Chiroscience Group - Re Research & Dev. Update
29 Settembre 1998 - 9:34AM
UK Regulatory
RNS No 5924x
CHIROSCIENCE GROUP PLC
29th September 1998
CHIROSCIENCE GROUP PLC
RESEARCH AND DEVELOPMENT UPDATE
Chiroscience Group plc, the emerging pharmaceutical company, is holding a
Research and Development Update, providing information to analysts and
investors about its gene to drug strategy - highlighting the status of its
early stage and later stage drug development programmes and reviewing the
progress made with its genetic analysis technologies.
Highlights:
- Inflammation, immunology and bone disease confirmed as the focus for
future discovery programmes
- Gene-based discovery strategy is creating value through the
identification of radically new targets for unmet medical need:
- Novel immune gene discovered, which is critically responsible for immune
response, and provides a target for new drugs treating autoimmune
diseases (see separate announcement)
- Unique bone strengthening gene located in human population, offering
potential for new drugs to reverse the effects of bone loss in
osteoporosis
- New systems for identifying genetic mutations offer new business
opportunities in Rapigene subsidiary, as evidenced in agreement with
Gemini Research (see separate announcement). Genomics collaboration with
Bristol-Myers Squibb is identifying MMP profile required for specific
tumour types
- Drug discovery programmes with corporate partners progressing well,
in and near clinical trials:
- D2163 MMP inhibitor for cancer demonstrates excellent blood levels in
single dose Phase I studies; multi-dose studies underway. Phase I/II
patient studies conducted by Bristol-Myers Squibb to commence early in
1999
- D1927 MMP inhibitor to enter Phase I clinical studies in October 1998
- PDE IV collaboration with Schering-Plough has discovered inhibitors with
superior competitive profiles for treatment of asthma, bronchitis and
emphysema
- Needleless and pain-free injection of local anaesthetics being
developed in conjunction with Powderject, in children and adults,
following excellent results from 5 Phase I/II studies (see separate
announcement). The first clinical trials in children started in September
1998
Chiroscience also provided an update on its additional clinical
programmes. d-threo-methlyphenidate continues to be progressed by Medeva,
and proceeds on track for its first regulatory submission at the end of
1999. The isomers of verapamil have demonstrated advantages in clinical
studies for the treatment of arrhythmia and angina. However, Knoll's
development focus no longer includes these cardivascular indications and
this collaboration will now be terminated, with Chiroscience retaining all
development rights. Discussions are ongoing with new partners,
particularly for products targeted at treating angina.
Dr Robert Jackson, Executive Director of Research and Development for
Chiroscience, said:
"The information we are presenting today demonstrates that we are a gene-
to-drug company. We have demonstrated our strength in four key areas:
gene discovery; drug discovery; drug development; and the strengths we can
use in future in-licensing opportunities. These programmes will all be
major contributors to Chiroscience's profit stream over the coming years.
In addition, we have created very valuable new systems for genetic
analysis and expect exciting news over the coming months in all our
programmes."
For further information contact:
Dr John Padfield, Chief Executive Giles Sanderson/Victoria
Dr Robert Jackson, Executive Springett
Director R&D Financial Dynamics
Rebecca Iveson, Investor and Media Tel: +44 (0)171 831 3113
Relations
Tel: +44 (0)1223 420430
Http://www.chiroscience.com
Notes For Editors:
Chiroscience Group plc
Chiroscience Group plc is an emerging pharmaceutical company which uses
its diverse technology platform to discover, develop and bring to market
novel medicines for improved healthcare. It has three businesses:
Chiroscience R&D, Rapigene and ChiroTech.
Chiroscience R&D's focus is on innovative small molecule drugs and related
diagnostics in the therapeutic areas of inflammatory disease, pain,
osteoporosis, cancer and autoimmune diseases. Its technology platform
allows the conception and development of receptor-based and enzyme-
inhibiting small molecule drugs with high selectivity of action. Rapigene
is involved in the creation of genomic technologies and services, which it
provides to Chiroscience R&D and partner companies' drug discovery
programmes. ChiroTech provides chiral technology services to
pharmaceutical and related industries, including Chiroscience R&D.
