inclacumab (PF-07940370) / Roche, Pfizer, Genmab - LARVOL DELTA

Functional Outcomes of Platelet NK Cell Complexes in People Living with HIV (IMMUNOLOGY 2025) - "In Rhesus macaques ( RMs ), treatment with inclacumab (INC) was given before and after SIV infection, and NK cell phenotypes and functions were monitored...Platelet-NK interactions lead to NK activation and cytotoxicity, potentially leading to NK dysfunction over time. These findings may inform future therapeutic strategies where platelet inhibitors could reduce chronic NK activation."

Human Immunodeficiency Virus • Infectious Disease • CD14 • IL2RA • NKG2D

Activated Platelets Render Functionally Deficient Natural Killer Cells in People Living With HIV (CROI 2025) - "Furthermore, Rhesus macaques (RMs) were treated with vehicle (n=5) or inclacumab, (n=5) at week -1 and week 2 post-infection and infected with SIV on day 0...In vitro, platelet-NK co-cultures confirm the formation of PNKCs, and both in vitro and in vivo studies implicate platelets as drivers in NK dysfunction. These results have important consequences on future immune cell therapeutics in which the inclusion of platelet inhibitors may enhance cure outcomes."

Human Immunodeficiency Virus • Infectious Disease • CD14 • CD69 • IL2RA • NCR1 • NKG2D

THRIVE-131: A Study to Assess the Safety and Efficacy of Inclacumab in Participants With Sickle Cell Disease Experiencing Vaso-occlusive Crises (clinicaltrials.gov) - P3 | N=243 | Completed | Sponsor: Pfizer | Active, not recruiting ➔ Completed

Trial completion • Genetic Disorders • Hematological Disorders • Pain • Sickle Cell Disease

A Study to Evaluate the Long-term Safety of Inclacumab Administered to Participants With Sickle Cell Disease (clinicaltrials.gov) - P3 | N=108 | Active, not recruiting | Sponsor: Pfizer | Recruiting ➔ Active, not recruiting | N=520 ➔ 108

Enrollment change • Enrollment closed • Genetic Disorders • Hematological Disorders • Pain • Sickle Cell Disease

THRIVE-132: A Study of a Single Dose of Inclacumab to Reduce Re-admission in Participants With Sickle Cell Disease and Recurrent Vaso-occlusive Crises (clinicaltrials.gov) - P3 | N=72 | Terminated | Sponsor: Pfizer | Completed ➔ Terminated; Study was terminated due to poor accrual and associated recrutiment challenges

Trial termination • Genetic Disorders • Hematological Disorders • Pain • Sickle Cell Disease

THRIVE-132: A Study of a Single Dose of Inclacumab to Reduce Re-admission in Participants With Sickle Cell Disease and Recurrent Vaso-occlusive Crises (clinicaltrials.gov) - P3 | N=72 | Completed | Sponsor: Pfizer | Active, not recruiting ➔ Completed

Trial completion • Genetic Disorders • Hematological Disorders • Pain • Sickle Cell Disease

Population Pharmacokinetic Modeling of Different Formulations of Inclacumab Using Phase 1 Data in Healthy Participants (ASH 2023) - "The PopPK of IV inclacumab in healthy participants was described by a 3-compartment disposition model with parallel linear and nonlinear clearances. Estimated relative exposure of Roche v0. 2 and GBT-manufactured inclacumab was similar, indicating comparability in drug exposure."

Clinical • P1 data • PK/PD data • Cardiovascular • Genetic Disorders • Hematological Disorders • Sickle Cell Disease

Inclacumab Reduce Preexisting Red Blood Cell Adhesion to Activated Endothelial Cells: In-Vitro Assessment of the Microfluidic Platform Endothelium-on-a-Chip (ASH 2023) - "Inclacumab is able not only to prevent the adhesion of RBCs to acutely and chronically activated HUVECs but is able to remove the preexisting adhesion and results in significant higher reduction compared to untreated. RBCs adhesion assay on Endothelium-on-a-chip is a novel and efficient way to study the efficacy of the new antiadhesive drug and could be used to monitor patient response to new therapies in SCD. Figure1: Effect of Inclacumab vs Crizanlizumab on removal of SCD RBC adhesion to heme activated HUVECs."

Preclinical • Genetic Disorders • Hematological Disorders • Sickle Cell Disease

A Study to Evaluate the Long-term Safety of Inclacumab Administered to Participants With Sickle Cell Disease (clinicaltrials.gov) - P3 | N=520 | Recruiting | Sponsor: Pfizer | Enrolling by invitation ➔ Recruiting

Enrollment status • Genetic Disorders • Hematological Disorders • Pain • Sickle Cell Disease

A Study to Evaluate the Long-term Safety of Inclacumab Administered to Participants With Sickle Cell Disease (clinicaltrials.gov) - P3 | N=520 | Enrolling by invitation | Sponsor: Pfizer | Trial primary completion date: Mar 2027 ➔ Nov 2028

Trial primary completion date • Genetic Disorders • Hematological Disorders • Pain • Sickle Cell Disease

