Q4 2020 Harpoon Therapeutics Inc Earnings Call
Ladies and gentlemen, please standby your harpoon therapeutics for Q2 thousand 20 of financial results and corporate update conference call will begin momentarily. Thank you for your patience and please standby.
[music].
Ladies and gentlemen, thank you for standing by and welcome to the Harpoon Therapeutics for Q2 thousand 20 financial results and corporate update conference call. At this time all participants are in a listen only mode. Please be advised the today's conference maybe recorded if you require any further assistance. Please press star zero on the call today from Harpoon are Jerry Mcmahon.
President and Chief Executive Officer, GA of beds, Chief Financial Officer, Natalie sacks, our Chief Medical Officer and hold your best friend, our Chief Scientific Officer. Following management's prepared remarks, we will be conducting a Q&A session basket of question during the session you'll need to press star one on your telephone I will now turn the call over to.
New Jersey, Georgia other bets.
Thank you operator, good afternoon, and welcome to Harpoon Therapeutics webcast and conference call for a discussion of the company's fourth quarter and full year 2020 financial results and of corporate update before I turn the call over to Doctor Mcmahon I would like to remind you that today's call will include forward looking statements. These forward looking.
Statements are based on harpoons expectations and assumptions as of the date of this call.
Each of these forward looking statements involve risks and uncertainties that could cause harpoons clinical development programs future results or performance to differ significantly from those expressed or implied by the forward looking statements.
Please refer to harpoons 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 available on harpoons website for information concerning factors that could cause harpoons 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 expectations, even as new information becomes available.
I will now turn the call over to Dr. Jerry Mcmahon, President and CEO of Harpoon Therapeutics.
Thank you, Georgia and thank you all for joining us on this call. This afternoon I'm very pleased with harpoons achievement of significant clinical scientific and operational milestones during the past year.
At the time of our IPO in February of 2019, our goal was to have for programs in clinical development by the end of 2020.
Harpoon achieve that goal, including starting two new clinical trials in 2020.
We maintain 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 H P. M for two for which is continuing in the dose escalation portion of the phase one to a clinical trial in patients with metastatic castration resistant prostate cancer.
We also advanced our other three tried check clinical programs, including H P. M 536 for the potential treatment of mesothelioma expressing tumors with a focus on ovarian and now including pancreatic and mesothelioma cancers.
Our third product candidate H P. M to one seven entered the clinic in April of last year with initiation of our phase one two clinical trial for multiple myeloma.
And finally in the second half of 2020, we submitted an <unk> initiated a phase one two trial for our fourth program H P. M. Three to a targeting DLL three for small cell lung cancer and other DLL three expressing tumors.
We also made significant progress with our proprietary pro tried check T cell engage your prodrug platform designed to remain in nerd systemically until its activation in the tumor.
We believe this platform can enable the safe targeting of more broadly expressed tumor antigens H.
The H P. M 601 has been nominated as a clinical candidate and becomes our first conditionally active T cell engage your program.
It targets the tumor antigen epithelium of cell adhesion molecule or F. Cam, 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.
It gives us a pro forma cash balance of approximately $258 million.
These resources are being deployed to further support the 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 Tri Tech technology and after that I will update you on our clinical development programs.
Harpoons Tri Tech technology platform is a novel and proprietary approach to engage T cells. The most potent killer cells of the immune system.
T cell engages our 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 can.
It is focused on oncology indications, but other uses would also be possible.
We believe our tried text out of a number of features that could be advantageous when compared to other immunologic approaches to the treatment of cancer.
First our Tri tax are modular by design and are about 75 per cent similar to one. Another the consists of three primary components that perform three different functions T cell binding.
Half life extension and tumor cell binding to.
To address half life extension, we utilize the domain that binds transiently to human serum albumin.
We utilize single domain antibodies for target binding in human serum albumin binding, which makes our molecule smaller and more flexible than would be possible with larger antibody derived fragments.
Furthermore of these domains are inherently very stable contributing to our platform. The potentially has very little off target activity and is therefore expected to have a therapeutic window of ideal for applications in solid tumors.
