TIDMAVCT
RNS Number : 1123Q
Avacta Group PLC
24 February 2021
24 February 2021
Avacta Group plc
("Avacta" or "the Group")
Business Update: Significant momentum in both Diagnostics and
Therapeutics Divisions
AffiDX(R) , SARS-CoV-2 Lateral Flow Rapid Antigen Test generates
excellent initial clinical sensitivity and specificity data
MHRA approves Clinical Trial Authorisation of first therapeutic
product candidate
Avacta Group plc (AIM: AVCT), the developer of innovative cancer
therapies and diagnostics based on its proprietary Affimer(R) and
pre|CISION(TM) platforms, is pleased to provide a business update
for the 12 months ended 31 December 2020 and post-period.
Preliminary results for the financial year ended 31 December 2020
are expected to be released mid-April.
Dr Alastair Smith, Chief Executive Officer of Avacta Group,
commented:
"The significant progress achieved in both the Diagnostics and
Therapeutics Divisions during 2020 has already enabled us to
deliver major value inflection points during the first weeks of
2021.
"We are very excited by the commercial potential of our
scalable, rapid coronavirus test. The recently announced clinical
data strongly reflects the excellent analytical performance
demonstrated in the lab and suggests that it may be, to date, the
most sensitive S1 spike protein lateral flow test. We are now
confidently proceeding into full clinical validation to support a
CE Mark, with a potential commercial launch for professional use
around the end of the first quarter of this year.
"Despite unprecedented pressures on the Diagnostics Division, we
now have in place the infrastructure to support the commercial
launch of this test. Importantly, we are close to completing the
establishment of a complex supply chain for the scalable
manufacture of the test kits and we are making timely progress in
instituting a quality management system to support the required
ISO13485 accreditation for medical devices.
"In line with commitments we made during the fund raise last
summer, in the Therapeutics Division we expanded our in-house
pre-clinical pipeline and also kept our partnered programmes moving
forwards, despite the restrictions of COVID-19 safe-working.
"In December, we submitted a Clinical Trial Authorisation (CTA)
to the UK's MHRA for our lead pre|CISION(TM) platform drug
candidate, AVA6000 Pro-doxorubicin, and I am delighted that we
recently received approval from the Agency to proceed with the
phase 1 study, which we expect will dose first patient around the
middle of the year.
"I am very proud of the Avacta team and how they have overcome
the substantial challenges presented by the pandemic and continued
to progress programmes and generate significant shareholder value.
I look forward to updating the market on the very exciting
milestones ahead of us in due course."
Operational Highlights
Diagnostics Division
-- AffiDX(R) SARS-CoV-2 Lateral Flow Rapid Antigen Test shows
excellent analytical sensitivity of 50 pg/ml of S1 spike protein
with a read time of 20 minutes. As far the Group is aware, this is
currently the most sensitive S1 spike lateral flow test available.
On 16 February 2021, we announced the initial clinical evaluation
of this test using anterior nasal swab samples (30 positive and 26
negative samples) which demonstrated a sensitivity of 96.7% for
samples with an infectious viral load (PCR Ct value < 26) and a
specificity of 100%.
-- BAMS(TM) SARS-CoV-2 Antigen Test clinical evaluation underway
at a UK NHS hospital site. Initial performance data are encouraging
and work is continuing to refine the assay protocol for use in the
clinical workflow on hospital-based MALDI-TOF instruments. On 28
January 2021 we entered a collaboration agreement with Bruker
Corporation to evaluate the clinical utility and commercial
potential of this test.
-- On 21 December 2020 we announced a licensing agreement with
Astrea Bioseparations Limited ("Astrea") for the use of the Affimer
platform in affinity purification applications; GBP0.5m upfront
payment and an ongoing services revenue stream plus a royalty on
future product sales by Astrea.
-- The Group is in the process of establishing ISO13485
accreditation, a critical quality assurance system for a developer
and legal manufacturer of diagnostic products and medical devices.
The Group passed the first audit by the Group's Notified Body (BSI
Group) and the final audit will occur in March 2021.
-- On 8 February 2021 we established a commercial partnership
with Mologic to provide Avacta with a faster route to market for
the lateral flow rapid antigen test by CE marking it for
professional use under Mologic's existing ISO13485 quality system.
The CE mark will then be transferred to Avacta after it receives
ISO13485 accreditation, which is expected by the end of March
2021.
-- The collaboration with Mologic also provides initial
manufacturing capacity for the lateral flow test with Global Access
Diagnostics (GAD) in addition to the agreements with BBI Group,
Abingdon Health and others that will provide manufacturing
capabilities that can be scaled to several million tests per
month.
