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

Good afternoon, everyone. Thank you for standing by, and welcome to the CytomX Therapeutics Conference Call. Please be advised that today's call is being recorded. [Operator Instructions] I would now like to hand the call over to your host for today's program, Chau Cheng, CytomX's Vice President, Investor Relations and Corporate Communications. Please go ahead.

Thank you, Jonathan. 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 relate to the future, they are subject to inherent uncertainties and risks, including the uncertainty 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.gov. We undertake no obligation to update any forward-looking statements, whether as a result of new information, future developments or otherwise. Earlier this afternoon, we issued a press release announcing results from our Phase II study of praluzatamab ravtansine in patients with advanced breast cancer. With us on today's call to discuss these results are Dr. Sean McCarthy, CytomX' Chief Executive Officer and Chairman; and Dr. Amy Peterson, President and Chief Operating Officer. Following the prepared remarks, 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, and the results we have released today reflect an important landmark in our continued development and optimization of the Probody therapeutic platform. Probody therapeutics are designed to be conditionally activated within the tumor microenvironment, offering the potential for the improvement of therapeutic index for multiple antibody and biologic formats. Praluzatamab ravtansine, also known as CX-2009, is our wholly-owned conditionally active antibody drug conjugate that targets CD166, a transmembrane glycoprotein that has been reported to play a role in multiple aspects of tumor biology, including angiogenesis and invasiveness. CD166 is highly expressed on the cell surface of many cancer types, and is an attractive ADC target. However, pursuing CD166 with a conventional ADC would be expected to be limited by its widespread presence on healthy tissues. Praluzatamab is designed to target CD166 in-tumor tissue with minimized target engagement and healthy tissues. The payload for praluzatamab is the maytansinoid DM4. Based on our first-in-human study of praluzatamab that was published earlier this year in clinical cancer research, we have demonstrated that CD166 can be a viable tumor target. In our Phase I study, single agent activity was observed in a variety of tumor types, most notably in patients with hormone receptor positive and triple-negative breast cancers and in several other cancer types. Based on these findings, we have conducted a 3-arm Phase II study in patients with HER2 non-amplified breast cancer from which we have today released our first results. Let me now hand you over to Amy to briefly review the data, and then I'll provide additional context before we wrap up and go to Q&A. Amy?

Thank you, Sean. Let me begin with a quick overview of the study design. This is a 3-arm Phase II study. Arm A evaluated praluzatamab ravtansine as monotherapy in patients with advanced hormone receptor positive HER2 non-amplified breast cancer, including HER2 low and HER2-non breast cancer. Patients were enrolled to Arm A regardless of the level of CD166 expression. All patients in Arm A were initiated at the dose of 7 milligrams per kilogram administered intravenously every 3 weeks. Arm B assessed praluzatamab also as monotherapy in patients with CD166 expressing triple-negative breast cancer. Two doses of praluzatamab were examined in Arm B, either 7 milligrams per kilogram or 6 milligrams per kilogram, each given every 3 weeks. Praluzatamab at 6-milligram per kilogram dose was also studied in combination with pacmilimab, our proprietary conditionally activated anti-PD-L1 antibody in patients with triple-negative breast cancer in Arm C of the study. To be eligible for this Arm, patients also had to be PD-L1 positive based on an FDA-approved test in addition to having CD166 expression. The primary endpoint for Arm A is confirmed objective response rate by central radiology review. Other efficacy endpoints were assessed by the investigator. As of May 13, 2022, 47 patients unselected for CD166 expression with advanced hormone receptor positive HER2 non-amplified breast cancer were evaluable for the primary efficacy end point. The overall response rate by central radiology review was 15%. The clinical benefit rate at 24 weeks defined per protocol as any response confirmed or unconfirmed or stable disease for 24 weeks was 40% by investigator assessment. Median progression-free survival was 2.6 months. Biomarker analysis is ongoing. The safety profile of praluzatamab ravtansine in Arm A was generally consistent with toxicities observed in Phase I and with the DM4 payload, namely high-grade toxicities or toxicities resulting in dose modifications were predominantly ocular or neuropathic in nature. Grade 3 or greater ocular and neuropathic treatment-related adverse events were 15% and 10%, respectively. A 30% of patients discontinued treatment for an adverse event. Again, all patients in Arm A were treated at the dose of 7 milligrams per kilogram. The toxicity profile of the starting dose of 7 milligrams per kilogram in Arm C was consistent with Arm A. Grade 3 or greater ocular and neuropathic treatment-related adverse events at this dose were 11% and 11%, respectively, and 21% of patients discontinued treatment for an adverse event. The tolerability profile at 6 milligrams per kilogram appears to be improved with this preliminary data cut in that grade 3 or higher ocular and neuropathic treatment-related adverse events at this dose were 3% and 0%, respectively. And as of May 13, no patient enrolled to this dose cohort has discontinued treatment for an adverse event. In Arm B, the overall response rate was -- I'm sorry, by central radiology review is less than 10% and did not pass the protocol-defined utility boundary. Enrollment to both Arms B and C will therefore be discontinued. We intend to present complete data from the study at a medical conference in the second half of 2022. In summary, praluzatamab demonstrated single-agent activity in a heavily pretreated patient population with advanced hormone receptor positive HER2 non-amplified breast cancer, a population that represents nearly 2/3 of all patients with advanced breast cancer. The results of 7 milligrams per kilogram are confounded by the toxicity observed at this dose. So further development will require investigation of the lower dose of 6 milligrams per kilogram in the hormone receptor positive subset. We're disappointed to have not seen more activity in triple-negative breast cancer, but our work in Arms B and C have given us important insights into the safety profile of praluzatamab at 6 milligrams per kilogram. With that, I will hand the call back over to Sean.

