APPENDIX 4: SEMINAR HELD AT KING'S
COLLEGE LONDON, GUY'S CAMPUS |
23 October 2012
Members of the Committee present were Lord Broers,
Lord Cunningham of Felling, Lord Dixon-Smith, Baroness Hilton
of Eggardon, Lord Krebs (Chairman), Lord O'Neill of Clackmannan,
Lord Patel, Earl of Selborne, Baroness Sharp of Guildford, Lord
Wade of Chorlton, Lord Willis of Knaresborough and Lord Winston.
A seminar was held at the Guy's Campus of King's
College London to provide the Committee with an opportunity to
discuss the Regenerative Medicine inquiry with academic experts,
industry representatives, funding organisations, and representatives
of the Department of Health, the Department for Business, Innovation
and Skills (BIS), and the Technology Strategy Board (TSB).
Professor Fiona Watt (Specialist Adviser to
the Committee), Chris Atkinson (Clerk), Cerise Burnett-Stuart
(Committee Assistant), Rachel Maze (Policy Analyst), and James
Tobin (Policy Analyst).
Presentation speakers: Dr Rob Buckle (MRC);
Dr Rupert Lewis and Dr David Griffiths-Johnson (Department
for Business, Innovation and Skills); Dr Mark Bale (Department
of Health); Dr Zahid Latif (Technology Strategy Board), Michael
Roundtable participants: Professor Charles ffrench-Constant
(University of Edinburgh); Professor David Williams (EPSRC
Centre for Innovative Manufacturing); Robin Lovell-Badge (National
Institute for Medical Research, London); Professor Amanda
Fisher (Imperial College London); Anthony Hollander (University
of Bristol); Professor Chris Mason (UCL); Steve Bates (BIA);
Becky Purvis (AMRC); Priya Umachandran (Wellcome Trust); Alex
Denoon, (Lawford, Davies and Denoon); and Tim Allsop (Pfizer).
Overview of UK Research Excellence in Regenerative
MedicineRob Buckle, Medical Research Council
Rob Buckle opened by providing a definition of Regenerative
Medicine treatments, including the approaches and timescale for
delivery. Concentrating on cell therapy, a number of approaches
were identified. The first, autologous cell therapies, employ
cell matter taken from an individual to treat that individual
(so called "self to self" treatments). There are currently
numerous clinical trials under way in this area, including for
the treatment of bone/joint, cardiovascular, eye, liver and neurological
disorders. In most cases, stem cells are removed from the patient,
often minimally processed, and then reintroduced as part of treatment
in the same area or bodily system. Results in heterologous systemstaking
stem cells from one area such as the bone marrow, and using it
to repair neurological issues for examplehave so far proven
In contrast, allogeneic cell therapies where the
donor and recipient are different (so called "one-to-many"
treatments) have potentially broader potential. However, their
use is dependent upon the use of immune suppression or donor matching
(as in bone-marrow transplants). There are currently clinical
trials underway in this area on skin conditions, stroke, Parkinson's
Disease, corneal repair, and Advanced Macular Degeneration (AMD).
There is also notable future potential in induced Pluripotent
Stem Cell (iPS)-based, and directly-differentiated cell-based,
treatments. Finally, a range of activity was being undertaken
on endogenous repair, which involves the use of growth factors
and small molecules to stimulate repair processes. The MRC, for
example, was funding such research in the areas of heart repair
and multiple sclerosis.
An examination of the therapeutic pipeline across
these areas revealed that there were currently 36 studies at the
preclinical-early stage of development (33 academic-led, and three
commercially-led.) Six studies were at the preclinical-late stage
(five academic-led, and one commercial). Finally, 19 studies were
at clinical phases I/II (14 academic-led, and five commercial).
When viewed by disease area, the largest number of studiesand,
indeed, in many cases the most developedwere muscloskeletal
and eye-related conditions.
With regard to the strength of the science base,
of the top five research nations (US, China, UK, Japan and Germany)
UK researchers generated more articles per researcher, more citations
per researcher, and more usage per article authored.
The UK's share of the top one percent of most highly cited papers
was 13.8% in 2010, second only to the USA. The UK citation impact
in regenerative medicine is also higher than for the UK science
base more generally.
The UK is also a leading collaborator for others, including the
USA and Germany.