-- Strengthened and expanded diagnostics management team with
the appointment of a Product Manager, Head of Product Development
and Operations Director.
Therapeutics Division
-- The Group has continued to make good progress with both
in-house and partnered programmes despite limitations on laboratory
staffing due to COVID-safe working practices.
o On 18 February 2021 the Medicines and Healthcare products
Regulatory Agency (MHRA) approved the CTA for AVA6000
Pro-doxorubicin, the Group's lead pre|CISION(TM) prodrug, for a
phase 1, first-in-human, open label, dose-escalation and expansion
study in patients with locally advanced or metastatic selected
solid tumours.
-- The Group anticipates dosing first patients in mid-2021
subject to COVID-19 restrictions on hospital resources with first
pharmacokinetics read-out possible before the year end.
o On schedule to select the next pre|CISION prodrug chemotherapy
clinical development candidate from the pipeline by the end of
2021. Lead programmes include AVA3996 a FAP<ALPHA> activated
proteasome inhibitor, AVA7500 a FAP<ALPHA> activated platin,
and AVA7000 a FAP<ALPHA> activated taxane.
o Significant progress with in-house Affimer bispecific
programmes towards selection of a clinical development candidate by
the end of 2021. Two new programmes initiated, building on the
AVA004 PD-L1 antagonist programme: AVA027, a PD-L1/TGf<BETA>
receptor trap combination and AVA028, a PD-L1/IL2 bispecific.
o In-vivo studies of the lead TMAC programmes ongoing to support
selection of a clinical development candidate from the pipeline:
AVA04-VbP and a second undisclosed Affimer-VbP programme.
-- On 18 August 2020 we announced the expansion of the existing
multi-target collaboration and development agreement with LG Chem
Life Sciences ("LG Chem") to include new programmes incorporating
Avacta's Affimer XT(TM) serum half-life extension system. The
agreement included an undisclosed additional upfront payment, plus
near-term pre-clinical milestones and longer-term clinical
development milestones totalling $98.5m with additional royalties
on all future Affimer XT product sales by LG Chem.
-- On 7 January 2021 we announced the license agreement with
Point Biopharma Inc to provide access to Avacta's pre|CISION(TM)
technology for the development of tumour-activated
radiopharmaceuticals. The terms of the agreement include a
significant, undisclosed upfront payment.
-- Rapidly established a highly experienced Clinical Development
Team. Appointed Neil Bell as Chief Development Officer on 11 August
2020. Additional key appointments of Head of Chemistry,
Manufacturing and Controls (CMC), Head of Clinical Operations and
Head of Translational Sciences will together manage an extensive
outsourced network of drug development service providers.
-- On 1 February 2021, AffyXell Therapeutics ("AffyXell"), the
joint venture with Daewoong Pharmaceuticals ("Daewoong"), closed a
series A venture capital investment of $7.3m to further develop its
pipeline of next generation cell and gene therapies.
Corporate
The Group's cash position at the 31 December 2020 was GBP48m
slightly higher than market forecasts.
This announcement contains information which, prior to its
disclosure, was considered inside information for the purposes of
Article 7 of Regulation (EU) No 596/2014 (MAR).
Disclaimer: AffiDx SARS-CoV-2 Lateral Flow Rapid Antigen Test
not currently for sale in the United States.
- Ends
For further information from Avacta Group plc, please
contact:
Avacta Group plc Tel: +44 (0) 844 414 0452
Alastair Smith, Chief Executive Officer www.avacta.com
Tony Gardiner, Chief Financial Officer
finnCap Ltd (Nominated Adviser and Joint Broker) Tel: +44 (0) 207 220 0500
Geoff Nash / Giles Rolls - Corporate Finance www.finncap.com
Tim Redfern - ECM
Stifel Nicolaus Europe Limited (Joint Broker) Tel: +44 (0) 207 710 7600
Nicholas Moore / Nick Adams / Fred Walsh / Ben Maddison www.stifel.com
FTI Consulting (Financial Media and IR) Tel: +44 (0) 203 727 1000
Simon Conway / Stephanie Cuthbert Avacta.LS@fticonsulting.com
Zyme Communications (Trade and Regional Media) Tel: +44 (0) 7787 502 947
Katie Odgaard katie.odgaard@zymecommunications.com
About Avacta Group plc - https://www.avacta.com
Avacta Group is developing novel cancer immunotherapies and
powerful diagnostics based on its two proprietary platforms -
Affimer(R) biologics and pre|CISION(TM) tumour targeted
chemotherapies.
