At Agenus, our extensive experience in immuno-oncology has led us to the forefront of cancer candidates with our three platform technologies:
Prophage™, an individualized vaccine made from a patient’s own tumor tissue
AutoSynVax™, a vaccine uniquely designed and manufactured for each patient based on their tumor profile
PhosphoSynVax™, an off-the-shelf vaccine targeting a novel class of tumor antigens.
All three platforms are designed to treat cancers based on the unique needs of each patient. Most cancer cells carry unique mutations or biochemical signatures (for example: protein phosphorylation patterns) that are not present in healthy cells. Our vaccines are either based on these specific mutations found in the tumor cells of the patient or on aberrantly phosphorylated proteins that are specific to different types of cancer and/or patient. Our platforms are designed to alert the patient’s immune system to recognize these differences by targeting mutant protein antigens. The result would be to attack cancer cells while leaving healthy cells unaffected.
The Prophage vaccine platform involves extracting peptides (protein fragments) from a patient’s tumor that are naturally bound to heat shock protein gp96 (HSPPC-96), allowing us to identify key proteins of interest. Subsequently, Prophage is designed to mobilize multiple immune processes to attack the tumor.
We are currently conducting clinical trials of Prophage vaccines in glioblastoma, a form of brain cancer. The standard of care treatment for glioblastoma is surgical resection, when possible, followed by radiation and chemotherapy. With today’s treatments, the vast majority of patients survive only 16 months or less.
At ASCO in June of 2015, we reported results from a single-arm, open-label, multi-institutional Phase 2 trial of Prophage in newly diagnosed glioblastoma (ndGBM) in combination with the standard of care treatment of surgical resection, radiation therapy and temozolomide chemotherapy. We reported that patients with ndGBM had a substantial improvement both in progression-free survival and overall survival with Prophage combined with standard of care compared to historical control data.
In addition, it was found that the most significant improvements (median progression-free survival approximating 27 months, median overall survival approximating 44.7 months) were seen in the seventeen patients with less elevated expression of the checkpoint protein PD-L1 on the circulating cells known as peripheral blood monocytes. This suggests that patients, who are thought to be less immuno-suppressed when first diagnosed with ndGBM, could benefit from adding Prophage vaccination to standard of care. It also raises the possibility that Prophage may be beneficial in the other half of patients who are more immuno-suppressed (those who have greater PD-L1 expression on peripheral blood monocytes at baseline) by adding checkpoint modulators that block PD-1 or PD-L1 to Prophage plus the standard of care.
The immune system has the capacity to “see” cancer antigens or mutated molecules on cancer cells as foreign or abnormal and unleash an attack that destroys these cancerous cells. However, the number of mutations varies from one patient’s tumor to another. Current research suggests that our natural immune defense mechanisms may be insufficient to eliminate cancers in cases where mutations are too few in number. Even when cancer cells display many mutations, they can evade effective recognition by the immune system through a variety of immunosuppressive mechanisms. Agenus’ AutoSynVax cancer vaccine is being designed to boost immune recognition of cancer antigens to a higher level than that which is achieved naturally. The vaccine therefore may help the immune system better recognize cancer antigens even if there are only a small number of them on a given patient’s tumor. AutoSynVax is expected to work synergistically with other forms of immunotherapy including checkpoint inhibitors and other checkpoint modulators that counteract immune evasion mechanisms.
AutoSynVax is an individualized vaccine made by combining synthetic versions of each patient’s own cancer antigens with heat shock protein 70 (HSP70). HSP70 is known to transport protein fragments called epitopes and to play a part in displaying them to T cells, immune cells that, when sufficiently activated, can mount a potent anti-tumor response. We identify the unique genetic sequence of an individual patient’s cancer and apply proprietary computational tools to predict which mutations, unique to that patient, are likely to be displayed by the tumor in the form of “neo-epitopes.” Accurate prediction of these neo-epitopes increases the likelihood that our AutoSynVax vaccine will stimulate a robust T cell response against tumors.
We then synthesize these neo-epitopes in the form of short peptide sequences. After linking these peptides to HSP70 in our GMP-certified manufacturing facility, we plan to administer AutoSynVax vaccine along with our QS-21 Stimulon® adjuvant to provide maximum efficacy. By including numerous synthetic cancer antigens in each patient’s AutoSynVax vaccine, we increase the likelihood that tumors will be recognized by the immune system.
Our third vaccine platform is PhosphoSynVax, based on technology we obtained when we acquired PhosImmune. PhosphoSynVax is being designed to induce immunity against a novel class of tumor specific neo-epitopes: those arising from inappropriate phosphorylation of various proteins in malignant cells. In cancer cells, the disruption of normal biochemical signaling can result in aberrant protein phosphorylation (the addition of phosphate groups on sites that would not be altered in normal cells). Some of these misphosphorylated proteins can be processed into antigens by the cellular machinery, resulting in presentation of this new type of antigen on the cell surface.
We have a library of more than one thousand proprietary phosphopeptide tumor target antigens characteristic of many different cancers, including lung cancer, specific leukemias, ovarian cancer, colon cancer and others. We believe that using our PhosphoSynVax vaccines to teach the immune system to recognize these neo-epitopes can lead to the destruction of cancer cells. This technology is thus unique to Agenus and potentially very powerful in various patients across cancer types.