Welcome everybody to Xencor's Analyst and Investor Assertion 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 Doctor. Ravandi, our investigator of our 14,045 AML trial.
And then I'll close with some remarks looking forward to 2019 for Xencor. So it's Dan Baffledehayat, CEO of Xencor. And thanks again for coming. This is our forward looking statements slide. So 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, so the blue section at the bottom of that antibody diagram to the left on the slide, I'd say to your right, the Fc domain. And we use that Fc domain. 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. And 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 4 ongoing clinical programs that are bispecific antibodies led by XmAb14045. And we have in aggregate across all of our platforms, 12 programs in the clinic between ourselves internally and our partners. That's a look at the pipeline. So the color coded purple bars are bispecific antibodies.
You can see this wave coming from the bottom and blue are our immune inhibitors. Now, 14,045 is the lead that the other 3 programs in the clinic are also all in oncology, XmAb13676, 18087 and 2,007 and 17. And I'll touch more on each of those in a bit. Now to the platform, this bispecific platform that we 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 to 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 2 different antibodies and trying to jam them together to bind 2 different antigens at once. The idea of the Fc engineering approach is to preserve what makes antibodies greater drug, much of which comes from the Fc domain. Again, the long half life stability, ease of production and just graft on the pieces that you need to be the bispecific antigen binding.
And so 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. And so this slide just shows a whole series of preclinical leads we had. And I can't even remember what target this was against or against multiple targets. But 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 1st generation, very short acting bispecific molecules like the BiTE platform. So 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.
And 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. And so this portfolio was built very rapidly in both internal programs. Now we have 3 in the clinic. And the partnerships with Novartis and Amgen show that the very rapid way you can build candidates from plug and play approach. So these are the 3 clinical programs, clinical stage programs that are CD3 bispecifics.
And in all cases, the preclinical assays for our 14,045, that's the CD123 for AML 13,600 six, that's our anti CD20 for NHL and CLL and XNAb18087, 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 that is sustained in time. So single injections or single infusions can last for days or weeks. And that's the design goal, antibody like PK with tuned potency that's tolerable. And that potency tuning is inherent to this format where you have separated on an Fc scaffold the 2 different binding domains that turns down the heat, so to speak, from what you had with the 1st generation bispecific platforms like the BiTE platform that were fantastically potent.
Now these molecules are still very potent. They turn T cells on using CD3 activation, but there's something like 100 fold less potent on a molar basis than a bite. And 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. It's lower potency and half life, I should say, to give scuttle an agent you could give with long action but tolerability.
So the specifics of design of XmAb14045 just to 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. And then on the CD3 side, we have a single chain FB 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 I just showed. And that's humanized, affinity optimized.
And importantly, it cross reacts with nonhuman primates, so we can do toxicology studies and hopefully safely find starting doses. So we ablated all the Fc gamma receptor binding out of the Fc domain, we're Epstein's ears, that was easy for us to do to avoid receptor mediated cross linking and nonspecific T cell activation. And 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. And we use standard contract manufacturers to do all of our work. So nothing special there.
Now with that, I'd like to turn over the presentation to talk about the Phase 1 interim data that was shown earlier today to Doctor. Farhad Ravandi. He's one of our investigators. He's the Jynneos, I think I said it right, and Stephen A. Last year, Professor of Medicine and Chief of the Section of Developmental Therapeutics in the Department of Leukemia at MD Anderson University of Texas.
Thank you.
Thank you. And I think some of you may have seen the full presentation, but we are going to just go over the details of the Phase I study. And 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. And of course, with completely new agents and in fact completely new concepts in AML therapy, I'm glad that we are doing or Zencor 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 perhaps alleviate the main toxicity, which is what we call cytokine release syndrome. And so this is a Phase I study.
And as I'm sure you're all aware, it's only possible to do these studies in patients with multiple relapse disease. And these are they have to be over the age of 18. And they have to have an adequate performance status, because obviously even if it's a relapse patient, 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. And patients who have had prior CD123 directed therapies were not able to participate and 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-four zero one that it's another CD123 directed drug, but that actually did not work in AML, but this is an immunotoxin and that's why they're going with the BPDCN in which it is working very well. And it has its own issues, which I'm not going to go into time. So this is given because of its short infusion and because of its longer half life, it's given by a 2 hour infusion once weekly times 4 with the cycles repeated every 28 days.
