Skip to content
What's on

Delivering novel therapies in the 21st century

Scientific meeting

Location

The Royal Society, London, 6-9 Carlton House Terrace, London, SW1Y 5AG

Overview

Image credit: skynesher

Delivering novel therapies in the 21st century is a two-day conference held by the Royal Society and Academy of Medical Sciences FORUM. Speakers will discuss recent scientific advances in therapeutic modalities and delivery. The meeting will also explore the infrastructure required to develop novel treatments and implications of these advances for policy and healthcare. Developments in areas including new immunotherapies, affinity reagents, bioelectronics, gene therapy and nanoparticle delivery will be considered within the broader context of personalised medicine, technology and data, regulation, value, access and care delivery.

Attending this event

This open event is free to attend and is intended for those with an interest in the life sciences sector, from a variety of backgrounds including academia, industry, government, the NHS, as well as regulatory, charitable and other scientific bodies.

Contact the Industry team for more information.

About the conference series

This meeting forms part of the Royal Society’s Transforming our Future series, and the Academy of Medical Sciences’ FORUM programme. The Transforming our Future meetings are unique, high-level events that address scientific and technical challenges of the next decade and bring together leading experts from wider scientific community, industry, government and charities.

The Academy’s FORUM programme brings together industry, academia and the NHS, and the charity, regulatory and wider healthcare sectors. It provides an independent platform to bring together leaders from across the life sciences sector to discuss scientific opportunities, technology trends, translational challenges and strategic choices in healthcare.

Event organisers

Select an organiser for more information

Schedule of talks

24 October

08:30-09:00

Registration

09:00-09:10

Welcome from the Royal Society and Academy of Medical Sciences

1 talk Show detail Hide detail

Sir John Skehel FMedSci FRS, Vice-President and Biological Secretary, The Royal Society
Professor Sir Robert Lechler PMedSci, President, Academy of Medical Sciences

Show speakers

09:10-09:40

Opening keynote: How do we make every promising drug target druggable?

1 talk Show detail Hide detail

Dr Menelas (Mene) Pangalos FMedSci, Executive Vice President, Innovative Medicines & Early Development Biotech Unit & Global Business Development, AstraZeneca

Abstract

The majority of today’s medicines are based on small molecule, protein or monoclonal antibody platforms. With an ever increasing need to better understand complex disease biology we need our scientists to be able to prosecute the best validated targets even if they are viewed as traditionally intractable from a traditional drug discovery perspective. Exploring novel drug modalities which complement existing strengths in small molecule and biologic platforms has the potential to open new therapeutic options.

Over the past few years we have made significant progress across seven additional drug discovery platforms, complementing existing capabilities in chemistry and protein engineering. These include modified mRNA therapies, antisense oligonucleotides (ASOs), oligonucleotide conjugates, bicyclic peptides, proteolysis targeting chimeras (PROTACs), anticalins and CRISPR. By combining our distinctive skills and technologies with those of our partners we are accelerating our goal to bring new medicines to patients in areas of high unmet medical need.

Show speakers

09:40-10:50

Discovery (part 1)

2 talks Show detail Hide detail

Chairs

Steve Rees, VP Discovery Biology, Discovery Sciences, AstraZeneca

09:40-10:00 Future opportunities for small molecule therapeutics

Dr Tony Wood, Senior Vice President, Platform Technology and Science, GSK

Abstract

The vast majority of small molecule drug discovery projects explored by medicinal chemists to date have targeted protein function, predominantly although not exclusively by blocking activity.  Typically leads are defined from high throughput screens and structure or substrate based design all of which are biased towards active site binders.  The past decade has seen the emergence of a number of technologies that are beginning to challenge this practise.  I will review progress in 3 areas during the presentation.  Namely, encoded library synthesis and screening that massively increases the number of compounds that can be evaluated in an unbiased binding mode, the emergence of small molecules that program protein targets for destruction and finally the evolution of chemical biology tools and technologies for assigning mode of action to cell based screening hits.  These technologies are poised to fundamentally change the landscape of application of small molecule drug discovery adding new mode of action options.

