to BioPharma Dive’s request for comment.

While a leading mRNA drug developer, BioNTech was not affected. In an emailed statement, the company said it continues to “believe in the potential of mRNA in medicine” in both infectious disease and in cancer.

Kagan believes positive data for mRNA cancer treatment could eventually sway the administration’s attitude toward the technology, but warned that its current policies will weigh on the field.

“When you cut back investment in this area, there's less chance for tangible innovation,” Kagan said.

Otello Stampacchia, managing director at life sciences investment firm Omega Funds, told BioPharma Dive that, while the firm doesn’t typically back vaccine developers, HHS’ messaging does affect investment broadly.

“It's super hard for a firm like ours to touch those things when there's such a clear political blowback," Stampacchia said.

Coller, who is also on the board of the Alliance for mRNA Medicines, noted that in a survey conducted by the group earlier in 2025, about half of respondents indicated their mRNA-developing companies had already experienced negative consequences from federal policy changes.

“These actions are scaring manufacturing and biotech away from the United States,” Coller added. “I think [the HHS announcement] was a shot across the bow to the industry that you're not welcome here anymore,” Coller added.

Coller and Kagan both agreed HHS’ actions give an opening to other countries like China to make up ground in mRNA drug development.

“China is accelerating, while the United States is killing the investments that they've already made and stifling new ones,” Kagan said. “That differential, sadly, is going to increase if we stay on this path.”

“The future is very bright for mRNA research in other countries,” Coller said.

Gwendolyn Wu contributed reporting.

Thorsten Stafforst remembers being told to stop wasting his time.

It was early last decade and scientists across the world were buzzing over a new tool, called CRISPR, that could precisely alter human DNA. Working in the German college town of Tubingen, Stafforst and fellow researchers at the local university were instead engrossed by the prospect of rewriting RNA, DNA’s chemical cousin.

“Everybody told me, ‘Why do you want to edit RNA?’” Stafforst said. “You can edit DNA now; that doesn’t make sense.”

Yet in 2012 they and, shortly afterwards, a group at the University of Puerto Rico figured out how to use a naturally occurring enzyme to swap out single “letters” in RNA sequences. Their discovery drew from research into the biology of octopuses and squids, which are adept at rewriting their own RNA. And as with CRISPR, the findings pointed to a novel way of treating disease. In a world newly enchanted by gene editing, however, their papers were met with far less acclaim.

More than a decade later, RNA editing is a fast growing corner of the biotechnology sector. About a dozen companies, from privately held startups to established biotech firms, are pursuing the technology. One already has early, but promising, clinical trial results. Others could follow soon. And large pharmaceutical companies, such as Eli Lilly, Roche and Novo Nordisk, have taken an interest.

RNA editing’s proponents say it may be safer and more flexible than DNA editing. Those advantages, they contend, will enable RNA editing to address more diseases, including common conditions that are now beyond genetic medicine’s reach.

“It has all the features of a technology that could leapfrog other editing technologies,” said Michael Ehlers, a general partner at Apple Tree Partners and the CEO of RNA editing startup Ascidian Therapeutics.

But RNA editing is far less tested than CRISPR, never mind other ways drugmakers already harness RNA to make medicines. Researchers and biotechs in the field aren’t yet sure whether RNA editing will work as intended, or whether it will prove as potent in humans as laboratory experiments have suggested. And one of the technology’s purported strengths may end up a flaw, as the transient nature of RNA editing’s effects could limit its benefit or force developers to administer it more often than desired.

Partly as a result, companies are testing out different approaches as they search for the best formula. “It’s still a very early technology,” Stafforst said. “We will have to learn how to make the best drugs, and that will take a while.”

Here’s where things stand:

What is RNA editing, and how does it work?

RNA molecules are shifty, versatile chains of nucleotides. While they can take different forms and hold various functions, their main job is helping cells turn the genetic information of DNA into proteins.

Sometimes, though, the final protein product looks different than the blueprint RNA translates. One way this occurs is by the work of enzymes that bind to RNA and switch one genetic letter for another. Those enzymes are named after what they do — adenosine deaminase that acts on RNA, or ADAR — and the changes they make can alter a protein’s shape or function. For instance, squids use ADARs to rewrite the expression of genes in their central nervous system.