And I think because of FDA requirements, we started the drug at very, very low doses at 0.003 microgram per kilogram. And 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 blast in their bone marrow and we gave the drug and unfortunately still didn't recover the counts, but the blast in the bone marrow were down to the level that we could consider as a response. I mean that was in I think in 2nd quarter or 3rd quarter. And then the DRC period or dose limiting toxicity, which is essentially the dose that causes serious toxicity.
And if it occurs in more than 2 out of 6 patients, it's considered dose limiting toxicity beyond which we don't want to go. And the period to assess this was different from days 1 to 22. That means after the patient has received all four doses of that cycle. And 67 subjects were enrolled and one patient had B cell ALL, the others had AML. Now 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. But I think the focus obviously is on relapse and refractory AML for which there are very limited options available. So all the subjects who had received dose of 1.3 microgram per kilogram, which was established in the cohort A or in Part A of the study, which was the part that was looking for the 1st infusion maximum dose, were eligible to be evaluated for efficacy because really that was really the lowest meaningful dose. Earlier course, as I mentioned, because of the FDA requirement, they had to give we had to give very, very low doses of the drug. And then the Cohort B or Part B was for the second and subsequent doses under our 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.
So Part B started with the lower dose that was established in Part A, 1.3 microgram per kilogram, and then we gave higher doses for 2nd and then subsequent doses, as you see at the bottom of the table. So the Part B2 or 2b is 1.3, then 2.3, 2.3 and then 4 micrograms. And in the latest cohort, I think we are doing 7 micrograms for the 4th dose. Am I correct, Wayne? Yes, that's right, which wasn't reported on this study.
So it is very complicated. And believe me, when we're doing this in the clinic, it is very complicated. You have to have good research nurses who are always thinking what they're doing and keeping in touch with the CRO and Zencor. So this is the characteristics of these 6 to 6 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, but you can see the range is pretty wide from 18 to 85. And about half of the patients were female and all of them had AML. Now 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're all focused on AML. And so median number of prior therapies, this is important because this just shows you how heavily pretreated these patients were, was 3 the median number. And you can see there were patients that have had as high as 8 number of prior therapies and 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. And 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 phylogenetics or chromosomes of the leukemia cells, We categorize these patients as favorable, intermediate and adverse. And 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. But 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.
And as we can see, about half of the patients were adverse. So a pretty tough population of patients. And you may say, well, why did you do that? And it's for obvious reasons that this is a Phase I study and you're not going to go and give it any drugs in a Phase I study to a highly curable patient. And the safety is actually there's a lot of numbers there.
But all those things that you see on the left are commonly occurring side of events that we see in relapsed and refractory AML fever, anemia, increased ALT, which is the liver enzyme. Typically, you see these patients, unfortunately, as you can imagine, are not doing extremely well. They're not doing that badly, but obviously, they're not well. And the most common side effect that was thought to be related to the drug was cytokine release syndrome. And this is a class of toxicity.
So it's seen in all of the T cell based therapies and essentially is related to the activation of T cells in by the engagement of the leukemic cells, whether it be by bispecifics or CAR T cells. And so you can see the majority of these were, however, not high grade or severe. Grade 3 or higher was only in 4 patients or 6% of the patients who received the drug. There were 5 patients who had elevations of ALC 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 and they are frequently associated with increased liver enzymes. But at least in these five patients, the investigators felt that this was this had a good possibility of being related to XBAB14,045. They tended to occur within 24 hour 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 4 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 to relate it to the drug. It didn't occur in the other 63 patients who received the drug. So it's not considered a DLP because we could easily manage it with analgesics. And 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 and that's why see it down there.
But at least with this, they were low grade and they tended to be just transient infusion related, a little bit of confusion. And that's you can get that even if any or anybody gets a fever, you can get a degree of little confusion, especially in elderly patients. So as I mentioned, cytokine release syndrome was the most common side effect and mostly occurred after the first dose. And 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 some of the more one of the more effective agents for killing lymphocytes. So we didn't give any steroids and we did get cytokine release syndrome. And that's why after the 3rd cohort, you can see we started premedding or premedicating patients with dexamethasone, which is a steroid or hydrocortisone as well as cyclone hydromine or and Tylenol. And severe events of cytokine release syndrome also occurred in the first dose, as you see there. And they usually tend to resolve very quickly within the after about 4 hours of infusing the drug.