THRIVE-131: A Study to Assess the Safety and Efficacy of Inclacumab in Participants With Sickle Cell Disease Experiencing Vaso-occlusive Crises (clinicaltrials.gov) - P3 | N=229 | Active, not recruiting | Sponsor: Pfizer | Recruiting ➔ Active, not recruiting | Trial completion date: Apr 2024 ➔ Aug 2024 | Trial primary completion date: Mar 2023 ➔ Aug 2024

Enrollment closed • Trial completion date • Trial primary completion date • Genetic Disorders • Hematological Disorders • Pain • Sickle Cell Disease

THRIVE-132: A Study of a Single Dose of Inclacumab to Reduce Re-admission in Participants With Sickle Cell Disease and Recurrent Vaso-occlusive Crises (clinicaltrials.gov) - P3 | N=67 | Active, not recruiting | Sponsor: Pfizer | Recruiting ➔ Active, not recruiting | N=280 ➔ 67

Enrollment change • Enrollment closed • Genetic Disorders • Hematological Disorders • Pain • Sickle Cell Disease

A phase 1 study in healthy participants to characterize the safety and pharmacology of inclacumab, a fully human anti-P-selectin antibody, in development for treatment of sickle cell disease. (PubMed, Eur J Clin Pharmacol) - "Inclacumab was well tolerated, with PK as expected for a monoclonal antibody against a membrane-bound target and a long duration of PD effects after both single IV doses, supporting a prolonged dosing interval."

Journal • P1 data • Genetic Disorders • Hematological Disorders • Sickle Cell Disease

IN VITRO COMPARISON OF THE EFFECTS OF INCLACUMAB VS CRIZANLIZUMAB ON REDUCING ENDOTHELIAL ADHESION OF RED BLOOD CELLS IN STANDARDIZED MICROFLUIDIC PLATFORM (EHA 2023) - "Inclacumab reduces the levels of RBCs adhesion to chronic and acute heme activated HUVECs compared to untreated samples and treated with Crizanlizumab, using in vitro microfluidic system. Endothelium-on-a-chip microfluidic platform is a novel system that can be used as companion in new drug efficacy study and could be used to monitor patient response to anti-adhesive therapies in SCD Sickle cell, Sickle cell adhesion, Red blood cell, Sickle cell disease"

Preclinical • Cardiovascular • Genetic Disorders • Hematological Disorders • Sickle Cell Disease

TRIALS IN PROGRESS: THE THRIVE STUDIES EVALUATING THE EFFICACY, SAFETY, AND LONG-TERM TREATMENT WITH INCLACUMAB, A P-SELECTIN INHIBITOR, IN PATIENTS WITH SICKLE CELL DISEASE (EHA 2022) - P3 | "Results Recruiting for both THRIVE-131 and THRIVE-132 began in October 2021 and is ongoing. Conclusion The THRIVE-131 and THRIVE-132 phase 3 studies will examine the efficacy of inclacumab in reducing VOCs and readmissions due to VOCs, and the THRIVE-133 OLE study will examine the long-term safety of inclacumab in individuals with SCD."

Clinical • Genetic Disorders • Hematological Disorders • Pain • Sickle Cell Disease

A Study to Evaluate the Long-term Safety of Inclacumab Administered to Participants With Sickle Cell Disease (clinicaltrials.gov) - P3 | N=520 | Enrolling by invitation | Sponsor: Global Blood Therapeutics | Trial completion date: Mar 2027 ➔ Nov 2028

Trial completion date • Genetic Disorders • Hematological Disorders • Pain • Sickle Cell Disease

Analytical comparability demonstrated for an IgG4 molecule, inclacumab, following transfer of manufacturing responsibility from Roche to Global Blood Therapeutics. (PubMed, Expert Opin Biol Ther) - "Inclacumab samples produced by GBT were found to be comparable to the Roche v0.2 inclacumab samples based on: (1) comparable primary and higher-order structures; (2) comparable purity profiles; (3) comparable potency, in vitro functional activities, and in vivo plasma exposures and pharmacokinetic profiles; and (4) comparable degradation patterns and kinetics under forced degradation conditions. Based on the design of this comparability study and the results obtained, the US Food and Drug Administration approved the changes to the manufacturing process and gave clearance for GBT to proceed with phase 3 clinical trials."

Journal • Cardiovascular • Coronary Artery Disease • Genetic Disorders • Hematological Disorders • Peripheral Arterial Disease • Sickle Cell Disease

Examining anti-inflammatory therapies in the prevention of cardiovascular events: protocol for a systematic review and network meta-analysis of randomised controlled trials. (PubMed, BMJ Open) - "These include (but are not limited to): non-steroidal anti-inflammatory drugs (NSAIDs), colchicine, prednisone, methotrexate, canakinumab, pexelizumab, anakinra, succinobucol, losmapimod, inclacumab, atreleuton, LP-PLA (darapladib) and sPLA (varespladib). The findings will be disseminated through a peer-reviewed journal. CRD42022303289."

