Ladies and gentlemen, thank you for standing by and welcome to the Q3 2020 Xencor conference call. At this time, all participants are in a listen-only mode. After the participant presentation, there will be a question and answer session. To ask a question during the session, you will need to press star one on your telephone. Please be advised that today's conference is being recorded. If you require any further assistance, please press star and zero. I would now like to hand the conference over to your speaker today, Charles Liles, Head of Investor Relations. Thank you, and please go ahead, sir.
Thank you, and good afternoon. Earlier today, we issued a press release which outlines the topics we plan to discuss today. The press release is available at www.xencor.com. Today on our call, Bassil Dahiyat, President and Chief Executive Officer, will provide updates regarding COVID-19 impacts as well as our partnerships. Allen Yang, Chief Medical Officer, will review updates throughout our clinical portfolio, and John Kuch, Chief Financial Officer, will review financial results. Then we'll open up the call for your questions. Before we begin, I would like to remind you that during the course of this conference call, Xencor management may make forward-looking statements, including statements regarding the company's future financial and operating results, future market conditions, plans and objectives of management for future operations, the company's partnering efforts, capital requirements, future product offerings, research and development programs, and the impacts of the COVID-19 pandemic on these topics.
These forward-looking statements are not historical facts, but rather are based on our current expectations and beliefs and are based on information currently available to us. The outcome of the events described in these forward-looking statements are subject to known and unknown risks, uncertainties, and other factors that could cause actual results to differ materially from the results anticipated by these forward-looking statements, including, but not limited to, those factors contained in the risk factor section of our most recently filed annual report on Form 10-K and quarterly report on Form 10-Q. With that, let me pass the call over to Bassil.
Thanks, Charles, and g ood afternoon, everyone. Xencor's approach to creating antibody and cytokine therapeutics is centered around our XmAb protein engineering platform. By making small changes to an antibody structure, specifically in its Fc domain, we can improve its natural functions and performance and create new mechanisms of action. The plug-and-play nature of our suite of XmAb Fc domains allows us to engineer nearly any antibody to have improved activity, longer half-life, or bispecific structure. This flexibility and portability enable us to take multiple simultaneous shots on goal in the clinic, and the proof of concept data we generate will guide which programs we independently advance, which we will partner, and which we will terminate.
We're focusing our R&D on the expansion and use of our XmAb bispecific platform to create antibodies that bind two or more different targets simultaneously, and also to engineer cytokines with structures optimized for particular therapeutic use. We're currently running six phase I clinical studies evaluating such XmAb bispecific antibodies. We continue to explore novel mechanisms of action for oncology treatments with our XmAb bispecific platform. We're presenting three preclinical programs at the Society for Immunotherapy of Cancer meeting, or SITC meeting, next week. Our B7H3 by CD28 bispecific is a preclinical program that targets a T-cell costimulatory signal via CD28 to the pan-tumor target B7H3. This creates an opportunity to enhance treatment in a wide range of tumor types with T-cell-targeted therapies like checkpoint inhibitors and CD3 engagers.
We're also presenting our PD-1-targeted TGF-beta receptor blocker for T-cell activation and our potency-engineered IL-12 program, both of which are engineered to enhance tolerability and duration of action while providing highly active immune stimulation in tumors. Before we move on to our clinical portfolio today, I'd like to provide an update on the impact of the COVID-19 pandemic on our operations. The pandemic did not significantly disrupt patient enrollment in our six ongoing clinical studies during the third quarter. Manufacturers that provide our drug supply, however, notified us that they're currently experiencing critical shortages of material used in their manufacturing processes. We have sufficient supplies of drug material to continue conducting our ongoing studies without interruption. However, we expect a small delay in the development timelines for the preclinical XmAb30819 program, our ENPP3 by CD3 bispecific for renal cell carcinoma.
Timelines for advancing additional early-stage programs into the clinic and for our ongoing clinical programs could be affected if the supply interruption goes longer than we currently estimate. The autoimmune IL-2 FC program, XmAb27564, however, is not affected by this, and the initiation of a phase I study is on track for early 2021. We'll continue to update you on manufacturing impacts from COVID if and when they emerge. Within the company, we're maintaining a requirement for non-laboratory employees to work remotely, and we're also continuing with our on-site measures to protect the health and safety of our employees and of our community. With that, Allen Yang, our Chief Medical Officer, will review updates to the clinical portfolio. Allen?
