REG - Avacta Group PLC - Avacta Reports Data at the AACR Annual Meeting

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09/04/2024 17:00

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RNS Number : 9090J  Avacta Group PLC  09 April 2024

 

 

This announcement contains inside information for the purposes of Article 7 of
the UK version of Regulation (EU) No 596/2014 which is part of UK law by
virtue of the European Union (Withdrawal) Act 2018, as amended ("MAR"). Upon
the publication of this announcement via a Regulatory Information Service,
this inside information is now considered to be in the public domain.

 

9 April 2024

 

Avacta Group plc

 

("Avacta" or the "Group" or the "Company")

 

Avacta Therapeutics Reports Data from the Ongoing Phase 1 Clinical Trial of
AVA6000 at the AACR Annual Meeting Demonstrating Clinical Proof-of-Concept
Showing Multiple Patient Responses

 

AVA6000 delivers high concentrations of doxorubicin to the tumor
microenvironment ("TME") relative to plasma, resulting in significant
antitumor activity in patients whose tumors have over-expression of Fibroblast
Activation Protein ("FAP")

 

FAP-enabled release of doxorubicin directly in the TME results in a favorable
safety profile, tumor responses and a wider therapeutic index compared to
standard doxorubicin dosing

 

Further development at the recommended dose for expansion is planned in 2H
2024 in specific tumor types with high FAP expression and anthracycline
sensitivity

 

 

Avacta Group plc (AIM: AVCT), a life sciences company developing innovative,
targeted oncology drugs and powerful diagnostics, today announces the
presentation of interim results from the Phase 1 clinical trial of peptide
drug conjugate AVA6000 at the American Association for Cancer Research
("AACR") annual meeting in San Diego, USA.

 

The results to date show that AVA6000, the first peptide drug conjugate in the
Avacta pipeline, has a favorable safety profile with concentration of the
warhead in the TME resulting in multiple responses in patients with high
levels of Fibroblast Activation Protein ("FAP(high)"), thus delivering
clinical proof-of-concept for AVA6000 and proof-of-mechanism for the
proprietary pre|CISION(TM) drug delivery platform.

 

Professor Udai Banerji, Lead Investigator for the AACR poster and the
Co-Director of the Drug Development Unit at The Institute of Cancer Research
and The Royal Marsden NHS Foundation Trust, commented:

 

"The trial of AVA6000 shows an opportunity to be able to localize an already
effective chemotherapeutic agent to tumors using innovative technology and
biomarker strategies, resulting in reduced side effects. I am enthusiastic
about the early findings and I'm looking forward to completing the Phase 1
trial and moving it to the next stage in development."

 

Dr Alastair Smith, Chief Executive Officer of Avacta, commented:

 

"The data being presented at AACR support our continually growing confidence
in the pre|CISION™ peptide drug conjugate platform.

 

"We have already observed compelling evidence in the ongoing clinical studies
of AVA6000 that the platform delivers a step change in the tolerability levels
compared with standard doxorubicin. The data we are presenting today
demonstrate that the derived doxorubicin is being achieved through tumor
cleavage, validating the platform further and giving us great confidence in
the future efficacy studies.

 

"The positive data we are continuing to observe supports our belief that
pre|CISION™ could be a game changer in cancer treatment, allowing patients
to achieve better outcomes with reduced side effects both with doxorubicin and
potentially other more potent warheads."

 

Christina Coughlin MD, PhD, Head of Research and Development at Avacta, added:

 

"Antibody drug conjugates have been a key focus of oncology research given
their known antitumor effects in multiple solid tumors. The proof-of-concept
data presented today with AVA6000 suggest that the peptide drug conjugate drug
class has several key advantages, particularly the tumor-specificity of the
release of doxorubicin through targeting FAP and simplicity of the
manufacturing process which results in significant savings in the cost of
goods.