Second our Tri Tech molecules are relatively small globular proteins that can be administered to patients by intravenous delivery and a one hour infusion every week or two weeks. The Tri Tech protein is about one third the size of a typical antibody and we believe the smaller size and globular shape of tried tax allows them to defer.
It was more freely into tumor tissue compared to antibodies.
And finally, our tri tax can be manufactured and chose cells in your standard methods of conventional antibody based manufacturing techniques. This completely avoids the cost and complexity of personalized our cell based therapies such as car T.
Utilizing all of these unique features are tried checks 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 engages and Brent successes seen in liquid tumors to solid tumors.
Now, let me review, where we are with our for clinical development programs.
Our lead Tri Tech product candidate H being for two for targets prostate specific membrane antigen or P. SMA for the treatment of metastatic castration resistant prostate cancer and continues in dose escalation of our phase one two a clinical trial.
At our December 2020 data update we reported debt for the highest fixed dose tested 160 nanogram per kilogram seven patients had been enrolled and one patient had achieved a confirmed partial response based on resist version one one criteria.
Three patients enrolled in this cohort had serum PSA reductions, including one with a reduction of 50% or PSA 50.
For this difficult to treat patient population. We are encouraged by these early results, we are continuing to enroll patients and to advance the dose escalation.
We are also able to employ step dosing in this trial, where patients are receiving of dose of 300 nanogram per kilogram. This allows for a faster advancement to much higher doses than a traditional fixed dose escalation of 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 <unk>.
As a reference point to keep in mind P. SMA is present in 85% to 90% of patients with advanced metastatic prostate cancer.
Market research shows the prostate cancer is the third leading cause of cancer death in the United States. There are approximately 174000, new cases, and 31000 prostate cancer deaths in the United States each year.
Our second tried check product candidate to enter the clinic H P and 536 targets Mesothelin.
Initially we began studying H P. N 536 in platinum refractory ovarian cancer and expanded enrollment to include metastatic pancreatic cancer patients and mesothelioma patients in this trial.
The feeling 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 H B and 536 is the first mesothelin targeted T cell engagement to enter clinical development.
Patients receiving weekly infusions of H, B and 536 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 in one step dose cohort up to six.
<unk> hundred nanogram per kill kilogram since the update we have advanced to a 1200 nanogram per kilogram step dosing cohort the.
The experience we have gained from HP and for two for has been beneficial owner of conduct of the phase III six trial, we expect to provide interim data from the ongoing dose escalation portion of the trial by and by the year end 2021, possibly at ESMO or at city as well as initiation of a dose expansion cohort.
In the second half of 2020 one.
Our third Tri Tech product candidate H P. M to one seven targets b cell maturation antigen or be CMA.
We initiated a phase one two 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 of collaboration option agreement with Abbvie and dosing of the first patient triggered a milestone payment of $50 million, which we received in June 2020, Inc.
January of 'twenty 'twenty, one H b into one seven received orphan drug designation from the FDA.
And of our December of clinical update we indicated we had treated six single patient fixed dose cohorts of five to 100, 810 micrograms, reflecting a more than 100 fold increase in dose within the first eight months of the trial are 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.
H P M. Three two Adas, our fourth tried check product candidate in the targets Delta like ligand three or DLL three a protein highly expressed in the majority of the small cell lung cancers and other DLL three expressing tumors.
We submitted an IND for H share in three to eight in the third quarter of 2020 and initiated the phase one two clinical trial in December which include 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 2020 one.
Despite the challenges of this past year. It was a period of impressive pipeline advancement for harpoon with for 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 off the shelf platform for T cell engages that reprogram of patients' own immune.
Sales to treat a wide variety of malignancies are 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 Jerry 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 a more detailed discussion.
Revenue for the fourth quarter ended December 31, 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 months period and full year periods. The increase in revenue was primarily due to the revenue recognized from the development of an option agreement with Abbvie signed in November of 2019.
I want to remind everyone that revenue recognition is a noncash 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 for initiation of clinical trials for <unk> HPN 40 for H P and 536, H P N two and seven and H P. N 328.
