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Ladies and gentlemen, thank you for standing by and welcome to the Harpoon Therapeutics 4Q 2020 Financial Results and Corporate Update Conference Call. At this time all participants are in listen-only mode. Please be advised that today’s conference may be recorded. [Operator Instructions] On the call today from Harpoon are Gerry McMahon, President and Chief Executive Officer; Georgia Erbez, Chief Financial Officer, Georgia Erbez, Chief Financial Officer, Natalie Sacks, our Chief Medical Officer and Holger Wesche, our Chief Scientific Officer. Following management's prepared remarks we will be conducting a Q&A session. [Operator Instructions]
I will now turn the call over to Georgia Erbez.
Thank you operator. Good afternoon and welcome to the Harpoon Therapeutics webcast and conference call for a discussion of the company's fourth quarter and full year 2020, financial results and a corporate update. Before I turn the call over to Dr. McMahon, I would like to remind you that today's call will include forward-looking statements. These forward-looking statements are based on Harpoon's expectations and assumptions as of the date of this call. Each of these forward-looking statements involves risks and uncertainties that could cause Harpoon's clinical development programs, future results or performance to differ significantly from those expressed or implied by the forward-looking statements.
Please refer to Harpoon's filings with the SEC, including its Annual Report on Form 10-K for the year ended December 31, 2020, which was filed today and which are also available on Harpoon's website for information concerning factors that could cause Harpoon's actual results to differ from those expressed or implied in the forward-looking statements discussed on this call.
Except as required by law, Harpoon assumes no obligation to update any forward-looking statements discussed on this call to reflect any change in the expectations, even as new information becomes available.
I will now turn the call over to Dr. Gerry McMahon, President and CEO of Harpoon Therapeutics.
Thank you, Georgia, and thank you all, for joining us on the call this afternoon. I am very pleased with Harpoon’s achievement of significant clinical, scientific and operational milestones during the past year. At the time of our IPO in February 2019, our goal was to have four programs in clinical development by the end of 2020. Harpoon achieved that goal including starting two new clinical trials in 2020. We maintained our commitment to driving multiple products forward for the potential treatment of cancers and the benefit they could provide to many cancer patients who have limited treatment options.
Some of the key accomplishments for Harpoon in 2020 included the progress of our lead product candidate HPN424, which is continuing in the dose escalation portion of the Phase 1/2a clinical trial in patients with metastatic castration-resistant prostate cancer. We also advanced our other three TriTAC clinical programs including HPN536 for the potential treatment of mesothelin-expressing tumors, with the focus in ovarian and now including pancreatic mesothelioma cancers.
Our third product candidate HPN217, entered the clinic in April of last year with initiation of a Phase 1/2 clinical trial for multiple myeloma. And finally, in the second half of 2020, we submitted an IND initiated a Phase 1/2 trial for our fourth program, HPN328 targeting DLL3 for small cell lung cancer and other DLL3 expressing tumors.
We also made significant progress with our proprietary ProTriTAC T cell engager Pro drug platform designed to remain inert systemically until its activation in the tumor. We believe this platform can enable the safe targeting of more broadly expressed tumor antigens, HPN601, has been nominated as a clinical candidate and becomes our first conditionally active T cell engager program. It targets the tumor antigen, epithelial cell adhesion molecule, or EpCAM, which is broadly expressed on a wide variety of solid tumors. It is currently undergoing additional preclinical and IND enabling investigations. We will keep you updated on our progress for this exciting program.
Recently, Harpoon strengthened its financial position significantly, with our successful follow on offering in January 2021 that raised approximately $108 million of net cash. The financial resources from this transaction, along with our existing cash, cash equivalents and marketable securities that are on the balance sheet of $150 million, as of the end of December, gives us a pro forma cash balance of approximately $258 million.
These resources are being deployed to further support and advance each of our clinical development and research programs to multiple potential value creating milestones for our shareholders.
Now, let me review some key aspects of our TriTAC technology. And after that, I will update you on our clinical development programs. Harpoon’s TriTAC technology platform is a novel and proprietary approach to engage T cells, the most potent killer cells of the immune system. T cell engagers are engineered proteins that physically connect a patient's own T cells to target cells that express specific proteins or surface markers. This results in the activation of T cells unleashing the natural power to kill the target cell by releasing potent cytokines and other factors. Our current pipeline of product candidates is focused on oncology indications, but other uses would also be possible.
