Although recombinant IL-2 (Proleukin®) has shown efficacy in the treatment of metastatic melanoma and renal cell carcinoma, it has major drawbacks, which result in a limited therapeutic window:

• IL-2 simultaneously promotes the proliferation of anti-tumor CD8 T cells and also tumor-protective regulatory T cells, resulting in limited efficacy.
• It is only active in the body for a short time, so it must be administered three times a day.
• Its toxicity limits the dose that patients can receive.

ANV419 is a unique fusion protein comprised of interleukin-2 (IL-2) fused to an anti-IL-2 monoclonal antibody that sterically blocks the binding of the IL-2 to the interleukin-2 receptor (IL-2R) alpha. As a result, ANV419 signals through the IL-2R beta/gamma which is present on tumor fighting cells but has markedly reduced signaling through the IL-2R alpha/beta/gamma which has been associated with toxicity and reduction of anti-tumor efficacy. ANV419 has a longer half-life compared to IL-2, shows good selectivity towards preferential expansion of NK and CD8+ T cells and has a good safety profile in clinical trials.

Anaveon has described the design, development and characteristics of ANV419 in a poster available here: SITC 2020 poster 571

Anaveon is investigating the safety and efficacy of ANV419 in the following ongoing clinical trials:

ANV419-001 First in Human Study (solid tumor / lung cancer)

The purpose of this study is to test the safety and efficacy of ANV419 (single agent) and in combination with ipilimumab in patients with relapsed/refractory advanced solid tumors. The results of the dose escalation study are available in The Journal for ImmunoTherapy of Cancer (JITC, 11.2023) here: link to the publication

OMNIA-1 (melanoma)

The purpose of this study is to evaluate the efficacy and safety of ANV419 monotherapy or the combination of ANV419 with anti-PD1 antibody or with anti-CTLA4 antibody in adult participants with advanced (unresectable or metastatic) cutaneous melanoma.

Tumor infiltrating lymphocytes (TILs) are powerful immune cells which infiltrate tumors and have the potential to kill tumor cells resulting in tumor regression and clearance.  However, tumors can make TILs ineffective by imposing a genetic program of ‘exhaustion’. Targeting IL-2 to TILs is an effective way to provide specific proliferation signals which overcome ‘exhaustion’.

ANV600 combines a unique non-blocking PD-1 targeting antibody with an IL-2Rβ/γ selective agonistic principle.  This bispecific molecule targets IL-2 to tumor-specific cells resulting in their proliferation and increase of their tumor-killing potential.  This molecule is unique because it can be used in combination with anti PD-1 therapy which is the standard of care for immunotherapy of several tumor types.  A description of ANV600 can be found here:  Anaveon ANV600 SITC 2023

A first-in-human, open-label Phase 1/2 study to evaluate the safety and anti-tumor activity of ANV600 as single agent and in combination with pembrolizumab in participants with relapsed/refractory advanced solid tumors is expected to start treating patients by Q2/2024.