Thanks, Bassil. Yesterday, the American Society of Hematology published an abstract containing updated data from our phase I study of vibecotamab in patients with relapse and refractory acute myeloid leukemia, which we will present in December. Vibecotamab is a CD123 by CD3 T-cell engager, one in a class of tumor-targeted bispecific antibodies that contain both a tumor antigen-binding domain, in this case, CD123, and a cytotoxic T-cell binding domain, such as CD3. CD3 bispecifics activate T-cells at the site of the tumor in order to potentially kill malignant cells.
Data emerging from the study suggests that the patients with AML having low baseline disease burden and specific T cell signatures may be more likely to respond to treatment with vibecotamab. The primary toxicity, cytokine release syndrome, is generally mild to moderate in severity when observed and is manageable. We continue to optimize the dosing regimen in this study. Along with our partner, Novartis, we are exploring opportunities to develop vibecotamab in patients with lower baseline leukemic disease burden, for whom an intermittently dosed CD123 targeting antibody could be a needed therapeutic option. Next, a phase I study of plamotamab, our CD20/CD3 bispecific antibody, continues to enroll patients with non-Hodgkin's lymphoma in chronic lymphocytic leukemia, with planned expansion cohorts to start in 2021. In addition, operational preparations are underway for a phase II monotherapy trial in diffuse large B-cell lymphoma and for a phase II combination therapy study as well.
Our third clinical stage CD3 bispecific antibody is tidutamab, which targets somatostatin receptor 2. Last month, we presented initial dose escalation data from the ongoing phase I study in patients with neuroendocrine tumors, or NETs. Tidutamab was generally well-tolerated at the recommended dose identified for the expansion portion of the study at 0.3 micrograms per kilogram priming dose and a subsequent 1.0 microgram per kilogram repeat dose. Peripheral blood biomarkers indicated tidutamab induced acute and sustained T cell activation. Dose-dependent increases in proliferation and activation markers of CD positive T cells, CD8 positive T cells were observed, which is consistent with tidutamab's mechanism of action. In 14 patients where we describe clinical activity, the best overall response was stable disease, and the median duration of treatment was approximately seven months.
We believe completion of enrollment and longer follow-up are required to evaluate progression-free survival and the clinical utility of tidutamab for patients with neuroendocrine tumors. Early next year, we plan to initiate an additional clinical study in patients with Merkel cell carcinoma and small cell lung cancer, which are somatostatin-2 receptor expressing tumor types known to be responsive to immunotherapy. In addition to these CD3 bispecifics, we have developed another suite of bispecific antibodies where the binding affinities are tuned for selective engagement of T cells, and we call these our tumor microenvironment activators. Selecting for dual checkpoint expression, for example, distinguishes these from combination therapy and most checkpoint inhibitors. T cells that have multiple checkpoint expression are typically found more in the tumor microenvironment than in the periphery.
Our design of this class seeks to more effectively reactivate these tumor-reactive T cells than existing therapies and is meant to potentially drive improved efficacy and tolerability compared to the dosing of separate anti-CTLA-4 and anti-PD-1 antibodies in combination. In mid-October, after abstracts from the SITC annual meeting were temporarily available to the public, we issued an 8-K with an abstract containing data from our ongoing phase I study evaluating XmAb20717, a dual PD-1/CTLA-4 checkpoint inhibiting bispecific antibody in patients with advanced solid tumors. The SITC meeting is next week, we won't review the abstract in its entirety now. In summary though, XmAb20717 continued to be well-tolerated in heavily pretreated patients, and we are encouraged by the antitumor activity observed in patients with various types of advanced solid tumors at the 10 milligram per kilogram dose level.
The study is currently enrolling patients with renal cell carcinoma to expansion cohort and continues to enroll patients with additional dose escalation cohorts starting at 15 milligrams per kilogram, as we did not reach the maximum tolerated dose. The expansion cohorts with melanoma, advanced non-small cell lung cancer, prostate cancer, and other cancers without approved checkpoint therapies are fully enrolled. The first studies evaluating two other clinical stage tumor microenvironment activators, XmAb22841 and XmAb23104, continue to enroll and dose patients with advanced solid tumors. Finally, we're developing a suite of cytokines, which are immune signaling proteins we have engineered with the XmAb bispecific Fc domains. We also tune the potency of these cytokines to improve their properties and make them more drug-like. For example, by slowing their receptor-mediated clearance and extending their circulating half-life.
