PCSK9 inhibiting antibodies(A-CUBE)

Corsera’s lead program is a dual-acting preventive RNAi candidate that is expected to enter the clinic this year.\n Industry giants Clive Meanwell, M.D., and John Maraganore, Ph.D., have unveiled Corsera Health, a new biotech aiming to disrupt the cardiovascular landscape with a once-annual preventive heart disease candidate and an artificial intelligence risk-predicting tool.“Imagine a world without cardiovascular disease. That\'s what we\'re aiming to do,” Corsera co-CEO Maraganore, founding CEO of RNAi pioneer Alnylam Pharmaceuticals, told Fierce Biotech in an interview.“This is the most important thing I\'ve ever done,” continued Maraganore, who has been involved in the discovery and development of several first-in-class drugs, such as anticoagulant Angiomax (bivalirudin). “This is an opportunity to really transform the future of medicine and save potentially millions of lives by preventing cardiovascular disease.”  “We\'re very good at treating heart attacks and strokes now,” co-CEO Meanwell said in a joint interview with Fierce.“But everyone we\'re talking to is really agreeing that preventing them in the first place would be a much better idea,” continued Meanwell, who helped create PE firm Population Health, Leqvio-developer and Novartis-acquired The Medicines Company, plus next-gen obesity biotech Metsera. The two biotech veterans have pooled their own money and brought in a few others to raise $50 million, money that is fueling the Boston-based company through the early stages. “It\'s not any formal investment group at this point,” Maraganore explained. “Obviously, we\'re going to raise more capital and bring in professional investors. But, to be honest, we\'ve wanted to keep control of the reins of this effort ourselves, without worrying about other voices and other things that might derail our conviction in what we\'re doing.” The heart of Corsera The money has powered discovery efforts for Corsera’s lead program, a preventive RNA interference (RNAi) candidate that is slated to enter the clinic before the end of this year.The dual-acting RNAi medicine is designed to reduce the production of two cardiovascular disease markers: PCSK9 for cholesterol and angiotensinogen (AGT) for blood pressure.The strategy is supported by data from Corsera scientific co-founder Brian Ference, M.D., that found early reduction in LDL cholesterol and blood pressure can prevent cardiovascular disease two to three times more effectively than intervening later in life. The Mendelian randomization included almost 370,000 participants and was shared as a late-breaking presentation at the European Society of Cardiology Congress.Corsera plans on filing an investigational new drug (IND) application for the PCSK9 monomer in about a month, according to Maraganore. The proposed dose-escalation study will evaluate the durability of the candidate over one year, he said.A second IND submission focused on the AGT biology will likely follow in four to six months, he said.The asset was discovered under a Corsera contract at Axolabs, a CRO/CDMO that touts its own RNA platform. The two companies have been working on the product’s design for the last two years.Corsera’s other key focus is an AI tool dubbed Klotho Health. The calculation tool is driven by causal AI and is built to predict an individual’s lifetime risk of heart disease. The tool quantifies the benefit that lowering LDL cholesterol—often referred to as “bad cholesterol”—and blood pressure can have on cardiovascular health.Currently, 10-year cardiovascular risk scoring is available, but Corsera’s AI approach differentiates itself because it can be used at any age for any time span, Maraganore explained.Together, the experimental RNAi medicine and AI tool make up Corsera’s proactive approach that the leaders hope will help intervene before cardiovascular damage occurs, subsequently slashing morbidity and mortality rates associated with the disease. Act III The two co-CEOs are industry titans on their own, but they also have a 30-year track record working with each other.“This is our third act, and it is, without a doubt, the most important of our three acts,” Maraganore said.Back in the ‘90s, when Maraganore invented a drug at Biogen, he partnered with Meanwell’s The Medicines Company to develop and bring the drug—now sold as Angiomax—to market. That was the first act.Then, in 2013, Maraganore-led Alnylam partnered with The Medicines Company again, this time on a drug called inclisiran, later sold as Leqvio.The siRNA injectable lowers LDL cholesterol and garnered the attention of Big Pharma Novartis. The Swiss drugmaker decided to acquire The Medicines Company for $9.7 billion in 2019 for the next-gen heart drug, which snagged FDA approval in 2021.  Now, the two are back together again and expect their efforts to shake up the cardiovascular space even more than before.The co-CEOs are viewing drug development differently than most this time. Corsera isn’t going for bigger: The biotech is aiming for easier.  “There\'s a bit of an obsession with ‘mine’s bigger than yours,’ usually,” Meanwell said, describing the focus on having best-in-class potency or effect. He cited the PCSK9 monoclonal antibodies space as an example, with different drugmakers zeroing in on LDL-lowering percentages, and also obesity drug developers’ intense focus on exact weight loss percentages.“But here, we\'re not necessarily going for ‘mine is bigger than yours,’” Meanwell continued. “We\'re going for ‘mine’s easier than yours, mine’s more reliable than yours, mine\'s lower cost than yours, more accessible than yours.’”And the duo believes Corsera is uniquely positioned to do just that. The table is already set  From past experience, the partners know how to bring new drugs to market at a lower cost. When the pair worked on Angiomax, they ran clinical evidence generation at about a third of the industry’s average cost for the same quality and speed, Meanwell said.“The tools that we need are already on the kitchen table,” Meanwell explained, referencing the two leaders’ combined expertise and industry innovations. “And what we\'re trying to do here is bolt them together in a new industrial model.”“The trick here is to—and I\'ll use the word ‘disrupt’ in a true Christensen sense—disrupt the way we think of cardiovascular disease,” he continued.The innovation theory centers on a new product that enters the bottom of an existing market and eventually displaces established competitors, normally by being more affordable and accessible.Meanwell believes the strategy is “the only viable way” to reach millions of people with heart health issues.But the two aren’t going at it alone. Joining the blockbuster pair at the table is fellow Corsera co-founder Chris Cox, co-founder and general partner of Population Health; Chief Operating Officer Rena Denoncourt, formerly of Alnylam; scientific co-founder and clinical advisor Brian Ference, M.D.; Chief Scientific Advisor Hans-Peter Vornlocher, Ph.D,; and co-founder and development advisor Peter Wijngaard, Ph.D.; among others. A stadium full of people At the heart of Corsera’s pitch is the fact that cardiovascular disease is the leading cause of death worldwide, with 21 million people dying every year. “That\'s a stadium full of people a day that die—46,000 [deaths] a day,” Meanwell emphatically described the figure. “It\'s just a colossal burden.”Corsera’s focus on preventive care and consumer wellness is designed to change the trajectory of cardiovascular disease for millions, an effort that would not only improve life quality and longevity but also cut down on healthcare costs and improve human productivity.“We\'re taking all the tools that are that have been put on the table—in part by us, but also by others—and putting them together to create something very disruptive,” Maraganore said.