The Affimer platform is an alternative to antibodies derived
from a small human protein. Despite their shortcomings, antibodies
currently dominate markets, such as diagnostics and therapeutics,
worth in excess of $100bn. Affimer technology has been designed to
address many of these negative performance issues, principally: the
time taken to generate new antibodies and the reliance on an
animal's immune response; poor specificity in many cases; their
large size, complexity and high cost of manufacture.
Avacta's pre|CISION targeted chemotherapy platform releases
active chemotherapy in the tumour, which limits the systemic
exposure that causes damage to healthy tissues, and thereby
improves the overall safety and therapeutic potential of these
powerful anti-cancer treatments.
The Group comprises two divisions: The therapeutics development
activities are based in Cambridge, UK and the Group is generating
near-term revenues from Affimer reagents for diagnostics,
bioprocessing and research, through a separate diagnostics business
unit based in Wetherby, UK.
Avacta's Diagnostics Division works with partners world-wide to
develop bespoke Affimer reagents for third party products. The
Group is also developing an in-house pipeline of Affimer-based
diagnostic assays including the AffiDX(TM) SARS-CoV-2 Lateral Flow
Rapid Antigen Test and a BAMS(TM) SARS-CoV-2 Assay in partnership
with Adeptrix Inc.
Avacta's Therapeutics Division is addressing a critical gap in
current cancer treatment - the lack of a durable response to
current immunotherapies experienced by most patients. By combining
its two proprietary platforms the Group is building a wholly owned
pipeline of novel cancer therapies deigned to be effective for all
cancer patients. In 2021 Avacta will commence a phase 1
first-in-human, open label, dose-escalation and expansion study of
AVA6000 Pro-doxorubicin, the Group's lead pre|CISION(TM) prodrug,
in patients with locally advanced or metastatic selected solid
tumours.
Avacta has established drug development partnerships with pharma
and biotech, including a research collaboration with Moderna
Therapeutics Inc., a multi-target deal with LG Chem worth up to
$400m, a joint venture in South Korea with Daewoong Pharmaceutical
focused on cell and gene therapies incorporating Affimer
immune-modulators, a partnership with ADC Therapeutics to develop
Affimer-drug conjugates and a collaboration with Point Biopharma to
develop radiopharmaceuticals based on the pre|CISION(TM) platform.
Avacta continues to actively seek to license its proprietary
platforms in a range of therapeutic areas.
To register for news alerts by email go to
www.avacta.com/investor-news-email-alerts
Business Update
Diagnostics Division
AffiDX(TM) SARS-CoV-2 Lateral Flow Rapid Antigen Test for
Potential Mass Deployment
During the past year Avacta, in conjunction with its partners,
has made exciting progress in the development of its Affimer based,
SARS-CoV-2 lateral flow rapid antigen test. Laboratory studies
indicate that it may be the most sensitive S1 spike protein lateral
flow test available [to date]. Furthermore, recently announced data
from initial clinical samples has shown a sensitivity of 96.7% for
patient samples with an infectious viral load, and specificity of
100%. On the basis of these excellent data, the Group is now
progressing to a full clinical validation with a larger number of
patient samples to CE mark the test for professional use, aiming to
bring the test to market in Europe around the end of the first
quarter of this year.
The test uses Affimer binders to the SARS-CoV-2 spike protein
and is capable of identifying individuals with infectious viral
loads using an anterior nasal swab sample. Such a test is suitable
for mass deployment to identify those people who are likely to
infect others so that they can isolate and reduce the spread of the
infection.
LFTs are a complement, not a replacement for PCR testing
How a diagnostic test is used, called the "Intended Use Case",
is extremely important and it must be adhered to in order to avoid
a test being used inappropriately. A rapid antigen test with high
specificity and good sensitivity can be used effectively to
identify the majority of people with a high viral load that makes
them infectious so that they can isolate themselves. Frequent
testing, at least once every few days and ideally daily, is
important so that as soon as the viral load of an infected person
becomes high enough to be infectious that person is identified.
The first challenge in developing a clinically useful rapid
coronavirus test for mass population screening is to understand
what viral load should be considered infectious.
Patient samples can be characterised in a number of ways but the
most common are:
-- Genome copies per millilitre (i.e. how many copies of the
virus RNA are present in a millilitre of sample).
-- Plaque forming units (pfu) per millilitre (i.e. how many
viable viruses that can infect cells and multiply are present in a
millilitre of sample). The number of pfu/ml and genomes/ml are
different because there is RNA present in samples that is not
assembled into viable virus particles. (i.e. the genomes per ml is
higher than the pfu per ml). These two measures of infection vary
in a way which has not yet been fully characterised but there is
probably between 10 - 10,000 more genomes/ml than pfu/ml in a
sample.