Actually, if there is any questions, I can always hold. There is no pressure of presenting it in 10 minutes. I just thought maybe somebody okay. So one of the things that has been seen with cytokine release syndrome is elevation of cytokines like interleukin 6. So this is commonly checked in various drugs that or cellular therapy that is going to activate T cells, so CAR T cells and bispecific antibodies.
As you can see here, the interleukin-six levels were higher after the first dose. And if I can show and the Cohort 2b where we had the step up dosing, so you increased the dose, you also saw a little bit higher interleukin 6. Consistent with the occurrence of cytokine release syndrome. And this is the thing that we are very hopeful about that we can be we will hopefully be able to replicate when we give more consistent dosing to a bigger number of patients. And also, I actually think, hopefully, if we have disease patients with lower disease burden, not patients who have had a prior therapy, 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. But this is very encouraging that we have seen 5 out of 18 patients who received at least a dose of 1.3 microgram per kilogram having some form of response, which is CR or CRI. And 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 comes back to normal. CRI is when you clear the bone marrow, but the blood counts remain subnormal. And by the way, I'm sorry, I'm explaining these things.
Maybe most of you know all of these definitions and I really am not Keep explaining. Keep explaining? Okay. Because I don't know the medical background on most of you, but or all of you actually, but 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. So if you can get the patient's immune system to control the disease for a protracted period of time, that's also it's not as good as getting a CR, but it's still a form of response.
So the majority of responses tended to occur within the 1st cycle of the therapy. But one of the things that people have been a little bit concerned about these immune activating agents in AML is low blood counts, but the fact that we actually got CRs or patients with complete response with recovery of the blood counts, that means that that's probably less of a concern at the moment. And I think we heard 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 safe stable disease had reasonably long duration of their responses and some of them continued on therapy for a good period of time. 1 of my patients had a CRI and was on it for about 5 or 6 cycles before he relapsed.
And he didn't want to go to transplant because he's an older gentleman, and he's actually also very aware of his costs. But so the responses can have been or can be durable in some of the patients, and these are the 5 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. But when a patient relapses after having had a prior response, everybody gets sent to a transplant because essentially, historically, that means you failed your non immunological therapy. So 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 refit for transplant, but couldn't have it because he wasn't fit enough due to cardiac issues. And you can see, I think the patient at the top is, if I'm correct, Wayne, is my patient who had about 5 or 6 cycles, but if you don't remember, that's and obviously, there's always hope to try to find question, sorry. That's okay, Doctor. Fadia. Last slide, you mentioned that the patient who did go on transplant in the presentation today at the bottom expired unfortunately due to graft versus host disease.
What about 2b there? It looks 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 a third or a half of these patients. So that was not my patients. I'm going to refer to Wayne because he knows all of these, I think much better than me, all these patients.
So that was a patient that had 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 ends 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 4th 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. So that's that whole dotted line is maintaining incomplete remission off therapy.
Could we go back to the waterfall plot also? The water one more. It doesn't seem like there's a dose response. And 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, I turned away you are and I couldn't hear you, sorry.
So 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 at the higher dose?
Again, I can only talk about my own patients that I've treated. And I could tell you that the very early doses accepted that morphological and that was my patient as well, the AMLFS. As one would expect, there was no activity. But the responses are beginning to occur in the more recent cohorts. There's no association with cytokine release syndrome.
And again, if Wayne, if you'd like to say anything on that.
Yes. I mean, I get to look at all the cases from all the sites. So good idea about what happens. I would say that this is a fairly narrow range of doses. So I'm not sure that we can say too much about a dose response necessarily just because we're not 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. So I would say it's much more critical whether it's the first dose or the subsequent doses, the first dose is definitely worth. 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, but I think we are now getting to the levels that we are actually beginning to understand or hopefully, we'll see start seeing more and more activity and possibly more CRS. But I think the use of the steroids is probably going to be preventing that.
Immune stimulation is a little more mild. So the best responders are actually not very don't have extremely severe CRS.
And I think probably I don't know if you went through many sessions on ASH, but you probably saw MRD written all over the place and every session you heard about MRD. I could tell you, I've been doing MRD for like 10, 15 years. And 10 years ago, if you said MRD, they didn't nobody knew what you were talking about. But now everybody is talking MRD. And that's an area that I'm very interested in.
