Challenge prizes for personalised medicines

england

Personalising Medicines Parker Moss and Piotr Gierszewski September 2020

Today most therapies are developed for a general patient group based on large and expensive clinical trials. Precision medicine will change that by tailoring therapies to each person’s genetic makeup, and hence improving the likelihood of it working.

• Precision medicine is made possible by digitisation of health records, affordable genome sequencing, and custom designed therapies.

• We are able to read the human genome and predict how people might respond to a particular treatment to make sure we choose the right one.

• Despite all of the promises, there are enormous challenges to the introduction of personalised medicine which require a novel approach to drug discovery.

Our vision The Personalised Therapies Challenge seeks to build on the recent advances in digital and bio-medical technologies to make therapies more effective and safer by accelerating the creation of new precision medicines.

The Great Innovation Challenge: Personalising Medicines

The promise of precision medicine Precision medicine, often referred to as personalised medicine, refers to a new approach to healthcare in which patients are diagnosed and treated according to individual attributes.

These attributes could be genetic, relating to how these are coded within our genes (the genotype) or observed once these genes are decoded and put into use (the phenotype), but also social or environmental influences. The essence of the field of precision medicine is that by treating patients as individuals rather than as a homogeneous group, we can improve the effectiveness of treatment, while reducing side-effects of medication. Precision medicine is in a period of breakout growth at the moment due to advances in some fundamental technologies: • The digitisation of health records, and the increasing application of artificial intelligence and machine learning to this growing source of data is enabling scientists and doctors to identify clinical and biological features in patient data that can reveal strong predictive associations, and in some cases, causal relationships to developing diseases, side-effects of drugs and overall response to treatment.

• The routine availability of genome sequencing, which reveals the recipe book of every individual human being, allows patient data to be analysed at the most fundamental feature of the individual, the DNA. The life sciences sector has demonstrated that diagnostics and therapeutics that target specific variants in a patient’s DNA can transform disease prognosis, survival or response to treatment in patients exhibiting those features, while having no or minimal effects on other patients. These individual features are called biomarkers, and the advent of genetic and other molecular imaging techniques has led to an entire industry of biomarker discovery, and drug development, and companion diagnostics, all focussed on targeting individual patient biomarkers.

• Lastly, drug development has gone beyond small molecule drugs which are cheap to manufacture and easy to dispense. These larger molecules are referred to as ‘biologics’ and their massive structures allow for a far more intricate modes of operation. For instance, some biologics like antibodies which are exceptional at recognising molecules, can be engineered to respond to a specific cell only if its surface is abundant in a particular signature molecule, but remain ineffective if there is not enough of it. Similarly, gene and cell therapies now create synthetic, engineered cellular therapies that are often custom designed for an individual patient, to target a specific biomarker and avoid rejection by that patient’s immune system. These complex and expensive therapies are often so targeted that they can have a curative effect on patients, requiring a single dose.

2

The Great Innovation Challenge: Personalising Medicines

The role of innovation Despite all of the promises above, there are enormous economic, regulatory, behavioural and ethical challenges to the introduction of personalised medicine. However, there is an equally great opportunity for a more robust development of personalised therapies with a high unmet clinical need.

Historically it is extremely expensive to bring a new therapeutic to market through the discovery and clinical development process, taking 10-15 years and costing $1bn per successful drug launch, without accounting for the high level of attrition in the field of drug development. However, such is the complexity of these recent biologic and cell and gene therapies that drug development costs are rising very fast, particularly in oncology.

At the same time, the addressable markets for these drugs are shrinking because we are increasingly stratifying patients into smaller and smaller subgroups according to their narrow biomarkers.

Rising costs and shrinking market sizes are leading to a funding crisis and for some rare diseases This is a total market failure, when the economics of an individual drug development programme is considered in isolation. Hence, it is crucial to create new funding models to incentivise biotech startups to apply their skills to these markets.

The ultimate goal is to raise the profile of rare diseases and create a track record for personalised medicine in this field to leverage future investment While these drugs are often extremely expensive, their potentially curative nature can save years of inpatient periods and years of chronic decline, meaning that the savings to the health system overwhelm the drug budget for the individual patients. Similarly, this field of personalised medicine will deliver enormous returns in aggregate because the techniques used to develop new therapies are often based on biological approaches that, once perfected, can be adapted to a wide number of individual diseases. Consequently, the entry barriers for tackling rare diseases through personalised medicine are not as high as is usually the case with novel drug discovery and a challenge prize could use this opportunity to recruit talent that might otherwise not consider applying their knowledge in this field.

