Why clinical trials matter?

The strategic goal of Hamlet Pharma is to develop novel cancer treatments for patients who currently lack therapeutic options. Conducting clinical trials is crucial to reach primary goals such as evaluating the therapeutic window for HAMLET in bladder cancer. We also aim to gain new insights that facilitate the drug development for Alpha1H and the diversification of our activities to include other indications.

Outcome of the Phase I/II trial in patients with bladder cancer.

Hamlet Pharma Ltd. is making great progress and has just concluded the first part of a clinical trial in patients with bladder cancer. Drug development often takes many years, due to complex development and approval processes. Based on our extensive prior experience, the drug candidate, Alpha1H, has passed a number of important milestones in a relatively short time and with moderate cost.

The results of the clinical trial will be announced shortly.

Clinical Trial Protocol

The safety and efficacy of Hamlet Pharma’s drug candidate Alpha1H is being investigated
for two years.
We are conducting a single centre, randomized double-blind trial in patients with non-muscle invasive bladder cancer. The trial compares Alpha1H to placebo and will determine the safety and efficacy of Alpha1H by measuring outcomes such as tumour size and cell death. The trial has enrolled 40 patients consecutively and after an interim analysis of safety and efficacy, the patients will be followed for two year.

Clinical Trial Organization

The clinical trial is being conducted at a leading European centre for bladder cancer studies, in compliance with European regulatory requirements. The investigator has prepared the clinical trial protocol jointly with Hamlet Pharma, as well as the study design and documentation for the ethics application. The subjects have received six intra-vesical instillations of Alpha1H or placebo.
The trial is being monitored by a well-respected Contract Research Organization (CRO), in accordance with applicable guidelines. The CRO ensures that the study meets both European and US FDA quality standards. In addition, they are responsible for Data Management, Statistics, and Pharmacovigilance.

Evaluation

The study is designed to collect data on safety (pharmacovigilance), tolerability, pharmacokinetics and pharmacodynamics of Alpha1H, and to evaluate the efficacy of Alpha1H as a cancer drug. The study will use cell shedding after instillations of Alpha1H as a biomarker of cancer cells death. This will be an important measure of effect, together with molecular endpoints.

We have rapidly and successfully developed important technologies to conduct and evaluate the clinical trials and evaluate the outcomes safety and efficacy.

These include:

The second generation drug candidate Alpha1H

Detailed molecular studies have allowed us to make a map of the protein and to identify domains responsible for the effect on tumour cells. Based on the science, we have developed a new synthetic drug candidate Alpha1H, which is the business end of HAMLET and kills tumour cells with similar efficacy.
The peptide can be synthesized in large amounts and activated by the addition of the lipid, just like HAMLET. We can now guarantee the supply of material needed to initiate placebo-controlled clinical trials.

GMP production

Clinical studies require large quantities of the drug candidate, produced in accordance with GMP, as well as documentation, according to the guidelines of the European authorities and the American FDA. The first manufacturing batch also called “engineering batch”, has been analysed with positive results.
Hamlet Pharma has successfully established large-scale production of the active compound Alpha1H with full GMP standards. The peptide-based technology has added precision, reduced the complexity of the GMP approval process and lowered production costs. In addition, the patent life of the peptide complexes lasts until 2031. The peptide production technology will also make it possible for the company to explore additional clinical indications and out-licensing of selected therapeutic areas.

Therapeutic effects in animal models

In animal studies local HAMLET treatment limited the progression of brain tumours, colon cancer, and bladder cancer, suggesting that HAMLET could be used to prevent tumour development in genetically susceptible individuals. Using the engineering batch of the synthetic Alpha1H complex, we have also shown that Alpha1H reproduces the therapeutic activity of HAMLET. against bladder cancer, in a murine model.

Toxicology and Safety Studies

A central goal of cancer therapy is to achieve selectivity for the tumour and minimal toxicity for healthy tissues. Tissue toxicity and side effects are still the norm, however, and even though new, targeted therapies act with greater precision, the notion of tumour-specific mechanisms of cell death is justly regarded with scepticism.
Yet, Alpha1H and HAMLET have not shown toxicity for healthy cells or tissues, in animal models or clinical studies. We are performing toxicity studies to exclude any unwanted effects of Alpha1H.

Regulatory Process

We have drafted key documents needed to initiate clinical trials, including the Investigator’s brochure, Clinical trial protocol, and Ethical application forms.