Thank you, Mark. Good afternoon to all of you joining us here in New York and on the webcast. I'm Kathleen Fredriksen, Director of Corporate Development. We are delighted that you have chosen to be a part of Progenics' first ever Investor and Analyst Day. Let me take a moment to get you oriented before be begin. We designed today's program to give you a deeper, longer look into topics that have been marked as areas of greatest interest to the investors and analysts with whom Mark and I speak at various industry events. So today, you'll hear a lot less from Mark than usual. Was that an audible gasp of relief or just me? And that will give you an opportunity to hear from our guest speakers and internal experts, who will cover targeted radiotherapy and molecular imaging, the important intersection of imaging and cancer therapeutics, updates on our clinical and R&D programs and our view of the business development landscape. Mark will wrap up at the end with reflections on the day.
We invite you to ask questions of our panelists at 2 points in the program this afternoon, and I would ask that you hold the questions for these allocated times, so we can keep the program moving and be respectful of your schedules. If you did not pick up a flash drive when you registered, please take one when you leave. We have loaded all of the presentation slides today and some additional animation slides for you to take with you.
With that, I invite our first speaker, Mark Baker, to get us started.
Mark R. Baker
Good afternoon, and welcome to the people here in New York and to those listening to us on the WebEx. It's our first Investor and Analyst Day, and thanks to all of you who poked and prodded and encouraged us to have an Investor and Analyst Day. And we plan to make this a regular occurrence. Today, it feels like a great coming-out party for us as we lay out for you our vision of becoming a preeminent oncology company. Today, we also launched our new website, and we invite you to visit that at www.progenics.com. And it's a great moment for us to meet -- for you to meet the managers and scientists who are leading the company forward, both new and old.
I'd like to spend just a minute introducing the managers of the company who are here in the room with us. And the first person I'd like to introduce is our newest member, Hagop Youssoufian. Hagop joined us just 3 weeks ago. He reminded me earlier. He comes to us with an amazing background in drug developments, both in big pharma and in biotech, most recently serving at ZIOPHARM and before that, as Chief Medical Officer at ImClone. Hagop, will you just stand up and let everybody see who you are? There you go. Thank you. Other senior managers present here with us: Bob Israel, Medical Affairs, there's Bob; Bill Olson, R&D, there's Bill; Ann Marie Assumma, Regulatory; Vivien Wong, Project Management, there in the back; Angelo Lovallo from Finance; and Jim Garrison from Business Development. Thanks, Jim.
That's courtesy of our lawyers. So I wanted to show you, if we have had an Analyst Day last year, which we didn't, this is how our pipeline would have looked. And this is the pipeline as it stands today. I don't want to bog us down with the CEO's vision, but I just want to provide you with a brief roadmap of what our programs and assets are as you hear about them in depth today. We have our imaging agents, our 1404 imaging agent, which is in Phase II development using the SPECT-CT camera systems. And also, we have an imaging agent currently in Phase I testing by an investigator.
We have our PSMA-targeted therapeutics, our antibody-drug conjugate, which you've been hearing about for many years, in Phase II as well, and also a small molecule program that came to us from Molecular Insight.
In addition, in the oncology area, we have our ultra-orphan Azedra for the treatment of pheochromocytoma and other diseases, which is under a SPA agreement with the FDA, and early-stage work we're doing in the kinase field.
Of course, a very important asset for Progenics has been RELISTOR, our treatment for opioid-induced constipation. We don't plan to give you any presentation with respect to RELISTOR today, but we'd be welcome -- we'd welcome questions in the Q&A period if you have questions about RELISTOR.
And finally, we have our partner programs, PRO 140 program. And our program in C. diff, and Jim Garrison from our Business Development Group will tell you about the partnering process and how that's adding value to Progenics.
So I'd like to take an opportunity to introduce to you John Babich. John was the founder of Molecular Insight, the company that we acquired in January. And it's been our very great privilege to get to know John over the last 6 months. He graciously has worked with us to transition the Molecular Insight assets and programs, and he's brought his knowledge and wisdom to our team. And for us, it's been a great time. He will be joining the faculty at Cornell in September, and hopefully, he'll get a little break before he turns to his new assignment. But we're pleased that he'll continue to work with us as an advisor. So starting us off, talking about targeted radiotherapy and molecular imaging compounds, this is John Babich.
John W. Babich
Thank you very much, Mark. It's a pleasure to be here and to see so many people braving the heat. So without much ado, I'm going to cover a number topics. One will be our prostate cancer imaging program, Azedra, the status of Azedra and some preliminary data on our molecular imaging -- sorry, molecular targeted radiotherapy of prostate cancer.
So first up, imaging prostate cancer. Obviously, prostate cancer is a significant healthcare issue. Globally, there's more than 1 million men who'll be diagnosed on an annual basis, and 0.25 million men will die every year from this disease, if not more. And we expect there to be a doubling in the number of patients with prostate cancer by 2030. Overall, in the United States, at least there's about 240,000 -- 250,000 new cases per year and about 35,000 deaths a year in the U.S. And obviously, this number is much greater and include the rest of the world. And we also know that this is not only a disease that has the opportunity for cure but also has an opportunity and a lot of unmet need in trying to wrestle with the issues of metastatic disease.
So if you look at the natural history of prostate cancer, you basically -- this diagram shows basically the PSA level of a patient through their history, assuming that they're not cured at the very beginning. PSA is an indicator of potentially something wrong, although not always the case, and then progression of disease and possibly the response to the disease, but it's not a great indicator at every step of the way. Patients go from being asymptomatic to symptomatic, from being non-metastatic to metastatic and being sensitive to androgen-deprivation therapy and then not. And so we know we have the potential for curing men very early on. If we catch the disease when it's isolated to the gland, then we have a very good chance of curing those patients. But if we find the patient after the disease has escaped the gland, then other than suppressing growth for some time with androgen-deprivation therapy, there is no cure for that disease. And so there's an opportunity, really, there as well. And we know that this space has been very heavily investigated by a variety of investigators and companies in terms of later stage.
What's the status of imaging in prostate cancer? Well, for those that are not that familiar with prostate cancer, from an imaging perspective, there's no way of really imaging primary disease. So this is a huge unmet opportunity. There's a lot of work going on in this space, primarily with MRI, some with ultrasound as well, but it's not really clear that you can see disease in the gland itself. In terms of nodal disease or the local spread or even distant nodal disease, CT and MRI are the mainstay, and the mainstay basically looking at, really, the change in size of nodes outside of a predetermined size criteria, which, right now, for [indiscernible], is about 1 centimeter. And then looking at distant metastases, really looking at bone scan, even with technetium and conventional [indiscernible], more recently with sodium fluoride as a PET imaging modality. But there's a -- prostate cancer working with the published date in AJR in 2009, and they really came to an interesting conclusion. The current stand at imaging techniques, such as ultrasound, MRI and CT nuclear medicine, cannot detect early disease, but they really don't do a good job in detecting the disease beyond that primary disease.
And that being said, we also know that if you look at the NCCN guidelines, that there are already algorithms for treating and managing patients based on data from imaging. And what we hope 1404 becomes is the new replacement for all of these places within the NCCN governance where imaging is indicator in order to make a treatment decision.
So here are just the initial clinical assessment. Depending on life expectancy and grade of disease, you would or would not ask for a bone scan. You would or would not ask for CT and MRI to evaluate a local regional spread.
If you go through the rest of the guidelines, you'll see there's also imaging required for doing radiation therapy. So IMRT, which is a way of trying to avoid damaging normal tissues but really focusing on the prostate cancer itself, requires that we have some other way of looking at this disease to determine whether or not the cancer is actually present in the area or the volume that we're going to radiate. And of course, if you look at post-prostatectomy recurrence, you really want to find out where the disease is, again, to either go in and do a second-look surgery or do radiation therapy, or to determine that either is going to be curative and then move the patient on to another treatment. Similarly, for radiation therapy recurrence, again, imaging is part of the workup and part of the management. So we're implementing a new imaging technique in which there's no answer to the data, but we're actually trying to supplement what's already required within the guidelines and actually bring a better way of imaging the disease.
The way we want to do it is through PSMA imaging, and that's really try to take a protein that's expressed on nearly all prostate cancers and find a way of binding an agent to that target. We like small molecules of Molecular Insight. We really -- we like the fact that there's a lot of work done with modifying antibodies. They gave us an idea what to go after from a target perspective. And there is a lot of similarities between what the targets we like and what was there already ahead of us in the antibody space. We really like small molecules because they have the ability to be manipulated relative to their pharmacokinetics, relative to their binding affinity, relative to their ability to clear from the normal tissues. And when you think about imaging as being able to see bright stars on a dark background, we really don't want a lot of light. We don't want other signal coming from things. We want to be very specific to the cancer. PSMA is lovely because it's on the external surface of these prostate cancer tumors. There is a enzymatic component to it. We know where that is. It's a poly -- it's a glutamate carboxypeptidase, and we know there's a substrate for that. And so that substrate becomes our lead structure, and I'll talk about it in more detail in a second.
If you look at the expression of this, it's almost on every prostate cancer that's been at least written about in the literature from an immunohistochemical perspective, somewhere from 85% to 100% of all tumors that have been written in order to show PSMA expression.
And one of the things we really like about this from a primary disease perspective is that that PSMA expression increases with Gleason score. So the early or low Gleason score, where the question is, is this really a tumor yet, or the very high Gleason score, where there's unequivocally an aggressive disease, PSMA expression goes up. And that actually is nice because we can actually see them. I'll demonstrate that to you.
Also, BPH has no PSMA expression on the external surface of the cells. So we're hopefully not going to be confounded with BPH in this case.
The work that we started back at Molecular Insight really had to do -- nothing to do with prostate. We're actually looking at NAALADase inhibition, which actually turns out to be a homologous protein. And we were looking at ways of inhibiting glutamate carboxypeptidase activity in NAALADase, where the enzyme will cleave glutamate from this small NAG peptide.
But what we had done once we knew what this was all about, we also realized back about 1998, 2000, the homology would allow us to go after prostate cancer with compounds that would also bind NAALADase. And we were working with a group at Georgetown, Alan Kozikowski, who had developed this compound for NAALADase inhibition, spinal cord injury, neuro generation, and it turned out that this compound, what was a [indiscernible] compound, was a very interesting compound, very simple to make. And you could derivatize the compound at the S1 prime region of this molecule, meaning that you needed only those 3 carboxylates that are in red to actually bind PSMA, and then you can manipulate this other area that we've shown you with that yellow outline.
And what that does is allow you to add things to that, not only where the nuclei is potentially drugs as well. So we actually went after this target with a technetium-labeled compound. We love technetium for all kinds of reasons. You don't hear about it much anymore. But 25 million nuclear medicine scans worldwide, 80% to 90% of them are done with technetium on a daily basis. Technetium is low cost. It's available everywhere, every hospital in the United States that's JCAHO-accredited has to be able to do nuclear medicine scanning with technetium and SPECT imaging. So it's everywhere, literally, in the Western world. And it's relatively inexpensive. It also allows you to make a final preparation of a drug in a pharmacy, in a nuclear pharmacy. Right now, Cardinal Healthcare is the biggest nuclear pharmacy business in the country, and they basically have 90% of the market in the U.S. -- or can touch 90% of the market.
So we can eventually put our compound as a GMP product into this vial, give it to nuclear medicine departments all around the world or Cardinal or other radio pharmacies. And every morning, they can prepare a syringe, send it to a hospital and have the studies done on a daily basis. It doesn't require GMP synthesis at that step, which is unlike a lot of PET radio -- actually, all PET radio pharmaceuticals are required to be synthesized at the time for that dose and the GMP methodology, on top of which we have our IP.
So the structures we started with are in the middle, the glutamate-urea-glutamate homodimer, then we went to these others. The 4 compounds on the edges of the slide have all been introduced into the clinic. The ones on the left-hand side were the first ones we put into man. They were iodine-123-labeled compounds because we had a hard time making the compounds on the right. Initially, that weren't highly hydrophobic. And then these compounds, I'll come back to them because it turns out that the bottom left-hand compound turns out to be a really interesting one potentially for therapy.
The one we'll talk about now is on the right-hand side. It's the 2 nanomolar compounds. It's our imaging lead. It's right now in our Phase II international study. So a little bit of background, just bore you a little bit with pharmacology. These compounds show very high affinity, both on a competitive binding assay, and we've looked at, literally, hundreds of compounds before we isolated these compounds that we took into the clinic, and also on the saturation binding curve. So both of them showing a low nanomolar affinity. They're very specifically -- taking these 2 results specific to PSMA. So if you look at the bars here on the left-hand side, LNCaP tumors which have PSMA expression have very high binding PC3s, which are also a human cell line, have no binding. And all the activity that we see on the LNCaPs can be obliterated with either cold compound, which will just displace it, or a compound such as PMPA, which is a compound that is being developed by Guilford Pharmaceuticals that also binds glutamate carboxypeptidase domain of PSMA.
