Corsera COO explains why the biotech is building an AI-powered risk assessment tool alongside RNAi therapies targeting CVD.
Earlier this month, US biotech Corsera Health announced an $80 million Series A raise, fueling its ambitious two-pronged strategy to push cardiovascular care towards a preventive model. The Boston-based company aims to pair long-acting preventive RNA interference therapies with an AI-powered platform designed to predict lifetime cardiovascular risk decades before disease manifests.
Rather than waiting for patients to cross treatment thresholds later in life, Corsera aims to identify individuals at elevated risk earlier and offer a well-tolerated preventive intervention in the form of a once-yearly injection. Oh, and the company also revealed it is already in clinical trials with the first component of a combined RNAi therapy – not bad going for an early stage startup.
Longevity.Technology: Co-founded by biotech industry veterans John Maraganore and Clive Meanwell, Corsera is focused on atherosclerotic cardiovascular disease, the world’s leading cause of death, which develops silently over decades through cumulative exposure to elevated cholesterol and blood pressure. In an interesting twist, alongside its therapeutic approach, the company’s AI-enabled risk prediction tool is being developed to help quantify the potential healthspan gains of intervening earlier. To explore the thinking behind Corsera’s dual focus on prediction and prevention, we sat down with chief operating officer Rena Denoncourt.
Having previously worked on RNAi medicines at Alnylam, Denoncourt led the TTR Amyloidosis franchise which included Onpattro, the first-ever RNAi therapeutic approved, and Amvuttra.
“As I was thinking about the next chapter of my career, I knew it had to be something big and bold – something that continued to have a major impact on human health,” she recalls. “The concept of having an impact on the number one global killer – responsible for 21 million deaths a year – was quite compelling. The more I learned about the background of the company and the concept of prediction and prevention, the more I knew I wanted to be part of that journey.”
Targeting two genes at once
In its recent funding announcement, Corsera also confirmed it had commenced its first-in-human clinical trial of a PCSK9-targeting RNAi therapy designed to lower cholesterol. Crucially, this is only the first part of the company’s therapeutic strategy, which it aims to combine with another RNAi therapy targeting angiotensinogen, a key driver of blood pressure, as part of a yearly preventative treatment.
“The goal is a once-annual subcutaneous injection, priced for broad accessibility, so it can truly have a population-level impact,” says Denoncourt. “Bringing all of this together results in a product with low disutility that changes the calculation for people – shifting them toward prevention rather than the current approach, where we let cholesterol and blood pressure rise and then try to bring them back down. That approach isn’t working, and we believe we can do better.”
PCSK9 and angiotensinogen are both well-validated targets in cardiovascular disease, and Denoncourt says Corsera has discovered novel molecules against these targets in partnership with Axolabs, a leading CRO in RNAi discovery.
“It’s critical that these molecules are both potent and highly specific, especially for such a large indication,” she adds, confirming that the company’s angiotensinogen program, will enter Phase 1 trial in mid-2026.
“Over time we’ll optimize the combined formulation so we ultimately have a single drug product targeting both pathways. We believe the biggest impact comes from targeting both genes together. A dual-targeting product simplifies things for the consumer – one simple injection with the greatest possible impact on changing the trajectory of cardiovascular disease over time.”
Developing for prevention
Of course, there are preventive medication options already available, but Denoncourt says these options are far from optimal.
“Yes, people could engage in prevention today – they could start in their 30s or 40s and take daily statins or antihypertensives,” she explains. “But the reality is that people don’t like taking daily pills. They start, they stop, and they don’t get the benefit of reducing cumulative exposure to LDL cholesterol and blood pressure.”
“What we’re trying to do is lower that disutility – that’s the game changer. That’s how we deliver the healthspan benefit we’re aiming for – extending the number of healthy years without heart attacks or strokes.”
Denoncourt also provides something of a hint about the commercial path Corsera plans to take with its RNAi medicine.
“We don’t envisage our therapy being constrained by today’s healthcare system,” she says. “To reach large populations, we’re thinking about disruptive, consumer-focused channels. There’s a lot to learn from the obesity market and from direct-to-consumer models more broadly. The goal is to reach people while they’re still healthy, rather than relying solely on traditional treatment pathways.”
On that point, how does Corsera plan on demonstrating that its therapy is appropriate for use by essentially healthy people?
“It’s an important question, and our thinking is still evolving,” says Denoncourt. “The concept is to enrich trials with people who have acknowledged lifetime cardiovascular risk but who are still healthy and don’t yet require guideline-directed medical therapy. That allows for placebo-controlled studies. The trials would likely have two components: one focused on validated biomarkers like LDL and blood pressure, and another cardiovascular outcomes trial run in parallel.”
Prediction as a component of prevention
The second pillar of Corsera’s approach is Klotho, the company’s AI prediction platform, which Denoncourt describes as “a new way of thinking about clinical guidance.”
“Existing risk prediction tools tend to have short time horizons, which inadvertently encourages people to wait until disease is more advanced,” she says. “Klotho is designed to provide a lifetime risk horizon. It may tell someone in their 30s or 40s that while their near-term risk is low, their lifetime risk is significant – and that starting earlier could meaningfully improve their healthspan.”
The model is trained on large datasets, but Denoncourt says the inputs are intentionally designed to be as simple as possible. Users input readily available information: cholesterol levels, blood pressure, age, smoking status, and family history. This information can be updated annually, allowing the model to update the individual’s risk trajectory in real time.
Importantly, Klotho also aims to quantify the benefit: how much healthspan could be gained by lowering their cholesterol and maintaining healthy blood pressure.
“That information empowers people to take action earlier,” says Denoncourt, explaining that the platform uses “deep causal AI” grounded in the underlying biology of ASCVD. “It’s not just built on population-based correlations; it incorporates biological understanding to enable individualized predictions.”
It’s unclear exactly when and how Klotho will be deployed, but Denoncourt says it’s important the tool has “broad accessibility and uptake.”
“We want it to be scientifically rigorous, transparent, supported by publications, and aligned with the medical community,” she says.
