Siva Therapeutics | Len Pagliaro, CEO

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Len Pagliaro  0:02  

Thanks very much, Steve was developing what we call targeted hyperthermia, which is a means of targeting therapeutic heat to tumors. And we're doing it in a way that's not commonly done and has advantages over the standard of care. Now, if we look at the way heat is typically targeted to tumors, first of all, the vast majority of devices out there for thermal treatment of cancer are ablative devices, they ablate tumors, they basically cook tissue indiscriminately. It works, but it's not selective. And some of the devices are expensive, required training not commonly available and so on. This is our solution, we call it targeted hyperthermia, it's 44 degrees Celsius, about 111 Fahrenheit, so we're not a bleeding tissue. But in 44 Celsius, good things happen. You stimulate the immune system, you take out cancer stem cells, you can increase perfusion to the tumor. So drugs can do their job better, and realistically, it will be used with drugs. And then finally, tumors shrink, because they have different metabolism from non tumor cells. Cancer cells are more heat sensitive than non cancer cells, they can healthy cells can withstand heat stress that cancer cells cannot. And that's due primarily to the induction of heat shock proteins in in cells, when they get heated to this temperature 44 Celsius. 44 is the best temperature to discriminate between those two effects between healthy cells and cancer cells. Here's the way we do it. It's a two component medical device system consisting of nanorods precision nanorods for injection, we've scaled manufacturing of these, they work extremely well. They're extremely safe, they're excreted in the urine and the feces, so on. And then there's a light source, which we call a Siva loom, it's an infrared light device, so it's not radiation, basically, you can think of it as a fancy heat lamp. Now, the Nano rods circulate through the body, they concentrate in tumors, and they absorb infrared light and turn that into heat. And they do that very, very efficiently. So you have heat emanating from within the tumor mass to components to medical devices, scaled manufacturing of the Nano rods, now to the pilot batch size with excellent results. And we have a prototype good prototype of the light device with an issued patent around it, and a gen two light device in development. So this technology solves two really important challenges in the field. The first is to target the heat to the tumor, ideally, you want to heat the tumor and only the tumor, and we can target the heat really well. Second, we want to achieve that temperature of hyperthermia, not ablation, hyperthermia, again 44 Celsius. So here's how the heat is targeted. The nanoparticles are essential for that they circulate through the body and they concentrate in the tumor with other types of therapy. And this includes lasers, radiofrequency ultrasound, and so on, you're basically directing energy from the outside in and it works, you can get a degree of heat to the tumor. With Nano particles, they infiltrate the body, they infiltrate the tumor concentrate in the tumor, and we can really have the heat emanating from within the tumor, which is where we want it. The difference between hyperthermia and ablation is significant. Now, here's an example with steak hope there are no vegetarians here and not to offend you if you are. But when you think about ablation, you're basically cooking tissue temperatures vary, but you're talking well done to medium well done. Steak if you want to think of it that way. Hyperthermia, on this scale is not even what's called blue rare. So we don't want to cook tissue, we just want to heat it up to the level that cancer cells are susceptible to, and healthy cells are not. And so you can really distinguish between good tissue and bad tissue that way. We have a lot of preclinical data. Here's an example of an animal study in which you can see a large multi lobe tumor 19 days out the tumors gone a little bit of scabbing on the surface of the skin. And this happens in animals very thin skin don't expect that to happen in humans. Day 59 animals healthy running around gaining weight no visible or palpable tumors carried the study out to 95 days which is a long time in mouse life. Two thirds of the animals we treated were alive, healthy, gaining weight and so on at 95 days. Finally sacrificing bit histology no evidence of tumor. By contrast, the drug of choice for this model all the animals were down by 28 days. So a significant improvement relative to drug of choice. And clearly the combination between the two is going to be very powerful heat can potentiate drug treatment it can potentiate radiation treatment and it can also be used as a neoadjuvant for surgery or initial target market is rectal surgery as a subset of colorectal surgery. Now there's several reasons for this. colorectal surgery is colorectal cancer, I'm sorry, is a huge cancer market right up there with lung cancer in the US and worldwide. And so if you segment out rectal cancer, that's about a third of the total market 6.6 billion. If we then further segment out early stage, stage one, stage two, perhaps early stage three, then we get down to what we believe is in obtainable market of 2.1 billion. So it's a substantial market. Several drivers behind this, the right tumor type, the right tumor biology, very good early detection, with tests such as color guard these days, so catching it earlier, of course, is always better. But importantly, there is a period now that's typically called watch and wait in rectal cancer and colorectal cancer. And that's because the effects of surgery can be devastating for patients. And so there's typically drug treatment early on radiation treatment early on, and then a watch and wait period. If the cancer goes into remission, terrific. If it doesn't, then surgery comes down the road. Well, that's a window where we can integrate. And we can integrate extremely well, we can integrate well with surgical workflow. And it provides an opportunity for existing treatments to be enhanced and improved by adding hyperthermia to the mix. Here's what we think the patient experience will look like outpatient procedure, minimally invasive, no real special tools or treatment needed except for the infrared light source, which can couple to a standard flexible endoscope. So the patient goes to the clinic one day, they have an injection, they come back 12 to 18 hours later, after the material, the Nano rods have circulated through the body concentrated in the tumor. And then they have a 10 minute treatment and discard quickly with infrared light in the region with a tumor or tumors. So a really quite a simple procedure. In animal studies, one treatment of one injection and one treatment with infrared light has been very, very effective. We don't know if that's going to be the case in humans. But clearly, it's not going to be a large number of treatments, perhaps. A number of advantages over competition, I won't go into all the details here close competition in the first couple of lines, and then more distant competition below that. But I think important features is that what we're doing is very, very safe. It's very minimally invasive. It is something that integrates well into current clinical workflows and requires a minimum of specialized equipment. Intellectual property, we've got an issued patent around the light device. Next one is in process a second generation light device, we've gotten an exclusive license around the polymer coating for nanorods critically important to make this all work. And we're working on a second generation patent for polymer coating. And then finally, a body of of knowledge, trade secrets and know how around manufacturing scaling, manufacturing is critical. We need to do this on a commercial level. This is not academic research. And so that's going to be turned into IP we anticipate over the next year. We've accomplished a lot over the years. And going forward, we've got a lot more to do. But we've got a pretty good roadmap for it and we have a pretty good feel for what we need to do. Initially, we're working on focusing on raising $2.1 million to complete large animal studies. And that's a fairly tractable project. We've got good plans in place for doing canine and mini swine studies. The next steps down the line will involve filing for the de novo pathway, we believe we will be on the de novo pathway, which is a good thing because it limits the scope of later clinical trials. So we're anticipating a pilot feasibility study of about 35 patients. And a pivotal study again as medical device of about 100 patients. encouraging signs in the industry, we see a lot of m&a activity around injectable medical devices. We've got a strong team, all of us on the core team on the left have developed products and brought them to market and a growing group of advisers. We're raising a 2.1 million round, as I mentioned, and we're about a quarter of the way into it with great investor response so far. So thank you very much.