-- Cycle time (Ct), which is the number of amplification cycles
of PCR required to detect the virus (i.e. a low Ct value means that
the person has higher viral load because it took fewer
amplification cycles to become detectable). Ct values vary between
different PCR tests, and even between different laboratories
running the same test, so this should also be taken into
account.
A reasonable assumption, based upon the growing combined
understanding of SARS-CoV-2 and COVID-19, is that a person is
infectious and likely to infect others if their viral load is >
10,000 genomes/ml (i.e. approximately > 100 pfu/ml and Ct <
25). According to recently published data from the Liverpool Covid
Smart Pilot [1] , a viral load of < 10,000 genome/ml leads to a
likelihood of infecting others of around 10%. Therefore, at this
low end of the infectious range the risk of infecting others
appears to be quite low. Whereas the risk of a person with a viral
load 1,000,000 genome copies/ml is around 50%. Highly infectious
people can have viral loads > 100,000,000 genome copies/ml.
With all this in mind, for a rapid antigen test to have clinical
utility (and therefore sustainable commercial value) it should be
able to detect SARS-CoV-2 viral load of a few hundred pfu/ml, or Ct
of 25 or below, or >10,000 genomes/ml. Clearly, the lower the
detection limit the better, and a test must be able to achieve this
limit of detection in real patient samples and not just in
contrived "clean" laboratory samples.
Laboratory testing suggests that the AffiDX(TM) SARS-CoV-2
Lateral Flow Rapid Antigen Test could be the most sensitive spike
antigen test so far available
The AffiDX(TM) SARS-CoV-2 Lateral Flow Rapid Antigen Test
detects the SARS-CoV-2 S1 spike protein and has an analytical limit
of detection (LOD) in nasal swab samples of 50 pg/ml. This can be
achieved with a visual read time of 10 minutes. The test line is
clearer if a longer read time is used, therefore a read time of 20
minutes has been adopted as the standard for this test.
How does this analytical sensitivity translate into pfu/ml of
virus which is the clinically relevant measure? Avacta has
established this relationship using Avacta's research ELISA for S1
protein and inactivated virus provided by Public Health England
(Porton Down, UK). Using this safe form of the virus, we have shown
that an analytical LOD of 50pg/ml corresponds to the amount of S1
spike protein in a virus sample containing 500 pfu/ml.
A significant proportion of the development time of the
AffiDX(R) SARS-CoV-2 Lateral Flow Rapid Antigen Test has been
focused on achieving this level of sensitivity in human saliva and
nasal swab clinical samples. The development work has been carried
out in-house and with our development partners using saliva and
anterior nasal swab samples taken from healthy volunteers to which
the S1 spike protein has subsequently been added to known
concentrations to generate a contrived clinical sample. The key
challenge in developing the test has been to get these complex
human fluids to flow properly in the device and to eliminate false
positive results arising from unknown material in nasal samples and
saliva. This has been achieved through detailed studies evaluating
a range of different additives to the lateral flow test and sample
extraction buffer for both nasal and saliva samples. The Group
announced in Q4 2020 that it would focus on anterior nasal sampling
because of the variability of saliva samples, although the test
works with both sample types. The UK Department of Health and
Social Care has also recently focused on nasal and other swab
samples rather than saliva.
In summary, the AffiDX(R) SARS-CoV-2 Lateral Flow Rapid Antigen
Test has excellent analytical sensitivity (LOD) of 50 pg/ml S1
spike protein, which appears sensitive enough to detect the lowest
viral loads of relevance to the Intended Use Case, with a read time
of 20 minutes. As far the Group is aware, this is the most
sensitive S1 spike lateral flow test available.
The analytical specificity of the Affimer reagents has been
reported previously with no cross-reactivity with the S1 spike
proteins from closely related coronaviruses: MERS-CoV S1,
SARS-CoV-1 S1, HC0V-229E S1, HCoV-HKU1 S1, HCoV-NL63 S1 or
HCoV-OC43 S1.
The test detects the D641G mutant of the original coronavirus
and the Group expects that the test will also detect the newer
coronavirus variants. Work is ongoing with Public Health England to
confirm this.
Initial clinical evaluation of AffiDx(TM) SARS-CoV-2 Lateral
Flow Rapid Antigen Test
The clinical performance of a diagnostic test cannot simply be
inferred from the analytical performance because of the complex
pathology of diseases which control the amount of a biomarker that
is available in a sample when added to the test. In the case of
COVID-19, there is a complex series of biological processes that
determine how much of the virus spike protein is actually present
in the anterior (front) part of the nose to be picked up on a swab
and then released into a buffer to be added to the lateral flow
test strip. A clinical evaluation of the test is the only way to
determine whether it is capable of identifying infectious
individuals.
