CytomX Therapeutics Inc (CTMX) 2020 Q1 法說會逐字稿

Good day, ladies and gentlemen, and welcome to the CytomX Therapeutics First Quarter 2020 Financial Conference Call. (Operator Instructions)

As reminder, this call may be recorded. I would now like to introduce your host for today's conference, Christopher Keenan, Vice President of Investor Relations. Chris, you may begin.

Good afternoon, and thank you for joining us. Earlier today, we issued a press release that includes a summary of our recent progress and our first quarter 2020 financial results. This press release and a recording of this call can be found under the Investors and News section of our website at cytomx.com.

With me today are CytomX President, Chief Executive Officer and Chairman, Dr. Sean McCarthy; and CytomX's newly appointed Chief Financial Officer, Carlos Campoy.

During today's call, we will be making forward-looking statements. Because forward-looking statements relate to the future, they are subject to inherent uncertainties and risks that are difficult to predict and many of which are outside of our control. Important risks and uncertainties are set forth in our most recent public filings with the SEC at sec.gov, including our Form 10-Q filed today. We undertake no obligation to update any forward-looking statements, whether as a result of new information, future developments or otherwise.

I will now turn the call over to Sean.

Great. Thanks, Chris, and good afternoon, everybody. Thanks for your patience as we were getting the call up and running. I gather there's quite a lot of call volume at the moment.

Anyhow, once again, good afternoon, and thanks for joining us. It's a pleasure to be here to provide an update on our progress during the first quarter of 2020. I'll begin today's call with a brief overview of our business operations against the backdrop of COVID-19. And then, we'll review first quarter highlights across the pipeline. I'll then turn the call over to Carlos, our new CFO, you just heard off from Chris, and Carlos will review our first quarter and financial results, and I'll wrap up. And then open the call up for questions.

Let me start by saying that all of us at CytomX hope that you and your families are well and keeping safe during the ongoing pandemic. The situation is impacting all of us in different ways, and it looks like it will continue to do so for some time. We are committed to ensuring the continued well-being of those involved with the conduct of our business. This includes the patients, the staff, physicians engaged in our clinical trials, the vendors and partners who support these trials and, of course, our dedicated employees who continue to impress with their drive and focus during these challenging times.

Despite the operational challenges presented by COVID-19, our team remains highly focused and very mindful that as the American Cancer Society has recently reminded us all, cancer is not waiting, and so neither are we.

At CytomX, we see a major opportunity to more effectively target therapeutic antibodies into disease tissues, generating new classes of anti-cancer therapies. We believe our unique Probody therapeutic platform represents a fundamental advance in the field of antibody engineering, and we are highly focused on using our platform to discover and develop a broad clinical pipeline of novel drug candidates to make a meaningful difference in the treatment of cancer. Our unique science offers the potential for new and highly effective anticancer therapies, including first-in-class molecules against novel undruggable targets, potentially best-in-class molecules against validated targets and new combination therapies.

Probody is our fully recombinant antibody prodrugs comprised of a therapeutic antibody and a mask designed to block the binding of the antibody to its target until the mask is removed. Mask removal is achieved specifically and selectively within cancer tissue by certain disease associated proteins called proteases that we know are present and active in most cancers. Proteases are in effect molecular scissors, which in the context of tumor progression, function to cut a path for invading and metastasizing cancer cells. Our Probody strategy is to leverage tumor proteases to localize antibody activity into cancer tissue, thereby decreasing target engagement in normal tissues and broadening or even creating a therapeutic window.

We have pioneered this new approach, that we believe has the potential to improve and optimize a range of antibody formats, including cancer immunotherapies, antibody drug conjugates and T-cell engaging bispecific antibodies.

Despite the emergence of COVID-19, we had a very productive and important first quarter towards the ongoing advancement of our strategy of developing innovative cancer therapies in areas of significant unmet medical need and with a particular emphasis on undruggable targets.

I'd like to start today's update with CX-2009, our wholly-owned Probody drug conjugate that targets the previously undruggable target CD166. CD166 is a tumor antigen that's expressed a high levels on most solid tumors, but it's also present on most normal tissues, ruling it out as a target for a conventional antibody drug conjugate. Our previously presented data from Phase I dose escalation in various solid cancers has shown CX-2009 to be well tolerated and clinically active as monotherapy at doses of 4 mgs per kg and above. This dose is the threshold of which drug conjugates comprising the DM4 payload, the warhead on CX-2009 have been shown by others to be active in the clinic.