On the right-hand side, just showing how these compounds internalize once they bind to PSMA. They actually get pulled in. And interestingly enough, the small molecules are retained for hours, if not days, within these cells. That actually turns into something really positive for us because it allows us to image these. This is a quantitative assessment of tissue distribution in mice with LNCaP tumors. So these are human PSMA-positive xenografts, and 15 minutes after injection, if you look at the red bars, the only thing you really see, there's a couple of organs that we see some activity early on, but the kidney and the tumor, the ones that stand out, and then after 15 minutes, basically, that's all you see is kidney and tumor. There is a good reason it's in the kidney, 2 of the reasons. One is there's very high expression of PSMA in the renal cells of the kidney in the mouse. And of course, the tumor has PSMA as well. So taking that data, here's the image of the same kind of xenograft. Only the tumor on the bottom left-hand side and the kidneys in the middle and a little bit of a bladder activity is seen in scans about 2 hours after injection. So these are part of the preliminary data before we took this into man. We took this into man under exploratory IND, and our preliminary findings were very, very interesting. We saw no signal whatsoever from the cold material at 200 or 300 times the human dose. So looking at this from a pharmacological perspective, other than binding PSMA, these compounds appear to have very little pharmacological activity in everything -- in all screens that we looked at. And some of these were classic [indiscernible] screens for receptors and transporters and other enzymes. So we have -- on top of which we'll wind up injecting about 20 micrograms of this compound into man for the clinical scan. So very high safety margin, we believe, to expect from this compound.
Clinical trials, we started them at Cornell Medical Center. We have a long history like Insight has, as well as -- as I came to Progenics, they also have been using Cornell as investigators of some of their trials with the PSMA ADC, and we have been working with many of the similar groups. With the nuclear medicine group, we've worked with for quite a long time here, and they were part of the initial trials that we performed. We did several Phase I studies under exploratory IND. And these included -- instead of looking for a needle in a haystack, these are -- I call them these haystack studies. We ran them to make sure the compounds work. We took them into man who had known prostate cancer by biopsy and also radiographic evidence of metastatic disease, looking for that first patient with a little bit of positive activity on a biopsy. We're actually looking for people that had well-developed metastatic disease so that we could actually look and see whether or not these compounds are going to work, we then backed into the pre-prostatectomy patient population.
So again, the IND was -- an exploratory IND, it allows you to actually move very rapidly into man and take multiple compounds of the same class into man and compare them in the same patients. This is the first subject that we had done, first normal subject. On the left-hand side, one of the technetium compounds, you see this mask, the snowman mask. And what you're actually picking up in the head is the lacrimal glands, the salivary glands and the parotid glands, all of which have PSMA expression. You then see, as you come down, I think I have a pointer here, sort of highlighted the liver and the kidneys, which have PSMA expression. You see loops of bowel, and there's a little bit of bladder down here with this compound. So this is about 4 hours after injection. This is a planar nuclear medicine scan. This is a patient looking at you, subject from behind. And again, this particular subject, it actually had been studied previously with our 1072 compound. And you see extremely similar patterns here, a little bit more in the liver with this compound. They're very similar in terms of the glandular activity in the kidney and the bowel.
This is one of the first patients we've done with 1405, and one of the things we're looking at is the ability to see disease anywhere in the body. If I focus you the 2-hour images, again, you see this sort of glands in the head. You see activity in the shoulders, from the front, and you see activity in the lymph nodes here. From behind, they become more clear. And this is looking at 2-dimensional image -- sorry, 3-dimensional body in a 2-dimension, so you're compressing this. But you see a lot of bladder activity all the way through here. And that's something that we don't like because this disease starts in the gland right below the bladder. This is 1404, which is the compound we eventually went with, and you can see here, although early on, after injection, there's some activity in the bladder. Once they void, there's very little activity in the bladder. Then that allows us to do a couple of things. We can see disease that's back where the prostate used to be. We can see these tiny little lymph nodes that are here that are adjacent to the bladder. But since we don't have the bladder, we can see nicely, and you can delineate all the bony lesions and soft tissue lesions.
This is the same patient. Now I just zoomed in. And this is his bone scan on the left-hand side. And what you see in the bone scan is disease in the skeleton, the shoulder, the ribs and the spine. You also see arthritis in the wrist, in the knees and the feet. If you notice, on the right-hand side, we don't pick any of the arthritis up, and this is -- there's a reason for that. We're not looking at bone remineralization, which is what the technetium fascinates at doing and what sodium fluoride would do. They're being pulled into the bone to recreate bone that's being damaged by the presence of tumor. We're actually looking at the presence of the tumor, so we're not picking up degenerative changes in bone. We're actually picking up the actual tumor mass that's sitting in the bone or sitting in normal tissue -- in soft tissues, such as here, these lymph nodes, these 2 tiny lymph nodes, and in the soft tissue within the prostatic fossa.
Here's another patient where we had -- or the only thing we had seen on this patient on the right shoulder is a hotspot. He had a very high level of circulating tumor cells. He had increasing PSA levels fairly quickly over time. And when we imaged him, we saw not only the shoulder lesion, but we saw about 70 different lesions all throughout his body, which, when we first looked at these planar images, there might be soft tissue. It turns out they're all in the bone marrow. This patient was studied again with a bone scan about 6 months after his first bone scan, and the lesions that we had seen in March are now showing up on the bone scan in June. And we weren't doing this for just comparison. We really wanted to just make sure we have patient [indiscernible]. So it opens up the question of whether or not we can actually image men with metastatic disease prior to bone scans going positive.
The second study we had done, and this is really the preamble to the Phase II, was to look at man pre-prostatectomy. So all the work we had done prior to the study, everyone had had metastatic disease or they were normal, and we didn't really see any uptake, focal uptake in the normal gland. But the question is could wee see disease in the gland. This was work done -- led by Doug Scherr, who's a urologist at Cornell. Here's a study of a man. He has a PSA of 10. He's got a high risk for having lymph node involvement based on the criteria, and we imaged him about a week before his radical prostatectomy. And then post the review, you can see there's some asymmetrical focal activity in the gland. Now that's not the best way to look at the gland. You really want to do a SPECT-CT where you get 3-dimensional imaging. The bottom is the CT scan of this individual's pelvis or lower body. And then we fuse that with the nuclear medicine scan, which is in this kind of hot-iron coloring. So here, we have -- the side on view is the bladder here. Here's the activity in the gland. Here's the gland out through a cross-sectional view. And this is a gland, the gland from a coronal perspective. And you see there's 2 lesions here. They're actually quite easy to delineate. They're separate, and they have different intensity and different sizes. And so one of the things we wanted to know is are we actually going to be able to correlate what we see on these pictures with the pathology. And so the pathology is given here in this rather cartoonish format, but it's very simple. The gland's not that interesting anatomically. It's kind of like a walnut. For this particular purpose, it's cut in 3 segments: top, middle and bottom. And it's cut again in segments into quarters. And so the pathology here is Gleason 7, on the right-hand, your right-hand side. And it tends to disappear towards the bottom of the gland. And if you look here in this, here, these are like sort of green-yellow. Green-yellow turns like a little bit red, and then it starts to fade again. And that's consistent with this pattern.
On the opposite side, where we have a Gleason 9 lesion, it doesn't really show up until about 2 or 3 slices in. And then it's quite large, actually, outside the capsule here. And what was nice about it, this is our first patient in a pre-prostatectomy setting, we're able to see disease in the gland. No other technology that I'm aware of can look at and delineate prostate cancer in the gland. And the uptake was proportional to the size of tumor that was in the gland. And it was correlated with the Gleason score. And then on immunohistochemistry, it actually correlates with PSMA staining. So this is a very nice correlation of all these factors, which really, were the founding logic for this, but obviously, we needed to do these studies in order to document that that was, in fact, the case and validated.
Another patient, this one has an intense lesion unilaterally in the gland. This is the SPECT-CT.
You see this incredible activity here below the bladder. In this case, this man hasn't voided his bladder very well. But it is unilateral. It's at least one more -- one side and then bilaterally. And if you look at his pathology, you see that this does cross the midline, and it does extend through the capsule. But it actually is present throughout all the slices that we looked at on pathology.
When you look at these scans, you see the bladder's still very hot as they showed you in the other scan. And then behind that and below that are all the slices that show the intensity of this. This is a Gleason 9 lesion in this patient. And this patient was actually very interesting because post-prostatectomy, his PSA did not go to 0. And the reason, we believe, and I think physicians at Cornell believe, is that this lymph node here, which is deep in the sacral bed, was not -- is not a lymph node that's usually dissected during radical prostatectomy. There's a lot of nerves, a lot of vessels back there. It's usually not a place where surgeons stick around. And it wasn't picked up on conventional imaging, and one of the reasons it wasn't picked on conventional imaging is because it's only 7 millimeters. And again, cross-sectional imaging is based on size. So something has to be better, bigger than 1 centimeter before it's questionable as to whether or not it's abnormal. And you can see there's incredible intensity of that small lymph node in this patient. So this would have been potentially game-changing for this patient if this one's already validated. And in this case, this patient is actually -- has 2 Gleason 7 lesions. You really can't see too much here on these planar images, but just higher sensitivity, more detail on this is actually on the SPECT-CT scans, really allow us to look at this. And this now, we're looking at Gleason 6 lesions. These are Gleason 7. The previous one was 9. The other one has both 7 and 9. This opens really the question for whether or not we can actually look at imaging as a way of doing active surveillance. The Phase II is a follow-on from these Phase Is. We think we have very nice preliminary data in the Phase Is to move into Phase II molecular insight study, that study back in June. It's a multicenter, multi-country study, and we're looking at the ability for 1404 to detect prostate cancer within the gland. The gold standard is pathology.
We're also collecting extended pelvic lymph node dissection as part of this, clinically indicated. And we're also collecting lymph nodes, we're doing MR on these patients. And we'll be basically comparing all those results at the end. These are all basically high-risk patients, high-risk for having lymph node involvement, because we want to get patients that have at least a 25% to 35% probability of having lymph nodes because we want to get data on how we compare, not just in the gland, the pathology, but outside the gland to other imaging modalities, such as MR.
So again, major challenges in prostate cancer treatment. There is a role for imaging. So this, again, is an extension of the -- the summary of the kill off manuscript in AGR 2009, that not only should we do a better job of what we're doing, we see the need for imaging within the NCCN guidelines, but we really think that there's more to an extension. Imaging can be used to extend the patient care. In here, the 4 areas here, diagnostic accuracy, basically, maybe even imaging before biopsy or at least guiding biopsies, stratifying patients, particularly in active surveillance, I'd just mention a Gleason 7 lesion or Gleason 6 lesion is a very faint uptake. If it's a small Gleason 6, maybe you actually image these patients over time, guiding focal therapy, whether you do cryoablation, whether you take a patient and do IMRT as primary and make sure you're making -- getting all the lymph nodes, obviously looking at recurrent disease, really to accurate in terms of where that disease is and how much is there is important and guide -- it will help guide treatment planning, and then looking at assess -- or assessing response to treatment in both a radiation oncology and a medical oncology setting.
So it's 1404. I have about 5 minutes left to go through 2 other programs, so I'm going to quickly go through Azedra. Azedra is a drug that we brought into the clinic several years ago, and is currently in a Phase II under an SPA. It's an ongoing trial, but recruitment had stopped when Molecular Insight ran out of money. And so I'll briefly run through this. It's a -- we have basically taken a technology that we felt was going to be able to improve targeted radiotherapy. On the left-hand side is an image of a patient with pheochromocytoma, injected with I-131 MIBG. MIBG has been around quite a long time, both for imaging and therapy of neuroendocrine cancers. But the application of the therapy was somewhat limited, and we believe that we have a particularly interesting way of doing this, and that was to -- let me just move forward here -- is that was to develop a technology that would allow us to produce large quantities of radioactive MIBG, with incredibly small amounts of mass associated with it. So if you think about targeting -- molecular targeting, and we consider this molecular targeting. Most of these targets are in a finite expression levels on them. And so if you were to scale up the synthesis of a therapeutic, and with it, bring a lot of cold drug, when you inject that drug, you're not only going to have the potential of it -- of the pharmacological effect of the drug itself, but you'll also going to have the cold drug competing for uptake at the -- inside of the tumor. And that would actually reduce your therapeutic benefit. We've actually looked at this in vivo, in pre-clinical models and shown pretty convincingly that getting rid of that cold drug actually increases your radiation dose response. And we also know that pharmacologically, we can go down 500-fold at least in the mass of material that's injected during the infusion of these relatively high levels of radioactivity. So we reduced the infusion-related toxicity, and we've also seen that as well.
