Unlocking Cell Epigenomics to Transform Disease Treatment
Despite decades of advances in biology and technology, small-molecule drug development—the cornerstone of therapeutic innovation—remains inefficient, hindered by outdated design paradigms. Traditional cancer therapies often follow a “one-drug, one-target” model, focusing on cell surface receptors or kinase signaling pathways. While sometimes effective, these approaches frequently suffer from limited durability, toxicity, resistance, and narrow therapeutic scope.
As Albert Einstein once said, “We cannot solve our problems with the same level of thinking that created them.” Parkside Scientific Inc., based in New York City, embraces this philosophy by pioneering a new model of drug discovery—one that addresses the root causes of disease through the lens of cell epigenomics and transcriptomics, moving beyond conventional signal-centric frameworks.
Rethinking the Roots of Disease
Cell functions are governed by gene expression patterns shaped by internal and external cues. While genetic mutations and aberrant signaling may trigger disease, it is often the widespread dysregulation of epigenomic and transcriptomic control—across diverse cell types—that drives disease progression. This insight reveals a powerful therapeutic opportunity: reprogramming gene expression to restore normal cell function.
One promising strategy involves targeting histone reader proteins—particularly bromodomains (BrDs)—which serve as key regulators of gene transcription.
Bromodomains: Gatekeepers of Gene Transcription
Gene transcription is controlled by epigenetic mechanisms involving histone modifications, chromatin remodeling, and transcription factor activity. BrD proteins recognize acetylated lysines on histones and other regulatory proteins, orchestrating complex gene expression programs. When dysregulated, these programs can lead to uncontrolled cell growth, fueling diseases such as cancer and chronic inflammation.
The BET family of BrD proteins has emerged as a prominent drug target. However, first-generation BET inhibitors—like Novartis’ Pelabresib[1], developed under the one-target model—have faced challenges in clinical trials, including dose-limiting toxicity and modest, short-lived efficacy as monotherapies.
Parkside’s Breakthrough: STAMP™ Technology
Parkside’s proprietary STAMP™ platform[2] is designed to overcome these limitations. Rather than narrowly inhibiting a single BrD protein, STAMP™ molecules modulate multiple transcriptional pathways simultaneously. This network-aware strategy enables the correction of dysfunctional gene expression at lower doses—reducing toxicity while enhancing therapeutic effect.
The lead candidate, PS1132, is a STAMP™-based BrD modulator that has demonstrated favorable pharmacokinetics and drug exposure in Phase I trials. Early results are compelling: PS1132 has shown strong safety and efficacy in both T-cell and B-cell lymphomas, with significantly fewer adverse effects—outperforming earlier BET inhibitors like Pelabresib by a wide margin.
Notably, trial participants had previously failed multiple standard therapies, including chemotherapy (CHOP), immunotherapies (anti-CD20/CD47, anti-CD20/CD3), and targeted agents (JAK1, PI3Kδ, BTK inhibitors). In this high-need setting, PS1132 offers renewed hope—and a compelling opportunity for strategic partnerships.
A Platform with Board Potential
Beyond hematologic cancers, Parkside’s STAMP™ platform is advancing next-generation BrD-targeting therapies for treatment-resistant solid tumors and chronic inflammatory diseases—including prostate and breast cancer, inflammatory bowel disease (IBD), multiple sclerosis (MS), and Alzheimer’s disease.
Join the BrD Drug Discovery Revolution
Parkside Scientific is redefining drug discovery through the power of cell epigenomics. To explore partnership opportunities, contact us at [email protected].
2025-04-03
[1] Pelabresib, acquired by Novartis ($2.9B), is seeking FDA approval for the treatment of myelofibrosis in combination with ruxolitinib.
[2] STAMP = Strategic Transcriptional Activity Modulator Paradigm.