CytomX Therapeutics, Inc. (CTMX) Earnings Call Transcript & Summary

Good afternoon, everyone. Thank you for standing by. Welcome to CytomX Therapeutics CX-2029 Preliminary Phase II Expansion Study Results Conference Call. Please be advised that today's call is being recorded. I would now like to hand the conference over to your host for today, Chau Cheng, CytomX's Vice President, Investor Relations and Corporate Communications. Please go ahead.

Thank you, Towanda. Good afternoon, and thank you for joining us. Before we begin, I'd like to remind everyone that during this call, we will be making forward-looking statements. Because forward-looking statements relates 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. We undertake no obligation to update any forward-looking statements, whether as a result of new information, future developments or otherwise. Earlier today, we issued a press release announcing preliminary Phase II expansion study results for CX-2029, our CD71-targeting conditionally activated antibody drug conjugate. We have Dr. Sean McCarthy, CytomX's President, Chief Executive Officer and Chairman; and Dr. Amy Peterson, Chief Development Officer with us on this call. Following the prepared remarks discussing the results, we will open the call up for Q&A. With that, let me turn the call over to Sean.

Thank you, Chau, and good afternoon, everyone. At CytomX, we are dedicated to destroying cancer differently. Achieving this goal requires bold and differentiated science, and we've spent the past decade defining and leading a novel approach to cancer treatment, namely the Probody Therapeutic platform, which enables the conditional activation of therapeutic antibodies. CX-2029, which is partnered with AbbVie under a global co-development agreement is one of the most advanced assets that have emerged from our platform. This potential first-in-class antibody drug conjugate, or ADC, targets CD71, the transferrin receptor. Present at high levels on many cancers, CD71 has been seen for decades as a target with great potential, but it presents a high bar for the development of anticancer therapeutics because of its widespread expression in healthy tissues. However, in our pioneering work, we have demonstrated in a dose escalation study published earlier this year in clinical cancer research that CD71 can be a viable tumor target. We are the first to have reached therapeutically active levels of a CD71-targeted ADC in patients, leveraging our Probody approach. Our work on CD71 underscores our determination to bring new treatments forward for people with cancer. Our collective battle against cancer requires unwavering commitment to true innovation and it's by continuing to push boundaries that we believe we will make the biggest difference. In our Phase I work, we have demonstrated that CX-2029 is clinically active with responses in late-stage refractory squamous non-small cell lung and head and neck cancers. This antitumor activity in 2 very difficult late line settings is now being further explored in our ongoing Phase II expansion study, and we're here today to report the preliminary findings from these expansions. I'll now hand over to Amy, who will go over the results in some detail with you.

