Avacta

Next gen pre|CISION data unveiled at triple meeting

Lighthouse | 24 October 2024

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  • New preclinical data on two next generation pre|CISION programmes presented at the 2024 EORTC-NCI-AACR Symposium provide the first detail on Avacta’s pipeline expansion beyond lead clinical asset AVA6000. Avacta’s proprietary pre|CISION drug delivery platform technology enables delivery of highly potent payloads directly to the tumour microenvironment (TME), potentially minimising systemic toxicities and improving patient outcomes.
  • AVA6103, the first second-generation pre|CISION peptide drug conjugate (PDC), targets delivery of exatecan, a potent topoisomerase I inhibitor, to the TME. Following cleavage by the FAP enzyme, it induces DNA damage and promotes cancer cell death. AVA6103 is designed to overcome exatecan’s severe dose limiting toxicities and short half-life by modifying its PK profile and improving tolerability via FAP-targeted release in the TME. Preclinical in vivo data show that AVA6103 successfully targets exatecan delivery to the TME (increasing its therapeutic index 75-fold), where it accumulates and inhibits tumour growth; complete responses were observed in a preclinical model.
  • AVA7100 is the first third-generation Affimer drug conjugate (AffDC), a new class of engineered biotherapeutic. It consists of a novel FAP-Affimer dimer conjugated to a pre|CISION PDC linker of an undisclosed payload. AffDCs have several advantages over ADCs (antibody drug conjugates), including smaller size, and are designed to increase further the specificity of payload delivery, potentially enabling treatment of patients with low tumour FAP expression. Preclinical data demonstrate that exposure of AffDCs to tumour cell lines or fibroblast cell co-cultures result in payload release through FAP cleavage, and tumour cell killing via the bystander effect (ie killing of both antigen-positive and antigen-negative tumour cells).
  • Separately, Avacta has guided towards an AVA6103 US IND application in Q425/Q126, with Phase I development to start in in Q126. AVA7103 development candidate selection is targeted for H225, with a potential IND application in H226. Ahead of this, preliminary data from the three AVA6000 Phase Ib expansion cohorts (in soft tissue sarcoma, salivary gland cancer, and triple negative breast cancer) are expected in Q225. These data will inform the design, and indication selection, of a potentially pivotal Phase II efficacy study planned for H225. Further details on pipeline plans and the pre|CISION platform are expected at Avacta’s London R&D Spotlight Event on 30 October.

Trinity Delta view: These early preclinical data provide first insights into the broad potential of Avacta’s pre|CISION technology and the emerging highly innovative pipeline. These novel PDC and AffDC therapeutics have the potential to deliver a variety of known potent drugs (payloads) directly to the TME, limiting systemic toxicities and improving the therapeutic window. These data, plus validation from AVA6000 (September 2024 Lighthouse), indicate that pre|CISION chemistry could overcome some drawbacks associated with ADCs (ie non-specific payload release) as well as also potentially being highly applicable in treating tumours with lower or more heterogeneous FAP expression. This includes difficult to treat cancers with high unmet need, which could be addressed by next generation PDCs and AffDCs.

Lighthouse

24 October 2024

Price58.0p
Market Cap£212.6m
Primary exchangeAIM
SectorHealthcare
Company CodeAVCT
Corporate clientYes

Company description

Avacta owns the novel pre|CISION technology platform, which improves potency and reduces toxicity of cancer drugs by only activating them inside the tumour. It also owns the IP for Affimer proteins, antibody mimetics with applicability as biologics for oncology therapeutics. 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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