Recently, Novartis announced that it would acquire Tourmaline Bio for approximately $1.4 billion in order to get its hands on a novel IL-6 inhibitor for the treatment of atherosclerotic cardiovascular disease (ASCVD) and other cardiovascular disorders. This ends up being an acquisition for a cash transaction of $48 per share with an equity value of $1.4 billion. This is good news for the big pharma because it adds another complementary drug to its pipeline, but there is a stipulation in that this deal has not closed yet. That’s because it is not expected to be finalized until Q4 of 2025. What this means is that in the meantime, both entities are going to operate independently until this final transaction closes.
The acquisition of Tourmaline was due to the novel anti-IL-6 monoclonal antibody pacibekitug. What makes this drug ideal is that it had already been evaluated in the phase 2 TRANQUILITY study. In essence, this is a clinical candidate that is already set to be tested in a large phase 3 study. Going back to the TRANQUILITY study, it is important to note that the patients recruited into it were those with chronic kidney disease (CKD). This is a bad disorder to have because the kidney starts to lose its ability to be able to filter out waste from the blood. Not only did the patients have to have this disorder, but they also had to have elevated levels of high-sensitivity C-reactive protein (hs-CRP).
Pacibekitug has the mechanism of action (MOA) of being an IL-6 inhibitor, which is a cytokine that drives inflammation in autoimmune and inflammatory disorders. The goal is to give this drug via subcutaneous injection and reduce inflammation in these CKD patients with elevated levels of hs-CRP. CRP, or c-reactive protein, is, as the name suggests, a protein, and it is formed by the liver in reaction to the body having inflammation. In essence, increased levels of hs-CRP is predictive of several disorders, some of which are cardiovascular disorders and CKD. This is why the TRANQUILITY study incorporated the primary endpoint to be percent change of hs-CRP through day 90.
The proof-of-concept of using an anti-IL-6 monoclonal antibody like pacibekitug was proven because the data release showed that all dosing regimens given to patients achieved a statistically significant p-value of p<0.0001. With that being said, the dosing cohorts of the drug were 25 mg quarterly, 50 mg quarterly, and 15 mg monthly. The more pronounced effect though came from the patients who took the dose of 50 mg quarterly, with an hs-CRP reduction of 86%. Although the 15 mg monthly dose of drug given came close to this dose, with an hs-CRP reduction of 85%. It is important to mention both of these doses being close in terms of reducing this biomarker, because now the company has flexibility in a phase 3 study to use either one for evaluation.
Speaking of the next study, upon release of such data, it was the goal to meet with the FDA to discuss the potential of initiating a phase 3 study for this program. Specifically, the goal is to start an outcomes trial targeting patients with ASCVD. Tourmaline Bio, though, didn’t hinge its entire future solely on the development of pacibekitug only in targeting patients with elevated levels of hsCRP in CKD or ASCVD. To that end, it had a productive pre-IND meeting and was able to receive clearance from the FDA to initiate a phase 2 proof-of-concept study targeting patients with abdominal aortic aneurysm (AAA). Such a mid-stage trial is set to kick off in the second half of 2025.
The point of being able to expand the use of pacibekitug in other inflammatory disorders is proven by this ability to go after AAA and also another indication known as thyroid eye disease (TED). What makes this disorder devastating is that it affects the tissues and muscles around the eyes of a patient. As you can imagine, this leads to a host of eye symptoms that they must deal with. One such symptom, known as proptosis (bulging of the eye), is used as an efficacy endpoint to determine disease severity in clinical trials. In order to see whether or not pacibekitug might be able to help treat patients with TED, it is being evaluated in the phase 2b spiriTED study. Data from this mid-stage trial is expected in early 2026.