Thank you, Amy. These results from our Phase II evaluation of praluzatamab supports single agent activity of this novel drug candidate in hormone receptor positive breast cancer where significant unmet need remains. However, we do not believe the duration of clinical activity at 7 mg/kg supports further evaluation of this dose. While we're encouraged by the emerging safety profile of 6 mg/kg, we don't plan to further advance this program alone, given current financial market conditions, and we will be seeking a partnership. This strategy will allow us to focus our resources on other areas of our clinical and preclinical pipeline. Before opening the call up for Q&A, I'd like to make a few additional comments on these data. When we first selected the DM4 payload for this program, we did so with the expectation that payload-related toxicities would be observed as with all ADCs since in the design of our conditionally activated ADCs, we mask the antibody and not the payload. The antibody masking component of the drug is designed to minimize on-target toxicities. And if we take a step back and look at the totality of our achievements with praluzatamab, we can say that our masking technology has allowed us to target CD166. However, dose optimization relating to payload toxicities has proven harder than we expected and more work is required. Now this has got a new theme in agency development, and it also runs in parallel with FDA's emerging guidance in Project Optimus. We believe this additional optimization work will best be achieved with a partner as we focus our resources elsewhere in our pipeline. We look forward to sharing further updates with you as our plans develop. In closing, I would like to thank our investigators and their staff and the team at CytomX. And as always, our most sincere gratitude goes to the patients who choose to enroll in our studies, and I want to again emphasize that we care for every patient, we learn from every patient, and we deeply and humbly thank everyone. Operator, we're now ready for Q&A.

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

Maybe just 1 for me. I'm wondering why the degree of payload-related toxicity you're seeing here is perhaps substantially higher than what was reported for other DM4 programs. As I go back and look at mirvetuximab's Phase III experience in its Phase III platinum-resistant ovarian cancer trial, their rate of discontinuation due to AEs was 5%, presumably their rate of keratopathy and ocular AEs was also lower than yours. So just wondering why, again, you're seeing sort of the degree of payload toxicity that's maybe in excess of what other DM4 ADCs have seen?

Joe, thanks for the question. I think -- I mean, to the best of our knowledge at this point, we think it's a function of the dose. So as we just outlined and we detailed in the press release today, it seems pretty clear that 7 mg per kg will not be a go-forward dose here. We are encouraged by in Arm B early experience we're having we've seen at 6 mg per kg, which is, of course, the dose that has been used from mirvetuximab. So that's -- at this point, we're still, of course, analyzing the data. But that's the best we can say right now.

Okay. And then maybe just a follow-up more high level, I guess. With these data, maybe where do you think the platform stands? And what are your priorities for the platform moving forward with development seemingly discontinuing here with 2009, at least internally?

Yes. So as I said, the conditional ADCs have multiple moving parts. Of course, the antibody that engages the target and the payload, and we are gaining more experience as time goes on. We've had to develop and optimize this novel class of therapeutics. We have -- we believe, based on the widespread expression of CD166 in normal tissues, we do believe this data, consistent with our Phase I data, shows that the masking approach can effectively diminish on-target toxicities in normal tissues, which would be expected with an unmasked ADC. It's the payload that we need to optimize. And as we all know, dose optimization of antibody drug conjugates can be challenging, and we have more work to do here before this asset is Phase III ready.

