All right, welcome back to the Cantor Fitzgerald Global Healthcare Conference. My name is Rick Bienkowski. I'm a Biotech analyst here on the team, and today I'd like you to please join me in welcoming Craig Tooman, President and CEO of Silence Therapeutics, who will be presenting on the company. So welcome, Craig, and the floor is yours.
Thank you. Thank you very much, and thank you for the Cantor team's invitation today. We'll start with our safe harbor statement. We may be making some forward-looking statements today. Please make note of that before making investment decisions. Silence is aptly named because we silence diseases through our precision engineered medicines. Very, very precise, and they're created with our own proprietary siRNA technology. This recently, in our clinical trials, has shown to have great efficacy, great safety, and real durability, so you'll hear about those as we go through the presentation. Silence at a glance, we're involved in advancing our own clinical programs. Also, we have proprietary siRNA technology that's being seen more broadly, platform technology and with partnerships, and that includes some collaborations that we'll also talk about. Starting with our clinical programs, our lead two programs are zerlasiran and divesiran.
Zerlasiran has gained a lot of attention in a very large cardiovascular market. It is completing a phase II, and we've been reading out that data as we go. Of course, it's for elevated Lp(a) in a genetic arena, and it is a Lp(a), as you know, is a risk factor for cardiovascular disease, impacting up to 20% of the world's population, so it's a very large, underserved market. It is not a U.S. issue, it is a global issue. Divesiran is for hematological disorders, so on the other end of the bookend. We're in a phase I/II program. We've largely read out phase I. We're continuing that and moving into a phase II initiation by year-end. So very exciting. This is in polycythemia vera, a rare blood cancer with significant unmet needs.
In terms of the platform, it has broad utility. We've seen it, as we've mentioned, in large areas and in rare diseases, but also some in between that we're studying, so very, very broad utility. We are enamored with the technology because also its durability, and it's reversible. So if you don't like the effect of this, you just stop taking it. It's fully reversible. We have focused on the liver initially in our RNAi programs, but we are starting to explore a little bit beyond the liver, and partners are pretty keen to have dialogues around that. We focused on liver because it has high productivity, and based on studies, a higher likelihood of approval versus the industry average. We have collaborations, partnered pipeline, over a dozen programs, up to $5 billion in potential milestones. We'll talk more about that.
Analyst coverage is growing. We have most recently added Jefferies on Labor Day to that, with a buy recommendation. We're in a very good financial position, with a cash runway into 2026. Silence has been involved in siRNA for over two decades. We've gone through the period of experimenting and moving the corporate arena from an AIM listing to a NASDAQ full listing and delisting AIM over this period of time, that's two decades. We've certainly done work in LNPs, but have more recently focused on GalNAc and siRNA and associated intellectual property. So that's where we're focused mostly today, and that's where you're seeing the data readouts in terms of the clinical programs. We are a global company, a small company, but very global, 120 employees or so. We are a PLC, so we are based in London.
Our office is in Hammersmith. We have labs in Berlin, Germany. A lot of our science has been occurring there for better part of two decades, and we have a New Jersey office in Hoboken, so very global. We call our technology basis the toolbox. It is the siRNA molecule specifically designed. It is also the linkers that we have designed in a proprietary fashion. And of course, we're utilizing GalNAc for that highly targeted delivery to the liver. We are always fine-tuning this technology, including the linkers, et cetera, to make sure that we're getting the best effect possible with what we have. Talked a little bit about how we're set up. It's actually great to have our wholly owned programs, but also our partner programs.
In biotech, as you know, you raise money, and then you use that money over a period of time. It's great to have the partner programs as well for sources of non-dilutive capital, and also to explore in areas scientifically that you may not explore yourself. We've had great luck with our programs, with our partners as well. This is how our pipeline looks today from a proprietary standpoint. We've talked about zerlasiran in the large Lp(a) arena. Divesiran, again, targeting TMPRSS6 for polycythemia vera. Very exciting program, incredible data. We'll talk more about that. The next two programs are complement programs that we brought in from Mallinckrodt. We had a relationship with Mallinckrodt, a great partnership. They are focused on later stage, so we brought those in an earlier stage, preclinically.
And then the next two are Hansoh, where we have three programs with them. Two of them, we have global rights outside of China, so those are proprietary outside of China. And then we have other multiple programs within our pipeline that are undisclosed, but we're very encouraged by. These are our partnership programs. AstraZeneca is a fairly broad program, including cardiovascular, renal, metabolic, and respiratory. This includes upfronts and an equity investment. And also very interesting that we've now moved into the first program in the clinic in February. So that is undisclosed, but it is our third program in the clinic. In terms of Hansoh, we have a relationship with them as well, upfront cash and milestones that will equate up to $1.3 billion if paid out.