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 for <unk> 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 was primarily attributable to lower legal expenses, partially offset by an increase in personnel expenses related to a higher head count and professional services to support our ongoing 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 31st two of 2019.
Net loss for the year ended December 31, 2020 was $49 9 million compared.
Compared to $55 6 million for the prior year.
Our Pune Therapeutics ended 2020 with $150 million in cash and cash equivalents compared to $155 $1 million as of December 31, 2019 net.
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 three point million dollars and 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 that we'd 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 11th 2021, resulting in a net cash proceeds of approximately $108 $1 million.
On a pro forma basis for the offering we completed in January of 2021, harpoons cash balance was $258 million.
For 2021, we are estimating cash used in 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 Tri Tech and pro tried tech platforms with four of our product candidates H P. M for two for five three.
Six to one seven and three to eight all in clinical development. We achieved the goal. We stated 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 for 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 the interim data updates for each of our for clinical programs for.
For for two for the dose escalation part of the Phase <unk> clinical trial is ongoing we're planning to present interim data and initiated 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 <unk> 536, the phase <unk> clinical trial is continuing to enroll patients in the dose escalation part of the trial. We are planning to present interim data from this trial by the <unk>.
We ended the year 2021, and initiated a dose expansion cohort in the second half of 2021.
For <unk>, two and seven we expect the present interim data from the dose escalation part of the phase one two trial in 'twenty 'twenty, one and initiate the expansion cohort in the second half of 2021.
For H P M. Three to wait we're planning to present interim data from the dose escalation part of our phase one two clinical trial in the second half of 2021.
So with that operator, we're now ready for questions.
Thank you as a reminder, task of your question you'll need the press star one on the telephone.
As for your question press the pound key please standby on for Paul.
Q&A roster.
Our first question comes from Jonathan Chang with the SPV Leerink you May proceed with your question.
Hi, guys. Thanks for taking my questions.
First question on H P. N for two for can you confirm whether or not an abstract has been submitted to ask how can you help set investor expectations out of the interim data.
Yeah, what I can say, Oh, hi, Jonathan.
Is that we have submitted an abstract for ESCO. Obviously, our hope is that this would be accepted and we could present some data from the ongoing trial there.
The data set will be comparable to what we presented at Ash go.
In June of last year, which is a very broad and comprehensive look at all of the the features of the clinical trial, let me turn it over to Natalie to give us a little bit more detail on that.
Sure. Thanks for the question Jonathan This is Natalie.
So again, we'd like to get as comprehensive as possible.
Date on the escalation portion of the trial remember the objectives of the first part of the trial are too.
Characterize safety activity pharmacokinetics.
Markers of T cell engagement markers of target engagement, such as C. T C. So of rich pharmacokinetics and primarily.
Pharmacodynamic dataset.
So all of the objectives of.
Of the trial I mentioned, we want to summarize the data and learnings to date.
Got it.
Second question, how should investors be thinking about the potential implications on HP unfortunate for the Novartis of vision study readout also expected in the first half of the year.
So jonathan's Gerry so obviously, we're paying close attention to that trial, it's an interesting trial.
With a small molecule P. S M a targeted agent of radio conjugate.
And it is conducting a in a late stage cancer population of prostate cancer population.
With the progression and survival as a potential endpoints for the trial so.
Where you 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 for two four 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 and how much to read through into the data, but we're still interested in those.
Those particular endpoints for the trial.
Understood.
And just last question here with.
With the Takeda acquisition of Maverick can you refresh our memories on the latest the Mellon and legal status for pro try attack and discuss what if any.
The impact of the acquisition has on your <unk> strategy. Thank you.
Well I will I will defer the question related to approach of our tech to the holder, but as it relates to the litigation matter with.
That's ongoing around this.
We can't comment on that and we will not be able to comment the comment on that today.
But maybe holder of we can talk a little bit about our.
Our platform and where we're focused.
Yeah.
So.