 

"Today's clinical data demonstrate that treatment of patients with metastatic
cancers with AVA6000 results in tumor responses with favorable tolerability in
patients whose tumors over-express FAP (FAP(high)).  Importantly, many of the
patients had experienced disease progression with prior lines of therapy.  We
believe these data support the further development of AVA6000 in a specific
set of indications with higher FAP expression and sensitivity to
anthracyclines. We look forward to providing further updates from the Phase 1
clinical trial in due course ahead of completion and moving to the next stage
of development, and updates to the Avacta pipeline implementing these results
in new programs."

 

pre|CISION(TM) technology

 

Many solid tumors have higher levels of FAP compared with healthy tissues.
Avacta's pre|CISION(TM) technology is designed to leverage the
tumor-specificity of FAP expression by rendering a therapeutic warhead inert
with the bound peptide moiety attached to the warhead, until it encounters FAP
and is cleaved, releasing active warhead into the TME. FAP targeted release of
the warhead specifically in the TME aims to reduce damage to healthy tissues
and systemic side effects, improving the tolerability for patients and
allowing optimization of the dosing schedule to improve efficacy.

 

Data demonstrate clinical proof of concept for AVA6000 with multiple patient
responses

 

Seven dose cohorts (n=42) were completed in the Phase 1a Arm 1 of the trial
with a dosing schedule of every three weeks ("Q3W") at the time of the data
cut-off on March 11, 2024. All 42 patients enrolled were evaluable for safety
(primary outcome measure) and for efficacy (secondary outcome measure). At the
time of the data cut-off, enrollment continues in the every two weeks ("Q2W")
Phase 1 Arm 2 dose cohort.

 

For analysis of the efficacy, cancer indications were categorized as FAP(high)
(soft tissue sarcoma and salivary gland cancer) or FAP(mid) (pancreatic
cancer, colorectal cancer, lung cancer and other malignancies). Patients with
indications considered FAP(low) were excluded from the trial. Among patients
with FAP(high) cancers (n=15), 2 partial responses and 3 minor responses were
observed, including:

 

·      A durable confirmed partial response in a 60-year-old male
patient with the diagnosis of undifferentiated pleomorphic sarcoma with
duration of response of 34 weeks. This patient had progressed on prior therapy
and imaging studies demonstrate near complete resolution of pleural metastases
with a reduction of 74% in the sum of longest diameters per RECIST version
1.1;

·      An unconfirmed partial response in a 79-year-old male patient
with salivary gland cancer with deepening of response to a 57% decrease in the
sum of diameters;

·      Two patients with dedifferentiated liposarcoma with minor
responses of >12% reduction in the sum of diameters; and

·      All four responders above remain on study at the time of the data
cutoff.

 

Meaningful stable disease of longer than 16 weeks and/or response was observed
in 10 patients resulting in a disease control rate of 10/15 (67%).  No
responses were observed among patients with FAP(mid) indications (n=27) and
stable disease >16 weeks was observed in 10 patients for a disease control
rate of 10/27 (37%).

 

Treatment with AVA6000 was well tolerated and a reduction in AVA6000-related
treatment-emergent toxicities as compared with standard dose doxorubicin was
noted with respect to both severe and mild to moderate toxicities. Regarding
severe toxicities (grade 3-4), a steep reduction in neutropenia was observed
when compared to standard dose doxorubicin (with AVA6000, 16.7% of patients
reported severe neutropenia vs 49% with standard dose doxorubicin). There were
no cases of febrile neutropenia in the AVA6000 trial compared to 16.5% of
patients receiving doxorubicin alone.  Reductions were observed as well in
toxicities that impact quality of life (any grade), including nausea (reported
by 33.3% of patients with AVA6000 vs 67% with doxorubicin) and mouth sores
(mucositis, 7.1% with AVA6000 vs 41% with doxorubicin). Other toxicities with
reductions include musculoskeletal pain, loss of appetite and constipation.
Two dose limiting toxicities were observed (cardiac failure and
neutropenia/thrombocytopenia), but in both cases the dose cohorts were
expanded and deemed safe.