So in total, the two partner programs equate to $5 billion in milestones. And as I mentioned, we have rights to two of those outside of China ourselves, so proprietary in a way. We are very focused on accelerating our lead proprietary programs. We'll talk a little bit about that. Advancing our partner programs, that's going well, and advancing and expanding our own proprietary platform. There was a point when, in these very tough markets, where people didn't want us to spend as much on the rest of the proprietary programs. I'm very pleased that we did not discontinue those, because there are some very exciting programs in those, and we continue to move those forward now. Let's talk a little bit about the clinical program, starting with the zerlasiran . So the zerlasiran targets Lp(a).
As I mentioned, it's an independent risk factor for cardiovascular disease, affecting 20-25% of the global population, depending on how you define that measurement, but it's becoming more standard in terms of the measurement. The Lp levels are genetically determined, so you know very early in your life what your Lp levels are. It is recognized as a major untreated risk factor in cardiovascular disease. Increasingly from the studies we see and the readouts we hope to see, we believe this will continue. Lp levels are not modifiable by approved medicines or lifestyle changes. So unlike cholesterol, total cholesterol, changing lifestyle will not alter this number. So we believe that what we have in zerlasiran is a real opportunity and potential for a major unmet medical need treatment.
It is amazing with Lp how early it can affect people, and this is just a couple of patients that we know well, who actually had experienced Lp in their forties and fifties. So it is a you know, pretty silent disease, and unless you get measured, and unless you look at some of your family history, you may not know what is looming here. So increasingly, people are going in to get tested, and they should. We believe zerlasiran has a very substantial market potential. As we've talked about, if you look at the cholesterol market, it's pretty similar in epidemiology in the US and the five major European markets. That cholesterol market had several entrants, you know, all selling multiple billions of dollars. And again, this is a genetic issue. This is not modifiable.
There's nothing you can do other than treatment here, so we look forward to being one of those early on and offering one of those treatments. The CV event risk significantly increases with high Lp levels. That's been established. You can see for heart attack, and heart failure, you're seeing 2-3x the increased risk based on the levels of Lp that you exhibit, and as I mentioned, it is a global issue. Increasingly, as the studies come out, you're seeing actually an inflection in CV risk, beginning at Lp levels that are much lower than originally assumed, and I think this is a natural progression in the disease, where people, as they do more work, are realizing that even at lower levels, you have significant cardiovascular risk, so stay tuned. I think you're gonna see more and more of this be published.
What that means is a wider patient pool for those of us that are helping people treat it. There's also growing awareness of Lp as a key cardiovascular risk factor broadly, and you're seeing it now being published in the popular press. So for example, NBC News now is running articles on Lp. We routinely now are asked by friends and people who know us, "Should I go get tested for Lp, and what can I do if I do have a higher Lp?" So it is something generally becoming better known, not just in the medical community. The major cardiovascular societies have been recommending Lp testing for some time.
If you look at AHA/ACC, you know, as early as two thousand and eighteen, you had the notion of family history and to be tested if you had a family history. 2021 , the Canadian Society, in 2022 , European Cardiovascular Societies, are asking for a measurement at least once in your lifetime. Why once in a lifetime? Again, because it's genetic. So in terms of the zerlasiran phase I program, two parts to it, the single dose and the multiple dose. We are looking at participants with Lp greater than 150 nanomoles per liter. Healthy volunteers in the single dose showed reductions up to 98%. Again, it's after a single dose, so pretty incredible, and very durable. You know, effects persisting over a five-month period.
In terms of the multiple dose, similar, and we'll look at that data in a minute, up to 99% reduction in Lp(a), and again, very durable. So we feel like this is a great program to be thinking about moving forward. We'll talk more about that, and no safety issues. This is our phase I multiple dose study data. As you can see, the blue is placebo. You can see the multiple doses given, the 200 mg and the 300 and the 450. What you can see, if you follow the 300 and the 450, is they largely lie over each other in the outcome out to 201 days, and so we've opted to go with the 300 milligram dose.
In terms of the phase II, evaluating ASCVD, with Lp(a) greater than 125, so a small reduction versus the 150, 60-week study. We're in the final readout of this as well in phase II. The primary endpoint was met 36-week, definitively, and if you look at the median maximum reduction, again, greater than 90%. Very well tolerated, no safety issues. So as I mentioned, we're gonna move forward into the phase III by the first half of next year with a 300 milligram dose. Let's talk a little bit about divesiran for hematological disorders. Polycythemia vera is a rare blood cancer. It is really excessive production of red blood cells, and the RBCs are something that you can measure in the hematocrit. RBCs is a portion of blood, is your hematocrit read as a percentage.
It is a serious chronic disease. There's a lot of concern by patients who have this disease about clotting, thrombosis, and it makes it particularly burdensome. It is a rare disease with approximately 150,000 people in the U.S. and 3.5 million worldwide, so it's on the larger side of rare disease. And diagnosed commonly for people in the 50-70 year age bracket. So the goal here is really to treat hematocrit and try to keep it below that controlled level of 45% and to reduce the cardiovascular major thrombotic events or episodes. People with polycythemia vera experience significant challenges. As we talked about, they have inconsistent hematocrit control, and it doesn't take too much above the 45%.