We believe our TriTAC have a number of features that could be advantageous when compared to other immunologic approaches to the treatment of cancer. First, our TriTACs are modular by design, and are about 75% similar to one another. They consist of three primary components that perform three different functions; T cell binding, half life extension, and tumour cell binding. To address Half Life Extension, we utilize a domain that binds transiently to human serum albumin. We utilize single domain antibodies for target binding and human serum albumin binding, which makes our molecules smaller and more flexible, that would be possible with larger antibody derived fragments.
Furthermore, these domains are inherently very stable, contributing to a platform that potentially has very little off target activity, and is therefore expected to have a therapeutic window ideal for applications in solid tumors.
Second, our TriTAC molecules are relatively small globular proteins that can be administered to patients by intravenous delivery in a one hour infusion every week or two weeks. The TriTAC protein is about one third the size of a typical antibody, and we believe the smaller size and globular shape of TriTACs allows them to diffuse more freely into tumor tissue compared to antibodies.
And finally, our TriTAC can be manufactured and chose cells and use standard methods of conventional antibody based manufacturing techniques. This completely avoids the cost and complexity of personalized or cell based therapies such as CAR-T. Utilizing all of these unique features our TriTACs are designed to connect with and convert a patient's own T cells to kill tumors. They are engineered to optimize the therapeutic index of T cell engagers and bring success as seen in liquid tumors to solid tumors.
Now, let me review where we are with our four clinical development programs. Our lead TriTAC product candidate HPN424 targets prostate specific membrane antigen or PSMA, for the treatment of metastatic castration resistant prostate cancer, and continuous in dose escalation of a Phase 1/2a clinical trial.
At our December 2020 data update, we reported that for the highest fixed dose tested 160 nanogram per kilogram, seven patients have been enrolled and one patient had achieved a confirmed partial response based on RECIST version 1.1 criteria. Three patients enrolled in this cohort had serum PSA reductions, including one with a reduction of 50% or PSA50. For this difficult to treat patient population we are encouraged by these early results. We are continuing to enroll patients into advanced the dose escalation. We are also able to employ step dosing in this trial where patients are receiving a dose of 300 nanograms per kilogram. This allows for a faster advancement to much higher doses than a traditional fixed dose escalation would allow. We're planning to present data from this trial at a medical meeting later in the first half of this year, most likely at ASCO.
As a reference point to keep in mind PSMA is present in 85% to 90% of patients with advanced metastatic prostate cancer. Market Research shows that prostate cancer is the third leading cause of cancer death in the United States. There are approximately 174,000 new cases and 31,000 prostate cancer deaths in the United States each year.
Our second TriTAC product candidate to enter the clinic, HPN536 targets mesothelin. Initially, we began studying HPN536 in platinum refractory ovarian cancer and expanded enrollment to include metastatic pancreatic cancer patients and mesothelioma patients in this trial. Mesothelin is expressed on malignant cells of ovarian and pancreatic carcinomas, mesothelioma, non-small cell lung cancer and breast cancer, among others.
While mesothelin has been the focus of some CAR-T efforts, HPN536 is the first mesothelin targeted T cell engager to enter clinical development. Patients receiving weekly infusions of HPN536 and the trial is proceeding in line with our expectations. At our clinical update in December 2020, we reported dosing 39 patients across nine fixed dose cohorts at 6 to 280 nanogram per kilogram and one step dose cohort up to 600 nanograms per kilogram. Since the update we have advanced to a 1200 nanograms per kilogram step dosing cohort. The experience we have gained from HPN424 has been beneficial in our conduct of the 536 trial. We expect to provide interim data from the ongoing dose escalation portion of the trial by the year end 2021, possibly at ESMO or as Tsitsi [ph], as well as initiation of a dose expansion cohort in the second half of 2021.
Our third TriTAC product candidate HPN217 targets B-cell maturation antigen, or BCMA. We initiated a Phase 1/2 clinical trial in April 2020 in the treatment of relapsed refractory multiple myeloma and are pleased by the progress of the trial. This program is covered by a collaboration option agreement with AbbVie, and dosing with the first patient triggered a milestone payment of $50 million, which we received in June 2020.