Clinical activity was observed in breast, head and neck and ovarian cancers with CX-2009, and we will be presenting updated data from Phase I dose escalation for this agent at ASCO in a couple of weeks.

In the fourth quarter of 2019, we announced the initiation of a Phase II expansion study of CX-2009 monotherapy in patients with hormone receptor positive HER2-negative breast cancer at a dose of 7 mgs per kg administered every 3 weeks, with the objective of enrolling up to 40 patients. Enrollment was initiated and patients were treated during Q1, but regressively, the COVID-19 situation led us to temporarily pause new patient enrollment and new site activation in this study. Our team continues to closely monitor emerging health authority guidance at IRB/Ethics Committee recommendations and our goal is to resume the CX-2009 clinical program as soon as practical.

Now staying with the theme of undruggable targets, I'd now like to turn to CX-2029,a CD71 targeting Probody drug conjugate that we're developing in partnership with AbbVie, and for which, in Q1, we announced the achievement of a major collaboration milestone.

Long considered a high potential but undruggable antibody drug conjugate target, CD71 is known as a professional internalizer, given its role of moving iron from the extracellular space into intracellular compartments. And it does this in all dividing cells. In fact, many consider CD71 to be the gold standard internalizer to assess the in vitro activity of antibody drug conjugates.

But the presence of CD71 on normal cells has been an impediment to its use as a drug target. CX-2029 is a Probody against CD71, conjugated to the cytotoxic payload MMAE. We recently announced the achievement of prespecified dose escalation success criteria for the CX-2029 Phase I dose escalation study, resulting in a $40 million milestone payment from AbbVie to CytomX. Data from this Phase I study will be the subject of an oral presentation at ASCO 2020.

The CytomX and AbbVie teams are now actually finalizing plans for the initiation of Phase II expansions as soon as possible. CytomX has the responsibility for advancing this program through initial proof of concept, whereupon, if successful, the program will transition to AbbVie for registrational studies and ultimate commercialization. CytomX retained significant U.S. commercial rights to this asset and is also eligible to receive double-digit ex U.S. royalties, should the product reach the market.

I'd now like to move to another unique R&D strategy that we're pursuing at CytomX, which is to use our Probody technology to generate first-in-class agents against undruggable targets in the context of T-cell engaging bispecific antibodies, which I will refer to, going forward as, TCBs. TCBs are highly potent therapeutics, which directs the activity of cytotoxic T-cells to tumors. This approach has the potential to take immunologically cold tumors and make them hot, opening many new avenues for cancer treatment. While clinical advances have been made with this approach in hematologic malignancies, notably with Amgen's CD19 CD3 bispecific Blincyto. Its application in solid tumors has been challenging. The reason for this is that the high potency of TCBs can target normal tissues with low antigen expression, resulting in significant toxicities.

For several years, we've been working at CytomX to research and optimize the Probody or masked versions of TCBs with an initial focus on the EGFR-CD3 target pair. Data published by others has shown that EGFR, whilst the well-validated oncology target is undruggable in the context of a CD3 bispecific, a conventional CD3 bispecific.

After this preclinical findings have shown that Probody TCBs against EGFR could induce tumor regressions and create a therapeutic window for this cancer target. These important findings served as the foundation for our ongoing collaboration with Amgen, which I'll speak about in just a few moments.

Building on our successful research on Probody TCBs, during Q1, we announced a major strategic collaboration in this area with Astellas. Under this new agreement, CytomX and Astellas will collaborate on 4 initial programs focused on the discovery, research, development and commercialization of Probody TCBs targeting undisclosed tumor antigens for the treatment of cancer. CytomX will lead early drug discovery activities with Astellas leading preclinical and clinical development and commercialization activities. Under the terms of the agreement, CytomX received an $80 million upfront payment and is eligible to receive future preclinical, clinical and commercial milestones of over $1. 6 billion, together with tiered royalties on product sales that range from high-single digits into the mid-teens.

For certain targets, CytomX may co-fund a predetermined portion of product development costs and become eligible to receive a prespecified portion of profits in the United States. CytomX may also later elect to co-commercialize products directed towards such targets in the U.S. Research work and the collaboration is underway, and we are thrilled to have Astellas as our newest partner.

