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Edited Transcript of CTMX earnings conference call or presentation 7-Nov-19 10:00pm GMT

Q3 2019 CytomX Therapeutics Inc Earnings Call

SOUTH SAN FRANCISCO Nov 9, 2019 (Thomson StreetEvents) -- Edited Transcript of CytomX Therapeutics Inc earnings conference call or presentation Thursday, November 7, 2019 at 10:00:00pm GMT

TEXT version of Transcript

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Corporate Participants

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* Amy C. Peterson

CytomX Therapeutics, Inc. - Executive VP & Chief Development Officer

* Christopher S. Keenan

CytomX Therapeutics, Inc. - VP of IR & Corporate Communications

* Robin Knifsend

CytomX Therapeutics, Inc. - VP of Finance

* Sean A. McCarthy

CytomX Therapeutics, Inc. - Chairman, CEO & President

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Conference Call Participants

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* Biren N. Amin

Jefferies LLC, Research Division - MD and Senior Equity Research Analyst

* Boris Peaker

Cowen and Company, LLC, Research Division - MD & Senior Research Analyst

* Mara Goldstein

Mizuho Securities USA LLC, Research Division - MD of Equity Research Department

* Mohit Bansal

Citigroup Inc, Research Division - VP and Analyst

* Robert John Burns

H.C. Wainwright & Co, LLC, Research Division - Associate

* Terence C. Flynn

Goldman Sachs Group Inc., Research Division - MD

* Varun Kumar

Cantor Fitzgerald & Co., Research Division

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Presentation

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Operator [1]

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Good day, ladies and gentlemen, and welcome to the CytomX Therapeutics Third Quarter 2019 Financial Results Conference Call. (Operator Instructions) 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.

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Christopher S. Keenan, CytomX Therapeutics, Inc. - VP of IR & Corporate Communications [2]

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Thank you, Sia. 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 and News section of our website at cytomx.com.

With me today are CytomX's President, Chief Executive Officer and Chairman, Dr. Sean McCarthy, CytomX's newly appointed Chief Development Officer, Dr. Amy Peterson; and CytomX's Vice President of Finance, Robin Knifsend.

During today's call, we will be making forward-looking statements. Because forward-looking statements relate to the future, they are subject to inherent uncertainties and risks that are difficult to predict, and many of which are outside of our control.

Important risks and uncertainties are set forth in our most recent public filings with the SEC at sec.gov, including our Form 10-Q filed today. We undertake no obligation to update any forward-looking statements, whether as a result of new information, future developments or otherwise. A webcast of this call will be available on the Investor Relations page at CytomX website at cytomx.com.

I will now turn the call over to Sean.

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Sean A. McCarthy, CytomX Therapeutics, Inc. - Chairman, CEO & President [3]

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Thank you, Chris, and good afternoon, everyone, and thanks very much for joining us. 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 CX-072 program. I'll then review progress with our partnered programs before turning the call over to Robin for the third quarter financial update. I'll then come back and provide some closing comments and 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 CytomX. 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. Prior to that, Amy was Vice President of Clinical Development at Medivation, where she was responsible for developing XTANDI and TALZENNA 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 CytomX, Amy is charged with oversight of a multidisciplinary team focused on advancing CytomX's clinical development activities and driving value creation and differentiated patient outcomes across the CytomX portfolio. We're delighted to have Amy joining our team at this important time in our evolution.

Here at CytomX, we see a major opportunity to more effectively target therapeutic antibodies into disease tissue, generating new classes of differentiated anticancer therapies. Our innovative approach to antibody localization into disease 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. Mask removal is achieved specifically and selectively within cancer tissue by certain disease-associated proteins called proteases. This unique approach offers the potential for new and highly effective anticancer therapies as either the best-in-class molecules against validated targets or first-in-class molecules against novel targets that are currently deemed undruggable. We are the leader in this emerging field of therapeutic antibody localization with 4 clinical stage programs, strong partnerships, and we are the first to have shown clinical proof-of-concept for this novel approach.

Our many accomplishments in recent years have brought us to an important inflection point as we transitioned 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 PD-L1 Probody, CX-072; our wholly-owned anti-CD166 Probody drug conjugate, CX-2009; the anti-CTLA-4 Probody, BMS-986249, being developed in partnership with Bristol-Myers; and the CD71 Probody drug conjugate, CX-2029, being developed by CytomX in partnership with AbbVie.

