Welcome, everybody to Xencor's Analyst and Investor Reception at ASH 2018. I'm pleased to have you all here. I'll be making a few remarks about Xencor's platform for bispecific antibodies in the company. I'll then turn the podium over to Dr. Ravandi, our investigator of our XmAb14045 AML Trial, and then I'll close with some remarks, looking forward to 2019 for Xencor. I'm Bassil Dahiyat, CEO of Xencor, and thanks again for coming. This is our forward-looking statement slide. I'll start by just setting up that Xencor, as you know, is an antibody engineering company. We focus on the bottom half of the antibody. This is the blue section at the bottom of that antibody diagram to the left on the slide, or I should say to your right, the Fc domain. We use that Fc domain, and we engineer its amino acid sequences.
We do molecular engineering to modulate both the immunological properties of the antibody, excuse me, as well as its overall structure. We use that ability to crack open that structure and put it back together again to make our bispecific antibodies. We have an expansive pipeline that's growing. We have four ongoing clinical programs that are bispecific antibodies led by XmAb14045. We have, in aggregate across all of our platforms, 12 programs in the clinic between ourselves internally and our partners. Let's have a look at the pipeline. The color code is purple bars are bispecific antibodies. You can see this wave coming from the bottom, and blue are our immune inhibitors. Now, XmAb14045 is the lead, but the other three programs in the clinic are also all in oncology: XmAb13676, XmAb18087, and XmAb20717. I'll touch more upon each of those in a bit.
Now, to the platform, this bispecific platform that we've created, we call it our XmAb platform. It's based on the idea that antibodies have great properties naturally as drugs. They're long-acting, they're easy to make, they're modular design, they're highly stable. Now, in bispecific antibodies, historically, it's been a challenge to preserve those properties because you're doing something unnatural. You're snipping different parts of the antibody off or different parts of two different antibodies and trying to jam them together to bind two different antigens at once. The idea of the Fc engineering approach is to preserve what makes antibodies great as drugs, much of which comes from the Fc domain. Again, their long half-life, stability, ease of production, and just graft on the pieces that you need to be the bispecific antigen binding.
Through a pretty comprehensive protein engineering effort, we built bispecific Fc domains that we can use in a plug-and-play manner across a wide variety of antibody leads. This slide just shows a whole series of preclinical leads we had. I can't even remember what target this was against, or against multiple targets. We took the approach of trying to rapidly jump into the space of bispecific antibodies once we had a platform that we thought could really open the floodgates and overcome a lot of the problems that hampered first-generation, very short-acting bispecific molecules like the BiTE platform. We took an approach we could just graft any variable domain binding, and that would be the long arm from any donor antibody against any tumor antigen.
We kept on the short arm constant, in the case of our early pipeline, just binding to the CD3 antigen to turn on T cells. This portfolio was built very rapidly in both internal programs. We have three in the clinic, and the partnerships with Novartis and Amgen show the very rapid way you can build candidates from this plug-and-play approach. These are the three clinical-stage programs that are CD3 bispecifics. In all cases, the preclinical assays for our XmAb14045, that's the CD123 for AML, XmAb13676, that's our anti-CD20 for NHL and CLL, and XmAb18087, that's our anti-somatostatin receptor 2. That's for neuroendocrine tumors. In all cases, you see both very potent but tolerable anti-target cell activity, but it's sustained in time. Single injections or single infusions can last for days or weeks. That's the design goal.
Antibody-like PK with tuned potency that's tolerable. That potency tuning is inherent to this format, where you have separated on an Fc scaffold, the two different binding domains that turns down the heat, so to speak, from what you had with the first- generation bispecific platforms like the BiTE platform that were fantastically potent. These molecules are still very potent. They turn T cells on using CD3 activation. But they're something like 100-fold less potent on a molar basis than a BiTE. We believe that gives you a greater window for control when you do get into animals, in the case of our preclinical work, or in humans in our clinical studies. That potency and half-life should work together. Lower potency and half-life, I should say, to give you an agent you could give with long action but tolerability.
