Leveraging Novel Biomarker Strategies to Improve the Success of Drug Discovery

Leveraging Novel Biomarker Strategies to Improve the Success of Drug Discovery

Background

Biomarkers are measurable indicators (e.g., a molecule, gene, or characteristic) that can identify a particular physiological process or disease in the body.

Biomarkers can be applied to any disease, and while symptoms in patients are often subjective, they provide an objective, measurable and robust way to characterise a disease. Measuring biomarkers can help predict, diagnose, and monitor disease and can identify how well the body responds to treatments.

Challenge

Drug discovery is a costly, time-consuming process, with many complexities. To progress potential new drugs into clinical trials, innovators must persuade investors or pharma partners to invest in their programmes. To get a drug to a patient, 60% of the costs and 70% of the time is spent in clinical trials; it is therefore expensive to incur delays and reputationally damaging to get it wrong. For that reason, it is difficult for innovators to secure investment without robust evidence demonstrating the probability of success.

It is vital to demonstrate a deep understanding of the clinical considerations to support drug development; such as what dosage is required, which patients it is best suited to, and how patients will respond to it.

Building a robust strategy to identify and test biomarkers can help innovators understand how their drug works and how it interacts in different patient populations. This information can be used to build scientific evidence that helps transition their drug through pre-clinical and clinical testing, reduce risks and ensures hypotheses are thoroughly tested.

However, generating these insights relies on cutting-edge technology and advanced, multi-disciplinary expertise, which means that the application of biomarker strategies to support success in the clinic is currently underutilised.

The expert biomarkers team at Medicines Discovery Catapult (MDC) has supported 43 organisations to develop a better understanding of their asset using biomarkers. MDC deploys state-of-the-art high-resolution biomarker technology and has the ability to source high-quality biosamples for research. Its combined expertise across different areas of drug discovery means that partners receive bespoke support to help address their drug discovery challenges.

Using biomarkers as a key tool to improve clinical success, MDC provides vital data to UK drug discovery innovators. It addresses unmet patient need across a range of priority diseases, including oncology, infectious disease, age-related multimorbidity, and neurology.

One of the companies MDC has supported is Alchemab Therapeutics, a biotech company developing novel therapeutics for patients with hard-to-treat diseases. It does so by harnessing the power of naturally protective antibodies.

In 2021, Alchemab received a Biomedical Catalyst early-award grant from UK Research and Innovation. The grant supported the development of a novel disease-modifying antibody therapeutic for Huntington’s Disease (HD), a neurodegenerative condition. There is currently no cure for HD, and treatment is primarily focused on symptom management.

Its pioneering collaboration with MDC combined Alchemab’s innovative antibody discovery platform with MDC’s expertise in pre-clinical cell models and advanced microscopy.

A further grant was awarded in 2022 to extend these studies, enlisting the support of MDC’s biomarkers team to:

• Identify the molecular biomarkers of patients with HD

• Establish a patient selection development strategy and highlight markers for clinical translation of their therapeutic for HD

• Characterise HD in vivo models to better understand pre-clinical tools for development of therapeutics for the disease

• Develop robust clinically ready assays to improve the translation of pre-clinical tests to the clinic.

Building on the earlier work conducted by MDC’s Cellular Sciences team, it has validated a novel assay (test) for quantifying different species of huntingtin (the HD-associated gene protein) in biological samples. This assay and other biomarkers have been used to identify differences in profiles between HD patient groups. In addition, the extensive profiling of a disease model is underway and will aid future pre-clinical studies.

Using the biomarker package data generated through its work with MDC, underpinned by the initial project with the Cellular Sciences team, Alchemab aims to progress to the clinical stage with its therapeutic.

“MDC has supported Alchemab in developing a potential therapeutic for Huntington’s Disease through innovative biomarker discovery, imaging and their general neurodegenerative expertise. The collaborative partnership with MDC has enabled us to work together to achieve multiple milestones in our HTT (huntingtin, the Huntington’s Disease-associated gene) programme. The partnership has allowed us to utilise capabilities at MDC, such as state-of-the-art PET imaging abilities, mass spec and agnostic biomarker discovery, which aren’t available elsewhere.”

Biomarker-enabled drug development programmes have been shown to have a higher success rate. They enable a full understanding of a candidate drug’s impact on biological processes, which enables drug candidates to progress successfully from cells to tissue models and then to patients.

Using its expertise in drug discovery and disease biology, underpinned by its technical capabilities, MDC develops and delivers bespoke targeted and exploratory biomarker solutions. These bespoke biomarker strategies provide partners like Alchemab with insightful answers and generate decision-making data packages that can accelerate the development of new medicines.

This is particularly important in areas of significant unmet patient need, such as neurodegenerative diseases, where biomarkers show great promise but are currently underutilised.

Impact

MDC enhances drug development by boosting innovators’ understanding of disease and drug responses through the generation of bespoke pre-clinical and clinical biomarker data using state-ofthe-art technology that is not readily available.

In doing so, MDC helps to give innovative new drugs the best chance of success as they progress through pre-clinical testing and improves the chance of them being approved for use in the clinic.

Supporting a more successful drug discovery process will result in a greater understanding of disease and more medicines being delivered to patients faster.

Gayle Marshall, Head of Biomarkers at Medicines Discovery Catapult, said:

“With an increased understanding of each individual patient’s disease, we become better informed of the therapeutic development required, the pre-clinical tools we need to support discovery of novel drugs and their application to patient care.

“MDC employs cutting-edge technology, along with access to high-quality human biological samples to address crucial clinical needs. These tools allow the identification and validation of new targets and biomarkers that can be used to assess disease progression, predict treatment response, and provide valuable insights into the effectiveness of potential drugs. These data are crucial to evaluating drug effects on specific disease pathways and help guide decision-making throughout the drug development process.”