The main funders of research in regenerative medicine
are the research councils, the Department of Health (particularly
through the NIHR), the TSB and research charities. Support is
largely provided by competitive, response-mode funding. However,
there are also areas where the direct stimulation of activity
is needed, and therefore targeted schemes (including translational
funding) are also provided. Funding is also directed at research
infrastructures, international partnerships, and capacity-building,
which receives approximately 10% of MRC funding in this area.
Research activity overall is co-ordinated through both the UK
Regenerative Medicine Forum and the International Stem Cell Forum.
In 2008, research council funding was approximately
£43.5 million which represented around 66% of the total research
spend on regenerative medicine. The MRC was the largest contributor
of this funding at £37.7 million (52% of the research council
total). The BBSRC contributed £12.8 million (18%), the EPSRC
£11.3 million (16%) and the TSB £8.8 million. The NIHR
and ESRC contributed approximately one percent of research funding
respectively. Since 2008, the MRC's financial contribution to
research in regenerative medicine has approximately doubled (£72.6
million per annum), with funding for 353 projects. When analysed
by "technology readiness level"a spectrum which
begins at underpinning research through to user adoptionthe
majority of research council spending on regenerative medicine
remains at the earlier "underpinning" or "preclinical/breadboard"
stages. Relatively small numbers of funded projects are at "early
clinical-prototype" or "user adoption" phases.
That reflects current understanding of the field, and how difficult
it is to translate projects into later stages of development.
In terms of current UK strategic investments, there
are a number of Centres of Excellence in regenerative medicine
research in the UK which the MRC and other research councils help
to fund. The MRC
is also engaged in strategic funding partnerships designed to
accelerate therapeutic development in this area, including with
the British Heart Foundation, and with the California Institute
of Regenerative Medicine. In November 2012, a joint £12 million
initiative between the Wellcome Trust and the MRC will be announced
on Human Induced Pluripotent Stem Cells. There is also the UK
Stem Cell Bank, which exists to provide human embryonic stem cell
lines in an ethically sourced and quality controlled manner, and
industry relationships in the form of Stem Cells for Safer Medicines
(SC4SM) public private partnership involving pharmaceutical companies
using this technology for drug development. Broader support for
the area is also provided through a number of NIHR Biomedical
Research Centres, and the Blood Transfusion Services which offer
distribution and manufacturing capability.
There remain a number of challenges which need to
be addressed in the field, however, as identified in the recent
UK strategic review. There is a need for better interdisciplinary
working between different groups such as biologists, bioengineers
and material scientists, and different regenerative medicine centres.
There are also issues with regard to controlling cell phenotype
and function, in terms of how they are differentiated to form
different tissues, while animal models used to test functionality
and safety are also not particularly predictive in this area.
Particular challenges also exist with regard to potency, or which
cells, how many and what mode of action will be needed for a potential
treatment, and immunomodulation, so that risks around transplant
rejection can be prevented. New tools and technologies will be
required for the development of regenerative medicine treatments.
How to meet demand for manufacturing facilities and GMP production
will also be an important issue. There is also regulatory uncertainty
in this area, including how phase I trials should be designed
to meet requirements and the appropriate level of monitoring and
follow-up. New business models will also be needed for commercial
Looking to the broader strategic approach to these
issues and challenges, A Strategy for UK Regenerative Medicine
was published in March 2012. The Strategy aimed to detail how
this area of fast-moving discovery science could be best exploited,
and to drive translational approaches and build on the UK's strong
science base. To this end, the Strategy documents an injection
of £95 million into new strategic funding over the next five
years which will be channelled into specific initiatives such
as the UK Regenerative Medicine Platform, the TSB Cell Therapy
Catapult Centre and new MRC and Wellcome Trust partnerships.
In response to a question on the comparative spending
ratios between the UK and the US on early science through to translational/commercial
stages, Dr Buckle said it was difficult to get an accurate
picture across American providers. However, he believed that they
would be broadly similar. When questioned on whether the relatively
low levels of translational funding (in comparison with earlier
stage research funding) demonstrated in both countries was the
result of a lack of resource or a lack of projects to fund, Dr Buckle
said that at the current time there was not a (comparatively)
large demand for translational funding. In response to a further
question on the funding of translational research, Dr Buckle
added that the MRC have a specific budget for translational science
in regenerative medicine, which has been set at a level capable
of satisfying the level of high quality demand, which had remained
steady over the last few years. The deployment of that budget
is managed through a funding committee formed four years ago,
and which has the capacity for industry partnership. With the
TSB, the MRC has also launched the Biomedical Catalyst Fund, which
aims to provide funding to bridge the "valley of death"
where proof of concept is needed before large scale investment
can be attracted, and which can absorb the demands of clinical
studies in this area as they emerge. Dr Buckle suggested
that the result of these various initiatives was a harmonised
funding landscape in this area.
