CytomX Therapeutics (NASDAQ:CTMX) Q3 2019 Earnings Call

0:00 Good day, ladies and gentlemen, and welcome to this Atomic Therapeutics third quarter 2019 financial results conference call. At this time, all participants are in a listen-only mode. As a 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.

0:20 Thank you, Thea. Good afternoon, and thank you for joining us. Earlier today, we issued a press release that includes a summary of our recent progress and third quarter 2019 financial results. This press release and a recording of this call can be found under the Investors in News section of our website at sitomx.com. With me today are Sitomx President, Chief Executive Officer and Chairman, Dr. Sean McCarthy, Sitomx Newly Appointed Chief Development Officer, Dr. Amy Peterson, and Sitomx Vice President of Finance, Robin Nifsent. 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.

1:06 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. Thank you, Chris, and good afternoon, everyone, and thanks very much for joining us.

1:35 It's a pleasure to be here to provide an update on our progress during the third quarter. I'll begin with an overview and some recent highlights, and then I'll turn the call over to Amy to review our recent clinical advances in our CX072 program. I'll then review progress with our partner programs before turning the call over to Robin for the third quarter financial update. I'll then come back and provide some closing comments that open up the call for questions. So let me start by first introducing a new voice on today's call. Recently we announced the appointment of Dr. Amy Peterson to the new role of Chief Development Officer at Cytomix. Amy brings over 20 years of experience in oncology clinical practice and drug development, having held multiple senior roles, including Chief Medical Officer of Immuno-Oncology at Beijing, where she created and led what is today recognized as a globally relevant oncology development organization.

2:32 Prior to that, Amy was Vice President of Clinical Development at Medivation, where she was responsible for developing Xtandi and Talzena in breast cancer. Amy also held a variety of leadership roles at Genentech, where she worked primarily on early stage oncology assets targeting multiple major pathways. Here at Cytomix, Amy is charged with oversight of a multidisciplinary team focused on advancing Cytomix clinical development activities and driving value creation and differentiated patient outcomes across the Cytomix portfolio. We are delighted to have Amy joining our team at this important time in our evolution. Here at Cytomix, we see a major opportunity to more effectively target therapeutic antibodies into diseased tissue, generating new classes of differentiated anticancer therapies.

3:21 Our innovative approach to antibody localization into diseased tissue is called the ProBody platform. ProBodies are 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. Thank you so much for joining us. and we are the first to have shown clinical proof of concept for this novel approach.

4:11 Our many accomplishments in recent years have brought us to an important inflection point as we transition from a research-focused platform company into an integrated R&D organization with multiple emerging product candidates. We had a productive third quarter marked by the continued advancement of our broad portfolio of wholly owned and partnered programs. These include our wholly owned anti-PDL1 ProBody CX072, are wholly owned anti-CD166 pro-body drug conjugate CX2009, the anti-CTLA4 pro-body BMS986249 being developed in partnership with Bristol-Myers, and the CD71 pro-body drug conjugate CX2029 being developed by Cytomix in partnership with AbbVie.

4:58 Let's begin with our lead clinical asset, CX072. CX072 is a probody therapeutic directed against the validated immuno-oncology target PD-L1. Our vision for CX072 is for this probody to become a differentiated foundation for combination anticancer therapies by making them safer and more effective. We have shown previously that CX072 is active as a monotherapy in multiple tumor types, and that the probody has the activity to be expected from a checkpoint inhibitor, providing the first clinical proof of concept for our unique platform. Regarding our CX072 monotherapy program, patient enrollment is now complete in the Part D expansion cohorts, studying CX072 at the dose of 10 mg per gig in multiple tumor types. Our most recent data presentation from these expansions at ASCO 2019 continued to demonstrate that CX072 functions as a checkpoint inhibitor with an encouraging efficacy and safety profile.