Last decade, Stafforst’s group in Germany and then another led by Joshua Rosenthal, a senior scientist at the University of Chicago’s Marine Biological Laboratory, discovered how to co-opt this system. In separate research papers, they described ways to shepherd ADAR enzymes to a specific spot on messenger RNA molecules and change the transcription of the associated protein. Stafforst’s group and a team of Stanford University scientists led by Jin Billy Li followed up in 2019 with a paper outlining a simpler approach.

Their findings opened up new possibilities for drugmakers. A targeted RNA edit could correct the effects of a gene mutation that causes the production of a harmful protein, or boost levels of a protein that’s lacking. It could be used to mimic helpful genetic variants, break apart troublesome interactions between proteins or target conditions without a genetic component altogether.

“There's a whole variety of different applications that are uniquely possible with RNA editing,” said Kris Elverum, CEO of Airna, a startup co-founded by Stafforst.

Biotechs are now attempting to prove they can turn that potential into medicines. Wave Life Sciences, one of the field’s leaders, uses strings of nucleotides to coax ADAR enzymes into making a specific edit. Its lead drug candidate, for an inherited disease called alpha-1 antitrypsin deficiency, or AATD, changes a letter on mRNA molecules, compelling the body to make a missing protein.

Other companies, like publicly traded ProQr Therapeutics and Korro Bio, as well as startups Airna, Shape Therapeutics and ADARx Pharmaceuticals, are pursuing similar ideas. “We’re all trying to get ADAR, this protein that sits inside of you, to actually make these edits very specifically, very safely, and not hit other adenosines throughout the RNA,” said Ron Hause, Shape’s senior vice president and head of AI.

There are differences in their approaches, though, ranging from the tools they use to screen for molecular guides, the RNAs they choose and the delivery methods they’re evaluating.

ProQr is trying to use its RNA editing therapies to induce the effect of variants known to protect against heart disease or to prevent toxic bile acid buildup in the liver. Korro is targeting AATD, as well as exploring how to correct for a troublesome genetic mutation in Parkinson’s disease. Shape is packaging ADAR enzymes into engineered viruses and sending them into the brain, where they could help treat neurological conditions.

There are other twists to the concept. Rather than try for single-letter changes, Amber Bio and Ascidian intend to rewrite whole stretches of RNA, akin to editing words or sentences in one go. Amber is using so-called Cas proteins — made famous with CRISPR — to make larger RNA edits. Ascidian, meanwhile, is editing “exons,” the sections of DNA that encode for proteins. It does so by using engineered molecules to replace a mutated exon with a functional version when DNA is converted into RNA.

These twists could allow RNA editing to be used for diseases caused by many different mutations rather than just one, or even broader groups of people with a particular condition. Ascidian’s first candidate, for a genetic eye condition called Stargardt disease, replaces more than 20 exons at a time.

Exon editing “really opens the aperture to a much broader patient population in any given genetic disorder,” said Ascidian Chief Scientific Officer Robert Bell.

What are the advantages over other technologies?

Gene editing research spread through biotech like wildfire over the past decade. A generation of biotech companies formed following the 2012 paper that first described the potential for CRISPR, a bacterial defense system, to be adapted to edit human genes. Since then, CRISPR science won a Nobel Prize, and a CRISPR drug for the blood diseases sickle cell and beta thalassemia reached market. Newer technologies like “prime” and “base” editing, designed to make more precise changes to DNA, have emerged, too.

CRISPR and its offshoots work by breaking DNA or rewriting genetic code — permanent changes that can carry unintended consequences. A wayward edit might disrupt the function of a healthy gene or, theoretically, turn cells cancerous down the road. That raises the bar for using gene editing, Stafforst argues. “You really need to have a fatal disease and a very bad prognosis,” he said. (Not everyone agrees, however.)

DNA editing therapies may also not be well suited for chronic conditions, or disorders for which people with the same underlying mutation experience variable symptoms or disease severity, said Korro CEO Ram Aiyar.

“You don't know environmental factors. You don't know what other genetic manifestations will lead to difference in severity, and you don't want to find that out after you treat them with a one-time therapy and find out that it doesn't really work,” Aiyar said.

RNA editing developers believe their technology can solve some of those problems. Mistakes caused by oligonucleotide-mediated editing should be able to be reversed without causing long-term harm. The transient effects of treatment would position drugmakers to treat acute conditions or to subtly dial protein expression up or down by adjusting dosing.