In January 2021 HPN217 received orphan drug designation from the FDA. And our December clinical update, we indicated we had treated six single patient fixed dose cohorts of 5 to 810 micrograms reflecting a more than 100 fold increase in dose within the first eight months of the trial. A presentation of interim data is expected in 2021, possibly at ASH and we expect to initiate a dose expansion cohort in the second half of 2021.
HPN328 is our fourth TriTAC product candidate and it targets delta-like ligand 3 or DLL3, a protein highly expressed in a majority of small cell lung cancers, and other DLL3 expressing tumors. We submitted an IND for HPN328 in the third quarter of 2020, and initiated the Phase 1/2 clinical trial in December, which includes step dosing as part of the protocol. We expect to present interim data from the dose escalation portion of the trial in the second half of 2021.
Despite the challenges of this past year, it was a period of impressive pipeline advancement for Harpoon. With four programs in the clinic, we look forward to providing clinical data from all of our product candidate programs in 2021 and beyond. We have a unique of-the-shelf platform for T cell engagers that reprogram a patient's own immune cells to treat a wide variety of malignancies. Our unique pipeline is well positioned to generate exciting data and drive shareholder value.
With that I will now turn the call over to Georgia for a discussion of our financial results for the fourth quarter and the full year 2020.
Thank you, Gerry. And good afternoon, everyone. I will provide a brief overview of our financial results here on the call and invite you to review our 10-K filed today for more detailed discussion. Revenue for the fourth quarter ended December 31st 2020 was $7.5 million, compared to $2.2 million for the fourth quarter ended December 31, 2019. Revenue for the year ended December 31, 2020 was $17.4 million compared to $5.8 million for the prior year.
During both the three month period and full year periods the increase in revenue was primarily due to the revenue recognized from the development and option agreement with AbbVie signed in November of 2019. I want to remind everyone that revenue recognition is a non-cash amortization of cash we have already received.
Research and Development expense for the fourth quarter of 2020 was $15.1 million, compared to $12.7 million for the fourth quarter ended December 31 2019. R&D expense for the year ended December 31 2020 was $52.6 million, compared to $41.6 million for the prior year.
The increase for both periods was primarily due to higher clinical development and personnel related expense, including conducting preclinical studies and continuation or initiation of clinical trials for HPN 424, HPN536, HPN217, and HPN328. These higher expenses were offset by a decrease in manufacturing costs, which resulted from a scale up of manufacturing activities in 2019 compared to 2020 to support our four TriTAC product candidates.
General and administrative expenses for the quarter ended December 31, 2020 were $3.9 million, compared to $4.3 million for the fourth quarter of 2019. General and administrative expenses for the year ended December 31 2020 were $16.2 million compared to $22.4 million for the prior year. The decrease is primarily attributable to lower legal expenses, partially offset by an increase in personnel expenses related to higher headcount and professional services to support our on-going operations as a public company.
The net loss for the fourth quarter ended December 31 2020 was $11.4 million, compared to $14.3 million for the fourth quarter ended December 31, 2019. Net loss for the year ended December 31 2020 was $49.9 million, compared to $55.6 million for the prior year. Harpoon Therapeutics ended 2020 with $150 million in cash and cash equivalents compared to $155.1 million as of December 31 2019.
Net cash used in investing activities for the year ended December 31, 2020 was $63.6 million primarily related to the purchase and maturities of marketable securities. Net cash provided by financing activities for the year ended December 31 2020 was $4.7 million, primarily comprised of approximately $3.0 million in net proceeds from the sale of our common stock pursuant to our controlled equity offering with Cantor Fitzgerald in October and November of 2020.
Net cash used in operations for the year ended December 31 2020 was $8.6 million. I would like to remind you that the cash balance at the end of the year does not include the follow on financing that closed on January 11, 2021 resulting in a net cash proceeds of approximately $108.1 million. On a pro forma basis for the offering we completed in January 2021 Harpoons cash balance was $258 million.
For 2021, we are estimating cash to use and operating activities will be approximately $85 million to $95 million. With that, I will now turn the call back over to Gerry.
Thank you, Georgia. I am very pleased with the tremendous progress Harpoon made during the past year, the momentum with which we have entered 2021 and the exciting potential of all of our product candidates and our proprietary TriTAC and ProTriTAC platforms with four of our product candidates HPN424 to 536, 217, and 328 all in clinical development. We achieved the goal we stayed at the time of our IPO in early 2019. We expect 2021 to be an exciting year for Harpoon. We plan to initiate expansion cohorts in three of our four clinical programs, and plan to provide data updates to our shareholders throughout the year.