The initial evaluation of Avacta's lateral flow rapid antigen
test with clinical samples has been carried out at two sites, one
in EU and one in the UK using patient samples with viral loads
confirmed by PCR. 30 positive samples were tested with Ct values of
26 and below, with half of those in the range 22-26, and the
lateral flow test identified 29/30 of these correctly as positive.
This indicates a clinical sensitivity of 96.7% for samples with a
Ct value below 26. Importantly, out of a total of 26 negative
samples tested with the lateral flow device, the test correctly
identified all 26 as negative, giving a clinical specificity of
100%. High specificity is critical for a lateral flow test for mass
screening so that large numbers of false positives are not
generated which would create a major burden on follow-on testing
resources, and result in a significant socio-economic cost of
unnecessarily isolating people.
As stated above, on the basis of these excellent initial data,
the Group will now progress to a full clinical validation with a
larger number of patient samples to CE mark the test for
professional use, aiming to bring the test to market in Europe
around the end of the first quarter of this year.
A vacta Diagnostics Division expects ISO13485 accreditation
around end of March 2021
Avacta's Diagnostics Division is currently in between the two
audits of the Group's Quality Management System that are required
by its external auditor in order to award ISO13485
accreditation.
Medical device manufacturing is a highly regulated sector in
which stringent quality systems and product performance
requirements must be satisfied. These regulatory requirements are
intended to ensure that manufacturers consistently design, produce
and place onto the market medical devices that are safe and fit for
their intended purpose. ISO13485 certification provides a practical
foundation for diagnostics and medical device manufacturers to
address these regulatory requirements and obligations of the
industry as well as demonstrating a commitment to device safety and
quality.
The Diagnostics Division has established a Quality Management
System and the first external audit by the Group's Notified Body
[2] (BSI Group) was passed in December successfully. The second and
final audit is scheduled for March 2021. A positive outcome of the
second audit will lead to ISO13485 accreditation. This
certification sets the organisational and operational framework for
all current and future diagnostic product developments and it is an
essential accreditation that underpins future commercial
success.
Mologic partnership enables near-term AffiDX(TM) CE Mark for
Professional Use
Whilst the Group establishes its own ISO13485 accreditation, in
order to achieve the fastest possible and lowest risk route to CE
marking, Avacta has established a partnership with Mologic Ltd. so
that the AffiDX(TM) SARS-CoV-2 Lateral Flow Rapid Antigen Test can
be CE marked for professional use quickly under Mologic's
established ISO13485 Quality System. The CE mark will then be
transferred to Avacta when it achieves ISO13485 accreditation,
which is expected at the end of March 2021. As part of the
collaboration between the two companies, Avacta and Mologic are
also exploring the possibility of combining Avacta's spike antigen
test with Mologic's nucleocapsid antigen test [3] in a single
device which would be a world first and has the potential to
deliver the most sensitive rapid antigen test possible. The two
companies will evaluate whether the two tests can be combined in a
single device and then make a commercial decision on whether to
pursue this second generation COVID-19 diagnostic.
Avacta will immediately be able access initial manufacturing
capacity through Mologic, in addition to scale-up manufacturing
capacity with BBI and Abingdon Health. Combined, these
manufacturing partnerships can scale up to several million tests
per month and potentially much higher with further investment.
Avacta is also continuing its discussions with other manufacturers
in the UK and overseas in order to be able to access additional
capacity to ensure that it can meet the expected demand.
The Group continues its commercial discussions with potential
customers for the AffiDX(R) SARS-CoV-2 Lateral Flow Rapid Antigen
Test and expects demand to be present for rapid testing for at
least two years and probably for longer. Only by having a
high-quality test that identifies the majority of infectious
individuals can this clinical need be translated into commercial
success and the Group believes that the recent initial clinical
data are extremely encouraging in that regard.
Healthcare services providers and governments are likely to be
the largest volume customers of a professional use rapid antigen
test and with an estimated price point in the mid-single digit GBP
range. A higher price point is anticipated for sales to corporates
for workforce testing.
BAMS(TM) SARS-CoV-2 Assay
BAMS assay could enable 1000 sample per day high throughput
COVID-19 testing in hospitals
In collaboration with Adeptrix Inc, Avacta has developed a mass
spectrometry assay on Adeptrix's BAMS(TM) platform which combines
enrichment of the sample using Avacta's SARS-CoV-2 spike protein
Affimer binders to improve sensitivity with the power of
mass-spectrometry for analysis. Up to one thousand samples per day
can be analysed by a single technician using BAMS, exceeding the
capacity of a single PCR machine.