The specifics of design of XmAb14045 just exemplify that approach. We took a CD123 binding domain, humanized it, and that's just the long arm or the Fab arm for the antigen-binding arm. Then on the CD3 side, we have a single-chain Fv that we optimized to be usable in a plug-and-play manner with many, many different antigens, and it's the same CD3 domain and the same Fc that we have for all three of those candidates that I showed. That's humanized, affinity optimized, and importantly, it cross-reacts with non-human primates, so we can do toxicology studies and hopefully safely find a starting dosage. We ablated all the Fc gamma receptor binding out of the Fc domain. We're Fc engineers. That was easy for us to do to avoid receptor-mediated cross-linking and non-specific T-cell activation.
We preserved all the good stuff of the Fc, the FcRn binding for half-life, the protein A binding site for manufacturing, and easy purification. We use standard contract manufacturers to do all of our work. Nothing special there. With that, I'd like to turn over the presentation to talk about the phase I interim data that was shown earlier today to Dr. Farhad Ravandi. He's one of our investigators. He's the Janiece, I think I said it right, and Stephen A. Lasher Professor of Medicine, and Chief of the Section of Developmental Therapeutics in the Department of Leukemia, MD Anderson Cancer Center, University of Texas . Thank you.
Thank you. I think some of you may have seen the full presentation. We are going to just go over the details of the phase I study. As I'm sure you're all aware, is dose-finding study, and the objectives are to find the first infusion and then second and subsequent infusion doses that can be easily tolerated by the patients. Of course, with a completely new agent and in fact, completely new concept in AML therapy, I'm glad that we are doing , or Xencor is doing a lot of pharmacokinetics and pharmacodynamic studies to try to help us better understand how this drug will work, and how we can actually perhaps alleviate the main toxicity, which is what we call cytokine release syndrome.
This is a phase I study, as I'm sure you're all aware, it's only possible to do these studies in patients with multiple relapse disease. They have to be over the age of 18, and they have to have an adequate performance status because obviously, even if it's relapse patients, they have to be able to tolerate the treatment and do not have too many problems that would actually masquerade the toxicities of the drug, or actually be counted as the toxicities of the drug, which is exactly what we don't want. Interestingly, we do allow prior allogeneic stem cell transplant, which is probably the most established form of immunotherapy, which we have had since late 1970s.
Patients who have had prior CD123-directed therapies were not able to participate, that's for obvious reasons, because we don't know what other CD123-directed drugs may do to the target for this agent. There are some CD123 drugs that are in development. There are no established FDA-approved CD123 drugs. I think you may have heard one of the talks after me, SL-401, that it's another CD123-directed drug, but that actually did not work in AML. This is an immunotoxin, and that's why they're going with the BPDCN, in which it is working very well. It has its own issues, which I'm not going to go into time. This is given because of its short infusion and because of its longer half-life; it's given by a two-hour infusion once weekly, times four, with the cycles repeated every 28 days.
I think because of FDA requirements, we started the drug at very low doses at 0.003 µg/kg . I believe we put the first several cohorts, and in fact, in one of the earlier cohorts, we did have what we call morphological leukemia-free state, which means that the patient had no blood counts but had blasts in their bone marrow. We gave the drug, and unfortunately, still didn't recover the counts, but the blasts in the bone marrow were down to the level that we could consider as a response. That was in, I think, in second cohort or third cohort. The DLT period, or dose-limiting toxicity, which is essentially the dose that causes serious toxicity, and if it occurs in more than two out of six patients, it's considered dose-limiting toxicity, that beyond which we don't want to go.
The period to assess this was different from days 1 - 22. That means after the patient has received all four doses of that cycle. 67 subjects were enrolled, and one patient had B-cell ALL. The others had AML. CD123 is not only expressed on AML cells but also a number of other hematological cancers, such as B-cell ALL. I mentioned BPDCN, which is a very rare, uncommon leukemia, and as well as other diseases like hairy cell leukemia. I think the focus obviously is on relapse and refractory AML, for which there are very limited options available.