Our first cytokine program and lead in our collaboration with Genentech is the IL-15 fused to its alpha receptor and our bispecific FC domain, which is XmAb24306, or RG6323. It targets the expansion and activation of T cells and natural killer cells and is not biased towards regulatory T cells like its cousin, the cytokine IL-2. Genentech is currently enrolling patients in a phase I study evaluating XmAb24306, initially as a monotherapy and then in combination with atezolizumab, their anti-PD-L1 antibody. We are planning to explore a number of our own combination studies after safety and dose in the ongoing phase I has been established. Our second cytokine candidate, XmAb27564, is an IL-2 FC fusion protein that we are planning to develop for patients with autoimmune diseases.
Similar to the IL-15 program, we reduced its potency and incorporated our Xtend technology in order for it to have more drug-like properties. As Bassil mentioned, we are on track to start dosing healthy volunteers in early 2021. We look forward to keeping you informed about all our clinical programs as they progress. Bassil?
Thanks, Allen. Now on to partnerships. A core part of our business is to complement our internal development portfolio with partnering. These partnerships generate payments from the licensing of XmAb technologies, the clinical advancement of XmAb candidates, as well as royalties from sales of approved products. There were no COVID-19 impacts to partnering revenue during the third quarter, but we will continue to monitor potential impacts, of course. Our many partnerships really highlight the plug-and-play nature of the suite of XmAb FC domains that we've created. With small changes to the FC structure that we've engineered, we can, for nearly any antibody, improve its activity, half-life, or readily create stable multivalent structures. We have 12 ongoing partnerships for XmAb technology, which have resulted in two marketed products.
Alexion's Ultomiris for rare blood disorders. Now MorphoSys's Monjuvi, or tafasitamab, as a first second-line treatment for patients with an aggressive form of lymphoma, diffuse large B-cell lymphoma. Unlike Ultomiris, where we just licensed the Xtend Fc technology to Alexion, we created tafasitamab, which MorphoSys licensed from us in 2010. Also initiated its clinical development running the phase I study. It's a CD19 antibody engineered with our XmAb cytotoxic Fc domain. MorphoSys has guided the decision on tafasitamab's European Marketing Authorization Application should be in the second half of 2021. The plug-and-play nature of our XmAb technologies enables partners to advance their programs with very few resources from us. We selectively license access to our XmAb technologies. We recently entered into an agreement with Omeros Corporation, providing them a non-exclusive license to our Xtend Fc technology.
As is typical for these types of agreements, Omeros is responsible for all development and commercialization activities for all candidates. We received an upfront payment of $5 million and are eligible to receive milestone payments and royalties. Finally, I just wanted to touch on progress our partners are making in advancing antibody therapies that incorporate Xtend FC domains for the treatment of patients with COVID-19. Alexion and Vir. Alexion is conducting a randomized controlled phase III study of Ultomiris in hospitalized patients with advanced COVID. Vir has non-exclusive access to our Xtend FC technology to extend the half-lives of VIR-7831 and VIR-7832, both novel antibodies that they're investigating as potential treatments for COVID-19.
Vir has commenced a phase III clinical study for VIR-7831 for the early treatment of COVID-19 patients who are at high risk of hospitalization. They plan to initiate a clinical study of VIR-7832 in the near future. Our partnership with Vir additionally demonstrates the broad applicability of Xtend across viral infectious disease, as their other antibody programs, VIR-3434 in hepatitis B virus infection and VIR-2482 in influenza A, are both advancing through early-stage clinical development. I'll hand the call over to John Kuch, our CFO, who will review the third quarter and first nine-month financial results. John?
Thank you, Bassil. During the third quarter, Xencor's portfolio of partnerships, collaborations, and licensing arrangements continued to generate strong cash flow, which help offset the growing investment in our pipeline of clinical and early-stage drug candidates. In this afternoon's press release, we reported cash equivalents, and marketable securities totaling $582.9 million as of September 30, 2020, compared to $601.3 million at December 31, 2019. The decrease reflects cash used to fund operating activities in the first nine months of 2020, offset by total proceeds of $89.1 million received in upfront payments, milestone payments, and royalties from licensing agreements. Total revenue for the third quarter ended September 30, 2020, was $35.4 million compared to $21.8 million for the same period in 2019.