The SARS-CoV-2 BAMS assay analytical performance has been shown
by both Adeptrix and Bruker [4] to hold promise as a high
throughput technique for COVID-19 screening in the clinical setting
and Avacta is evaluating the assay in the clinic with a view to CE
marking it as a diagnostic for professional use.
Initial attempts to access patient samples through the
government's CONDOR programme have been very disappointing and
recent information indicates that these data also cannot be used to
CE mark the test. Avacta has therefore established two
collaborations with clinical teams outside of the CONDOR and FALCON
programmes. In collaboration with these teams the BAMS assay
protocol has been simplified and amended to fit into the clinical
work processes and the Group is working with its collaborators to
determine the sensitivity of the BAMS assay when run on the type of
mass spectrometers that are predominantly installed in hospital
laboratories.
This evaluation is expected to continue for another two or three
weeks and the Group is establishing outsourced manufacturing
capacity for the BAMS tests in collaboration with Adeptrix so that
it is in a position to formally validate the diagnostic product as
soon as possible. Avacta is also in discussions with a large
commercial partner to provide a route to market for the BAMS
assay.
Non-COVID Diagnostics Update
Recently the Group entered into a license agreement with Astrea
for the use of the Affimer platform in affinity purification
applications.
Astrea is a leading provider of affinity separation solutions to
the pharmaceutical and biomanufacturing industries. It is a
division of Gamma Biosciences, the life sciences tools platform
created by KKR, to build a leading position in next-generation
bioprocessing for advanced therapies.
This is an important validation of one part of the Group's
business model for non-therapeutic Affimer applications - that of
third party technical evaluations of bespoke Affimer reagents
generated for a specific application leading to licensing of those
Affimer reagents and long term royalty based revenue streams.
Astrea has evaluated certain Affimer reagents for affinity
separation resulting in the agreement between the two companies for
a non-exclusive license for the use of the Affimer technology in
this field.
The agreement includes a GBP0.5m upfront payment to Avacta which
gives Astrea the rights to generate and develop Affimer reagents
in-house for affinity separation using an Affimer library to be
provided by Avacta. It also provides Astrea with an option to
convert the agreement into an exclusive license if certain
commercial performance criteria are met over the next three years
and subject to the payment of an additional undisclosed option
exercise fee.
Avacta will receive royalties on future sales of Astrea's
purification products that contain Affimer reagents.
Although the pandemic has affected the Group's business
development activities, it continues to generate new projects and
to work on established Affimer evaluations with partners to
generate further license agreements.
The Group is also developing an in-house pipeline of Affimer
based diagnostic tests. Resources have been focused during 2020
primarily on the immediate COVID testing opportunities, and since
the lateral flow test is now in clinical evaluation the Group is in
a position to begin to refocus its research and development
resources onto non-COVID diagnostic tests, which include assays for
D-dimer, cortisol, vitamins D and B12 and CRP. Avacta has recently
appointed a Product Manager who will join the Group in March whose
role is to define the market opportunity and performance
requirements for new tests to feed the product development pipeline
in the future. This appointment is part of a wider expansion of the
Diagnostics Division's management team which includes a Product
Manager, Head of Product Development and Operations Director.
During the pandemic, in order to maintain a COVID safe working
environment the Group has not been able to have all laboratory
staff on site at the same time and has worked two teams. New CAT 2
laboratory facilities in Wetherby have been completed and equipment
that has been installed is now being validated to satisfy the
requirements of ISO13485. The new facilities will house about 20
staff and the Group expects therefore to be able to get all staff
who cannot work from home back on site from February.
Therapeutics Division
Wholly-owned pre|CISION and Affimer Drug Pipeline
The Therapeutics Division has also had to work two teams in
order to maintain social distancing in the laboratories in
Cambridge, effectively reducing laboratory staffing to half its
normal capacity. Nevertheless, the Group has continued to make
progress with both in-house and partnered programmes.
Approval of CTA for AVA6000, the Group's lead pre|CISION(TM)
prodrug, is a key milestone
The Group achieved a significant milestone with the submission
in Q4 2020 and subsequent approval on 19 February 2021 from the
MHRA (Medicines and Healthcare products Regulatory Agency) of the
Clinical Trial Authorisation (CTA) for AVA6000 Pro-doxorubicin, the
Group's lead pre|CISION(TM) prodrug, for a phase 1, first-in-human,
open label, dose-escalation and expansion study in patients with
locally advanced or metastatic selected solid tumours. The Group
anticipates dosing first patients in mid-2021, subject to COVID-19
restrictions on hospital resources, with first pharmacokinetics
read-out possible before the year end.
