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ALS-6000-101 Phase 1a Three-Weekly Dose Escalation Safety Study Data

The data confirm the pre|CISIONTM platform’s ability to transform the safety profile of doxorubicin  through tumour targeting 

Cohort 7, the final cohort in the three-weekly dose escalation safety study of AVA6000, has completed enrolment and is ongoing 

A fortnightly dosing study to optimise the selection of the Phase 2 dose is now screening patients in the United States 

 

Avacta Group plc (AIM: AVCT), a life sciences company developing innovative, targeted oncology drugs and powerful diagnostics, is pleased to provide detailed pre-clinical, clinical and pharmacokinetic data from the Phase 1a dose escalation study of its lead pre|CISIONTM programme, AVA6000, a tumour activated form of doxorubicin.

The key conclusions drawn from the data for AVA6000 to date are:

  1. The pre|CISIONTM platform targets the release of a chemotherapy to the tumour as intended. The data show that the pre|CISIONTM modification is cleaved specifically by Fibroblast Activation Protein (FAP), an enzyme present in high concentrations in many solid tumours compared with healthy tissue. In the case of AVA6000, this targets the release of doxorubicin to the tumour microenvironment, concentrating the active cytotoxic drug within the tumor microenvironment and limiting systemic exposure to the chemotherapy.
  2. AVA6000 has significantly improved the safety and tolerability of doxorubicin. A significant reduction in the frequency and severity of the known doxorubicin toxicities has been observed across the dosing range. A maximum tolerated dose has not been reached in the three-weekly dose escalation study despite dosing approximately 3.5x the normal level of doxorubicin in the highest and final dose cohort in this part of the Phase 1a study.
  3. AVA6000 has shown encouraging preliminary clinical signs of anti-tumour activity. Preliminary results in the Phase 1a trial demonstrate activity of AVA6000 in patients with tumours with high FAP activity, validating the mechanism of action of AVA6000. For example, a 59-year-old male patient with Undifferentiated Pleomorphic Sarcoma (UPS) has shown a reduction in tumour volume of 65% with a duration of response >6 months and ongoing. A number of other patients with different cancer types have shown smaller ongoing reductions in tumour volume or stable disease.
  4. The next steps with AVA6000 involve optimising the patient population, dose and schedule in order to increase efficacy and tolerability of doxorubicin treatment via pre|CISIONTM. Given the favourable safety data from the three-weekly dosing study, a fortnightly dosing study, which is now screening patients with high FAP levels in the United States, will assist in optimising the schedule and dose for a potentially pivotal Phase 2 study in 2024.

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

“Targeting potent therapies to the tumour, while limiting the systemic toxicity that often characterises these therapies, is one of the holy grails of cancer drug development. The data we released today show that the pre|CISION™ modification is cleaved specifically by FAP, and not by other human enzymes, and this mechanism can be used to target the activation of a chemotherapy to the tumour microenvironment, significantly reducing the systemic exposure and improving the safety of the drug.

“The encouraging safety and tolerability observed with the pre|CISION™ platform facilitates optimisation of dosing used with existing chemotherapies by exploring higher and more frequent doses and/or more treatment cycles. The ability to target the activation of a toxic drug to the tumour tissue also makes it possible to consider using even more potent cytotoxics that could not previously have been administered as systemic chemotherapies for safety reasons.

“The potential of the pre|CISIONTM platform to change the way in which potent cytotoxic drugs are delivered, improving cancer patients’ quality of life and treatment outcomes, is truly remarkable.” 

Dr William Tap, Chief, Sarcoma Medical Oncology at Memorial Sloan Kettering Cancer Center, NY also commented: 

“These initial clinical data are encouraging and demonstrate that the novel drug delivery mechanism of AVA6000 has the potential to demonstrate single agent activity in patients with solid tumours that express high levels of FAP. The safety data when compared with standard doxorubicin are highly encouraging and demonstrate the power of the pre|CISION™ platform to avoid normal tissue effects while concentrating the toxin in the tumour microenvironment.”

Avacta’s Chief Executive Officer Alastair Smith, Chief Scientific Officer Fiona McLaughlin and Consultant Christina Coughlin will present a detailed review of the AVA6000 preclinical and clinical data, followed by investor Q&A, on the Investor Meet Company (“IMC”) platform at 11:00am GMT. This presentation will be made available via the Company’s website after the meeting.

Investors who already follow Avacta on IMC will automatically be invited to join the live stream. Investors who do not have an IMC account can sign up for free at https://www.investormeetcompany.com/avacta-group-plc/register-investor and then click “Add to meet” on the Avacta page in order to receive an invitation.

  • Download the data deck here.