Returning now to our Amgen partnership. I'm also delighted to report that we have recently advanced a lead Probody TCB candidate against EGFR that we call CX-904 into IND-enabling studies. This is the first pro TCB from our platform to reach this important landmark. CytomX is responsible for IND filing, which is targeted for late 2021 and for early clinical development. We're very pleased with this excellent scientific progress with our Amgen alliance and with the growing excitement around the potential of the Probody TCB space, as also evidenced by our new partnership with Astellas.

Moving now to our potential best-in-class programs, CX-072, our wholly-owned anti-PD-L1 Probody and BMS-986249, the anti-CTLA-4 Probody partnered with Bristol Myers Squibb.

The CX-072 was the first Probody we advanced into the clinic, and it has provided us with crucial insights and the first clinical proof-of-concept for our platform. We'll be presenting long-term follow-up data from the CX-072 Phase I/II study as an oral presentation at ASCO.

In Q1, as part of our portfolio reprioritization, we announced the termination of the Phase II program combining CX-072 with ipilimumab, the anti-CTLA-4 antibody in patients with relapsed or refractory melanoma. This decision followed a reevaluation of the evolving clinical competitive and commercial landscape in immuno-oncology, taken together with the impact of the COVID-19 pandemic. We continue to evaluate opportunities for the further advancement of the CX-072 program and we plan to initiate combination studies with our second wholly-owned program CX-2009 later this year.

During Q1, we also announced an important pipeline milestone in our foundational oncology collaboration with BMS. The leading edge of this alliance is the anti-CTLA-4 Probody BMS-986249.

CTLA-4, the target of ipilimumab, is the prototypical checkpoint target, and blocking this mechanism has proven highly effective in the treatment of patients with melanoma and other cancer types, both as monotherapy and in combination with PD-pathway inhibitors. While a very important advance, CTLA-4 blockade can cause severe immune-related toxicities, creating a clear opportunity for a Probody version of this agent to improve tolerability, increased duration of treatment and potentially improved activity. BMS and CytomX have previously presented preclinical proof-of-concept for CTLA-4 Probodies at several major research conferences and Phase I clinical data for this Probody will be presented at ASCO.

Based on these Phase I findings, BMS recently initiated a randomized Phase II expansion study comparing the tolerability and activity of BMS-986249, plus nivolumab, to ipi plus nivo in frontline metastatic melanoma. The advancement of the CTLA-4 Probody into this study triggered a milestone payment of $10 million from BMS to CytomX.

This is an important study, that if positive, has the potential to place the ipilimumab Probody on a registrational path.

Moreover, this work is a terrific example of what we set out to do with our platform when it was first conceived of, and we're excited about its potential for cancer patients.

Additional recent progress within our BMS alliance includes the initiation of the dose escalation phase of another clinical study, a Phase I/II study for a second anti-CTLA-4 Probody. We call this BMS-986288. And this is based on a modified version of ipi.

The second clinical Probody program demonstrates BMS' ongoing commitment to our technology platform as a way to potentially unlock additional value in the CTLA-4 mechanism and across other targets.

Before handing over to Carlos, I want to also note that we continue to strengthen our executive leadership at CytomX and with the appointments in Q1 of Carlos, our CFO; and also Dr. Alison Hannah as Chief Medical Officer. Carlos and Alison bring -- each bring over 30 years of leadership experience from across their respective domains, and we are absolutely delighted to welcome them to the team.

I would now like to turn the call over briefly to Carlos.

Thank you, Sean. I'm very pleased to be here. I'd like to review the financial highlights for the first quarter ending March 31, 2020. Revenue for the quarter was $50 million compared to $29 million in the corresponding period in 2019. The increase was primarily due to the partial revenue recognition of the $40 million milestone earned from AbbVie associated with the CX-2029 project and $10 million related to the milestone earned from BMS associated with the initiation of the Phase II randomized cohort expansion of BMS-986249.

Research and development expenses were $43 million for the quarter compared to $36 million in the corresponding period in 2019. The increase was largely attributed to license and sublicense fees associated with milestones and upfront payments earned in the first quarter of 2020.

General and administrative expenses were flat compared to the corresponding period in 2019. We ended the quarter with cash, cash equivalents and investments totaling $247.9 million compared to $296.1 million as of December 31, 2019.

Our achievements in existing and new partnerships during Q1 have resulted in $130 million in milestone and upfront payments to CytomX that are not reflected in our end of Q1 cash balance. I would like to underscore the company's continued strong track record of executing strategic business development transactions to broaden our pipeline and access additional non-dilutive operating capital. We expect our strong balance sheet to allow us to comfortably meet projected operating requirements into the second half of 2022, assuming no new collaborations or financings.