Let's begin with our lead clinical asset, CX-072. CX-072 is a Probody therapeutic directed against the validated immuno-oncology target, PD-L1. Our vision for CX-072 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 CX-072 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 CX-072 monotherapy program, patients enrollment is now complete in the Part D expansion cohorts, studying CX-072 at the dose of 10 mg per kg in multiple tumor types. Our most recent data presentation from these expansions at ASCO 2019 continue to demonstrate that CX-072 functions as a checkpoint inhibitor with an encouraging efficacy and safety profile.

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 CX-072 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 a combination of CX-072 with other anticancer agents. Recently, we announced a major company milestone with the entry of CX-072 into Phase II clinical studies to further evaluate the activity and tolerability of CX-072 plus the anti-CTLA-4 antibody, ipilimumab, in patients with relapsed or refractory melanoma. We believe this combination has the potential to become a best-in-class regimen, not only for melanoma, but also for several other cancer types where either each agent alone or the combination has already demonstrated activity.

I'd like to spend a few minutes providing some additional context on this newly launched Phase II study. Many of you will know that the approved dose of ipilimumab as monotherapy is 3 milligrams per kilogram. But when given in combination with nivolumab, the PD-1 inhibitor, it's essentially limited to 1 mg per kg for reasons of poor tolerability, yet it's well established that a dose response exists for ipilimumab's anticancer 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 keg every 3 weeks.

Take, for example, the 2 studies by BMS, CheckMate 227 and CheckMate-9LA. Both of these studies evaluated chemotherapy versus the combination of ipi plus nivo, 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 1 mg per kg, but instead of being administered every 3 weeks, it was now administered only every 6 weeks.

AstraZeneca has also reported some recent success in non-small cell lung cancer, namely in their POSEIDON trial, demonstrating superiority of the combination of tremelimumab, their CTLA-4 inhibitor, when given in combination with durvalumab, their PD-L 1 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 1 mg per kg.

So each of these studies represent a significant down dosing, in fact, as much as sixfold from the dose and schedule of the CTLA-4 inhibitor when administered as a monotherapy.

We think there is significant room for improvement here. Our Phase II study, PROCLAIM-CX-072-002 will evaluate CX-072 plus 3 milligrams per kilogram of ipilimumab and will allow us to explore the extent to which we can push the combination dose of ipi to its approved monotherapy dose with the objective of driving meaningful anticancer activity in a population of patients with high unmet medical need.

This study 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 registrational studies. We look forward to providing initial data from this program in 2020.

Moving on now to our second wholly-owned drug candidate, CX-2009. This is a Probody 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 it's 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.

I would now like to turn the call over to Amy to give some additional background and context on our newly launched Phase II study of CX-072.

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Amy C. Peterson, CytomX Therapeutics, Inc. - Executive VP & Chief Development Officer [4]

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Thank you, Sean. First, I just want to say how thrilled I am to be here as a member of the CytomX 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 I study, which evaluated the combination of varying doses of CX-072 plus ipilimumab, and which underpins our recently announced Phase II study. PROCLAIM-CX-072-001 enrolled a heavily pretreated patient population and one that is not typically thought to respond to checkpoint inhibition. This trial evaluated CX-072 dosed at 0.3 to 10 mg per kg, in combination with ipilimumab dosed at 3 to 10 mg per kg.

Updated data as of October 2019 snapshot showed that among 27 evaluable patients who received ipilimumab combined with CX-072, the disease control rate defined as stable disease or better was 37%, 5 patients achieved a confirmed objective response, including 1 patient with a complete response. This represents an overall response rate of 19%. The median duration of response was 14.6 months.

Importantly, 4 of the 5 responders are still on treatment as of this latest data snapshot.

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 CX-072. 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 and, combined with the observed safety profile, creates 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-CX-072-002 is an open-label, non-randomized, multicenter Phase II clinical program. As Sean mentioned, ipilimumab will be dosed at the approved monotherapy dosing schedule of 3 mg per kg every 3 weeks. This dose of ipilimumab will be given in combination with our PD-L1 Probody, CX-072, at a fixed dose of 800 milligrams, which is the dose equivalent of 10 mg per kg. This combination will be administered for 4 cycles every 3 weeks, after which patients will continue with CX-072 monotherapy until disease progression.

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.

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 1/3 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 stops 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, despite benefit. And as you have heard from Sean, this is exactly where we believe the tumor-targeting specificity of our Probodies mass platform could be advantageous to patient outcomes, either by reducing the systemic toxicities to allow for continued exposure or by actually improving the responses and duration of response.

Finally, 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 Probody 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.

