About KTX-1001
KTX-1001 is an oral, first-in-class, selective MMSET catalytic inhibitor that suppresses H3k36me2 in patients with relapsed and refractory multiple myeloma (RRMM) with a focus on patients with the t(4;14 ) genetic translocation. This study will evaluate the safety, tolerability, and preliminary efficacy of KTX-1001.
We developed KTX-1001 to provide a targeted therapy that specifically addresses the underlying cause of cancer for these multiple myeloma patients. KTX-1001 is the first therapeutic agent to enter the clinic that directly targets overexpression of MMSET.
About Multiple Myeloma
Multiple myeloma is a cancer of plasma cells.
Treatment options for patients with multiple myeloma have improved significantly within the past decade. However, a disparity remains for patients with poor prognostic factors, including high-risk mutations like a t(4;14) translocation.
15-20%
Approximate percentage of multiple myeloma patients identified as t(4;14) positive.
In healthy tissue, the MMSET gene, located on chromosome 4, is expressed at normal levels.
The expression of the MMSET gene is regulated by a DNA element called an “enhancer”.
MMSET activity leads to the generation of H3K36me2 marked nucleosomes, which are found on active chromatin.
With low level activity of MMSET, there is little H3K36me2, and transcription of genes at chromatin is turned off.
There is no oncogenic activity because proper MMSET regulation and methylation produces plasma cells with normal expression of MMSET protein levels.
In healthy tissue, the MMSET gene, located on chromosome 4, is expressed at normal levels.
In t(4;14) multiple myeloma, translocation in plasma cells occurs, in which both chromosome 14 and chromosome 4 break in two. Instead of re-attaching correctly, the broken pieces of each chromosome re-attach to the other chromosome half to create two abnormal, hybrid chromosomes referred to as der(4) and der(14).
The consequence of the t(4;14) translocation is that the MMSET gene is now placed next to a strong “enhancer” element from chromosome 14. This causes a significant increase in the transcription of MMSET, thus creating a large increase in the expression of MMSET protein.
The increased expression of MMSET enzyme leads to an increase in H3K36me2-labeled nucleosomes. This in turn switches chromatin from being off, to being on. As a result, there is expression of cancer-promoting genes that drives the conversion of normal plasma cells into cancerous multiple myeloma cells.
KTX-1001 inhibits MMSET, which reduces the methylation and turns off the expression of genes that multiple myeloma cells need to be cancerous.
Treatment with KTX-1001 selectively treats t(4;14) multiple myeloma.
KTX-1001 is a first-in-class highly potent inhibitor that specifically blocks the enzymatic activity of MMSET.
Treatment with KTX-1001 in t(4;14) multiple myeloma acts as a precision medicine by blocking the activity of the excessive MMSET enzyme. A decrease in H3K36me2 shuts down chromatin and turns off the expression of genes that multiple myeloma cells need to be cancerous.
