Trinity Delta AVA6000 shows signs of successful tumour targetting

AVA6000 shows signs of successful tumour targetting

Lighthouse | 17 January 2023

Share this note

Avacta has announced AVA6000 has successfully completed the fourth dose cohort of the Phase I study, with a very favourable safety profile and a marked reduction in the incidence and severity of the toxicities typically associated with doxorubicin. Importantly, tissue biopsies from six patients, representative of a variety of tumours and dosages, confirm the release of active doxorubicin at the tumour site. The tumour drug levels are materially higher than levels seen in the bloodstream at equivalent timings, suggesting pre|CISION does work as expected.
AVA6000 is a pre|CISION prodrug of the well-established cytotoxin doxorubicin, that began a two-part Phase I trial in August 2021. This is a typical open-label, multi-centre dose escalation study exploring safety, although some efficacy signals may be noted. The study was originally planned to have four cohorts of three to four patients each, for a total of 15 to 20 patients, to establish the maximum tolerated dose (MTD).
However, with 19 patients treated to date, the encouraging safety profile means that the MTD is yet to be found, therefore the study is expected to proceed to higher dose cohorts to determine this important parameter. These additional cohorts are expected to complete during H123 and will inform the recommended dose that is taken into the Phase Ib part of the trial. The Phase Ib portion will enrol up to three cohorts of 15 to 20 patients each. We note that it is at Phase Ib that evidence of preliminary anti-tumour effects should typically be seen.
Avacta’s pre|CISION platform allows for the highly selective and precise activation of chemotherapy drugs within a tumour, offering the potential to enhance efficacy and, importantly, reduce systemic toxicities for many commonly used cancer therapies. It employs a substrate which is specifically cleaved by an enzyme (FAPα) that is highly upregulated (10x to 100x more) on the surface of tumour cells. AVA6000 is the lead programme and if it successfully demonstrates proof-of-concept it would lead to a portfolio of similarly acting oncology prodrugs.

Trinity Delta view: The pre|CISION platform underpins the near- and medium-term prospects of Avacta’s Therapeutics division, and the progress of the lead programme AVA6000 effectively acts as validation of the pre|CISION platform’s tumour targeting potential. Biopsy results demonstrate a materially higher doxorubicin tumour localised concentration than in equivalent blood levels, while the fourth dosage cohort results again demonstrate lower toxicities and side-effects than would have been predicted. Although the addition of higher dose cohorts extends the results of the Phase Ia element of the trial into H123, the delay should be viewed as a positive. Successful proof-of-concept should provide the blueprint for an extensive pipeline of related products. Further detail may be shared at Avacta’s upcoming Therapeutics Division Science Day (February 23). AVA6000 is the largest single element of our rNPV model, £61.6m (equivalent to 23.2p a share), of our current Avacta valuation of £587m (or to 221p per share).

Lighthouse

17 January 2023


Price	138p
Market Cap	£367m
Primary exchange	AIM
Sector	Healthcare
Company Code	AVCT

Corporate client	Yes

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

Philippa Gardner
pgardner@trinitydelta.org
+44 (0) 20 3637 5042

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.