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Sean A. McCarthy, CytomX Therapeutics, Inc. - Chairman, CEO & President [5]

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Thanks very much, Amy. So I'd like to turn now to our 2 most advanced partner programs, our 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 Probody 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 IIa expansion cohort of its ongoing first-in-human trial with the mass version of ipilimumab that we have generated within the collaboration. This trial is designed to further evaluate the safety and efficacy of BMS-986249, the ipi Probody, 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 2 principal reasons. Firstly, the advancement of this program into a large randomized study obviously signals their satisfaction with the Phase I findings that we expect the BMS team to present at a future date. Secondly, this study has the potential to be a powerful proof-of-concept for our technology platform in demonstrating that Probody technology can favorably impact the therapeutic index towards a more effective version of ipilimumab. Improved tolerability of the Probody has the potential to allow higher or longer treatment exposure, increasing the chances of achieving or sustaining antitumor responses.

I want to also emphasize here that our work at CytomX that you just heard about with our CX-072 Probody plus ipi, that combination taken together with BMS' advancement of the ipi Probody plus nivo into Phase II offers broad potential to demonstrate the value of our platform and the value it can bring to this important and still most validated I-O/I-O combination. 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 continue to advance CX-2029, the clinical program for this first-in-class Probody 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-comer 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.

CytomX retains co-development and certain profit split and co-commercialization rights for this asset, and we look forward to sharing additional information on CX-2029 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 2 research targets available to AbbVie under the discovery agreement and it triggered a $10 million payment to CytomX a few months back.

So let me now turn the call over to Robin for a brief review of financials.

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Robin Knifsend, CytomX Therapeutics, Inc. - VP of Finance [6]

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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/or 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, offset by decreases in laboratory contracts, services and supplies as a result of manufacturing time lines.

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.

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Sean A. McCarthy, CytomX Therapeutics, Inc. - Chairman, CEO & President [7]

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Thank you, Robin. So thank you again to everyone on the call for joining us today. This is a very exciting time for CytomX 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 it back over to Chris.

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Christopher S. Keenan, CytomX Therapeutics, Inc. - VP of IR & Corporate Communications [8]

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Sia, please open the call for questions.

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Questions and Answers

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Operator [1]

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(Operator Instructions) Varun, your line is open.

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Varun Kumar, Cantor Fitzgerald & Co., Research Division [2]

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First, on 2009, if you can remind us on what's the gating factor here? Should we think it's more like managing safety for ocular and liver tox. And a related question on that, should we expect a press release some time and before year end for this program?

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Sean A. McCarthy, CytomX Therapeutics, Inc. - Chairman, CEO & President [3]

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Varun, thanks for the questions. So as you know, where we're at with 2009 is continuing to -- 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 -- has had a particular focus on ocular prophylaxis and looking to understand more about the relationship between dose ocular prophylaxis and the duration of time we can keep patients on drug. So that work has been progressing well, and we remain on track for a communication between now and the end of the year on our specific next steps for the programs. I'm not going to guide today on exactly what form that would come in, but we are on track to provide additional guidance.

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Varun Kumar, Cantor Fitzgerald & Co., Research Division [4]

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And another question on 072, the PD-L1 program. So if I understand correctly, the current Phase II idea there is to have or maintain the ipi dose at 3 mg per kg. But if you can 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?

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Sean A. McCarthy, CytomX Therapeutics, Inc. - Chairman, CEO & President [5]

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Yes, it's 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 I 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 multiple doses of Probody and ipi. So 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.

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Varun Kumar, Cantor Fitzgerald & Co., Research Division [6]

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Okay. And maybe just last one, if I may. On triple-negative breast cancer, certainly, it's one indication where we have seen activity from both 072 program as well as 2009. 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 near term?

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Sean A. McCarthy, CytomX Therapeutics, Inc. - Chairman, CEO & President [7]

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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 CX-072 is for this differentiated Probody to become a centerpiece with combinations. The ipi combination is the first one that we're moving into Phase II. 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 TNBC, 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. Again, as we like to say, we'll do the right deals at the right time. And -- but we do think, given that the program could become very broad, very quickly, that a partnership in due course could make a lot of sense.

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Varun Kumar, Cantor Fitzgerald & Co., Research Division [8]

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Welcome, Amy.

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Amy C. Peterson, CytomX Therapeutics, Inc. - Executive VP & Chief Development Officer [9]

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Thank you, Varun.

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Operator [10]

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The next question is from Mohit Bansal with Citi.

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Mohit Bansal, Citigroup Inc, Research Division - VP and Analyst [11]

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Welcome, Amy, from my side as well. Maybe if you could start with talking a little bit about the status of your Amgen partnership, that, I don't recall if you had mentioned that on this call. And when can we see data from the AbbVie CD71 program?

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Sean A. McCarthy, CytomX Therapeutics, Inc. - Chairman, CEO & President [12]

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Great. 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 -- we're 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 Probody setting. So we're very enthusiastic about that modality. Regarding AbbVie and 2029, no guidance yet on specific timing of a program update.