5:58 Clinical activity was seen in multiple tumor types, including triple negative breast cancer, anal squamous cell carcinoma, and cutaneous squamous cell carcinoma. Previously presented clinical pharmacokinetic and biopsy data has shown that CX072 behaves as designed, remaining stable in circulation and demonstrating intratumoral activation at levels achieving target saturation. Taken together, these findings provide a very strong foundation for potential clinical differentiation from other PD inhibitors and for combination of CX072 with other anti-capsa agents. Thank you very much. Thank you very much.

7:32 Yet it's well established that a dose response exists for ipilimumab's anti-cancer activity. In recent years, experimental regimens testing the combination of PD inhibition plus CTLA-4 inhibition have used lower and lower doses of the anti-CTLA-4 agent due to poor tolerability, some even lower, in fact, than the already low dose of 1 mg per kg every three weeks. Take, for example, the two studies by BMS, Checkmate 227 and Checkmate 9LA. Both of these studies evaluated chemotherapy versus the combination of ipi plus nevo either alone or in combination with chemotherapy in patients with previously untreated non-small cell lung cancer. Of particular note, in both of these studies, the dose of ipilimumab was one mg per kg, but instead of being administered every three weeks, it was now administered only every six weeks.

8:24 AstraZeneca has also reported some recent success in non-small cell lung cancer, namely in their Poseidon trial. demonstrating superiority of the combination of tremolumab, their CTLA-4 inhibitor, when given in combination with dervalumab, their PD-L1 inhibitor, and chemotherapy versus chemotherapy alone. Notably, the dose of CTLA-4 in this study was fixed at 75 milligrams, or again, the equivalent of one mg per kick. So each of these studies represent a significant down-dosing, in fact, as much as six-fold, from the dose and schedule of the CTLA-4 inhibitor when administered as a monotherapy. Thank you very much. also offers additional potential proof of concept for our platform technology, whilst also laying a foundation for the advancement of this combination into other indications and hopefully into other potential registration studies.

9:41 We look forward to providing initial data from this program in 2020. Moving on now to our second wholly-owned drug candidate, CX2009. This is a pro-body drug conjugate targeting a unique tumor antigen called CD166. conjugated to the microtubule inhibitor DM4. CD166 is the most advanced of our novel targets and is well poised to help us better understand our ability to target the untargetable. CD166 is an effective internalizer of antibodies that is expressed at high levels on most solid tumors, but is also present on most normal tissues. Having completed dose escalation and presented encouraging Phase I data earlier this year at AACR, We are currently in the dose refinement stage and anticipate announcing next steps with this program towards the end of 2019.

10:33 I would now like to turn the call over to Amy to give some additional background and context on our newly launched PACE-2 study of CX072.

10:41 Thank you, Sean. First, I just want to say how thrilled I am to be here as a member of the Cytomix team and very pleased to be joining all of you on the call today. Thank you for your participation. I want to start with a review of the dose escalation portion of the Phase 1 study, which evaluated the combination of varying doses of CX072 plus ipilimumab, and which underpins our recently announced Phase 2 study. Proclaim CX072-001 enrolled a heavily pretreated patient population and one that is not typically thought to respond to checkpoint inhibition. This trial evaluated CX072 dosed at 0.3 to 10 mg per kg in combination with ipilimumab dosed at 3 to 10 mg per kg.

11:35 Updated data as of an October 2019 snapshot showed that among 27 evaluable patients who received ipilimumab combined with CX072, the disease control rate defined as stable disease or better was 37%. Five patients achieved a confirmed objective response, including one patient with a complete response. This represents an overall response rate of 19%. The median duration of response was 14.6 months. Importantly, Four of the five responders are still on treatment as of this latest data snapshot.

12:24 The combination was generally well tolerated with no new safety signals observed. Of the 27 patients treated across all doses, grade 3 or 4 treatment-related adverse events were reported in 9 patients, or 33%, and grade 3 or 4 immune-related adverse events were reported in 6 patients or 22%. The recommended combination dose for further investigation was determined to be 3 mg per kg of ipilimumab with 10 mg per kg of CX072. We believe that the achievement of a 19% overall response rate in a late-stage, heavily pretreated population of patients with tumors not necessarily known to respond to checkpoint inhibition is encouraging.