All the subjects who had received a dose of 1.3 µg/kg, which was established in the Cohort A or in Part A of this study, which was the part that was looking for the first infusion maximum dose were eligible to be evaluated for efficacy because really that was the lowest meaningful dose. Earlier cohorts, as I mentioned, because of the FDA requirement, we had to give very low doses of the drug. The Cohort B or Part B was for the second and subsequent doses, and there are preclinical studies or studies in the lab that have shown that if you start with a lower dose, you get less of the cytokine release syndrome when you give higher subsequent doses.
Part B started with the lower dose that was established in Part A, 1.3 µg/kg , and then we gave higher doses for second and then subsequent doses, as you see at the bottom of the table. The Part B.2 or 2B is 1.3 µg , then 2.3 µg , 2.3 µg , and then 4 µg, and in the latest cohort, I think we are doing 7 µg for the fourth dose. Am I correct, Wayne?
Yeah. That's right.
Which wasn't reported on this study. It is very complicated, and believe me, when we're doing this in the clinic, it is very complicated. We have to have good research nurses who are always thinking what they're doing and keeping in touch with the CRO and Xencor. These are the characteristics of these 66 AML patients.
As I mentioned, there was one patient with B-cell ALL who was enrolled but was not reported on this analysis because it's a different disease. Their median age was 61 years, but you can see the range is pretty wide, from 18 - 85 years old. About 50% of the patients were female, and all of them had AML. You may say, "Why did you put that there?" Because, as I mentioned, initially, the study was open to any CD123-expressing leukemia, but we all focused on AML. Median number of prior therapies, this is important because this just shows you how heavily pre-treated these patients were, was three, the median number, and you can see there were patients that have had as high as eight number of prior therapies. About 30% have had prior allogeneic stem cell transplant.
86% were reported by the various investigators participating in the study to have been refractory to the last treatment they received. That means they got a treatment and had essentially no response. The risk categories, I don't know if you need me to go through that, but when we see patients with AML, based on what we call cytogenetics or chromosomes of the leukemia cells, we categorize these patients as favorable, intermediate, and adverse. I actually tell all my patients that favorable is the most, well, it's actually not a very correct name because there is no favorable leukemia, obviously. That means that they essentially have a likelihood of a better outcome with standard therapy as opposed to the adverse patients who really have a very poor likelihood of having any long-term good outcome.
As we can see, about 50% of the patients were adverse, so a pretty tough population of patients. You may say, "Well, why did you do that?" It's for obvious reasons that this is a phase I study, and you're not going to go and give any drugs in a phase I study to a highly curable patient. The safety is actually, there's a lot of numbers there. All those things that you see on the left are commonly occurring side effects or events that we see in relapsed and refractory AML: fever, anemia, increased ALT, which is a liver enzyme. Typically, you see these in these patients, unfortunately, as you can imagine, are not doing extremely well. They're not doing that badly, but obviously, they're not well.
The most common side effect that was felt to be related to the drug was cytokine release syndrome. This is a class toxicity, so it's seen in all of the T-cell- based therapies and essentially is related to the activation of T-cells by the engagement of the leukemic cells, whether it be by bispecifics or CAR T cells. You can see the majority of these were, however, not high grade or severe. Grade 3 or higher was only in four patients, or 6% of the patients who received the drug. Now, there were five patients who had elevations of ALT and AST. I mentioned to you a lot of these patients tend to have this, but the number of drugs that can cause elevation of liver enzymes, so we are always very aware of this.
This population of patients tends to be on antifungal medicines, they are frequently associated with increased liver enzymes. At least in these five patients, the investigators felt that this had a good possibility of being related to XmAb14045. They tended to occur within 24 hours of the infusion and tended to be associated with other features that we see in cytokine release syndrome, which are fever, chills, low blood pressure, rapid pulse. Because of this, there is a feeling that this may be actually a component of the cytokine release syndrome in these five patients. We did have four patients who had back pain and headache, and again, because in those four patients it tended to occur every time we infused the drug, we also felt that that's probably likely related to the drug. It didn't occur in the other 63 patients who received the drug.