Our financial position is strong, and we have the resources in place to continue advancing our pipeline. Before we jump into Q&A, let me quickly review our anticipated near term milestones, which includes interim data updates for each of our four clinical programs.
For 424, the dose escalation part of the Phase 1/2a clinical trials is on-going. We're planning to present interim data and initiate a dose expansion cohort in the first half of this year. We anticipate a second data update from the expansion cohort by the end of 2021. For HPN536, the Phase 1/2a clinical trial is continuing to enrol patients in the dose escalation part of the trial. We are planning to present interim data from this trial by the end of the year 2021 and initiate a dose expansion cohort in the second half of 2021.
For HPN217, we expect to present interim data from the dose escalation part of the Phase 1/2 trial in 2021 and initiate the expansion cohort in the second half of 2021. For HPN328, we're planning to present interim data from the dose escalation part of our Phase 1/2 clinical trial the second half of 2021.
So with that operator, we are now ready for questions.
Thank you.[Operator instructions] Our first question comes from Jonathan Chang with SVB Leerink. You may proceed with your question.
Hi, guys, thanks for taking my questions. First question on HPN424, can you confirm whether or not an abstract has been submitted to ASCO? Can you help set investor expectations as the interim data update?
Yes, what I can say, hi Jonathan is that we have submitted an abstract for ASCO, obviously, our hope is that this would be accepted. And we could present some data from the on-going trial there. The data set will be comparable to what we presented at ASCO in June of last year, which is a very broad and comprehensive look at all the features of the clinical trial. Let me turn it over to Natalie to give a little bit more detail on that.
Sure. Thanks for the question, Jonathan, this is Natalie. So again, we'd like to give as comprehensive as possible update on the escalation portion of the trial. Remember the objectives of the first part of the trial are to characterize safety, activity, pharmacokinetics markers of T cell engagement, markers of target engagements such as CTC, so a rich pharmacokinetic and pharmacodynamic data set. So all of the objectives of the trial I mentioned, we want to summarize the data and learnings today.
Got it? Second question, how should investors be thinking about the potential implications on HPN424 from the Novartis vision study readout also expected in the first half of the year?
So Jonathan, this is Gerry. So obviously, we're paying close attention to that trial. It's an interesting trial with a small molecule PSMA targeted agent, a radio conjugate and it is conducting in late stage cancer population prostate cancer population with progression and survival as Potential endpoints for the trial.
So we really want to learn from a trial like that, because in concept, this could be a patient population of interest for us as we think about how to bring 424 to patients. So it's a it's a trial that we have a lot of interest in. But of course, it is a different modality, although it's the same target. So we have to be cautious in how much to read through into the data. But we're still interested in those particular endpoints for the trial.
Understood. And just last question here. With the Takeda acquisition of Maverick, can you refresh our memories on the latest development and legal status for ProTriTAC and discuss what if any, impact the acquisition has on your ProTriTAC strategy? Thank you.
Well, I will I will defer the question related to ProTriTAC to Holger, but as it relates to the litigation matter with that's on-going around this, we can't comment on that. And we will not be able to comment that comment on that today. But maybe Holger, we can talk a little bit about our platform and where we're focused.
Yes, I mean, so our platform is, the ProTriTAC platform aims at bringing the TriTAC advantage of increased stability, and presumably fewer side effects to more tumor targets, less safe targets, enabling us to dose an inactive ProTriTAC for Pro drug rather than it gets activated in the patient's tumor and increasing the therapeutic index there and allow us to go after targets and indications you will be able to after before. Jonathan, any concrete question for me regarding the platform?
I guess, I was curious to know if there were any implications from that acquisition, on your strategy for development, the platform?
Yes, I mean, is this a developing story as of today, I'm not aware of any such impact. But I would say, I have the exact same information about this acquisition as you do. And I think we have to wait a little bit to learn more about this really means in details.
Got it. Thank you.
Thank you. Our next question comes from Tyler Van Buren of Piper Sandler. You may proceed with your question.
