VAX014 intratumoral / Vaxiion Therap - LARVOL DELTA

Intratumoral Administration of VAX014 Induces Tertiary Lymphoid Structure Formation (SITC 2025) - "Accordingly, IHC analysis revealed a significant increase in the number of TLSs in VAX014-treated tumors compared to saline-treated tumors in both models (mean of 0 vs. 2.5 for MB49 and 0 vs. 2.2 for MC38) which were comprised of varied aggregates of CD11c+ DCs, CD4+ and CD8+ TILs, and PNAd+ HEVs within the tumor parenchyma. CD19+ B-cells were present but not always associated with immune aggregates.Conclusions These findings support that i.t. VAX014 induces TLS formation, suggesting TLS formation may contribute to the substantiated ability of VAX014 to potentiate response to anti-PD-(L)1 ICB.Ethics Approval These studies were conducted under animal protocol number 22-05-004Mc, approved by the Institutional Animal Care and Use Committee at San Diego State University."

IO biomarker • Oncology • Solid Tumor • CD4 • CD8 • ITGAX • PD-1

Phase 1 Study of Intratumoral VAX014 with Dose Expansion in Combination with Pembrolizumab or Nivolumab in Patients with Advanced Solid Tumors (SITC 2025) - P1 | "STUDY02002393). All participants in the study gave informed consent prior to enrollment."

Clinical • Combination therapy • Metastases • P1 data • Oncology • Solid Tumor • STING

Vaxiion Therapeutics Announces Completion of Phase 1a Dose Escalation and Initiation of a Phase 1b Dose Expansion Study for Intralesional Administration of VAX014 in Combination with PD-1 Directed Checkpoint Blockade (PharmiWeb) - "Eighteen heavily pretreated solid tumor patients were treated with VAX014 across five dose levels in the dose escalation segment of the study. In the first nine patients, a single tumor was injected with a fixed dose volume whereas the last nine patients were allowed to have multiple tumors injected. Across dose levels, VAX014 was well tolerated as monotherapy and provided strong evidence of immune-mediated antitumor activity in both injected and non-injected tumors...Based on current enrollment rates, the Company anticipates enrolling up to 30 patients in the next 12 months."

Trial status • Solid Tumor

VX0120: Phase 1 Study of Intratumoral Administration of VAX014 With Expansion in Combination With a Checkpoint Inhibitor in Subjects With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=43 | Recruiting | Sponsor: Vaxiion Therapeutics | N=32 ➔ 43 | Trial completion date: May 2026 ➔ Nov 2026 | Trial primary completion date: May 2026 ➔ Aug 2026

Checkpoint inhibition • Enrollment change • Trial completion date • Trial primary completion date • Oncology • Solid Tumor

VAX014 Activates Tumor-Intrinsic STING and RIG-I to Promote the Development of Antitumor Immunity. (PubMed, Mol Cancer Ther) - "These collective findings differentiate VAX014 from OVs by elucidating the ability of this agent to elicit antitumor activity in STING- and/or RIG-I-positive solid tumors and provide evidence that STING/RIG-I agonism is part of VAX014's mechanism of action. Taken together, this work supports the ongoing clinical investigation of VAX014 treatment as an alternative to OV therapy in patients with solid tumors."

IO biomarker • Journal • Oncology • Solid Tumor • STING

VAX014 activates multiple STING-mediated innate immune pathways to facilitate in situ immunization (SITC 2024) - "Conclusions These findings are consistent with recent reports indicating that STING agonism can activate multiple innate immune signaling pathways to control tumor growth in murine solid tumor models. Ethics Approval The described studies were approved by the Institutional Animal Care and Use Committees of San Diego State University and Dartmouth College, respectively."

Oncology • Solid Tumor • IFNAR1 • STING

VAX014 activates multiple STING-mediated innate immune pathways to facilitate in situ immunization (SITC 2024) - "Conclusions These findings are consistent with recent reports indicating that STING agonism can activate multiple innate immune signaling pathways to control tumor growth in murine solid tumor models. Ethics Approval The described studies were approved by the Institutional Animal Care and Use Committees of San Diego State University and Dartmouth College, respectively."

Oncology • Solid Tumor • IFNAR1 • STING

Phase 1 study of intratumoral administration of VAX014 in subjects with advanced solid tumors (SITC 2024) - "24-280). All participants in the study gave informed consent prior to enrollment."

Clinical • IO biomarker • Metastases • P1 data • Breast Cancer • Melanoma • Oncology • Solid Tumor • Triple Negative Breast Cancer • PD-L1 • STING

Phase 1 Study of Intratumoral Administration of VAX014 in Subjects With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=32 | Recruiting | Sponsor: Vaxiion Therapeutics

Metastases • Trial completion date • Trial primary completion date • Oncology • Solid Tumor

Phase 1 Study of Intratumoral Administration of VAX014 in Subjects With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=32 | Recruiting | Sponsor: Vaxiion Therapeutics | Not yet recruiting ➔ Recruiting | Initiation date: Jul 2023 ➔ Nov 2023

Enrollment open • Metastases • Trial initiation date • Oncology • Solid Tumor

VAX014 as a novel oncolytic agent for STING and RIG-I-positive solid tumors (SITC 2023) - "Conclusions VAX014 activates both the murine STING and RIG-I pathways and the presence of tumor-intrinsic STING and/or RIG-I leads to optimal antitumor activity of VAX014 following i. t. administration. This unique mechanism pairs STING and RIG-I agonism and subsequent Type I IFN production with oncolysis-mediated availability of tumor antigens, which together, may lead to better antitumor T cell priming."

IO biomarker • Oncology • Solid Tumor • Urothelial Cancer • STING

Intralesional administration of VAX014 facilitates in situ immunization and potentiates immune checkpoint blockade in immunologically cold tumors. (PubMed, J Immunother Cancer) - "Intratumoral administration of VAX014 stimulates local immune activation and robust systemic antitumor lymphocytic responses. Combination with systemic ICB deepens systemic antitumor responses to mediate clearance of injected and distal non-injected tumors."

Checkpoint block • Checkpoint inhibition • Journal • Immune Modulation • Melanoma • Oncology • Solid Tumor • CD8

Intralesional administration of VAX014 facilitates in situ immunization and potentiates immune checkpoint blockade in immunologically cold tumors (J Immunother Cancer) - "VAX014 demonstrated strong immune-mediated tumor clearance of injected tumors coinciding with significantly elevated CD8+ TILs and upregulation of multiple immune pathways essential for antitumor immune responses....Combination with systemic CTLA-4 blockade improved survival and elevated TILs but did not improve clearance rates of non-injected tumors. Immunotranscriptomes of non-injected tumors from this treatment combination group exhibited upregulation of multiple immune pathways but also identified upregulation of PD-1."

Preclinical • Melanoma • Oncology • Skin Cancer • Solid Tumor

Phase 1 Study of Intratumoral Administration of VAX014 in Subjects With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=32 | Not yet recruiting | Sponsor: Vaxiion Therapeutics

Metastases • New P1 trial • Oncology • Solid Tumor

Intratumoral administration of VAX014 cooperates with checkpoint blockade to reprogram tumor immune microenvironments and clear injected and noninjected tumors (SITC 2022) - "Conclusions VAX014 stimulated rapid local immune activation and lymphocyte-mediated clearance of injected tumors following i.t. administration. When combined with systemic ICB blockade, this treatment effect was systemically expanded to control or eliminate distal noninjected tumors while promoting protective antitumor immunologic memory."

Checkpoint inhibition • IO biomarker • Oncology • CD8 • CTLA4