If you look here, 45%-50% to get 4x more likely death or CV cause from thrombotic events if you're in that area. So pretty significant challenge, if you will, if you're a patient with high hematocrit. The patients are often iron deficient, and some of the treatments actually exacerbate that iron deficiency. And the disease burden, as we talked about, what they really have to do is multiple phlebotomies, and we'll look at that in a minute, three in six months or five in the last year. But if you're leading into that whole notion of all the phlebotomies you need to have prior to treatment, it is a real challenge, and fatigue can result from that.
So I think if you see some of the symptom, symptomatology, you'll see here, as referenced by a patient, that fatigue is a real issue. As I mentioned, there's a lot of concern about the thrombosis by patients, and I actually know some of them. That is a real fear, particularly when they wanna travel. Divesiran has the potential to be the first siRNA in PV. We're very pleased about that, that Silence is first in class. It targets TMPRSS6, and it modulates hepcidin, and hepcidin regulates iron. So we'll look at that, cause and effect in a minute. The proof of mechanism we have demonstrated in healthy volunteers in our study, and then the positive results now that we've seen and portrayed largely from the San Diego, the PV trial phase I, the results are very clear.
We also have fast-track and orphan drug designation for polycythemia vera. In terms of the phase I study of divesiran in PV, it was open label, so we were able to see the data throughout the study. The inclusion criteria included a PV diagnosis, at least three phlebotomies in the last six months or five in the last years, I've mentioned, and you'll see that as we look back before treatment in terms of the effect. You can also have a stable dose of cytoreductive agents, no hematocrit threshold leading into the phase I open label study. We'll control for that most likely in the phase II, but we did not in the open label, which is interesting. In terms of the dosing and follow-up, we evaluated 3, 6, and 9 milligrams per kg.
It was administered subcutaneously every six weeks, sixteen-week follow-up period, and then, that makes a total duration of the study 34 weeks. As of now, we're at 21 patients enrolled. I'll show you a data set in a minute. It's a few fewer patients, earlier cutoff, but this is 21 patients enrolled, and you can see here the number of patients in each cohort. So this chart, we're very pleased to show you. You can see the three cohorts and the three colors. If you look at the screening and the treatment, hopefully, that's clear from the bottom. We have backed up to look at the red dots. Those are the phlebotomies prior to, in the look-back period, prior to the screening and treatment period, and you can see how many there are by patient.
Then you can see where the treatment occurred, and in the three cohorts, you can see only three phlebotomies in that post period. Two of them were actually at high hematocrit levels. They were not at the controlled group coming in, and one was at the very end of the period, not within the treatment period, but within the review period. So if you look at this, and you look at that middle cohort, and you imagine that those two phlebotomies were only with a high hematocrit, if you look at the control group, we had 100% control for those that came in well-controlled to stay at 45% or better. So just an incredible efficacy. As we mentioned, divesiran elevates hepcidin.
You can see, as we're dosed here quickly, that uptick in the hepcidin level, that demonstrates that we're hitting the target in the right way. And the effect of that in both cohorts are that you brought down hematocrit below 45%, again, in both cohorts. And really importantly, divesiran has been very well-tolerated to date. No preclinical signals, no drug-related SAEs, no withdrawals, and very mild injection site reactions, which you would expect with this sort of treatment, but all grade one and fully resolved. So very, very exciting data, and we'll look to continue to move this into phase II, as I mentioned, by year-end. So in summary, key investment highlights, we are advancing multiple wholly owned clinical programs, just have great data on both of those programs. Zerlasiran targeting cardiovascular market, we think with multi-billion dollar potential.
Divesiran poised to be the first siRNA in PV, so first-in-class, and by nature of these results, we think also best-in-class. We are also progressing the existing partnerships and new opportunities with AstraZeneca and with Hansoh. We have quite a few other companies actually, now that they've seen the results that we're putting forth, increasing interest in partnering with us around the GOLD platform more broadly. And as we mentioned, the proprietary siRNA technology platform, we think it really is just in the early stages as one KOL calls it. He really thinks it's revolutionary, not evolutionary, and we agree with that. So we're looking forward to continuing to explore in the pipeline and with partners, what we think is just a great technology. Thank you.
My team is here, and, we're here for the duration of the day, so we look forward to taking any of your questions, either here or in the hall or in the one-on-one rooms. Yes?
As you design your phase II trial, what are you looking for in terms of overall patient population numbers? In different ranges, or you might not be able to say.
Yeah. So the question is around the magnitude of the phase II trial in d ivesiran. We haven't disclosed that yet, but we're actively working on that, of course, and looking very carefully at the group that gave us the phase I open label result to see what we can learn from that to roll that into the phase II, because it was originally designed as a Phase I /II trial. It will not be, not likely be a really large trial.
Will you disclose it by the third quarter, or any year end, or are you waiting more?
We have a good track record of disclosure because we're a smaller company and things are more material, so as soon as we can, we'll disclose that to you. It is also a very competitive space, as you know. So thank you very much. We're here around, and if you want to grab a coffee or chat with us afterwards, feel free. Thank you.