“It’s a class of new medicines that we can open up as a field,” said Wave CEO Paul Bolno.

Bolno’s company and others will build on the decades of work already done by makers of RNA-based therapies like antisense oligonucleotides and small interfering RNAs. Wave and ProQr are following a similar playbook, for example. Their treatments consist of specially engineered RNAs that enter liver cells with the help of a sugar molecule, not a microscopic virus or other substance the body may reject as foreign.

“We can take advantage of that history, but now apply it to the field of editing,” Bolno said.

Developers hope the end result is drugs with the power of gene editing, but that more closely resemble “traditional” drugs, said Elverum, Airna’s CEO.

“We’re all much more comfortable with medicines that can help us today, but give us the flexibility of being able to adjust based on how our health evolves in the future,” Elverum said. “It’ll take the word ‘editing’ and flip it on its head.”

Roadblocks remain, of course. Current ADAR-based approaches are only able to make a specific single-letter change in RNA, limiting their potential to such diseases that involve those letters. Drugmakers don’t yet know whether the edits they make will be efficient enough to produce a therapeutic benefit, how long that might last or if unexpected safety issues will crop up.

“The most important next step will be clinical proof that the modality, in principle, works,” Stafforst said in August 2024.

Which companies are working on it?

By the tail end of 2024, there were at least 11 companies developing therapies that edit RNA in one way or another.

Wave, which went public in 2015, has spent years working on multiple methods of RNA drugmaking. But in recent years it’s added RNA editing capabilities to its mix and formed an alliance with GSK.

ProQr made its Wall Street entry in 2014 and also recently made RNA editing a focus. The company was developing antisense oligonucleotides for eye diseases, but changed course after a clinical setback. It has a research partnership in place with Eli Lilly.

Korro, which was co-founded by Rosenthal, is a newer arrival on public markets. The company was formed a decade ago and raised more than $200 million from private investors before going public through a reverse merger in 2023. It’s working with Novo Nordisk. Beam Therapeutics, an established biotech in gene editing, is dabbling in RNA editing too.

Joining those companies are a new crop of startups.

Ascidian, which launched in 2022 with the backing of Apple Tree, already has a collaboration with Roche. It’s one of only a few companies, along with Wave and South Korea’s Rznomics, to start a clinical trial for an RNA editing drug.

Airna emerged from stealth in 2023 with $30 million in funding led by Arch Venture Partners. Like Wave and Korro, it is investing in AATD research. New Enterprise Associates, Decheng Capital and Breton Capital, among others, have poured nearly $150 million into Shape Therapeutics via two funding rounds. Shape is working on RNA editing therapies for the brain through a deal with Roche, according to Hause.

ADARx Pharmaceuticals is making drugs that can either silence or edit messenger RNA. It has around a dozen programs in development across genetic, cardiometabolic and central nervous system diseases, one of which is in clinical testing, according to its website.

The field is still attracting new entrants. Radar Therapeutics emerged in 2024 with a $13 million seed round. Amber took in a $26 million seed round in 2023.

“I'm hoping all of us are successful, because we all go at it [from] a different direction,” said Korro CEO Aiyar. “A rising tide will raise all boats here.”

As with initial efforts by CRISPR biotechs, many of these companies are targeting the same diseases. And insiders believe the RNA editing field could undergo some of the same ups and downs as gene editing. Aiyar noted how every new technology goes through a hype cycle, when exuberance is followed by disillusionment and, later, a rebound that actually delivers workable products.

“There are folks that still really don’t know where RNA editing fits in the landscape,” he said.

While initial clinical data may “derisk” RNA editing, afterwards comes the work of making drugs that last longer, are more powerful and, eventually, solve thorny health problems. Stafforst, at the University of Tubingen, envisions a future when RNA editing will be used to adjust signaling cues in metabolism, opening up its use in treating heart and metabolic conditions.

“There’s still enough to do for the next 20 years,” he said.

An experimental RNA editing medicine from Wave Life Sciences helped study participants with a rare liver and lung disease produce a protein their bodies can’t make, but wasn’t as effective in testing as investors had anticipated. 

