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Working to improve pipeline efficiency using genomics

Although the Food and Drug Administration approved a record number of novel therapeutics in 2020, only one drug out of 10 (about 10%) that enters clinical trials is ultimately approved by the FDA. That is a problem, and a costly one at that.

Developing a safe and efficacious drug is quite challenging, as evidenced by a Biostatistics study, which found that 2015’s total revenue from the entire pharmaceutical industry was $1.2 trillion, and $150 billion was spent on R&D. The sobering statistic is that approximately $112 billion of that R&D spent in 2015 (nearly 75%) can be directly attributed to failed clinical trials.

Imagine any other industry where a 10% success rate would be considered acceptable. Imagine only 10% of Uber rides getting passengers to their destinations. Or just 10% of children graduating high school. Yet, for drug development, this has been the norm for decades. It also means that many patients in need of new treatments never received them.

Beyond numbers to patients

Meanwhile, many people with chronic, complex diseases such as multiple sclerosis (MS) need better treatment options. MS, which causes irreversible damage to the central nervous system, is a complex, chronic and incurable condition. It is marked by attacks that gradually deteriorate a person’s ability to function, due to losing an information flow within the brain and between the brain and body. Worldwide, more than 2.3 million people have an MS diagnosis.

While current treatments can help slow progression, there is no cure for MS currently. Scientists do not know what causes MS, and they believe that a combination of factors may be at play. Approximately 200 genetic variants (changes) that may increase a person’s risk of developing MS have been identified.

Why genomics can provide hope

By exploring the relationship between genomics, the environment and other supposed risk factors, Genuity Science hopes to better understand the possible causes of MS. Having a deeper understanding of the causes will accelerate the process of finding and developing better diagnostics and more effective treatments for this complex disease.

The idea is to get to the root causes of disease and stop its progression, rather than focusing on just treating symptoms. Genuity Science believes that if they can identify what is driving cellular behaviour and dictating phenotype, they can help biopharma build more effective therapeutics. This approach can improve efficiency, which in turn, improves drug discovery and development. Hope for improvement comes from numerous areas—from tackling novel and interesting targets to identifying more suitable clusters of patients who are likely to respond to a given therapy.

Genuity Science’s experience, along with recently published studies, demonstrates the benefit of genomics to help validate novel drug targets. Genomic validation of a target can increase the likelihood of a drug development program’s success by roughly two-fold.1,2 To date, this has largely been attributed to increased confidence in efficacy—decreasing Phase 2 or 3 failures. However, there is also evidence that improving patient stratification based on genomic biomarkers yields better study designs and more precise outcomes for clinical trial managers.

Imagine if a pharma company’s pipeline is twice as likely to succeed. For every 10 assets in a drug development pipeline, what if two are successful instead of only one? That can cut R&D costs in half and expand the segment of patients benefiting from those therapies. A lower cost of treatment could mean better access for the patients who need therapy, leading to improvements in efficiency, as well as outcomes.

The importance of leveraging large-scale genomics data

Although there is much hope, many in the field still express scepticism that this approach will deliver on what scientists claim. That scepticism likely comes from undue and irrational exuberance around the utility of genomics in the early days of this technology. With reference to the Gartner Hype Cycle, genomics has gone through most of the early phases of that cycle.

The rapidly increasing interest and excitement for genomics in medicine were based on a trigger—the completion of the Human Genome Project in 2003. That excitement reached a fever pitch as next-generation sequencing technologies emerged in the market. The peak of this hype was driven by the belief that the industry could understand diseases in much more detail, so it would be able to target and treat diseases in superior ways. Now sitting squarely in the trough of disillusionment, the slope of enlightenment is within reach by creating a better and more complete picture of complex diseases and disease subtypes, but genomes alone will not get us there.

Even with the ability to read someone’s whole genome sequence, doing something with that data or deriving disease insight from the data remains difficult. That understanding is complex because high-impact, disease-causing, single-gene variants with Mendelian inheritance patterns are not as relevant in common, complex diseases. However, by combining high-quality sequencing with high-depth phenotypic data, the field is on the cusp of connecting low-frequency, high-impact variants to difficult-to-treat diseases. These findings are critical to identifying novel targets for therapeutic development and biomarkers linked to things like disease progression.

Genuity Science is in a unique position to push this approach forward because they have the tools necessary to extract insights from large-scale genomic data combined with deep longitudinal clinical data. Their scientists and researchers work to build large datasets with the right make-up of participants—datasets enriched with individuals with key disease characteristics, outcomes, and progression. Their lab can sequence samples from those participants to generate high-quality whole genome sequence data. Its scientists have deep domain expertise in the disease areas on which they are focused. And the effort to translate data to insight is powered by Genuity Science’s purpose-built analytical platform.

The question that remains is, “Have targets with genomic validation been identified?” The short answer is yes.

Genuity Science began with MS and continue to identify targets in partnership with their pharmaceutical partners. Examples of genomically-validated targets are growing—PCSK9 and SLC30A8 are the best known, but others exist as well.3–5 They are generating insights from these data more efficiently than ever before because they can now do it at scale.

Targets identified in their research programs are expected to have an increased likelihood of success in development programs. In theory, fewer billions of dollars spent on development means better drugs coming to market faster and fewer patients waiting for the right treatment.


1. King, E. A., Davis, J. W. & Degner, J. F. Are drug targets with genetic support twice as likely to be approved? Revised estimates of the impact of genetic support for drug mechanisms on the probability of drug approval. Plos Genet 15, e1008489 (2019).

2. Nelson, M. R. et al. The support of human genetic evidence for approved drug indications. Nat Genet 47, 856–860 (2015).

3. Nioi, P. et al. Variant ASGR1 associated with a reduced risk of coronary artery disease. New Engl J Medicine 374, 2131–2141 (2016).

4. Rich, K. A., Roggenbuck, J. & Kolb, S. J. Searching Far and Genome-Wide: The relevance of association studies in amyotrophic lateral sclerosis. Front Neurosci-switz 14, 603023 (2021).

5. Shapiro, M. D., Tavori, H. & Fazio, S. PCSK9: From basic science discoveries to clinical trials. Circ Res 122, 1420–1438 (2018).

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