Avacta

AVA6000 set to start US Phase I studies in early-2022

Lighthouse | 29 November 2021

Share this note

  • Avacta has received FDA approval to start Phase I studies of AVA6000 in the US. The IND clearance, ahead of our expected timeline, allows the current UK study (ALS-6000-101) to be expanded into US clinical sites. This first-in-human study, which started at the end of August, is an open-label, multi-centre trial investigating intravenous (IV) AVA6000 monotherapy in up to 80 patients with locally advanced (unresectable) and/or metastatic FAP-positive solid tumours. It consists of an initial dose escalation phase followed, if successful, by a dose expansion phase.
  • AVA6000 is a FAP-activated prodrug of the established cytotoxin doxorubicin and is the first of Avacta’s therapeutic programmes based on its proprietary pre|CISION This exquisitely exploits the fact that FAPα (fibroblast activation protein alpha) protease enzyme is highly upregulated in over 90% of solid tumours, yet its expression is very low in most healthy adult tissues. pre|CISION employs a substrate that is sensitive to cleavage by FAPα, creating a novel drug that is only activated in the tumour site. This selectively increases active drug concentration at the target site and reduces overall systemic levels.
  • Doxorubicin is an effective and widely used anthracycline chemo-therapeutic that is part of standard of care in several tumour types. Cumulative toxicity, especially cardiotoxicity, typically limits its use to only six cycles (typically 60-75mg/m² every three weeks until 450mg/m² is reached). Despite its toxicity limitations, and being a generic drug, doxorubicin consistently posts global sales of over $1bn annually. AVA6000 offers the prospect of enabling more treatment cycles to be carried out before reaching the cumulative cardiotoxic dose. If proven successful, the US and EU market opportunity is estimated at c $1.5bn pa in advanced soft tissue sarcomas, breast, and ovarian cancers.
  • Completion of the UK Phase Ia dose escalation is expected by Q222, and that of the Phase Ib dose expansion anticipated by mid-2023. Patient enrolment in the first US clinical site is expected to start in early-2022. The dose escalation stage, involving c 20 patients with a variety of locally advanced or metastatic solid tumours, will determine safety and tolerability (although some efficacy signals may be noted) and establish the recommended dose for the Phase Ib stage. This will confirm safety and tolerability and explore preliminary anti-tumour activity.

Trinity Delta view: The extension of the AVA6000 Phase I study into the US, ahead of our expectations, is an endorsement of Avacta’s clinical team’s efforts and the quality of the preclinical package. Positive outcomes in reducing doxorubicin’s systemic toxicity will be important in establishing proof of concept of the pre|CISION platform. A broader pipeline of pro-drugs whose clinical utility would benefit from improved efficacy and reduced toxicities is being progressed. We value Avacta at £710m, or 280p per share, with the Diagnostic opportunities representing £133m and the Therapeutic pipeline rNPV £559m.

Lighthouse

29 November 2021

Price120p
Market Cap£304m
Primary exchangeAIM
SectorHealthcare
Company CodeAVCT
Corporate clientYes

Company description

Avacta owns two novel technology platforms: Affimer and pre|CISION. Affimer proteins are antibody mimetics being developed as diagnostic reagents and oncology therapeutics. pre|CISION improves potency and reduces toxicity of cancer drugs by only activating them inside the tumour. Successful clinical trials would be transformative for Avacta.

Analysts

Lala Gregorek
lgregorek@trinitydelta.org
+44 (0) 20 3637 5043

Franc Gregori
fgregori@trinitydelta.org
+44 (0) 20 3637 5041

Disclaimer

Trinity Delta Research Limited (“TDRL”; firm reference number: 725161), which trades as Trinity Delta, is an appointed representative of Equity Development Limited (“ED”). The contents of this report, which has been prepared by and is the sole responsibility of TDRL, have been reviewed, but not independently verified, by ED which is authorised and regulated by the FCA, and whose reference number is 185325.

ED is acting for TDRL and not for any other person and will not be responsible for providing the protections provided to clients of TDRL nor for advising any other person in connection with the contents of this report and, except to the extent required by applicable law, including the rules of the FCA, owes no duty of care to any other such person. No reliance may be placed on ED for advice or recommendations with respect to the contents of this report and, to the extent it may do so under applicable law, ED makes no representation or warranty to the persons reading this report with regards to the information contained in it.

In the preparation of this report TDRL has used publicly available sources and taken reasonable efforts to ensure that the facts stated herein are clear, fair and not misleading, but make no guarantee or warranty as to the accuracy or completeness of the information or opinions contained herein, nor to provide updates should fresh information become available or opinions change.

Any person who is not a relevant person under section of Section 21(2) of the Financial Services & Markets Act 2000 of the United Kingdom should not act or rely on this document or any of its contents. Research on its client companies produced by TDRL is normally commissioned and paid for by those companies themselves (‘issuer financed research’) and as such is not deemed to be independent, as defined by the FCA, but is ‘objective’ in that the authors are stating their own opinions. The report should be considered a marketing communication for purposes of the FCA rules. It has not been prepared in accordance with legal requirements designed to promote the independence of investment research and it is not subject to any prohibition on dealing ahead of the dissemination of investment research. TDRL does not hold any positions in any of the companies mentioned in the report, although directors, employees or consultants of TDRL may hold positions in the companies mentioned. TDRL does impose restrictions on personal dealings. TDRL might also provide services to companies mentioned or solicit business from them.

This report is being provided to relevant persons to provide background information about the subject matter of the note. This document does not constitute, nor form part of, and should not be construed as, any offer for sale or purchase of (or solicitation of, or invitation to make any offer to buy or sell) any Securities (which may rise and fall in value). Nor shall it, or any part of it, form the basis of, or be relied on in connection with, any contract or commitment whatsoever. The information that we provide is not intended to be, and should not in any manner whatsoever be, construed as personalised advice. Self-certification by investors can be completed free of charge at www.fisma.org. TDRL, its affiliates, officers, directors and employees, and ED will not be liable for any loss or damage arising from any use of this document, to the maximum extent that the law permits.

Copyright 2021 Trinity Delta Research Limited. All rights reserved.