Revenues in the third quarter included milestone revenue from MorphoSys related to approval of Monjuvi, licensing revenue from Omeros, and royalty revenue from Alexion. Compared revenues from the same period of 2019, which were primarily reflects milestone revenue from the Alexion, Amgen, and Novartis collaborations. Total revenue for the nine months ended September 30, 2020, was $80.8 million, compared to $153.2 million for the same period in 2019. Revenues for the nine-month period in 2020 include royalty revenue from Alexion, milestone revenue from MorphoSys, and licensing revenue from Gilead, Aimmune, and Omeros, compared to licensing and collaboration revenue from Genentech and Astellas, and milestone revenue from Alexion, Amgen, and Novartis collaborations in 2019. Research and development expenditures for the third quarter ended September 30, 2020, were $44.5 million compared to $29.8 million for the same period in 2019.
Total R&D expenses for the nine months ended September 30th, 2020, were $121.9 million, compared to $91.3 million for the same period in 2019. Additional spending on R&D for the third quarter and first nine months of 2020 over amounts for the same period in 2019 is primarily due to increased spending on our clinical programs, including plamotamab, XmAb20717, and our IL-2 FC cytokine development program, XmAb27564. General administrative expenses for the third quarter ended September thirtieth, 2020, were $7.6 million, compared to $6.3 million in the same period in 2019. Total G&A expenses for the nine months ended September thirtieth, 2020, were $22.1 million, compared to $17.5 million for the same period in 2019.
Additional spending on G&A for the third quarter and the first nine months of 2020 over amounts for the same periods in 2019 is primarily due to increased compensation costs related to additional general administrative staffing and spending on intellectual property, including patents and licensing costs. Non-cash stock-based compensation expense for the nine months ended September 30, 2020, was $23.1 million compared to $24.7 million for the same period in 2019.
Net loss for the third quarter ended September 30, 2020, was $12.6 million, or $0.22 on a fully diluted per share basis, compared to net loss of $10.2 million or $0.18 on a fully diluted per share basis for the same period in 2019. The higher net loss reported for the third quarter of 2020 compared to the same period in 2019 is primarily due to increased R&D spending over increased revenue earned during the period. For the nine months ended September 30, 2020, net loss was $55.6 million, or $0.97 on a fully diluted per share basis, compared to net income of $53.8 million or $0.92 on a fully diluted per share basis for the same period in 2019.
The net loss reported for the nine months ended September 30, 2020, compared to net income reported for the same period in 2019 is primarily due to higher collaboration licensing revenue reported in 2019 compared to 2020, and increased spending on R&D programs in 2020 over 2019 amounts. The total shares outstanding were 57.4 million as of September 30, 2020, compared to 56.7 million as of September 30, 2019. Based on current operating plans, projected spending, and expected proceeds from our partnerships and collaborations, we expect to have cash to fund research and development programs and operations into 2024, and to end 2020 with between $525 million and $575 million in cash equivalents, and marketable securities. With that, we would now like to open up the call for your questions. Operator?
As a reminder, to ask a question, you will need to press star one on your telephone. To withdraw your question, press the pound key. Please stand by while we compile the Q&A roster. One moment. Our first question comes from Ted Tenthoff of Piper Sandler. Please proceed.
Hey, thanks so much, guys, and nice update. I wanted to ask with respect to XmAb14045, your CD123 for AML. Definitely was intrigued to see the clean safety and some responses there. Maybe you can go into a little bit more detail in terms of what next steps might be and then sort of potentially do that in combination with other agent specs?
Thanks, Ted. I'll just state at the outset, of course, we have some restrictions because of our ongoing partnership with Novartis around XmAb14045 about how much we can say. I don't know, Allen, do you want to comment on the population?
Yeah, I have to be cautious here, but it was kind of an interesting scientific observation that we found more activity in patients with a lower burdens of disease, and there are specific populations in people with myeloid malignancies that will have lower burdens of disease. Ted, I'm sorry I can't say more at this time, but I think it's fairly obvious where you could go with this.