With that, I'll turn the call back to Sean.

Great. Thanks, Carlos.

So to wrap up, CytomX had a very strong first quarter of 2020, with many key achievements across our preclinical and clinical programs in our existing partnerships and in the formation of a major new strategic alliance. We have a strong balance sheet to advance our pipeline and weather market uncertainty. And we're looking forward to ASCO, of which we have multiple presentations that will provide important updates on all of our clinical stage programs. I am very proud of the CytomX team for staying intensely focused in these challenging times, as we drive towards making the biggest difference we can for patients with cancer.

So thanks all for your time today. We wish the very best to you and your families. And Chris, please now open the call up to questions.

Operator, we'll take our first question.

(Operator Instructions)

Our first question comes from Peter Lawson with Barclays.

Our next question comes from Peter (sic) [Chris] Marai with Nomura Instinet

CD166 -- Can you hear me okay?

Yes, sir. You were muted in the beginning. You came on halfway.

Okay. I'm sorry about that. So what I mentioned is the toxicity around the CD166 program versus the CD71. I'm just curious about the payloads being used here. And the internalization profiles of the targets, given that CD71 is very efficient in internalizing, does that impact the type of payload that you chose to use? I noticed that you 2 different payloads for these products.

Also for the CD71 PDC, I'm curious about what would some expected on target toxicities might look like versus toxicities due to the payload in general?

Yes. Thanks for the questions. So first of all, with regards to the payloads, going back several years, when we designed the Probody drug conjugate strategy, we made a very conscious decision that the first 2 Probody drug conjugates to take into the clinic that we would work with, the most established warheads or payloads, if you like. And DM4 was selected for the CD166 program through an alliance with ImmunoGen and MMAE, which at the time was the second most validated payload. We were able to access that through our alliance with AbbVie via their alliance with Seattle Genetics. And so frankly, we could have used -- it could have ended up being the other way around. That's just the way it played out at the time. We considered those 2 payloads to be the most and best validated at that time.

In terms of the toxicities with DM4, we've known for a long time that the principal toxicity with DM4 is ocular tox. That's exactly what we saw at the higher doses in our dose escalation in Phase I, is something that is manageable in the form of ocular prophylaxis. So that's something that we're implementing in the ongoing Phase II study.

With regard to CD71 and MMAE, the principal toxicities with MMAE are a little bit different to DM4. They're more hematologic in nature. And that's what we saw in our preclinical studies and hematologic toxicities that we're looking out for in the clinic.

With regards to CD721 on target toxicity, it's very difficult to say. With CD166, just as an example, the target is expressed on most normal tissues and you could, therefore, infer that you may see toxicity of any kind. In fact, in the clinic, we really didn't see any evidence of on target toxicity with our reported data on CD166. We'll provide the data on CD71 Phase I dose escalation in a couple of weeks at ASCO.

Our next question comes from Terence Flynn with Goldman Sachs.

Maybe just following up on -2029. Based on the animal data, is there any reason to think that the activity would be more robust in lymphoma, let's say, relative to the solid tumor setting? And then can you remind us in the Phase I trial, if you only enrolled patients that had high levels of CD1 expression. Was that a cutoff? Or are you going to look at that prospectively now, when we see the data at ASCO?

Terence, thanks for the questions. I'll take the second question first. Patients were not preselected for high target levels in the study, but that is something we're looking at prospect retrospectively, of course. And with regards to lymphoma, the Phase I dose escalation has allowed us to enroll solid tumors and lymphoma. We'll obviously report the patient population when we present the data. The preclinical work was mostly focused on the solid tumor side of things.

Our next question comes from Robert Burns with H.C. Wainwright.

And congrats on the quarter. Just 2 questions, if I may. So the first 1 is, could you provide some additional color as to the indications you're considering exploring in the Phase II expansion based on the data you've seen for CX-2029.

And my second question is, similar to what you did for CX-2009 with regards to the preclinical assessments of combining it with CX-072. Have you been warned any preclinical assessments evaluating potential synergy for CX-072 plus CX-2029? And if so, are you planning on evaluating that combination in the clinic?

Yes. Robert, thanks. Great questions. Not prepared already to comment on Phase II indications at this stage for -2029. but of course, they will be guided by all -- everything that we know to this point.