All of petrol and as you know the Fortunately Tech platform aims at bringing the right took advantage of increased stability and presumably the fewer side effects to more tumor targets, let's take the targets, enabling us to dose of inactive for trucks for the prodrug of then gets activated in the patient's tumor hence increasing the therapeutic index.
Allow us to go off the targets and indications you're unable to go after before.
One of them.
Any concrete question for me regarding the platform.
I guess I was curious to know if there were any.
Occasions from that acquisition on your strategy for development of the platform.
Yeah.
Is this a developing story as of today I'm not aware of any such impacts, 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.
Sure.
Thank you. Our next question comes from Tara Bancroft with Piper Sandler You May proceed with your question.
Hi, guys. Thanks for taking the questions I.
I guess I'll I'll stay on that topic I'm kind of curious if you consider other prodrug technologies like those mechanics or out of the next.
How would you compare the debt your.
Pro Tri Tech platform and are you developing additional aspects of this platform the address other masking technologies for instance.
Joe.
Well, let me start to just say that.
Obviously, there are many companies now pursuing ways to bring T cell engaging <unk> 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 of logical extension of the advantages we saw and tried Tac.
So.
I'm going to turn it over to hold of now to give you more detail about that.
Thanks Terry.
The question I mean, you talked kind of the horribly surprised to hear that you of course think of up for some of the superior to the competitors after looking at.
That's the landscape you think there's reason for the just to point out a few of things. Although modality is in lot of fee based will be toward flights of carries on the tried take advantage of not having the right, but it looks like it's G receptor binding at Sullivan's.
Most of the work competitor does for us.
What I personally think of two outstanding attributes of all of our platform. It's the after the close of the past one of them is that Oh platform. A couple of half life, two activation and that means when the drug gets accessed it loses its half life, which is the addition of safety switch meaning.
We can be a little bit more demand in terms of when and where our drug is getting close.
You'd call them accumulate after activation.
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 them, but due to the competition basically how many of you maintained the try to take advantage of the avoid the of fee based related issues.
We have some especially true in Melbourne.
The couple of them half half left much of those.
And our expectation eating potentially lead to an increased therapeutic index.
That was the first part of your question I think that was the second part of the recalling correctly.
Yeah, I guess, maybe just a little debt.
More information on the you know if you are developing any other kind of masking technology right.
Alright. Thank you. So yes, I would say innovation that helpful. Never stops the are constantly working on all of our platforms and yes, you have other aspects looking at evaluating however, do you have some other types of disclose but instead of the true.
For the S.
Other approaches reach maturity, while at the year of people continue updating you.
Thanks, so much.
Sure.
Thank you. Our next question comes from Yigal <unk> with Citigroup you May proceed with your question.
Alright, great. Thanks for taking the questions I just had one on the H P. M 328 is the <unk>.
The screen for expression of DLL, three and small cell lung cancer for <unk>.
And the expectation that the expression of the target is high in the tumor so you won't need to screen and additionally, what other tumor types would you go after that have high D O L. Three expression.
Yes I'll.
I'll start the the of.
The answer is Jeremy and I will turn it over to Natalie So.
We don't believe we need to select for patients for DLL three the prevalence.
And expression of this target is actually quite.
The unique and quite profound in many ways.
It does track to the neuroendocrine features of small cell lung cancer compared to typical add known squamous cell carcinomas of of the lung.
So its price pretty unique in that regard.
And.
And you know from that viewpoint, we also know that the data that emerged from <unk>.
M. Gen last year related to targeting DLL three.
For the T cell engagements was quite Inc.
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 NAV.
Natalie a question related to other of tumor types.
Sure So where we're doing both in response to your two part question of as Jerry mentioned for small cell lung cancer. We are we do not regard piece of selection has required a hallmark of the Tri Tac.
Form is that cell, killing can be achieved with extremely low target antigen density. So in fact for all four ongoing 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 debt.
And with the level of expression, which was too low however.
However for the other tumor types, which don't necessarily have a reasonable chance of D. L. L. Three expression, we are relying on pathology.
And we will accept any tumor type we've evidence in pathology.