Chiroscience Group plc is listed on the London Stock Exchange and is based
in Cambridge and Stevenage, UK, and Seattle, Washington, USA
Research and Development Update
At Research and Development Updates for financial audiences held in London
on September 29th 1998, and to be held in New York on October 9th 1998,
Chiroscience Group plc discussed the progress in the principal drug
discovery programmes within Chiroscience R&D, its drug discovery business,
and the genetic analysis technologies which form the basis of its
subsidiary Rapigene Inc.
Introduction
Chiroscience Group plc has now established a fully integrated drug
discovery business. Of its earlier, single-isomer developments,
Chirocaine is in the last stages of product registration, and the filing
for registration of d-threo-methylphenidate by development partner Medeva
plc is scheduled for the end of 1999. The studies on the isomers of
verapamil have demonstrated clinical advantages in angina and arrhythmia;
however, Knoll have decided not to proceed with commercialisation and new
partnerships are under discussion, as Chiroscience has retained the
rights.
This Research and Development update gives further detail on the Group's
genetic analysis technologies and applications, examples of significant
progress in two gene-based approaches to disease treatment and its
development of novel selective drugs for disease treatment.
The drug discovery activities are focused on inflammatory and
immunological diseases (such as asthma, psoriasis and inflammatory bowel
disease) and bone and joint diseases (osteoporosis and arthritis), with a
secondary focus on cancer. All these diseases affect large numbers of
patients and there are no effective disease-modifying treatments available
at present. Furthermore, demographic trends worldwide are such that all
these diseases will continue to represent a very considerable economic
burden upon healthcare providers as the population ages and as patients
demand improved quality of life.
The Group will also consider other areas where its resources and skills
can be effectively applied. An example of this is the development of the
local anaesthetic lignocaine, in the Powderject needleless delivery
system, described later in this document.
The Group is using a range of new technologies and techniques, including
genetic analysis tools, to make the drug research and development process
more effective, reducing the cost and time to market of new drugs, as well
as improving the outcome. Chiroscience is determined to remain
competitive and at the forefront of drug discovery.
GENETIC ANALYSIS
Genetic analysis is now central to any company involved in drug discovery.
Rapigene's genetic analysis technologies represent leading approaches to
the study of genetically-based disease through the use of proprietary
chromatographic and mass spectroscopic systems created in the Company.
With a focus on the discovery and detection of Single Nucleotide
Polymorphisms (SNPs) - the single mutations often associated with disease
- these technologies could be used by a variety of customers to define and
study the genotypes of affected patients and hence to identify better
those patients who should be entered in clinical trials and treated in
clinical practice. Studies that use SNPs to understand how an individual
responds to a drug is part of a new area of research known as
pharmacogenomics.
There is an increasing demand for rapid, accurate identification of
genetic polymorphisms within the pharmaceutical, agricultural and
forensics industries. The technical challenges of SNP discovery
presented by this demand are formidable and Rapigene is establishing a
leading position in this area. Rapigene's SNP detection technologies are
based upon DNA hybridization reagents and cleavable mass spectrometry
tags, which are both proprietary and for which patent applications have
been filed.
Using these technologies, Rapigene can incorporate into a robust assay
virtually any SNP that has been associated with almost any condition.
Rapigene plans to market its SNP detection capabilities to pharmaceutical
companies which would use SNP genotyping in their drug development
programmes.
Once discovered, an SNP can be associated with different diseases through
conducting population studies. This will allow patients to be treated
with more specific drugs, as tests will show patients' likely response to
different drug therapies. Further monitoring will reveal the patient
response to the selected therapy, raising overall life expectancy and
quality of life, while tracking for the emergence of any new disease.
NOVEL IMMUNE SYSTEM GENE
Chiroscience R&D's discovery programmes make integrated use of both human
and mouse genetics. The use of mouse genetics permits the analysis of
disease states that would be difficult or impossible to study using human
populations. One such programme examined a strain of mice which have a
progressive, lethal autoimmune disease. The gene responsible for this
disease in mice was cloned in 1998 within the Company and subsequent work
has allowed us to identify the corresponding human gene.
This gene (on which patents have been filed) is novel and its protein
product is responsible solely for the control of immune responses.