13:16 And combined with the observed safety profile, create a strong foundation for this novel molecule's entry into Phase II clinical testing. So, let's move on then to our recently announced Phase II study. Proclaim CX072002 is an open-label, non-randomized, multi-center Phase II clinical program As Sean mentioned, ipilimumab will be dosed at the approved monotherapy dose and schedule of 3 mg per kg every 3 weeks. This dose of ipilimumab will be given in combination with our PD-L1 probody, CXO7-2, at a fixed dose of 800 mg, which is the dose equivalent of 10 mg per kg. This combination will be administered for four cycles, every three weeks, after which patients will continue with CX072 monotherapy until disease progression.

14:12 The first cohort to be enrolled in this Phase II study are patients with advanced melanoma who have previously progressed on a PD pathway inhibitor given either as monotherapy or in combination with other non-checkpoint agents. Measurement of the overall response rate is the primary objective of this study, with secondary objectives being safety and tolerability and other measurements of activity, including progression-free and overall survival, as well as the duration of response in those patients achieving partial responses and or complete responses. The study follows a Simon 2-stage design in which Stage 1 will enroll approximately 40 patients. We expect initial data from this stage in 2020.

15:02 Stepping back now, our rationale for evaluating the combination in this setting is in large part due to the persistent high unmet need. While great advances have been made with checkpoint inhibition in metastatic melanoma, approximately 40% of patients never respond to initial PD inhibition. and an additional one-third or more will progress despite an initial response to checkpoint inhibition. So you can see when you add these numbers up, the majority of patients stop their checkpoint inhibition therapy for lack of ongoing benefit. Additionally, from studies in melanoma as well as in other indications, we also understand that over 25% of patients will discontinue their treatment due to a toxicity Thank you for joining us.

16:22 There are data demonstrating responses are possible with the combination of CTLA-4 plus PD inhibition in patients previously treated with PD inhibition. We are hopeful that our pro-body platform combined with the higher dose of CTLA-4 agent could further improve outcomes in this unmet need population. Let me finish by restating how excited I am to join Sean and CytomX at such a thrilling time and to be a part of this group of passionate and talented people committed to putting the patient first and improving outcomes in difficult-to-treat settings. With that, I will turn it back over to Sean.

17:08 Thanks very much, Amy. So I'd like to turn now to our two most advanced partner programs, our BMS Alliance first, Our two most advanced partnered programs are BMS Alliance first, which stems from our foundational 2014 worldwide oncology agreement, continues to make excellent progress. The leading edge of this collaboration is our work on the discovery and development of a pro-body version of ipilimumab, which is aimed at increasing the therapeutic window for this important antibody and target. BMS is preparing to initiate a randomized phase 2A expansion cohort of its ongoing first-in-human trial with the masked version of ipilimumab that we have generated within the collaboration.

17:55 This trial is designed to further evaluate the safety and efficacy of BMS 986249, the IPI pro body, in combination with nivolumab versus IPI plus Nivo. Should this program ultimately reach the market, CytomX is eligible to receive additional milestone payments and royalties that reach the double digits. This BMS study is of particular importance for two principal reasons. Firstly, the advancement of this program into a large randomized study obviously signals their satisfaction with the Phase 1 findings that we expect the BMS team to present at a future date. Thank you very much. Thank you. I want to also emphasize here that our work at Cytomix that you just heard about with our CX072 ProBody plus IPI, that combination taken together with BMS's advancement of the IPI ProBody plus NEVO into Phase 2 offers broad potential to demonstrate the value of our platform and the value it can bring to this important and still most validated IO-IO combination.

