Tourmaline Bio’s lead candidate sparkled in a mid-stage data drop, prepping the biotech to develop the former Pfizer asset further in a pair of cardiovascular indications.
Pacibekitug, an antibody targeting interleukin-6, hit the primary endpoint in the phase 2 Tranquility trial by sharply reducing levels of C-reactive protein (CRP), a biomarker for cardiovascular disease risk, in patients with chronic kidney disease, Tourmaline reported May 20.
New York-based Tourmaline is developing pacibekitug, also called TOUR006, for atherosclerotic cardiovascular disease (ASCVD) and abdominal aortic aneurysm (AAA), according to the release, with plans to start a phase 2 study in AAA later this year. AAA is the term for an enlarged area of the aorta, the body’s main artery, which can rupture and cause life-threatening bleeding.
The biotech is also drawing up designs for a potential phase 3 trial in ASCVD, Tourmaline said in the release, and will disclose more information later this year after speaking with regulators.
The Tranquility trial enrolled 143 patients with elevated levels of CRP and chronic kidney disease, who are at high risk of ASCVD. CRP levels were measured 90 days after treatment began. One group of patients received 50 mg of subcutaneous pacibekitug on day one and day 90, another received 25 mg on the same schedule, and the third group was administered more frequent 15 mg doses, on days one, 30, 60 and 90. The 15 mg group was also given two further doses, on days 120 and 150.
The biotech described the resulting drop in CRP levels as measured at day 90 as "rapid, deep and durable." The 50 mg group saw an average reduction of 86%, the 25 mg group saw 75%, and the 15 mg group experienced a drop of 85%, compared to a 15% reduction in the placebo group.
"Importantly, this is the first time that pacibekitug or any IL-6 inhibitor has been tested in a clinical trial with quarterly dosing," Sandeep Kulkarni, M.D., Tourmaline's co-founder and CEO, said in the release. "It is well-recognized that less frequent administration has the potential to enhance patient adherence and ultimate clinical benefit."
There were similar rates of adverse events across the treatment and placebo groups, according to the release, with most being mild to moderate in severity. Fifty-six per cent of patients in the placebo group experienced an adverse event, compared to an average of 54% for patients across all treatment arms combined. Meanwhile, rates for serious adverse events were 11% and 10%, respectively. Two patients discontinued treatment due to adverse events, one in the 50 mg group and one in the 15 mg group.
One patient in the 25 mg group died from a fatal case of COVID-19.
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.
Pacibekitug originated at Pfizer, with Tourmaline licensing the asset in 2022. In addition to the cardio indications, the biotech is also testing the former Big Pharma antibody in a phase 2 trial in the autoimmune disorder thyroid eye disease. Pfizer had previously studied pacibekitug in Crohn's disease, lupus and rheumatoid arthritis.
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.