Show speakers

10:05-10:25 Bicyclic peptides as novel therapeutics

Dr Kevin Lee, Chief Executive Officer, Bicycle Therapeutics

Abstract

Bicyclic peptides or Bicycles® are a new therapeutic modality combining the attributes of antibodies, small molecules and peptides within one molecule. Bicycles® can be used as standalone therapeutics or coupled to deliver various therapeutic payloads, including cytotoxins, immune modulators, radionuclides or nucleic acids in a tissue selective manner. Bicycle Therapeutics’ has unique proprietary technology for the discovery of Bicycles® and is focused in oncology where Bicycle Toxin Conjugates® (BTCs) selectively deliver toxins to tumours, killing them with a high degree of precision and minimal effects on healthy cells. BTCs take advantage of Bicycles’ inherent properties of high target affinity and specificity, fast penetration into the tumour and low systemic exposure, combined with rapid renal elimination. BT1718, Bicycle’s lead BTC is currently under clinical exploration in collaboration with CRUK. Bicycles®also offer a range of unique opportunities in immune oncology and other therapeutic areas outside oncology.

Show speakers

10:30-11:00

Coffee

11:00-12:40

Discovery (part 2)

4 talks Show detail Hide detail

Chairs

Steve Rees, VP Discovery Biology, Discovery Sciences, AstraZeneca

11:00-11:20 The landscape for new biologics formats

Dr Jane Osbourn, VP Research and Development and Site Leader, MedImmune

Abstract

Antibody engineering has come of age and there are now over 500 antibody therapeutics in clinical development and nearly 70 approved for a wide range of different disease indications. Amongst these, there are many examples of antibodies with engineered properties such as increased potency, half-life extension and improved stability. The landscape for biologics therapies is evolving to deliver additional functionality with the introduction of novel formats, such as bispecific antibodies, peptide-antibody fusions, scaffolds and antibody -drug conjugates. Case studies will be presented illustrating the benefits of different formats and how they can be applied in different disease settings.

Show speakers

11:25-11:45 Antigen-targeted TCRs in cancer immunotherapy

Dr Bent Jakobsen FMedSci, Chief Scientific Officer, Immunocore and Scientific Founder, Adaptimmune

Abstract

Cancer immunotherapies function to harness the body’s own immune system to eradicate cancer cells. Critical to this process is the T cell, capable of directing potent and antigen-specific immune responses. T cell receptor (TCR) antigens are short intracellularly processed peptides presented on the cell surface, offering distinct advantages over antibody-based therapies that recognise secreted or cell surface proteins. Here, we describe two novel platforms designed to overcome the limitations of the natural T cell response to deliver high-affinity engineered TCRs to an identified and validated target antigen. The platforms can be distinguished based on a cellular versus soluble approach. SPEAR (Specific Peptide Enhanced Affinity Receptor) T cell therapies targeting MAGE-A10, MAGE-A4, AFP and NY-ESO are progressing through clinically studies in multiple solid and hematologic cancers. The lead soluble ImmTAC® (Immune mobilising monoclonal TCR against cancer) molecule, IMCgp100, has entered pivotal monotherapy trials for the treatment of patients with metastatic uveal melanoma.

Show speakers

11:50-12:10 Antisense oligonucleotide therapy for Huntington's disease - results from the first HTT lowering clinical trial

Professor Sarah J Tabrizi FMedSci, Director of UCL Huntington's disease centre, UCL Institute of Neurology

Abstract

Background: HD is an autosomal dominant neurodegenerative disease caused by CAG repeat expansion in the HTT gene resulting in polyglutamine expansion in the mutant huntingtin protein (mHTT) with a toxic gain-of-function disease mechanism. No disease-modifying treatments are currently available. In transgenic rodent models of HD, suppressing HTT production delays disease progression and reverses disease phenotype. A comprehensive drug discovery effort, including extensive preclinical testing, was undertaken to design a well-tolerated ASO with high specificity to human HTT mRNA that potently suppresses HTT production.