That's suggestive of D. L. L. Three expression. So theres a number of pathologic features but you meet that criteria. So the short answer is any tumor type with some evidence of pathologically of DLL three expression, we're particularly interested in prostate cancer or the so called Neuro index.
Phenotype of prostate cancer, which is increasingly incidents I think in part because of the selective pressure of the novel androgen targeting medicines and there's Uh huh.
Strong interest in the field right now to find them.
Medicines that are our our effective for those patients.
We're barely few options exist so prostate.
With neuroendocrine features is important and will be enrolling nose and then in addition, any other patient tumor types.
With characteristics of DLL three expression.
Thank you.
Just one housekeeping question regarding the dose expansion plans for 536% to one seven have you determined what dose you will be expanding at for most of two studies.
The answer that initially so.
They're all ongoing Escalations and of course, we don't have any.
Precision to the doses that will drive the expansions.
For 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 the maximum tolerated dose then of course, you have of limit but at this point.
We have not achieved an MPD on our two lead programs and we continue to explore doses to see which doses.
The warrant expense.
Moving forward in the case of 536 that expansion will probably be of tumor specific expansion again. This is a trial that is enrolling three tumor types. So the <unk>.
Spansion, we'll 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.
The question sure.
Nothing else the App.
Thank you Jerry think of an island.
Thank you. Our next question comes from Ash, the Gagliano what day.
True of Securities You May proceed with your question.
Hi, guys good to speak to you all and thanks for taking my questions.
Hi, Jared if you've already answered the one I just had about M. T. D. So let's really focus on for two for what comes after the 300 milligram dose are you going to go into 600 or given that you have some data in hand with 536 would you feel comfortable of jumping to the 1200.
Nanogram step dose and I got the follow up after that.
Yeah, you know the.
The and now they can get into more of the nuance here the the.
The determination of any dose whether it's the step dose.
Or a fixed dose.
Is determined based on an analysis of course of.
Of.
Various factors and.
Although we have increased the dose.
Three three fold in many cases and 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 of 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.
Understand the question I, just wanted to clarify that the doses of cross the trials don't the heat in the same way although.
These are all tried tax.
They don't have the exact same potency for various reasons. So 600 million of HIMSS of Guam is not the same of 600 milligrams of say the other so learnings from one dose on one trial don't necessarily influence the absolute dosing of another trial, if thats what youre asking.
So.
We mentioned.
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 and HP, Inc. For two for an up to 1200, an H P. N 536.
And we don't have further updates today about dosing, but of course, we'll be sharing more data throughout the year.
Okay, great chances that the my second my next question I had thanks, a lot guys I appreciate it.
Okay.
Yes.
Thank you. Our next question comes from Jack the Jar with Roth Capital Partners. You May proceed with your question.
Hi, guys just a couple of different questions for you I think the first is I really like the pool of data that we're going to see the sea air, particularly plenty of first your program. So just kind of wanted to get a sense of how concrete the dot is going to be because I think that early data. We're just kind of looking at safety the use of exit that day.
And things like that and so you know are you only going to have data that we can drive comparisons fine.
And then the second one is just you know you'll be doing does the expansion. This year at what point of you're going to start considering probably you know some combo of like Io combos, and then third is that as you know delek.
I'm glad you are in the clinic with that and you know are we likely to see you're expanding into other tumor types like the that's what the Mesothelin program and then the last one yeah. I think this one is public from the home they're at or actually Gary can answer. This one as well just wondering you know as you continue to expand your pipeline beyond the you know these program.
That we have are you gonna do you spoke of one of the <unk> or are you gonna yeah more with you try tack and I'm. Just wondering you know that's the protect tackling some of efficacy on the table and it gets more costly if you don't need of 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 the whole grow and start with your last question first because I'm not sure of it completely remember the first two questions at this point, but the.
The last question <unk> was invented for those targets in which if you were to have a tri tech debt was.
Completely.
Active from the moment of infusion it might.
Limit the utility of the drug because of.
Two T cell activation against normal tissues and so the.
The Inc.
Intent of our first development program H P. M 601 is to explore a target that is has broad potential utility of.