With regard to the combination, as you rightly point out, we have -- we previously reported preclinical data at AACR last year, showing the potential for CD166 Probody drug conjugate to synergize with PD-1, PD-L1, and that work underpins our ongoing strategy to move into the combination of -2009 and -072, which is planned for later this year.

With regards to -2029, it's too early to say. But as another drug conjugate, it certainly makes conceptual sense that, that could be combined with a PD agent of 1 kind or another. But we don't have anything more to say about that at this time.

Our next question comes from Peter Lawson with Barclays.

This is [Mitchell] on for Peter. Can you guys hear me now?

Yes.

Yes.

Okay. Sorry, I had to redial. And I don't know what happened. So had a couple of questions for you guys. The first 1 is for your CD71 data at ASCO, what kind of data might we see? How many patients? And how might that change from the abstract to the time of the presentation?

Really not able to comment on that right now. Abstract will be published, I guess, next week. And we may be in a position to provide some additional guidance at that point. But not much more we can say at this point. I'm sorry to say.

Understood. And then, just wanted to ask about how you guys are thinking about data release in a virtual world and what that changes in terms of physician engagement and dialogue and things like that.

We are going to do the very best we can. I think we're still -- no, but seriously, I think we're all still learning to some extent what the final process is going to be. So -- but yes, we'll certainly do the very best we can and we'll make ourselves available to answer questions as well.

Our next question comes from Boris Peaker with Cowen.

Great. Can you hear me, guys?

Yes. We can.

Great. So my first question on the -2009 study that's currently on hold, just curious in terms of patients that are enrolled in the study. How consistent are these patients going through their follow ups? And just what are potential concerns about data quality, if they start missing some of their appointments?

Yes, Boris. I mean I think that's the question that relates to everyone, right, in this -- at this moment in time and don't have anything -- I don't have anything specific to say about that, other than -- that is a risk, of course, that patients that have been on study may have challenges getting back into the centers at which they're being treated. We're still in the relatively early stages of figuring out what that impact is going to be.

I guess maybe just follow-up on it, because you've done some questions on that from the investors. Are these patients going to hospitals for follow up? Or these in outpatient setting?

I don't want to comment on that specifically, Boris, at this point, but it's going to be a combination of those.

Got you. And maybe my last question is for the -2009,compound, can you set expectations for data presentation at ASCO? Specifically, what should investors be focused on?

Boris that was -2029?

Yes. No, -2009. Yes.

-2009. Yes. So tracking back to last year at AACR, that was the last data update on the Phase I, -2009 work. So this will be the first update. And effectively, the completion of the Phase I study for CX-2009, completion of the dose escalation. So it's going to be additional follow-up. It's going to be additional patients. Most importantly, data that would -- the data that supports our advancement of -2009 into hormone receptor positive HER2 negative breast cancer at the dose of 7 mgs per kg. So the data should make it clearer to investors what underpinned that decision, clearer than the data set that was presented a year ago.

Our next question comes from Mara Goldstein with Mizuho.

Great. I have 2 questions. One is just a clarification on the cash runway. I believe you said it doesn't include any other partnerships, but does it anticipate any other milestones from the existing programs that you already have, including any resources that you may use to fund programs? Is the first. And then also, I'm hoping that, you might be able to just provide an update on BMS collaboration. Clearly, you have candidates that are advancing, but memory serves you, BMS has the option for additional targets? And are there any time limit or constraints around those targets in which they might come back to you?

Yes, Mara. So regarding cash runway, I'll comment. And Carlos may want to jump in too. But we always make very conservative assumptions around milestones from existing deals. So while there may be some element of milestones factored into that runway guidance, is going to be pretty conservative. Now that said, we actually have a pretty good track record of earning milestones in these deals, as I'm sure you'll agree. So -- but we are, for the guidance purposes, pretty conservative. Carlos, anything to add to that?

No. Nothing to add.

Great. And then regarding BMS. Yes, you're right, Mara. They do. Going back to the expansion that we did a few years ago, they still do have the ability to select additional targets. We haven't disclosed the timeline under which they need to select those targets. But they don't have forever. There was a backstep on that. And we're in active dialogue with them as to additional target selections and getting additional programs up and running, which we're very excited to do.

Okay. And if I could just ask 1 other question on CX-2009 in terms of -- the trial has been temporarily paused at this point due to current environment. But can you speak to how many patients actually began dosing within that trial?