Hi, guys, thanks for taking the questions. I guess I'll stay on that topic. I'm kind of curious. If you consider other pro drug technologies like those from Xintanix [Ph] or Amunix. How would you compare the your ProTriTAC platform? And are you developing additional aspects of this platform that address other masking technologies for instance?
It’s Gerry, Yes, well, let me start I’m just saying that we're obviously there are many companies now pursuing ways to bring T cell engagers into the tumor microenvironment. And you referenced some companies doing that. And from the very beginning, we wanted to do something with our platform, that would be a logical extension of the advantages we saw on TriTAC. So I'm going to turn it over to Holger now to give you more detail about that.
Thanks, Gerry. Yes, I mean, you're not going to be overly surprised to hear that we of course, think our platform is superior to be competitive. And after looking at the landscape, we think there's reason for that, just to point out a few things. Our modality is not Fc base, so before TriTAC carries on the TriTAC advantage of not having liabilities like Fc receptor binding, and so on and so forth with most of our competitors have.
What I personally think are two outstanding attributes on our platform as we have disclosed in the past. One of them is that our platform couples Half-Life two activation. And that means when the drug gets active, it uses its half-life, which is additional safety switch, meaning we can be a little bit more lenient in terms of when and where our drug is getting cleaved. Because it can't accumulate after activation, that we think raises the possibility of an increased efficacy compared to competitors that don't do that. It's just one example of how we think we are superior to that. But through to the competition, basically, finally we maintain the TriTAC advantage, we avoid the Fc based related issues. And we have some special tricks, like the coupling of Half-Life to activation in our expectation leading potentially to an increased therapeutic index. That was the first part of your question. I think there was a second part if I recall correctly.
Yes, I guess maybe just a little bit more information on, if you're developing any other kind of masking technology?
Right, thank you. So yes, I would say innovation that hopefully never stops, we are constantly working on all our platforms. And yes, we have other aspects, we're looking at evaluating however, we have not publicly disclosed that it’s a little bit too early for that. But as other approaches reach maturity throughout the year, we will continue updating you.
Thanks so much.
Thank you. Our next question comes from Yigal Nochomovitz with Citigroup. You may proceed with your question.
All right, great. Thanks for taking the questions. I just have one on HPN328, is the plan to screen for expression of DLL3 in small cell lung cancer or the expectation that the expression of that target is high and that tumor c won't need to screen? And additionally, what other tumor types would you go after that have high DLL3 expression?
Yes, I'll start the, the answer. This is Gerry, and then I'll turn it over to Natalie. So, we don't believe we need to select for patients for DLL3, the prevalence and expression of this target is actually quite unique and in quite profound in many ways. It does track to the neuro endocrine features of small cell lung cancer compared to typical ad known squamous cell carcinomas of the lung. So it's pretty unique in that regard. And from that viewpoint, we also know that the data that emerged from Amgen last year related to targeting DLL3, for T cell engagers was quite encouraging in treating patients broadly, who have small cell lung cancer, so we don't have any requirement to do that, in this initial trial. Natalie, a question related to other Tumor types?
Sure. So we're doing both in response to your two part question. As Gerry mentioned, for small cell lung cancer, we are we do not regard patient selection as required. A hallmark of the TriTAC platform is that cell killing can be achieved with extremely low target antigen density. So in fact, we're all for on-going clinical trials. We take all comers during escalation, we do examine retrospectively the expression of the target to enhance our learnings. But again, given the potency of the molecule or the approach, we could not persuade ourselves that there was a level of expression which was too low.
However, for the other tumor types, which don't necessarily have a reasonable chance of DLL3 expressions, we are relying on pathology, and will accept any tumor type with evidence in pathology. That's suggestive of DLL3 expression. So there's a number of pathologic features which meet that criteria. So the short answer is any tumor type, with some evidence, pathologically, of DLL3 expression. We're particularly interested in prostate cancer, or the so called neuro endocrine phenotype of prostate cancer, which is increasing in incidence, I think, in part because of the selective pressure of the novel androgen targeting medicines. And there's an strong interest in the field right now to find medicines that are effective for those patients where very few options exist.
So prostate, with neuro endocrine features is important and we'll be enrolling nose and then in addition, any other patient tumor types with characteristics of DLL3 expression.
Thank you. Just one housekeeping question regarding the dose expansion plans for 536 and 217. Have you determined what those two will be expanding at for those two studies?
