At Geneos, we believe that the clinical benefit we are observing in our ongoing trials will result in our Personalized Therapeutic Cancer Vaccines (PTCV) serving an important role in new treatment paradigms for cancer.
Cancer vaccines aim to teach one’s immune system to fight their own cancer. At Geneos, we startat the beginning – by respecting the fundamental importance of including virtually all of a patient’s tumor-specific neoantigens to create an optimal therapeutic vaccine. These neoantigens arise from gene mutations in the tumor as a patient’s cancer progresses. With Geneos’ DNA-based vaccines, the days of first trying to outsmart cancer by pre-selecting so-called high value neoantigens, are over. Past approaches have been hampered by the limited carrying capacity of other vaccine platforms, i.e., the inability to deliver the full complement of neoantigens. These algorithm-based approaches have, unfortunately, hampered success rather than unlocking it Geneos has a radically simple idea: why not just include virtually all of a patient’s neoantigens and let nature decide which ones are relevant to unleashing the desired immune response? The fundamental importance and value of doing so is now being borne out in extensive immunological mechanism of action studies from analysis of our emerging clinical data.
In our ongoing clinical trial for second line treatment of hepatocellular carcinoma (HCC), the industry-leading carrying capacity of our PTCVs enables the great majority of our patients to get vaccines with all of their neoantigens, and we have manufacturing solutions at the ready to increase this to 100 percent should doing so prove to offer meaningful additional clinical benefit.
Given the unpredictable nature of cancer, returning a patient’s vaccine for administration as quickly as possible is equally a top priority. Once we obtain the tumor biopsy from a patient, we are able to rapidly manufacture their personalized vaccine and deliver it to the patient within six to eight weeks. Further improving manufacturing speed is of utmost importance, and we have a clear path to achieving a turnaround time of three to four weeks upon commercialization.
Geneos’ PTCVs use the patient’s own immune system to induce CD4 and CD8 T cells against the tumor. The neoantigen-targeting PTCV, along with local administration of intradermal IL-12 (T cell-stimulating cytokine), is delivered via our proprietary electroporation (EP) device. pIL12 plus EP serve to optimize the effectiveness of peripheral vaccination and ensure an effective CD4+/CD8+ T cell response to those neoantigens, as has been seen in all patients studied. CD8 T cells are key cells of the immune system, seeking out and destroying foreign cells, including cancer cells. Additionally, because our immunizations occurs in the periphery, just as is typical for the other vaccinations with which we are all familiar, an impairment of the tumor microenvironment cannot hamper vaccination effectiveness. Finally, the effectiveness of Geneos’ PTCVs is not limited by low tumor mutational burden, an attribute of many of the cancers proving most recalcitrant to other immunotherapies. Thus, if successful, they could potentially be used to treat all tumor types.
Data from the ongoing second-line HCC clinical trial are particularly remarkable given that HCC is, in fact, a tumor with exceptionally low mutational burden, for which immune checkpoint inhibitors such as anti-PD1/PDL1 molecules (Keytruda®, Opdivo®, Tecentriq®, Imfinzi™, Bavencio® and others) have shown very limited activity.
As borne out by clinical data, Geneos PTCVs show the capacity to turn even these “cold” tumors “hot” and as such, when combined with an anti-PD1/PDL1, synergize to offer meaningful therapeutic benefit.
We believe that the accumulating clinical evidence strongly suggests that Geneos’ neoantigen-specific therapeutic cancer vaccines may offer an important foundational approach, with meaningful clinical benefit, to treat cancers which other current immunotherapies cannot.