Yeah. Regarding combination agents, I think we did observe also a correlation of response to people who express certain T cell markers, so w e would potentially explore that as well. The next step is as Novartis and Xencor advance along the timeline to getting the next set of groups of patients enrolled, we'll be able to disclose things more fully.
Thank you so much for the update.
Thanks, Ted.
Thanks.
Thank you. Our next question comes from Peter Lawson of Barclays. Please proceed.
Hi, everyone. This is Mitchell on for Peter, and thank you for taking our questions. For vibecotamab, I can appreciate how you can't say so much about positioning, but could you talk about maybe the bar for AML in this population and how you see that, and then maybe your view on peer CD123/CD3 data in the space?
Yeah. Without commenting too much on peer data, I think that the populations that are possible with this agent, if we focus on low leukemic burden, there's a variety of different bars depending on the specific subpopulation. It's hard to give you an answer to that, but we do have good ideas about what the bar is without also disclosing, unfortunately, things we can't disclose.
Okay. I think you've mentioned potential other indications that the asset could go into. Do you have any ideas of where you might be able to take it beyond the low burden AML?
I would say it's low burden myeloid diseases in general, that they're pretty broad expressers of CD123, things from myeloid lineages, and there's a variety of myeloid malignancies.
Okay.
Beyond, in addition to AML.
Great. Thanks so much.
Thank you. Our next question comes from Gregory Renza of RBC Capital Markets. Please proceed.
Hi, guys. This is Ying Wang for Greg. I also have a question on vibecotamab. I was just wondering, in light of the recent publication on another CD3/CD123 bispecific that demonstrated association between (two three mutations) and complete response to AML, just wondering what your thoughts are on the read-through there, and have you explored or plan to explore the potential in subpopulations of AML patients with specific mutations? Thank you.
Yeah, I don't think specific mutations are how we orient this molecule. CD123 is a pan marker in various myeloid malignancies, and so we think of it from a broader use perspective, focusing now on where we see lower disease burden. I don't think there's too much read-through from there. Does that answer your question?
Yeah, t hey did. Thanks. I have another one, if I may. Just wondering what's your level of confidence in the tolerability of XmAb20717 based on the data so far, and how do you think the design of the molecule contributes to its differentiation from other PD-1, CTLA-4 bispecific or combination therapy?
Yeah, I'll comment on the design, and then, Allen, maybe you should jump in and talk about our tolerability observations. The design of the molecule was so that to take advantage of its bispecific structure, it allowed us to design a molecule that requires cooperative binding in order to have strong binding, cooperative binding to both PD-1 and CTLA-4. There's only one PD-1 binding domain, only one CTLA-4 binding domain. They have fairly modest affinity, so if there's only one target or the other on the cell, they're not going to stick too well, which means they don't have a terribly high affinity to cells that have low expression of one or the other of the markers. You have to have both. If you have both markers, you get nice avid binding. You have both arms able to grab on and pull yourself onto the cell.
That was so we would focus the molecule's activity at de-repressing these checkpoints on specific subpopulations that are typically more over-represented in tumor microenvironments. That's the double positive checkpoint cells. That's the distinction of the design, and the hope there was to activate the cells that matter for better tolerability and efficacy profile. That's the essence of the design, and I think that's distinct certainly from a combination therapy of two different antibodies, but it's also distinct from most of the PD-1/CTLA-4 bispecific antibodies that are in early clinical development alongside 20717. Allen, maybe you want to touch on the tolerability and the nature of AEs that we see.
Yeah. We're very pleased with the tolerability profile to date. As Bassil alluded to the design, it's hard to demonstrate differences in safety in a clinical study, especially a phase I clinical study from predecessor molecules. With that said, there seems to be a suggestion that the AE profile is slightly different. We're seeing a lot of rash, w e don't tend to see colitis. The way the study was designed, the 10 milligrams per kilogram was our top dose, and we didn't hit an MTD, so we're continuing to dose escalate now at 15 milligrams per kilogram, to see if we can dose higher. The idea is if you have better tolerability, you could possibly dose higher and then get more efficacy. We still have to see what the maximum tolerated dose is.