We like the target here. The target is the norepinephrine transporter. It's expressed at a very high level on a lot of neuroendocrine cancers, which have their embryonic origins back in the cells that create the neural crest or the adrenal glands. And so there's a lot of hormonal activity of these. Not only do they have receptors for hormones, they also produce a lot of hormones and they have a lot of side effects associated with the presence of those tumors, not just the malignancy invading structures, but also giving off lots of nasty -- neuro -- sorry, endocrine hormones that debilitate patients. So you look at target expression, 90% of all the neuroblastomas and 90% of all pheos expressed in norepinephrine transporters, so these -- they make a very nice target for this drug and about 60% of carcinoid. Right now, there's not good postsurgical treatment for these diseases. Carcinoid, eventually, and also somatostatin is a very popular and successful drug. The patients only can be maintained on somatostatin analogues for about 18 to 24 months before they become symptomatically refractory. So there isn't really a lot to offer these people post surgery, and certainly, nothing to offer them once they've relapsed.
We've done 4 studies, including the ongoing study within the Phase I that duplicate in those symmetry, then we move to 2 different studies to define a maximum tolerated dose in adults with pheo. We did a study where we defined the toxicity of a single administered dose without bone marrow rescue in neuroblastoma. We did a dose escalation study, where autologous bone marrow rescue was part of the protocol. And this had been previously described by basically the COG and many consortiums throughout, mainly here in the U.S., and other pediatric oncologists in the Europe. So that disease is a much more aggressive disease in pheo and carcinoid and requires a much more aggressive therapeutic impact.
A registrational trial is designed for -- in a very interesting way. The agency, I think, was looking to help us get this drug to market. They were looking for a way to get this study done under Phase II to get an NDA. The only way they could do that is if they -- if we were able to show a clinical benefit to patients based on that trial. And the clinical benefit that they proposed to us, which we eventually accepted, was the reduction in the antihypertensive medications that are required to control the symptoms in a patient with pheo. The indication would be for the treatment of pheo, but the clinical benefit, in this case, which was the sort of legal regulatory bridge for a single-arm, open-label trial to get an NDA was showing clinical benefits. So about 50% of all pheo patients wind up to be extremely hypertensive. They're on a multiple number of drugs for -- to control the hypertension. And so we're looking at dropping that by 50%, all the drugs at least 50%, and for a 6-month duration. The plan was to get 2 doses, approximately 3 months apart, and also, secondary endpoints, to collect as much data as we could on the real classic tube responses, resistant and the biomarkers. We enrolled 49 patients and we dosed 41 of those patients.
The plan and the protocol was that we needed a 25% overall response rate, and that was at the primary endpoint. So out of the 58, which was our end, we needed 15. Since the math doesn't work out, you can't get 25 out of 58 without having body parts left over. But right now, where we wound up with this trial is that we have 35% response rate in the patients that received 2 doses and 32% response rate for the primary endpoint in patients who had received at least one dose. So we picked up one other patient who had only received a single dose. And if you look at everybody, we actually had a significant amount of patients had some type of antihypertensive response with the drug. And again, this not an antihypertensive drug, but it's basically shutting down production of catecholamines in the tumor as tumor response continues. And therefore, the antihypertensive drugs are being withdrawn from the patient. Otherwise, they'd be unable to function because they're so heavily medicated.
This is just a quick snapshot of all of the patients that had any response to antihypertensive therapy. They are all showing what the criteria was for the cut off of 6 months, so many of these patients had a much longer duration antihypertensive meds.
If you look at recess response per protocol, the patients that again received 2 doses, that's 12 out of 34, 41%, but also 12 out of 41 for the full analysis set. We define the moderate response of 15% to 30%. And again, here, we have another 15%, and there was a lot of stable disease, most of these patients were relapsed, refractory and progressing.
This is a wonderful plot of the recess response. Color-coded, the green is the partial response and purple is, assuming it comes out purple, is the moderate response, then stable and progressive. And the yeses and nos here, basically indicating whether or not they met the primary endpoint or not. Same with the biomarkers. So we're seeing very nice activity of this drug in this population and this the their response. So we're looking at -- at 12 months, 93% of the patients were still alive and 70% were still alive at 24 months.
Common AE is related to really GI disturbance and also hematological. We know that the radiation from I-131 is going to drop, is going to hit the bone marrow. And you're going to can see neutropenia, thrombocytopenia. But we had no infection related to neutropenia, we had no bleeding related to thrombocytopenia in this case. So we had, overall, 88 subjects were exposed to our drug in these trials. Short- and long-term AEs were acceptable and manageable, again, that nobody needed to be -- nobody was -- and had clinical sequela from their numbers. Because of the high specific activity, the [indiscernible] mass, we're injecting roughly about 80 to 120 micrograms of drug for every 500 millicuries that these patients received. We could push that into 15 to 30 minutes, which is actually really a helpful way of making this logistically less complex than in usual. The other preparations that have been used, where there's a lot of cold MIBG, somewhere between 1 and 4 hours is required to infuse that drug.
Quick case study, and I know I'm running behind here. So a patient in the University of Pennsylvania by Dr. Prima was treated by Dr. Prima. He had a history of unresectable paraganglioma, which is a from a pheochromocytoma that originates somewhere other than the adrenal gland. And in 2009, 2010, he became basically a very fatigued and was losing weight. He wasn't eating. He began our treatment in August of 2010. He came in on a wheelchair to HOP. He did well, even though he had a grade 3 neutropenia, he tolerated the therapy well. He had some very large -- enlarged lymph nodes that are involved with tumor, which I'll show you a CT of. It was chromgranin A, it was about 600 at its high, normal is around 35. And that had decreased to 20 by 12 months after. And he was -- by the time the 12-month visit was up, he was off his hypertensive medications and he was walking. So this is one of those cases that keeps you want to work. Here's the CT of -- cross-sectional CT of this lymph node involvement in the lower abdomen and over the course of 6 and 12 months, the shrinkage that you see that graphically represented as well. This is some of the longest diameters. In children, Azedra was -- we basically published a paper last June just describing the MTD study. This is in heavily pretreated children with neuroblastoma, they're refractory and relapsed. We imaged these patients and then we basically looked at 12, 15, and 18 millicuries per kilogram, all of them had bone marrow on hand, all of them regrafted nicely. And there were no grade 3 or 4 non-heme toxicities associated with this therapy. And if you're familiar at all in neuroblastoma, MIBG is the most active single agent for neuroblastoma and COG right now has a study where they're looking to move MIBG up earlier in the induction component. And we did see what we think as a dose response relative to these dose cohorts in the study.
This is just one patient, pre-imposed. Applications here in carcinoid, I think they're significant. We see a very nice data here from the Duke Group, the saffron paper showing nice dose response. We've been up at 500 millicuries. We see a big difference in overall survival benefit over 400 millicuries.
A lot of the top city -- oncology centers have involved with us, both with children, and as well as in the pheo. And I think there's a very big interest across-the-board in neuroendocrine cancer to have MIBG available as an approved drug.
In my last 30 seconds, I will just touch on targeted radiotherapy of prostate cancer. I've mentioned that we had done work. It's the compound here in gold, it's 1095. This was one of the compounds we've, again, published on -- it was published in March 2013. It's a small molecule inhibitor, very similar to all the characters -- I described 1404, it's very similar characteristics with this compound as well. It's labeled with iodine on this aromatic ring here. It's extremely stable to the iodination, but it's also stable in vivo. And this is an amazing finding for such a small radiolabeled compound, but this is some of the work that we published in 2000 -- just earlier this year. And these are the 1072 compound and 1095. This is a patient who has both sacral bony disease and bilateral lymph node involvement. And you can see incredible uptake from half-hour, or rather 24 hours of this track of lymph nodes all the way up to the patients.
So we looked at this and we realized that, these compounds have the potential now to move the isotope from iodine, to I-123 to I-131. And we looked at this in animals with I-131, and we came out with a very nice response here, single dose, dose escalation study in animals, where with one dose, that would equal -- probably, roughly, it would be about 200 millicuries in the patient on a meter squared basis. We're getting these -- we had to stop the study. These animals were alive for nearly a year before we stopped the study and sacrificed them. So we had a very nice response. This is just showing the treatment versus the vehicle group at 70 days. And we obviously had done a lot of work as we put this in man several years ago. So again, we don't see any pharmacological or toxicological signal coming from these compounds. And having presented this to our colleagues in Heidelberg, they contacted us and said that we have the ability through an approach in Germany, which allows physicians, under a particular law, to treat men or treat any patient with experimental medication, if they failed all conventional therapies. It's not a trial, but they have the ability to do that under the practice of pharmacy and medicine. And so they synthesized the compound and they have actually shared with us some of the data. This is a work that was spearheaded by Professor Uwe Haberkorn, who has headed the Heidelberg University Hospital Nuclear Medicine Department, as well as the German Cancer Research Center Nuclear Medicine Hospital. Today, they have treated roughly 28 men with our 45 therapies, and they've seen some very interesting efficacy responses in men who have failed all types of chemotherapy, androgen deprivation, docetaxel, enzalutamide, abiraterone, so it's an interesting group of patients. This is a snapshot of the world [indiscernible] best PSA response. So more than half of these patients are having at least a 50% reduction in PSA after one treatment. This is one of the more compelling images from this work, and that is a 4- or 5-day image of the patient who's been injected with the compound labeled I-124 and an image in a pet scanner. And basically, if you'll recall, the sort of mask here, these glands in the head, you can see the eyes up here and then the salivary glands, but this patient has numerous bone lesions. And what we're amazed about, really, is the ability to track this out for 5 days. What was even more amazing with this is that when they treated that man, they tracked him out for 17 days and we still saw lesions in the same tumors that I just showed you, almost 3 weeks. If they had -- probably would've scanned them later, they would've seen it still. But this actually tells you something about the potential of the small-molecule approach with this comp and at least for targeted radiotherapy. This is one patient who had only soft tissue disease in the abdomen. He was treated once. His PSA dropped from 200 to undetectable, and still undetectable after 1 treatment with 1095.
That's his CT, pre-therapy and post-therapy, so he's had a complete response on CT and a complete response by PSA. Not everyone is as lucky as that individual. This is more of the case with a very heavily metastasized to the skeleton. This patient had disease for -- with cancer for a long lime, that failed pretty much everything that's available today. I think the only thing that patient hadn't had was Medivation at that time. But he had the Medivation 3100 compound, but he had abiraterone, and it failed multiple regimens of docetaxel. And he was treated -- the first time he was treated, he had a very nice PSA response. He had a very nice response in terms of pain. He was treated a second time, he was treated a third time. So he wound up surviving about 18 post his abiraterone failure, with basically minimal toxicity associated with these therapies. So basically, the therapy is induced. Again, a hematological response, a reduction in leukocytes and platelets, none of which ended being treated. And these are the scans of that patient, prior to therapy, after the first therapy, after the second therapy. And I mentioned he was treated a third time.
Just one more last patient. Soft tissue disease, only in this patient. These are pet scans using a different PSMA imaging compound, pre and post therapy. And then the last slide is really just how that progressed after his second therapy. So almost all of these patients' disease has gone after a second therapy, and the major complaint in Heidelberg of this therapy is boredom because once they get injected with the compound, they have to sit in the hospital for several days and watch TV and do crossword puzzles.
So the opportunity, I think, for us, and I think it just came out in New England Journal of Medicine, the final manuscript from Alpharadin. They're not targeting the cancer, they're targeting the bone, the remodeled bone, which I think is a great beginning of looking at the use of targeted radiotherapy in prostate cancer. And we've designed the Phase I study and it's under discussion right now at Progenics. And I thank you for your time.
Mark R. Baker
Well, thank you, John. Next up, we have Jonathan Simons, who will be speaking to us about the intersection of imaging and cancer therapeutics. Jonathan is the President and Chief Executive Officer of the Prostate Cancer Foundation and had spent a great privilege to be working with the Prostate Cancer Foundation over the past years and seen the amazing impact that they have had on the treatment of that disease. Jonathan is going to join us by phone from the offices of the Prostate Cancer Foundation in California. So Jonathan, can you hear us.
Jonathan W. Simons
I can. How's the audio?
Mark R. Baker
You sound great. So go right ahead, and we'll follow along with the slides here.