Thank you, Sean. Before getting into the data, let me walk everyone briefly through the study design. There are 3 parts to this Phase I/II study. Part A was a traditional 3 plus 3 dose escalation design starting at a dose of 0.1 milligrams per kilogram administered intravenously every 3 weeks and that escalated up to 5 milligrams per kilogram. Starting at 2 milligrams per kilogram, additional patients could be enrolled into Part B, a biopsy cohort. And Part C, encompassing the expansion cohorts currently in progress was designed to enroll up to 25 efficacy evaluable patients per cohort at the recommended Phase II dose of 3 mg/kg. Per protocol, the expansion cohort allows for the inclusion of all patients from Part B diagnosed with the cohort-specified tumor type, who were also treated with 3 mg/kg. The Phase II expansion cohorts include squamous non-small cell lung cancer, squamous head and neck cancer, esophageal and gastroesophageal junction cancers and also diffuse large B-cell lymphoma. The esophageal cancer cohort includes both adenocarcinoma and squamous histologies. We are focusing today on the squamous lung and head and neck cohorts, and I should note upfront that these patients were not selected based on CD71 expression. As of the data cut date of October 29, 2021, 23 patients with squamous lung and 29 patients with head and neck cancer received at least one dose of CX-2029 at 3 mg/kg and comprised the safety population for these 2 indications. This population of 52 patients includes all 5 patients with either lung or head and neck cancer who were enrolled in Part B at the dose of 3 mg/kg, specifically 2 with lung and 3 with head and neck. The median follow-up time in these 52 patients was 3.8 months and ranged from 0.2 to 20.1 months. This was a heavily pretreated patient population, with the median number of prior therapies in the metastatic setting being 2 for squamous lung with a range of 1 to 5 and 3 for head and neck with a range of 1 to 9. All patients with lung cancer had received prior platinum-based chemotherapy and prior checkpoint inhibition therapy. And of those who've had a neck cancer, all but one patient had received prior platinum-based chemo and all but 2 had been previously treated with a checkpoint inhibitor. Let's begin with the squamous lung cancer cohort. As of October 29, 2021, 16 squamous lung patients were considered efficacy evaluable in that they had at least one post-baseline assessment. The response rate by local investigator was 18.8%. This includes one confirmed partial response from Part B, one confirmed partial response from Part C and one unconfirmed partial response from Part C that confirmed 7 days after the data cut date. Both responses in Part C were ongoing as of the data cut date and the duration of response in the patient from Part B was 5.6 months. The disease control rate defined as complete or partial response or stable disease at the first post-baseline assessment in these 16 patients was 87.5%. To put these preliminary monotherapy results into context, several randomized studies conducted in second or third-line squamous lung cancer report an overall response rate to docetaxel between 8% and 11%. This response rate is in patients who are checkpoint inhibitor naive, and I want to reemphasize that the patients enrolled in our study were all checkpoint inhibitor experienced, and this, of course, is a growing patient population given the widespread use of checkpoint inhibition in squamous lung cancer. As an additional reference point, nivolumab, approved by the FDA in 2015 for the treatment of patients with previously treated metastatic squamous non-small cell lung cancer as monotherapy, reported overall response rates of 20% and 12.8% in the second and third-line setting, respectively. Given the prior treatment regimens and the unselected nature of the study population, we are encouraged by the continued activity in patients with squamous lung cancer and the response rates that we have observed to date is consistent with our targeted response rate of 20%. We remain focused on completing enrollment of 25 efficacy evaluable patients. Moving now on to head and neck cancer. 25 patients with head and neck cancer were considered efficacy evaluable. There was one confirmed partial response at the time of data cutoff for an objective response rate of 4%. The disease control rate was 56%, including the confirmed response and one unconfirmed partial response, which will not confirm. This was a heavily pretreated patient population with a median of 3 prior therapies and response rates in this setting tend to be in the single digits. Enrollment into the head and neck cohort is closed. Let's turn now to safety. The tolerability profile of CX-2029 is consistent with that reported from the Phase I experience and no new signals were identified. As with our Phase I experience, the most common Grade 3 treatment-related adverse event in the 52 patients that received at least one dose of CX-2029 at 3 mg/kg was anemia, observed in 67.3% of patients. The next most common event was decreased neutrophil count at 9.6%, grade 3, plus one additional patient with a grade 4 event. Infusion-related reactions occurred as grade 1 or 2 events at 69.2% and were infrequently reported as grade 3 events at 3.8%. As of the data cut date, 8 patients with squamous lung and 5 patients with head and neck were still on treatment. The most common reason for treatment discontinuation was disease progression at 44%. Only 3 patients or 5.8% discontinued CX-2029 for a treatment-related adverse event, 2 for grade 2 anemia, and one for grade 3 anemia. Treatment-related adverse events leading to either dose interruption or reduction were 40% and 35%, respectively, with infusion-related reactions being the most common event leading to dose interruption and anemia being the most common event leading to dose reduction. The anemia has continued to be managed with red blood cell transfusion, dose delays and dose reductions. Importantly, none of the responding patients discontinued treatment for anemia. We are conducting additional analyses on the potential utility of erythropoietin stimulating agents, ESA, to treat CX-2029 associated anemia. We now have approximately 20 patients who have received ESAs. And while an obvious benefit has not yet been observed, analyses are ongoing. In summary, we're encouraged by the clinical activity observed with CX-2029 patients with refractory squamous lung cancer. We will continue to investigate the mechanism of anemia as well as interrogate patient tissue samples to potentially identify patient selection strategies that could enrich for those more likely to benefit from treatment with this novel drug candidate. Now I'll hand the call back to Sean.