In response to a question about the role of charitable
organisations, Dr Buckle said that they were very much acting
as partners with the research councils in translational research.
He added that industry interest in this area is largely represented
by small and medium sized enterprises rather than "big pharma",
with companies involved in both the development of treatments,
and the development of tools and technologies. The MRC is explicitly
trying to encourage industry partnership with targeted funding.
First RoundtableWhat potential does regenerative
medicine hold to treat disease in the next 5-10 years?
The discussion began with a short introduction from
each external participant providing a brief overview of particular
points of interest. The potential impact of small molecule therapies,
not least because it is a model that pharmaceutical companies
are already very comfortable with, was highlighted. The benefits
provided by cell reprogrammingthe technology for turning
different types of somatic cells back into stem cellswere
It was argued that any supposition that human iPS
or human embryonic stem cells should be used for cell replacement
was argued to be potentially naive. One possible alternative focus
for research attention might be "directed reprogramming",
whereby rather than turning a differentiated cell right back into
an embryonic stem cell it is turned into a required material that
is perhaps mid-way (or at some other point) in the differentiation
Autologous therapies were already being deployed.
Whilst such therapies were not perfect, they illustrated that
it was possible to remove, manipulate, and then reinsert cells,
and provide some demonstrable therapeutic effect. It was felt
that there was considerable tractability in this area, which would
only increase over the next few years as these therapies continue
to develop and improve. Tissue engineeringusing cells to
create tissues outside the body and then implant themwas
also identified as a key area for potential. However, considerably
more development in the fundamental science would be required,
and developing a suitable business model could be particularly
Niche derived factorsfactors made by the local
environment where the stem cells exist, and which control the
activity of those stem cellsand their small molecule agonists
and antagonists could be very important over the next 5-10 years.
The benefits derived in the next 5-10 years were
very much going to be governed by what is currently in clinical
trials. According to the clinicaltrials.gov database, (excluding
duplicates) there were around 1, 900 trials ongoing. The overwhelming
majority were clinician-sponsored, a mode which, it was suggested,
historically has not had good results, principally as a result
of issues such as lack of later-stage funding. Public companies,
rather than clinicians, tend to be well set up for such later
stage trials. There were estimated to be about 45 public companies
engaged in around 60 active trials, roughly split between 40%
at phase I, 40% at phase II, and 20% in phase III. It was argued
that there would only be a very small number of therapies coming
through in the next 5-10 years, although there was potential for
treatments for very small patient groups to progress faster.
Manufacturing capability was identified as an issue.
A large scale therapy which would be distributed widely to a large
number of patients was unlikely in the next 10 years, as the processes
necessary for the scale-up of such treatments did not currently
exist. More positively, the UK does possess considerable strength
in the area of gene therapy, and the increasing convergence of
gene and cell therapies in particular presents a considerable
area of future potential.
It was suggested that the level of translational
activity in the UK was low in comparison to other countries with
more permissive regulatory regimes, which was of particular concern.
The UK Stem Cell Bank was identified as a key resource,
particularly given the presence there of clinical grade stem cell
lines for research. It was suggested that commercial actors seldom
dealt with the UK Stem Cell Bank, preferring instead to deal directly
with those who had deposited lines there. Furthermore, as there
is currently no mechanism for the long-term exclusive use of a
cell line by a company developing a cell therapy, and no ability
for a company to control how deposited cells are used, there exists
a barrier to commercial investment.
Second PresentationMark Bale, Department of
Health; Rupert Lewis and David Griffiths-Johnson, Department of
Business, Innovation and Skills: the Policy Environment
Mark Bale outlined that the approach of Government
since 2000 had been to take a neutral perspective with regard
to the source of stem cells, but to be as supportive and enabling
as possible with regard to regulation pertaining to derivation,
clinical trials and therapeutic application. That work takes place
within the wider constraints imposed at a European level.
