pacibekitug (TOUR006) / Pfizer, Novartis - LARVOL DELTA

TRANQUILITY: Pacibekitug Safely Lowers hs-CRP in ASCVD, With Deepak Bhatt, MD (HCPLive) - "The treatment period lasted 6 months, followed by a follow-up period of an additional 6 months. The primary endpoint was median time-averaged percent change in hs-CRP through day 90, adjusting for baseline. The key secondary endpoint was the percentage of participants achieving time-averaged hs-CRP below 2 mg/L through day 90. Additionally, investigators noted the percentage of participants achieving hs-CRP reductions of ≥50%....By day 90, the median time-averaged percent reduction in hs-CRP was 86% for the 50 mg dose, 75% for the 25 mg dose, and 85% for the 15 mg dose, versus 15% for the placebo arm (all P <.0001). Several patients achieved hs-CRP reductions ≥50%, and the percentage of patients with hs-CRP <1 mg/L at day 90 was 60%, 45%, and 65% for the 50 mg, 25 mg, and 15 mg arms compared to 13% for placebo (all P <.0001)."

P2 data • Atherosclerosis • Cardiovascular • Chronic Kidney Disease

Novartis will present new data from 33 abstracts across its Cardiovascular, Renal, and Metabolic (CRM) disease portfolio at the upcoming American Society of Nephrology (ASN) Kidney Week 2025 in Houston, Texas and American Heart Association’s (AHA) Scientific Sessions 2025 in New Orleans, Louisiana, advancing scientific insight into these critical disease areas (Novartis Press Release)

Clinical data • Autosomal Dominant Polycystic Kidney Disease • Cardiovascular • Chronic Kidney Disease • IgA Nephropathy

A Phase 2 Multicenter, Randomized, Double-Blind, Placebo-Controlled Study of Monthly or Quarterly Subcutaneous Administration of the Interleukin-6 Inhibitor Pacibekitug in Patients With Elevated High-Sensitivity C-Reactive Protein and Chronic Kidney Disease: 90-Day Analyses from TRANQUILITY (AHA 2025) - P2 | "IL-6 inhibition with quarterly dosing of pacibekitug significantly reduced hs-CRP levels, with no safety signals at 90 days. To our knowledge, pacibekitug is the first IL-6 inhibitor to demonstrate significant and sustained reductions in hs-CRP with quarterly dosing."

Clinical • P2 data • Cardiovascular • Chronic Kidney Disease • Infectious Disease • Inflammation • Nephrology • Renal Disease • CRP • IL6

Novartis completes acquisition of Tourmaline Bio (GlobeNewswire) - "Pacibekitug’s differentiated anti-IL-6 mechanism offers a scientifically compelling approach to residual inflammation – a key driver of atherosclerotic cardiovascular disease. We look forward to collaborating with Tourmaline’s team to further advance this promising asset and continue strengthening our ability to deliver potentially transformative therapies for diseases with high unmet need."

M&A • Atherosclerosis • Cardiovascular • Inflammation

Novartis to acquire Tourmaline Bio, complementing cardiovascular pipeline with pacibekitug for the treatment of atherosclerotic cardiovascular disease (ASCVD) (Novartis Press Release) - "...Novartis will acquire a Phase 3 ready asset which will complement its existing cardiovascular disease portfolio...Novartis will, through an indirect wholly owned subsidiary, commence a tender offer to purchase all outstanding shares of Tourmaline common stock...Following completion of the tender offer, Novartis expects to merge the acquiring subsidiary with and into Tourmaline, resulting in Tourmaline becoming an indirect wholly owned subsidiary of Novartis....The transaction is expected to close in the fourth quarter of 2025..."

M&A • Atherosclerosis • Cardiovascular • Immunology

A Multicenter, Randomized, Double-Blind, Placebo-Controlled Ph2 Trial of Pacibekitug SC Quarterly or Monthly in Patients with Elevated hs-CRP and Chronic Kidney Disease: TRANQUILITY 90-Day Results (ESC-WCC 2025) - No abstract available

Clinical • Cardiovascular

Tourmaline Bio To Present New Phase 2 TRANQUILITY Data At ESC Congress 2025 (RTTNews)

P2 data • Chronic Kidney Disease

Tourmaline Bio Announces Positive Topline Results from the Ongoing Phase 2 TRANQUILITY Trial Evaluating Pacibekitug in Patients with Elevated High-Sensitivity C-reactive Protein and Chronic Kidney Disease (GlobeNewswire) - P2 | N=143 | TRANQUILITY (NCT06362759) | Sponsor: Tourmaline Bio, Inc. | "A total of 143 participants were enrolled in the TRANQUILITY trial. Of this total, 126 participants comprised the primary analysis population. Baseline characteristics were generally balanced between groups...Results of post-hoc sensitivity analyses of the primary endpoint in the intention-to-treat (ITT) population, i.e., all randomized participants, were highly consistent with the primary analyses...As of the data extract date, the cumulative incidence of any adverse event (AE) was 54% in the pooled pacibekitug group, compared with 56% in the placebo group."

