Unlocking Cell Epigenomics to Transform Disease Treatment
Despite decades of advances in biology and technology, small-molecule drug development—the long-standing gold standard in therapy—remains inefficient, constrained by outdated design paradigms. Traditional models, such as the “one-drug, one-target” approach commonly used in cancer treatment, typically focus on cell surface receptors and kinase signaling pathways. While these approaches can yield targeted therapies, they often fall short due to limited efficacy, toxicity, and drug resistance.
As Albert Einstein famously 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 mindset—leading a new era in drug discovery by targeting cell epigenomics and transcriptomics, moving beyond conventional, signal-centric strategies.
Rethinking the Roots of Disease
Cells regulate gene transcription in response to both internal and external signals. While many diseases originate from genetic mutations or disrupted signaling, it’s often the dysregulation of epigenomic and transcriptomic control—across multiple cell types—that drives disease progression. Targeting histone reader proteins, such as bromodomains (BrDs), offers a powerful way to restore normal gene transcription and cellular function.
Bromodomains: Master Regulators of Transcription
Gene transcription depends on histone modifications, chromatin remodeling, and transcription factor activity. BrD proteins bind acetyl-lysine marks on histones and other regulators, orchestrating transcriptional programs that can, when dysregulated, contribute to uncontrolled cell growth. Among these, the BET protein family, a well-characterized subset of BrDs, has emerged as a therapeutic target in cancer and inflammatory diseases. However, first-generation BET inhibitors—such as Novartis’ Pelabresib[1]—have shown limited success due to dose-limiting toxicity and short-lived efficacy as monotherapies.
Parkside’s Solution for Intractable Diseases
Parkside’s proprietary STAMPTM technology[2] is designed to overcome these limitations by engineering small molecules that modulate multiple transcriptional mechanisms in parallel. Unlike conventional BET inhibitors, STAMPTM BrD drugs selectively engage BrD proteins across complex regulatory networks—correcting abnormal gene expression at lower doses while minimizing toxicity and improving therapeutic impact.
The company’s lead candidate, PS1132, a STAMPTM BrD-targeting compound, has demonstrated favorable pharmacokinetics and drug exposure in Phase I trials. Early results are encouraging, with PS1132 showing promising safety and efficacy—outperforming first-generation BET inhibitors like Pelabresib in both T-cell and B-cell lymphomas, and with minimal adverse effects.
Importantly, these patients had previously failed standard therapies, including chemotherapy (CHOP), immunotherapies (anti-CD20/CD47, anti-CD20/CD3), and targeted agents (JAK1, PI3Kδ, BTK inhibitors). Given the limitations of these widely used therapies—many of which are staples in large pharmaceutical pipelines—PS1132 offers a compelling opportunity for strategic partnership.
A Platform for Board Impact
Beyond hematologic cancers, Parkside’s STAMPTM platform is also 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
To explore partnership opportunities, contact us at [email protected].
2025-04-01
[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.