Our Research

TP-0184 (ACVR1 Inhibitor)

TP-0184 is an investigational inhibitor of activin A receptor type 1 (ACVR1) kinase.1

ACVR1 As A Potential Target In Chronic Diseases and Cancer

In chronic inflammatory conditions, ACVR1 is constitutively activated due to proinflammatory cytokine signaling.2 This results in increased transcription of hepcidin, a peptide liver hormone that functions as a master regulator of serum iron levels, particularly in response to inflammation.2 The elevated levels of circulating hepcidin leads to low serum iron and anemia of chronic disease (ACD).ACVR1 mutations have been identified in several tumor types including diffuse intrinsic pontine gliomas (DIPG) and endometrial cancers.3,4,5

Preclinical Activity

TP-0184 has shown activity in decreasing hepcidin expression, increasing bioavailable iron, and restoring normal levels of hemoglobin through the inhibition of ACVR1 in preclinical models of anemia driven by acute and chronic inflammation and by cancer. Additionally, TP-0184 has shown preclinical activity in several models of tumors that are driven by ACRV1 signaling, including diffuse intrinsic pontine glioma (DIPG), a rare pediatric brain tumor with recurrent activating mutations in ACVR1.

Clinical Development

A phase 1, first-in-human, trial of oral TP-0184 is currently being conducted in patients with advanced solid tumors.

TP-0184 is an investigational agent and is not approved by the US FDA or any other regulatory authorities.

ACVR1 is also known as activin receptor-like kinase 2 (ALK2).

  1. Peterson P, Kim W, Haws H, et al. The ALK-2 inhibitor, TP-0184, demonstrates high distribution to the liver contributing to significant preclinical efficacy in mouse models of anemia of chronic disease [Abstract]. Blood. 2016;128:263.
  2. Peterson P, Soh KK, Lee YS, et al. ALK2 inhibition via TP-0184 abrogates inflammation-induced hepcidin expression and is a potential therapeutic for anemia of chronic disease [Abstract]. Blood. 2015;126:273. 
  3. Buczkowicz P, Hoeman C, Rakopoulos P, et al. Genomic analysis of diffuse intrinsic pontine gliomas identifies three molecular subgroups and recurrent activating ACVR1. Nat Genet. 2014;46(5):451-456.
  4. Taylor K, Mackay A, Truffaux N, et al. Recurrent activating ACVR1 mutations in diffuse intrinsic pontine glioma. Nat Genet. 2014;46(5):457-461.
  5. Zhao B, Pritchard J. Inherited disease genetics improves the identification of cancer-associated genes. PloS Genet. 2016;12(6):e1006081.