Jonathan W. Simons
Thanks. The first slide should read the Intersection of Imaging and Cancer Therapeutics. And it is fair to say that I'm delighted to give this set of observations, I guess, and we're very grateful to Progenics as philanthropists. Not often, and probably discussed with analysts that there'd be great corporate citizenship. But if you can turn it to the second slide, Slide 2, Progenics is supporting one of the most gifted PhD scientists in an unrestricted way, in a peer-reviewed way to Dana-Farber, just as a great supporter of cancer research. And when I was asked by Mark and the team at Progenics to participate, I jumped. For any analyst who would to like to support young prostate cancer scientists around the world for $75,000 a year, for 3 years, you would have our [indiscernible] philanthropic interest as well. Because these young scientists right now, these young Thomas Edison phenocopies, which I'll talk about in the end, the molecular imaging that are going to generate this revolution in theranostics through molecular imaging for prostate cancer. By way of multiple disclosures, I don't have any financial interest or transaction arrangement with Progenics. As I said, Progenics has supported a young investigator at the Dana-Farber Cancer Institute that's actually working on transcription factors that are central to the lethality of prostate cancer. Human prostate cancer, who claim the life of a U.S. man every 80 minutes around the clock, 365 days the year in this country. It's the second most common cause of death in men from cancer. And the work I'm going to present today is a prospective on molecular imaging. But none of this actually directly relates to the talk you have heard previously, but it all relates to this new extraordinary area of imaging. The foundation doesn't endorse commercial companies or products, although we're very excited. Like the New England Journal today, we did a lot of the translational science research on radiopharmaceuticals at MD Anderson, which sort of paved the way for Radium-223's proof of concept trials and actually, FDA approval as I'll talk in a second. Our foundations are very interested in progress rotations and that absolutely includes the science around PSMA. And because we also support cutting-edge research in many ways, there's no assurance that a funded investigator of ours in Progenics won't collaborate in the future. We've created partnerships, academic partnerships with over 70 biotech and pharmaceutical companies over the 20-year history of the foundation. And every FDA-approved drug for prostate cancer, if you jump ahead to Slide 4, has our foundation's footprint in terms of academic science and drug development.
I may not make forward-looking statements intentionally, but I am going to give a prospective about what I think is very exciting and very important and very critical for the entire future of oncology in molecular imaging or in the kind of imaging that was presented in the previous talk. And it's -- whatever anybody does with their money as a basis -- investment on the basis of this academic presentation, I'd like to remind everybody listening that the last for-profit that I ran, although I led a large cancer center before I came to this foundation as CEO, my last for-profit was my paper route into the New York in 1974. So this will have the heavy professorial and a scientific and medical prospective, and that's what it will be.
If you're now on Page 4, what is amazing is that, and partly as a consequence of actually this foundation and the [indiscernible] the NIH budget in the 90s, we've seen 6 new FDA-approved drugs in the last 38 months, if I recall it correctly, for advanced prostate cancer. Radium-223 is in the New England Journal today, Alpharadin enzalutamide, that was a grant to Charles Sawyers at the dawn of that at UCLA. We have abiraterone. We have sipuleucel-T, cabazitaxel and denosumab from Amgen. And actually, there are a number of more very interesting targeted treatments in development. This is a glorious period of time right now in terms of thinking about reducing death and suffering from prostate cancer. And what's going to be essential for these new drugs in their combination is a far better way than all the 20th Century has provided in terms of informing a patient whether or not treatment is working, not working or more is needed. And I would give a prospective that the future of all reimbursement for these types of new approaches to cancer are going to be evidence based on the use of technology that actually reduces overall the unnecessary use in one direction of medicines, where the disease is refractory, and on the flip side, allows the use of even more treatment where response is detected earlier, or longer duration of treatment is required. Everything that we've FDA-approved, fundamentally, has been done simply by evaluating who's alive and dead after treatment as overall survival. None of these studies have really been enabled by the molecular imaging you've heard about before and I'll briefly outline for you in this talk.
Next slide, that will be Slide 5. And why molecular imaging, I think, is like the incandescent lightbulb in the age of gas lamps and kerosene lamps, why I think that pun is intended about new pictures in oncology is that molecular imaging offers, for the first time, the possibility to actually quantify, ultimately, or count the actual amount of cancer in a patient's body. Our current CT scan only really detects 10th of the 11th power total cancer cells. We simply can't seek micro metastatic prostate cancer, other cancers at the level that are required. Also, as you've heard in the last talk, being able to manage anatomically with the one lymph node that's admitting the lethal clone after surgery with curative intent to make the difference potentially between cure and failure to cure at a time when cure is still possible. So anatomic management of prostate cancer, in particular, opens up again with new molecular imaging.
As I'll talk briefly later, we are learning more and more about mixed responses or patients who have, let's say, 40% to 60% of their cancer cells go to remission and who retain basically a 30% to 40% of clones that are resistant to treatment 1, but might be sensitive to treatment 2 and 3 if you could actually see the mix response in real time, rather than wait on the obligate 3 to 8 to 12 months for things to grow back, with its consequent disadvantage in terms of total tumor burden.
And for regulatory science or for drug development or a platform to accelerate for biotech and pharma new agent, quantitation of durable responses, in the same way we've revolutionized the development for HIV, quantitation of durable responses may be the real way forward to de-risk a lot of the investigational drugs and also encourage patients to participate in clinical trials because you can actually see in real time that these medicines are working for you.
And finally, the FDA has already signaled that its keen interest, at least, at ODAC is in the integration of molecular imaging and new imaging with new agents because our existing biomarkers, at least single-channel biomarkers, have been largely nonpredictive of a great treatment benefit.
On Slide 6 is my observation that -- basically, the imaging for patients. Patients will follow the technology and practice really will follow the technology because the patients will be driving practice. This is obviously the classic x-ray by Röntgen and basically, for almost 100 years, this was the body of radiology that one learned at -- in medical school. Its flaws, although significant, don't change the fact that the standard of care for, fundamentally, a great deal of primary care of medicine to this day is plain films, although they're digitized now.
The problems with two-dimensional thinking is -- are sort of defined on page -- on Slide 7. This is a patient with non-small cell lung cancer, which is the cloudy stuff you see in the -- along the ribs. The perspective change that's been required in all of oncology is to get out of 2-dimension plane fields or shooting x-rays through the body where density of calcium, in large part, is the signal and get to the actual requirement for modern treatment of cancer patients, which is the amount that the physician and the -- basically, the activity of cancer, not just the presence or absence, which is plain x-ray can clearly define the presence of lung cancer, but is actually the kinetics or the biology of the disease. And that's where our Precision Oncology is taking us now.
And on Slide 8, what's really happened with molecular imaging is that we've found that there's been a moment of sort of Brunelleschi thinking in imaging. For those who are classically educated, Filippo Brunelleschi really invented the concept in the Renaissance of perspective and sight line. It is not that people didn't see in 3 dimensions. But to quote Helen Keller, who was probably the greatest spokesperson about what the future molecular imaging really is, Helen Keller wrote once in braille, "It is a terrible thing to see and have no vision." And it's been the ability in the Renaissance to think about perspective and start to think 3-dimensionally that sort of fact that is fast-forward, basically, the entire human mind.
And if you turn to the Slide 9, it's been these young physician scientists and physicists and computational biologists, 4 of whom whose data I will present lightly today. It's these type of human capital which is going to be essential in the great value creation of molecular imaging. And all of these 4 that our foundation funds, Steven Cho and Marty Pomper at Johns Hopkins and Glenn Liu and Robert Jeraj at the University of Wisconsin have competed against every other molecular imager in nuclear medicine. They've competed in international competitions to be funded. But what's exciting about this field and exciting about the last talk as well is that they're deeply integrated into the actual clinical -- the daily clinical care of patients. And one can start to assemble data sets around patients in real time with these 3-dimensional images.
This didn't use to happen. Radiology was largely siloed. Pictures were taken, pictures were read, reports were sent back. But it's actually the integration, this new 3-dimensional perspective of being able to see, talk about anatomy, talk about biochemistry, talk about genomics and then talk about which experimental or existing drugs to use. It's this sort of integration, which you've heard about in the last talk as well, it's this integration of perspective like Brunelleschi, which is going to be the standard of care, I predict, in the future of oncology. It will not be possible to take care of a cancer patient or a prostate cancer patient, I would predict, within the next 10 years, without both genomic information and molecular imaging information that makes the treatment plan precise and in real time.
And since everything is digital now, both the scans can be read, clinicians in the clinic and radiologists and actually, image processors, all can be around, actually, the same real time images with the patient basically on Skype as well. This kind of Brunelleschi phenocopy or changing the perspective to the whole patient and imaging the disease activity down to the single cancer cell, we think this is really the -- this is going to be reduced to the standard of care in the next 10 years.
On Slide #10, I just thought, in a didactic, I'd provide some culture at all, just some concepts for those listening about what defined molecular imaging in the 21st century. The most important point is bullet point 3, which is you're looking for something that's abnormal. The chest x-ray just looks for calcium, essentially, or density changes with x-rays. But molecular imaging is, what is actually going on at the biochemical and the genomic level. So it's an opportunity to have, basically, the ground truth of the disease activity, basically, cell-by-cell, theoretically, in a patient's body. And the other fascinating aspect of molecular imaging is our ability to look very early in the history of the disease, not just late when the disease is advanced.
If you turn to the 11th slide, I put up, again, just professorially a set of current imaging radiotracers. You heard about technetium, you've heard a lot about PSMA antibodies. There are an early set and there'll be more set of radiotracers or imaging agents that are tailored very specifically to the cancer type. In most cases now, that's under study. For example, their efforts to light up, so to speak, the antigen receptor, which is the target of 4 of our new anti-prostate cancer drugs, or in the case of PSMA, target a over, over, over expressed flag, basically, that a prostate cancer flies that a normal cell will not. And of course, prostate cancer claims the life of a man every 80 minutes around-the-clock, largely because it will occupy and own the bone marrow in the bone. Most prostate cancers are failed because of catastrophic late effects from bone marrow failure and cytokines', basically, inflammatory effects.
And so basically, anything to do with bone remodeling is of great interest in terms of making medicines for advanced prostate cancer that will put a patient back into remission.
There are others. This is just early survey. And there'll be enormous value -- next slide. There'll be enormous value, however, in their full integration, as you heard in the last slide, into our existing imaging capability.
So presented actually in Slide 12 is a fusion, and there will be more and more of this fusion technology of a 69-year-old man who got enzalutamide that FDA approved. Actually, what you see kind of glowing in yellow -- yellow-gold, is the hottest areas, the hottest areas in the last scan of the androgen receptor taking up the drug. By the way, this is enzalutamide, this was just FDA approved. And this kind of data helped accelerate the approval of this drug.
And in Slide B, what you see is a very significant anticancer response because all those site metastasis that are glowing gold-yellow had simply been silent. And this actually -- one could have actually taken care of this patient and, actually, not in the research framework. But in concept, one could treat to best response just on the basis of this FDHD PET/CT image in the context of using this new experimental drug. And why we're so interested in these kinds of scans is the possibility that we could actually quantify, ultimately, the amount of -- basically, the amount of cancer that's been eliminated over time.
And as you can see, at this proof-of-concept slide, as well beyond diagnosis and staging, one could use a single -- this information for a targeted radiotherapy if there was a single spot left, let's say, in the vertebral body of the second lumbar region. And this is the proof-of-concept that Theragnostics work in prostate cancer. In other words, you can have both an experimental drug and an experimental imaging agent, and they can be codeveloped. We see this as a terribly interesting area for the future of oncology.
The probes on Slide 13 come in sort of 4 types. Most of this, again, is background information, but the most interesting probes, all 4 are theoretically very interesting. Phenotypic probes can tell you whether or not a cell is dividing or whether it's in low oxygen or what kinds of proteins it might be making. There are targeted probes that can actually light up, so to speak, pathways or antigens for antibodies that would guide the use of a drug or an antibody. There are actually probes in development that watch cancer cells and how fast they're moving. This may be very important for defining whether or not the margins have been cleared. And also, disease activity with immunotherapy. And of course, there is a great deal of interest in lighting up certain genes, which give additional information potentially for what other drug-- experimental drugs that might be used.
But the concept of this slide is that our R&D in molecular imaging probes is only at the beginning, not at the end of the field, and they'll be a very important advances in the imaging probes over the next few years, we believe. And this -- these kinds of discoveries will be coming out of academic laboratories, small groups of chemists and cancer biologists. There's not an organized -- to the best of our knowledge, there's really not an organized industry for a molecular approach development, but there is an extraordinary excitement about individual inventor creativity in academic institutions where the chemistry is more and more possible and where nuclear medicine, the scientists and cancer biologists are working more and more together.
At the University of Wisconsin, on Slide 14, I just wanted to give you another example of how far along you can take PET imaging, traditional PET imaging, with sodium fluoride PET tracer, and then develop a software to objectify and quantify in a patient, with enormous anatomic precision, where there's disease activity and where there's not. This is the work of Glenn Liu and Robert Jeraj, and the QTBI is their -- basically, is their anagram for quantitative -- basically, the new kind of quantitative software for assessing this technology. The highlight I wanted to give posttreatment was just that our ability to personalize this treatment for patients and show them a disease activity on investigational drugs has never been greater and will begin to be greater. And actually, there is interest in creating apps for iPhones for patients so they can track along their own QTBI in terms of their own bone scan.
