Trinity Delta ESMO 24: compelling data for AVA6000 and pre|CISION

ESMO 24: compelling data for AVA6000 and pre|CISION

Lighthouse | 17 September 2024

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Updated Phase Ia data at ESMO 2024 demonstrated that AVA6000 was safe and well-tolerated with standard (every three weeks, Q3W) and more frequent (fortnightly, Q2W) dosing, with no serious cardiac safety signals. Several ongoing durable RECIST responses in patients with FAP^high tumours were observed, despite being heavily pre-treated. AVA6000, the first peptide drug conjugate (PDC), is a PDC form of doxorubicin specifically cleaved by Fibroblast Activation Protein (FAP) in the TME (tumour microenvironment). At the latest cut-off, ten dose cohorts (n=57) were evaluable for safety, with 49 efficacy-evaluable patients; eight patients remain on study.
Three partial responses (PR, >30% reduction in sum of longest diameters, SLD) and four minor responses (MR, >10% and <30% reduction) were observed in FAP^high patients (n=23). These included in two salivary gland cancers (SGC) with FAP-negative tumours but stromal cell FAP expression, notably a durable confirmed PR (46.2% SLD reduction) at 12-weeks (patient now discontinued due to lifetime maximum doxorubicin dosing), and an MR (14.6% SLD reduction at eight-weeks) in a patient in the Q2W arm who remains on trial. In FAP^mid cancers (n=26), there were two MRs.
AVA6000 had a more favourable tolerability and safety profile, with reduced severe, moderate and mild treatment emergent toxicities (eg neutropaenia, cardiac safety) vs standard doxorubicin at both dosing frequencies. An MTD (maximum tolerated dose) has not been identified in either dosing arm.
Fundamental changes in the pharmacokinetics (PK) of doxorubicin released from AVA6000 vs conventional doxorubicin administration included extension of plasma half-life by c 40%, and more limited distribution into normal tissues (reducing systemic toxicities). Importantly, tumour biopsies (n=9) taken 24-hours after first AVA6000 dose indicate that tumour FAP levels appear not to correlate with the concentration of released doxorubicin in the TME, suggesting that lower FAP activity is still sufficient for active drug (‘warhead’) release. This could potentially extend the applicability of the pre|CISION platform to FAP^mid tumour types, using novel warheads.

Trinity Delta view: Data presented at ESMO 2024 provide further proof of concept, confirming that AVA6000 works as designed at both Q3W and more frequent Q2W dosing, with selective targeted release of the drug warhead (doxorubicin) in the TME, resulting in lower toxicities than standard doxorubicin and preliminary efficacy in cancers that over-express FAP and are doxorubicin sensitive. These data should guide dose and indication selection for the planned expansion cohorts in H224. Excitingly, PK data insights point to the broader potential and applicability of the pre|CISION platform in treating solid tumours with lower FAP expression (or stroma-only expression of FAP). We look forward to additional disclosures about the therapeutics pipeline and how Avacta intends to deploy the pre|CISION platform in creating novel TME targeting therapies. Ahead of H124 interims on September 30, and a pipeline review/science day in Q424, we reiterate our Avacta valuation of £675m, equivalent to 188p/share.

Lighthouse

17 September 2024


Price	70.0p
Market Cap	£249.8m
Primary exchange	AIM
Sector	Healthcare
Company Code	AVCT

Corporate client	Yes

Company description

Avacta owns two novel technology platforms: pre|CISION and Affimer. pre|CISION improves potency and reduces toxicity of cancer drugs by only activating them inside the tumour. Affimer proteins are antibody mimetics with applicability to oncology therapeutics and diagnostic reagents. 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

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