Good morning, thank you guys for joining us here today. My name is Cameron Bozdog, and I'm part of Jason Zemelis' mid-cap biotech team at Bank of America. I'm very pleased to introduce Dr. Diana Brainard, CEO of AlloVir. Good morning. To start, perhaps can you give us a quick overview of AlloVir and your VST therapies for those who maybe aren't as familiar?
Sure thing. Great to be here. Thanks for the invitation. My name's Diana Brainard, if you didn't catch that, and I'm CEO of AlloVir. At AlloVir, we're a late clinical stage, biotech company focused on virus-specific T-cell therapy. That's non-gene edited cell therapy for immunocompromised patients who lack the immunity to fend off these infections on their own. Our lead program is phase 3, and I'm sure we'll get to that in a moment.
Perfect. Can you kind of speak a little bit more on the underlying platform and some of the differentiating characteristics, especially how you're managing the risk of allorejection?
Sure. We are a platform company. We are focusing most of our resources right now on advancing our lead program, posoleucel. What our platform is focused on the production manufacturing of virus-specific T-cell therapy, which again can target single or multiple viruses, generating materials from healthy volunteers and growing up cells in a fashion that eliminates non-virus specific T-cells and produces on the back end a mixture of CD4 and CD8 virus-specific T-cells that can then be used to treat and importantly prevent infection in immunocompromised patients. Posoleucel, our lead program, targets adenovirus, BK virus, CMV, EBV, HHV6, and JC virus, which are the viruses that cause the primary morbidity and mortality in transplant recipients. When you talk about allorejection of the cells themselves, part of the driver for the survival of our cells is the antigen, the virus itself.
That's driving expansion of the cells in vivo as well as persistence. That other piece is the immunocompromised status of the host. As the host, whether it's a stem cell transplant recipient or a kidney transplant recipient, as their own immunity grows over time as immunosuppression decreases, as the host's own immune system grows, our cells are no longer necessary and are cleared physiologically.
To follow up here, how shelf stable are the VSTs and how quickly can you go from prescription to administration?
part of the beauty of the VST platform is that we have an off-the-shelf product that can create a bank from a relatively small number of donors to reach patients within 48 hours. The way that works, the reason that's possible is because you only need partial HLA matching to have safety and efficacy. This is well understood in the field of virus-specific T-cells, and we've demonstrated this with our programs as posoleucel as well as ALVR106, our respiratory program in the clinic. In terms of shelf life, in academic centers, these cells are traditionally stored for up to 5 years.
We don't have five years of stability on our process, but we've generated stability now such that we believe when we're in the commercial launch stage, we should have at least a year and growing of that stability to support really a robust bank that can be used and replenished as needed.
Great. Let's switch to your lead asset posoleucel. What's the unmet need like in transplant patients for options to treat these six viruses you mentioned previously?
Sure. We're phase 3 right now, we're in stem cell transplant recipients. There the unmet need is very high, with about 90% of patients post-allo stem cell transplant reactivating at least one of our target viruses. We estimate around 70% of patients will go on to have clinically significant infection, meaning they have clinical signs or symptoms of disease, or they've required empiric treatment for a high viral load and high risk of progression. While the risk is very high, you never know which virus is going to emerge as causing morbidity and mortality and getting patients kind of off the track on their recovery post-transplant.
That's why we started initially in phase 3 trials, but we've added in a preventative approach because there was an overwhelming pull from the community to say, you know, if you could get in early with your cells and prevent patients from getting sick in the first place, this would have an even higher impact. We're seeing that now with the pace of enrollment in our phase 3 study.
Touching a little bit on the data you've seen so far. In the phase 2, 88% of patients were free of clinically significant infections through 14 weeks. Can you put this into context for us?
Sure. We have now 3 positive phase 2 datasets with posoleucel. The first was in the treatment setting, refractory and resistant patients, where we had over a 90% response rate across our 6 different target viruses. That study's been published. It came out of the Baylor College of Medicine. More recently, we had a phase 2 prevention study, which enabled the initiation of phase 3 study that started last year. Those results were presented at ASH initially in 2021, and then again in 2022, and most recently at EBMT. Like you said, really a dramatic response whereby 88% of patients after dosing at the primary endpoint week 14 were free of clinically significant infections, so hadn't developed one or more of these infections that are so common in the post-transplant space.
We were really happy to see that now we have the longer-term follow-up, and we've reported at the European meeting in March. That our day 400 non-relapse mortality rate was 0% in these patients. It's a single arm study, so we don't have a control arm. If you look in the literature at what you might expect in a high-risk allo transplant patient population, the reported rates of non-relapse mortality range between 9% and 16%. We're really excited with this idea that not only can you prevent near term morbidity of these infections, but you can also really help the patient on that trajectory towards recovery and preventing all of those non-relapse-related problems such as infection, but also graft-versus-host disease, organ dysfunction, which are all interrelated from becoming an issue and getting a patient into trouble.
Great. For those remaining 12% of patients, did they experience any improvements, for example, less disease burden? Why do you think they didn't receive this full benefit?
