OVERVIEW: Axatilimab (SNDX-6352) and Chronic Graft Versus Host Disease


Donor-derived, pro-inflammatory macrophages are dependent on CSF-1R signaling and have been shown in preclinical studies to be responsible for symptoms associated with chronic graft versus host disease (cGVHD). Syndax believes that CSF-1R blockade with axatilimab (SNDX-6352) may reduce the number of these pro-inflammatory macrophages and play a meaningful role in the treatment of chronic graft versus host disease.1
Syndax has initiated the AGAVE-201/NCT04710576 study to further explore this hypothesis.
SNDX-6352-502 MOA
SNDX-6352 MOA
CSF-1 has been shown to promote the growth and differentiation of donor derived monocytes into macrophages which, in turn, promote fibroblast activation and collagen production resulting in the various organ manifestations observed in patients with cGVHD.2

Source: Adapted from MacDonald, KP, et al. HSCT – Hematopoietic stem cell transplantation. Blood. 2017;5(129):13-21.

References:

  1. A phase 1 study to evaluate SNDX-6352 in subjects with active cGVHD. ClinicalTrials.gov identifier: NCT03604692. https://clinicaltrials.gov/ct2/show/NCT03604692. Updated August 6, 2019. Accessed May 6, 2020.
  2. Data on file. Syndax Pharmaceuticals, Inc.
  3. Alexander K et al. CSF-1-dependant donor-derived macrophages mediate chronic graft-versus-host disease. Journal of Clinical Investigation. October 2014. 10.1172/JC195935. 4367-4280.
  4. MacDonald, KP, et al. HSCT – Hematopoietic stem cell transplantation. Blood. 2017;5(129):13-21.