Journal • Retrospective data • Review • Atherosclerosis • Cardiovascular • Congestive Heart Failure • Dyslipidemia • Heart Failure • Immunology • Inflammation • Myocardial Infarction

THRIVE-131: A Study to Assess the Safety and Efficacy of Inclacumab in Participants With Sickle Cell Disease Experiencing Vaso-occlusive Crises (clinicaltrials.gov) - P3 | N=240 | Recruiting | Sponsor: Global Blood Therapeutics | Trial completion date: Oct 2023 ➔ Apr 2024 | Trial primary completion date: Jul 2023 ➔ Mar 2023

Trial completion date • Trial primary completion date • Genetic Disorders • Hematological Disorders • Pain • Sickle Cell Disease

A Study to Evaluate the Long-term Safety of Inclacumab Administered to Participants With Sickle Cell Disease (clinicaltrials.gov) - P3 | N=520 | Enrolling by invitation | Sponsor: Global Blood Therapeutics

New P3 trial • Genetic Disorders • Hematological Disorders • Pain • Sickle Cell Disease

Characterization of Two Anti-P-Selectin Monoclonal Antibodies (mAbs): Crizanlizumab Shows Comparable or Stronger Effects Versus Inclacumab across Cell Adhesion Assays in Vitro (ASH 2021) - "While the SPR/Biacore data suggested higher P-selectin binding affinity for inclacumab compared with crizanlizumab, there was a stronger inhibition of P-selectin-mediated cell adhesion with crizanlizumab vs inclacumab in other well-characterized functional in vitro assays. In microfluidic flow adhesion bioassays, blockage of cell adhesion from SCD whole blood and leukocytes was comparable for both mAbs. In summary, these data indicate that comparable or stronger blockage of cell adhesion with crizanlizumab vs inclacumab does not require superior P-selectin binding affinity."

Preclinical • Genetic Disorders • Hematological Disorders • Sickle Cell Disease

Preliminary Results of a Phase 1 Study in Healthy Subjects Administered Inclacumab, a Fully Human IgG4 Anti-P-Selectin Monoclonal Antibody in Development for Treatment of Sickle Cell Disease (ASH 2021) - "Overall, the results support a Phase 3 dose of 30 mg/kg every 12 weeks in patients with SCD-related VOCs. Funding: This study was supported by Global Blood Therapeutics."

Clinical • P1 data • Cardiovascular • Contact Dermatitis • Dermatitis • Dermatology • Genetic Disorders • Hematological Disorders • Immunology • Musculoskeletal Pain • Pain • Sickle Cell Disease

A Study of a Single Dose of Inclacumab to Reduce Re-admission in Participants With Sickle Cell Disease and Recurrent Vaso-occlusive Crises (clinicaltrials.gov) - P3; N=280; Recruiting; Sponsor: Global Blood Therapeutics; Not yet recruiting ➔ Recruiting; Initiation date: Jul 2021 ➔ Oct 2021

Clinical • Enrollment open • Trial initiation date • Genetic Disorders • Hematological Disorders • Pain • Sickle Cell Disease

GBT Reports Second Quarter 2021 Financial Results (GlobeNewswire) - P2a, N=155; HOPE Kids (NCT02850406); P=Obs, N=300; RETRO (NCT04930328); Sponsor: Global Blood Therapeutics; "Presented new data from the Phase 2a HOPE-KIDS 1 Study at the European Hematology Association (EHA) 2021 Virtual Congress that showed children with SCD ages 4 to 11 years treated with Oxbryta achieved significant improvements in hemoglobin levels; Initiated the RETRO and PROSPECT data registries...Initial results from the RETRO study...demonstrating that after 12 months, 50% of patients had a greater than 1 g/dL increase in hemoglobin....Initiated two global, randomized, placebo-controlled, pivotal Phase 3 trials evaluating the safety and efficacy of inclacumab...Initiated a Phase 1 trial of GBT601 in SCD patients, with a goal of providing proof-of-concept data by the end of the year; Enrollment of pediatric expanded access protocol (EAP) is exceeding expectations and GBT plans to increase the number of patients from 50 to up to 150."

Enrollment change • Observational data • P1 data • P2a data • Hematological Disorders • Sickle Cell Disease

GBT Reports Second Quarter 2021 Financial Results (GlobeNewswire) - "Achieved Oxbryta® (voxelotor) tablets net sales of $47.6 million in the second quarter, an increase of 51% year-over-year. On a sequential basis, sales increased 22%, primarily driven by patient demand....Most recent healthcare provider survey (n = 278, completed in June-July 2021) confirms continued high levels of satisfaction with Oxbryta, including its ability to keep SCD under control for patients....Oxbryta continues to have broad payer coverage, with more than 90% of covered lives...Research and development (R&D) expenses for the three months ended June 30, 2021, were $51.8 million...The increase was primarily due to an increase in external costs related to the company’s preclinical programs, and Oxbryta and inclacumab programs."

Commercial • Sales • Hematological Disorders • Sickle Cell Disease