Len Pagliaro, Siva Therapeutics - Targeted Hyperthermia Against Cancer | LSI Europe '22

Transcription

Len Pagliaro  0:03  

Thanks very much, Danny appreciate it. So there are a lot of thermal treatments that are used for cancer currently. But the overwhelming majority of them are for ablation, very high temperatures that essentially cooks in teenagers tissue. It works, but it's non selective. And it's either capital equipment like this, or it's equipment that's designed to be used as part of major surgery. So high cost, not commonly available, invasive, and so forth. The approach we're developing, and this is initially for colorectal cancer is going to be much simpler in terms of the patient experience and in terms of the provider experience as well. It'll be minimally invasive, and it'll integrate into existing clinical workflows. Now, there are several important things that targeted hyperthermia does that ablation does not it stimulates the immune system, it kills cancer stem cells, which tend to make tumors come back, of course, that's why they return over time, it increases perfusion to the tumors, so the drugs can do their job better. And then finally attracts tumors directly because tumors have different metabolism from non tumor cells. Hyperthermia, and ablation are very, very different. They're both heat. But if we think about cooking meat, it's it's quite different. ablation is medium, well, too well done. It's thoroughly cooked meat. Hyperthermia is not even what on this scale is called blue rare. So they really are quite different. We don't want to cook tissue, we want to warm it up to this gentle temperature. And the reason is that cancer cells are more heat sensitive than non cancer cells. So cancer cells tend to go into a cycle of Apoptosis and necrosis when they are heated, healthy cells can withstand that stress. And that's because of the induction of heat shock proteins, which tend to be overexpressed in cancer cells. So there's a natural selective mechanism. That's part of the cancer process. Now, the way we do this is with a two component system, there's a lot of work that's gone into developing the system. But importantly, it's easy to use, and it integrates into clinical workflows. So the first component is nano rods, they're injectable, nanorods, systemically injected nanorods, they're truly Nano 12 by 45 nanometers, very safe, clear the body and so forth. The second component is infrared light, so it's not radiation, it's infrared light, basically, it's a fancy heat lamp. And the two together combined to make what we call targeted hyperthermia. And so that's heat that emanates from within tumors. Now, there are two main challenges in the field of thermal therapy for cancer that these approaches solve. The first is targeting the heat to the tumor, ideally, you want to hit the tumor and only the tumor. Second, is achieving this level of hyperthermia instead of ablation, it's higher than a high fever, but not that much. And it turns out, it's harder to achieve and maintain that temperature than it is to ablate tissue. And we can do both of them. The way the material gets concentrated in tumors is because of the natural physiology of tumors, tumors as they grow, need more blood flow, and the capillaries that supply blood tend to get leaky leaky vasculature. It's known as the EPR effect. And that enables us to develop particles that will concentrate in tumors, they'll basically leak into tumors faster than they leak out, reaching a maximum concentration and tumors 12 to 18 hours after injection. The second thing that this does is enabled us to heat from the inside out. So the current technologies that are out there, and this is radiofrequency magnetic and so on, they're basically heating from the outside and you're directing energy from the outside in, and you're passing through healthy tissue on the way to the tumor. When nano particles are added to the equation, they concentrate in the tumor, infrared light passes through tissue harmlessly passes through up to a centimeter up to an inch, I'm sorry, to a half centimeters of tissue. And then to get deeper into the body. Of course, we can go through endoscopes flexible endoscopes, with the infrared light. And so you can direct the infrared light wherever you want, it will be absorbed by those narrow rods and then they readmitted very, very, very efficiently as heat. So heat emanates from within the tumor, and the nanorods are concentrated in tumors. So the heat is concentrated to the tumor. We have a lot of preclinical data from small animal studies from laboratory studies. Just to give you an idea, a snapshot of some of the data. Basically, there are two things you want to do in cancer. You want tumors to get smaller and you want animals to live longer. When you're doing animal studies, and we do both of those tumor volume decreases, and the survival of the animals increases dramatically. This is an example of a study in rodents, where you can see a large tumor mass on the left, same animal and all the pictures, tumors gone in the middle. 59 days out The animal is fine healthy, we actually carried this particular study out to 95 days, which is a long time for animal studies. All the animals that were still alive, two thirds of the animals were still alive, they're healthy running around, no evidence of tumor histologically. In contrast with the drug of choice for this model, all the animals were down by 28 days, so a significant improvement over drugs. Our initial market is rectal cancer as a subset of colorectal cancer. It's an important market with an unmet need a large market and one that has great need, because surgeons delay surgery for rectal cancer because of the grave side effects of rectal cancer surgery. devastating for lifestyle. So a huge unmet need and an area where we can integrate into clinical workflow. Patient experience will be very simple. They go in one day, they get a systemic injection of Siva rods, they come back to the clinic 12-18 hours later, and they get a 10 minute treatment with infrared light using a flexible sigmoidoscopy. A lot of advantages over competition. We don't look to compete directly with surgery, radiation, drugs, we are the only offering out there that we know that can provide true hyperthermia this gentle temperature 44 Celsius that we know of. We have strong intellectual property company on patent and exclusive license to another patent know how and trade secrets around the manufacturing process which is critical and more patents in development. We've done a lot over the past several years, in terms of getting grants in terms of proof of concept completed a very rigorous program funded by the federal government in the US the Nanotechnology Characterization Lab. And that brings us to where we are now, which is raising two and a half million dollars to complete large animal studies get permission to go into the clinic, we will be on the denovo pathway, which means that we anticipate a pilot feasibility study about 35 patients and then a pivotal study of about 100 patients with series A and B raises subsequently of 8 million and $20 million. There's a lot of encouraging sign in the industry currently in terms of m&a activity in the interventional oncology space, including injectable particles that are now being acquired by by major medtech companies. So very encouraging for us. We've got a strong team. Our core team on the left has three members, all of whom have brought products to market in previous companies, three of which have been med tech companies, several of which have been drug companies, drug development companies and tools for drug discovery, and a growing list of advisers on the right strong advisors. We're currently raising $2.5 million round. As I mentioned, the overall objectives are very simple to complete large animal studies and prepare to enter the clinic in the US very excited to announce that we do have a significant commitment from a strategic partner for this round already. So we anticipate closing in q4 of this year. So I'll stop there. Thank you very much.