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Mohit Bansal, Citigroup Inc, Research Division - VP and Analyst [13]

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Got it. Helpful. And then maybe a little bit just going back to the PROCLAIM study and the expansion plan you are planning. So just trying to understand conceptually, when you add ipi highest dose or maybe a little bit higher dose, like 3 milligrams but lower, and we're talking about what do you expect to see, would you expect to see more responses? Or do you think the path of the response is what? What would you see, based on the site prior trials, if patients can be dosed higher?

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Sean A. McCarthy, CytomX Therapeutics, Inc. - Chairman, CEO & President [14]

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So there have been studies in this patient population of ipi/nivo, specifically in the relapsed/refractory setting is pretty clear that adding ipi on top of a PD-1 inhibitor, PD inhibitor, if you like, can elicit a pretty respectable response rate. I mean the data sets are relatively small, but response rate's in the 40% range, plus or minus. And 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. Does that help answer the question?

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Mohit Bansal, Citigroup Inc, Research Division - VP and Analyst [15]

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Yes. It does.

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Operator [16]

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The next question is from Mara Goldstein with Mizuho.

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Mara Goldstein, Mizuho Securities USA LLC, Research Division - MD of Equity Research Department [17]

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So I understand you're limited as to what you might be able to say on the CX-072 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 CX-2009 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?

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Sean A. McCarthy, CytomX Therapeutics, Inc. - Chairman, CEO & President [18]

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Mara, on the second question, was that 2009 or 2029?

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Mara Goldstein, Mizuho Securities USA LLC, Research Division - MD of Equity Research Department [19]

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Sorry. On the Probody drug conjugate.

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Sean A. McCarthy, CytomX Therapeutics, Inc. - Chairman, CEO & President [20]

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Yes, on 2009. Right. Yes, 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 I study in the all-comer setting. We know that ipi/nivo at lower doses can be effective in this patient population. So we're optimistic that we're going to see something here. So -- but we're not setting specific goals from the Simon I stage just get.

Regarding 2009, again, to restate our goal between now and the end of the year is to communicate on dose and indications for moving into the expansion phase, and that's really as much as we're able to say at this point.

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Mara Goldstein, Mizuho Securities USA LLC, Research Division - MD of Equity Research Department [21]

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Okay. And if I could just follow up on the 072 program. I know it's a small number of patients, but will you be able to glean out any differences in responses between, let's say, those patients who did not have any initial response to checkpoint inhibitors to those who lost response?

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Sean A. McCarthy, CytomX Therapeutics, Inc. - Chairman, CEO & President [22]

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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 I stage.

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Operator [23]

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The next question is from Boris Peaker with Cowen.

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Boris Peaker, Cowen and Company, LLC, Research Division - MD & Senior Research Analyst [24]

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My first question is on 072 and, I guess, maybe addressed to Amy. Just from the regulatory perspective, if you decide to advance the 072 into pivotal combo studies with ipi, will you have to include monotherapy arm of 072 or monotherapy if ipi or some kind of for combinatorial reasons?

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Sean A. McCarthy, CytomX Therapeutics, Inc. - Chairman, CEO & President [25]

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Boris, this is Sean. Let me kick that one off and then hand over to Amy. So 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 could do for us in this area of high unmet 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.

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Amy C. Peterson, CytomX Therapeutics, Inc. - Executive VP & Chief Development Officer [26]

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Yes. 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. So 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.

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Boris Peaker, Cowen and Company, LLC, Research Division - MD & Senior Research Analyst [27]

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Great. And further on the PROCLAIM 072 study, when will we see monotherapy data? And how important is monotherapy activity?

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Sean A. McCarthy, CytomX Therapeutics, Inc. - Chairman, CEO & President [28]

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So we continue to -- as I mentioned 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.

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Boris Peaker, Cowen and Company, LLC, Research Division - MD & Senior Research Analyst [29]

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

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Sean A. McCarthy, CytomX Therapeutics, Inc. - Chairman, CEO & President [30]

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

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Operator [31]

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The next question is from Biren Amin with Jefferies.

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Biren N. Amin, Jefferies LLC, Research Division - MD and Senior Equity Research Analyst [32]

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Sean, maybe can you talk a little bit about the big picture on 072. The compound has been in the clinic since end of 2016. However, I think what we've seen with other companies is that they've been somewhat creative in terms of pivotal single-arm studies in other tumor types and have just been, I think, more aggressive. So at what point can we expect that from CytomX and 072?