It's not considered a DLT because we could easily manage it with analgesics. At the bottom, on your right side, you see neurological events, and that's another thing that we see with cytokine release syndrome with these immune-activating agents. That's why you see it down there. At least with this, they were low grade, and they tended to be just transient infusion related, a little bit of confusion. You can get that even if anybody gets a fever, you can get a degree of little confusion, especially in elderly patients. As I mentioned, cytokine release syndrome was the most common side effect and mostly occurred after the first dose. This is what Xencor and others have seen with these agents: that it tends to occur with the first dose, even in animal studies, and it just abates with subsequent doses.
In the first few cohorts, we did not give any pre-meds. I think with all of these agents, we are a little bit reluctant to give steroids because you're trying to activate T cells, and steroids are one of the more effective agents for killing lymphocytes. We didn't give any steroids, and we did get cytokine release syndrome. That's why after the third cohort, you can see we started pre-medding or pre-medicating patients with dexamethasone, which is a steroid or hydrocortisone, as well as diphenhydramine and/or TYLENOL. Severe events of cytokine release syndrome also occurred in the first dose, as you see there. They usually tended to resolve very quickly after about four hours of infusing the drug. Actually, if there's any questions, I can always hold. There is no pressure of presenting it in 10 minutes. I just thought, you know, he told me. Okay.
One of the things that has been seen with cytokine release syndrome is elevation of cytokines like interleukin-6. This is commonly checked in various drugs or cellular therapy that is going to activate T cells, CAR T cells, and bispecific antibodies. As you can see here, the interleukin-6 levels are higher after the first dose. If I can show, under the Cohort 2B, where we had the step-up dosing, you increase the dose, you also saw a little bit higher interleukin-6, consistent with the occurrence of cytokine release syndrome. This is a thing that we are very hopeful about, that we will hopefully be able to replicate when we give more consistent dosing to a bigger number of patients.
Also, I actually think, hopefully, if we have patients with lower disease burden, not patients who have had eight prior therapies, you may be able to see more activity as well. Obviously, when you have a very tough population, getting response is also very tough, but that's true of virtually all phase I studies. This is very encouraging that we have seen five out of 18 patients who received at least a dose of 1.3 µg/kg having some form of response, which is CR or CRI. For those who don't know the definition of CR and CRi, CR or complete response is when you clear the bone marrow from leukemic cells, and your blood counts come back to normal. CRi is when you clear the bone marrow, but the blood counts remain subnormal. By the way, I'm sorry I'm explaining these things.
Maybe most of you know all of these definitions. I really am not. Please keep explaining. Keep explaining? Okay. Because I don't know the medical background of most of you, all of you, actually. That's why I'm trying to be a little bit. There was stable disease, and that's potentially useful because you're activating the patient's immune system. If you can get the patient's immune system to control the disease for a protracted period of time, that's also not as good as getting a CR, but it's still a form of response. The majority of responses tended to occur within the first cycle of the therapy. One of the things that people have been a little bit concerned about all these immune-activating agents in AML, is low blood counts.
The fact that we actually got CRS or patients with complete response with recovery of their blood counts, that means that's probably less of a concern at the moment. I think we had this in one of the sessions, that it seems that with a lot of these CD123-directed therapies, we are not getting what we all worried about, and that is protracted, very prolonged low blood counts. The patients who did get a response, as well as those who had the stable disease, had reasonably long durations of their responses, and some of them continued on therapy for a good period of time. One of my patients had a CRi and was on it for about five or six cycles before he relapsed. He didn't want to go to transplant because he's an older gentleman, and he's actually also very aware of his costs.