Design/Methods: In this first-in-human, multi-center, double-blind clinical trial (NCT02519036), 46 patients were randomized (3:1) to receive four doses of IONIS-HTTRx (RG6042) or placebo by monthly bolus intrathecal (IT) injection followed by a 4-month untreated period. Five ascending-dose cohorts were enrolled with independent Data Safety Monitoring Board review of safety, PK and target engagement prior to dose escalation.

Results: IONIS-HTTRx was well-tolerated at all doses tested.  Adverse events were mostly mild and unrelated to study drug. There were no adverse trends in laboratory parameters. No patients prematurely discontinued from treatment. ASO was measurable in CSF and plasma. Significant, dose-dependent reductions in CSF mHTT were observed.

Conclusions: ASO technology has the potential to provide disease-modifying benefits to patients with neurodegenerative diseases. In this Phase 1/2a trial in early stage HD patients, IONIS-HTTRx delivered via IT injection was well tolerated with no study drug-related adverse safety signals during the treatment or follow-up periods.  Significant dose-dependent reductions in CSF mHTT were observed, suggesting that IONIS-HTTRx is a promising therapeutic for the treatment of HD.

Study Supported By: Ionis Pharmaceuticals

Authors: Sarah J Tabrizi, Blair Leavitt, Bernhard Landwehrmeyer, Edward Wild, Carsten Saft, Roger Barker, David Craufurd, Josef Priller, Hugh Rickards, Anne Rosser, Holly Kordasiewicz, Christian Czech, Eric Swayze, Daniel A. Norris, Tiffany Baumann, Irene Gerlach, Scott Schobel, Anne Smith, Roger Lane, C. Frank Bennett - on behalf of the study teams

Show speakers

12:15-12:35 Bioelectronics

Dr Kristoffer Famm, President, Galvani Bioelectronics

Show speakers

12:40-13:30

Lunch

13:30-15:05

Delivery (part 1)

4 talks Show detail Hide detail

Chairs

Professor Molly Stevens FREng, Professor of Biomedical Materials & Regenerative Medicine/Research Director for Biomedical Material Science, Imperial College London

13:30-13:50 Chair's introduction

Professor Molly Stevens FREng, Professor of Biomedical Materials & Regenerative Medicine/Research Director for Biomedical Material Science, Imperial College London

Show speakers

13:50-14:10 Virus based gene delivery

Professor Richard Jude Samulski, Professor of Pharmacology, Gene Therapy Center, University of North Carolina School of Medicine

Show speakers

14:15-14:35 Delivery CRISPR nanoparticles

Professor Daniel G Anderson, Professor of Applied Biology, Associate Professor of Chemical Engineering, and member of the Koch Institute for Integrative Cancer Research, MIT

Show speakers

14:40-15:00 Generation and testing of clinical-grade engineered exosomes to facilitate therapeutic targeting of oncogenic KRAS in pancreatic cancer

Dr Raghu Kalluri, Professor and Chairman, Department of Cancer Biology and Director, Metastasis Research Center, University of Texas MD Anderson Cancer Center

