Clinical Pipeline

Clinical Pipeline

ProductIndicationStatus
Belumosudil (KD025)
(ROCK2 Inhibitor)
Chronic
Graft-Versus-Host
Disease (cGVHD)
  • Primary endpoint met in pivotal trial
  • Participating in FDA’s Real-Time Oncology Review (RTOR) pilot program
  • Q4 2020: NDA submission planned
Systemic Sclerosis
  • Phase 2 clinical trial ongoing
KD033
(anti-PD-L1/IL-15 fusion protein)
Immuno-oncology
  • Phase 1 clinical trial ongoing

About Belumosudil

Our late-stage product candidate, belumosudil (KD025), is an orally administered, selective inhibitor of Rho-associated coiled-coil kinase 2 (ROCK2), a signaling pathway that modulates immune and fibrotic processes. A pivotal study of belumosudil is ongoing in patients with chronic graft-versus-host disease (cGVHD), a complication following hematopoietic cell transplantation (HCT) that results in multi-organ inflammation and fibrosis. A Phase 2 clinical trial of belumosudil is also underway in systemic sclerosis (SSc), a chronic immune disorder characterized by fibrosis of the skin and internal organs. ROCK mediates cell movement, shape, differentiation and function. Kadmon’s research has helped define the role of ROCK in the pathogenesis of many diseases, including immune and fibrotic diseases. Specifically, our 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 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].

Belumosudil has demonstrated clinical activity and generally was well tolerated in a Phase 2a trial in cGVHD (KD025-208). Enrollment is complete in ROCKstar (KD025-213), a pivotal clinical trial of belumosudil in adults and adolescents with cGVHD who have received at least two prior lines of systemic therapy. In November 2019, we announced that belumosudil met the primary endpoint at the planned interim analysis of ROCKstar.  The FDA has granted Breakthrough Therapy Designation to belumosudil for the treatment of cGVHD after at least two prior lines of systemic therapy. The FDA has also granted Orphan Drug Designation to belumosudil for the treatment of cGVHD. Belumosudil is being reviewed under the FDA’s Real-Time Oncology Review (RTOR) Pilot Program.

[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

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 Phase 2 clinical trial of belumosudil (KD025-209) in patients with diffuse cutaneous SSc.

[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.