Mind the Gap: Understanding How to Progress Your Project Towards Translation
May 17, 2023
The "Gap” or "Valley of Death” is often mentioned in discussions of translation and commercialisation in biomedical research. It's vaguely understood as the space between the preclinical and clinical; the disconnect between basic scientific findings in a laboratory and a tangible product for patient use.
While there are many reasons why a promising discovery fails to translate into a treatment, in Australia, there is a distinct phenomenon whereby projects are unable to reach a stage where they are attractive for investment by pharmaceutical companies, venture capitalists, government or philanthropic organisations. It’s possible for research on a potential target to be published in a high-impact journal but not generate any interest for further commercialisation from the broader sector. The BioCurate team brings funding, industry expertise and hands-on management to help scientists translate their promising biomedical discoveries into high quality preclinical candidates to accelerate commercial outcomes.
Why does this gap exist, what is the experimental data needed to bridge this gap and how exactly can BioCurate help?
What makes a project attractive for investment?
Projects need to be attractive to investors. The process of bringing a novel treatment to regulatory review and approval can take more than 10 years and over USD $200 million (using the example of development of a small molecule in oncology). With such financial risk, only the most promising projects with the greatest commercial opportunity are considered for investment. Therapeutic candidates need to be supported by rigorous, reproducible and robust scientific evidence. That is, there needs to be a convincing case as to why a novel therapeutic candidate should be further developed.
Projects are attractive for investment when they address:
- Unmet medical need
- Clear commercial and licensing potential
- Differentiation (preferably on efficacy) from other approaches on the market, or in clinical development, or from those that have failed in development
- Verified link to human disease – target validation
- Available and predictive biomarkers
- Intellectual property (IP)
- Must have potential for novel IP. Existing IP is not necessary
- No known Freedom to Operate (FTO) issues
- Clearly defined regulatory and clinical pathway
- Must be supported by robust, reproducible scientific data
What is the “gap” and why does it exist?
The therapeutic development pipeline can be segmented into a number of stages. While most modalities will go through similar stages, the processes involved at each stage may vary slightly. The following is the typical pathway in the development of a small molecule drug:
- Basic Research & Target Identification (ID)
- Target Discovery
- Lead Identification
- Lead Optimisation
- Preclinical Development
- Clinical Trials
- Regulatory Review & Approval
Often, biomedical research that takes place in academic settings ends at the Basic Research & Target ID stage. Here, a target of interest (gene or protein) with a potential role in disease is identified through data mining (bioinformatics), genetic association studies, expression profile experiments, pathway and phenotypic analysis or functional screening.
Industry, however, rarely invests in projects at this stage as it is deemed “too risky.” An analysis by BioCurate has found that the majority of deals are done at the “pre-clinical” stage, not Target Discovery, and that return on investment is highest when exiting at the Lead Optimisation stage (Figure 1). Here, risk has been mitigated to an acceptable level whereby industry is prepared to invest the millions necessary to further develop a candidate.
As such, there is an expertise gap between where academic research ends and where industry begins (Figure 2). This gap commonly covers the Discovery Phase which includes Target Discovery, Lead Identification and Lead Optimisation activities. This means that promising projects that have produced high-impact publications may be left languishing with their potential unfulfilled.
How to close the Gap
To close this gap, academic scientists need to undertake further research activities to reach the Lead Optimisation stage. With this data at hand, industry is more likely to invest with the aim of putting a novel therapeutic candidate on market. But what does this entail?
1. Target Discovery and Validation
At this stage, academic researchers need to experimentally demonstrate that a target is directly involved in a disease process, and that modulation is likely to have therapeutic efficacy. Experiments/tools may include:
- Expression analysis
- Mechanism of Action studies
- In vitro function assays
- In vivo validation experiments
2. Lead Identification or Hit-to-Lead
Here, “hits” from screening campaigns are transformed to “leads” through refinement of compound potency and selectivity. This can include activities such as:
- High-throughput assay development
- Hit identification
- Secondary and orthogonal screening
- Hit-to-lead development
- Structure-based drug design
- Structure activity relationship studies
- Target engagement studies
3. Lead Optimisation
This stage involves the refinement of lead compounds, culminating in the identification of a preclinical candidate demonstrating on-target activity and in vivo efficacy. This may involve:
- Lead characterisation
- Structure activity relationship studies
- Optimising lead potency, efficacy & specificity
- ADME (absorption, distribution, metabolism and excretion) assays
- Target engagement studies
- PK (pharmacokinetic)/PD (pharmacodynamic) efficacy studies
- Pre-GLP (good laboratory practices) toxicology studies
Why is it so difficult to close the Gap?
Closing the gap is difficult because of the breadth and depth of expertise needed to undertake, analyse and understand the data generated in the Target Discovery, Lead Identification and Lead Optimisation stages. For example, with the development of a small molecule, these three stages alone may require a team consisting of:
- Project leader
- Computational chemist
- Medicinal chemist
- Molecular biologist
- ADME specialist
Regardless of the modality, a multidisciplinary diverse team with specialised expertise is critical in providing all the skills and knowledge needed to progress a project. Academic researchers cannot do it alone. BioCurate is here to help close the Gap.
BioCurate’s team of experts bring hands-on industry experience and a global track-record in the successful development and commercialisation of a range of therapeutic modalities spanning a diverse array of diseases.
BioCurate is unique in that not only does the company provide funding opportunities, but the BioCurate team works collaboratively with academic researchers in a hands-on manner to conduct discovery activities. As well as BioCurate’s licensed portfolio of projects that receive funding and expertise to reach the “exit” stage of investment by Venture Capital or large Pharma after Lead Optimisation, BioCurate provides support for early-stage projects so that they can achieve the first steps described above. By funding early Proof of Concept studies and then actively driving the translation of projects utilising the team’s expertise in rigorous biopharma business practices, BioCurate is there for the long haul, as opposed to many other funding bodies.
BioCurate is committed to supporting and mentoring talented academic researchers to help translate their projects, and to ultimately fulfill our joint vision of delivering clinical impact to patients through the development of new therapies.