Abstract

Exosomes are extracellular vesicles generated by all cells and are naturally present in the blood. Exosomes have a remarkable ability to efficiently transfer genetic material, including exogenously loaded siRNA, to cancer cells. The mutant form of the GTPase KRAS is a key driver of pancreatic cancer but remains a challenging therapeutic target. Here we show enhanced retention of exosomes, compared to liposomes, in the circulation of mice was likely due to CD47-mediated protection of exosomes from phagocytosis by monocytes and macrophages. Exosomes derived from normal fibroblast-like mesenchymal cells were engineered to carry short interfering RNA, or short hairpin RNA specific to oncogenic KrasG12D, a common mutation in pancreatic cancer. Compared to liposomes, the engineered exosomes (known as iExosomes) targeted oncogenic KRAS with an enhanced efficacy that was dependent on CD47 and was facilitated by macropinocytosis. Treatment with iExosomes suppressed cancer in multiple mouse models of pancreatic cancer and significantly increased overall survival. Our results demonstrated an approach for direct and specific targeting of oncogenic KRAS in tumors using iExosomes. In order to translate this discovery into the clinic, we developed a bioreactor-based, large-scale production of clinical-grade exosomes employing good manufacturing practice (GMP) standards. A standard operating procedure was established to generate engineered exosomes with the ability to target oncogenic Kras (iExosomes). The clinical-grade GMP iExosomes were tested in multiple in vitro and in vivo studies to confirm suppression of oncogenic Kras and an increase in the survival of several mouse models with pancreatic cancer. We performed studies to determine the shelf life, biodistribution, toxicology profile, and efficacy in combination with chemotherapy to inform future clinical testing of GMP iExosomes. Collectively, this report illustrates the process and feasibility of generating clinical-grade exosomes for various therapies of human diseases.

Show speakers

15:05-15:35

Tea

15:35-16:20

Delivery (part 2)

2 talks Show detail Hide detail

Chairs

Professor Molly Stevens FREng, Professor of Biomedical Materials & Regenerative Medicine/Research Director for Biomedical Material Science, Imperial College London

15:35-15:55 Shaken and stirred: Ultrasound-enhanced drug delivery

Professor Constantin Coussios, Professor of Biomedical Engineering (Drug Delivery), Head of the Biomedical Ultrasonics, Biotherapy & Biopharmaceuticals Laboratory, Oxford University

Abstract

The thermal and mechanical effects produced by ultrasound have a major role to play in enabling therapeutics to cross biological barriers, such as those presented by the highly irregular vasculature and elevated interstitial pressure in tumours, or the cellular membrane. We first present results from a first-in-man clinical trial (TarDox) of targeted drug delivery to liver tumours using thermosensitive liposomes in combination with mild hyperthermia delivered non-invasively using focused ultrasound. In a further development, a mechanical effect of ultrasound, known as acoustic cavitation, is exploited for convective transport of therapeutics. This approach necessitates lower-intensity ultrasound delivered from a portable device and does not require drug modification or encapsulation. In oncology, sub-micron cavitation-inducing particles co-administered with small-molecule drugs, therapeutic antibodies or viruses are shown to increase both the penetration and total dose delivered to tumours following systemic administration, significantly enhancing their therapeutic efficacy even at a reduced systemic dose.

Show speakers

16:00-16:20 Cancer evolution and immune escape: TRACERx

Professor Charles Swanton FMedSci, Translational Cancer Therapeutics Laboratory Group Leader, The Francis Crick Institute

Abstract

Increasing evidence supports complex subclonal relationships in solid tumours, manifested as intratumour heterogeneity. Parallel evolution of subclones, with distinct somatic events occurring in the same gene, signal transduction pathway or protein complex, suggests constraints to tumour evolution that might be therapeutically exploitable. Emerging data from TRACERx, a longitudinal lung cancer evolution study will be presented. Drivers of tumour heterogeneity change during the disease course and contribute to the temporally distinct origins of lung cancer driver events. APOBEC driven mutagenesis appears to be enriched in subclones in multiple tumour types. Oncogene, tumour suppressor gene and drug induced DNA replication stress are found to drive APOBEC mutagenesis. Evidence that intratumour heterogeneity and chromosomal instability is finely tuned will be presented, to create sufficient diversity for adaptation mitigating the risks of excessive genome instability resulting in cell autonomous lethality. On-going chromosomal instability, manifested as Mirrored Subclonal Allelic Imbalance (MSAI) is found to be a major driver of intratumour heterogeneity in non-small cell lung cancer, contributing to parallel evolution and selection. The finding of subclonal driver events, evidence of ongoing selection within subclones, combined with genome instability driving cell-to-cell variation is likely to limit the efficacy of targeted monotherapies, suggesting the need for new approaches to drug development and clinical trial design and integration of cancer immunotherapeutic approaches. The clonal neo-antigenic architecture may act as a tumour vulnerability, targeting multiple clonal neo-antigens present in each tumour to mitigate resistance and treatment failure. The role of cancer genome instability driving immune evasion and HLA/MHC loss and immune escape will be presented.

