The majority of MND clinical trials, including trials using repurposed drugs fail due to lack of efficacy. As such there remains an urgent unmet need for safe and effective MND treatments.

Ensuring success in MND clinical trials needs to start with optimal preclinical decision-making, meaning the adoption of an enhanced, evidence-based approach to preclinical research so that only the most promising repurposed drug candidates are progressed into clinical studies.

Through LifeArc’s Translational Challenge in MND, this funding programme aims to boost drug repurposing in MND by investing at least £5 million in preclinical translation.

LifeArc will fund high quality innovative proposals that set out a rigorous evidence-based approach to the preclinical translation of repurposed drug candidates and drug candidate combinations, uniquely including funding for independent replication of project results through LifeArc.  This will contribute to building a strong body of evidence to enable evidence-based decision making on which repurposed drugs should enter into biomarker guided clinical studies and clinical trial platforms for MND. This includes existing UK platforms: EXPErimental medicine Route to Success in Amyotrophic Lateral Sclerosis (EXPERTS-ALS), and MND systematic multi arm adaptive randomised trial (MND-SMART).

LifeArc MND drug repurposing programme USP

• LifeArc is a hub for drug repurposing expertise and translational research.
• LifeArc is providing £5m investment for repurposed drug and drug combination approaches.
• Rigorous and evidence-based approaches to preclinical drug repurposing are a priority.
• Proposals will focus on preclinical data packages with independent replication of data.
• Better informed decisions on drug progression into EXPERTS-ALS and MND-SMART trials.
• Supporting next generation of translational scientists with beneficial ECR funding terms.

LifeArc workshop on Drug Repurposing for MND

This webinar has now taken place.  A recording of the full webinar is available to watch here.

Through this Drug Repurposing Programme LifeArc will commit at least £5m to fund up to five successful projects as part of LifeArc’s Translational Challenge in MND.

This significant investment will be exclusively focused on preclinical translation of repurposed drug candidates for MND including drug candidate combinations.

Proposals will focus on generation of  high-quality preclinical data packages and independent replication of data two areas that have been historically underfunded in academia but are critical for drug discovery.

We will fund high quality proposals from the UK MND research community and MND research groups internationally, that demonstrate the potential to transform the way in which repurposed drug candidates are de-risked for clinical trials.

We will also provide beneficial funding terms for early career researchers, to ensure programmes can attract and retain the most talented post-doctoral scientists.

LifeArc will also reduce barriers and enable access to appropriate support and infrastructure.

LifeArc can provide a hub of expertise offering translational research advice and mentorship as well as providing access to a collaborative network of potential project partners to enable the best chance of project success.

Your project will benefit from LifeArc drug repurposing know-how and capabilities to ensure your project considers all relevant preclinical, clinical and regulatory steps necessary to enable repurposed drug candidate discovery and development.

LifeArc has a track record in drug repurposing through its existing work and partnerships, with UKRI to generate a toolkit for drug repurposing; and through its partnership with Remedi4all.

LifeArc also recognises that not all applicants will have the internal resources and pre-existing relationships required for end-to-end project delivery.  There will also be the opportunity to outsource defined parts of the research plan to LifeArc or Contract Research Organisations (CROs) with appropriate expertise and capabilities to conduct GLP studies to generate reliable preclinical data to inform regulatory decision making.

We will work closely with funding recipients to identify where access to LifeArc, a CRO or other partner is in the best interests of the project. However, applicants will need to articulate (at full application stage) a clear plan as to what capability, tools or facilities will be accessed to deliver the proposed research plan, including through collaboration or with project partners including outsourced CRO work. LifeArc will provide support to engage 3rd party delivery partners as needed (e.g, development of a CRO statement of works and acting as the point of contact).

LifeArc will actively engage with applicants and project teams throughout the lifecycle of the project (including helping develop the full application). Support will be tailored to individual project needs (defined at the full application stage).

Support may include:

Signposting and making connections with LifeArc delivery Partners including CRO’s repurposing/regulatory experts and public and patient engagement panels as needed to ensure project outputs are aligned with repurposing/regulatory/scientific/PPI advice.

1:1 Mentorship and advice to shape project plans including but not limited to drug discovery, disease area insight, experimental work package and milestone-based project design, intellectual property considerations and advice/signposting for the appropriate clinical and regulatory pathways.

Applicants should focus their proposals on the preclinical stage of drug discovery and development for repurposed drug candidates. For guidance we would like to refer applicants to the following white paper ‘Guiding principles for drug discovery and development in amyotrophic lateral sclerosis’.

In addition, further information on the different stages of drug repurposing can be found here.

• To have a higher chance of success, applications must have existing preliminary data to demonstrate that a drug target is linked to disease, either through genetic evidence and/or evidence for disease biology involving the target.
• Existing evidence for a druggable target may include expression data in relevant tissue, linkage to ALS in humans confirmed through bioinformatic approaches, target expression studies in human tissue and evidence from relevant in vitro and/or in vivo
• Applicants must also be able to demonstrate an early case for the proposed repurposed drug candidate in MND, supported through existing preclinical evidence in relevant disease models.
• Evidence in human-based cell models that shows on-target modulation with the repurposed drug candidate results in disease phenotype modification is particularly desirable, however we will also consider projects that show clear plans to generate this necessary evidence in early milestones.
• Project plans in addition should aim to generate repurposed drug candidate preclinical data packages for target validation, efficacy, safety and PK/PD studies in vivo to demonstrate appropriate target tissue exposure and target engagement.
• Project plans should also focus on validation of available biomarkers of repurposed-drug target engagement for MND or have plans to identify and validate novel biomarkers that may be translatable from preclinical models to MND patients.

Independent replication / robustness

• Applicants will need to include replication of key results through an independent laboratory in their project plans. LifeArc can provide support and funding to facilitate this either through its own world-class laboratories or third parties.  This will be an essential step to ensure data robustness and to ensure translatable results for future clinical development programmes.

Biomarker identification and development

• The development of the repurposed drug candidate for MND should be accompanied by inclusion of a strategy for appropriate target engagement biomarker identification and/or validation to demonstrate target engagement is linked to MND.
• Key outcomes of this type of study may include information on optimal drug dose for MND and if the dose level achieves desired therapeutic effects.
• Use of surrogate biomarkers to inform on the relationship connecting dose and efficacy are also encouraged.

Preclinical development projects

• Applicants will also receive support through LifeArc to generate data packages including ADME, toxicity/safety and PK/PD studies to measure levels of target tissue exposure, target engagement and drug pharmacological activity consistent with MND TPPs.
• The preclinical development phase of the repurposed drug candidate may be carried out by partner CRO’s to GLP standards, this provides robust assurance that the repurposed drug candidate is likely to be safe and effective in the clinic. This phase will be complemented by use of relevant biomarkers that may also improve the use of the therapeutic in patients.
• Repurposed drug candidates that have been rigorously tested and approved will then exit into existing experimental medicine platforms including EXPERTS-ALS. This will include a progression strategy for clinical development, regulatory process, and potential involvement of commercial organisations.