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Sean A. McCarthy, CytomX Therapeutics, Inc. - Chairman, CEO & President [33]

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Well, it's -- Biren, 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 CX-072 because as a Probody, not an antibody, and the first Probodies are going to 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, showing that the drug clearly is active as a prodrug antibody, it's effective, it's effective in combination with ipi. And we've now announced a very clear next step in an area of significant unmet medical need taking the combination into relapsed/refractory melanoma.

As we said on the call, we do believe that there's going to be potential for the ipi/072 combination potentially in a range of different tumor types where we already know that ipi/nivo is effective, but has not been advanced due to toxicity issues or not being able to dose high enough.

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.

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Biren N. Amin, Jefferies LLC, Research Division - MD and Senior Equity Research Analyst [34]

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Got it. And then 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 ipi/nivo so we can actually delineate the differentiation of 072? And then, I guess, a second part of the question is, given PD-1 is 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?

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Sean A. McCarthy, CytomX Therapeutics, Inc. - Chairman, CEO & President [35]

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Yes, great question. The -- it's a stepwise thing, isn't it? So at this stage, we think this is the right experiment to do for the Probody. And given the unmet medical need in this patient population, exposing these patients to 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, Biren.

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Biren N. Amin, Jefferies LLC, Research Division - MD and Senior Equity Research Analyst [36]

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Got it. Okay. And then, I guess, on -- you mentioned that at some point, you would evaluate a partnership for 072. Can you just talk about where your efforts are for CX-188, the PD-1 Probody? I believe you're evaluating partnerships for that program as well.

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Sean A. McCarthy, CytomX Therapeutics, Inc. - Chairman, CEO & President [37]

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Well, as you know, the PD-1 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.

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Operator [38]

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The next question is from Terence Flynn with Goldman Sachs.

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Terence C. Flynn, Goldman Sachs Group Inc., Research Division - MD [39]

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Maybe, again, just another big picture one. Sean, you referred to some of the recent Bristol data for Opdivo, Yervoy in front line 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 II trial that you're expecting them to advance into?

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Sean A. McCarthy, CytomX Therapeutics, Inc. - Chairman, CEO & President [40]

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Terence, second question...

(technical Difficulties]

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Operator [41]

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Ladies and gentlemen, please stand by.

Okay. We'll go with Robert Burns with H.C. Wainwright.

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Robert John Burns, H.C. Wainwright & Co, LLC, Research Division - Associate [42]

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So just 2, if I may. So as we saw from the press release last week across the 27 patients in the Phase I PROCLAIM-CX-072 dose escalation trial, 33% of patients experiencing G3/4 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 us some color as to what percentage of first-line melanoma patients currently receive Opdivo plus Yervoy or just an anti-PD-1 monotherapy regimen?

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Sean A. McCarthy, CytomX Therapeutics, Inc. - Chairman, CEO & President [43]

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Robert, good to hear from you. So we have 20 patients in the study treated at 3 mg per kg of ipi, and I believe I'm right in saying that the response rate among those patients is 25%, and hence, the Grade 3 (inaudible) is the same. It's 25%. So you're right, that 33% number is a slight uptick from what we presented previously, but the numbers broadly speaking in this study have held up really very well since the first presentation.

Does that help?

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Robert John Burns, H.C. Wainwright & Co, LLC, Research Division - Associate [44]

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Yes, that helps. And then just some color as to overall treatment patterns and prescribing patterns within first-line melanoma would be helpful, if you can?

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Sean A. McCarthy, CytomX Therapeutics, Inc. - Chairman, CEO & President [45]

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Yes. Let me hand that with Amy to comment on that.

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Amy C. Peterson, CytomX Therapeutics, Inc. - Executive VP & Chief Development Officer [46]

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Yes. So we obviously were very thoughtful in how we decided on this particular cohort. And although treatment or prescription patterns in frontline melanoma in U.S. and predominantly at academic centers focuses more on the combination, we found that, that is not actually necessarily true when we go out into the community where physicians are really more focused on minimizing the side effect profile and increasing tolerability. And oftentimes, they will withhold the CTLA-4 agents until the patients have progressed and/or they've determined that an additional agent is as needed.

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?

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Operator [47]

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And there are no further questions.

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Christopher S. Keenan, CytomX Therapeutics, Inc. - VP of IR & Corporate Communications [48]

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All right. Operator, thank you very much. Sean?

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Sean A. McCarthy, CytomX Therapeutics, Inc. - Chairman, CEO & President [49]

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Yes, 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 through 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 a data-rich and milestone-rich 2020. So thank you again for your time.

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Operator [50]

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Ladies and gentlemen, thank you for participating in today's conference call. You may now disconnect.