The responses have been or can be durable in some of the patients, and these are the five patients. A couple of them did go to an allogeneic stem cell transplant, which in the relapsed and refractory setting is the goal of all therapy. As in, when we treat AML in the frontline setting or for the first time, there are subsets of the AML that we don't send to transplant. When a patient relapses after having had a prior response, everybody gets sent to a transplant. Essentially, historically, that means you failed your non-immunological therapy. You're going to use transplant, which, as I mentioned to you, is the most established immune-based therapy for the last 40 years. One patient was referred for transplant but couldn't have it because he wasn't fit enough due to cardiac issues.
You can see, I think the patient at the top is, if I'm correct, Wayne, is my patient who had about five or six cycles, but if you don't remember, that's. Obviously, there's always a hope to try to find Question. Sorry.
Yeah. That's okay, Dr. Ravandi.
The last slide, you mentioned that the patient who did go on to transplant in the presentation today at the bottom expired, unfortunately, due to graft-versus-host disease. What about 2b there? It looked like it was a CRi, and then the patient passed. What was the characteristic of that, if you don't mind explaining, or if you know?
I only treated, I think, about 33% or 50% of these patients. That was not my patient. I am going to refer to Wayne because he knows all of these, I think, much better than me.
Okay.
All these patients.
That was a patient that had an initial very good response, continued on into a complete remission, but was quite elderly and quite infirm, and ended up not ending up wanting to prolong her therapy any longer and ended up going to hospice. The patient was in remission at the last time they were seen, but it was more of a general decline in their physical status. The patient on the fourth, the next up from the bottom, is a patient that was referred for transplant but was unable to receive a transplant because of cardiac issues, but stayed in remission and is still in remission as far as we know, off therapy. That whole dotted line is maintained in complete remission off therapy.
Could we go back to the waterfall plot also? One more. It doesn't seem like there's a dose response. Can you maybe comment on the side effect profile that you're seeing and the dose escalating into the higher doses, and if there's any predictor of the patients that are going to respond?
I'm sorry. Because of where you are, I couldn't hear you. Sorry.
Sorry. I guess it seems like there's not a dose response, and so I was wondering if you could comment on the adverse event profile in the context of the responses? If there's anything about patients that you might be able to predict a response, and the rationale for going into higher doses, and if you're seeing better responses with the higher doses?
Again, I can only talk about my own patients that I've treated. I could tell you that the very early doses, they accepted that morphological, and that was my patient as well, the MLFS. As one would expect, there was no activity. The responses are beginning to occur in the more recent cohorts. There's no association with cytokine release syndrome. Again, if Wayne, if you'd like to say anything on that.
Yeah. I get to look at all the cases from all the sites, so I have a good idea about what happens. I would say that this is a fairly narrow range of doses. I'm not sure that we can say too much about a dose response necessarily just because we're looking also at flat dosing versus priming dose with step-up dosing too. I would say that there is a sort of a flat response between dose and severity of CRS. We started getting CRS at dose level 3, and we were able to continue to escalate up until dose level 10 without any problems until the very end. I would say it's much more critical whether it's the first dose or the subsequent doses. The first dose is definitely worse.
As to dose response, I think for how much there is a dose response, I think we have to see at higher doses whether we're going to get much more. I think there's just not enough range here to see much.
I think you may say 66 patients. I think we are now getting to the levels that we are actually beginning to understand, or hopefully start seeing more and more activity and possibly more CRS. I think the use of the steroids is probably going to be preventing that.
Well, as you may have guessed, we actually see less CRS, I think, in responders. I think that their target cells are much numerous than this. The immune stimulation is a little more mild. The best responders are actually don't have extremely severe CRS.
I think probably, I don't know if you went to many sessions at ASH, but you probably saw MRD written all over the place. On every session, you heard about MRD. I can tell you I've been doing MRD for 10, 15 years, and 10 years ago, if you said MRD, nobody knew what you were talking about, but now everybody's talking MRD. That's an area that I'm very interested in. I don't know if Xencor is, but that's going to be a huge area in the future. That essentially means when you give these patients whatever form of therapy, historically we gave them cytotoxic chemotherapy, but now we're more and more giving some of the targeted agents and hypomethylating agents, et cetera. You still put not all the patients in remission.