19:19 We hope to have more to say about the details of the BMS study initiation in the near future. Moving now to our partnership with AbbVie, during Q3 we continued to advance CX2029, the clinical program for this first-in-class pro-body drug conjugate targeting CD71. CD71 is widely expressed on normal tissues and therefore is considered to be an undruggable target for conventional antibody drug conjugates. CytomX has continued dose escalation in this initial phase of this study in the all-commerce setting. We at CytomX have the responsibility for advancing this program to initial clinical proof of concept, whereupon, if successful, the program will transition to AbbVie for registrational studies and ultimate commercialization.

20:04 CytomX retains co-development and certain profit split and co-commercialization rights for this asset, and we look forward to sharing additional information on CX2029 in due course. AbbVie also recently selected a second research target under the company's 2016 discovery agreement, again reflecting continued endorsement of our platform and forward momentum in this alliance. This is the second of two research targets available to AbbVie under the discovery agreement, and it triggered a $10 million payment to Cytomix a few months back. So let me now turn the call over to Robin for a brief review of financials.

20:38 Thank you, Sean. I would like to review selected financial highlights for the third quarter. We ended the third quarter with cash, cash equivalents, and investments totaling $325.7 million compared to $436.1 million as of December 31, 2018 and $349.1 million as of June 30, 2019. Our strong balance sheet allows us to comfortably fund operations into the second half of 2021 assuming no new collaborations and our financing. Research and development expenses were $28 million for the quarter compared to $27.5 million in the corresponding period in 2018. The slight increase was attributable to increases in personnel-related expenses primarily due to an increase in headcount, consulting expenses resulting from increased clinical trial activities, and the allocation of IT and facilities-related expenses driven partly from an increase in headcount.

21:40 by decreases in laboratory contracts, services, and supplies as a result of manufacturing timelines. General and administrative expenses were $8.5 million compared to $8.1 million in the corresponding period in 2018. Revenues for the quarter were $10.7 million compared to $12.5 million in the corresponding period in 2018. The decrease was primarily due to a $1.7 million decrease in revenue under the CD71 agreement with AbbVie due to ongoing dose escalation. With that, I will turn the call back over to Sean. Thank you, Robin.

22:25 So thank you again to everyone on the call for joining us today. This is a very exciting time for cytomics as we see our clinical pipeline advancing. and as we continue to explore the full potential of our ProBody platform, we'll be providing additional pipeline guidance before year end and we look forward to a potentially data-rich 2020. With that, I would like to open the call up for Q&A and hand back over to Chris.

22:49 Theo, please open the call for questions. At this time, I would like to remind everyone that if you would like to ask a question, to press star 1 on your telephone keypad now. We'll pause for just a moment to compile the Q&A roster. Varun, your line is open. Hi. Good afternoon, everyone, and thanks for taking the questions. First, on 2009, if you can remind us on what's the gating factor here? Should we think it more like, you know, managing safety for ocular and liver tox?

23:37 And a related question on that, should we expect a press release sometime before year-end for this program?

23:47 Hi, Varun. Thanks for the questions. So, as you know, where we're at with 2009 is continuing with dose refinement with the objective of selecting dose and indications for potential expansions. And as we communicated previously, the work we've been doing over the last several months has been Thank you very much. Thank you, Sean. And another question on 072, the PD-L1 program.

24:49 So if I understand correctly, the current trace to the idea there is to have or maintain the EP dose at 3 mg per kg. But if you can, you know, maybe tell us what's the internal or what you guys are thinking in terms of response rate to expect in this refractory patient in melanoma. which can inform or potentially moving into other tumor types.

25:16 Yes, an important question. We're not ready to guide on specific response rates at this point, but I would just point you back to the summary that Amy provided of the Phase 1 dose escalation data where we saw a 19% response rate in the all-comer setting, which obviously is very encouraging. And by the way, that was across and multiple doses of ProBody and IPI. So, you know, we're optimistic about this study, but we're not providing specific guidance at this stage on exactly what we're looking for in terms of target response rate. But obviously we want to make a significant difference for these patients. Okay, thank you very much. And maybe just a last one, if I may. On, you know, triple negative breast cancer, certainly it's one indication where we have seen activity from both 072 program as well as 2009.

