Pelacarsen

To bring pacibekitug into its pipeline, Novartis is paying $48 per share of New York-based Tourmaline Bio.\n Novartis is paying $1.4 billion to get its hands on Tourmaline Bio and its former Pfizer cardiovascular drug that impressed in a phase 2 study earlier this year.At the center of the deal is pacibekitug, an antibody targeting interleukin-6, which hit the primary endpoint of a phase 2 study in May by sharply reducing levels of C-reactive protein (CRP), a biomarker for cardiovascular disease risk, in patients with chronic kidney disease.Tourmaline had pitched that study as the launch pad for developing pacibekitug as a treatment for atherosclerotic cardiovascular disease (ASCVD) along with other cardiovascular diseases. Interleukin-6 is a proinflammatory cytokine, and inflammation is known to be a driver of atherosclerosis. The liver produces CRP in response to inflammation, and patients with atherosclerosis typically have higher levels of the protein in their blood.“With no widely adopted anti-inflammatory therapies currently available for cardiovascular risk reduction, pacibekitug represents a potential breakthrough in addressing residual inflammatory risk in ASCVD with a differentiated mechanism of action targeting IL-6,” Novartis Chief Medical Officer Shreeram Aradhye, M.D., said in this morning’s release.“Inflammation is a major driver of cardiovascular disease, and the team at Tourmaline has made significant progress with this asset,” Aradhye added. “We are excited to bring pacibekitug into the Novartis portfolio and collaborate with the Tourmaline team to advance its development as we diversify our efforts in cardiovascular care.”To bring pacibekitug into its pipeline, Novartis is paying $48 per share of the New York-based biotech—equivalent to $1.4 billion—which marks a significant increase on the $30.18 price that Tourmaline’s shares closed at on Monday and is well above the $20 at which the company’s stock entered the year.The Tranquility phase 2 trial, which boosted Tourmaline’s fortunes, enrolled 143 patients with elevated levels of CRP and chronic kidney disease, who are at high risk of ASCVD.Individuals who received 50 mg of pacibekitug saw an average reduction in CRP levels at Day 90 of 86%, while a 25-mg group saw 75%, and the 15-mg group dropped 85%, compared to a 15% reduction in the placebo cohort. At the time, the biotech described the drop in CRP levels as “rapid, deep and durable,” while pointing out that the study marked the first time that an IL-6 inhibitor had been tested in a clinical trial with quarterly dosing.Pacibekitug originated at Pfizer, with Tourmaline licensing the asset in 2022. In addition to the cardio indications, the biotech has been testing the antibody in a phase 2 trial in the autoimmune disorder thyroid eye disease, while Pfizer had previously studied pacibekitug in Crohn\'s disease, lupus and rheumatoid arthritis. “Our mission at Tourmaline has been to establish new standards of care in areas of high unmet medical need, and today’s transaction announcement both underscores our commitment to that focus and also delivers compelling shareholder value,” Tourmaline CEO Sandeep Kulkarni, M.D., said in the Sept. 9 release.“Novartis shares our conviction in the critical, but largely unaddressed, role of inflammation in driving cardiovascular diseases and will be an ideal partner to accelerate the development of pacibekitug,” Kulkarni added.Tourmaline got a boost for advancing its sole asset in 2023 through a reverse merger with Talaris Therapeutics, which put Tourmaline on the Nasdaq with a $75 million private placement.For Novartis, the acquisition of Tourmaline follows a summer in which the Swiss pharma padded out its cardiovascular pipeline via a multifaceted collaboration with Chinese siRNa biotech Argo Biopharmaceutical and a four-year pact with ProFound Therapeutics.Novartis’ cardiovascular offering already includes the bad-cholesterol–lowering med Leqvio alongside the heart failure medication Entresto. The pharma’s late-stage pipeline features pelacarsen, an antisense med aimed at preventing cardiovascular events in patients with elevated levels of lipoprotein(a).

Today’s agreement with Argo Biopharmaceutical follows a deal in January 2024 that saw Novartis hand over $185 million upfront.\n Novartis has returned to Argo Biopharmaceutical with $160 million in upfront cash to explore various cardiovascular meds in the Chinese biotech’s siRNA pipeline.The latest deal will allow Novartis to explore ANGPTL3—an RNAi therapeutic in phase 2 trials—in a combination study for dyslipidemia. The Swiss pharma will also have first right of negotiation to secure the license to ANGPTL3 further down the line.This morning’s multifaceted agreement also gives Novartis the license to a preclinical liver-delivered siRNA candidate outside of China. The drug is due to enter an international phase 1 study next year, and the companies have the option to share profits in both China and the U.S.Finally, Novartis has secured the option to license the ex-China rights for two discovery-stage, next-gen molecules being developed for mixed dyslipidemia and a related lipid disorder called hypertriglyceridemia.As well as the $160 million upfront fee, Argo will also be in line for milestone and option payments that could add up to $5.2 billion, alongside tiered royalties. Novartis also plans to participate in Argo’s next equity financing round.Today’s agreement follows a deal in January 2024 that saw Novartis hand over $185 million upfront for rights to two of Argo\'s clinical-phase RNAi cardiovascular disease programs.Dongxu Shu, Ph.D., and Patrick Shao, Ph.D., both of whom once worked at Arrowhead Pharmaceuticals, co-founded Argo in 2021. When they announced the first collaboration with Novartis last year, Shu called the alliance the “first significant overseas out-licensing transaction in the RNAi field from a Chinese biotech company.”In this morning’s release, Shu said the company was “thrilled to deepen our collaboration with Novartis, a global leader in cardiovascular, renal and metabolic areas.”“This new collaboration further supports the innovation engine Argo has built to deliver best-in-class siRNA therapeutics while building a top-tier clinical development team across multiple geographies,” Shu added. “Argo’s ambition is to become a global biotech, and corporate development activities are an important component to expand the reach of our hepatic and ex-hepatic siRNA therapeutics.” Novartis’ cardiovascular offering already includes the bad-cholesterol–lowering med Leqvio alongside the heart failure medication Entresto. The pharma’s late-stage pipeline features pelacarsen, an antisense med aimed at preventing cardiovascular events in patients with elevated levels of lipoprotein(a).“Long-acting siRNAs which are designed to deeply and durably target disease-causing proteins represent an important paradigm shift in prevention and treatment of cardiovascular diseases,” Shaun Coughlin, M.D., Ph.D., global head of cardiovascular and metabolism at the Novartis Institute for Biomedical Research, said in today’s release.“We are excited to build on our work with Argo through these new agreements, which include additional molecules,” Coughlin added.Back in June, Novartis doled out $25 million upfront as part of a four-year pact with ProFound Therapeutics to create new treatments for heart disease.