Avacta Group
plc
("Avacta"
or "the Group" or "the Company")
Avacta Reports Pipeline
Advances with Two Novel Programs at the EORTC-NCI-AACR Molecular
Targets Symposium in Barcelona
LONDON - Oct. 24, 2024 - Avacta Therapeutics (AIM:
AVCT), a life sciences company
developing next generation peptide drug conjugates (PDC) targeting
powerful anti-tumor payloads directly to the tumor, today announces
scientific presentations of two novel programs in its pipeline at
the 2024 EORTC-NCI-AACR Symposium on
Molecular Targets and Cancer Therapeutics in Barcelona, Spain. The presentations include data from two
preclinical oncology assets, AVA6103 and AVA7100, from Avacta's
pipeline of pre|CISION® product candidates.
Both presentations take place today
in the Antibody Drug Conjugate (ADC) poster session at the
Symposium.
Avacta's pre|CISION®
product candidates are designed to be activated specifically in the
tumor microenvironment (TME), thereby enabling improved antitumor
activity while reducing systemic toxicities. Each peptide drug
conjugate (PDC) in the Company's pipeline is comprised of an active
antitumor drug (known as a payload) linked to the pre|CISION
peptide, which renders the payload inert and is cleaved only within
the tumor by the action of Fibroblast Activation Protein, or FAP,
expressed in the cancer associated fibroblasts in the TME. The
pre|CISION® technology addresses key limitations of
ADCs, namely (1) non-specific payload release that results in
significant off target toxicities, and (2) the complexity of the
bystander effect, which is necessary to target antigen-negative
tumor cells and thus to treat antigen-low populations. The
pre|CISION platform addresses these limitations by releasing
payload only in the tumor microenvironment and optimizing the
bystander mechanism of action.
AVA6103 is a pre|CISION-enabled PDC
comprised of the pre|CISION peptide linked to exatecan, the most
potent topoisomerase I (topo I) inhibitor in clinical development.
AVA7100 is a part of a new class of pre|CISION®-enabled
Affimer® drug conjugates with potential
applications in multiple cancer types, including those with lower
levels of FAP in the tumor. AVA6103 and AVA7100 are expected to
enter IND-enabling studies in late 2024 and 2H 2025,
respectively.
The details of these advances in the
pre|CISION® technology are presented below.
Christina Coughlin, MD PhD, CEO of Avacta,
commented:
"We are encouraged by the preclinical data from AVA6103
demonstrating that FAP-enabled exatecan induces DNA damage and
drives cancer cell death and we look forward to advancing this
promising therapy toward the clinic. The preliminary data from
AVA7100 demonstrating that exposure to Affimer® Drug
Conjugates (AffDCs) results in drug cleavage, release of the
payload and tumor cell kill as a bystander function are exciting
for this entirely new class of therapies.
"These presentations showcase the evolution of our
pre|CISION® platform technology to selectively deliver
highly potent payloads directly to the TME, while minimizing
exposure in normal tissues and optimizing patients' outcomes. Our
first program, AVA6000, demonstrates a
four- to six-fold increase in the therapeutic index in the clinic
and in preclinical models. With the advances in the platform, we
are now seeing a 75-fold increase in therapeutic index with our
recently announced exatecan program, AVA6103 in preclinical models,
suggesting that AVA6103 could have an unprecedented safety profile
in the clinic. Potent topoisomerase I inhibitors are the payloads
of ADC therapies in the clinic, although the non-specific release
of these payloads can lead to severe off-target toxicities.
Given the lack of these toxicities in our first program and the
broad reach of the topoisomerase I inhibitor class, we see our next
programs as having great potential for true impact in patients with
high unmet need."
AVA6103 Results
In a poster titled
"The novel peptide drug conjugate AVA6103 is a FAP-enabled
pre|CISION®
medicine which
targets Topoisomerase I to the tumor microenvironment via FAP
cleavage" in vivo
data were presented that demonstrate the ability
to target and accumulate the active warhead in the tumor
microenvironment, resulting in tumor growth inhibition with
AVA6103.