26:06 So I was curious how you guys are thinking currently for this indication. Certainly there is a lot of unmet need in this indication, and I could see some large pharma being interested to partner, potentially partner for any combination. So any color for triple negative, how you guys are thinking in near term?

26:29 I think there are a couple of different questions there, so let me answer both of them. As we commented, and we've consistently commented, our vision for CX072 is for this differentiated pro body to become a centerpiece of combinations. The IPI combination is the first one that we're moving into phase two. We have always said that we would consider it to be a potential combination partner for other molecules coming from our pipeline, and the concept of combining 072 with 2009 we think is pretty interesting. to do that in TMBC obviously is a possibility. No specific guidance at this point. Regarding partnership, we do continue to believe that the 072 program would benefit from a partner at the right time.

27:18 Again, as we like to say, we'll do the right deals at the right time. But we do think, given that the program could become very broad very quickly, that A partnership, given that the program could become very broad very quickly, that a partnership in due course could make a lot of sense. Thank you very much, Sean, and welcome, Amy. Thank you. Thank you, Viram.

27:40 Okay, operator, let's move on to the next question. The next question is from Mohit Bansal with Citi. Please go ahead.

27:48 Great. Thanks for taking my question, and I welcome Amy from my side as well. Maybe if you could start with talking a little bit about the status of your ambient partnerships. I don't recall if you have mentioned that on this call. And when can we see data from the FBCD71 program? Thank you.

28:15 Great. Hi, Mohit. Thanks for the questions. So with regards to Amgen partnership, we focused our comments today on our clinical assets and the Amgen partnership continues to be preclinical. It's doing some very foundational research and discovery work in T-cell bispecific probodies in that alliance and that continues to be the case. So no specific update at this stage other than the We're increasingly convinced that T-cell bispecifics are going to be a very important modality, particularly in the pro-body setting. So we're very enthusiastic about that modality. Regarding AbbVie and 2029, no guidance yet on specific timing of a program update.

29:04 Right. Helpful. And then maybe a little bit just going back to the program study and the expansion plan you are planning. So Just trying to understand conceptually, when you add the highest dose or maybe a little bit higher dose, like 3 mg per kilogram you're talking about, what do you expect to see? Would you expect to see more responses or do you think the depth of the response is what would you see based on the prior trials if patients can be dosed higher?

29:41 So there have been studies in this patient population of ipi-nevo, specifically in the relapsed refractory setting. It's pretty clear that adding ipi on top of a PD-1 inhibitor, PD inhibitor if you like, can elicit pretty respectable response rates. I mean, the data sets are relatively small, but response rates in the 40% range, plus or minus. And, you know, so this is a patient population that has a very good chance of responding to our combination, particularly at the 3 mg per kg dose, which has not been, to our knowledge, tested in this population yet. So we're breaking new ground with this particular dose and combination.

30:29 Does that help answer the question?

30:31 Yes, it does. It does. Thank you very much. The next question is from... The next question is from Mara Goldstein with Mizuho.

30:42 Great. Thanks so very much for taking my questions. So I understand you're limited as to what you might be able to say on the CX072 program, but I'm curious as to If you cannot give specific numbers sort of conceptually, what is considered clinical success for that program and what would be the next steps assuming that you achieve that? And then secondarily, on the CX2009 patient cohort that was previously treated, will you be able to provide updated data on those patients when you talk about next steps for that program?

31:15 Hi, Mara. On the second question, was that 2009 or 2029?

31:21 Sorry, on the pro-body drug conjugate.

31:26 Yes, on 2009. Right, thanks. Yeah, again, we need to get this study launched, and we don't have any specific guidance on our target response rate, but as I said... We have effectively a 20% response rate in our Phase 1 study in the all-camera setting. We know that ipinevo at lower doses can be effective in this patient population, so we're optimistic that we're going to see something here. But we're not setting specific goals from the Simon 1 stage just yet. Regarding 2009, again, to restate our goal between now and the end of the year is to communicate on Thank you very much. Thank you. I think you're right that the numbers are going to be small, so we'll be looking at that, but I don't know that we would be guiding to being able to draw any conclusions from this Simon 1 stage.