In addition, in the abstract, there was a Grade 5 and a Grade 4 event. I can add some color to that. The patient with the Grade 5 pancreatitis did have pancreatic involvement and metastases, and the one with the Grade 4 myocarditis had a non-small cell lung cancer that involved the myocardium. That is something that's in the abstract, but I think this helps to understand the AE profile. We're actually very pleased with the data so far.
Got it. Thank you very much.
Thank you.
Thank you. Our next question comes from Jonathan Chang of SVB Leerink. Please proceed.
Hi, guys. Thanks for taking my questions. First question, can you provide any more color on the planned plamotamab monotherapy and combination studies in DLBCL?
At this time, all we're really able to say is that they're phase II studies that were both in relapsed/refractory DLBCL and looking at specific groups of patients or defined populations within there, but more details will be forthcoming. I think that the strategy, though, has always been that the broad use of a CD20/CD3 is going to depend on the strategy you have for how you combine it with other agents, because there's so many agents of different MOAs that work in non-Hodgkin lymphoma. What we've seen for the last 20 years with the success of Rituxan chemo is that combining them in the right way gives you the best outcomes. I think we're going to have a whole new generation of these combination regimens to choose from going forward.
A monotherapy in this setting could give you rapid acquisition of data and a much faster-to-market strategy to try to have both prongs going. As I said, we'll have more details forthcoming as the final operational plans and nuances lock into place.
Got it, t hank you. Just second question, still on plamotamab. When could we see updated data from that program?
We will be presenting updated data next year, and we'll give specifics on the exact timing of that as we get a little closer to the data disclosures.
Got it, t hank you very much.
Thank you. Our next question comes from Tom Shrader of BTIG. Please proceed.
Hi. This is Kaori for Tom. Thanks for taking our questions. For autoimmune disorders, I believe two different approaches are being evaluated in the clinic. One is to suppress auto CD8 or effector T cells. The other, like yours, which is to stimulate or activate T reg. Can you tell us what are the advantages and what type of autoimmune disorders make sense for your approach?
Yeah, I think that it's sort of suggesting too much to think that anybody really understands the specific cellular etiology and drivers of any particular autoimmune disease. I recall not too many years ago, MS was considered a T-cell driven disease, and RA was considered a B-cell antibody driven disease. Yet, of course, you see highly effective MS treatments from B-cell targeting therapies like Ocrevus, and you see highly effective therapies when you look at T-cell blocking therapies in RA, like Orencia. I think simple descriptions of what drives the disease makes it hard to decide a priori what a particular agent or particular mechanism of action, which specific disease types it might benefit. I think that means that we have to look at the factors like population unmet need, the preclinical models that'll help us pick the indications for our autoimmune IL-2 program.
But I'm not-
Got it.
a big believer that there's detailed enough mechanistic understandings of the vast majority of autoimmune diseases to really dial yourself in like that.
Sure, r ight. Yeah, that makes sense. Just the last one from me. With all the engineering going around the IL-2 molecules to avoid CD25 binding, which seems to prevent Treg activation and vascular leak syndrome, at least pre-clinically, how is the IL-15 approach different from these novel attenuated IL-2 molecules?
IL-15, and this is for our oncology program, our XmAb24306, currently in phase I studies with Genentech, our partner. IL-15 doesn't bind the CD25 or IL-2 alpha receptor. It just doesn't. I think that's a critical feature that you might be able to tune away IL-2 alpha receptor binding or eliminate it by pegylating in the right spot. IL-15 starts out as baseline. That's, we believe, just an inherent benefit and a risk reducer. The other factor is the potency reduction we do is dependent on, or rather, was selected to have really the minimal amount of potency you could have and still activate the cells.
I can't comment on the exact degree of how people attenuated the potency of their molecules, but we think having a single defined composition of matter that has a specifically well-known potency is an advantage over, say, mixtures of differing potencies or kinetically variable potencies based on some chemical reaction around the molecule. Having it attached to our FC domains with our Xtend technology on it to sort of smooth out those bumps, I think is also a benefit, and we'll see how that all plays out in the humans, in our 24306 program.
That's helpful. Thank you.
Thank you. Our next question comes from Etzer Darout of Guggenheim Securities. Please proceed.
Great. Thanks for taking questions, and congrats on the updates here and the progress. Just a couple from me. First, just went back to ClinicalTrials.gov to remind myself of the other two checkpoint TME bispecifics. Just sort of given we've been dealing with COVID for the better part of the year, just wondering about the progress of these programs, and in phase I, and when we could expect to see clinical data from those two assets.