 

Thus, the safety profile of AVA6000 administered on a once every three weeks
basis was favorable compared to standard dose doxorubicin and the first arm of
the Phase 1 did not identify a maximum tolerated dose.

 

Pharmacokinetic and pharmacodynamic modelling in the trial demonstrate that
AVA6000 delivers a high concentration of doxorubicin to the tumor
microenvironment relative to plasma, as designed in the pre|CISION™
platform. This concentration of the warhead in the TME results in antitumor
activity in tumors with reported high expression of FAP. In addition,
exposure-response modelling and comparison with serum FAP suggests the
derived, free doxorubicin is generated by tumor cleavage of AVA6000 versus
peripheral blood cleavage.

 

Based on this very favorable three-weekly dosing safety profile, Avacta
continues to enroll patients in the two-weekly dosing safety study. The
combined data from the three-weekly and two-weekly studies will provide
information to allow Avacta to define the dose and schedule to be used in
efficacy studies.

 

Patients can be dosed in parallel in the two-weekly dose escalation study and
Avacta remains on track to begin the dose expansion efficacy study in the
second half of 2024 in the US. The data from the expansion study will be used
to inform the optimal choice of a single indication for the Phase 2 efficacy
study which will follow the expansions, subject to FDA approval.

 

 

-Ends-

 

 

For further information from Avacta Group plc, please contact:

 

 Avacta Group plc                                                           Tel: +44 (0) 1904 21 7070

 Alastair Smith, Chief Executive Officer                                    www.avacta.com (http://www.avacta.com)

 Tony Gardiner, Chief Financial Officer

 Michael Vinegrad, Group Communications Director

                                                                            Tel: +44 (0) 207 710 7600

 Stifel Nicolaus Europe Limited (Nomad and Joint Broker)                    www.stifel.com (http://www.stifel.com/)

 Nicholas Moore / Nick Adams / Samira Essebiyea / Nick Harland / Ben Good

 Peel Hunt (Joint Broker)                                                   Tel: +44 (0) 207 418 8900

 James Steel / Chris Golden / Patrick Birkholm                              www.peelhunt.com (http://www.peelhunt.com)

 ICR Consilium (Media and IR)                                               avacta@consilium-comms.com (mailto:avacta@consilium-comms.com)

 Mary-Jane Elliott / Jessica Hodgson / Sukaina Virji

 

About Avacta Group plc - https://www.avacta.com (https://www.avacta.com/)

 

Avacta Group is a UK-based life sciences company focused on improving
healthcare outcomes through targeted cancer treatments and diagnostics.

 

Avacta has two divisions focused on therapeutics and diagnostics.

 

Avacta Therapeutics: a clinical stage oncology biotech division harnessing
proprietary therapeutic platforms to develop novel, highly targeted cancer
drugs.

 

Avacta Diagnostics: focused on supporting healthcare professionals and
broadening access to diagnostics.

 

Avacta has two proprietary platforms, pre|CISION™ and Affimer(®).

 

The pre|CISION™ platform is a highly specific substrate for fibroblast
activation protein (FAP) which is upregulated in most solid tumours compared
with healthy tissues. The pre|CISION™ platform harnesses this tumour
specific protease to activate pre|CISION™ peptide drug conjugates and
pre|CISION™ antibody/Affimer® drug conjugates in the tumour
microenvironment, reducing systemic exposure and toxicity, allowing dosing to
be optimised to deliver the best outcomes for patients.

 

The lead pre|CISION™ programme AVA6000, a peptide drug conjugate form of
doxorubicin, is in Phase 1 studies. It has shown a dramatic improvement in
safety and tolerability in clinical trials to date compared with standard
doxorubicin and preliminary signs of clinical activity in multiple patients.

 

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