And for which previously there's been shown some evidence of a tissue toxicity. So.
That is really the goal of our first program.
But the holder can address that as well as future products that we're focusing on in the company.
Currently.
Thanks Terry.
Jerry pointed out for them.
On the one level.
The off certain targets.
Let me take a step back the developed approach high tech to be able to go after targets. The comp grew after the streit Tex for safety reasons as Jerry pointed out in the S. One answer to your question use Proto Mitek for things of the comps you would strike tech like targeting outcome now.
Now the.
And then implied in my answer is that the target that you can use tried taken through Christmas Avi when the switch from try to protracted for the woods targets.
And everything else being equal of my answer would be likely know because in principle. The and you can keep things simple the will keep things simple so for trying to ease more complicated than for mitek.
For my very scientific point of view is an added liabilities just due to complexity the can avoid but I will.
But as you know these compounds in the clinic force Playtech spinoffs plastics and the clinics to what types of hopefully going to be in the clinic soon.
Or at some point in the future and if you get the startup you're going to adjust our position there but as of today.
I looked at the optimal for different kinds of targets in terms of different indications for the I see the next to each other but again this is going to be driven by data.
For the next few years.
Okay.
Your question on DLL three I think that was your third question what was that one again.
Yeah as you say it is very interest in targeting I was just wondering if you can expand to other tumor types like you've kind of done with you Miss the feeling program in terms of expanding to other tumors.
Yes.
Nathalie just gave an answer to that and we.
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 for sure and hi.
But so the.
The the comparison to five to six it's a slightly different strategy. So it's a good question. So 536, H B N price with six of the Mesothelin targeting tried Tac.
<unk>.
<unk> decided to enroll patients that we believe have tumors that are known to express mesothelin and we'd limited batch of ovarian cancer patients.
Pancreatic cancer patients and mesothelioma patients. So all three of those mesothelioma in particular are well characterized as tumor types that <unk>.
Express Mesothelin.
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 D. L. L. Three like you said, where you have one tumor type that expresses the all doing quite well small cell.
But we're also including in the escalation other tumors that show that they have D. L. L. Three expression.
Right. So that that's a cash that could be anything it could be some number of peanuts or neuroendocrine tumors of prostate cancer.
So there they are coming in and not by the type of cancer, they have but that they're showing that they have DLL three expression. So it's a bit of of different tactic, but both of them take different tumor types.
Then per deal all three H B and <unk> based on what we learn we can we can start different expansion cohorts you can do a basket again tumor agnostic just making sure you have DLL three expression you can do small cell because you know the express.
Deal all three without checking so I hope that addresses your question. They both they both the capture different tumors, but kind of in a different way if that makes sense, one is by indication and monies by pardon the expression.
Okay.
Okay.
And then said well you had a question around comp you had 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 in late stage disease and those are under active consideration as we think about different expansion cohorts for the program Natalie any comments around that.
The real brief just building on what you said you know for oncology at the paradigm of of combination regimens, obviously to sort of maximize efficacy against hard to treat diseases.
And.
There's two approaches or at least I think I have the simple way in my mind to keep it simple either there's a mechanistic or scientific rationale for a combination.
Or there is.
Our standard of care combination that makes sense or you need to understand how your drug the works with the existing standard of care.
So that.
That those two buckets provide a lot of options for us obviously, we can consider I O combinations.
There was the rationale for a combination with PD PD Lone inhibition, you know of T cell therapies. There is rationale in some tumor types to.
The combined with standard of care, such as PARP inhibitors, which apply to a number of different tumor types with chemotherapy.
It's actually a reasonable thing to do with.
Hormone blockade in prostate cancer. So the answer of sort of yes, yes, and yes, we're thinking carefully about a rational combination strategies for each program based on the tumor type.
And our protocols and approach allow us to pursue that in expansion of.
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.
Giving some thought to what combinations make sense.
Perfect very helpful. Thanks for all of the updates and looking forward to the data readouts.
Okay. Thanks.
Alright. Thank.
Thank you. Our next question comes from Arlinda Lee with Canaccord you May proceed with your question.