Speaking directly to the issue of regulation, Dr Bale
said that the Government are conscious of the perception that
there is a multiplicity of regulators. However, there were very
good reasons for the established system. Responding to a question
on why the Government had chosen not to locate the regulation
of all research functions within the Human Research Authority
(HRA), as it had originally intended, Dr Bale said that the
Government had undertaken consultation on this issue. He added
that in his view, stem cells and other regenerative medicine treatments
constituted a very small proportion of the responsibilities of
the HFEA and HFAit was not their core business. Therefore,
to remove these functions from those bodies and to place them
in the HRA, for example, might in fact increase the resource necessary
to deal with them. There might be a need to take on new staff
for example, where this expertise already exists in the existing
Dr Bale continued by outlining which regenerative
medicine treatments and processes, and at what stage, were currently
within the remit of which regulator. Dr Bale acknowledged
that the regulatory structure may appear complicated, but said
that there had been considerable efforts to raise awareness and
increase understanding through initiatives such as the Stem Cell
Toolkit, alongside workshops and further guidance materials.
Rupert Lewis outlined the recent steps that BIS had
taken to support the development of regenerative medicine, including
the creation of the Cell Therapy Catapult. He also pointed to
the work undertaken by the British Standards Institute, which
had published a number of standards and guides on issue areas
such as the use of human cells for clinical application. Measures
were also available to improve access to finance, such as the
use of tax credits and the TSB's Regenerative Medicine Programme.
Dr Lewis added that there were particular programmes which
aimed to address the problem of the "valley of death",
including Enterprise Capital Funds which seek to leverage private
sector investment and demonstrate potential to venture capital.
The Enterprise Investment Scheme also exists to provide tax relief
Dr Lewis then highlighted the potential implications
of the recent European Court of Justice ruling in Brüstle
v Greenpeace. Dr Lewis said that the Government was concerned
about the potential impact of this decision for research using
human embryonic stem cells, and had made representations to the
European Commission on this issue. The Intellectual Property Office
had also issued a revised practice note in light of this ruling.
Dr Lewis said that reaction to the decision across the research
community had been mixed. He noted that, whilst there was concern
if an invention could not be patented, the complexity and expertise
needed to develop a regenerative medicine treatment could still
provide commercial protection and exclusivity in the absence of
Dr Lewis noted the wide recognition of the potential
of regenerative medicine as a growth opportunity internationally.
A number of countries were currently investing in regenerative
medicine, particularly in the area of translational research.
While some countries such as Japan had chosen to focus on particular
areas (iPS cells), the UK had retained a broad approach, preferring
to be led by the science. The UK has particular areas of strength
in research impact and collaboration, and on the number of companies
operating in the area.
Zahid Latif then outlined the role of the Technology
Strategy Board in supporting regenerative medicine. As a funder,
a key challenge for the TSB was to go to business and find out
what was necessary to secure investment into regenerative medicine.
Clinical studies proving efficacy was identified as a key requirement,
as was the need to invest in the underpinning tools and technologies
necessary to develop regenerative medicine, as well as the treatments
themselves. Dr Latif said the final area that the TSB needed
to examine and "unpack" was value systems and impact
modellingi.e. what is regenerative medicine, is it a product
or a service? How should the reimbursement challenges be addressed
as a result? The TSB ran a series of competitions for funding
from 2009-11 to focus on these areas.
Dr Latif continued by highlighting that the
business and operating models present in the regenerative medicine
sector differed significantly from traditional pharmaceutical
models. As a result, funding programmes had to be designed in
a particularly bespoke way in order to address key concerns, including,
for example, access to finance. Dr Latif identified a number
of success stories, where companies had benefitted from such an
approach. Further work, including the creation of the Biomedical
Research Catalyst, is currently being undertaken in order to overcome
issues such as the "valley of death". Finally, Dr Latif
highlighted the work of the Call Therapy Catapult, which provides
access to knowledge and expertise as well as access to the finance
which companies need.
Members of the Committee raised the question of whether
the current regulatory environment facilitated the development
of regenerative medicine, or presented a potential barrier to
that development. A discussion about access to finance, an unclear
and complex regulatory system, and uncertainties about reimbursement
followed. It was pointed out that the regulatory rules are the
same across Europe. What may be different is the UK is the presence
of multiple regulators, and the need to work with different regulators
depending in the stage and type of treatment under development.
The outreach work that was being done by the regulators to industry
in order to overcome any uncertainties or apprehension was outlined.
However, it was pointed out that whilst the regulatory environment
in the UK was well-regarded, the multiplicity of regulators in
the UK created an environment where inconsistent and occasionally
contradictory advice was given, and there was no mechanism to
resolve such inconsistency.