Alterations in the gene's function lead to severe autoimmunity and
premature death and as such, the activity of the gene product is required
for the normal function of the immune system. Diseases where this gene
may have an important role include cancer and autoimmune diseases, such as
asthma, psoriasis and inflammatory bowel disease. This discovery uncovers
a previously unknown biological pathway for understanding and modulating
the immune response. Chiroscience is studying the function of this gene,
which will lead to new drug discovery targets and to unique opportunities
for the augmentation or inhibition of immune responses.
OSTEOPOROSIS: GENE-BASED APPROACH TO DISEASE TREATMENT
Osteoporosis is a major disease in the over 60s. It is most common in
women, but occurs increasingly in men. The progressive loss of bone
density leads to a high risk of fractures of the hip, wrist and spine. In
addition, individuals lose the ability to care for themselves, become
increasingly immobile and many die as a result. The annual incidence of
osteoporotic fractures is estimated to be 1 million within the US alone.
This is twice that of heart attack and more than four times that of stroke
or breast cancer. Current economic costs of treating osteoporosis is in
the region of $10 billion and is rising significantly.
No therapy exists which will significantly increase bone density.
Chiroscience R&D is working with a unique population which includes
individuals with extremely strong bone. Bone density increases throughout
their life, i.e. they have a genetic disorder whose effects are the
opposite of osteoporosis.
During the past year, the company has mapped the gene which causes this
disorder to the chromosome on which it is located, built a map of this
area, and identified all the genes within this region. The current work
will relate these findings to the clinical history of about 100 patients
and their family members, and thereby single out the mutant gene. When
the identity of the gene is discovered, its function will be validated and
a small molecule drug developed to mimic the action of the mutation - to
lay down more dense bone. This will provide a totally novel treatment for
osteoporosis, resulting from using a human genetic mutation as a surrogate
for drug action.
MATRIX METALLOPROTEINASE INHIBITORS (MMPIs)
MMPs are a family of enzymes which break down tissue components in the
body for the purposes of growth and repair. Research has shown that the
uncontrolled over-production of MMPs is involved in the pathology of many
diseases, including cancer and inflammatory conditions such as arthritis
and inflammatory bowel disease (IBD). Any MMP inhibitor used to treat a
disease must have a carefully-defined selectivity in order to produce the
required efficacy while not inhibiting other metalloproteinase enzymes
which may cause side effects.
Cancer
Under a development and marketing agreement signed in February 1998,
Bristol- Myers Squibb (BMS) and Chiroscience are progressing the clinical
development of Chiroscience's drug, D2163, in repeat dose Phase I studies,
with Phase I/II trials in cancer patients planned for the first quarter of
1999.
D2163 is an inhibitor of a broad range of MMPs which are known to be
associated with the growth and spread of tumours, but does not inhibit
metalloproteinase mediated shedding events, which may be associated with
the side effects which have become associated with first generation
inhibitors. Indeed, this new generation compound has not exhibited any
deleterious effects on tendons or joints in animal studies. The compound
has, however, demonstrated anti-angiogenic activity - the suppression of
growth in blood supply to tumours - which is one of the most important
activities attributed to MMPIs in cancer.
D2163 has been dosed in volunteers from 25mg to 900mg. Data from this
Phase I study indicates that D2163 achieves good plasma levels and is well
tolerated. The long half life of D2163 indicates that the compound
continues to demonstrate good potential as a therapeutic agent.
The clinical programme is backed by an active research collaboration with
BMS. Different MMPs may be implicated in different types of cancer (for
example there is a variation in the MMPs expressed in breast, prostate,
and lung cancer), and Rapigene's technologies are being used to define the
optimal selectivity required for specific tumours, and to discover new
members of the MMP gene family. Chiroscience's scientists are thus able
to design the next generation compounds targeted towards specific tumour
types and the other disease states (for instance, inflammation) in which
specific MMPs are found to play an important role.
Chiroscience will enter D1927, the additional oncology candidate licensed
to BMS, into Phase I clinical trials in October 1998.
Inflammation
Chiroscience believes that MMPIs will be applicable to other clinical
endpoints, such as rheumatoid arthritis and inflammatory bowel disease.
