Good afternoon, everyone. Thank you for standing by. Welcome to the CytomX Therapeutics First Quarter 2022 Financial Results Call. Please be advised that today's call is being recorded. I would now like to head to call over to your host for today, Mr. Chau Cheng, CytomX Vice President, Investor Relations and Corporate Communications. Please go ahead.

Thank you, Cindy. Good afternoon and thank you for joining us. With me today are Dr. Sean McCarthy, CytomX's Chief Executive Offices and Chairman; Amy Peterson, President and Chief Operating Officer; and Carlos Campoy, Chief Financial Officer. Earlier today, we issued a press release that includes a summary of our first quarter 2022 financial results and highlights the important progress we made during the quarter. We encourage everyone to read today's press release and the associated materials, which have been filed with the SEC. Additionally, the press release and a recording of this call can be found under the Investors and News section of our website. Please note that 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, including the uncertainties surrounding the COVID-19 pandemic 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-K that was filed today. We undertake no obligation to update any forward-looking statements, whether as a result of new information, future developments, or otherwise. With that, I'll now turn the call over to Sean.

Thank you, Chau, and welcome back, Carlos. Good afternoon, everyone, and thanks for joining us for an update on recent progress of CytomX. Let me begin today's call by reaffirming our commitment as an organization to making the biggest difference we can for people with cancer. Our dedication to destroying cancer differently is embodied in our robust therapeutic pipeline that represents the potential for conditionally activated biologics to lead to new and differentiated anti-cancer therapies. Conditional activation holds great promise, and we remain highly focused on delivering new therapies based on our world-class research and development capabilities. Leveraging our Probody therapeutic platform, we now have six experimental therapeutics in development. During Q1, we made great progress executing toward important data readouts from our lead programs. Now, I want to stress upfront that we understand that in the current protracted bear market for small and mid-cap biotech, judicious financial stewardship has never been more important. At CytomX, a central tenet of our integrated financial strategy has been the formation of foundational partnerships with global biopharma companies, including AbbVie, Amgen, Astellas and Bristol-Myers Squibb. These alliances have not only broaden the impact of our technology platform by increasing the number of Probody therapeutic candidates being advanced into clinical studies, but they've also added considerable financial resources in the form of non-dilutive capital, enabling us to consistently maintain balance sheet strength. We ended this past quarter with $263 million in cash and liquid assets, providing sufficient resources to advance our pipeline. We also continue to be active with our business development efforts relating to our platform and to our product pipeline. I'd like to make a few specific comments on our pipeline programs before handing over to Amy for additional perspective. Our most advanced wholly-owned drug candidate, the conditionally activated ADC, praluzatamab ravtansine,…

Thank you, Sean. As mentioned, we continue to focus on execution of our Phase 2 study. And to that end, have achieved important milestones. Beginning with praluzatamab ravtansine, I'm pleased to share that Arm A of our three-Arm Phase 2 study has completed enrollment towards our goal of 40 efficacy evaluable patients with formal receptor positive HER2 non-amplified breast cancer. With this study milestone achieved, we are reaffirming our plans to report data from this monotherapy cohort in the second half of this year. As a reminder, the primary endpoint of the study is overall response rate. However, the focus to better assess for clinical benefit is on key secondary endpoints of clinical benefit rate at 24 weeks or CBR-24 and progression free survival, the latter being a critical endpoint for a registrational study in the setting. Study conduct in Arm B designed to evaluate praluzatamab as monotherapy in patients with PD-166 expressing triple-negative breast cancer and Arm C designed to examine the combination of praluzatamab plus pacmilimab are anti-PD-1 Probody therapeutic in patients with PD-L1 positive and CD166 positive TNBC is ongoing. And we remain on track for initial data from Arm B in the second half of 2022. I would now like to move CX-2029; our CD71 directed conditionally activated MMAE conjugated ADC, which is being developed in partnership with AbbVie. In December 2021, we reported an encouraging preliminary response rate of 18.8% and a disease control rate of 87.5% in 16 efficacy evaluable patients with platinum and checkpoint inhibitor refractory squamous lung cancer. I'm delighted to share that we have completed enrollment towards our goal of 25 efficacy evaluable patients and continue to track to a data update in the second half of 2022. Let's now turn our attention to the third treatment modality to which our…

