Checkpoint inhibitors have transformed cancer treatment, unleashing T cells to attack immunogenic tumors with unprecedented success. Yet, many patients either fail to respond or eventually relapse, highlighting the need for more potent strategies. To bridge this gap, we are developing next-generation engineered IL-2 therapies designed to supercharge checkpoint inhibitors. By expanding tumor-reactive, T cells within the tumor microenvironment, these novel therapies aim to reinvigorate the immune response, offering new hope for patients who remain resistant to current treatments.

Recombinant IL-2 (Proleukin®) has shown efficacy in metastatic melanoma and renal cell carcinoma, but its potential is hampered by major drawbacks. Its therapeutic window is narrow, as it simultaneously boosts both tumor-fighting CD8+ T cells and immune-suppressing regulatory T cells (Tregs). Adding to its challenges, Proleukin’s short half-life demands frequent dosing, while severe toxicities further limit its use.

To overcome these barriers, Anaveon developed ANV419, an engineered IL-2 variant designed to selectively activate IL-2Rβ/γ signaling—expanding effector CD8+ T cells and NK cells while avoiding Treg activation and toxicity. Clinical studies confirmed its favorable pharmacokinetics, predictable immune activation, and improved safety, yet its monotherapy efficacy remained limited, largely due to insufficient activation of tumor-specific CD8+ T cells. These findings paved the way for ANV600, a next-generation IL-2 therapy specifically engineered to drive robust CD8+ T cell activation within the tumor microenvironment, pushing the boundaries of IL-2-based cancer immunotherapy.

ANV600 combines 2 specific components:

• An IL-2Rβ/γ-selective agonist, preferentially activating CD8+ T cells and NK cells while avoiding Treg expansion. An IL-2 molecule is fused to an antibody that sterically blocks the binding of the IL-2 to the interleukin-2 receptor (IL-2R) alpha. As a result, ANV600 signals through the IL-2R β/γ 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.
• A non-blocking PD-1-targeting antibody. ANV600 leverages PD-1 expression as a biomarker for tumor-reactive T cells, ensuring IL-2Rβ/γ-selective agonist is selectively delivered to activated T cells within TME. This enhances immune activation inside tumors, maximizing efficacy while minimizing off-target effects. Additionally, the non-blocking nature of this PD1-targeting component allows combination therapy with anti-PD-1 treatments, making it highly compatible with standard immunotherapy approaches.

A description of ANV600 can be found here:  Anaveon ANV600 SITC 2023.

ANV600 is currently being evaluated in an open-label Phase 1/2 clinical trial to assess its safety and anti-tumor activity in patients with relapsed or refractory advanced solid tumors. The trial includes both monotherapy and combination therapy with pembrolizumab, leveraging ANV600’s synergy with PD-1 inhibitors.

Find out more about Study Expand-1 (ANV600-001).

Checkpoint inhibitors have revolutionized treatment and outcomes for patients with immunogenic tumors by re-invigorating T cells in the tumor microenvironment (TME). However, a significant number of patients relapse or do not respond to check point inhibitors. Anaveon has developed a unique approach to increase the cytotoxicity of CD8+ T cells in the TME and markedly increase their ability to kill tumor cells.

IL-21 can augment anti-tumor responses by increasing the cytotoxic function and persistence of CD8+ T cells and by reducing regulatory T cells (Tregs) but can also dampen the immune response by reducing antigen presentation by dendritic cells. ANV700 is designed to direct IL-21 selectively to tumor reactive T cells in the tumor microenvironment and thus harness the anti-tumor effects of IL-21 while at the same time avoiding systemic exposure of the cytokine and unwanted side effects.

ANV700 combines a unique non-blocking PD-1 targeting antibody with an IL-21 Proximity Activated Cytokine (IL-21 PAC). The PAC consists of a tuned anti-IL-21 antibody which strongly attenuates the potency of IL-21 while allowing selective cis-signaling on PD-1 expressing cells. As a result, ANV700 potently augments the cytotoxicity and persistence of tumor infiltrating CD8+ T cells resulting in clearance of tumors in mouse models. A description of ANV700 can be found here: Anaveon ANV700 SITC 2024.

Immunosuppressive drugs are the cornerstone of transplant medicine, shielding grafts from rejection but often at a steep cost. Calcineurin inhibitors (CNIs), the backbone of most clincial regimens, excel at preventing acute rejection but come with serious drawbacks. Their use is linked to nephrotoxicity, hypertension, neurotoxicity, metabolic disturbances, and an increased cancer risk—complications that can drastically shorten both graft and patient survival. The search for safer, more effective alternatives that preserve graft function without these toxic trade-offs remains a critical and long-standing goal in transplantation medicine.

Alloreactive T cells act as the immune system’s gatekeepers, swiftly identifying donor antigens as foreign and triggering rejection of transplanted organs. By selectively removing these cells, the body’s overall immune defense can be maintained while preventing the graft from being attacked. Research suggests that targeting alloreactive T cells not only enhances graft function and patient outcomes but also opens the door to groundbreaking therapeutic strategies. Even more promising, eliminating these cells may foster immune tolerance, allowing recipients to accept their new organ without the lifelong burden of immunosuppressive drugs.

Programmed cell death protein 1 (PD-1) is expressed on the surface of T cells following activation, serving as a regulatory checkpoint to modulate immune responses. In the context of transplantation, alloreactive T cells upregulate PD-1 upon activation, making PD-1 a valuable marker for identifying the pathogenic set of T cells.

ANV200 is an Anaveon proprietary antibody which binds to a specific epitope of PD-1 that does not block PD-1L binding and signaling. ANV200 has been engineered as an efficient depletor of PD-1 expressing cells in vitro and in vivo and is currently being developed for transplantation and autoimmune diseases.