For example, D1927 and compounds from a newer series of inhibitors have
demonstrated activity in models of inflammation. Several of
Chiroscience's more recent compounds have a significantly improved
pharmacokinetic profile over Ro32-3555, Roche's MMPI compound in Phase
II/III trials, and these compounds demonstrate good oral activity in
experimental models of inflammation. Work is underway in collaboration
several international groups aimed at understanding the application of
MMPIs in inflammatory bowel disease and osteoporosis.
PHOSPHODIESTERASE IV (PDE IV)
Chiroscience continues its collaboration with Schering-Plough on the
discovery and development of new orally-active anti-inflammatory drugs
which selectively inhibit the enzyme, PDE IV. The treatment of
respiratory disease, particularly asthma, is the primary focus of this
highly productive collaboration. Lead compounds have been discovered
which have a superior profile over competitors. In particular, they
demonstrate enhanced efficacy and reduced side effects, leading to an
improved therapeutic index.
Chiroscience's approach to discovering active, non-emetic PDE IV
inhibitors was validated in Phase 1 clinical trials with its first
compound, D4418, which was specifically studied to prove this important
principle. However, compounds with an enhanced efficacy profile, ideally
targeting both the early- and late-phase responses observed in asthma, are
required in order to compete successfully in this changing marketplace
following the introduction of the leukotriene antagonists. New lead
compounds from the collaboration have demonstrated improved potency and an
excellent absorption profile in preclinical models compared to both D4418
and competitor compounds, indicating that a once a day treatment should be
possible.
A new area of significant interest for PDE IV inhibitors is Chronic
Obstructive Pulmonary Disease (COPD) which affects 15 million patients in
the US alone, and more than 40 million worldwide. This constitutes three
main diseases: chronic bronchitis; emphysema; and chronic bronchiolitis.
Current therapies for COPD include inhaled beta agonists, such as
salbutamol, and systemic theophylline, which provide symptomatic relief
only and do not address the underlying disease. Inhaled steroids are also
used in more advanced disease, but these have a range of undesirable side
effects. PDE IV inhibitors should be able to modify the disease because
they have the potential to address the three main features of the disease:
inflammation; bronchoconstriction; and airway damage.
POWDERJECT LIGNOCAINE
Chiroscience and PowderJect are collaborating on a joint development in
which Chiroscience is responsible for the clinical development of local
anaesthetics in the PowderJect needleless injector system. PowderJect are
developing and manufacturing the device and the drug product.
The initial focus has been on Dermal PowderJect Lignocaine and the
development of a revolutionary new method of providing rapid onset, pain-
free, needleless topical anaesthesia. Market research has demonstrated
that a major unmet medical need, and a very important use of this product
for the future, is in children. Dermal PowderJect Lignocaine should
eliminate the pain, fear and anxiety associated with needle injections and
allow procedures to be conducted within 5 minutes of application. Current
alternative products take up to 40 minutes to work.
Four Phase I and one Phase II clinical trials have been completed, all of
which achieved their objectives. In these studies, 110 adult subjects
received Dermal PowderJect Lignocaine. The trials have demonstrated that
it is effective at a range of clinically relevant anatomical sites and has
an acceptable safety profile. A Phase I study exploring surrogate
endpoints using Laser Doppler technology, which is a method of measuring
changes in blood flow, will be started shortly. If this exploratory
research correlates changes in blood flow with anaesthesia, it could offer
the opportunity to measure the onset, area and duration of anaesthesia in
a non-invasive manner.
Two Phase II Paediatric studies are being conducted the UK, starting in
September and October of this year. These studies will measure pre-
procedural (the taking of blood samples or cannulation) dermal analgesia
in children aged 4 to 12, to ascertain the optimal device characteristics
of Dermal PowderJect Lignocaine. Results from these studies are due in
the first half of next year. Adult trials will be conducted in parallel
with the paediatric studies. The clinical trials are expected to recruit
over 500 paediatric patients, and are focused on making a regulatory
submission in the year 2000. The use of levobupivacaine in this delivery
system is also being explored.
PowderJect Dermal Lignocaine is a trademark of Powderject Pharmaceuticals
plc
END
MSCSESFUAUAUFFU
Grafico Azioni Amedeo Res (LSE:AMED)
Storico
Da Giu 2024 a Lug 2024
Grafico Azioni Amedeo Res (LSE:AMED)
Storico
Da Lug 2023 a Lug 2024
