In this episode of IOL Radio, we speak with Dr Albert DeNittis, a radiation oncologist at Lankenau Cancer Center in Wynnewood, Pennsylvania. Dr Dennitis is here to discuss NuView Life Science’s VPAC1, a peptide platform that detects the overexpression of specific receptors that appear only on the surface of malignant cells for early diagnosis and therapy of cancer.
Ami Peltier [00:00:00] Hi, and welcome to IOL Radio. I’m Ami Peltier, managing editor of IO Learning, a digital publication geared toward interventional oncologists, and the news source for the Symposium on Clinical interventional oncology. In this episode of IOL Radio, we’ll speak with Dr Albert DeNittis, a radiation oncologist at Lankenau Cancer Center in Wynnewood, Pennsylvania. Dr DeNittis is here to discuss NuView Life Science’s VPAC1, a peptide platform that detects the overexpression of specific receptors that appear only on the surface of malignant cells for early diagnosis and therapy of cancer. Welcome, Dr. DeNittis, and thank you for being here today. Let’s begin with the concept of binary cancer diagnostics and Theranostics. How does NuView’s approach differ from current cancer therapies?
Albert DeNittis [00:00:58] Okay, let's start out by saying, this isn’t a brand new concept. This has been around since the 1950s, but I think the science is finally catching up. So when you ask me what it is, it's a combination of using our ability to detect and diagnose cancer, but use the same techniques attaching therapeutics to compounds that would be used in diagnostics for the purpose of treating the cancers also. So, we have radio-pharmaceuticals and radio-diagnostics that have been around for a long time — one being thyroid cancer, correct? So you can treat thyroid cancer looking at Iodine-131. You can take a pill. You can diagnose thyroid cancer with Iodine-123 and you can treat thyroid cancer with Iodine-131. And what we do there, is we take advantage of what we call the cell’s ability to recognize something as foreign, and use it as part of their own, as in the case of thyroid cancer. Thyroid cells take up iodine, so you exploit that and you deliver a radio-therapeutic to kill the cancer. So, we’re just basing that on how cells normally act, not exploiting the intricacies and the complexities of cancer itself. So, now fast-forward to 2020 and you know, NuView Life Sciences is a clinical-stage oncology company based in Park City, and they've been around for a few years, but I really think things are coming together in that the discovery of certain receptors on cancer cells are to the point where we can exploit very exciting diagnostics and therapeutics.
Ami Peltier [00:03:02] Tell me about NuView’s VPAC1 technology
Albert DeNittis [00:03:06] So, Matt Thakur is a researcher at Thomas Jefferson University. He's brilliant, and basically he looked at developing an in vitro application of what's called a NuView VPAC1 oncology platform, utilizing proprietary peptides (which he discovered), constructing a target against a vasoactive intestinal peptide (VIP) and a pituitary adenylate cyclase-activating peptide receptor. So, what that all means is, the VIP receptor is on all cells in your entire body and it's what’s called a g protein-coupled receptor superfamily. They are responsible for lots of bodily functions. However, it's been discovered that the VPAC receptor is upregulated on cancer cells by millions of times.
Albert DeNittis [00:03:59] So, Dr. Thakur, in his genius, discovered a proprietary peptide that could bind to both the VPAC1 and VPAC2, and the PAC1 receptors, because they're over-expressed in the malignant cancer cells. At the earliest stages of arthrogenesis, what they do is they recruit blood vessel formation. So they're there at the onset. So you have a cancer cell that's doing its thing. It's sitting there in the extracellular matrix, and before it grows, it has to recruit blood vessels, and that's what some of these VIP receptors do. So, what's so exciting is, when I was asked to look at all this for the company, I was brought in to be on the medical board to be part of the development of the Theranostics. So, when I read through what the company has done, both with early detection diagnosis, and where we are with the potential to explode the clinical trial arena in the Theranostics, it was so exciting.
Ami Peltier [00:05:00] Right, the potential for this therapy sounds amazing. Now, tell me — which types of cancer might be most amenable to this technology?
Albert DeNittis [00:05:13] So, the receptors have been found in breast, prostate, endometrial cancer, and bladder cancers are 100% upregulated. And then you have other epithelial tumors, like head and neck and lung and pancreas, that are also upregulated but not to 100%. So you have colorectal upregulation of 96%; you have pancreas, 58%; you have lung, 65%. So, although there's not as many millions of times of amplification on some of these tumor cells, you can still exploit it because they are upregulated and then they're very detectable.
