Preclinical development of new nucleoside-based drug against leukemia

Introduction

The current treatment landscape for leukemia, particularly concerning AML (acute myeloid leukemia) and MDS (myelodysplastic syndrome), is constrained by the instability of hypomethylating agents which are regularly used in elderly, medically non-fit patients (high-risk). This instability restricts their spectrum of application, leaving a significant gap in effective treatment options.

Despite research into alternative therapeutic approaches, the need for a mild treatment option with high success rates in this patient population remains unmet.

Proposed Solution

Carbacitabin (CAB) emerges as a promising solution to these challenges. This novel epigenetically active compound exhibits enhanced stability against hydrolytic cleavage and enzymatic metabolization.

In AML PDX mouse models, CAB demonstrates significantly improved efficacy and vastly reduced toxicity, making it an optimal candidate for leukemia treatment, particularly for those high-risk patients.

Funding and Objectives

Funding from the ERC PoC aims to support essential preclinical steps towards fully realizing the potential of CAB. These steps include:

1. Further optimization of the lead structure of CAB to enhance targeting.
2. Thorough preclinical studies to evaluate the safety and efficacy of CAB.
3. Scaling up the synthesis of CAB to meet the demand for large-scale production required for preclinical and subsequent clinical trials.

Intellectual Property and Market Position

Furthermore, efforts to solidify intellectual property (IP) protection and conduct an in-depth freedom-to-operate (FTO) analysis are necessary to safeguard CAB's market position.

Spin-off Company and Stakeholder Engagement

Establishing a spin-off company dedicated to the clinical studies of CAB will require engagement with essential stakeholders, including:

• Potential investors
• Pharmaceutical partners
• Legal advisors
• Regulatory consultants

This comprehensive approach will ensure the effective translation of CAB from bench to bedside, bringing new hope to patients, especially those battling AML and MDS.