Let me answer that initially. So, they're all on-going escalations. And of course, we don't have any precision to the doses that will drive the expansions or any of our trials, before we do the work. And so, a lot of this will be driven by the data we see that emerges at the various doses. Obviously, if one achieves a maximum tolerated dose, then of course, you have a limit, but at this point, we have not achieved an MTD on our two lead programs and we continue to explore doses to see which doses warrant expand.
Moving forward, in the case of 536, that expansion will probably be a tumor specific expansion. Again, this is a trial that is enrolling three tumor types. So expansion will most probably involve the treatment of a particular tumor type moving forward. Natalie, anything else you want to add on this question?
No, we look forward to giving data updates throughout the year on that question. Sure. Nothing else to add to that.
Thank you Gerry. Thank you Natalie.
Thank you. Our next question comes from Asthika Goonewardene with Truist Securities. You may proceed with your question?
Hi, guys, good to speak to and thanks for taking my questions. Gerry, you've already answered what the one I just had about MTD. So let's really focus on 424. What comes up to 300 milligram dose? Are you going to go into 600? Or given the adjusting data in hand with 536? Would you feel comfortable jumping to the 1200 nanograms step dose? And I got to follow up after that.
Yes, Natalie can get into more of the nuance here. The determination of any dose, whether it's a step dose, or a fixed dose is determined based on an analysis, of course, of various factors. And although we have increased the dose, three, threefold in many cases in step dose, we obviously have a lot of discretion as to the actual increment, as well as we want to do multiple steps. And all those are, are under consideration. So it's not formulaic in that regard. And let me turn it over to Natalie to add more color to that.
Sure, if I understand the question, I just want to clarify that the doses across the trials don't behave in the same way, although these are all TriTAC. They don't have the exact same potency for various reasons. So 600 nanograms of one is not the same as 600 nanograms of say the other. So learnings from one dose on one trial don't necessarily influence the absolute dose on another trial, if that's what you're asking. So as we mentioned, in the December data release, we're exploring step dosing across the trials. We're looking at that time, we said, we're looking at 300 in HPN424, and up to 1200, and HPN536. And we don't have further updates today about dosing. But of course, we'll be sharing more data throughout the year.
Okay, great. That actually answers the -- my second, my next question I had. Thanks a lot, guys. Appreciate it.
Okay.
Thank you. Our next question comes from Zegbeh Jallah with ROTH Capital Partners. You may proceed with your question.
Hi, guys. Just had a couple of different questions for you. I think the first is I really like the flow of data that we're going to see this year, particularly from your first year program. So just kind of want to get a sense of how concrete the data is going to be. Because I think the early data, which is kind of looking at safety, the use of [Indiscernible] and leftism, and things like that, and so are we really going to have data that we can draw comparisons from, and then the second one is just, you'll be doing those expansions this year, at what point are you going to start considering probably, some combos, like IO combos and then third is that, DLL3 is exciting, glad you're in the clinic with that. And, are we likely to see you expanding into other tumor types like that for the visit feeling program and then the last one yes, I think this one is probably for Holger or actually Gerry can answer this one as well. Just wondering, as you continue to expand your pipeline beyond these, these programs that we have, are you going to just focus more on the ProTriTAC or are you going to expand more with your TriTAC? And I'm just wondering, does the ProTriTAC win some efficacy on the table it is just more costly that if you don't need it, why use it? Or, is it just better? And you're just going to continue with that moving forward?
Well, let me start and hand it over to Holger, let's start with your last question first, because I'm not sure I completely remember the first two questions at this point. But the last question, ProTriTAC was invented for those targets in which if you were to have a TriTAC that was completely active from the moment of infusion, it might limit the utility of the drug because of T cell activation against normal tissues. And so the intent of our first development program, HPN601, is to explore a target, that is has broad potential utility. And for which previously, there's been shown some evidence of tissue toxicity. So that is really the goal of our first program. But Holger can address that as well as future products that we're focusing on in the company, currently.
So as Gerry pointed out, so on one level, there are certain targets. Let me take a step back, we developed ProTriTAC to be able to go after targets, we can't go after with TriTACs for safety reasons. As Gerry pointed out and there's one answer to your question, use ProTriTAC for things that we can't TriTAC like target [Indiscernible].
