REG - Avacta Group PLC - Avacta Reports Pipeline Avances at EORTC

AvactaAnnouncement

24/10/2024 07:00

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RNS Number : 3872J  Avacta Group PLC  24 October 2024

 

 

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:

 

 Avacta Group plc

 Michael Vinegrad, Group Communications Director       https://avacta.com/ (https://avacta.com/)
 Peel Hunt (Nomad and Broker)                          www.peelhunt.com (http://www.peelhunt.com)

 James Steel / Chris Golden / Patrick Birkholm
 ICR Consilium

 Mary-Jane Elliott / Jessica Hodgson / Sukaina Virji   avacta@consilium-comms.com (mailto:avacta@consilium-comms.com)

 

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/
(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/ (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/
(https://avacta.com/investors/investor-news-email-alerts/) .

 

 

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