Instrumental in achieving the CTA submission milestone was the
appointment of Chief Development Officer, Neil Bell, who has
rapidly established a highly experienced Clinical Development Team
including a Head of Chemistry, Manufacturing and Controls (CMC),
Head of Clinical Operations and Head of Translational Medicine
appointed in-house to manage an extensive outsourced network of
service providers.
In AVA6000, Doxorubicin has been modified with Avacta's
pre|CISION(TM) chemistry, which renders the modified drug inactive
in the circulation until it enters the tumour micro-environment.
Here it is activated by an enzyme called FAP (fibroblast activation
protein), which is in high abundance in most solid tumours but not
in healthy tissue such as the heart. AVA6000 has been shown in
animal models to significantly increase the amount of active drug
in a tumour compared with the heart and should thereby improve
tolerability and achieve better clinical outcomes for patients
Phase 1 study will be clinical proof-of-concept of the
pre|CISION platform
The phase 1 study is a first-in-human, open-label, multi-centre
study to be carried out in the UK in patients with locally advanced
or metastatic solid tumours which are known to be FAP positive
including pancreatic, colorectal, breast, ovarian, bladder and
non-small cell lung cancers, squamous cell carcinoma of the head
and neck and soft-tissue sarcoma.
The dose-escalation phase of the study, which will be carried
out in 15-20 patients, is designed to evaluate the safety of
AVA6000 in humans and establish the appropriate dosing levels for
the dose expansion phase of the study.
The dose expansion phase will consist of up to three studies in
specific tumour types to further evaluate safety and tolerability
and to explore the anti-tumour activity of AVA6000 when
administered as a monotherapy. This phase of study will comprise
45-60 patients in total.
If the AVA6000 study shows that the pre|CISION chemistry is
effective in reducing systemic toxicity of Doxorubicin in humans,
then it can be applied to a range of other established
chemotherapies to improve their safety and efficacy. This would
open up a pipeline of next generation chemotherapies for the Group
with significant clinical and commercial value in a chemotherapy
market that is expected to grow to $56 billion by 2024.
Group rapidly making progress to expand proprietary pre-clinical
therapeutics pipeline
A significant proportion (c. GBP40m) of the funds raised through
the placing in the summer of 2020 has been allocated to the rapid
expansion of the pre-clinical therapeutics pipeline and the
efficient translation of this pipeline into clinical development
candidates during 2021 and beyond.
The Group is on schedule to select the next clinical development
candidate by the end of 2021 from the pre|CISION prodrug pipeline.
Lead programmes include AVA3996 a FAP<ALPHA> activated
proteasome inhibitor, AVA7500 a FAP<ALPHA> activated platin,
and AVA7000 a FAP<ALPHA> activated taxane. These are being
developed in close collaboration with Professor William Bachovchin
at Tuft's University School of Medicine.
Good progress has also been made with the in-house Affimer
bispecific programmes towards selection of a clinical development
candidate by the end of 2021. Two new programmes have been
initiated that build upon the AVA004 PD-L1 antagonist programme:
AVA027, a PD-L1/TGfb receptor trap combination and AVA028, a
PD-L1/IL2 bispecific.
The Group will update shareholders and the wider market in
detail on the biological, clinical and commercial rationale for the
selection of these pre|CISION and Affimer therapeutic programmes
during Q2 2021.
In-vivo studies of the lead tumour microenvironment activated
drug conjugate (TMAC) programmes are ongoing to support the
selection of a clinical development candidate from the pipeline.
The first of these programmes is AVA04-VbP, a TMAC combining a
PD-L1 Affimer antagonist with Val-boro-pro (also known as IDASH)
which is a DPP9/9 inhibitor. The second TMAC programme combines an
Affimer against an undisclosed target with VbP. The Group will
update shareholders when a full in-vivo data set has been generated
and the Group is in a position to select a candidate for clinical
development.
Partnered programmes continue to expand
The Group has established several significant therapeutic
partnerships with biotech and pharma partners including Moderna
Therapeutics Inc., LG Chem Life Sciences, Daewoong Pharmaceuticals,
ADC Therapeutics and recently with POINT Biopharma. Despite the
effects of the pandemic, the Group has continued to make solid
progress on those programmes in which Avacta plays an active
research and development role (LG Chem, Daewoong and ADC
Therapeutics).
