Clinical Pipeline

Clinical Pipeline

ProductIndicationStatus
REZUROCK
(belumosudil)
(Selective ROCK2 inhibitor)
Chronic
Graft-Versus-Host
Disease (cGVHD)
  • FDA approved for the treatment of adult and pediatric patients 12 years and older with cGVHD after failure of at least two prior lines of systematic therapy
Systemic Sclerosis
  • Open-label Phase 2 clinical trial ongoing; initial data expected YE 2021
  • Phase 2 placebo-controlled clinical trial ongoing
KD033
(anti-PD-L1/IL-15 fusion protein)
Immuno-oncology
  • Phase 1 clinical trial ongoing

About cGVHD

Chronic GVHD (cGVHD) is a common complication following hematopoietic cell transplantation (HCT). In cGVHD, transplanted immune cells (graft) attack the patient’s cells (host), leading to inflammation and fibrosis in multiple tissues. Approximately 14,000 patients in the United States are living with cGVHD, and approximately 5,000 new patients are diagnosed with cGVHD per year[1].

[1] Bachier, CR. et al. ASH Annual Meeting 2019, Abstract #2109. Epidemiology and Real-World Treatment of Chronic Graft-Versus-Host Disease Post Allogeneic Hematopoietic Cell Transplantation: A U.S. Claims Analysis.

cGVHD: Inflammation and Fibrosis in Multiple Organs

Anatomy Diagram

About Belumosudil

Belumosudil, is an orally administered, selective inhibitor of Rho-associated coiled-coil kinase 2 (ROCK2). Kadmon’s research has helped define the role of ROCK in the pathogenesis of immune and fibrotic diseases.

Kadmon’s research has demonstrated that belumosudil helps to resolve immune dysregulation by down-regulating pro-inflammatory Th17 cells and increasing regulatory T (Treg) cells.

Belumosudil Mechanism of Action

ROCK is downstream of major pro-fibrotic mediators and regulates multiple fibrotic processes, including stress fiber formation, myofibroblast activation and pro-fibrotic gene transcription. Belumosudil down-regulated key fibrotic processes in preclinical models, including profibrotic gene transcription, stress fiber formation, myofibroblast activation and collagen deposition.

Belumosudil in Systemic Sclerosis

Systemic Sclerosis (SSc) is a chronic immune disorder characterized by fibrosis of the skin and internal organs. Currently, there are no FDA-approved targeted therapies for SSc, which affects 75,000 to 100,000 people in the United States[2]. Belumosudil, Kadmon’s ROCK2 inhibitor, has demonstrated activity in preclinical sclerodermatous models. Enrollment is ongoing in a randomized, placebo-controlled, Phase 2 clinical trial of belumosudil (KD025-209) in 60 patients with diffuse cutaneous SSc. Enrollment is also ongoing in an open-label, Phase 2 clinical trial of belumosudil (KD025-215) in up to 15 patients with diffuse cutaneous SSc. Initial data from this study are expected by year-end 2021.

[2] American College of Rheumatology. “Largest study evaluating survival in systemic sclerosis patients following lung transplantation.” Press release, November 16, 2014.

KD033

KD033 is an anti-PD-L1/IL-15 fusion protein and is the lead molecule from our IL-15 fusion protein platform. KD033 is a novel immunotherapy designed to stimulate innate and adaptive immune responses directed to the tumor microenvironment:

  • IL-15 is an immunostimulatory cytokine that expands key tumor-fighting immune cell types, including natural killer (NK), natural killer T (NKT) and memory T cells without expanding immunosuppressive Treg cells, allowing for robust and durable anti-tumor responses
  • KD033 is designed to direct IL-15 activity to the tumor microenvironment of PD-L1-expressing tumors to achieve a greater therapeutic window

A single dose of KD033 demonstrated robust in vivo pharmacological activity and inhibited tumor growth across multiple syngeneic mouse models.

A Phase 1 clinical trial of KD033, KD033-101, is ongoing in patients with metastatic or locally advanced solid tumors.