Show speakers

16:30-17:30

Panel session: Manufacturing challenges

1 talk Show detail Hide detail

Chairs

Dr Nicholas Medcalf, Senior Innovation Lead in Advanced Therapies, UK Research and Innovation, Innovate UK

Dr Annette Bak, Head of Advanced Drug Delivery, AstraZeneca (Sweden)
Keith Thompson, CEO, Cell and Gene Therapy Catapult
Dr Derek Adams, Chief Technology and Manufacturing Officer, Bluebird Bio
Professor Richard Jude Samulski, Professor of Pharmacology, Gene Therapy Center, University of North Carolina School of Medicine

Show speakers

17:30-18:30

Drinks reception

25 October

09:00-09:30

Registration

09:30-09:35

Opening remarks

1 talk Show detail Hide detail

Sir John Skehel FMedSci FRS, Vice-President and Biological Secretary, The Royal Society

Show speakers

09:35-11:10

Novel therapies: data, technology and regulation (part 1)

3 talks Show detail Hide detail

Chairs

Professor Dame Angela McLean DBE FRS, Professor of Mathematical Biology, University of Oxford and Co-Chair, Data Theme Community Group of Interest, Royal Society

09:40-10:05 The potential for genomics to transform drug discovery

Professor Peter Donnelly FMedSci FRS, CEO, Genomics PLC and Professor, Statistical Science, University of Oxford

Abstract

Currently 90% of drug candidates taken into clinical trials fail to be approved.  Drug targets are often motivated by studies in model systems, but the modulation of these targets often fails to be effective in humans, underlining out relative lack of understanding of human biology.  Analysis of human genetic variation and its phenotypic consequences offers the potential to study perturbations of human biology directly.  Combining large-scale genomic data sets now allows simultaneous analysis of thousands of different phenotypes so that for the first time it is possible to exploit what has been called Nature’s clinical trial so as to begin to reveal the human wiring diagram.  The resulting biological insights offer a powerful new approach to empower target discovery and other aspects of drug development.

Show speakers

10:10-10:35 Is Digital Health the snake oil of the 21st century?

Keith Errey, CEO, Isansys Lifecare Ltd

Abstract

At the June 2016 Annual Meeting of the American Medical Association, CEO James L Madara, M.D speaking of “Digital Health” observed “From ineffective electronic health records, to an explosion of direct-to-consumer digital health products, to apps of mixed quality – it's the digital snake oil of the early 21st century.” Without doubt “Digital Health” has been greatly hyped over the last few years and has come to mean different things to different people. However, by considering alternative definitions of digital health and understanding the origins of “digital snake oil” a new realisation of digital health is presented. Based on the concept of the “digitised patient” represented in the form of high resolution dynamic physiological images, this view points to new clinical pathways and more efficient ways of delivering care both in and out of hospital.

Show speakers

10:40-11:05 How can we harness the data revolution? The potential of AI

Professor Iain Buchan, Director of Healthcare Research, Microsoft Research

Show speakers

11:10-11:40

Coffee

11:40-13:00

Novel therapies: data, technology and regulation (part 2)

2 talks Show detail Hide detail

Chairs

Professor Dame Angela McLean DBE FRS, Professor of Mathematical Biology, University of Oxford and Co-Chair, Data Theme Community Group of Interest, Royal Society

11:40-12:05 Novel approaches to assessing the safety and efficacy of new medicines

Sir Michael Rawlins GBE Kt FMedSci, Chair, Medicines and Healthcare products Regulatory Agency

Abstract

Traditional approaches to investigating the safety and efficacy of new medicines are primarily based on randomised controlled trials. There is, however, increasing interest in newer techniques that include adaptive designs, basket trials, umbrella trials, step wedge trials, ring trials and - in some circumstances - Baskerville trials. The advantages and disadvantages of these approaches will be discussed.