And our next question comes from the line of Boris Peaker. Your question, please, from Cowen.

So first, on this data set, will you be reporting the CD166 expression level at some point in the future in these patients? Or maybe do we know how the CD166 level in the responding patients maybe compared to the nonresponders?

Yes. Boris, thanks for the question. So before our -- talking about Arm A, of course, holding this as the positive arm, so patients, as Amy described, were enrolled regardless of CD166 expression. We have seen in the past consistently the CD166 is broadly expressed in this type of breast cancer. So consistent with our Phase I findings, all patients in Arm A for whom we have tissue do express CD166, and so that's consistent with our earlier findings. And we continue to evaluate outcomes according to this expression and other biomarkers. And we'll report that at a later date.

Got it. And more general question. So now with the 2009 development discontinued or put on a back burner, do you plan to advance any novel wholly-owned drugs into your pipeline? And if so, when will we be seeing that?

Yes. And I think back burner is a reasonable way to put it. I think the data set, as we're obviously going into this Phase II study, our hope was that we would emerge from Phase II with a clearer go to Phase III, but that's not where we are. So we will be looking for alternative ways to advance the asset in a partnership. With regards to the pipeline, we maintain a robust R&D engine. We have multiple programs in earlier stages of development, which we will plan to continue to advance into the pipeline in due course, and you will be hearing more about that from us in due course.

And our next question comes from the line of Roger Song from Jefferies.

Maybe Sean, Amy, can you provide additional color around the Arm A? Do you have any patients reduce the dose from 7 mg per kg to 6 mg per kg or even below? What is the safety profile or the efficacy kind of profile look like for those patients?

Roger, you were breaking up a little bit there. Could you maybe repeat the question?

Yes, sure. So my question is for the Arm A. Do you have any patients dose reductions from 7 mg per kg to 6 mg per kg or even below mg per kg? What are the kind of safety and efficacy profile look like for those patients?

Yes. Amy, why don't you take that one?

Sure. Roger, thanks for the question. Dose reductions are a standard part of all protocols and dose reductions did occur in Arm A, and these data will be forthcoming.

Got it. Okay. And then so for -- I just want to confirm for the 2029, do you still expect for the final data for tumors, mainly non-small cell lung cancer data in the second half? And what about the other 2 cohorts for the GEJ and DLBCL? Would -- should we expect any data this year?

Yes. So regarding the non-small cell lung cohort, we remain on track for that update in the second half, as we have previously communicated. We have no additional guidance at this point on the other cohorts just yet.

[Operator Instructions] And our next question comes from the line of Peter Lawson from Barclays.

Sean, just your thoughts on the cash runway with [ Proref ] being put on the back burner?

Yes. So we'll be working that through. Obviously, we did last report cash at the end of Q1 of north of $260 million, which we have remarked is runway into 2023 -- well into the second half of 2023. Obviously, that is a pretty robust cash position, and we're assessing the cash runway implications of putting 2009 on a back burner here and looking for a partnership. So that is the analysis that is in progress.

Got you. And then how many lines of therapy had the patients that -- hormone receptor positive patients, how many lines of therapy have they received?

So yes, Amy will be happy to take that one, I'm sure.

Sure. We actually didn't disclose that, but we will be presenting that. The eligibility for Arm A did require probably prior CDK46 inhibition, but it also allowed anywhere from 0 to 2 prior cytotoxics. Single agent hormonal therapies were not counted, let doublets in combination with cytotoxics were. So we'll have that data at the time of presentation.

Got you. And just the current state of conversations around potentially partnering [ Proref ], if those have started or what stage you're at?

Can't really comment on that, Peter, other than the goal that we have of securing a partner for the program to realize the potential in this asset that we've shown has clear single-agent activity in hormone receptor positive breast cancer. Work in progress.

Perfect. And then just on the cash runway, was that well into '23 or well into the second half of '23.

I'll have to refer to our prior disclosures, but our current guidance on cash runway has not changed from prior comments. We will be looking at it closely, and we will provide updated guidance as appropriate.

[Operator Instructions] And our next question comes from the line of Rob Burns from H.C. Wainright.

This is Mitchell, on for Rob. Just 2 from us. I was wondering if you could talk about the baseline characteristics for Arm A and how that might have led to responses or not responses, if you can comment on that? And then separately, is there a best fit patient population that you can start to identify as the data emerge for praladuzumab?