I don't know if Vencore is, but that's going to be a huge area in the future. And that essentially means when you give these patients whatever form of therapy. And historically, we gave them cytotoxic chemotherapy, but now we're more and more giving some of the targeted agents and hypomethylating agents, etcetera. You still put not all the patients in remission. And the patients you put in remission, a lot of them you detect this thing called MRD.
And patients who have the MRD are going to relapse. This has been shown by various assays of MRD. So agents like this drug as well as similar drugs can have a big role in trying to mop up this MRD. And 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 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 blincidororblazolumab. So that's and talking about the disease burden, if you establish these agents or this drug as a effective drug to eradicate MRD, it would be essentially a very useful drug for us to treat AML. And 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's 5 responders versus 13 non responders where they had data available. So 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 2. Any questions?
Jonathan Chang from Leerink. Hi, Doctor. Vande. 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 14,045 positions within that landscape?
So 2, 3 years ago, we were desperate in AML and we were very jealous of myeloma because they were getting drugs approved every day and sort of like we haven't had a drug for 18 years and we were almost upset with the FDA that we thought they were picking on us. And 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. But now we have over the last 2 years several drugs as you know, 3 drugs just a week before ASHA approved. So a number of these are targeted drugs, oral 3 inhibitors, oral IDH inhibitors. So they are changing the field.
That's why it talks 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. So and in order to get MRD, many of us believe you need immune based therapies like bispecifics. But there's nothing to say that these agents are not good for just relapsed AML. Bilinatumomab was approved for relapsed ALL with response twice as much as traditional chemotherapy.
So the reason I guess I'm a bit biased because that's one of my favorite areas of clinical work, the MRD. But I think despite the fact that we are getting approvals, there's a 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 14,045 to other CD123 programs in development? And how would you compare these early data to the other early data sets we've seen?
So SL-four zero one is only for BPDCN and that's a very, very, very small number of patients. That's about 100 patients in U. S. A year. I'm really talking small.
The MacroGenics compound, the Amgen compounds, the ones that are ongoing are continuous infusion. So 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, but 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.
And they can have their own issues. One of the issues that have been seen is immuno occlusive disease of liver and that's an area that FDA is very anxious about. So and that's something you don't get with bispecifics.
Before we really anybody else to undertake, we can maybe John and do you want to follow-up afterwards. I don't want to just keep Doctor. Ravani at the podium forever.
Take a real quick sense back over here, Basil, and Doctor. Ravandi. Thank you again. So 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.
Wayne knew that I was going to look at him and ask him, can you please take this one?
You're asking for clairvoyance is what you're asking for. It's I mean, I have to say, I've never done a Phase I trial that had this many cohorts. But I think it's been very useful to do these escalations. We really had to start at the level we did. I mean, it was not really much of a question about it.
But it thinks that not only we dose escalated, but we've also changed the schedule in terms of the priming dose and the step up dose. We're considering 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. So it's a little hard to know exactly where we are. I mean, I think we have an active dosing schedule right now that we could move into clinical trials, other clinical trials. I think it's worthwhile probably to keep working on perfecting the dose a bit more.
But I think we can move ahead right now if we needed to.
But 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 2 than Phase 3 and then suddenly you realize, oh, I wish I had gone one dose higher, then you will be really not doing yourself a favor. So I think the best thing is to get the most optimal dose. It doesn't matter how many cohorts you need to do. But I think I always say your Phase 1, if you get maximum tolerated dose, that's a different story.
But 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, Doctor. Avani. Let's give Doctor. Avani a hand. I think my hiccups just came back.
So congratulations everybody. So 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 fifty-fifty worldwide co development cost share and real collaborative relationship. So that's embedded in our Novartis collaboration, but we've been doing all of the actual Phase I execution work to date. So 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 to 18 months. So 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. And we do have the other 2 right below it are also CD3 bispecifics. You can say that's one of the 2 targets, the direct T cell co engagers that drive cytotoxic T cell function to a tumor antigen.