Specifically, the key findings from
the poster demonstrate:
·
The therapeutic index of exatecan is significantly
increased by pre|CISION enabling, specifically the maximum
tolerated dose of pre|CISION exatecan (AVA6103) observed is 75
times that of conventional exatecan in a daily dosing
regimen
·
AVA6103 optimizes the bystander effect where the
conjugate is only cleaved by FAP-positive fibroblasts, and released
exatecan can enter FAP-negative cancer cells
·
High intratumoral warhead concentrations are seen
at 4hr and 24hr timepoints for several pre|CISION exatecan
compounds, with up to 50-fold higher warhead concentrations in the
tumor versus plasma in a patient-derived xenograft
model,
o AVA6103 inhibits tumor growth, with complete responses noted
in a preclinical treated model engineered with human FAP expression
(HEK-FAP) tumors. Increased survival was also shown in this model
treated with AVA6103 compared with other models with
vehicle-treated tumors.
AVA7100 Results
A poster titled "Affimer® Drug Conjugates (AffDC) targeting
Fibroblast Activation Protein-α deliver highly toxic warheads to
the tumor microenvironment by leveraging the pre|CISION®
release mechanism" include data demonstrating that exposure
of tumor cell line or fibroblast cell co-cultures to AffDCs results
in drug cleavage, release of the warhead and tumor cell kill as a
bystander function.
Specifically, the key findings from
the poster demonstrate:
·
With non-internalizing Affimer protein binding and
extracellular warhead release by FAP, the AffDC optimizes the
bystander effect, leading to effective killing of antigen-positive
and antigen-negative tumor cells
·
AffDCs have an antigen-binding region of 14kDa
(single-domain) or 28 kDa (two-domain) that is 10-20% of the size
of an antibody, optimizing tumor penetration. AffDCs may be rapidly
engineered for optimal biophysical and functional
characteristics.
·
The FAP AffDC molecules exhibit a broad range of
FAP binding (including potency up to single-digit picomolar, pM)
combined with highly tumor-specific warhead release by leveraging
the preCISION linker to release warhead directly in the tumor
microenvironment and target that delivery to tumors with low FAP
expression
For further information from Avacta
Group plc, please contact:
About the pre|CISION® Platform
The
pre|CISION® platform comprises an anticancer payload conjugated to a
proprietary peptide that is a highly specific substrate for
fibroblast activation protein (FAP) which is upregulated in most
solid tumors compared with healthy tissues. The
pre|CISION® platform harnesses this tumor specific protease to cleave
pre|CISION® peptide drug conjugates and pre|CISION® antibody/Affimer® drug conjugates in the tumor
microenvironment, thus releasing active payload in the tumor and
reducing systemic exposure and toxicity, allowing dosing to be
optimized to deliver the best outcomes for patients.
About AVA6000: FAP-enabled doxorubicin
The lead
pre|CISION® program AVA6000, a peptide drug conjugate form of doxorubicin,
is in Phase 1 studies. It has shown an improvement in safety and
tolerability in clinical trials to date compared with standard
doxorubicin and preliminary signs of clinical activity in multiple
patients.To register for news alerts by email go
to https://avacta.com/investors/investor-news-email-alerts/.
AVA6103: FAP-enabled PDC targeting Topoisomerase
I
AVA6103 is a pre|CISION-enabled PDC
comprised of the pre|CISION peptide linked to exatecan, the most
potent topoisomerase I inhibitor in clinical development. Exatecan
has demonstrated clinical activity in breast, gastric, lung and
pancreatic cancers; however, it is associated with severe
dose-limiting toxicities and a short half-life in patients that led
to discontinuation of its monotherapy development. AVA6103 is
designed to enable patients to obtain the therapeutic benefit
associated with exatecan, while limiting the systemic exposure
associated with its poor tolerability.
AVA7100: pre|CISION® FAP Affimer Drug Conjugate (AffDC)
AVA7100 is a
pre|CISION®-enabled Affimer® drug
conjugate, a new class of therapies being developed by Avacta with
potential applications in a variety of cancer types, including
those with lower levels of FAP in the tumor.
Affimer® molecules are small proteins that are
engineered to bind to a target molecule in the same way that an
antibody does, but with several advantages, including smaller
molecule size and a broad range of binding affinity. AVA7100
consists of a novel FAP-Affimer conjugated to a pre|CISION-peptide
linker with multiple options for the payload.
About Avacta Group plc - https://avacta.com/
Avacta Group is a UK-based
life sciences company focused on improving healthcare outcomes
through targeted cancer treatments and diagnostics. Its clinical
stage oncology biotech division Avacta Therapeutics is harnessing
the proprietary pre|CISION® platform technology to develop
novel, highly targeted cancer drugs. Avacta
Diagnostics focuses on supporting healthcare professionals and
broadening access to diagnostics. To register for news alerts by
email go to https://avacta.com/investors/investor-news-email-alerts/.