The patients you put in remission, a lot of them, you detect this thing called MRD. Patients who have the MRD are going to relapse. This has been shown by various assays of MRD. Agents like this drug, as well as similar drugs, can have a big role in trying to mop up this MRD. We've seen this that doing that, you actually improve the chance of a cure. Not only by the fact that they tend to do better after transplant, and this has been shown on multiple studies that if you go to a transplant with MRD, you're bound to relapse after transplant. Whereas if you go to transplant without MRD, there is a good chance of doing very well. There is absolutely no FDA-approved drug for MRD for AML.
There is one in ALL, which I'm sure you all probably know about, BLINCYTO or blinatumomab. Talking about the disease burden, if you establish these agents or this drug as an effective drug to eradicate MRD, it would be essentially a very useful drug for us to treat AML. Sorry, I think we went through this, but this is looking at CD123 blast expression in the bone marrow in the responders versus non-responders. You can see the numbers are small. There are five responders versus 13 non-responders where they had data available. You can't say an absolute conclusion about this, but at least with this number of patients, there hasn't been a difference between the two. Any questions?
Jonathan Chang from Leerink. Hi, Dr. Ravandi. I'd love to get your high-level thoughts on how you see the AML landscape evolving with the various updates we've seen at ASH this year, and how do you see XmAb14045 positioned within that landscape?
Sure. Two, three years ago, we were desperate in AML, and we were very jealous of myeloma because they were getting drugs approved every day, and it felt like we haven't had a drug for 18 years. We were almost upset with the FDA that we felt they were picking on us. I really mean that, as in the AML people felt that we were being picked on and because they were approving drugs for myeloma just based on event-free survival, and they wouldn't do it for AML. Now we have, over the last two years, several drugs, as you know. Three drugs just a week before ASH approved. A number of these are targeted drugs. Oral FLT3 inhibitors, oral IDH inhibitors. They are changing the field. That's why I talked about MRD.
I think that's a very important area because none of these agents or none of these strategies give you 100% response with complete MRD negativity. In order to get MRD, many of us believe you need immune-based therapies, like bispecifics. There's nothing to say that these agents are not good for just relapsed AML. Blinatumomab was approved for relapsed ALL, with response twice as much as traditional chemotherapy. The reason, I guess, I'm a bit biased because that's one of my favorite areas of clinical work, the MRD. I think despite the fact that we are getting approvals, there's big, vast amount of improvement that's needed for AML therapy in both younger and older patients.
We've also seen several CD123 data sets at this year's ASH. How would you compare XmAb14045 to other CD123 programs in development? How would you compare these early data to the other early data sets we've seen?
SL-401 is only for BPDCN, and that's a very small number of patients. That's about 100 patients in the U.S. a year. I'm really talking small. The MacroGenics compound, the Amgen compounds, the ones that are ongoing are continuous infusion. The fact that you have a long-acting, short infusion drug, that gives Xencor an advantage. Other people are looking at extended half-life, short infusion bispecifics. The ones that are presented, these were the ones. Now, there's also immunotoxins. That's drugs that are directed at CD123 with a toxin attached to it. They can have their own issues. One of the issues that have been seen is veno-occlusive disease of liver, and that's an area that FDA is very anxious about. That's something you don't get with bispecifics.
Maybe if anybody else who has questions, we can maybe, Jonathan, do you want to follow up afterwards? I don't want to just keep Dr. Ravandi at the podium forever.
Just to get a real quick sense. Back over here, Bassil and Dr. Ravandi, thank you again. As we kind of move into this portion B of the study, just remind us how many patients and how many escalations are in that before we kind of figure out what the right dose? What the right schedule is? Thank you.
You know, Wayne knew that I was going to look at him and ask him, "Can you please take this one?"