Ami Peltier [00:05:45] Oh, very interesting. So tell me, what are the upcoming or ongoing trials on VPAC1?
Albert DeNittis [00:05:52] So NuView holds exclusive global licensing in the agreement with Thomas Jefferson University and Matt Thakur. He’s director of the Laboratories of Radio-pharmaceutical Research and Molecular Imaging, Professor of Radiology and Radiation Oncology. So, we've been brought in to help expedite the Theranostics. Now, there's been a lot of research already done with diagnostics and early detection going back to 2017. There have been some amazing tests; this was initially developed looking at the potential use in PET [positron emission tomography] scanning. So, PET scanners detect the upregulation of physiology, which means it gobbles sugar. The sugar molecule injected into someone's body can be detected because tumor cells love sugar. They're using it in an expedited way to grow quickly. But you can also have an infection and things in PET scans that confuse whether it's something infectious, whether it's something — a lymph node, per se, that's doing its thing and surveying people's immune systems and doing its job by clearing cancer cells — they can light up too, because they're metabolically active at that point. So, until you have tissue and a diagnosis of a patient using tissue — that’s still the gold standard. There's never been a test to replace that.
Albert DeNittis [00:7:31] So, Matt Thakur develops a peptide with Thomas Jefferson University that binds to the VPAC receptor and on the other end of our peptide, you can bind something to survey a patient and look for cancer. So, in this case, it's copper-64. Copper-64 is a radio-pharmaceutical target with a half life of 12 hours. Copper-64 is a beta emitter and a photon emitter, and what that can do, is you can detect the presence of that in a PET scanner. So, by bonding to the upregulated VPAC receptor, with a peptide in between, and then you bind that to copper-64, you can detect where cancers are in the human body, and it's not based on physiology. It's based on the direct upregulation of the cancer receptor related to the actual malignancy. So it's very exciting, because it cuts out all background noise. There's no background uptake in the liver. There's no background excretion of glucose in the bladder (which obscures bladder), there's no background upregulation in the brain, which obviously is the most active organ in our body, so you really don't count on PET scans to look at somebody's brain, you have to do MRIs or CAT scans. So, this gets rid of the background and because you have a test which can perform early detection in the earliest stages of cancer, it can potentially have a sensitivity and specificity greater than PET scanners today. Some of those studies have been done, and they're very exciting.
Albert DeNittis [00:9:15] So, take it one step further. So now we have the ability to detect all those cancers I spoke of in a PET scanner. A cyclotron has to be modified to make copper-64. It's not that hard to do. So, wherever you have cyclotrons around our country or all around the world, you can actually modify your current cyclotron to produce copper-64.
Albert DeNittis [00:09:45] So, the biggest study, I think, that makes this very exciting is a study published in 2017 by Traboulsi and Gamella and Thakur. It looked at 141 men with prostate cancer diagnosis; 139 men presented with upregulation of VPAC receptor on cells shed in the urine. So how exciting is that? You have a potential for a liquid biopsy of extremely early-stage cancers shed in the urine before they could even be discovered with PSA [prostate-specific antigen]. We had a 97% upregulation detection in the urine. What you do is, you have the V pack receptor, then you have the exclusive peptide which we spoke of, and you can connect that to an orange fluorescence called a fluorophore — a chemical that will light up under light microscopy. So, you will have a way to detect cancer cells in the urine just by looking at it under light microscopy, which is unheard of. We don't need any expensive $3000 test. NuView has developed a test strip — you can analyze the urine, and the calculated sensitivity and specificity of this new diagnostic urine test based upon all the studies that have been done for both patients with prostate cancer and BPH [benign prostatic hyperplasia] was 99.3% and 100%, respectively. So it's crazy. You can also look at shed cells in endometrial cancer in the urine. You can look at bladder cancers. You can look at upper urothelial cancers.
Albert DeNittis [00:11:30] If you look at the prostate cancer landscape, there's about 1.8 million biopsies done here in our country — 1.5 of which are negative. So we have a test that can detect cancer in the urine, which could negate the number of men having to go for biopsy to detect the cancer. So now we do PSAs on 1.8 million men, and in all those 1.8 million men, when they’re elevated, we have to have a prostate biopsy. Like I just said, 1.5 million are negative. This test can help direct which patients really need biopsy. So if you can spare 1.3 million biopsies a year, you can potentially save billions of dollars. It will save our country, it will save our government, and it will save billions of dollars. Not to mention, any undue ill effects from the biopsy themselves, such as infection, inconvenience, and pain. So, you have a test here that not only can be beneficial in early detection and early diagnoses, it can help direct the future of millions of people per year with cancer and take them to the appropriate next steps. Now, that's where I kind of come in.