In 2024, Wave revealed promising results from the first two volunteers with alpha-1 antitrypsin deficiency to receive a single dose of its therapy in a clinical trial. On Sept. 3, it said “therapeutically relevant” protein levels were observed in patients who’d received several doses, and similar results were seen in patients who received a single, higher dose.

Wave said the findings support “monthly or less frequent dosing” and added that there were no serious adverse events or study discontinuations. Still, the amount of so-called AAT protein expressed in people who’d received that higher dose — or multiple administrations of a lower dose — wasn’t much greater than what was seen in those who got one low dose. Wave shares fell after the Sept. 3 announcement.

Wave’s treatment, WVE-006, was the first of its kind to reach human testing.

WVE-006 edits RNA, the messenger molecules that turn DNA into proteins. That approach is seen as a potentially safer and more flexible alternative to DNA editing and, accordingly, has drawn interest from an array of investors and drugmakers. But RNA editing is also far less proven, making each study update from Wave a referendum on the concept. 

Wave in 2024 reported that, after receiving a single, 200 milligram dose of WVE-007, the first two patients in its trial began producing the “wild-type” AAT protein their bodies normally can’t. The total levels of AAT protein — including that important wild-type version — reached, on average, about 11 micromolars in blood plasma concentration within 15 days. That result surpassed investor expectations and met a threshold set by regulators for approval of AAT augmentation therapies. 

Investors were hoping to see more powerful effects in Wave’s latest update, which involved eight patients who received a 400 mg dose and eight who’d gotten a series of twice-monthly injections at the lower dose. According to Wave, the former group hit about 12.8 micromolars of total AAT protein, on average, while the latter got to 11.9 micromolars. Wave said all side effects were deemed mild to moderate, and that there were no notable elevations in liver enzyme levels, which can be a sign of organ damage. 

Wave also said a single patient spiked to over 20 micromolars during an “acute” response to the type of “exacerbation” that can damage the lungs of people with AATD. That finding suggests WVE-006 can help patients produce “protective protein when needed,” CEO Paul Bolno told analysts on a conference call. 

The data show the therapy “can rise to meet the occasion, wherever it is, to drive down and protect during exacerbations,” he said. “That is the functional cure.” 

Despite that apparent promise, Wave shares fell as much as 22%. Protein levels for the multidose group “narrowly hit” what Jefferies analysts projected as a positive result, while the higher dose data missed the firm’s mark, wrote Roger Song. Excluding the one patient with an acute response, the single dose group achieved a mean 11.8 micromolars of AAT protein, roughly the same result as the multidose group. The findings require “a bit more digestion” than WVE-006’s last readout, added Mizuho Securities’ Salim Syed. 

Still, multiple analysts came to Wave’s defense. The share sell-off reflects “outdated investor expectations,” wrote Leerink Partners’ Joseph Schwartz, as the findings show “higher levels of AAT protein do not appear to be required to drive efficacy and protection in AATD.” Song and Syed added that all study groups hit the mark set by regulators, even if not by much. 

The results are “still clinically meaningful,” Syed wrote. 

Wave is testing monthly administrations of the higher dose and expects to deliver results in early 2026. Korro Bio, meanwhile, will share early results for a rival RNA editing drug for AATD later in 2025.

GSK has global rights to Wave’s AATD medicine under a broad partnership the companies signed in 2022. 

Atalanta Therapeutics, a Boston biotechnology company making medicines for the brain from RNA molecules, in January 2025 raised $97 million to bring its first two drug candidates into clinical testing.

The Series B round was co-led by EQT Life Sciences and Sanofi Ventures and involved seven other high-profile backers, including Novartis’ venture arm. Since publicly launching in 2021, the startup has now raised some $260 million, including upfront payments from partnerships with Biogen and Roche.

The funding will advance research originating from the lab of University of Massachusetts professor Craig Mello, whose work some three decades ago helped unearth a drugmaking method known as RNA interference. Medicines built this way use tiny, synthetic RNA strands to silence genes from making harmful proteins. While a handful have reached market, they’re mostly limited to disease targets in the liver.

Atalanta is part of a new generation of companies trying to broaden the reach of RNAi by delivering the medicines into other tissues. Over the last few years, companies like Switch Therapeutics, Judo Bio and City Therapeutics have emerged with twists on RNAi.