And with that concept, if you would go to Slide 15, you can see another example, in this case, from Marty Pomper and Steve Cho, of actually fusion images where actually the patient's treatment was altered at L4 because of the ability to fuse and actually see a PSMA-active disease in 1 site. We had a very good overview of the state of science in the last talk.
But I just wanted, on Slide 16, to make the sociologic observation that these centers that are able to integrate the kinds of technology you've heard about are going to be the centers with the leading data and are going to be the centers that I would forecast the reimbursement -- the reimbursers are going to be paying attention to, as well, because there can be cost savings as well as expense in having a more customized approach to treating each patient, including an observation that additional treatment might not be necessary.
With the remaining time, I just wanted to hit a few last concepts. All of the imaging that we get in the clinic routinely, on Slide 17, is qualitative: it's presence or absence, it's bigger or smaller.
But sodium fluoride PET/CT, on Slide 18, and the ability to see more cancer, which you heard about in the last talk, on Slide 19, is simply going to be a part of the transparency of 21st century oncology. We're going to see more -- we are seeing more cancer, but that permits us actually to develop longer durations of treatment or alter our doses and schedules in order to accommodate the fact that we're taking on greater tumor burden.
One of the best examples of this, the SUV on page -- on Slide 20, is not your motor vehicle, but it's actually the Standardized Uptake Value or pixel value. You can actually see that this is a lesion in space where the sodium fluoride tech above really gives you a lot more insight into bone activity than one can get with any existing technology. And I would forecast that there'll be several different kinds of imaging that may be needed for certain kinds of patients: bone, soft tissue, the genotype of the cancer, that will make for a far more precise oncology.
I've tried to make, on Slide 21, the case for change. We see many heterogeneous responses or partial responses or some cancer cell dying and some growing. We're simply going to need to be treating patients with molecular imaging data that's telling us what's left that's growing in order to develop our next generation of drugs. This is absolutely required technology if we're going to end death and suffering from advanced prostate cancer.
The physiological relevance of, on Slide 22, of -- these kinds of imaging, I've just sort of depicted. But the key thing is that it can be done in real time. And if biology, like bone response or surface expression of PSMA is a part of what the radiologist gives an oncologist, not simply water motion by MRI or inflammation or more qualitative things.
And if you just jump ahead to Slide 23, what you can see again is that we can develop, with PET imaging like this, a suspective real-time assessments of every single lesion in the patient. And the -- there is no way the 20th century ever was able to talk to a patient with this level of precision anatomically.
I'm going to skip through. I provided some data from Drs. Liu and Jeraj about how the software actually performs, with their permission, in terms of proof-of-concept already that reading out individual lesions may change the actual plan of care for a patient. And on Slide 27, the integration of all of that is fundamentally a patient who has both the red and green. This is false color, of course. But the red is what's still growing, and the green is what's been put into remission, in this case, with an anti-androgen. And this is going to revolutionize, I would forecast, our ability to treat far earlier lesions that are resistant with our current targeted therapy. And I would make an outrageous claim that -- but I don't think it's that outrageous -- is that our patients will begin to demand actually molecular imaging in time, when there's a greater transparency to the mixed responses we get with our exciting new medicines.
I'll just jump basically to Slide 29, that hit one last time that PSMA is an important case study in all of prostate cancer because of its overexpression in prostate cancer. It's really been quite credential -- I think that's the right word, a very important surface target. And there is work to do as well because there are probably 200 more surface targets, with PSMA clearly in the lead, in terms of understanding and overexpressing. But we've only began to -- we're going to start to illuminate even the surface of prostate cancer cells. And of course, using PET where MRI and CT can't help us is quite established in the field of lymphoma.
Just trying to make the point on Slide 30 that we now manage to cure lymphoma on the basis of cancer -- managing cancers we can't see by CT or MRI, but by the use of PET. And for those who feel that molecular imaging hasn't yet found a place in oncology, I would just simply direct them to all of the lymphoma literature, which, you heard in the last talk, is the application of molecular imaging to prostate cancer in the same way 18F-fluorodeoxyglucose was applied in PET imaging to lymphoma treatment. The concept is proven that molecular imaging can actually change the outcomes for patients in terms of cure versus failure to cure.
And in the remaining one minute, on Slide 31, I have given you some interesting chemistry. There is much more chemistry coming, but PSMA is highly expressed. There are up to 1 million PSMA molecules per cell, and it's still the leading candidate surface target in all of prostate cancer oncology for molecular imaging research, dependent of the technology.
And I'll just jump to Slide 33 in the interest of time. The molecular imaging, it's my view, personal view, and I think of the -- our entire field that 3 areas of oncology are going to be liberated. We're going to be able to choose what treatment's right for an individual patient based on this 21st century technology. We're going to be able to do it in real time, and it's going to be -- the third thing is really going to be a toolkit for creating partnerships with patients, including actually patient-derived apps on iPhone so they can follow their own treatment.
We think that the optimization of a lot of this requires R&D support, government foundation, industry. It's going to take significant numbers of clinical trials to accomplish this, although we feel that patients are going to be excited to participate because they can see, like the oncologist, what's happening in their body and follow it actually with false color imaging, et cetera.
The last 2 points, I think, are very important, too. It's that software development, which you heard a lot about in the last talk as well, is going to be essential and a very important aspect beyond just the chemistry in terms of reading signal versus noise and following over time. And Centers of Excellence like Johns Hopkins and Cornell and Wisconsin and others are really going to be where the early data is going to emerge for these important technologies.
So on Slide 34, the bottom line, I guess, is we need, as a community, to be supporting early Thomas Edisons who, rather than creating an incandescent bulb, for instance, want to light up cancer cells in the ways that oncologists can develop drugs to cure a patient or detect cancers earlier. And we need, as much as possible at this time, the engagement of all aspects of our society, the investment community, the for-profit community, the government community, other than the academic community, the patients. We all need to see that the time has come for molecular imaging to get the full resources it needs.
I'd be happy to answer any questions and I appreciate the opportunity to speak today.
Mark R. Baker
Well, thank you, Jonathan, for that talk. And yes, we'll take time now to take questions for Jonathan or for John Babich, focusing around imaging or our radiopharmaceutical programs.
Mark R. Baker
Please use the mic.
Where is reimbursement on molecular imaging, Jonathan?
Jonathan W. Simons
Well, half the lymphoma is reimbursed. So I think the concept is that if you can show a patient benefit a peer-reviewed literature that ends up in the New England Journal or The Journal of Clinical Oncology as formats, patients should get it and they do.
Mark R. Baker
And for me, obviously, we need to demonstrate the clinical benefit of imaging. There's no question that pictures, just for pictures' sake, may struggle to get reimbursement. But I think as those 2 talks that we just had showed, imaging in this context can lead to incredible information to guide clinicians and patients in making difficult decisions, including the decision to forgo therapy or surgery, which could have a very positive benefit overall on costs. If you can avoid the significant costs of therapy and benefit through watchful waiting, which imaging might lead to, there could be a very favorable benefit from an imaging perspective. John, did you want to say something about that? John Babich?
John W. Babich
Yes. When we had our investigator kick-off meeting for the 201 study in Europe, we had a very big debate about showing the images to the virologists prior to prostatectomy. And it brought up a question. I think the question is relevant to reimbursement. And that is, a lot of them were anxious that they would be operating on a patient who had a metastatic disease, that this agent would show that their conventional technology wouldn't show and that, that would be a detriment to the patient. And that they've been involved, some of these investigators who are well-known urologists in Europe, they have been involved in studies where they were doing studies just like this but with, say, the C-11 choline, which is something that's been relatively recently promoted as a way of imaging prostate cancer. And they had gone and taken out someone's prostate, obviously made them impotent, et cetera, and created other issues, only to find out afterwards that the patient had a metastatic disease in the bone. So they weren't going to cure that patient. And so finding a disease like this and not doing something that -- obviously, these things, well, we didn't talk about it -- that Dr. Simons, the impact on men when they do have treatment is dramatic. And so that information is clearly important, and I think it'd be hard to argue not paying for a study that would avoid such damaging processes and therapies.
Mark R. Baker
Great. Thanks, John. There was a question over here. Amy?
Yes. With regard to the asymptomatic patient that presents with the elevated PSA. This imaging test was done, it's confined to the gland. What would be the relevance in the treatment paradigm with regard to that? And another question. Does molecular imaging show data before enzyme elevation shows that -- what's going on with the tumor?
Mark R. Baker
John, do you want to take those? Amy?
Jonathan W. Simons
Was that John or Jonathan?
Mark R. Baker
John, you could take the first shot.
John W. Babich
You can get the second one, Jonathan. So just relative to what we have experienced. So certainly, we wouldn't think of imaging as a screening technique, right? So PSA is probably a pretty good screening technique. We are actually excited about the opportunity to actually see disease in the gland at a very early stage, and that could be helpful in a patient who has had an elevated PSA who goes through a biopsy and basically is negative but continues to have elevated PSA or continues to have some sort of urinary issue, which needs to be addressed. And so maybe what we would imagine, and one scenario is, PSA testing would drive you to get a scan prior to even maybe a biopsy or a post-biopsy if the biopsy is negative and you continue to have elevated PSA. So that's something -- it's actually pretty new. I mean, the ability to see disease there is actually quite unique. We would never expect to replace a screening test as simple as PSA, but we think we can augment what happens after that information comes through. And I certainly would love to hear what Dr. Simons thinks about that.
Jonathan W. Simons
Well, I agree. I think it's still -- it's going to be a very interesting application of molecular imaging to find men who have a biochemical recurrence and elevated PSA after surgery radiation, where the only active area may be a lymph node that's emitting into the circulating blood lethal cells that haven't colonized the bone. And this is not science fiction. We're aware of some of this data. It's just very early. The way to think -- I believe the way to think about this is not to think of it as a CT scan or an MRI but ability to look for living and potentially lethal cancer cells and the new kind of GPS-enabled satellite technology. And the consequences of that may be very important, anatomic location, the amount and the biology. And actually localizing these lesions for a biopsy, which may be theranostic as well. All of that is actually in the standard of care of how we take care of lymphomas, and now we have 5 new drugs for advanced disease prostate cancers, have more FDA-approved novel agents in the last 3 years than any other common malignancy. So our -- we don't necessarily use these medicines early enough or in combination that are scientifically rational. So molecular imaging opens up this approach to thinking about patients as if they have a lymphoma, where a significant remission is the treatment intention, not the palliation alone.
Mark R. Baker
Did we get to both of your questions there?
Mark R. Baker
Good. Other questions? There's one in the back.
Mark, can you remind me where you are with the Azedra regulatory path?
Mark R. Baker
So we're in discussions with the FDA over whether we need to complete that trial. You'll recall from John Babich's presentation that Molecular Insight had an SPA calling for the treatment of 58 patients.
Molecular Insight ran out of money and stopped the trial as to the enrollment of new patients. The trial continued in terms of following patients, that's 41 patients. The percentage response met the SPA criteria but the -- and the number of patients did not. So we're asking the FDA the question whether they would accept a submission with the data from the 41 patients or whether they're going to require us to conclude that trial, reopen it and enroll the additional 17 patients. We're in that phase of discussion with the FDA and I'm expecting that we'll have an answer in the coming weeks or possibly, next few months and then we'll make our plans. For me, the difference isn't all that significant and that it requires us to get manufacturing of that drug back up, which we would have to do in any case. So I personally would be okay with either outcome. We're not pressing the FDA but we feel, as John mentioned in his talk, that the FDA is interested in getting this treatment for this unmet need and so perhaps, we'll be open to that possibility.
One more question?
Can you just remind me how many patients there are with pheochromocytoma and how many of them are being treated with radiotherapy now?
Mark R. Baker
So when we acquired Molecular Insight, we got their market data, around the number of patients, and we did some work with respect to that. We have, since acquiring the company, engaged our own work and have I've taken a real deep dive to answer that question. So I would prefer not to guide you to anything specific now until I feel that I have the data that I've been able to control. So hopefully, in the coming months, we'll be able to give you bigger picture of the data. The market here is not huge in numbers. 1,000 patients would, perhaps, be a very round number, of the number of patients annually that might use this compound. And so it definitely is an ultra-orphan indication. But the impact on the patients, we do feel, from a commercial perspective, that the treatment could garner the types of payments that we see for similar ultra-orphan indications. So I think the commercial opportunity is of a great size, particularly for a company of the size and capabilities of Progenics.
Good. So we'll line up the Q&A session. Jonathan, great thanks for taking time from your day and for making that great presentation to you. And thanks to John Babich. And we'll let you go Jonathan. Thank you.