Now, your question is, and then implied in my answer is that there are targets when you can use TriTAC. And your question is, are we going to switch from TriTAC to ProTriTAC those targets? And everything else being equal my answer would be likely no, because in principle, when we can keep things simple, we will keep things simple. So ProTriTAC is more complicated than TriTAC, which from my very scientific point of view is an added liability just due to complexity, if I can avoid that, I will. But as you know, these compounds are in the clinic, both TriTAC. And TriTAC are in the clinics for TriTACs are hopefully going to be in the clinic soon or at some point in the future. And as we get started, we're going to adjust to our position there. But as of today, when I look at them as optimal for different kinds of targets, and hence different indications, so they I see them next to each other. But again, this is going to be driven by data over the next few years.
Okay, as your question on DLL3, I think that was your third question. What was that one again?
Yes, I was just saying I was very interested in target and was just wondering if you're going to expand to other tumor types, like you've kind of done with your entire [Ph] program in terms of expanding to other tumors?
Yes. And Natalie just gave an answer to that. And, we have that plan. In fact, we are including other tumor types in our phase one dose escalation. Natalie, do you want to briefly indicate that again, maybe?
Sure, sure. And hi, Zegbeh. So the, the comparison to 536, it's a slightly different strategy. So it's a good question. So 536 HPN536, the Mesothelin targeting TriTAC, we decided to enroll patients that we believe have tumors that are known to express Mesothelin. And we limited that to ovarian cancer patients, pancreatic cancer patients and the Mesothelioma patients. So all three of those Mesothelioma in particular, are well characterized as tumor types that express Mesothelin. They're all included us in escalation. And we have the opportunity to do expansion cohorts for any and all of those. So that's in contrast to DLL3, like you said, where you have one tumor type that expresses DLL3 quite well, small cells, but we're also including in escalation, other tumors that show that they have DLL3 expression. Right? So that's, that's a could be anything could be some neuropeania [Ph] or neuroendocrine tumors or prostate cancer. So they're, they're coming in, not by the type of cancer they have, but that they're showing they have DLL3 expression.
So it's a bit of a different tactic, but both of them take different tumor types. And then for deal all DLL3 HPN328, based on what we learn, we can we can start different expansion cohorts, you could do a basket, again, tumor agnostic, just making sure you have DLL3 expressions, you can do small cell, because they express DLL3 without checking. So I hope that addresses your question. They both, they both capture different tumors, but a kind of in a different way if that makes sense. One is by indication, and one is by product discretion.
Okay, thanks Natalie.
And then Zegbeh you have a question around comp, you got a question around combinations? And probably it's easiest to answer that in the context of the prostate trial where we know there are various standard-of-care products out there, where we could consider combining it and late stage disease. And those are under active consideration as we think about different expansion cohorts for the program. Natalie, any comments around that?
Sure, real brief. Just building on what you said. For oncology, it's a paradigm of combination regimens, obviously, to sort of maximize efficacy against how to treat diseases. And I, there's two approaches, or at least, I think I have a simple way in my mind to keep it simple. Either there's a mechanistic or scientific rationale for a combination. Or there's a standard-of-care combination that makes sense. Or you need to understand how your drug works with the existing standard-of-care.
So that those two buckets provide a lot of options for us. Obviously, we can consider IO combinations. There's a rationale for combination with PD, PDL1 inhibition. With T cell therapies, there's rationale and some tumor types to combine with standard-of-care, such as PARP inhibitors, which applied to a number of different tumor types with chemotherapy is actually a reasonable thing to do with hormone blockade and prostate cancer. So the answer is sort of yes, yes. And yes, we're thinking carefully about rational combination strategies for each program based on the tumor type.
And our protocols and an approach allow us to pursue that in expansion. Of course, we anticipate monotherapy activity for all of our compounds, and we strive to demonstrate that, but at the same time, we're already doing preclinical work, and giving some thought to what combinations makes sense.
Perfect, very helpful. Thanks for all the updates and looking forward to that data read outs.
Okay.
Allright, thanks.
All right. Thank you. Our next question comes from our Arlinda Lee with Canaccord. You may proceed with your question.
Linda, can you hear us?