So in this case is of 13,676, that's our CD20 antibody again and our XmAb18087 is the somatostatin receptor 2 targeter. So those are the internally, at least executed CD3 bispecific antibodies. And Amgen, our partner, has in Phase 1 now a CD38, CD3 antibody called AMG424. That's a very ambitious target. It's a broadly expressed antigen across a lot of healthy tissues.
And so they use 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 and they've guided they could perhaps have data in 2019. And then just tonight at 8 o'clock, 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, but at the bottom of the slide, AMG-five zero nine, that's for prostate cancer, that's against an undisclosed target.
And so that's the second one we can add to the pipeline. So those are the CD3s, but now I'll touch on our next set of bispecific antibodies, starting with XmAb20717 here and then XmAb22841 and 23104. Those are all targets targeting the tumor like environment that target T cell checkpoints. So the idea we had for exploiting our bispecific platform was to be able to target 2 checkpoints at once in one injection with 1 molecule. There certainly advantages of simplicity there, potentially cost of therapy.
But 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 up regulating checkpoints. So it's been widely observed and published widely that in a tumor microenvironment, T cells tend to have multiple checkpoints up regulated or at least more so than T cells in the periphery. And so 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. And so we hope to focus that de repression activity in T cell upregulation where it might be needed most. And so we went after 3 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 MLD, to your intrinsic immunity, right? So we tried 3 different drug we developed 3 different drug candidates.
The first one, exonab2717 started in Phase 1 in July. That targets PD-one and CTLA-four on T cells. So those are the 2 most established T cell checkpoint targets, approved drugs, both have monotherapy function if you hit 1 of the other target at once. And we figured that was an approach that this leverages well understood biology or at least the best understood biology. The second one to list, XmAb22841, we just filed the IND for.
We hope to have patients on study in first half of twenty nineteen. That one targets 2 checkpoints, CTLA-four, so just like 2717, but also LAG-three, a checkpoint with clinical data that certainly indicates that repression of LAG-three can have a positive impact at the least when it's in combination with PD-one antagonism. And so 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-one therapy like nivolumab or pembrolizumab. So that's the exF-two thousand eight hundred and forty one thesis. Can we have a triple checkpoint blockade?
The last one was we wanted to include binding to a co stimulatory molecule and actually agonize that. And in this case, we chose ICOS and I'll tell you why in second, and combine that with PD-one inhibition, probably the most active single checkpoint. So again, 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-one ICOS as a combination? Why CTLA-four LAG-three is the best pair to use on top of a PD-one?
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. So again, a very empirically driven approach.
So just leaving you with milestones and goals for 2019, we do expect to initiate clinical trials. So first, outside of the oncology space that we do expect the Phase 3 study for XmAb5871, which we just are now allowed to start calling it's INN obexelimab. That will we hope to start that in IgG4 related disease next year. We also expect to initiate the Phase 1 studies for the 2 checkpoint bispecific studies talked about, XmAb22841 and XmAb23104. And we expect to submit the IND for the newest element of our pipeline that's exploiting our bispecific platform, which is our IL-fifteen, so a cytokine that's T cell activating our IL-fifteen molecule XENF23104.
And then data readouts we expect on 3 bispecific programs next year, our CD20, CD3 and SST are 2 CD3 T cell co engagers. We hope to have initial Phase 1 data out of during 2019. And then we expect to have a first look at some interim Phase 1 data from our XmAb20717, the first of our checkpoint bispecifics. Bispecifics. So looks like the field today at this week's ASH has 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 to 24 months, and I think that's going to mirror a continued expansion in the field.
And so there's a lot to watch for in bispecifics, a lot of biology we're going to learn about. Not everything is going to be a winner, but 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 we've guided through 2023. We ended last quarter with about just about $550,000,000 in the bank.
So we're positioned to try to attack these problems in a robust way. We're certainly willing to entertain more questions. I hope that Doctor. Ravani can stay a few more minutes. If there's any more questions for him, we'd be happy to address them.
Thank you. I'll 15 is 24306. I'm sorry, did I misread the number? I'm sorry, yes. No, it's actually Oh my gosh, yes.
That's yes, boy, we all proofread it 15 times and we got it wrong. So this line here, we'll submit IND application for XmAb for IL-fifteenile-fifteen receptor alpha, that should be XmAb-two thousand four hundred and thirty six. Our apologies for that. We'll correct those for the ones we post on the website. Oops.
And no hiccups. I've had them since Friday. Thank you.