Thank you, Amy. CytomX continues to have a strong balance sheet. As of March 31, 2022, we had $263 million in cash, cash equivalents and investments, which we project will be sufficient to support operations well into 2023. For the first quarter 2022, revenue was $17 million, compared to $16 million for the corresponding period in 2021. The increase was largely related to the CD-71 collaboration with AbbVie. R&D expenses increased $8 million to $31 million during the three months ended March 31, 2022, compared to Q1 2021. The increase was driven by contract and service expenses in manufacturing and development in support of our preclinical and clinical portfolio. G&A expenses were $10.5 million during the first quarter 2022, an increase of $1.3 million compared to the same period in 2021. The increase is mainly in personnel and professional expenses. As Sean previously mentioned, we exercised judicious financial stewardship with our capital and will continue to manage our cash resources strategically. I may now turn the call over to Sean.

Thanks, Carlos and Amy. In closing, I would like to again emphasize the terrific execution by the CytomX so far this year. We remain on track for important data readouts in the second half from our Phase 2 ADCs. And we have also continued to advance several earlier-stage programs to maintain a broad and deep pipeline. Our versatile and multimodality platform supported by our ever growing understanding of the tumor microenvironment continues to provide us with optionality both within our own programs and in our ongoing work with our biopharma partners. We remain as passionate as ever in our quest to destroy cancer differently. Before we open the call up for Q&A, let me express my sincere gratitude to our retiring board members, Fred Gluck and Dr. John Scarlett. Both gentlemen have been with CytomX for many years, and their contributions have been instrumental and invaluable to our growth. And I wish them all the very best for the future. So with that operator, please open up the call for Q&A.

Thank you. [Operator Instructions]. And your first question from Kaveri Pohlman. Your line is now open.

Hi. Good afternoon. Thanks for the update. I have a -- my first question is regarding 2009, how different is the safety profile of this ADC from ImmunoGen's ADC, especially in terms of ocular events because this is a higher dose that you're evaluating?

Yes, hi Kaveri. Thanks for the question. Let me kick that one off. So the -- first of all, the payload for 2009 praluzatamab is, as you know, DM4, this is the maytansine, the same payload that's ImmunoGen is indeed using on mirvetuximab. And as we've reported previously, our Phase 1 experience, the principal toxicity that we -- that we encountered as expected was ocular toxicity. We are taking measures to manage that with mandatory prophylaxis in the Phase 2 setting. We've described the various elements of that prophylactic regimen previously. But in general terms, our experience in Phase 1, with 2009, was pretty consistent with what ImmunoGen has seen in their programs and we will be reporting, of course, initial Phase 2 data on both the activity and the safety side second half of this year.

Got it. And for HER positive, HER2 negative breast cancer how feasible is it to get an ORR? Is it that a lot of these patients have bone disease, which makes the durability more reliable readout like the RBC? Just wanted to get some insight there.

Yes. It's another great question. And the etiology of the disease, you are quite right to point out that these patients, particularly in the late line setting as they come onto our study, are quite challenging to achieve objective responses in. That said, the primary endpoint for our study is ORR. But the more meaningful endpoint we believe and our investigators and advisors would agree with us is CBR-24, of course, as a clinical benefit rate for 24 weeks, which of course, is a surrogate ultimately for PFS, which would be the most important registrational endpoint as this program moves forward. So it is a significant consideration within the context of hormone receptor positive disease as you quite rightly point out.

That makes sense. And maybe a last one on the cytokine program. What's your rationale for selecting IFN-alpha as the lead asset? And how different it is from IL-2L which is -- which also kind of drives IFN-alpha in the lead?

Yes. Well, we have a broad cytokine program. There are multiple programs that we're working on. We haven't disclosed any of the additional cytokines beyond interferon yet, but we do see a terrific opportunity for our conditional activation marketing technology to have an impact broadly in this field where there's huge potential. Interferon is the first -- we like interferon given it's validation. It was indeed the first immunotherapy to be approved going back several decades., there is a fairly broad clinical experience with interferon, both in terms of what it's known to be able to do as a single agent and in combination, but perhaps most importantly, what's known about its limitations from a safety standpoint and therefore the room for improvement using our technology. So interferon alpha-2b, again, a well validated mechanism in immunooncology that we believe we can add significant value to. But as I said, also the leading edge of a broad-based program at the company.

Got it. Thanks for taking my question.

My pleasure.

Your next question from Gavin Scott. Your line is now open.