P2 data • Chronic Kidney Disease • Immunology • Inflammation

Tourmaline Bio to Present Topline Results from the Ongoing Phase 2 TRANQUILITY Trial of Pacibekitug on May 20, 2025 (GlobeNewswire) - "Tourmaline Bio, Inc...will host a conference call and webcast on Tuesday, May 20, 2025 beginning at 8:30 a.m. ET to present topline results from the Phase 2 TRANQUILITY trial evaluating pacibekitug in patients with elevated high-sensitivity C-reactive protein and chronic kidney disease."

P2 data • Chronic Kidney Disease • Immunology

Tourmaline Bio Reports Fourth Quarter and Full Year 2024 Financial Results and Recent Business Highlights (GlobeNewswire) - "Tourmaline remains on track to report topline data from the TRANQUILITY trial in the second quarter of 2025...Tourmaline expects to provide additional details on a planned Phase 2 proof-of-concept trial in AAA after topline results from the TRANQUILITY trial are reported in the second quarter of 2025...The Phase 2b spiriTED trial remains ongoing, and Tourmaline continues to expect topline data from this trial in the second half of 2025."

P2 data • P2b data • Chronic Kidney Disease • Thyroid Eye Disease

spiriTED: A Study to Investigate Efficacy and Safety of TOUR006 in Participants 18 to 80 Years of Age With Thyroid Eye Disease (clinicaltrials.gov) - P2 | N=81 | Recruiting | Sponsor: Tourmaline Bio, Inc. | Trial completion date: Feb 2026 ➔ Nov 2026 | Trial primary completion date: Feb 2025 ➔ Nov 2025

Trial completion date • Trial primary completion date • Ophthalmology • Thyroid Eye Disease

TRANQUILITY: A Study to Evaluate TOUR006 in Patients With Chronic Kidney Disease and Elevated Hs-CRP (clinicaltrials.gov) - P2 | N=143 | Active, not recruiting | Sponsor: Tourmaline Bio, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Chronic Kidney Disease • Nephrology • Renal Disease

Modeling to Inform Dose Selection for TOUR006, a Fully Human Anti-IL-6 Antibody, for Treatment of Thyroid Eye Disease: Effect of Gender and Liver and Kidney Function on Modeling the Optimal Dose Regimen (ATA 2024) - "The simulations for 20 mg and 50 mg q8w of SC TOUR006 predict that these doses/regimens will likely target ≥90% CRP suppression from baseline in most typical TED subjects without needing weight-based adjustment. The effects of additional parameters on dose modeling will be addressed in the presentation."

Late-breaking abstract • Inflammatory Arthritis • Ocular Inflammation • Ophthalmology • Rheumatoid Arthritis • Rheumatology • Thyroid Eye Disease • CRP • IL6

Tourmaline Bio Initiates Clinical Development of TOUR006 for Cardiovascular Diseases with First Patient Dosed in Phase 2 TRANQUILITY Trial (GlobeNewswire) - "Topline data anticipated in the first half of 2025 with potential to advance TOUR006 toward Phase 3 readiness for atherosclerotic cardiovascular disease (ASCVD) and other cardiovascular diseases...Tourmaline Bio...announced that the first patient has been dosed in its Phase 2 TRANQUILITY trial, marking the initiation of its clinical development program for TOUR006, a long-acting, fully human, anti-IL-6 monoclonal antibody, for the treatment of atherosclerotic cardiovascular disease (ASCVD) and other cardiovascular diseases. TRANQUILITY is a randomized, double-blind, placebo-controlled trial enrolling patients with inflammatory risk, manifesting as elevated high-sensitivity C-reactive protein (hs-CRP) at baseline, and chronic kidney disease (CKD)."

P2 data • Trial status • Cardiovascular • Chronic Kidney Disease

TRANQUILITY: A Study to Evaluate TOUR006 in Patients With Chronic Kidney Disease and Elevated Hs-CRP (clinicaltrials.gov) - P2 | N=120 | Recruiting | Sponsor: Tourmaline Bio, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Chronic Kidney Disease • Nephrology • Renal Disease

TRANQUILITY: A Study to Evaluate TOUR006 in Patients With Chronic Kidney Disease and Elevated Hs-CRP (clinicaltrials.gov) - P2 | N=120 | Not yet recruiting | Sponsor: Tourmaline Bio, Inc.