Yes. Thanks for the questions. We'll be disclosing the full details of the study at a later date. We would just refer you to the eligibility criteria for the study that Amy has already detailed and that we've disclosed previously. I think your question regarding best fit, it's really a question around biomarkers. And we have a lot of work ongoing, again that we'll report at a later date, including, as we discussed earlier on, looking at relationships between target level and other potential markers that we can characterize. So work in progress.

[Operator Instructions] Our next question comes from the line of Mara Goldstein from Mizuho.

I have a question on Arm B. Have you looked at the breakdown between patients who received the 6 mg per kg versus 7 mg per kg? Do you have enough insight to kind of conclude whether there's a compromise in terms of activity at 6 milligram versus 7 milligram even though it's safer?

Yes. Great question. And too early to comment on that other than to say that in our prior studies, we have -- and if you look at our clinical cancer research publication on praladuzumab, clinical activity began to manifest at doses of 4 mg per kg and above. We know, of course, from the extensive work that ImmunoGen has done at 6 mg per kg that this can be an active dose. We need to do more work to be able to formally answer that question.

Got it. And just another kind of related question, like the learning from this particular payload applies to like other programs, like 2029 or future program like 2043? Or are they different type of payloads, and required just some thinking about it?

Yes, great question. Yes, of course, we're continually learning here about the platform and the payload, how to manage payload toxicities velocity. The payloads on 2009, on praladuzumab, and 2029 are different. The payload on 2029, as you may recall, is MMAE, and accordingly, the toxicity profiles are quite different. I think, again, just to take a step back and talk for a moment about the design of these first conditional ADCs that we've advanced into the clinic, 2009 and 2029, we -- and I commented on this in my remarks earlier. We selected these payloads because their toxicity profiles were and continue to be relatively well understood. And that's allowed us, in this case, with praladuzumab to be able to ascertain that the overall tox profile looks like payload toxicities. And that's an important design feature for these types of widely expressed first-in-class targets like CD166 that we're addressing because there are so many normal tissues we wanted to be able to discern payload tox from potential on-target tox in healthy tissues. We haven't seen any significant on tissue -- normal tissue toxicity, which again shows that the masking technology can get us to therapeutic levels we do see the payload tox. So I think moving forward, as we think about further iteration of our conditional ADCs, we are giving a lot of thought to what would the next payloads be, how does the masking strategy and target selection relate to payload strategy, learning from everything that we've seen so far in the clinic. So this is a long-term game. And with these studies, we have learned a tremendous amount about how to develop and optimize this novel class of drug.

Got it. Got it. And last question, just a bit more -- can you provide a bit more color on the runway in terms of the spending on 2009? Should we think about it -- is it going to be removed like moving forward from this quarter? Or like can you like add additional color on that?

Not at this stage. I think, as I said, we're not providing any formal modification of cash guidance at this point. We need to do that work and we'll come back. But obviously, we would expect spending on this program that had been planned as we were preparing to move the asset into a registrational study, we would expect the spending to drop considerably. But we'll have more details on that in due course.

[Operator Instructions] Our next question comes from the line as a follow-up from Peter Lawson from Barclays.

The discontinuation rate, I think, went up from Phase I to Phase II from like 8% to 30%. What do you think drove that?

So yes, again, we'll be presenting much more complete data later in the year. The Phase I data at each of the doses assessed where we escalated to 10 milligrams per kilogram, of course, at each dose level, it's a relatively small number of patients. We selected 7 mg per kg based on the Phase I study with what looked like an attractive tolerability profile in that relatively small number of patients. And this is a new study, a different study, and we'll be doing more work to analyze this data and presenting that additional analysis a bit further down the road.

And then just on 2029, what should we expect to see? I know there's an update in the second half for both head, neck and non-small cell lung cancer. Just if you can give us any details around what do you expect to present in the second half?

Well, just to recap what we presented end of last year with 2029 in squamous non-small cell lung cancer, we demonstrated in 16 efficacy-evaluable patients a response rate of close to 19%, which we were encouraged by at the time. And we are fully enrolling -- actually, I think we did indeed comment on our last earnings call that enrollment is complete towards the 25 patients in that cohort, and we expect to have that data in the second half. So we're looking obviously for that response rate to be maintained. We think it's, like I said, an encouraging response rate in squamous non-small cell lung cancer patients in the post checkpoint inhibitor setting.

Thank you. This does conclude the question-and-answer session of today's program. I'd like to hand the program back to Chau Cheng for any further 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.

Thank you, ladies and gentlemen, for your participation in today's conference. This does conclude the program. You may now disconnect. Good day.