Atalanta CEO Alicia Secor, who has led the company since its founding by Mello and two other UMass researchers, said her company aims to “overcome the historical challenges” of sending oligonucleotide therapies into the brain.

The company links two small interfering RNAs together in a way that’s meant to allow them to penetrate deeply and durably into brain tissue. Atalanta claims its approach can create RNA medicines that potently impact neurological disease targets, while sidestepping some of the toxicity issues that have hampered past attempts.

“We have kind of cracked the code for delivering oligonucleotides effectively to the brain,” she said.

Atalanta hadn’t previously revealed the drugs it’s working on. Secor says the company has 10 programs in development, led by drugs for Huntington’s disease and a genetic form of epilepsy.

A progressive, neurodegenerative condition, Huntington’s has proven a tough target for drugmakers. Several experimental therapies, among them high-profile prospects from Roche and Novartis, failed in testing in the last few years.

Atalanta’s therapy, dubbed ATL-101, muffles the gene making the “huntingtin” protein, which, when misformed in people with Huntington’s, clumps up in neurons. Secor says it could succeed where others have failed because of the “sustained” and “deep brain penetration” it’s designed to achieve.

“Nothing's really worked, but nothing's really done what we are showing the ability to do,” she said.

A second drug called ATL-201, meanwhile, targets a gene called KCNT1, mutations in which can cause a form of epilepsy that can’t be controlled with anti-seizure medications. Preclinical testing suggested ATL-201 may be able to reduce the frequency of seizures, Secor said.

Atalanta is also working on therapies for chronic pain and Alzheimer’s disease.

“The universe of targets is expansive,” Secor said, “because the unmet needs in these diseases remains so high.”

Atalanta’s Series A round in 2021 was funded exclusively by F-Prime Capital.

Novartis is once again taking aim at Parkinson’s disease, through a deal with Arrowhead Pharmaceuticals that could be worth billions of dollars.

The deal, announced Sept. 2, revolves around a preclinical drug that Arrowhead designed to silence the genetic instructions for “alpha-synuclein,” a protein tied to Parkinson’s disease and other brain-eroding illnesses. Novartis has now agreed to pay $200 million for an exclusive license to research, develop, manufacture and commercialize the drug.

Arrowhead could receive an extra $2 billion or more by hitting certain development goals and collecting royalties on any resulting products. Per deal terms, Novartis will also be able to select additional disease targets outside of Arrowhead’s current pipeline to advance using the latter’s drugmaking technology, which centers on a technique called RNA interference.

The companies plan to close their agreement sometime in 2025.

For each program Novartis licenses, Arrowhead will do all the preclinical research that regulators require before they clear a drug for human testing. Novartis would then take charge of the programs, ushering them through the remaining experiments and onto market.

“We believe that one way to effectively target core drivers in Parkinson’s and other neurodegenerative diseases requires completely novel approaches to deliver RNA medicines to the brain,” said Fiona Marshall, president of biomedical research at Novartis, in a statement.

Arrowhead’s technology has “great potential to achieve the type of widespread and effective delivery in key brain structures that will be necessary to see the full benefit of RNA medicines in neurodegeneration,” Marshall added.

Like many neuron-destroying diseases, Parkinson’s has proven exceptionally difficult to treat. In 2024, a potential therapy developed through a partnership between Novartis and Belgium-based UCB came up short in a mid-stage study that enrolled more than 450 participants. Around the same time, Roche disclosed that a Parkinson’s drug it’s been developing for over a decade flunked a second key study — though the company has since determined there were enough positive signals to push the drug into late-stage testing.

AbbVie has hit snags as well, terminating in recent years a couple Parkinson’s-focused collaborations with smaller biotechnology firms. Yet the company did score two wins in this space in 2024 by securing approval for a drug now sold as Vyalev and by notching surprisingly strong clinical results for a molecule it picked up through the nearly $9 billion acquisition of Cerevel Therapeutics.

For Arrowhead, which has already partnered with or licensed drugs to Amgen, GSK, Takeda Pharmaceutical, and Johnson & Johnson, the agreement with Novartis represents another big pharma vote of confidence in the company’s technology.

While Arrowhead currently has no commercial products, that may change soon. The company has submitted for approval a medicine for a rare condition that impairs the body’s ability to break down fats, and expects to hear a verdict from the Food and Drug Administration by mid-November.