Thanks for taking my question. Just on praluzatamab and patient selection criteria for cohort C, I don't think you've disclosed the respective PD-L1-CD166 cutoff, but what does the epidemiology data suggest on the prevalence of this population? And can you maybe provide some color on the accrual rate for cohort C? Thank you.

Just -- thanks, Gavin, for the question. Let me just clarify the question, because you weren't coming across super clear to us, and then I'll ask Amy to comment. So I think the question is about the, really the size of the population in Arm C of the praluzatamab Phase 2 study, which is of course, studying the combination of praluzatamab with our PD-L1 Probody pacmilimab. That was the question, right?

Yes. That was the second part. The first part was just, on the patient selection criteria and cutoffs. I don't think you've disclosed that in the past, but just any color there as well.

That's right. I'll take the first part. So you're correct, we haven't disclosed that. But regarding the patient, the epidemiology, if you like, a PD-L1 plus CD-166, I may ask Amy to comment on that briefly.

Sure. So PD-L1 expression, the prevalence is pretty well known. There are a couple of different diagnostic tests that can be used to establish PD-L1 expression. And so, we allow patients who are PD-L1 positive by any one of those tests. With regard to overlap between CD-166 and PD-L1 expression, there really is no reason to believe that they would either be convergent or divergent. The amount of overlap is a function of the expression of CD-166 and the expression of PD-L1 in triple-negative breast cancer. So we are continuing to look at CD-166 expression levels and PD-L1 is a requirement. And I think what we've said before is that PD-L1 population, the PD-L1 positivity rate is about 35% of triple-negative breast cancer.

Okay. Thanks. And just a follow up. When you present data, will you stratify it by any varying expression levels?

Yes. So let me just briefly comment on that. In triple-negative breast cancer, our experience in Phase 1, which we've we presented and published, was consistent with the heterogeneity of the disease in that CD-166 expression is rather variable across that the patients that we enrolled in Phase 1, it was a fairly small number of patients. It was ten or 11, as I recall. We saw about half of the patients who had high CD-166, high meaning IHC of two or above -- score of two or above. So, we are, of course, very interested in understanding the relationship between CD-166 expression and clinical activity, particularly in triple-negative given that the targeted expression is heterogeneous, it may lead to patient's selection strategies in the future. We'll have a lot more to say about this, of course, with the Phase 2 data that we present in the second half of the year.

And your next question from Peter Lawson. Your line is now open.

Great. Thanks for taking the questions, and congrats on the enrollment of Arm A. Do you think we see a timing difference between data from Arm A and data from Arm B? And then just if you could walk through the -- your expectations of the amount -- number of patients we should see and bar essentially for that Arm A data. Thank you.

Yes. Hi, Peter. So right now, we're working toward giving an update on both Arms A and B, at the same time sometime in the second half. That's our goal. As Amy mentioned in her comments, Arm A, a hormone receptor positive, is fully enrolled. The goal there has been to get to 40 efficacy available patients. And so that will be the data set that we will share later in the year. Triple-negative Arm B enrollments moving along well. We'll have what we would refer to, as a meaningful number of patients in Arm B at that same time, that's what we're working towards. Triple-negative enrollment has been a little slower, of course, given the different patient population. In terms of the bar, let me hand over to Amy just to comment briefly on -- and I think the question was specifically with regard to Arm A and what we -- what we're looking for there. And I think we've discussed this previously, but maybe we can just reiterate that.

Sure. Happy -- happy to do so. And this comes to us from collaboration with our steering committee and speaking with people like Dr. Sarah Solano and our expectation or our desire is that -- or their desire for something that would be interesting would be, really, a CBR-24 rate that's around 30% or higher and progression free survival rate that is really three to four months.

Got you. Thank you. Then, Sean, just kind of, I guess, on more strategic and forward-level question. Just with retiring Board members, any changes you anticipate. Just what kind of ads you will make there? Or who would be added there? And then, just thoughts about partnerships and in addition to partnerships, we've heard a lot from pharma about increased likelihood of partnerships happening. Just your thoughts would be great.