32:50 All right. Thank you very much. The next question is from Boris Peeker with Cowan.

32:57 Please go ahead. Good evening. My first question is on 7.2, and I guess maybe addressed to Amy. Just from the regulatory perspective, if you decide to advance the O7-2 into pivotal combo studies with IPI, will you have to include monotherapy arm of O7-2 or monotherapy of IPI or some kind for combinatorial reasons?

33:24 Hey, Boris, it's Sean. I'll let me kick that one off and hand over to Amy. Regulatory strategy I would say is in the early stages of being developed for the program. We're highly focused on this first 40 patients to see what this combination can do for us in this area of high medical need. At the end of the day, the regulatory path that we follow is going to be very much a function of the activity that we see of the combination. So a little hard to comment at this stage. Let me ask Amy to add to that.

33:55 Yeah, I think The only thing that I would add is given the nature in which the regulatory environment has evolved in the last couple of years, I think everybody's hopeful that we don't have to conduct as rigorous evaluation of what monotherapy might be or what standard of care therapy might be. There's certainly a lot of studies that are attempting to look at real-world data as they file for registrational approval. Suffice it to say that we are going to be as creative as we can and we will do whatever we do in collaboration with the health authorities globally.

34:38 Great. And then further on the Proclaim 072 study, when will we see monotherapy data and how important is monotherapy activity?

34:50 So we continue to, as I mentioned on the In the prepared comments, the enrollment in the Part D expansion cohorts is now complete. We continue to collect and analyze that data, and we will give an update on monotherapy strategy again between now and the end of the year.

35:07 Great. And lastly, on CD166 as a target, is there any competitive development that you're aware of?

35:15 No. Pleased to say that we continue to blaze a trail with that first project. clinical stage novel target of ours. So nothing that we're aware of at this point.

35:27 Great. Thank you very much for taking my questions.

35:30 Thanks, Boris. The next question is from Byron Amin with Jefferies. Please go ahead.

35:37 Yeah. Hi, guys. Thanks for taking my questions. Sean, you know, maybe can you talk a little bit about the big picture on 072? The compound's been in the clinic since end of 2016. However, you know, I think what we've seen with other companies is that they've been somewhat creative in terms of pivotal single arm studies and other tumor types. And they've just been, you know, I think, more aggressive. So at what point can we expect that from Cytomix and 072?

36:04 Well, hey, Byrne. Good to hear from you. As you know, we've taken the approach over the last several years of casting a fairly wide net to really characterize what we describe as the efficacy fingerprint of CX072 because as a probody, not an antibody, and the first probody to go into patients, it was always intended to teach us a lot about how the platform works and also how this product candidate works. I believe we have learned a lot. We presented a reasonable amount of data over the last couple of years. Thank you very much. potentially in a range of different tumor types where we already know that ipinevo is effective but has not been advanced due to toxicity issues or not being able to dose high enough.

37:10 Last comment I would make is that Dr. Peterson here is rather well known I think for her broad and aggressive clinical development strategies and we will be looking for her to develop those for us as we move forward.

37:28 I've got a follow-up, I guess, just on the new Phase II trial that you've announced. Why not add a comparator of ipinivo so we can actually delineate the differentiation of O7-2? And then I guess a second part of the question is, given PD-1 is a frontline standard of care in melanoma, I'm going to assume that all of these patients will be retreated with PD-1 in your study, so why not also evaluate the combo in the frontline setting?

38:06 Yeah, great question. It's a stepwise thing, isn't it? So at this stage, we think this is the right experiment to do for the pro body, and given the unmet medical need in this patient population, exposing these patients to PD-1 Running Control Arms, we didn't think would be the right thing to do. We also see potential in the long run to bring this combination forward in the treatment regimen. So it's a stepwise approach, Bernd.