You're asking for clairvoyance, that's what you're asking for. I have to say, I've never done a phase I trial that had this many cohorts. I think it's been very useful to do these escalations. We really had to start at the level we did. It was not really much of a question about it. I think that not only have we dose escalated, but we've also changed the schedule in terms of the priming dose and the step-up dose. We're looking at other different schedules to see if giving smaller doses more frequently or for a short period of time helps. We're looking at a lot of different things. It's a little hard to know exactly where we are. I think we have an active dosing schedule right now that we could move into other clinical trials.
I think it's worthwhile probably to keep working on perfecting the dose a bit more. I think we can move ahead right now if we needed to.
I actually agree that you really need to, because when you do the phase I, that's your final chance, if you see what I mean. If you stop at a low level and start doing large scale phase II, then phase III, then suddenly you realize, "Oh, I wish I'd gone one dose higher," then you'll be really not doing yourself a favor. I think the best thing is to get the most optimal dose. Doesn't matter how many cohorts you need to do, but I always say your phase I, if you get maximum tolerated dose, that's a different story. If you're not, then you really need to get to somewhere where you're really comfortable you've got the best strategy.
Thank you so much, Dr. Ravandi. Let's give Dr. Ravandi a hand. I think my hiccups just came back, congratulations, everybody. Just to remind everybody, XmAb14045 is part of our Novartis collaboration, where they licensed ex-U.S. commercial rights. Xencor has all U.S. commercial rights still wholly owned, as well as we set up a, thank you, a 50/50 worldwide co-development cost share and real collaborative relationship. That's embedded in our Novartis collaboration, but we've been doing all of the actual phase I execution work to date. Now, to jump to the bispecific pipeline writ large, I'll give you a quick preview of what's coming up over the next 12-18 months. At the top of this slide is XmAb14045, our most advanced bispecific antibody. It started in the clinic first. We reported data for it first, that was just today.
We do have the other two right below it, are also CD3 bispecifics. You can see that's one of the key targets. Direct T-cell co-engagers that drive cytotoxic T-cell function to a tumor antigen. In the cases of XmAb13676, that's our CD20 antibody again, and our XmAb18087 is the somatostatin receptor 2 targeter. Those are the internally, at least, executed CD3 bispecific antibodies. Amgen, our partner, has in phase I now a CD38/CD3 antibody called AMG 424. That's a very ambitious target. It's a broadly expressed antigen across a lot of healthy tissues. They used really to the fullest, the tunability of potency and half-life that the XmAb platform offers in trying to find that sweet spot of tolerability and activity. They got really promising product profile in non-human primates.
Now, they're in humans, they've guided, they could perhaps have data in 2019. Just tonight at 8:00 P.M., while you were sitting here, they announced that there's another program that's in preclinical development. I don't know if they've given a specific clinical start timeline, at the bottom of the slide, AMG 509, that's for prostate cancer, that's against an undisclosed target. That's a second one we can add to the pipeline. Those are the CD3, now I'll touch on our next set of bispecific antibodies, starting with XmAb20717 here, XmAb22841 and XmAb23104. Those are all targeting the tumor microenvironment and they target T cell checkpoints. The idea we had for exploiting our bispecific platform was to be able to target two checkpoints at once in one injection with one molecule.
There's certainly advantages of simplicity there, potentially cost of therapy. More biologically oriented was our desire to focus on the T cells that are probably most involved in potentially attacking tumors, and that the immune system is sort of shutting down by upregulating checkpoints. It's been widely observed and it's published widely that in a tumor microenvironment, T cells tend to have multiple checkpoints upregulated, or at least more so than T cells in the periphery. We designed a bispecific antibody to have preferential binding by really tuning the affinity down again, right? This idea of potency tuning. There's just a right amount. You don't want to have too much.
