Len Pagliaro Presents Siva Therapeutics at LSI USA '23

Transcription

Good morning. I'm really pleased to report this morning the merger of two companies that will have a big impact on medical device cancer treatment, the two companies Siva Therapeutics and Sona Nanotech. And I'm going to describe a little bit why this merger makes so much sense. Now, Steve has been developing a cancer treatment called targeted hyperthermia for a number of years and that cancer treatment relies very specifically on nanoparticles, gold nanorods. And they have to be made the right way. They have to be made with precision so it's a key tool. Sona Nanotech has developed a patented technology for manufacturing gold nanorods, the best that anybody's been able to identify so far. And so it's really a very logical merger of capabilities. It's a mutual unlocking of value. It's a great combination. And if everything goes well, the merger will actually close by the end of today. So it's a very exciting time for us. Now, a little background on Sona Nanotech, they have gold nanorod technology that's been used primarily for diagnostics. So far, lateral flow assays, as you all know, are very important for rapid reads, quick diagnostics. Bringing together Siva and Sona will really enable a more value added use of the nanorods for a therapeutic application. Colorectal cancer is our initial clinical target. So when you start something like this, you think where are we going to apply it? Well, as I'm sure you all know, colorectal cancer is growing. It's something that has been increasing both in frequency and affecting people who are younger and younger. Importantly, there are more and more early diagnostics for colorectal cancer, it's being caught earlier, which is, of course good for everybody. But it means that the potential to treat colorectal cancer with our medical device approach is increasing all the time. And that's a very exciting thing for all of us. So here's how we're going to apply targeted hyperthermia. Tht to colorectal cancer, two components to the system. As I mentioned, there are precision gold nanorods for injection, these are injected systemically intravenously. The second component of the system is what we call a Siva loom. It's an infrared light device, so not radiation, it's an infrared light device. The infrared light in this case, is directed through a flexible sigmoidoscopy. We're working now on development of the next generation of this device, it will basically be a fiber that passes through a free channel in the scope hooked up to a console outside. So the patient will be will be experiencing a fairly normal flexible sigmoid sigmoidoscopy and the physician will be using a tool that they're used to that they use all the time to integrate into clinical workflow. Now, the way this works is that the Nano rods are injected systemically, they circulate through the body and they concentrate in tumors, because of the leakiness of tumor vasculature known been in the literature for decades. It's called the EPR effect, enhanced permeability and retention. It occurs more in some tumor types and others. So you have to pick the right tumor type, of course, and colorectal cancer, rectal tumors are a really great initial target for this because they have a high degree of that abnormal, spongy vasculature. When you do this, we see a concentration of the Nano rods in the tumor of about seven fold over non tumor tissue. So they're not only in the tumor, but that differential is enough to really help target the heat to the tumor with the application of the infrared light. And the way this works is that the the rods absorb that infrared light and they re emit the heat. And very importantly for the treatment, they're re emitting that heat from within the tumor. So other technologies that are out there, radiofrequency microwave ultrasound, and so on, you probably are familiar with them direct heat to tumors, or energy to tumors, but they do it from the outside in. So you're passing through healthy tissue on the way into the tumor. It works to a degree but you're getting collateral damage. If you concentrate the heat in the tumor and you're heating the tumor from the inside out, which is what you want to do, then you're getting a much better response, you're minimizing collateral damage. And importantly, our goal is to heat only to a very gentle therapeutic temperature. And so most of what's out there when you're talking about thermal therapy for cancer is ablation, ablation works but it's non selective ablation, very high temperature that will basically cook anything that's in the way. Does it work? Yes, but you'll get collateral damage and it's not the one most elegant way, and certainly not the most effective way to treat tumors. On. On the other hand with with hyperthermia, gentle hyperthermia, we're going for a temperature of about 44 degrees Celsius or 111 Fahrenheit. And so this if you think about cooking meat, we're not even at the blue rare stage. This is a little bit higher than a high fever, but not that much. Important things happen at that temperature, you get stimulation of the immune system, you get shrinkage of the tumor, because tumors have different metabolism from non tumor cells, you get increased perfusion to the tumor, so drugs can do their job better. And probably this will be part of combination with drugs. And then finally, you get inactivation of cancer stem cells, which are the reason of course, why tumors come back all the time, with other kinds of treatments. So a number of good things happen at this gentle hyperthermia temperature that do not happen with ablation. We have a lot of preclinical data. These are small animal studies reduction in tumor volume on the left. And then on the right, you can see a model in which there's a large multi lobe tumor on the mouse at day zero. This was using hyperthermia in conjunction with drugs and comparing drug alone, hyperthermia alone and then the combination. And with the drug alone, all the animals were down by by 28 days with hyperthermia. 1/3 of the animals were still alive at 95 days, with the combination two thirds of the animals were still alive at 95 days. So that's an excellent result right there. We sacrifice the remaining animals did histology no evidence of tumor histologically. So certainly a very durable remission from the tumor. It looks like it's going to have similar results in large animal studies, which we're preparing to start right now a little bit more about the other aspects of Sona and Siva as a merged company. Sona has developed a number of gold nanorod based diagnostics, these are lateral flow diagnostics, you're probably familiar with things like pregnant pregnancy tests, and of course, COVID tests, a lot of activity in that field. Two that are in development currently are, first of all, a concussion test, which is very important. The growing awareness of traumatic brain injury, we heard something about that last night in the fireside chat, and then also a bovine tuberculosis test. That's another that's another disease, which is a big deal in countries, particularly in the UK. So having rapid, early, accurate tests for that with good sensitivity, and good specificity is critically important. We have a strong management team. Just a quick overview here. David Regan, Sona CEO is is here at this meeting as well. And a good team, both on the scientific side, the business side and the finance side. And we also have a very impressive group of Board of Directors and group of advisers for a company our size, we have a number of really luminaries in the field of med tech on the board and a number of luminaries in the field of science of both cancer and nanotechnology on the advisory board. So it's up there and thank you very much.