Thanks, Amy. We are very pleased to have made this significant progress during 2021 with our ongoing studies of CX-2029, a novel first-in-class conditional ADC targeting the transferrin receptor. While these latest results are preliminary, we're particularly encouraged by the emerging signal for metastatic squamous lung cancer and the potential for meaningful clinical benefit in this difficult-to-treat disease. Given the lack of therapeutic options in the post-checkpoint inhibitor setting for squamous lung cancer, we believe these initial Phase II results bring into focus a potentially significant commercial opportunity for CX-2029 to address. We'll continue to work closely with our partner AbbVie on this program, and we look forward to completing the expansion phase of the study in 2022. As we look ahead to 2022, we'll remain intensely focused on execution and what we anticipate will be a busy year, with multiple milestones ahead, including the initial data readouts for our CX-2009 Phase II program in breast cancer; the launch of a Phase I dose escalation study of CX-904, our conditionally activated T-cell bispecific, jointly developed with Amgen; as well as further updates from the CX-2029 study. We look forward to sharing our additional progress as we drive towards these milestones, and we thank you for your continued time and support. In closing, I would like to thank our investigators and their staff and our development team at CytomX, all of whom have had to continue to endure the challenges of the ongoing pandemic. Our most sincere gratitude, of course, goes to the patients who choose to enroll in our studies. We care for every patient, we learn from every patient, and we deeply and humbly thank everybody. Operator, we're now ready for Q&A.

[Operator Instructions] Our first question comes from the line of Joe Catanzaro with Piper Sandler.

Maybe just a couple from me. So Amy, you mentioned there at the end and have emphasized that this is an unselected squamous lung population, but you've previously spoken to challenges around CD71 as a biomarker. So where do you see opportunity to potentially refine this population? And then as a follow-up, you cited docetaxel and even nivolumab's original approval in 2015. But do you guys still see 20% as the response rate hurdle here in squamous lung?

Joe, it's Sean. Let me kick off those questions and then hand over to Amy. Thanks for the input. So let me take the second question first. Obviously, this is still preliminary data. This is an ongoing study. We'll see where this comes out once we complete our goal of enrolling 25 efficacy evaluable patients. As you know, we've guided in recent months towards an ORR in the region of 20% as being what we were looking for that would be meaningful. And we're tracking towards it. I think it's too early to say, either ourselves or in the context of our partnership with AbbVie, what would come next or ultimately where this drug candidate would fit in, but we are encouraged by this activity, which is consistent with the activity that we saw in Phase I dose escalation. Regarding the biomarker, as we published in Clinical Cancer Research earlier this year, in the Phase I setting, there was no obvious relationship that jumped out between target level and response. We continue to explore that in the context of these expansions. I would just point out, this is a pretty unique target given how rapidly it cycles off the cell surface and we do have much to learn in the future and we will continue to investigate. Amy, anything to add from your side?

No, you covered all of the points that I was writing down as you were talking. Thanks, Sean. That's great.

Okay. Thank you, Joe.

That's helpful. If I could just squeeze in one quick follow-up. So of the 7 lung cancer patients who were safety evaluable, but not efficacy evaluable, how many of those are still on treatment, but just hadn't reached their first post-baseline scan?

I'll hand that one over to Amy.

Joe, so there are 8 squamous lung cancer patients who are still on treatment as of the data cut date. Two of those were responders. And then the rest of those are -- make up the rest of the population. And we still have 9 efficacy evaluable patients to go. So not every patient is going to be efficacy evaluable, and we don't yet know those numbers.