Tuning it just to the point where you're going to favor binding to double positive cells, where cells that only have one checkpoint target or the other that you're going after are going to have less binding. We hope to focus that derepression activity and T cell upregulation where it might be needed most. We went after three distinct biological hypotheses with this approach because, there's really fundamentally, immunology has not gained a fundamental understanding of what's really driving tumor resistance to your innate, rather not innate, that means something in immunology, to your intrinsic immunity, right? We developed three different drug candidates. The first one, XmAb20717, started in phase I in July. That targets PD-1 and CTLA-4 on T cells.
Those are the two most established T cell checkpoint targets, approved drugs, both have monotherapy function if you hit one or the other target at once. We figured that was an approach that leverages well-understood biology, or at least the best understood biology. The second one on the list, XmAb22841, we just filed the IND for, we hope to have patients on study in first half of 2019. That one targets two checkpoints, CTLA-4, just like XmAb20717 , also LAG-3, a checkpoint with clinical data that certainly indicates that repression of LAG-3 can have a positive impact, at the least when it's in combination with PD-1 antagonism.
The idea here was let's create a molecule that enables triple checkpoint blockade because it's designed to be used on top of a baseline of an anti-PD-1 therapy like nivolumab or pembrolizumab. That's the XmAb22841 thesis. Can we have a triple checkpoint blockade? The last one was we wanted to include binding to a costimulatory molecule and actually agonize that, and in this case, we chose ICOS, and I'll tell you why in a second, and combine that with PD-1 inhibition, probably the most active single checkpoint. A third distinct hypothesis because we want to leverage something we understand well, our bispecific platform, which can create really robust molecules quickly, to try to answer questions we don't understand very well, the biology that really can only be riddled out in humans. Why did we pick PD-1/ICOS as our combination?
Why CTLA-4/LAG-3 is the best pair to use on top of the PD-1? Well, we did the empirical exercise. We can make bispecific antibodies really rapidly in the lab, and we tested in a variety of preclinical models in vitro and in vivo, which ones gave the most effective T cell function amplification. Those are the pairs that you see there. Just leaving you with milestones and goals for 2019. We do expect to initiate clinical trials. First, outside of the oncology space, that we do expect the phase III study for XmAb5871, which we just are now allowed to start calling its INN obexelimab. We hope to start that in IgG4-related disease next year. We also expect to initiate the phase I studies for the two checkpoint bispecifics I just talked about, XmAb22841 and XmAb23104.
We expect to submit the IND for the newest element of our pipeline that's exploiting our bispecific platform, which is our IL-15, a cytokine that's T cell activating, our IL-15 molecule XmAb23106. Data readouts we expect on three bispecific programs next year are CD20/CD3 and SSTR2/CD3 T cell co-engagers we hope to have initial phase I data out of during 2019. We expect to have a first look at some interim phase I data from our XmAb20717, the first of our checkpoint bispecifics. The field at this week's ASH had had the field of bispecifics, really an explosion of data relative to what the trickles had been to date from a variety of companies across a variety of targets.
We think that our pipeline is going to have a similar kind of expansion over the next 18-24 months, and I think that's going to mirror a continued expansion in the field. There's a lot to watch for in bispecifics, a lot of biology we're going to learn about. Not everything's going to be a winner; that's why we have to use our platforms to try a lot of different biologies to see if we can get new therapies forward for patients. I'll leave you with we're well set up to try to attack these problems. We have cash runway that's guided through 2023. We ended last quarter with just about $550 million in the bank, we're positioned to try to attack these problems in a robust way. We're certainly willing to entertain more questions.
I hope Dr. Ravandi can stay a few more minutes if there's any more questions for him. We'd be happy to address them. Thank you.
Quick correction. IL-15 is XmAb24306 .
I'm sorry, did I misread the number? I'm sorry. Yes.
No, it's actually.
Oh my gosh, yes.
It's respective on the slide.
Yeah. Boy, we all proofread it 15 times. We got it wrong. This line here, we'll submit IND application for IL-15/IL-15 receptor alpha, that should be XmAb24306. Our apologies for that. We'll correct those for the ones we post on the website. Oops. No hiccups today. I've had them since Friday. Thank you.