Jonathan W. Simons
Thanks so much.
Mark R. Baker
Mark R. Baker
Okay. We're going to switch speakers now and focus on our PSMA ADC program, and we'll have a presentation by Bob Israel.
Robert J. Israel
Hello. Good afternoon. It's good to be here. I think -- right now, I'd like to just go over our PSMA program. This has been presented a number of times to some of the National Cancer meetings, so you may be familiar with a lot of the data. We have a little bit more to talk about here. And I think that -- I probably don't have to say after John Babich's talk, but PSMA is an attractive target for cancer therapy, for sure. But this is just a couple of slides, it's attractive both because of its biochemical properties. It is an integral non-shed membrane protein that's on the external surface of the prostate cancer cell. It does have an activity, carboxy pepatase activity, and it rapidly internalizes which -- this is just a graph that shows quickly internalizes once the antigen is bound by an antibody. It is also unrelated to PSA, despite the fact that it shares at least 3 letters.
In addition, the expression pattern also makes it attractive and that is near ubiquity on prostate cancer, both are primary and metastatic lesions. And as John Babich had mentioned, it has increased with androgen suppression, also increases with disease progression. And so it's attractive prognosis for imaging, but also for therapy. And I think, recently, the interest of even other companies in this target really validates PSMA as a target.
Normal tissues has very limited expression and in prostate cancer, as opposed to normal prostates. Within extra cellular there is a variant called PSM prime, which is in the cytoplasm of normal prostate. You may have heard of the imaging compound called ProstaScint, which targets PSMA, but it is a completely different antibody. That antibody targets an internal domain of PSMA and not external. But the fact that the FDA approved that, does validated it as a target in some way.
PSMA on prostate cancer is a negative prognostic feature. If you take a prostatectomy stain, a tissue, for PSMA expression, those with a low PSMA expression, if you follow them out, they had a very low -- lower, much lower risk of biochemical relapse. Whereas, high PSMA expression had a higher rate of relapse later. So it is a negative prognostic feature. The worst the prostate cancer, are the more aggressive, potentially, the more PSMA it expresses. So again it makes it also an attractive target to go for the probably the most aggressive of prostate cancers.
So another interesting thing about PSMA, although it's called prostate specific member antigen, it's also expressed on non-prostate cancer. But the differences in non-prostate cancer, or many non-prostate cancers, is expressed on the neovasculature and the luminal aspects of the neovasculature of those tissues. Whereas, in prostate cancer, it's expressed on the tumor cell. But it makes even non-prostate solid tumors potential therapeutic targets for a PSMA therapy or even a PSMA antibody drug conjugate. Here's a cartoon that in the prostate cancer, it's on the external sort of the prostate cancer cell, but not on the neovasculature, interestingly. But in non-prostatic or in many non-prostatic solid tumors, it's actually present on the luminal surface of the neovasculature, indicating that potentially it's of necessity for the tumor itself.
The drug that we have been developing actively, and it's now probably midway through Phase II, has been an antibody-drug conjugate PSMA, utilizing the cyanogenic technology on the MMAE toxin, which is cleaved by cathepsin B and is the same technology that is used on the approved drug, ADCETRIS, which has been quite successful for Seattle Genetics. The antibody -- our antibody is a fully human IgG 1 that has a very high affinity towards PSMA antigen on the cell surface, and it is novel. It is specific for the dimer, which is the form that PSMA occurs in on a prostate cancer cells.
So the way this drug works, here is the monoclonal antibody that's loaded with the payload of auristatin. And our molecule has the average of about 4 auristatin molecules per antibody. It binds PSMA on the cell surface and then is internalized into an endozome, whereas cathepsin B cleaves the linker, releasing free MMAE into the cell. The MMAE then binds tubulin, and it results in apoptosis of the cancer cell.
Just to present briefly what has been presented in a number of major meeting including ASCO, ASCO-GU. We also presented it at the AUA and also at the Prostate Cancer Foundation, a scientific retreat. Our Phase I study where we gave the drug on 2-, 3-week regimen, which is similar to the ADCETRIS drug, and looked for response in a number of other things. And patients who did well or benefited from it went on to an extension study.
This study looks for patients that had a good performance status, but all these patients had metastatic progressive prostate cancer, castration-resistant. And all of them that were status post -- or the eligibility was status post to treatment with docetaxel at a minimum and many have had multiple prior set of toxic chemotherapy regimens, as well as previous treatment abiraterone and enzalutamide. So these patients really were very end-stage and had very few treatment options. The endpoints of this study were safety and to try to find a dose that we would go into Phase II with, as well as looking for antibodies -- potential antibodies against PSMA ADC. And there was a big component of the study looking for the PK, pharmacokinetics of PSMA and its components, as well as to look for some anti-tumor effects, and that would be in terms of measuring PSMA and as well as circulating tumor cells.
This is a waterfall plot of the responses. The colors are a little bit hard to see. What we're seeing here is the responses to PSA, PSA reductions occurring primarily at the higher doses, as we get above 1.8 milligrams and 2.0 milligrams per kilogram. That's where we're seeing some nice negative deflection of PSA in these patients.
Move on ahead. We're also looking at circulating tumor cells, which as you may know is becoming an important prognostic feature and following prostate cancer patients. And this shows the same thing -- a lot of negative deflections and decrease in circulating tumor cells, especially at the doses of 1.8 milligrams and above.
Let me show you just a couple of representative cohorts, this is the 2.0 milligrams. And what we're seeing -- from the, say, 1.8 milligrams and 2.0 milligrams, all the way up, we're seeing about the same thing, which is anywhere from a 20% to 40% major response in PSA. Here's an example of just -- of the 2.0 milligrams with 5 patients here. Many of the patients would have a very rapid, within the first or second cycle decrease of the PSA, and maintain for really out to a number of months, even 6 months or so. This patient came down, but it ultimately went up. And other patients just had a less significant response. We're still above the 30%, which is generally, according to the prostate cancer working group 2, a still notable PSA reduction. And here's some CTC responses.
So in -- pretty much all the cohorts, in the range of 1.8 milligrams and above, we're seeing that kind of nice responses in the Phase I study. Here's at the -- the highest dose we went to, which was 2.8 milligrams, and we had, again, probably about half of the patients had a good reductions in PSA and CTCs as well.
Patients. We have now about 10 patients from this Phase I who went on to extension study for longer-term treatment. We've had patients -- I cut this off, but we have had patients on this study for up to a year or even more. And as you can see, patients have had long reductions in PSA and these are also accompanied by symptomatic reductions and patients that follow even bone scans that weren't part of the study. But we know, anecdotally, that they were followed at their institutions and patients that have other clinical measures of response to the PSMA ADC.
As far as the PK goes, this is all very consistent with what has been seen with the Seattle Genetics ADCETRIS product, and that is a very well-behaved PK. The half-life of the parent compound, the antibody drug conjugate is about 2 days. But the MMAE has always stayed a very big difference from the parent PSMA ADC, there's at least 1,000-fold difference on the concentrations at any time. And a very significant importance whenever you're dealing with a biological agent, no antibodies to PSMA ADC were observed in any subject.
Of course, everyone's interested in the toxicity of the treatment, and that is the reason for doing the Phase I study. The drug is well-tolerated, but the dose living toxicities of this drug, similar to ADCETRIS, are associated with the auristatin toxin. And it's almost identical to what you can see in the package insert for ADCETRIS, which is neutropenia, which is dose-limiting and this is reversible liver function test. And after a number of cycles, there will be neuropathy, which can be dose-limiting.
So to summarize the Phase I. We have demonstrated a proof-of-concept in patients with highly refractory metastatic castrate-resistant prostate cancer, and we have seen some durable and significant responses in these heavily pretreated patients. And the responses have been robust over a range of doses. And as I said, if we look carefully at all the doses, we've got the cohorts from 1.8 milligram and up, that we're seeing about that same kind of proportion of patients that have good responses. And the tolerability has been good. Neutropenia, some peripheral neuropathy and is reversible LFT elevations, which is what has been seen with the approved drug, ADCETRIS, and the PK is predictable again, exactly what one would expect with this kind of antibody-drug conjugate.
So based upon that data, we have launched into a Phase II trial in chemo experience metastatic castrate-resistant prostate cancer. And then we recently announced that we had passed the halfway mark and that study is accruing well. That is an open-label study. That is, all the patients on this study now are abiraterone and/or enzalutamide experience, in addition to being docetaxel refractory and they may have had at least one other -- they may have had 2 or fewer cytotoxic chemo regimens. So everyone's had docetaxel. Many have had cabazitaxel, or even carboplatin and mitoxantrone or a number of other things. So they're again heavily pretreated and there is certainly -- of need in this population. This study will look longer up to 8 doses, which is about 6 months, and then there's extension that can even go beyond that.
What we're looking for here is what everyone had been asking us about in the Phase I trial, is are we seeing any changes in imaging and tumor size. And so there's a big concentration on looking at RECIST criteria on imaging and a number of other items, including biomarkers. And Bill Olson will talk about that following my talk here. We're assaying for PSMA on the CTC substance, this is part of Bill's talk. As well as looking for PSMA on immunohistochemistry of the biopsy specimens even at the time of diagnosis. And as I said, it's accruing well and we look forward to having some results on this, according to the time lines that Mark have set forward.
So what are the Phase II endpoints of this? Well, we're going to -- everyone looks at PSA, and we have to look at PSA, but there's clearly been some guidelines with the prostate cancer working group, 2 publications. So we're going to certainly look at the change in PSA over the 12-week period of time, maximum decline. The assessments were a decrease of about, probably, should be 30% or 25%. But in the Tc-WG2 [ph], a 30 percentage point decrease of that, as well as decrease of greater than 50% and other things like doubling time. We'll look at that, even though it doesn't have as much meaning or change in flow. But we're going to do a lot of imaging, looking for tumor responses not only in bone, which is sometimes hard to have a target lesion, as you know. But in visceral nodal mets, those patients that have that, even though they won't be the majority of patients, we'll carefully apply the RECIST criteria. We have an independent contractor that is reviewing all the scans independently for objective responses in CRPR and progressive disease.
We're also looking at circulating tumor cells and the time to response including PSA and tumor measurements disease progression. Of course, all these stays ultimately we had to look at overall survival, and we'll get a good idea of how we'd have to structure our Phase III trial as well as progression-free survival, duration of antitumor responses related to an old patient case [ph] at this thing, skeletal-related events as well, which are important. And careful analysis of pain scores including the brief pain inventory, the short form. And the fatigue, which is a very, very common in chemotherapy, it is something called a brief fatigue inventory. Both of these, validated scale that we're regularly looking at on these patients. Pain, and not just in pain score, which is the BPI, but also analgesic consumption.
In addition, quality of life, we feel that a more targeted therapy like PSMA ADC, because of its targeted nature and less toxicity than nonspecific or non-targeted chemotherapy, we'll have an advantage in quality of life. We're using the FACT scale, which is the functional activity of cancer therapeutics, I think. The FACT-G is a general one, and this is -- we're using a FACT-P, which is more specific for prostate cancer involved in this, as well as the safety assessments using the NCI common toxicity scale, the newest one, which is version 4.03.
Bill, also, will talk in much more detail about that. But suffice to say, we don't have 100% patients who are responding. And why is that? And we always want to know that. So we are looking for PSMA expression in those patients. What is the reason why some patients respond, others do not respond. So we're also looking at PSMA expression on circulating tumor cells. And again, Dr. Olson will be addressing this in much more detail. But the data that we come through in the analysis of this will be used in a Phase III study to be able to at least maybe increase the rate -- response rate amongst our patients, or certainly be able to get us a potentially companion diagnostic at the time of approval.
And of course, there's the follow-on indication. Just looking at prostate cancer, there's been a lot of interest amongst our own investigators and other prostate cancer docs try to use this upfront. That is after hormonal therapy, but before docetaxel. And it makes a lot of sense that you'd use a more targeted therapy upfront. And so that's the one other potential study that we've been looking at the feasibility and drawing up some plans for, which is to look in a loan in chemo-naive patients. It's something that we'd like to potentially do. Also, in combination with the anti-androgens.
And you've heard both from Dr. Babich and myself that giving the anti-androgens -- increased the expression of PSMA on the cell surface, so giving this drug in combination with the anti-androgen is actually is a good idea, and something that we'd certainly like to explore. It is also the non-metastatic setting, which would be a biochemical relapse is an obvious clinical recurrence. And some of the studies that have been done, neoadjuvantly with abiraterone, for example, prior to prostatectomy, where you could potentially use this agent, if on biopsy, you see a heavy expression of PSMA, there may be some interest in looking at treating with PSMA ADC even neoadjuvantly or adjuvantly.