Our next question comes from the line of Anupam Rama with JPMorgan.

On the treatment-related anemia discontinuations, anything worth noting in the baseline characteristics for those patients? And then also just a clarification question. Are you guys going to be continuing to enroll patients in the head and neck expansion cohort based on these data?

Anupam, again, I'll hand those over to Amy.

Thanks, got it. So in terms of baseline characteristics, Anupam, we are actively looking at what those might be. Not everybody experienced anemia and not everybody experienced grade 3 anemia. However, we don't have an answer to that question today. As far as the head and neck squamous cell carcinoma cohort, that cohort is closed to enrollment. We'll continue to follow the patients who are still on study and report any meaningful updates when they're ready.

Our next question comes from the line of Roger Song with Jefferies.

So one quick question that is related to the disease control. So it seems that disease control is pretty high for either cohort. Do we have a sense how durable are those disease controls? And the other thing is, I think, Sean, you guided the 20% ORR as potentially kind of approvable hurdle. So any comments around the durability of the response.

Yes. Roger, thanks for the questions. I'll quickly take those. So really too early to comment on durability of responses. We did mention, as Amy mentioned on the call, the lung patient from Part B of the study was on drug for more than 5 months. The 2 PRs in the Part C lung cohort remained on drug at the time of the data cutoff. But the follow-up on these patients as of this data cutoff is still relatively short. So not a lot more to say about that at the moment. With regards to future strategy, multiple converging data points lead us to that 20% range for a targeted ORR here and obviously way too early to talk about what an approval strategy would be, something that we'd have to discuss closely with our partner. But again, just to reiterate, we continue to be encouraged by what we're seeing here in squamous lung and look forward to rounding out this cohort to the full 25 patients.

Got it. Another quick one is, you will have the CX-2009 in breast cancer next year. So any guidance around the other 2 cohorts for the CX-2029, the DLBCL and GEJ?

No additional guidance at this point. You're right that with regard to, 2009, CX-2009, the breast cancer Phase II study is ongoing. As we reported at our last earnings call, we've been making good progress with enrollment and we are on track for initial data for the breast cancer study in 2022. No additional guidance at this point on the other cohorts in the 2029 study.

Our next question comes from the line of Kaveri Pohlman at BTIG.

For head and neck, do you see any opportunity in combination with checkpoint inhibitors? Because the 56% DCR rate clearly tells that the drug is active. And for non-small cell, how important is stable disease in this setting?

Yes, Kaveri, let me comment on head and neck, and I'll hand over to Amy to comment on the lung question. Regarding the head and neck cohort, actually, I would say for both of these tumor types, potential combination with checkpoint inhibitors would be something that should be considered to be explored based on what we already know about checkpoint sensitivity to these cancer types. The stable disease is interesting. We agree with you. Of course, we would certainly have like to have seen a somewhat higher ORR, but this is where we are right now. And this is something we will continue to discuss with AbbVie. I would emphasize in the squamous lung setting, obviously not lost on us that the tolerability profile of 2029 does look to be combinable with a checkpoint inhibitor and that's something, again, that we'll be discussing with our partner. But let me hand over to Amy for further comments on the lung side of things.

Thanks, Sean. Okay. So the question was, how important is stable disease in lung in this setting? These are very refractory patients. So they, on average had at least 2 prior therapies for metastatic disease, some several more than that. And so prolonged stable disease can actually be meaningful, especially if the stable disease on this treatment is longer than, for example, their response to a prior therapy. And those sorts of investigations we'll conduct and be able to report on when we have some more mature data, but stable disease can be very important.

Our next question comes from the line of Mara Goldstein with Mizuho.

So I had a question on the anemia in patients who experienced dose interruption or reduction. And can you provide any color on the length of that interruption and/or the reduction in those 2 groups, firstly? And then secondarily, I'm wondering if you can also provide some color on any discussion that you've had with AbbVie at this point in time on this data.

