About Epigene Therapeutics

Epigene Therapeutics Inc. was created by the NEOMED Institute in December 2017. Our chief executive, Frank Giles, leads a team that is advancing novel epigenetic modulators for the treatment of patients with cancer. These unique agents, including NEO2734 and NEO1132, have been generated from multiple distinct proprietary chemical series and scaffolds. This year's IND/CTA/EudraCT and Orphan Drug Designation filings for our lead molecule, NEO2734, are on track with initiation of clinical studies scheduled to immediately follow.

NEO2734 is an orally-bioavailable, first-in-class, multi class epigenetic modifier that inhibits the Bromodomain and Extra-Terminal domain (BET) family (epigenetic "readers") and the Cyclic AMP response element binding protein (CREB)-binding protein (CBP) and E1A interacting protein of 300 kDa (EP300 or P300) [CBP/P300] paralogs (epigenetic "writers"). NEO2734 is the first clinically-applicable agent to have these multiple capabilities. The significant activity of NEO2734 in a broad spectrum of in vitro and in vivo models of hematological malignancies and solid tumors, including marked superiority to BET or CBP-P300 inhibitors, has been established in collaborations with physician-scientist colleagues in leading academic centers of excellence. In 2018, these data were presented at the annual meetings of EHA (European Hematology Association – data on acute myeloid leukemia [AML]); ESMO (European Society for Medical Oncology – data on colon and prostate cancers); and ASH (American Society of Hematology – data on lymphomas).

NEO2734's in vivo activity in both SPOP mutated and wildtype prostate cancer, again with significant superiority to that of BET or CBP-P300 inhibition, was presented at this year's ASCO/ASTRO/SUO (American Society of Clinical Oncology/ American Society for Radiation Oncology/Society of Urologic Oncology) Genitourinary Cancers Symposium. Further data on NEO2734's activity in lymphoma will be presented at the impending AACR (American Association for Cancer Research) annual meeting and has been submitted to EHA's annual meeting (data on AML) with updates on its activities in NUT carcinoma and sarcomas in preparation. These data are being used to optimize the focus of NEO2734's initial clinical studies.

NEO2734's Targets

The Bromodomain (BRD) and Extra-Terminal domain (BET) family of proteins are key regulators of epigenetic control. Modulation of epigenetic 'readers' such as BRDs is a recognized developmental therapeutics priority. Cyclic AMP response element binding protein (CREB)-binding protein (CBP) and E1A interacting protein of 300 kDa (EP300 or P300) (P300/CBP) are highly homologous BRD-containing transcriptional co-activators ('writers') that regulate a number of important cellular events through their acetyltransferase activity. Inhibitors of BETs are in development, being studied alone1, or in combination with other class inhibitors (eg, tyrosine kinase inhibitor2; BCL-2 inhibitor3). The synergistic effect of JQ1 (a prototypic BET inhibitor) and a CBP/P300 inhibitor has been demonstrated.4

1. Lin et al, 800/10, AACR 2018
2. Liu et al., Mol Cancer Ther; 13 (5) May, 2014
3. Cai et al, LB-261/5, AACR 2018
4. Picaud et al., Cancer Res; 75(23) Dec 1, 2015

We have developed a series of molecules that exhibit dual inhibition of both BET and CBP/P300 from which NEO2734 has emerged as lead clinical candidate. In addition to NEO2734, the Epigene Therapeutics pipeline includes a second (chemically distinct from NEO2734) dual BET and CBP/P300 inhibitor (NEO1132) and a CBP/P300 inhibitor lead generation program.