But we have non-prostatic tumors. I mentioned that on non-prostate cancers, PSMA has expressed many of them on the neovasculature. There is a study that's going to be starting probably later this year at Brown University Oncology Group as an investigator IND in gleoblastoma, which has a very high rate of expression of PSMA ADC. So we look forward to seeing what the Brown group comes up with. But there's obviously other non-prostatic tumors that there's certainly a big medical need and these are other studies that can be done.
So to conclude my quick and brief synopsis of what's happening with the PSMA development program. We have a Phase II compound that utilizes what is a proven ADC technology, and that is the validated technology that ADCETRIS, an approved drug now uses and it targets a validated cancer antigen, which is the PSMA antigen. We have demonstrated robust antitumor activity, really across a range of doses, anywhere from the 1.8 milligram per kilogram up to the 2.5 milligram. And we are now developing as well a biomarker or companion diagnostic in conjunction with our Phase II trial. And there is a strong support for use in other tumors, [indiscernible] tumors. And in fact, there's one study under an investigator IND by Brown, is probably the first of these studies to be done.
So I thank you very much and look forward to talking to you later.
Mark R. Baker
Thanks, Bob. Next up is Bill Olson talking about biomarker development.
William C. Olson
So good afternoon, everyone. It is a real pleasure to describe our efforts with regards to biomarkers as part of the PSMA ADC program. This isn't an element of the program that we had described previously. So it's a pleasure to have this opportunity. And then also, use it as an example to emphasize our broader commitment to personalize medicine or physician medicine.
So just one quick slide to make sure we're all in the same page with regard to this issue. So conventionally and especially for cytotoxic cancer therapies, the drugs are administered to broad groups of patients in an unselected fashion, despite knowing that only a minor percentage of the patients may actually respond to or benefit from therapy. Whereas, others may receive treatment without deriving benefit and may, in fact, experience toxicity. So the whole idea of precision medicine, of course, is to use a biomarker or some other strategy to change that equation, to enrich for patients who are likely to have beneficial outcomes to treatment. And thus, enable the other patients to pursue more promising options.
So these obviously aren't new concepts. The slides just summarizes some of the important oncology drugs whose use is tied to a particular biomarker. And what we've plotted here is just the timeline for the first FDA approval of those agents. So I think it's widely appreciated that the availability of a test for HER2 overexpression accelerated the development of Herceptin in breast cancer, and that test was critical for expanding its views to other indications. Glivec is another important example. Glivec, of course, is an important multi-targeted kinase inhibitor. And different biomarkers enable it's different activities to be exploit for treating different tumors. So I mean there's many important examples. But maybe just one other the point is, this trend continues to accelerate with 3 approvals already this year of such agents, and really the number is 4, if we include the afatinib, which was approved last week by FDA for the treatment of EGFR-mutated non-small cell lung cancer.
So these concepts are just embedded through our oncology portfolio. So John Babich gave a terrific summary of the compounds that were developed at Molecular Insight. And I guess, I just like to emphasize that with drugs like Azedra and the MIP-1095, we really have the perfect theranostic, where the therapeutic agent and the diagnostic agent are chemically identical.
So with Azedra, one simple uses a baby dose of Azedra to ensure that the patient's tumors avidly uptake the drug before treating with a larger therapeutic dose. With 1095, the situation is similar in that diagnostic and therapeutic agents are the same chemical. Only the nature of the radioisotope has been changed to -- for in this case, to take advantage of the resolution of PET imaging that we heard earlier. We're developing MIP-1404 as a stand-alone imaging agent. But one could see how this agent could be used as a companion diagnostic really for any PSMA-targeted therapy, including our antibody-drug conjugate. And again, I'll have a few slides which will describe the scope of the biomarker studies in that program.
So I mean, Bob did a wonderful job summarizing the Phase I data and the rationale for biomarker studies. So just briefly, again, we did see a range of responses to treatment in the Phase I study. Again, there were a group of patients that had the deep endurable reductions in PSA and circulating tumor cells and maybe other signs of antitumor activity. There was another group of patients that had stable disease over that 12-week period and even longer. And that may represent clinical benefit for this group of patients with very advanced disease, and really few other treatment options.
Collectively, these patients represent well over half of the patients treated at the higher doses. But there is another group of patients that progressed right through therapy. And the standard baseline parameters that were collected as part of the study really didn't allow us to distinguish the responders from the nonresponders. So the goal is, in Phase II, to see if we can identify a biomarker, which would allow us to prospectively identify those patients who would be good candidates for therapy.
So PSMA ADC is a targeted agent. So target expression would provide a -- maybe predictive of response. On the one hand, we've heard that PSMA is expressed nearly universally in prostate cancer. So when we question the value of measuring PSMA. On the other hand, as we've heard also, prostate cancer is a very heterogenous disease. It encompasses these indolent forms that don't pose an immediate threat to the patient and don't require immediate treatment and it includes these more aggressive forms that are deadly and other types of forms that we're treating. PSMA tends to be expressed at higher levels in these more aggressive forms of disease, but also amongst patients with the aggressive disease. The level of PSMA expression can vary from patient to patient.
We know from some preclinical studies that the level of PSMA is very important for the activity of our agent. And we even have some quantitative understanding of the level of PSMA expression that's important for selective antitumor activity and really maximum cell killing. In the Phase II study, as we've mentioned, PSMA expression is one of several biomarkers that is being examined and these biomarker tests were developed with a nod to the future. We think PSMA ADC can address important treatment needs both in the U.S. and elsewhere. And so the biomarkers have to be something that could be used alongside PSMA ADC around the world. The slide just summarizes some of the approaches we're taking. A common approach for biomarker analysis is for us to take us in a section of tissue and analyze it for the present [indiscernible] and some biomarkers by immunohistochemistry or other methods. We have an excellent immunohistochemistry method that if we're looking at the level of PSMA expression within prostate cancer, and this same method, as Bob mentioned, can be used to look at neovascular expression of PSMA in non-prostatic tumors and, really, that might be the best use of this test. In the issues relate to the challenges in getting contemporary metastatic disease from patients with boney lesions rather the type of tissues we get for this analysis typically or tissues from early-stage disease, when a disease
was confined to the prostate and maybe before the patient has received any treatment. So these evaluations may be of value, but we also recognize that the disease may evolve as it spreads throughout the body and adapts to different modes of therapy. So for that, we're also looking at contemporaneous biomarkers that we can access in the blood and this include the circulating tumor cells that we referred about earlier. These are, of course, these rare and robe tumor cells that break away from the main tumor mass and travel throughout the body and may be important for establishing new tumor sites.
In the Phase I study, we enumerated these cells and looked at how the numbers change following treatment with the ADC and we found that we could readily detect these cells in most of the patients. In Phase II, we're continuing to enumerate the cells and look at changes, but we're also going one step further, and looking at the level of PSMA expression on those cells. We're also looking at biomarkers that may be present in the plasma or liquid portion of blood.
And of course, we now have another very powerful tool for assessing PSMA expression. We have the ability now to perform PSMA imaging of these patients and get really a global view of the extent of PSMA positive disease in the bodies of these individuals.
So this is one of the capabilities that first sparked our interest in Molecular Insight. The acquisition was completed after the trial was underway, so we won't be able to obtain images from all of the patients treated in the study. But we do hope to obtain such images for some of the patients in the Phase II study of PSMA ADC. And I'd really think that this capability sets this product apart from, say, other antibody drug conjugates or even other targeted therapies, which rarely have a molecular targeted imaging agent available for the same target.
So this slide just summarizes the different biomarker evaluations that are ongoing in the trial. As we mentioned, we moved in PSMA expression on the tumor cell by immunohistochemistry, PSMA expression on circulating tumor cells by each of 2 different platforms, and I'll have more to say about that in just a minute. We're also performing standard clinical laboratory tests for markers of neuroendocrine disease and this is chromogranin A and neuron-specific enolase. Let me and Bill just take a moment to explain. We discussed earlier how prostate cancer is heterogeneous. It's also adaptable and it's known that most prostate cancers of course, start out as prostate adenocarcinoma, the most common form and the form that expresses abundant levels of PSMA. But it's also known that prostate cancer can adapt or transform to a different phenotype called neuroendocrine prostate cancer. Neuroendocrine disease often occurs after prolonged androgen suppression and this form of the disease can express lower or even no PSMA. So these simple tests give us some insight as to whether the patient may have a significant amount of neuroendocrine disease.
And in addition to these very defined and focused tests, we are performing more unbiased evaluations of potential biomarkers by proteomic, genomic and transcriptomic analysis, and stay tuned for more on these methods later on.
So I would just like to take you through some of the types of information that we obtained with one particular methodology. This is looking at circulating tumor cell data using the technology from Epic Sciences. It is a relatively young company, but it's committed to developing circulating tumor cell technology as a companion diagnostics. And the technology is really quite powerful. So in this approach, one simply takes blood from a patient and place it out on different slides. Unlike other CTC methods, there's really no attempt made to separate the circulating tumor cells from the more abundant lymphocytes. So there's less potential to lose cells in that process and it offers at least a theoretical potential for us to be able to measure CTCs and examine the expression of PSMA in most or all of the patients.
So in this technology, what one does is, again, they place the cells and then we stain them with a series of different dyes. One that binds the DNA to a [indiscernible] looking at nucleated cells and say, not cell debris; another dye for Epstein's lymphocytes, and as you can see, most of the cells in the cell division are lymphocytes, as you would expect; a third dye for keratin. Now, this is an epithelial marker and of course, epithelial cells normally remain in tissues, they're not found in the blood. This is a sign of a circulating tumor cell.
Next, we stain with an antibody for PSMA and finally, one can overlay the images. And you can begin to see how the PSMA-positive circulating tumor cells can be visualized. And this technology really provides a wealth of information. We can get the overall numbers of circulating tumor cells in the blood of those patients. We get information regarding the number or percent of those cells that are PSMA positive. We get information regarding intensity and cellular localization of PSMA on those cells. And these are 3 circulating tumor cells from a single individual with prostate cancer. And so you can begin to see how even within a single patient, the intensity of PSMA expression can vary from one cell to another.
Now, we get this information for this individual circulating tumor cell, we also get this information for clusters, a circulating tumor cell. We get information about whether the CTCs appears like they're in a growth modes or dying or apoptotic. And we can also look at cells that wouldn't otherwise meet the classic definition of a circulating tumor cell and may be ignored by other methodologies. So it's a lot of new information. It really provides a window in some respect into some intricate tumor biology, some of which may prove important for response to treatment with our drug.
So just in terms of methodology, again, we're generating a fair amount of biomarker data by these different methodologies. We're comparing it with outcome's data, according to the end points that Bob described, PSA reductions, changes in circulating tumor cells, time to progression, and other endpoints. We're evaluating cutoffs for each of the biomarkers that might distinguish responders from nonresponders. We would like a simple biomarker assay involved, say, a single measurement, but we recognize that the situation may be more complex, so we're looking at relationships between biomarkers and potential signatures of response.
And just by way of example of the types of information that we gain. So here's a sample data from the Phase II study of PSMA ADC, so each dot represents a different patient from the trial. We've divided these patients into 2 groups, depending on whether they are positive or negative for a given biomarker and then, we plotted their response according to this qualitative scale. So again, every point is a different patient. The horizontal bars represent the median response of the different groups and perhaps you can begin to appreciate even with this very limited data set, we begin to see responses fall along the lines of these particular biomarkers, such that in this case, the biomarker-positive patient, at least, thus far appears to be the better candidates for therapy with PSMA ADC. So obviously, this is a very preliminary data. It's very early days.
Our hope is that such trends continue and maybe even strengthen as we progress through the trial.
So this slide just illustrates that there's a clear path to co-development of the drug and the biomarker or companion diagnostic if we need one. So just as there was early stage development PSMA ADC, so there was early stage development of the biomarker assay. Phase II is the real critical point for evaluating the drug and the biomarker. Our hope is that Phase II yields a suitably predictive biomarker that could then be validated in Phase III and then coregistered and launched worldwide alongside the ADC.
And so this is the pathway that assumes that the biomarker is a noble measurement. It's not part of the practice of medicine, such as PSMA expression, and it would be developed as a companion diagnostic. And that is the path we are planning for. The task is simpler if the biomarker is a standard clinical laboratory test.
So this is my final slide. Just to summarize, Progenics is developing a portfolio of targeted anticancer agents and we are committed to ensuring that they're used in a way that maximizes patient benefit. We have several biomarkers that are being evaluated in the ongoing studies of PSMA ADC, and we see a clear pathway for co-developing the drug along with a biomarker or companion diagnostic moving forward. So I'll end there and thank you for your attention.
Mark R. Baker
Thanks, Bill. Next up is Jim Garrison talking about our business development strategy.
