When we look at current metastatic melanoma competition, e.g. epacadostat (IDO1-inhibitor) plus pembrolizumab (anti-pd1), T-vec plus pembrolizumab, yervoy (anti-ctla4) plus opdivo (anti-pd1), PV-10 (rose bengal - now plus pembrolizumab), you'll notice several things:
First, these are all-comers trials and they aren't exceeding 58% response rates even in some subpopulations of stage III & IV metastatic melanoma. Moreover, complete responses rarely approach 25% in combinations. PV-10 has demonstrated good complete response efficacy in only cutaneous melanoma patients, and they have to treat lesions individually.
Second, most of these treatments aren't doing much for visceral lesions, which are a HUGE deal in advanced metastatic melanoma. Yervoy plus opdivo does appear to be reducing these lesions, but safety is a significant concern.
Third, many combination therapies are attempting to drive immune responses through the experimentation with multiple novel monoclonal antibodies. The problem is that most of these monoclonal antibodies, i.e. checkpoint inhibitors, simply reduce the number of suppressor cell cytokines. In other words, they aren't actually functioning to increase the number of activated and differentiated CD8 tcells, they simply reduce the percentage of cytokines that would otherwise prevent EXISTING cells from attacking tumor cells. To be clear, these mabs do have a positive effect on responses - see anti-CTLA-4 as an example - but they don't have the punch that would be found in an agent that actively recruits antigen presenting cells, stimulates t-cell expansion, and upregulates pd-1 positive phenotypes in TIL - see EP IL-12. Moreover, mab combinations appear to be causing many serious adverse events, and in some cases up to 40% of patients drop out of treatment (see combination yervoy and opdivo).
As far as Immunopulse going into deep or visceral tumors, we have no idea how well the new device and approach works. But, like you said, we should know more next month. I am very curious myself, because it could turn a one trick pony into a team of galloping ponies if they are able to safely apply the new device and plasmid payload as efficiently as they do with melanoma. There is a clear abscopal effect with EP IL-12 treatment; if they can get to those deep and visceral tumors, then I'm serious when I say the sky is the limit. Anti-pd-1 agents appear to be working in every single solid tumor indication thus far investigated (with the exception of BMY who allowed NSCLC patients with low PDL1 tumor phenotype - duh, of course an anti pd-1 won't work on those patients!). Therefore, all of these tested solid tumor types have PDL1-positive cells that can be treated using an anti-pd-1 or anti-pdL1 checkpoint inhibitor agent. All that's needed is an immune boost to drive more pd-1-positive TIL, and there probably isn't anything better than intratumoral IL-12 to accomplish that task.
Aside from the technology, which I'm obviously excited about, we do need clarity on future funding like you said, especially considering the runway is now shortened to Q3 2017. I have been trying really hard to resist the temptation to say "this company is so undervalued", but I think the threat of dilution to advance through clinical trials is keeping folks at bay.
Also, we may have some idea how well Immunopulse EP IL-12/pembro will work in metastatic melanoma, but efficacy was based on a retrospective study. The interim phase II combination data being presented next month will certainly either support or refute the retrospective study data.
Nearly every company that is using checkpoint inhibitors - and it's a lot of them! - would benefit from a therapy that would hypothetically extend use into a much larger patient population. The refractory patient population is a combination of non-responders, partial responders, and recurrent complete responders. With less than 20% of all patients showing durable complete responses with any combination of therapy, what you're left with is a large refractory population in a second-line setting for advanced metastatic melanoma. There is simply way too much incentive to ignore Immunopulse, but again, everyone needs to see the data first.