No, I really can't. But as I said, our goal is to get 40 patients enrolled into that study. So we really can't say -- can't speak to how many patients have been enrolled. And unfortunately, now we can't speak either to timing of data because it's just got so uncertain, but we're doing everything we can to get that program back on track and be able to provide some clearer guidance in the future.

Our next question comes from Etzer Darout with Guggenheim Securities.

Great. Most have been answered. But just wanted to follow up with a couple of questions here. So first, Sean, maybe for CX-072, just wondering what's next for the PD-L1 Probody? And what -- maybe we could learn from the ASCO presentation as far as prospective sort of monotherapy or maybe even other combinations beyond sort of a CTLA-4 combination for that asset. And Carlos, maybe if you can talk about the pace of R&D spend throughout the rest of 2020, to the extent that you can, given the Q1 number?

Yes, great, Etzer. So with regard to -072, the ASCO presentation, as I mentioned, will be -- really will round out the Phase I, the Phase I/IIa work that we've done on the program so far. So you'll recall that the program advanced to enrollment of patients into a number of small expansion cohorts of around 15 patients in a number of different tumor types, some of which were expected to be at -- to respond to a checkpoint inhibitor, some of which were a bit more speculative. So the data update on monotherapy will include really the rounded out data and some fairly lengthy follow-up on patients from the monotherapy expansions, in addition to some -- an update on the Ipi combination Phase I dose escalation.

In terms of where we go next with the program, it continues to be an active program at the company. We are, to some extent, shifting gears towards combinations with our own pipeline assets like -2009. And that said, we do continue to talk to potential partners, and we also continue to evaluate other emerging combination opportunities. So there's plenty that we can potentially do in the future. But right now, the most immediate next step will be the combination with -2009, with the indication to be disclosed at a later date. And Carlos?

Great. And Carlos could comment on the R&D?

Yes, absolutely. So we're not guiding full year trend but beyond our cash runway that we mentioned. But I do want to point out, as I mentioned during the formal remarks, that Q1 included a series of onetime expenses associated with licenses and sublicenses that are related to the milestones and upfront payments that we earned during the quarter. So that's the extent of the guidance I can give you.

Our next question comes from Joe Catanzaro with Piper Sandler.

Just maybe 1 quick 1 from me on 2029. Would you be able to detail the dose escalation schema used in this study, as it compares to the 2009 dose escalation, specifically, where single patient dose escalation cohorts initially used. Were you able to start a higher dose, giving any learnings from -2009, things along on those lines?

Yes. Joe, the only thing I would say, as I believe I said previously on this particular program is that, we actually started at a pretty low dose, given the nature of the target. CD71 -- CD71 is the idea and it is a tough target to try in drug. So and we know from preclinical work that we've done, that's engaging CD71 in cynomolgus monkeys, is lethal at quite low doses. So for various reasons, including those, we began dose escalation at a -- I think it's fine to say at a lower dose than -2009. I can't say anything more than that right now, but a lot of this will be shared and is being prepared to be shared at ASCO.

Okay. Got it. And maybe just 1 quick one. I'm not sure if you have any insight into this, but the Phase II randomized portion of the Bristol study, would you happen to know if the nivo/ipi dosing they're using is consistent with CheckMate 067 or have they sort of switched to the 3 plus 1 that they've used in other studies?

I can't give any specifics there. The dosing and schedules, there are 5 arms in that study, and the doses and schedules being evaluated have, of course, been informed by what was observed in the Phase I dose escalation. That data, the Phase I data will be presented by BMS in poster form at ASCO. And we'll -- that's really all we can say right now about the doses and schedules that they're using. But the goal, of course, of this program, the masking of ipi, the goal of masking ipi is to effectively give enough of this agent in the clinic, to get to more effective outcomes for patients. And the doses and schedules that they are moving forward in the Phase II are consistent with that.

Our next question comes from Mohit Bansal with Citigroup.

Great. And congrats on all the progress you have made this quarter and last quarter as well. So a couple of questions from my side. So on -2009, if I remember correctly, from the last data set, the activity was there, but there was a little bit of -- we probably see -- safety issue was there, but the responses was not durable until the last update. Now that you are moving with the monotherapy arm in the subset of breast cancer, is it fair to assume that you have tackled the durability issue here?