The urgent response to COVID-19 has shown that it is possible to improve the coordination of research, fast-track evidence generation and improve regulatory, manufacturing and reimbursement decisions in public health emergencies. There are candidate vaccines that similarly use tried and tested methods which are being adapted to SARS-CoV-2 antigens. It’s unclear whether these advancements to the drug discovery process will inspire long-term systemic change. However, there are tangible opportunities in replicating this favourable ecosystem much sooner within the boundaries of a challenge-driven drug discovery platform.

3

The Great Innovation Challenge: Personalising Medicines

With high-tech approaches like precision medicine, our research shows that challenge prizes have effects far beyond the incentive alone. We have found that they: • Help galvanise action around a shared vision: by shining a light on underserved diseases they could help focus attention on particular gaps or opportunities.

• Help give credibility and visibility to teams working on them: by signalling government support and independent validation, they could help attract publicity and investment to teams taking part.

• Help innovators develop their solutions: by building in access to relevant data, support with delivering clinical trials and navigating the regulatory obstacles, prizes could help accelerate the process and build confidence in the innovations created.

Opportunities for challenge prizes Nesta Challenges recommends a competition focussed on the most promising genetically targeted precision therapies, and zero in on the area of overlap where: • A therapeutic area has a very high unmet need (poor outcomes) for a small number of patients that are unlikely to attract pharmaceutical investment; • The class of drug is suited to very rapid clinical development (for example antisense oligonucleotide therapies have been shown to go from discovery to patient treatment in less than a year).

Once the right therapeutic area and a class of drug are identified, the challenge prize would be leveraged as a drug development platform which ensures: a. A coordinated end to end process of discovery, clinical trial, and manufacture and implementation of precision therapeutics is delivered via a proactive partnership with the UK health system, using UK innovators, hospitals, and coordination with UK regulatory bodies; b. Grant pre-approved access to the high quality data required for biomarker discovery to enable fast-paced analysis and interpretation from the start of the research project taking part in the challenge; c. Recruitment of applicants who can demonstrate that a lump sum prize money granting mechanism (as opposed to traditional grants and awards) will enable them to bring together multidisciplinary skills, de-risk and accelerate the development of a successful drug development programme.

4

The Great Innovation Challenge: Personalising Medicines

Further information Nesta Challenges Nesta Challenges exists to design and run challenge prizes that help solve pressing problems that lack solutions. We shine a spotlight where it matters and incentivise people to solve these issues. We are independent supporters of change to help communities thrive and inspire the best placed, most diverse groups of people around the world to take action.

We support the boldest and bravest ideas to become real, and seed long term change to advance society and build a better future for everyone. We are part of the innovation foundation, Nesta. A full list of our current challenge prizes is available on our website at www.challenges.org Genomics England Genomics England works with the NHS to bring forward the use of genomic healthcare and research in Britain to help people live longer, healthier lives. Genomics is a groundbreaking area of medicine that uses our unique genetic code to help diagnose, treat and prevent illnesses. It is already being used in the fight against COVID-19. Established in 2013, Genomics England launched the world-leading 100,000 Genomes Project with the NHS, demonstrating how genomic insights can help doctors across the NHS, and building a foundation for the future by assembling a unique dataset. The project was achieved thanks to patients and participants helping to shape it and guiding decisions on data and privacy.

Genomics England is now expanding its impact. Our next chapter involves working with patients, doctors and scientists to improve genomic testing in the NHS and help researchers access the health data and technology they need to make new medical discoveries and create more effective, targeted medicines for everybody.

To discuss the content of this challenge brief, contact: Piotr Gierszewski, Senior Researcher, Nesta Challenges piotr.gierszewski@nesta.org.uk Parker Moss, Chief Commercial & Partnership Officer, Genomics England parker.moss@genomicsengland.co.uk

58 Victoria Embankment London EC4Y 0DS +44 (0)20 7438 2500 challenges@nesta.org.uk @NestaChallenges www.challenges.org Nesta is a registered charity in England and Wales with company number 7706036 and charity number 1144091.

Registered as a charity in Scotland number SCO42833. Registered office: 58 Victoria Embankment, London, EC4Y 0DS.

5