In August 2020 Avacta agreed to expand the existing multi-target
collaboration and development agreement with LG Chem to include new
programmes incorporating Avacta's Affimer XT(TM) serum half-life
extension system. The expansion of the partnership includes an
undisclosed additional upfront payment, plus near-term pre-clinical
milestones and longer-term clinical development milestones
totalling $98.5m for two therapeutics to be developed using the
Affimer XT technology. Under the terms of the extended agreement,
LG Chem has the exclusive rights to develop and commercialise, on a
world-wide basis, Avacta's Affimer PD-L1 inhibitor with Affimer XT
serum half-life extension.
The expanded partnership also provides LG Chem with rights to
develop and commercialise other Affimer and non-Affimer
biotherapeutics combined with Affimer XT half-life extension for a
range of indications and Avacta could earn an additional $55m in
milestone payments for each of these new products.
In addition, under the agreement Avacta will earn royalties on
all future Affimer XT product sales by LG Chem.
Post-period end the Group entered into a new license agreement
with POINT Biopharma Inc. to provide access to Avacta's
pre|CISION(TM) technology for the development of tumour-activated
radiopharmaceuticals.
The radiopharmaceutical market is expected to grow to $15
billion by 2025 [5] and there is a substantial opportunity to grow
much faster if safety and tolerability of these effective
treatments can be improved. POINT Biopharma is a clinical-stage
pharmaceutical company focused on developing radioligands [6] as
precision medicines for the treatment of cancer.
Avacta's proprietary pre|CISION(TM) chemistry can be used to
modify a radioligand drug to form a tumour-activated prodrug. The
prodrug form is inactive in circulation until it enters the tumour
micro-environment where it is activated by an enzyme called
fibroblast activation protein (or FAP) that is present in high
abundance in most solid tumours but not in healthy tissue. Avacta's
pre|CISION (TM) technology therefore has the potential to improve
the tolerability and achieve better clinical outcomes for patients
compared with standard radiopharmaceuticals by targeting the
radioligand treatment more specifically to cancer cells.
The agreement provides POINT with an exclusive license to the
pre|CISION (TM) technology for use in the first radiopharmaceutical
prodrug the company intends to develop, and a non-exclusive license
to the pre|CISION(TM) platform for the development of a broader
pipeline of FAP-activated radiopharmaceuticals.
Under the terms of the agreement, Avacta will receive an upfront
fee and development milestones for the first radiopharmaceutical
prodrug totalling $9.5m. Avacta will also receive milestone
payments for subsequent radiopharmaceutical prodrugs of up to $8m
each, a royalty on sales of FAP-activated radiopharmaceuticals by
POINT and a percentage of any sublicensing income received by
POINT.
The Group continues to make excellent progress in its
collaboration with Daewoong Pharmaceutical through the joint
venture, AffyXell . AffyXell was established in January 2020 by
Avacta and Daewoong as a joint venture to develop novel stem cell
therapies. AffyXell is combining Avacta's Affimer platform with
Daewoong's mesenchymal stem cell (MSC) platform such that the stem
cells are primed to produce and secrete therapeutic Affimer
proteins in situ in the patient. The Affimer proteins are designed
to enhance the therapeutic effects of the stem cells creating a
novel, next generation cell therapy platform.
The Group recently announced, post-period end, that the joint
venture with Daewoong Pharmaceuticals called has closed a Series A
venture capital investment of $7.3m to further develop its pipeline
of next generation cell and gene therapies. The Series A funding
has been raised from a group of venture funds including Samsung
Venture Investment Corporation, Shinhan Venture Investment,
Smilegate Investment, Shinhan Investment Corporation, Kolon
Investment, Stonebridge Ventures, and Gyeongnam Venture
Investment.
The capital raised will be used by AffyXell to continue the
development of MSCs engineered to produce Affimer molecules
generated by Avacta that inhibit inflammatory and autoimmune
pathways and promote tissue regeneration.
While initially focusing on inflammatory and autoimmune diseases
and prevention of organ transplant rejection, longer term goals
could also include applications in regenerative medicine,
infectious diseases and oncology.
[1]
https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/950695/s0958-liverpool-covid-smart-evaluation.pdf
[2] A Notified Body is an organisation that has been designated
by a member state of the European Union to ensure that products
that are sold in the EU conform to the technical requirements. A
Notified Body also conducts audits of Quality Management Systems,
and a company's adherence to its Quality Management System, in
order to award and maintain ISO13485 accreditation for medical
device development and manufacture.
[3]
https://mologic.co.uk/mologic-receives-ce-mark-approval-for-professional-use-covid-19-rapid-antigen-test/
[4] Link to Bruker application note: https://bit.ly/3jla8Rq
[5] https://www.marketresearchfuture.com/reports/radio-pharmaceutical-market-1650
[6] For more information about radioligands visit https://www.radioligands.org
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