Right. We like to guide on when we're going to have clinical data, when we're pretty close to getting those disclosures going. Note, those two programs started about a year after our XmAb20717 program, which we just had our first data disclosures over the last few months. They're about a year less mature, having been in the clinic now for something like 15 or 16 months each. I can't say until we get closer and have more definitive information to tell you when we would update those programs. They are both actively enrolling. They have not had, either of them, any meaningful impacts from COVID-19. They both have dose escalation and expansion cohorts baked into them that we should be able to talk to people about in due course, and hopefully not that long, but we can't give any specific guidance right now.
Yeah, no, that's helpful. That's helpful thank you. Second question, just wondered, I guess to the extent that you can speak to this, any major differences in patient characteristics that you can speak to in the upcoming vibecotamab data relative to sort of the previously reported data back in ASH 2018?
I guess within the bounds of the abstract, I don't know, Allen, if there's much we can say about the different-- I'm assuming you're asking about demographics, Etzer.
Yeah.
Yeah. Go ahead, Allen.
There haven't been any significant change to the inclusion/exclusion criteria, so in terms of population shifts of the total patients enrolled, there's probably not going to be changes.
Yeah. It wouldn't reflect our insights around the kinds of patients in the lower disease burden that were better likelihood of response. It would not reflect that.
Great. Awesome. Well, I can always follow up as well after the presentation, but thank you.
Thank you.
Thank you. Our next question comes from Gabriel Fung of Mizuho Securities. Please proceed.
Hi there. This is Gabriel on for Mara Goldstein . Just a question here on the IL-15 24306 candidate. How are you thinking about the planning of expansion studies moving forward? Would these be more of combinations with portfolio products? Leaning more towards established external candidates? Does the agreement with Genentech have any restrictions on which targets either party can explore?
I'll take that one. In terms of timing, of course, you have to establish safety and dose schedule with the agent before we can kick off other combinations. We would look at not just our own internal candidates, but also third-party molecules, some of which have been predefined in the contract that we're planning on doing combination studies with, some of which we can just propose and initiate. There are some restrictions around, of course, creating problematic safety signals and things like that. Those are par for the course for combination studies. Also we cannot, and we would not want to, have the same exact mechanisms of action compete with each other within the overall study approaches. Right?
It'll be fairly broad, and we know Genentech has a pretty broad view beyond just in the phase I, doing that initial combination with tesolizimab, which is something that's been disclosed.
Right, g ood. Also, just one extra quick question on your comment about vibecotamab earlier, when you discussed that you see more rash than colitis. Could you provide more color as to your discussions with the physicians on the trial as to how meaningful this difference is, and if maybe a physician would prefer a rash over colitis events for the drug?
Yeah. Allen, you want to take that without obviously speaking for all the doctors and oncologists in America?
Yeah. Again, just to clarify, it wasn't for vibecotamab, it was for XmAb20717, our PD-1 CTLA-4.
Right.
I think it's still early in the development to say that we're going to sort of distinguish it based on its safety profile. I think it does suggest differences in the design of the molecule, and it's doing the things that we're hoping it's doing. At this stage, I'm optimistic, but I'm not going to go and say that people are going to use or prescribe differently based on the AE profile. That's always been challenging in oncology, because when you talk to oncologists, it's always about efficacy.
Got it. Thank you very much.
Sure.
Thank you. Our next question comes from Arlinda Lee of Canaccord. Please proceed.
Hi. Thanks for taking my questions. I had questions about your dose escalations for XmAb14045 and vibecotamab. Neither of these you've reached an MTD, and I'm wondering if you're still in dose exploring, what you're looking for to decide on a go-forward dose. On XmAb14045, do you think that going into a lower burden myeloid malignancy would have the same dose? I'm curious on the better efficacy that you're seeing. Are you also seeing lower CRS? Thank you.
There's several layers of questions there. Maybe to start with the first, you're talking about one program here, vibecotamab, right?
The 20717. Well, mainly the vibecotamab, also 20717. You haven't.
Okay. Now I can multiply all that by two. Hold on a sec. Let me just make a note.
Okay.