Hi guys. Thanks for taking my questions and congratulate, we're looking forward to all the data that's coming out this year. I had maybe a broader question about your appetite for additional collaboration. Are you planning on taking all of these forward yourself? I mean, it's upto 217, I guess, which has the collaboration there. And can you remind us on the AbbVie side, at what point is the handoff happening after your Phase 1/2, but how much are you going to have to hand over just expansion data or dose escalation data efficient? Thank you very much.
Yes, well, I'll answer AbbVie the second. So on the case of the trials, obviously, these are Phase 1/2a or Phase 1/2 trial. So having data from those trials, it's important to us. Before we even think about whether we want to work with other companies, I think we feel good about the targets and the programs and we want to see that we have the capital to see that data. So there's no real reason for us to enter into anything specifically around the programs until we generate those datasets.
In the case of the AbbVie collaboration, that was an option deal or is an option deal that was started when the program was built preclinical. And the goal there was to have a potential late stage development commercial partner for us. And so we're generating, hopefully Phase 2 data that would allow them to make a decision of whether or not to license the asset for the $200 million plus milestones and royalties, so the option agreement really gives us an opportunity to work with them at the appropriate time. So that's the way that dealer doctors, hopefully that answers your question.
Thank you.
Thank you. Our next question comes from Colleen Kusy with Baird. You may proceed with your question.
Hi, good afternoon. Thanks for taking our question. So on HPN536 and the last update was largely focused on ovarian, will the next update later this year include additional tumor types? Or would we expect that to be likely focused on ovarian as well?
Yes, no, the medical conference update will be a comprehensive look at the trial, including all of the patients that have been enrolled from the three tumor sites that we mentioned. In December, we just thought it was interesting to highlight a couple of patients in the ovarian part of this study that showed possibly some evidence of early anti tumor effect that albeit at lower doses than what we're pursuing right now.
But the goal at the medical conference in the second half of the year would be to have a broad comprehensive look at the trial in the same way that we're going to be presenting a data, broad data set for the 424 trial, hopefully at ASCO, okay.
Great. Thank you. And then just a quick follow up. So for HPN601, I'm still in early stages, but any lead indications that look the most interesting to you at this stage?
Well, we we've mentioned, the gastrointestinal tumors are particularly interesting. EpCAM is broadly expressed on many tumors, but from a portfolio point of view, we don't have a product focused in that area. And that would, I think, complement the rest of the portfolio to have some tumor types that are not represented by our other programs.
Great, thank you. Thank you.
Thank you. Our next question comes from Robert Driscoll with Wedbush Securities. You may proceed with your question.
Thanks. Good afternoon, guys. Just one quick question for me. I'm just thinking about the various dose regimens being evaluated for HPN424. Could you see some flexibility being built into any kind of selected regimen for the expansion cohort? And maybe got going forward how you might think about continuing to refine that dose? Thanks.
Yes, no, it's a very good question. Because this is something that is quite dynamic, and we are pursuing many ways to advance dose escalation. Natalie comments around that?
Yes, I agree. And if what you mean is, is can we on one hand, explore a particular dose and expansion to get a little better characterization of its activity and safety profile? And also escalate at the same time, it is similar or in different patients? Yes, we have the flexibility to do that.
Got it. Thanks, guys.
Thank you. Our next question comes from Sean [Indiscernible] with H.C. Wainwright. You may proceed with your question?
Hi, thank you for taking my question. Actually, so my question had been already answered. But just a quick one, with multiple expansion cohort initiating in second half 2021, what would be the impact on the R&D expenses on second half 2021 and maybe 2022?
Yes, well, let me just clarify. So the current protocols that we have are Phase 1/2a or Phase 1/2 trials. So the expansions as we've described them have already been, we can model those expenses appropriately. Obviously, these are not, we're not talking about new protocols. New protocols, of course, would be incremental. But maybe I'll turn it over to Georgia to ask answer that question. Yep.
So the guidance that we gave does include everything that we've been talking about today in terms of expansion cohorts and political plans for 2021 and we have not given guidance for 2022 as of this time.
Okay, sounds good. Thank you.
Okay, well thanks….go ahead.
I’m not showing any further questions at this time. I now like to turn the call back over to Gerry McMahon for any further remarks.
Yes, just briefly thank you all once again for joining the call today. If you have any additional questions, please feel free to contact. Yes, have a good evening everybody.
Thank you. Ladies and gentlemen, this concludes today’s conference call. Thank you for participating. You may now disconnect.