New P2 trial • Chronic Kidney Disease • Nephrology • Renal Disease

spiriTED: A Study to Investigate Efficacy and Safety of TOUR006 in Participants 18 to 75 Years of Age With Thyroid Eye Disease (clinicaltrials.gov) - P2 | N=81 | Recruiting | Sponsor: Tourmaline Bio, Inc. | Phase classification: P2b ➔ P2

Phase classification • Ophthalmology • Thyroid Eye Disease

spiriTED: A Study to Investigate Efficacy and Safety of TOUR006 in Participants 18 to 75 Years of Age With Thyroid Eye Disease (clinicaltrials.gov) - P2b | N=81 | Recruiting | Sponsor: Tourmaline Bio, Inc.

New P2b trial • Ophthalmology • Thyroid Eye Disease

Tourmaline Bio Announces FDA Clearance of Investigational New Drug (IND) Application for TOUR006, an anti-IL-6 antibody with a differentiated profile for the treatment of thyroid eye disease (TED) (GlobeNewswire) - "Phase 2b trial of TOUR006 is expected to report top-line clinical data in the first half of 2025...Tourmaline Bio, Inc...today announced U.S. Food and Drug Administration (FDA) clearance of Tourmaline’s IND application for TOUR006....The planned Phase 2b trial of TOUR006 in TED is expected to evaluate 20mg and 50mg doses against placebo given by a subcutaneous injection every eight weeks. The approximately 81 participants planned to be enrolled (27 in each arm) will be moderate to severe TED patients who are in the active phase of disease. The primary endpoint for this trial will be proptosis response, or reduction of abnormal eye protrusion, measured at week 20."

IND • New P2b trial • P2b data • Immunology • Thyroid Eye Disease

Model-Based Meta-Analysis on the Efficacy of Biologics and Small Targeted Molecules for Crohn's Disease. (PubMed, Front Immunol) - "The most achievement in clinical remission (defined as CDAI less than 150) and clinical response (defined as the reduction in CDAI for 100 or 70) was observed in the simulation for PF-04236921 and infliximab, respectively. The most improvement in IBDQ was shown in tofacitinib. In general, tumor necrosis factor (TNF)-α inhibitors were the most effective biologics, and the highest efficacy of small targeted molecules was observed in janus kinase (JAK) inhibitors. These findings have important implications for clinical practice in CD."

Retrospective data • Review • Crohn's disease • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease • Oncology • CRP

[VIRTUAL] Efficacy of Biological Agents for the Management of Systemic Lupus Erythematosus: A Systematic Review and Network Meta-Analysis (CRA-AHPA 2021) - "These 20 RCTs investigated the following biologics: belimumab, anifrolumab, ustekinumab, atacicept, baricitinib, blisibimod, epratuzumab, IL-2, lupuzor, PF-04236921, rontalizumab, sifalimumab, and tabalumab... The NMA identified that belimumab, anifrolumab and ustekinumab demonstrated greater response in comparison to placebo, when measured using SRI. This systematic review identified that there was heterogeneity in the outcome measures and endpoints used. In the future, the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach will be applied to rate the quality of the evidence, and to gain insight into methodological pitfalls that could have negatively altered the results of RCTs."

Retrospective data • Review • Complement-mediated Rare Disorders • Glomerulonephritis • Immunology • Inflammatory Arthritis • Lupus • Lupus Nephritis • Nephrology • Systemic Lupus Erythematosus • IL2

Subcutaneous Treatment In Randomized Subjects To Evaluate Safety And Efficacy In Generalized Lupus Erythematosus (clinicaltrials.gov) - P2; N=183; Completed; Sponsor: Pfizer; Active, not recruiting -> Completed

Trial completion • Biosimilar • Immunology • Lupus • Non-Hodgkin’s Lymphoma • Reperfusion Injury

Subcutaneous treatment in randomized subjects to evaluate safety and efficacy in generalized lupus erythematosus (BUTTERFLY) (clinicaltrials.gov) - P2, N=183; Sponsor: Pfizer; Active, not recruiting -> Completed.

Trial completion • Immunology • Lupus

Beyond Xeljanz: An inflammation & immunology portfolio blooms at Pfizer (Pink Sheet - Informa) - “Pfizer is…hoping that pipeline drugs, including next-generation JAKs, will stand out by addressing unmet medical need in indications like lupus…and inflammatory bowel disease….Pfizer is testing the IL-6 inhibitor for Crohn’s and lupus in Phase II tests.”; Company is also studying JAK1 inhibitor in lupus.

Pipeline update • Immunology • Inflammatory Bowel Disease • Lupus

Safety, pharmacokinetics, and pharmacodynamics of a human anti-IL6 monoclonal antibody PF-04236921 in healthy subjects (EULAR 2012) - Anticipated publication at EULAR 2012

Pharmacokinetic and pharmacodynamic study • Immunology • Lupus