Thank you. By way of introduction, as Mark said, Jim Garrison. The 2 gentlemen before me had a little bit more tenure at Progenics. I think they're total is about 35 to 40 years. I've been with Progenics about 1.5 years. So you know before that, I was 5 years at a multinational pharmaceutical company called Progenics Pharmaceuticals where I was the VP of Business Development, looking to grow the U.S. business and we did some really good deals there, but when I had the opportunity to join Mark and the management team in here, Progenics, and advance this vision of becoming a preeminent oncology company, it was an opportunity that I couldn't pass up.
So when I joined, I mean, you heard a lot today about the things that we brought in and what we're doing, but when I joined, the strategy, as I said, was just getting kick started to be a truly integrated oncology company. But there was good science being done for the last 20 years in other areas, and so we developed some really great compounds that while we couldn't fund them in-house and they no longer fit with our strategy, they deserved and needed to be developed outside. And so our goal was to find very good homes for these compounds. And specifically what I'm going to talk today about are the 2 compounds. Up here, PRO 140, which is a CCR5 monoclonal antibody for HIV, and another monoclonal, PRO 391, which is used for C. diff infection.
So the first thing we did was we looked at what we had as an asset and -- as assets, and looked at what we'd wanted out of a partner. We needed a company where this was going to be a strategic fit for them. We wanted to make sure that they had the wherewithal to continue the development of each one of these programs and when I mean wherewithal, of course, I mean monetarily and resource wise, but also that they had the commitment to the space and to get these programs moving forward.
And lastly, of course, we wanted to make some money on it. So we want to recoup some of our investment with some money up front and then also on the back end also.
A little bit about PRO 140, it was established -- look, Progenics, one thing I've learned in my 1.5 years is that there's great science coming out here. And so this was a Phase II product for HIV, again, a monoclonal. It had a very good efficacy profile. You saw a good viral load reduction and good tolerability. And there was differentiation also. Work was being done on a auto-injector for infrequent subcu dosing, so there was a niche for an area where this can truly get to an unmet need in the HIV space.
My work was somewhat eased a little bit. The skids were greased because there was a lot of, for lack of a better word, buzz about the product out there in the medical community. We presented it at certain meetings. There were papers published on this. So people knew about the opportunity and once we decided that we were going to look for a partner, not only were we making calls, but we were getting calls.
Ultimately, we decided on a company called CytoDyn. I'm not sure how many people know about CytoDyn, but they are a small publicly traded company, specifically focused in the area of monoclonals and specifically focused in the area of HIV. So while small, you could see they would be the perfect partner for PRO 140. And then now, if you follow CytoDyn, you'll see that this has become their primary focus in the development in their R&D efforts.
The opportunity of taking PRO 140 and doing the deal with CytoDyn was able -- it allowed us inside Progenics to continue to enhance our out-license and expertise. Obviously, Mark and the team -- it was not like there were no process. Mark and the team did a great job with Relistor and Salix. But this was a little bit of a different animal, so we had to continue to get a process in place where we were going to be able to talk with companies and get this transferred out.
Specific to this deal, we had to help CytoDyn to deal with contingent on them getting some financing. So we helped them out with that and we continue to support them. We are truly a partner with the 2 companies that we've out-licensed to. And so it's an ongoing process, sort of an evergreen process. And here are the terms. We got $3.5 million upfront from CytoDyn at the commencement -- now, where they are now, again, is in Phase II and so, at the commencement of Phase III, we get a milestone of $1.5 million, at filing, $5 million and a royalty of 5% on sales.
The other asset, PRO 391, another monoclonal antibody, specific to treat C. diff infection. Again, established on good science, but as opposed to PRO 140, which was a Phase II compound, this is a preclinical asset, but a favorable preclinical work has established this as kind of teed up for those IND-enabling studies. And as with PRO 140, the buzz out there about this opportunity was there. People knew about the compound and so when we went out and started talking about it, again, the calls were coming in along with the calls going out. And we had actually a couple of large pharmas very interested in this opportunity. And that's a nice place to be when you could pick and choose from a couple of nice term sheets. So ultimately, though, we chose a partner that we thought was best and that was MedImmune.
I don't think I have to give you too much information. You probably know MedImmune is the R&D arm now of AstraZeneca. So this asset is in very good hands and they're moving it in the clinic now.
So what we got? For a preclinical asset, I think we did very well up front. We got $5 million up front, we announced this last year, and there are meaningful milestones, meaningful throughout the development program. So where you would envision getting milestones, that's where we are. Royalties commensurate with what you would expect from a preclinical asset. So those single digit, they are tiered based on sales and there's actually a milestone for an additional indication. So if it goes beyond C. diff, we have a milestone for that us also. So we found 2 very good homes for these assets and good partners. And again, I think it speaks to the great science coming out of Progenics.
That's it. Mark?
Mark R. Baker
Thanks, Jim. So what a wonderful group of talks we had this afternoon. Anytime you can combine Helen Keller, Thomas Edison and a Renaissance architect in a single talk, you know you've really heard something. Thanks to Jonathan Simons for that. And I don't believe Jonathan was aware, but the research that he described by Marty Pomper and Steve Cho at Johns Hopkins is on a compound, the PET compound, that we acquired the rights to through the Molecular Insight. So I think you can see the depth of our work in that segment.
Just 2 thoughts that I wanted to leave you with as we close today and then we'll move on to our final Q&As. First, you saw it in Jonathan's talk, this concept of a theranostic, I don't know if I really like that word, but therapy and diagnostics, theranostic. When I was at the ASCO meeting this year, and what an amazing meeting that was in terms of the developments in oncology and just a sheer number of people there. And when I stood in front of our poster, it seemed like the world just walked by me and what I heard from KOLs was their incredible excitement about the ability to image and treat. I have to say I use even simpler language and I say, see and treat visualize cancer. If I could have you leave with any thought today, it's that what our work we hope can accomplish is the ability to see cancer and to treat it. And this is what clinicians want. And this is what I think will drive the acceptance of these products and hopefully, commercial success in terms of reimbursement as we develop sophisticated ways to see cancer, to treat cancer in a targeted way and to follow it until [indiscernible] hopefully, I believe, much longer life cycles of patients with cancer. The second and last thought I wanted to leave with you is that I view my goal as the leader of this company, is to build a balanced company. And by balanced, I don't mean spread wide and thin. But what I mean is a company that has the best potential to generate the value for shareholders.
You see that we've made a big bet around the PSMA antigen because we believe it to be perhaps the best oncology target. But we are diversifying our risk by using antibody drug conjugate technology, by using radionuclide technology, by investing heavily in therapeutics, but also investing heavily in imaging agents that may reduce the need for therapeutics, but fit with the needs of our society in terms of the treatment of cancer.
We're diversifying across different areas of oncology, including our work with the Azedra product, treating an ultra-orphan indication, perhaps the type of indication for which there may be an opportunity for Progenics to become a commercial organization. We want to be balanced, we want to be focused, we want to develop great drugs, and we appreciate you spending the time with us this afternoon. I'll now open it up for Q&A on what we've presented or we can go back to the earlier presentations as well if questions have risen. And here's one here.
I certainly appreciate the thoughtfulness that goes behind developing therapies as well as diagnostics, and what I would like to know is in terms of your strategy, specifically for PSMA ADC as you approach the end of the Phase II trial, do you anticipate that you'll wait for the companion diagnostic to be ready? Or do you expect that you'll just proceed with the Phase III and the companion diagnostic will come along at some other state, at some later date?
Mark R. Baker
Brian, I think that we're very well positioned there because with respect to PSMA expression, if that proves to be the biomarker that we would choose to predict response, I think we're in a wonderful position to move that right into Phase III development. And then it would be available at commercial launch. If the biomarker is some other attributes, perhaps we will be lucky and that attribute will relate to something that can be studied with a simple blood test. You saw in Bill's presentation that we are looking at chromogranin A, for example, or a C, if those were possible markers, they could be accomplished through a very simple blood test. But it is possible that the biomarker we find in our proteomic analysis or our genetic analysis could be more complicated and that could lead to an addition to the clinical development path. But what I hear somewhat clearly, I'm sure all of you are hearing it, is what this society needs is therapeutics that are tailored, targeted to particular patients. And so if we can show what -- Bill showed that very preliminary data where we see a biomarker beginning to indicate response, if we can show that to be the case, increase the response rate by selecting the patients that will respond, I think we're offering to society, to the payors, to the patients, a drug that will be highly effective, and therefore I think we're -- dramatically increases our chance of success. So sorry for that long answer and I can't predict all the outcomes, but I'm hopeful that we're going to have something that will work and that will be ready to go.
On the ADC, I had a question about the neuropathy. I saw that you have a couple of instances of grade 3 and that was dose limiting, but can you talk about how neuropathy is handled per protocol in the Phase II? And it's emergence, I suppose?
Mark R. Baker
So we have been seeing a few cases of neuropathy, the patient population that we're studying are at post-chemo setting and so all of the patients on trial are coming with the use taxanes. We are seeing most neuropathy arise in patients who -- where neuropathy had arisen in their prior treatments. So it doesn't seem to be treatment emergent and most of those patients with respect to treatment with PSMA ADC, but perhaps it is bringing back neuropathy that has been seen in the past. There's no question that, that's a very important side effect that we're following closely. So far, I'm not seeing that it should impact the development of that, but it's something we're looking at closely.
For the PSMA Phase II, given that it's an open-label study, any thoughts as to what you would want to see in response, whether it's in the whole or selected population that would give you encouragement to move forward. What do you think would be a win on PSMA or any other endpoint for that matter? And assuming you move ahead in this very end-stage prostate cancer indication and especially given all the proliferation of therapies out there, any thoughts on possible comparator arms in the Phase III?
Mark R. Baker
So it's -- what a great time was spent for prostate cancer patients, and I think Jonathan's slides showing how many therapeutics have been approved, a lot through the efforts of that great organization, the Prostate Cancer Foundation. It's wonderful news. But no patient has been cured and many months have been added to the lives of men suffering from prostate cancer, but unfortunately, too many men are dying. The androgen down regulator space has been the area of greatest achievement. And to me, that is a great development from our perspective of the PSMA target because the data indicates that starving tumor of that hormone up regulates PSMA expression. So it ought to marry well with our targeted therapeutics and our targeted imaging agents.
In the development of prostate cancer therapeutics, there is now a pretty well-trod path that the androgen down regulators followed, and we are following beginning with the end stage patients and I think we will have to follow that path. We are certainly looking for opportunities to treat patients early on and I think with the success of the androgen down regulators, you'll see how drug development companies are able to move upstream, if you will. And I would hope that PSMA ADC will follow that path. But a great, great promise of antibody drug conjugates is that of targeted chemotherapy. And so for me, the best commercial home for our drug will be pre-systemic chemotherapy. And if we're able to show its efficacy and safety, you would use the targeted chemotherapy before you went to the systemic chemotherapy. I think that the patient population is changing because of the androgen down regulators. We do see, as Bill mentioned in his talk, changing characteristics for patients as they come to the end stage. And so, it's a dynamic field, which we love because we're a small company and we think that we can turn on a dime, we think that we can take advantage of this change in setting.
"What would constitute a win?" is a question I fall to sleep with most nights and hopefully -- and my mind is processing overnight. Certainly, I'm encouraged by the level of activity that we saw in Phase I. But the biomarkers seen, to be truthful, are a little crude, right. Is PSA a good indicator, currently? I'm not so sure. And we do see wonderful therapies. Alpharadin, just in the New England Journal today, they have no effect on PSA similarly with prevention [ph]. Circulating tumor cells, as I speak to KOLs, it certainly seems like a better prognosticator. But it's early days and we're building data. Amazing that we can look at individual circulating tumor cells with the technology that Bill talked about. So that makes me very excited. If we saw that kind of response rate we saw in Phase I and we're able to have a predictive biomarker that would boost that by x percent, would that be a win? Yes, I think so. And it would be a win for the patients who, having failed androgen therapy, are facing extremely limited choices. My personal hope, but I'm speaking, and not as a scientist to you but a great student of this disease, is that our drug could be used in combination or in sequence with the androgen down regulators prolonging life. Very recent data showing that starving the tumor for hormones could have negative side effects. And so, is there a way to prolong that period of time where androgen down regulation works by extending -- with the use of our drug?
The one thing about the setting, speaking from a commercial perspective, is that there's very little that's efficacious for patients post-chemotherapy. The remaining therapies have significant toxicity and very low efficacy. It could be mitoxantrone, it could be other drugs in that space who would be our comparator arm in Phase III. Those are possibilities, but we haven't made any final decisions and of course, we'd have to speak to the agency before finalizing that. Other questions?
Well, thank you so much for your time here, the people with us in New York, and to those listening on the WebEx, we greatly appreciate the ability to talk to you about Progenics, and have a great day. Thanks.
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