Ami Peltier [00:12:52] Can you tell us more about the role that you’re currently playing in the research of VPAC1 technology?
Albert DeNittis [00:13:00] So I was brought on as a radiation oncologist to evaluate the potential use in Theranostics or the actual treatment. So, right now, myself, and another doctor, Gil Padula. He’s brought on in the same capacity. So, we were both brought on because we've had a lot of clinical trial experience. I’m head of the Clinical Cancer Research Program at Main Line Health, which is a four-hospital system. I had a national grant looking at many different cancers and bringing cancer (trials) to the community. It's the same set of cancer clinical trials that are in academics, so there were 33 grants that went out nationally — it was called the National Cancer Oncology Research Program.
Albert DeNittis [00:13:50] So, through the NIH, in the clinical trials evaluation program they give out money to bring cancer clinical trials close to home so people don't have to travel into the big cities to be offered a clinical trial. And through these national mechanisms, both myself and Dr. Gil Padula sat on many committees to develop clinical trials nationally and set national trial clinical trial policy. For instance. I just served my term the last 3 years on the Anal-Rectal Task Force to the NIH, where you partake in evaluating clinical trials, evaluate all the newest clinical research being done, all the newest molecular research, and all the newest benchtop research, and you try to come up with translational programs that would benefit patients and moved science forward. So, we were kind of brought on here to this company to try to integrate our clinical trial experience and move forward on a national level.
Albert DeNittis [00:14:49] Now that being said, Paul Crowe, the CEO of the company has done an amazing job bringing together U.S. clinical trial sites looking at the early detection. So, there’s many clinical trial sites that Paul has brought on. There's the NIH, there is Thomas Jefferson, of course, Johns Hopkins, UCSF. We also have Jay Bishoff at Utah. It's called Intermountain Medical Center in Salt Lake City, Utah. He's a urologist there, and he's been a fantastic lead in helping develop and bring validation tests to some of the early scientific research that we looked at, looking at not only the diagnostics but the prostate cancer test for early detection. He's done another validation study which confirmed the initial studies done by Dr. Thakur.
Albert DeNittis [00:15:49] So, where we are now with that is, we're looking at trying to develop an FDA regulatory pathway to produce a prostate cancer test kit for early detection class 2 approval, looking at an ID (or investigational device) exemption. So, we're looking at hopefully filing soon an F10K for class 2 for a breakthrough device at the FDA. Just send a urinanalysis to try to help diagnose at an early stage. You’d have a down-migration of once again detecting tumors that were in basically infancy compared to where they are now, and that's kind of where we are.
Albert DeNittis [00:16:36] We're excited, looking at, not only, you know, you talked about binary. So you have diagnostics combined with treatment. So we talked about the use of copper-64. So, you can change that. You can remove copper-64 and add another radioisotope, copper-67. So, copper-67 now is a higher energy which has a half-life of 2.5 days. It's a beta-emitter, so what that means is, the energy isn't just for diagnostics, it can be used for therapy. So, as a radiation oncologist, I use lots of different beta-emitters in what I do to treat different cancers. But beta-emitters inject an energy. It's a particle and it can basically blow holes in the cancer DNA when it's close enough. So, if you have a VPAC receptor, you incorporate through the binding peptide. The copper-67 is taken into the cell and because it's a highly deadly beta-emitter, this will blow holes in the DNA.
Albert DeNittis [00:17:46] So, how does that work? That not only allows you to image where the tumors were previously, but allows you to kill the cancer because as we all know in the cancer community, you exploit the therapeutic ratio. You can kill cancer cells, because when you blow holes in their DNA, cancer cells can't regenerate or fix the DNA breaks like normal cells can. So normal cells have proteins like ligands and topoisomerases that will fix damaged DNA. Cancer cells don’t, so once you break the DNA, the cancer cells should die off and go away forever. That's the plan. So that's what we're hoping. This is really new, exciting technology that’s going to allow, not only this company, but many companies in the future moving forward, to exploit the molecular discrepancies in cancer cells.