38:43 Got it. Okay. And then I guess you mentioned that at some point you would evaluate a partnership for 07-2. Can you just talk about where your efforts are for CX188, the PD1 ProBody? I believe you were evaluating partnerships for that program as well.

39:02 Well, as you know, the PD1 ProBody we elected earlier this year to not move into clinical development, and we've always thought that a partnership around the program at the right time could make some sense. Whether a partnership on One of those assets and not the other would be doable remains to be seen. But all I can really say is that we continue to be interested at the right time in partnering the PD program. Got it. Thank you. The next question is from Terrence Flynn with Goldman Sachs. Please go ahead.

39:45 Hi. Thanks for taking the question. Maybe again, just another big picture one. Sean, you referred to some of the recent Bristol data for Opdivo, Yervoy in frontline lung, a couple of studies that came out. Just wondering your thoughts on the implication of these data, maybe for your programs. And then I'm not sure if you can comment on this, but what tumor types would you expect Bristol to focus on for the 249 plus Opdivo phase two trial that you're expecting them to advance into? Thank you.

40:16 Hi Terence, second question first. Ladies and gentlemen, please remain on the line Ladies and gentlemen, please continue to stand by.

42:38 The conference will resume momentarily. Hello? You're reconnected, sir.

42:58 Oh, okay. Go ahead. Hello? Hello?

43:07 Hello. Okay, we'll go with Robert Burns with HC Wainwright.

43:18 Hi, and thank you. Hey, thanks for taking my question, guys. So just two, if I may. So as we saw from the press release last week across the 27 patients in the Phase 1 proclaimed CX072 dose escalation trial, 33% of patients experiencing G34 treatment-related adverse event rate, which appears to have ticked up from the prior 25 that we saw. And I was just curious, what was the rate in patients who were treated at the recommended Phase II dose? And then my second question was, could you give some color as to what percentage of first-line melanoma patients currently receive Opdivo plus Yervoy or just an anti-PD-1 monotherapy regimen? Thank you.

44:06 Hey, Robert. Good to hear from you. So we have 20 patients in the study treated at three mgs per gig of IPI, and I believe I'm right in saying that the response rate among those patients is 25%, and the incidence of grade 3, 4 AEs is the same. It's 25%. So

44:30 you're right. That 33% number is a slight uptick from what we presented previously, but the number is

44:35 broadly speaking in this study have held up really very well since the first presentation.

44:42 Does that help? Yeah, that helps. Thank you. And then just in color as to overall treatment patterns and prescribing patterns within first-line melanoma would be helpful if you can.

44:56 Yeah. Yeah, let me hand over to Amy to comment on that.

44:59 Yeah, so we obviously were very thoughtful in how we discussed decided on this particular cohort. And although treatment or prescription patterns in frontline melanoma in the U.S. and predominantly at academic centers focuses more on the combination, we found that that is not actually necessarily true when you go out into the community where physicians are really more focused on minimizing the side effects profile and increasing tolerability. and oftentimes they will withhold the CCLA-4 agent until the patient has progressed and or they've determined that an additional agent is needed.

45:44 So there are opportunities in the U.S. and as well certainly in other regions of the world where the doublet is not commonly the go-to prescription. Those are areas where we've taken into consideration for our sites and have expanded into regions such as Korea and Australia and New Zealand specifically for that. Does that answer your question?

46:13 Yes. Thank you so much. Sure. And there are no further questions.

46:23 All right. Operator, thank you very much. And Sean? Yeah, great. Thanks, everybody, for your time today. Again, it's been an exciting Q3 for CytomX, exciting year, and we're looking forward to continuing to move this novel pipeline forward. And as I said, as we come to the end of 2019, we're beginning to get line of sight to what has the potential to be data-rich and milestone-rich 2020. So thank you again for your time. Ladies and gentlemen, thank you for participating in today's conference call. You may now disconnect.