Or Linda can you harriss.
Hi, guys.
Thanks for taking my question and.
Congratulate and we're looking for to all of the data that's coming out this year.
Okay.
Maybe a broader question.
About your appetite for additional collaborations and are you planning on taking all of these forward yourselves.
I mean, except for 207, I guess, which has the.
The collaboration there.
And can you remind us on the at the side at what point.
Okay.
It's the handoff happening after the phase one two day how much.
Are you going to have to handover just expansion data or dose escalation data sufficient.
Thank you very much.
Yeah, well I'll answer of the the second so in the case of the trials. Obviously these are phase <unk> or phase one two trials so.
Having data from those trials, it's important to us.
Before we even think about whether we want to do.
Work with other companies I think we feel good about the targets and the programs and we want to see that and we have the capital to see that data. So theres 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.
<unk> started when the program was still preclinical.
And the goal there was to have a potential.
Late stage development and commercial partner for us.
And so we're generating.
Hopefully phase two data that would allow them to make a decision of whether or not the license the asset.
For the $200 million plus milestones and royalties so the option agreement.
Sure.
Really gives us an opportunity to work with them at the appropriate time.
So that's the way that deal is structured hopefully that answers your question.
Thank you.
Okay.
Okay.
Thank you. Our next question comes from calling Gucci with Baird. You May proceed with your question.
Hi, good afternoon, thanks for taking our question.
On the H P. N of 536, I know the the lots of things largely self instead of Varian will the next update later. This year include additional tumor types of would we expect that to the likely focus on ovarian as well.
Yes, no the the the medical conference update will be a comprehensive look at the trial.
Including all of the patients had been enrolled from the three tumor types 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, it, albeit lower doses than what we're pursuing right now, but the goal at the <unk>.
The medical conference in the second half of the year would be to have a broad comprehensive look of the trial in the same way that we're going to be presenting a data of broad dataset for the for two four trial hopefully at Astro.
Okay, great. Thank you and then just two quick follow ups of for H P of <unk> 601, obviously still in early stages, but any lead indications that look the most interesting to you at the stage.
Well, we've mentioned the gastrointestinal tumors are particularly interesting <unk> is broadly expressed on many tumors, but.
From a portfolio of point of view, we don't have of 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.
Yes.
Yeah.
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 H been courting for could you see some flexibility of being built into any kind of selected regimen for the expansion cohort.
And maybe going forward, how you might think about continuing to refine that dose. Thanks.
Yes, the answer very good question.
Because this is something that is quite dynamic.
And we are for.
The suing many ways too.
Vance the dose escalation Natalie comments around that.
Yeah I agree.
What you mean.
Is is can we on one hand explore a particular dose and the expansion to get a little better characterization of its activity and safety profile and also escalate.
At the same time, it is similar or different patients, yes, we have the flexibility to do that.
Got it thanks guys.
Thank you. Our next question comes from Sean Kang with H C. Wainwright you May proceed with your question.
Alright. Thank you for taking my question actually I'm. So all of my question have been already answered, but just a quick one with multiple expansion of COVID-19 initiating in second half of 'twenty, one would it be the impact on the R&D expenses.
For second half of 'twenty, one and maybe 'twenty two.
Yeah, well, let me just clarify so the current protocols that we have our phase one two of our phase one two trials. So the expansions as we've described them have already.
Ben.
You know.
We can model of those those expenses appropriately. Obviously these are not we're not talking about new protocols, new new protocols of course would be incremental but maybe I'll turn it over to Georgia to the S answer that question, yes. So the guidance that we gave does include everything that we've been talking about today in terms of the expansion cohort.
Parts and the clinical plans for 2021, and we have not given guidance for 2022 is at this time.
Okay sounds good thank you.
Yeah.
Okay well thanks.
Oh go ahead.
I'm not showing any further questions at this time I would now like to turn the call back over to Jerry 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 us have a good evening everybody.
Thank you ladies and gentlemen. This concludes today's conference call. Thank you for part of the spending you may now disconnect.
Yeah.
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Okay.
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Yeah.