Albert DeNittis [00:18:42] When you look at the money you can save and what you can do with this internationally? I mean, on the stage of global health, this is a home run. We've been looking for things that we can bring to second- and third-world countries that would be easily implementable through governments. Some of these foreign governments in Africa, they're giving you money to implement these types of tests. As a radiation oncologist, I think in the last Global Health Summit. I think we're short 5000 or 5500 linear accelerators worldwide, but the expense in bringing that to fruition to treat patients that are geographically spread out and the patients have to come to the machine? While things have been done and things are moving forward, something that you could bring to the people like this on a global health initiative is another home run. So this company, when I tell you is, I think, poised to bring so much good to not only the United States, but I think all patients worldwide. I think we're really at an exciting time here.
Ami Peltier [00:19:46] Now, can you tell us anything further about any specific current trials, or perhaps anything that’s in the planning stages at this point?
Albert DeNittis [00:19:56] So along with Gil Padula and myself, Dr. Jill Helmke, she's a certified nuclear pharmacist, doctor of pharmacy with 25 years of pharmacy experience and clinical research. She’s practiced nuclear medicine for 15 years at Vanderbilt University, specializing in positron emission technology and tomography, and she's part of the team. She has a unique ability in radio-pharmaceuticals and has been instrumental in developing and putting together the entire program so we can be able to use it in detection and diagnosis.
Ami Peltier [00:20:34] Has the COVID epidemic affected your research timeline in any way?
Albert DeNittis [00:20:38] We were on fire in February and everybody flew out to Philadelphia and we had a great meeting, and then COVID hit. So, it really put a damper, the last 4 or 5 months, we’ve been just dealing with what we have to in clinic and flying by the seat of our pants, but I think now that 2 vaccines have just been announced, hopefully in the next 6 months to a year, we’ll really see some sense of normalcy. So we're working hard, and what we want to do is, we want to develop these clinical trials and we have a team of people, like I said, through the NIH. We've had calls with the NIH, and their urologic team, University of Washington, Baylor, and Intermountain Medical Center with Dr. Jay Bishoff, and I think we're all going to be poised to take this to the next level.
Albert DeNittis [00:21:19] We have a multi-country conglomeration of people coming together. People who have been in the oncology arena for — you know, I've been in it for 22 years now — (we see) the same old things. Immunotherapy, chemotherapy. This is indeterminate of a specific cell type by having a potential molecular target. This is different.
Ami Peltier [00:21:41] Do you have any final thoughts on the future plans to study VPAC1?
Albert DeNittis [00:21:47] You know, the clinical trials from the treatment side, I just want to run through on a national level through hopefully all the infrastructure that's been there forever — the clinical cooperative groups that are all run for the NIH, because that gives the project real teeth and it gives us the ability to put people in on a national level fairly quickly. Now, we don't have to go that route. We can have our own consortium of U.S. clinical trial sites, which I think we do. We may not need to go that route, but I think (VPAC1) is really safe. It doesn't look like there's any damage to organs based on other previously used radio-pharmaceuticals. Same energy. Same binding capacity. Same excretion. The half-life of our radio-pharmaceuticals is even less than what’s currently used in clinical practice, which means it's not exposing kidney, liver, bladder to potentially harmful beta rays; they're just excreted fairly quickly. They don’t bind to normal cells.
Albert DeNittis [00:22:55] I think this has the potential to impact even cancers like pancreas cancer. We've been doing the same thing for pancreas cancer since the 1980s. Changing sequencing of chemotherapy, changing sequencing of potential immunotherapy, how we deliver external beam radiation (5 fractions vs 25 or 28) and that sequencing, and trying to marginalize patients and getting them to the surgical table. Think about what you can do for almost a nearly complete death sentence for pancreas cancer. With a 58%-60% upregulation on pancreas, this may double or triple survival times with pancreas or lung cancer patients. The trials have to be done, but I think looking at this just logically and how you can really exploit the therapeutic ratio, like I said, I think this has the potential to impact so many people's lives.
Ami Peltier [00:23:48] Thank you so much, Dr. DeNittis! This has been a fascinating conversation, and I really appreciate you taking the time to come speak with us today. I look forward to seeing the clinical trials on the VPAC1 peptide as you explore this technology in the coming years. That wraps up this episode of IOL Radio. Thank you again to Dr. Albert DeNittis for being my guest today. To view a transcript of this podcast or to listen to more episodes of IOL Radio, please visit our multimedia page at www.iolearning.com. Thank you for listening!
To learn more about VPAC1 technology, visit https://nuviewlifesciences.com.