Mohit, so you're right to say that as of AACR of last year, so we reported at that time 7 unconfirmed PRs. And 1 of the -- were challenges at the time with the study was that, because we had not -- for good reason, we had not instituted ocular prophylaxis from the outset because we really wanted to get a full view of the safety profile of the drug candidate. What that meant was that the upper doses, the mid-level to upper doses, many patients came off. Patients were coming off the course with disease progression, certain patients were coming off for ocular toxicity. So -- and that is in large part why those responses were not ultimately confirmed. So we do have additional experience with the drug candidate now in Phase I. That will be shared at ASCO. Coming up soon. And in Phase II, we are actively mandating ocular prophylaxis. And we've also picked a dose, 7 mgs per kg, where we see clinical activity, of course, and also where we are confident the ocular mitigation can be effective. So the Phase II study is set up to give us the best opportunity to keep patients on drug for extended periods of time, to really see what this drug candidate can do in a more focused, less heavily pretreated patient population.

Got it. And then 1 other question on the CD71 program. Since AbbVie has opted in for the program -- I'm sorry. Opted in for the program, is it -- so can you just comment on the criteria behind the milestone payment and what went into -- what kind of data they had to see for you -- for them to actually move forward with the program?

Obviously, the milestone is a significant milestone, the $40 million payment. That milestone is intended to fund the ongoing work that we'll be doing as we run the clinical program and move into the expansion cohorts. In terms of the criteria that triggered the milestone, that what we call the dose escalation criteria that were specified at the time that we put the agreement in place a few years ago. And while those criteria have not been disclosed, essentially, they are -- they were designed to mark the completion of Phase I -- successful completion of Phase I dose escalation to point the way to Phase II expansions in select tumor types at a specific dose. So that's what we needed to achieve, and that's why the milestone was taken.

Our next question comes from Biren Amin with Jefferies.

Maybe if I could just start on -2029, Sean. On clinictrials.gov, if I look at the exclusion criteria for the Phase I/II trial, there seems to be some criteria related to iron metabolism disorders and use of iron chelators. So maybe can you just talk about the CD1 target and how it interferes with anemia as our chelators?

Well, CD71 is, by definition, the transferrin receptor. The transferrin receptive functions as to internalize iron complex to transferrin and get iron into dividing cells. So it's a fundamental component of iron metabolism. And so that was something that was done as a precautionary measure in Phase I, really not knowing what we would see in the clinic. So that's really all we can say about that.

Okay. And then I guess in the cynos study, if I look at that data from a few years ago, I think you tested -2029, along with some other Probody mass antibodies. And I think the reason to choose -2029 is that the other compounds saw some weight loss. So I guess my question is, how well do you think the lack of weight loss in cynos with -2029 translates into human study, given I think that cyno model dosed the animals twice at 3 weeks apart. And so do you think there might be safety issues that may arise in patients receiving several cycles of therapy?

I'm missing that, I'm not exactly sure what data you're referring to there. Maybe we could take that off-line. What I would say is that the cyno data that we have for the most part discussed -- there are 2 components there. One is we demonstrated, I think, pretty convincingly that in a head-to-head comparison of antibody drug conjugate to Probody drug conjugate that, if you take neutrophil count as a surrogate of hematologic tox, that in the unmasked version, that is a very toxic molecule in cynos with neutrophil counts plummeting and animals not surviving for much more than a week. Whereas with the Probody, neutrophil counts do fine. And so -- and remember, as I mentioned earlier on the call, the principal -- the principal toxicity from MMAE would be expected to be hematologic. So those experiments have been very important in showing the masking in preclinical studies has the potential to open a therapeutic window for the target. We did present an update on data at World ADC in London earlier this year. That update, including some of the nonclinical studies, looking at tox in cyno in a bit more detail, which, again, emphasize that the principal toxicities in cyno are indeed hematologic. I'm not sure what data you're referring to regarding weight loss. We should maybe look at that off-line.

Okay. I mean, we can certainly touch upon it later today when we talk. And I guess, I have a last question, separate program on the EGFR with the IND filing at the end of 2021. Can you just talk about whether you're pursuing T790 mutations with that program?

I can't talk about that at this point.

Thank you. And I'm not showing any further questions at this time. I would now like to turn the call back to management for any closing remarks.

Great. Thanks very much. Well, just to summarize again, it was a very strong quarter for the company, despite the macro environment. And we look forward to catching up with all of you guys next quarter. Take care.

Ladies and gentlemen, this concludes today's conference call. Thank you for participating. You may now disconnect.