We had 3 patients with clinically significant infections, and of course, we looked at them very closely to try to figure out is there anything we can glean from these data and, you know, incorporate changes phase 3. i would say one piece of information that became clear was one of the patients had received high-dose steroids, pulse steroids for an exacerbation of graft-versus-host disease. High-dose steroids will eliminate T cells, circulating T cells. That's how they function. That's why they're given in the setting of graft rejection. What we did phase 3 was recognizing that that could interfere with the persistence of posoleucel, create some flexibility around our dosing. In our prevention study, we're giving 7 doses over a 12-week period.
If a patient gets pulsed with steroids, which is generally a very short-term period, then they can either redose right after that, or they can hold the dose and wait until those steroids come down to an acceptable level, which is basically less than one milligram per kilogram of prednisone or its equivalent. We can't really say whether the course of those illnesses were less severe. It's possible. They certainly, all three of those patients recovered and did well, but without a control arm, it's hard to know. It is something we'll look at in phase 3 when we have a placebo arm as well as a larger sample size.
Touching on your phase 3 that's underway, is this registrational, and, what are the current timelines as far as readouts, filing, and approval?
We have 3 phase 3 trials for 3 distinct first-to-market indications. Our 2 phase 3s are first for hemorrhagic cystitis, the second is for adenovirus infection/disease, then our prevention study is also a phase 3 registrational trial for the prevention of all 6 of these viruses in stem cell transplant patients. We anticipate wrapping up all of those trials this year and having data readouts in 2024.
Great. You recently reported data for BK virus in kidney transplant data. Can you briefly remind us of the risk of BKV in these patients?
. You know, solid organ transplant patients have a different type of immunosuppression than stem cell transplant recipients. It's generally less intense, but it's longer term. They are also subject to adverse outcomes from viral infections, but their clinical manifestations and picture can be a little different. One of the most significant viral infections is BK virus-associated nephropathy in kidney transplant recipients. Kidney transplant is the most common solid organ transplant globally with about 80,000 transplants per year globally. Because BK virus is ubiquitous, most of us acquiring it during childhood, about 20% of kidney transplant recipients will reactivate BK virus. There's no approved therapy, those patients are therefore at risk for progression to damaging effects on the kidney called BK virus nephropathy.
The issue is that not only are they at risk for that, but the only tool that physicians have now to address that problem is to reduce immunosuppression, to try to help the body's own immune system fight the virus. In doing so, by unleashing the body's immune system, you can engender graft failure. These patients, it's very clear in the presence of high BK viral load, have higher rates of graft rejection, poorer outcomes over time because of this dance between controlling the virus and controlling graft rejection. That's why we went into this population as our first step into solid organ transplant patients.
What we found was that in the double-blind placebo-controlled phase two trial we did in the placebo-treated patients as compared to the posoleucel-treated patients, there was a much higher viral load reduction in the patients who got posoleucel. We looked at that over a 24-week period. Dosing was for the first 12 weeks, and we found that across the board, high rates of viral suppression, and most notably, the highest rates of viral load decline were seen in the high viral load patients. Those are the patients who are really at highest risk for progression to nephropathy, that's important to know for our next study. We also found a dose response where the patients getting more frequent posoleucel had deeper virologic responses. A higher proportion of them had a greater than one log viral load decline.
Both of those will factor into our decisions in terms of next steps moving ahead, and we're working with regulators on figuring out what that next step will look like.
Perfect. You kind of briefly touched on regulators, but what do you think they're looking for in terms of outcomes? What % of patients do you think need to be clinically free of significant infections?
With our phase 3 indications, we have RMAT designation for each of them. That's really enabled us to have a lot of regulatory interaction. We have PRIME designation in Europe, these are all first to market indications where there's no approved therapy. That's really important because it enables us to set up the unmet medical need and have a dialogue around what's a really truly meaningful clinical endpoint for patients. It differs based on the trial. Focusing on prevention, where we've looked is at what letermovir has done for CMV in the transplant space. letermovir has reduced the risk of CMV infection by about 50%. Doesn't go to zero, but in high risk allo patients, goes from about 60% to 30%.
What we've heard from physicians is if you can do that, and you can do that for all six of the viruses, that's gonna be a home run, and we'd love that, especially if it comes without a risk for viral resistance, if it's well tolerated, and if it can do these other things like, reduce rates of graft-versus-host disease, lower rates of non-relapse mortality. That's really where we've set our sights, at lowering the bar by about 50%.
Great. With our last minute or so here, can you talk about your long-longer term applications? Where do you think the platform could have, you know, additional utility?
Posoleucel is our first step, and we see that as, you know, launching in 2025 into stem cell transplant patients, moving into solid organ transplant patients, and there will continue to be other immunocompromised patient populations at risk. We, you know, have given compassionate use to patients, for example, CAR-T recipients, patients pre-transplant. As the number of immunomodulatory modalities increase for the treatment of malignancy as well as other conditions, these viruses will only continue to grow, and we see that as a real opportunity with posoleucel. Beyond posoleucel, we also have a respiratory virus product which is in phase 1b/2a, which is very exciting. Behind that, a hepatitis C program, and the potential to really do a lot more using VSTs, for example, as a platform for CAR-T.
Perfect.
Out of time.
Looks like we're out of time.
Thanks.
Thank you so much for joining us, and I hope you guys all have a great rest of your day.
Great. Thank you.
Mm-hmm.