Third PresentationMichael Hunt, ReNeuron
Michael Hunt, Chief Executive of ReNeuron opened
his presentation by providing a brief background about the work
of ReNeuron, and their work as a small company taking a regenerative
medicine treatment through basic research into clinical trials.
Mr Hunt then outlined some of the challenges the company
faced going forward, including securing finance to develop further
avenues of treatment so far unexplored due to those financial
constraints, the specific concerns of ensuring purity and potency
of cell lines, and broader issues of developing an effective business
model and negotiating the regulatory landscape. Speaking in particular
to those regulatory burdens, Mr Hunt said that in his experience
the processes involved had often proved to be complex, inefficient,
and subject to considerable overlap between regulatory agencies.
By way of illustration, he said that ReNeuron had been subject
to eight different inspections, by three regulatory bodies, in
the preceding twelve months. Mr Hunt said if reviews could
be implemented to make the regulatory process more timely and
proportionate, the UK would be more attractive to those seeking
to develop regenerative treatments such as themselves.
Turning to the issue of funding, Mr Hunt said
that private investment into UK companies was currently small
in comparison to other areas, notably the United States. He said
that, despite the progress being made in the field both in the
basic science and translationally, investors were still demonstrating
reluctance to commit funding. Similarly, with regard to publically
provided funding, there were some funds available in the UK for
translational research, but again this was a fraction of what
small companies in the US were able to access.
Looking at positives in the UK landscape, Mr Hunt
said that in general the UK Government had proven to be supportive
of regenerative medicine, and there were increasing levels of
research council funding available. He also particularly welcomed
the establishment of the Cell Therapy Catapult. Finally, Mr Hunt
highlighted the benefits presented by the NIHR and the NHS, and
the presence of trade bodies particularly focused on regenerative
Second RoundtableWhere could the Committee's
inquiry best add value?
Moving around the table, suggestions were heard regarding
the areas where the Committee might be able to add the most value
and the key questions that it might seek to address in its inquiry.
It was argued that one of those areas should be the
regulatory framework and the creation of an active mechanism to
pull products through from basic research, through clinical trials,
Another view was that it was best to focus on what
was achievable in regenerative medicine, in comparison to what
was considered aspirational, and how one engaged the full community
In addition to examining regulatory issues, guidance
provided to companies working in the field should be considered.
It was suggested that, given the timing of the inquiry, the ongoing
discussions on the EU Horizon 2020 programme would be a particularly
pertinent issue to consider. The development of effective business
models was a key issue, requiring close interaction with regulators,
and also dialogue across the regenerative medicine community.
Another area where the Committee might add significant
value, where there is currently uncertainty, was the adoption
of treatments and technologies in the NHS. It would be important
to address the issue of stem cell tourism, not least with regard
to unscrupulous providers preying on those desperate for treatment.
It was considered vital that the Committee examine adoption and
reimbursement, not least in balancing up-front costs with potential
long-term savings, with a view to convincing Government to provide
more support and assistance in these areas. It was also important
to concentrate on the finance and funding gap which currently
Attention should be given to the small and niche
products being developed as well as the so-called "blockbuster
treatments". Support for the key role of large and small
charities in addressing issues such as access to finance and adoption
of regenerative treatments by healthcare providers including the
NHS could be considered. It was argued that advice and support
services need to be significantly improved. The possibility of
early-phase reimbursement should be explored.
It was suggested that translation and commercialisation
were often confused when in reality they were two very different
parts of the development pathway. The UK was very good at basic
research, getting better at translation, but extremely poor at
commercialisation. In order to develop the UK's regenerative medicine
sector, this last issue in particular needed significant focus.
Access to finance, and a need for Government support to encourage
investment was also highlighted. Finally, the significant challenges
in terms of trial design and implementation, and the need for
a skilled workforce to meet these challenges, merited attention.
336 According to the findings of BIS: International
Comparative Performance of the UK Research Base, 2011. Back
Op. cit. Taking stock. Back
They include the Stem Cell Institute in Cambridge, with the MRC
in partnership with the Welcome Trust; the MRC Centre for Regenerative
Medicine in Edinburgh; the EPSRC, BBSRC, TSB Medical Technologies
Centre in Leeds; and the ESPRC Centre for Innovative Manufacturing
in Loughborough. Back
The principle route for this funding would be from the MRC to
a university, who would then subcontract to a company. Back