Yes. Great. Thanks, Peter, for the questions. Regarding the Board, once again, I want to thank Fred and Chip for their service over many years and know nothing really to add at this point on any additional Board evolution. I'm very happy with where we are from a governance standpoint. And again, we wish Fred and Chip all the very best. Regarding partnerships, as we -- as I mentioned on the -- on the call, business development has been an integral part of our business plan really since we got the company going. And we always realize that the breadth of our technology would both benefit from partnering in terms of the application of the technology across multiple modalities and programs. And also, of course, serve to a fairly significant extent as a financing mechanism for the company, which has allowed us to really do a lot over the last few years. And Amy mentioned that the 500 patients that we've been able to treat, we have an incredible depth of experience with conditional activation, given the funds we've been able to raise, both on the equity and the non-dilutive side. Our partnerships continue to be strong. We're absolutely thrilled with the progress we continue to make with all four of our partners, and we continue to have discussions about potential new alliances. And as I've always said, we will do the right deals at the right time.

Your next question from Roger Song. Your line is now open.

Great. Thank you for taking our question. So a couple of from us. The first one is, just curious about the next step for the 2009, and particularly for the TNBC part given you have monotherapy and the combo, would you weigh the combo data before you would make a decision for the monotherapy moving forward?

Yes. Hi, Roger. So, I think it's too early to comment at this stage. And we're highly focused is, as you could hopefully tell from the comments on the call right now on executing to these important datasets. We will, specifically with regards to triple-negative breast cancer, of course, we do expect to have the data for monotherapy in advance of the combination, partly because of the need to screen Arm C for both -- for patients with both PD-L1 and CD-166. We previously guided and continue to guide that Arm C will come in 2023. So it's really too early to comment on any potential next steps.

Okay. That's understood. Maybe just a quick one. Last one from us. The -- in terms of the other cohort for 2029. Any comments around the enrollment and time -- timeline for the data readout?

No -- no comment on timing. We continue to enroll across the multi-cohort study. We've reported today the significant progress that the team has been able to make in lung. We're very interested to see that full 25 patient cohort data, given the encouraging 18.8% response rate that we shared in December of last year and enrollment continues in the other cohorts. No updates on timing at this point.

Your next question from Boris Peaker. Your line is now open.

Great. Thank you. So my first question is on your ipilimumab Probody though, one partner with BMS. Could you comment on any timing updates on what should we be expecting some data there?

Yes. Hi, Boris. So the ipi-Probody, otherwise known as the BMS-986249 continues to make progress in the randomized Phase 2 frontline melanoma study. It also is being studied by BMS in three other tumor types and also not to lose sight of the Probody version of the non-fucosylated version of ipi that is also in the clinic in Phase 1. We do not have any updates at this point on timing as to when that data will be available or shared.

Great. And maybe on 2029, can you comment on the CD71 receptor? What is the biologic function of this receptor? Is that known?

Yes. It's actually very well characterized. CD71 is the transparent receptor. It's biological function is to bind, to transferrin in the blood and allow transferrin complex with iron to enter cells where the iron is delivered to the cellular metabolic machinery. The thing that's most interesting about the target is that, it's actually one of the first proteins that was used to describe the biochemical process of receptor-mediated endocytosis. It cycles off of the cell surface very, very quickly. And for that reason has been thought of for a long time as a potentially ideal target for an antibody drug conjugate to deliver payload into cells. The problem is the target is present on all normal tissues because of course, all normal tissues require iron for their metabolism. So it's been a very difficult target to drug until we deployed the Probody technology and that's the basis of our program CX-2029

And can you look at iron as a biomarker for some kind of engagement or activity then in this case?

We haven't really looked at that in depth. I don't know that that would ultimately be fruitful in the clinic. What we've observed and we've had a lot of work in the clinic as you know, we haven't seen any obvious correlations or issues with iron metabolism or even the metabolic state of iron metabolism in patients coming on to study. So, it's something that we continue to think about, but not, not really a significant workstream for us at the moment.

And your last question from Mitchell Kapoor. Your line is open.

Hey there. Thanks for taking the questions. The first one just for the second half data for Arms A and B for praluzatamab. Thinking about the holistic profile. Could you kind of describe what would be meaningful and then what would be considered beyond meaningful kind of a great profile out of the datasets?

Thanks, Mitch, for the question. I think we'll -- I think we'll stick with the meaningful if you don't mind it. I'll ask Amy to comment.