I think the places we're still nailing down the details around dosing regimen for XmAb14045 are around exactly the schedule of priming doses to give. That's that piece. That's always the last bits of details. It's fair to say that the restrictions around dose changing and escalation within a patient that we had put on us by the FDA coming off the clinical hold just definitely make that a little slower of a process. That's fair to say, that that made it definitely more difficult. You then asked the question about lower burden disease having necessarily the same or a different dose. Allen, you might want to take that. I guess you would expect more flexibility around the tolerability of the agent with lower disease burden, though.
Yeah. It's a great question, Arlinda. It's really around not so much the dose, but remember, we're giving ours intermittent dosing, so every other day or weekly, and it's the schedule and how quickly you can escalate. We know that you can give fairly high doses that can be tolerated, but they have to be sort of primed, and you have to sort of move up to that dose. It's really a balancing act of how quickly do you want the dose to go up and how high do you need it to go up to get the efficacy that you want to see. I think there's a little bit of work that still needs to be done there. Clearly, if you have lower burdens of disease, you may need a different dose or schedule.
I don't think we have that completely figured out yet.
Lower CRS with lower burden disease.
Sure.
I don't know that we have enough data to even comment on that, though nothing jumps out.
Yeah. We are watching that. I will say from the history of bispecific, that has been sort of demonstrated, clearly with BLINCYTO, the higher leukemic burden has more CRS, et cetera. It's something that we would expect to see, and we will keep an eye out for that.
For 717, because we saw activity at 10 mg per kg, we did expand there, and it's a tolerable dose, and we're exploring higher, but we're not letting exploring higher doses hold us back from really pushing forward with 10 mg per kg and then maybe adjusting later if higher is really well-tolerated and suggests it might give us an incremental bit of activity. We are confident that 10 mg per kg is an active dose.
Okay, great. Thank you.
Thank you. Our next question comes from Zhi Shu of Berenberg. Please proceed.
Thanks very much. Congrats on the progress. A few questions here. In your prepared remarks, you mentioned about the strategy for companies to decide which program to move forward and which program to terminate. I guess at the current state of all the assets, which ones would you say that you would definitely move forward?
Well, they're all moving forward right now to get that key proof of concept data that gives you that ability to make the decision. That's essentially where most of our programs stand. I think our plamotamab and 20717 programs are at that point where the proof of concept data is emerging as we observe, right? It doesn't all happen at once in these open label oncology trials. Data emerges and rolls out and gives you the directions to take. We're in the midst of that decision process for how to advance plamotamab and 20717, and we're actually optimistic about both. I think we feel pretty confident that both are going to continue advancing. For the others, we await data, and we'll have the thumbs up, thumbs down on those as data emerges.
Okay, great. For IL-12 and IL-15, I understand both are for oncology. Based on, I guess, preclinical or translational data, do you see the difference in terms of which indications for a slider program?
Not really. I think that they both have a broad activity at improving T-cell function and number. I don't think there's anywhere near the granularity of data you would want to look at indication based on their specific mechanisms.
Mm-hmm. Okay, understood. Finally, for the IL-2 program for autoimmune disease, I understand that you mentioned eventually probably this will be partnered out as companies focus on oncology. When do you think will be a good time for the company to start looking? Do you want to get the phase I data ready, or are you looking for parties outside right now?
I would actually park the idea that we're definitely gonna partner the IL-2 program. I think it really comes down to the indication strategy that we select, that we're right now pulling all the pieces together on, that we would implement immediately after we come out of our healthy volunteers dose escalation, which we hope happens very quickly, because that's the beauty of healthy volunteer studies in these autoimmune indications, just to get your mechanism of action, your pharmacodynamics, your PK nailed down. That indication strategy is gonna drive whether we want to keep the asset for the long haul or partner it. I think that we have to be realistic that sometimes in autoimmune disease, partnering is what you need to do. I don't want to make that a predicate, if that's what we're definitely going to do with that program.
We'll be able to give more color on that as we can start publicly disclosing our strategy.
Got it. Thank you very much.
Thank you. I would now like to turn the call back to Bassil Dahiyat for closing remarks.
Thank you very much, operator, and thank you everybody for joining us today. Take care of yourselves. Have a great evening. We look forward to updating you again over the coming weeks.
Ladies and gentlemen, this concludes today's conference call. Thank you for participating, and you may now disconnect.