Yes, Mara, thanks for the questions. So I'll take the AbbVie question first and I can't comment on that at this point, as I'm sure you'll understand. Let me hand over to Amy to talk about those reductions and interruptions. And I think there is really our Phase I experience that I think we're most able to talk to you given that this is still very much work in progress in the expansions. But let me hand over to Amy.

Mara, thanks for the question. So with regard to dose interruptions and dose reductions. The dose reductions were predominantly going from 3 to 2. And interruptions could have been anywhere from 1 week, 7 days, up to, I believe, even a little bit longer. But I don't have the median days of dose interruption. Dose reductions do seem to help, just as they did in the Phase I dose escalation, but how much is something that we really need to interrogate with a little bit more statistical rigor, and we'll also look at the intervention of ESAs and how that may have contributed to anemia recovery.

And do you have any sense yet of that 40.4% interruption, 34.6% reduction, what those were sort of in Phase I versus now kind of thing?

So those would only be in the 5 patients who were from Phase I, right? So we haven't teased that out. It is knowable, but it's only the 5 patients who were dosed at 3 mg/kg and who had either squamous lung or head and neck that we could carry into this patient population. So it wasn't a lot.

Our next question comes from the line of Peter Lawson with Barclays.

I may have missed this, I apologize. But are you seeing deepening responses? I guess, I mean, fundamentally, what would the spider plots look like for some of these patients?

Yes. Peter, we commented briefly on this a little while ago. This is still ongoing work. And so it's really too early to comment in real depth about duration of response. What we've observed and commented on today are the fact that the Part B patients included in this analysis in lung was on drug for more than 5 months. The 2 responders in lung in the Part C setting remained on drug as of the data cutoff at the end of October. And I would also point out that the head and neck responder here was also on drug for almost a year. So it's still an evolving picture in terms of overall durability response, and the spiders and so on and so forth will be presented at a future date once the data is a little more mature.

Got you. And you may have mentioned this, I apologize, the median lines of therapy for lung and head neck patients, what was that?

Yes, it's a really important point, and I'll hand over to Amy to reemphasize the late-stage nature of these patient populations.

Yes. Thanks for the question, Peter. So for lung cancer, the median number of prior therapies in the metastatic setting, so this does not include whether or not they had neoadjuvant or adjuvant, this is just at the time of their diagnosis of metastatic unresectable disease, the median number of prior therapies in lung cancer was 2. So we're in the third line, basically, of metastatic disease. The range was 1 to 5. And for head and neck, same thing, this is in the metastatic setting, so it does not include neoadjuvant or adjuvant therapy, the median number of priors was 3. So we were in the fourth line basically in this indication and the range of prior therapies was from 1 to 9.

Got you. And then were there kind of any narratives there around some of the patients that responded in the sense of carrying particular mutations or failed particular therapies that we should be thinking about?

Nothing that we're reporting at this point, Peter. That will come. Great question, but that will come at a future update. Work in progress.

And I don't know if you mentioned it, but you mentioned there were 2 PRs. There were PRs into Part C. How long were they on study for?

Yes. Again, we're not commenting on the specific duration of response, but those 2 patients were both on drug, remaining on drug, at the time of the data cutoff. One of those PRs confirmed 7 days after that data cutoff, so shortly after the cutoff. But those were ongoing PRs.

Okay. What's the reason for not commenting on the length of the PRs? That seems to be a -- could be a really important element there.

Well, I think we'll be commenting when we have a more complete picture of this cohort overall.

Got you. And when is that next update?

We're not specifically guiding, Peter, right now as to exactly when the next update will be. But of course, hopeful for 2022.

Thank you. I'm showing no further questions in the queue. At this time, I would like to hand the call back over to Chau Cheng for his closing remarks.

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.

Ladies and gentlemen, this concludes today's conference. Thank you for your participation. You may now disconnect. Everyone have a wonderful day.