Sure. Sure. Meaningful. So again, going back to hormone receptor positive HER2 non amplified. That's -- that's the patient cohort that we enrolled in Arm A. That enrollment is complete and the goal was to get 40 efficacy data from 40 efficacy evaluable patients. And here, we're focusing on the endpoints that are really more extrapolatable and important to registrational studies, those being progression free survival and clinical benefit rate at 24 weeks. Here, we're looking for something that would be CBR consistent with 30% and PFS that is three months or better. I think anything north of that is going to be in your up the best case scenario. So that's what we're looking for in Arm A. In Arm B, this is monotherapy in patients with CD-166 expressing triple-negative breast cancer. There the bar is a little bit different. Response rates can be meaningful and certainly durability of response can be meaningful and response rates can form the basis of accelerated approval studies. Sacituzumab being the most recent example of this in triple-negative breast cancer. Here, we're looking for response rates that are really upwards of 20%. And according to our KOLs and our steering committee, we're looking for PFS that exceeds one scan. So that is greater than two months. And why are we seeing that? Well, the ASCENT trial that was the Phase 3 study of Sacituzumab versus chemotherapy had response rates of 5% in the chemotherapy arm and median progression free survival of 1.7 months. And Sacituzumab got full approval on the basis of that study and went from accelerated to two-fold. And so, we are in very likely the post Sacituzumab setting where there really isn't a whole lot of treatment options. So really 20% to 30% response rate and a PFS that is greater than two months would be something that we would be happy with.

Great. Thank you. And then on the recent ACR data, if you could just talk about the implications for the activated -- conditionally activated cytokine profile for your pipelines and just kind of what that data signifies for you all.

Yes. Absolutely. So the work is presented at ACR extended from the in vitro characterization of the masking strategy for interferon alpha through to the in vivo -- in vitro and in vitro evaluation of the anticancer activity of the molecule, both in mask form and in unmasked protease activated form. And then we also have extended our work into some preliminary assessment of tolerability in cynomolgus monkeys. And the data taken together show very clearly that we've broadened the therapeutic window for interferon alpha-2b very significantly through localizing the activity into tumor tissue, localizing, if you like, the immunobiology that is stimulated by interferon alpha-2b into the tumor microenvironment. And we think this offers huge potential for the opening of a therapeutic window for interferon in cancer patients as a monotherapy. But I think even more importantly in the combination setting, and the goal overall of this program is to over time will be, of course, to make a difference in patients where they are -- they're either unresponsive or have become refractory to immunotherapies. So we see a lot of potential for this program, both ourselves and with our advisors. We're very excited about moving it forward. And as I also mentioned, it's just one of a broad-based program that we now have at the company evaluating our marketing technology to improve the therapeutic window of a wide range of different cytokines.

Mara Goldstein. Your line is now open.

Hi. This is Supawat for Mara Goldstein. I have a question on CX-2029. And I am sorry, this has already been asked by someone on to the line. So in terms of the esophageal cancer and [indiscernible] cancers and DLBCL, have you guided or -- what's your expectations in terms of the response rate? In terms of the go or no go decision? Thank you.

Yes. Thanks for the question. We haven't really discussed that yet. I think that the question was asked a little earlier, excuse me, a little earlier on regarding the timing and our -- the current status of the 2029 program is that we continue to enroll across, the expansion cohorts, where, as Amy mentioned in her comments, we've been highly focused on getting the lung cancer cohort fully enrolled to really further flesh out that signal that we reported at the end of last year in squamous lung. And we'll be providing additional updates on timing for the other cohorts as the year goes on. But nothing else really we can say today.

Got it. And for the lung -- on other lung cancer, I think you may have guided previously on the ORR rate of 20% if that's still the threshold for that indication?

Yes. Hi. I'll take. This is Amy. I'll take that question. So let me just step back a little bit and remind people what is the context of what happens in these patients in this setting? So the there's not a lot of information that we have with regard to response rate in squamous lung cancer patients who have refractory to both the platinum and a checkpoint inhibitor. With that said, when we look at the information that is available to us, for example, the randomized studies with docetaxel, and you look at what docetaxel -- how docetaxel performs in the second line following a platinum, not a checkpoint inhibitor as well, but just a platinum, the response rates, there are 8%, 10%. They're very, very low. And so we think 20% is actually pretty encouraging, given it's not just platinum refractory, it's platinum plus checkpoint inhibitor refractory squamous lung.

At this time, I would like to hand the call back over to Chau Cheng for his closing remarks.

Yes. On behalf of the executive team, I'd like to thank you all very much for joining us this afternoon. We look forward to updating you in the future on our ongoing progress.

And this does conclude today's conference call. Thank you all for participating. You may now disconnect, and have a great day.