Show speakers

12:10-13:00 Panel discussion

Professor Peter Donnelly FMedSci FRS, CEO, Genomics PLC and Professor, Statistical Science, University of Oxford
Keith Errey, CEO, Isansys Lifecare Ltd
Professor Iain Buchan, Director of Healthcare Research, Microsoft Research
Sir Michael Rawlins GBE Kt FMedSci, Chair, Medicines and Healthcare products Regulatory Agency
Professor Jonathan K.C. Knowles, Visiting Professor, Medical Sciences Division, University of Oxford

Abstract

This panel session, chaired by Professor Angela McLean FRS, will discuss the future for data, technology, and regulation.

Show speakers

13:00-14:00

Lunch

14:00-15:30

Session 2

3 talks Show detail Hide detail

Chairs

Sir John Skehel FMedSci FRS, Vice-President and Biological Secretary, The Royal Society

14:00-14:25 How can we value novel medicines? A health economic perspective

Professor Lou Garrison, Professor Emeritus in the Comparative Health Outcomes, Policy, and Economics Institute, University of Washington

Abstract

In February of this year, a Special Task Force (STF) of the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) published its report and recommendations on “A Health Economics Approach to US Value Assessment Frameworks.”  In assessing the potential value of novel medicines, the STF recommended that US public and private payers begin with a metric that compares incremental costs with incremental health benefits—with the latter measured in terms of quality-adjusted life years (QALYs) gained:  this is used in numerous country health systems and particularly by NICE in the UK.  Taking the cost-per-QALY metric as a starting point, the STF recommended to expand the concept of value and augment its measurement to include novel elements of value, such as insurance value, the value of hope, real option value, and scientific spillovers.  As a co-chair of the STF, Professor Garrison will provide an overview of the report, focusing on the implications for defining, measuring, and assessing the value of novel medicines globally.

Show speakers

14:30-14:55 Fairness and access to novel therapies

Dr Jacoline Bouvy, Senior Scientific Adviser, National Institute for Health and Care Excellence

Show speakers

15:00-15:25 The boundary between cognitive enhancement and treatment

Professor Barbara Sahakian FMedSci, Professor of Clinical Neuropsychology, University of Cambridge

Abstract

While many people monitor their physical health using mobile devices and wearable technology to preserve their physical health, they rarely consider improving and monitoring their brain health. If we are going to have good mental capital and wellbeing throughout our lives, it is imperative that we consider mental health as being every bit as important as physical health and move to game-changing initiatives which include early detection and early effective treatment of neuropsychiatric disorders. Cognitive enhancing drugs, such as methylphenidate and modafinil, which were developed as treatments are increasingly being used by healthy people. Cognitive abilities are becoming progressively more important for work performance and successful competition in a global environment. However, work-stress, long hours, lack of sleep, shift work, and jet lag affect cognitive functions. Therefore, increasingly, healthy people are reported to use cognitive-enhancing drugs, brain-training apps and non-invasive brain stimulation to maintain or improve work performance.

Show speakers

15:30-16:00

Closing keynote: How does the healthcare system need to evolve to take advantage of new medicines?

1 talk Show detail Hide detail

Professor Dame Julie Moore, Professor of Health Systems, Warwick University

Show speakers

16:00-16:05

Closing remarks

1 talk Show detail Hide detail

Sir John Skehel FMedSci FRS, Vice-President and Biological Secretary, The Royal Society

Show speakers

16:05-17:00

Tea and networking

Related events

Delivering novel therapies in the 21st century

A joint Royal Society Transforming our Future conferences in the life sciences, supported by AstraZeneca, with the Academy of Medical Sciences FORUM.

The Royal Society, London 6-9 Carlton House Terrace London SW1Y 5AG UK