Tovinontrine

“People see cardio as not just the province of Big Pharma anymore,” Cardurion CEO Peter Lawrence told Fierce Biotech in an interview. Cardurion Pharmaceuticals was made flush in 2021 thanks to a $300 million investment from Bain Capital. Now, the biotech is looking to challenge the statin-dominated cardiovascular status quo with a $260 million series B fundraising round. Bain also participated in this latest raise, which was led by Ascenta Capital. Other new investors include NEA, GV, Fidelity Management & Research Company, Millennium Management, Farallon Capital Management, Invus, Blue Owl Healthcare Opportunities, Delos Capital and Digitalis Ventures. Cardurion was founded by Michael Mendelsohn, M.D., a physician-scientist and previous global head of cardiovascular research at Merck, to develop new therapies for heart failure and other cardiovascular diseases. After forming a collaboration with Takeda in 2017, the biotech emerged with lab space, development resources and licenses to a bunch of Takeda assets. CEO Peter Lawrence, who joined in 2020, credits Cardurion’s success over subsequent years despite a tough market to general excitement about cardiovascular diseases and specific enthusiasm for Cardurion’s first-in-class drugs. “People see cardio as not just the province of Big Pharma anymore,” Lawrence told Fierce Biotech in an interview. “We have two clinical stage assets, three ongoing proof of concept trials, any one of which, if successful, could be somewhat transformational for a patient population.” Cardurion plans to harness the fresh funds to support later-stage clinical trials of its two leading drug candidates, a phosphodiesterase-9 (PDE9) inhibitor called CRD-750 and a calcium–calmodulin-dependent protein kinase II (CaMKII) inhibitor called CRD-4730, both of which are currently in phase 2 clinical trials. CRD-750 is being tested for both types of heart failure: heart failure with preserved ejection fraction, and heart failure with reduced ejection fraction. More than six million adults in the U.S. have heart failure, and heart disease is the leading cause of death in the nation. When the heart is stressed, it depends on a messenger molecule called cyclic guanosine monophosphate (cGMP) to regulate its response. PDE9 plays a role by breaking down cGMP so it isn’t overabundant, but in heart failure, this can lead to a lack of the needed cGMP for the heart to respond to stress. CRD-750 binds to PDE9 and prevents it from breaking down cGMP, which Cardurion thinks will allow the signaling molecule to build up and alleviate heart failure symptoms. “At each step of the way, preclinically and then clinically, the hypothesis has held,” Lawrence said. He believes CRD-750 has the potential to become the standard of care for heart failure. CRD-4730 is being tested for a rare genetic disease called catecholaminergic polymorphic ventricular tachycardia, which causes heart arrhythmia. Cardurion also plans to expand its CaMKII inhibitors into other, more common cardiovascular diseases. “Big Pharma has been trying to get CaMKII inhibitors in the clinic for almost two decades,” Lawrence said. “This is actually the first-ever CaMKII inhibitor that's been taken into human clinical testing.” In addition to furthering its own drugs, Cardurion plans to use series B funds to pursue and purchase other assets. The biotech is currently eyeing one or two preclinical targets that have shown great potential, Lawrence said, and he thinks Cardurion’s robust M&A strategy helped make the company enticing to investors. “It's a high bar because we have great internal assets,” the CEO said. “But if we see something that we love, targets that we think are going to be important, we're going to try and figure out a way to bring them in and get going on them.” Lawrence has been on the other side of the dealmaking table, too; he oversaw the $2.7 billion sale of oncology biotech ArQule to Merck & Co. in 2020. While Cardurion is interested in partnering with Big Pharma, he said, his focus is on pumping up the biotech’s independence. “Having been in and around M&A for 30 years, I think you can never build to [acquisition],” Lawrence said. “We're building the company to have a long gestation.”

Backed by a new $260-million series B financing, Cardurion Pharmaceuticals is looking to shake up the heart disease arena with a pair of first-in-class drug candidates, including a possible Entresto (sacubitril/valsartan) competitor.The biotech plans to funnel the proceeds primarily into later-stage trials for CRD-750, a PDE9 inhibitor to treat heart failure, and CRD-4730, a CaMKII inhibitor aimed at a rare genetic arrhythmic disease called catecholaminergic polymorphic ventricular tachycardia (CPVT).The financing round was led by Ascenta Capital, with participation from a roster of new and existing investors. "We…are very impressed with the significant clinical data the Cardurion team has generated for their innovative cardiovascular drug candidates, with strong initial validation for targeting these untapped signaling pathways," commented Evan Rachlin, co-founder and managing partner at Ascenta, who joins Cardurion's board.Its lead programme, CRD-750, is currently being evaluated in two Phase II trials involving 640 patients with heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF). According to CEO Peter Lawrence, the company's approach to targeting PDE9 represents a novel mechanism for activating the natriuretic peptide receptor signaling pathway.When the heart is stressed and experiences wall tension, it releases natriuretic peptides. These peptides bind to a receptor on heart cells, starting a process that produces cyclic GMP and ultimately triggering several actions that help the heart relax, reduce hypertrophy and prevent fibrosis."PDE9 is effectively putting a brake on the pathway by metabolising cyclic GMP, which is that critical second messenger. By taking off the brake, we think that we can get a much different and higher level of activity in the pathway and therefore greater outcomes benefit," he told FirstWord.This mechanism builds upon the success of Novartis' Entresto, which also activates the natriuretic peptide receptor signaling pathway but at the receptor level. Lawrence added that "Entresto is a great drug, don't get me wrong, but it is not doing everything that needs to be done in this pathway. We think we can do better."More to follow.