Q4 2019 Earnings Call

Good day, ladies and gentlemen, and welcome to decide to make therapeutics fourth quarter 2019, and full year financials conference call.

Operator: Good morning, ladies and gentlemen, and welcome to the CytomX Therapeutics Fourth Quarter 2019 and Full Year Financials Conference Call. At this time, all participants are in a listen-only mode. As a reminder, this call may be recorded. I would now like to introduce your host for today's conference, Christopher Keenan, Vice President of Investor Relations. Chris, you may begin.

Hi, all participants are in listen only mode. As a reminder, it's called May be recorded.

I'd now like to introduce your host for today's conference Christopher Kenan, Vice President of Investor Relations, Chris You may begin.

Christopher Keenan: Thank you, Lee. Good afternoon, and thank you for joining us. Earlier today, we issued a press release that included a summary of our recent progress in fourth quarter 2019 and full year 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 President, Chief Executive Officer, and Chairman, Dr. Sean McCarthy.

Thank you Lisa good afternoon. Thank you for joining US earlier today, we issued a press release that includes a summary of our recent progress in fourth quarter 2019, and full year financial results.

This press release and a recording of this call can be found under the investors in news section of our website at <unk> Dot com.

With me today or say towards President Chief Executive Officer, and Chairman Dr., John Mccarthy say Telmex, Chief Development Officer, Dr., Amy Peterson, and say Thomas Vice President of Finance Robin Nixon.

Sean A. McCarthy: John McCarthy, CytomX Chief Development Officer Dr. Amy Peterson, and CytomX Vice-Chancellor

Robin Nifson: and Representative of Finance, Robin Nifson. 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-K filed today. We undertake no obligation to update any forward-looking statements, whether as a result of new information, future developments, or others. I would now like to turn the call over to Sean.

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 in many of which are outside of our control.

Important risks and uncertainties are set forth in our most public recent filings with the FCC at FCC dotcom, including our form 10-K filed today, we undertake no obligation to update any forward looking statements whether as a result of new information future developments or otherwise I would now like to turn the call over Sean.

Sean A. McCarthy: [inaudible]

Sean A. McCarthy: Great. Thank you very much, Chris, and good afternoon, everyone. Thanks very much for joining us. It's a pleasure to be here to provide an update on our progress during the fourth quarter and throughout 2019. I'll begin with an overview and some recent highlights across the pipeline, and we'll then turn the call over to Amy to review our LEAD CX-072 and CX-2009 programs in more depth. Robin will then review our fourth quarter and four-year financial update, and I'll wrap up with upcoming 2020 milestones before opening up the call for questions.

Great. Thank you very much Chris and good afternoon, everyone. Thanks, very much for joining us it's a pleasure to be here to provide an update on our progress through the fourth quarter and throughout 2019.

I'll begin with an overview and some recent highlights across the pipeline and we'll then turn the call I would say maybe to review our lead six or seven two and since 2009 programs in more depth Robin will then review, our fourth quarter and fully up and actually what they and I'll wrap up with upcoming Twentytwenty milestones before opening up the team for questions.

Sean A. McCarthy: At CytomX, we see a major opportunity to more effectively target therapeutic antibodies into disease tissue, generating new classes of anticancer therapy. We believe our unique pro-body therapeutic platform represents a fundamental advance, and we are highly focused on the discovery and development of a broad clinical pipeline of novel drug candidates to make a meaningful difference in the treatment of cancer. Our unique science offers the potential for new and highly effective anti-cancer therapies, including potentially best-in-class molecules against validated targets, first-in-class molecules against novel undruggable targets, and new combination therapies. 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 the cat's tissue by certain disease-associated proteins called proteases.

That's why topics, we see a major opportunity to more effectively target therapeutic antibodies into diseased tissue generating new classes of anticancer therapies.

We believe our unique property therapeutic platform represents a fundamental advance and we are highly focused on the discovery and development of a broad clinical pipeline of novel drug candidates to make a meaningful difference in the treatment of cancer.

Our unique science offers the potential for new and highly effective anticancer therapies.

Putting potentially best in class molecules, I guess validated targets.

First in class molecules, I guess novel Undruggable targets and you combination therapies.

Properties are fully ready competence antibody pro drugs comprised of a therapeutic antibody and they mosque designed to book the findings the antibody to its target until the mask is removed Moscow removal is achieved specifically and selectively within cast the tissue by certain disease associated proteins cool proteases.

Sean A. McCarthy: This allows us to localize antibody activity into cancer tissue, decreasing target engagement in normal tissues, and broadening, or in fact, even creating a therapeutic window. We have pioneered this new approach that we see as an important evolution of the therapeutic antibody field, with broad potential to improve and optimize a range of antibody formats including cancer immunotherapies, antibody drug conjugates, and T-cell engagement by specific antibodies. This is an exciting time for our company as our pipeline continues to mature, as our partnerships advance, and as our research engine continues to produce innovative new molecules. In total, today, we have more than 20 programs at various stages of discovery and development within our proprietary pipeline and in collaboration with our partners.

This allows us to localize antibody activity into cancer tissue decreasing target engagement in normal tissues and voting or in fact, even creating a therapeutic window.

We have pioneered this new approach that we see as an important evolution of the therapeutic antibody field with broad potential to improve and optimize a range of antibody formats, including cancer Immunotherapies I study drug conjugates and teesside engaging by specific antibodies.

This is an exciting time for our company is a pipeline continues to mature as our partnerships advanced and as our research engine continues to produce innovative new molecules.

In total today, we have more than 20 programs at various stages of discovery and development within our proprietary pipeline and in collaboration with our partners.

Sean A. McCarthy: Since our first presentation of clinical data for our platform less than two years ago, we have now generated and presented a wealth of data to support clinical proof of concept for our technology. And our three most advanced programs have all recently progressed into focused phase two clinical studies. We expect to provide several significant data updates throughout 2020.

Since our first presentation of clinical data for our platform less than two years ago. We have not generated in presented a wealth of data to support clinical proof of concept for technology and a three most advanced programs civil recently progressed into focus to phase two clinical studies.

We expect to provide several significant data updates throughout 2020.

Sean A. McCarthy: Earlier this week, we announced an important pipeline milestone in our foundational oncology collaboration with Bristol-Myers Squibb. The leading edge of this alliance is the anti-CTLA-4 probiotic BMS 986249. CCLA-4, the target of ipilimumab, is the prototypical checkpoint target, and blocking this mechanism has proven highly effective, both as monotherapy and in combination with PD pathway inhibitors, in the treatment of patients with melanoma and in many other cancers. While a very important advance, ipilimumab can cause severe immune-related toxicities, creating a clear opportunity for a pro-body version of this agent to improve tolerability, increase duration of treatment, and potentially improve activity.

Earlier this week, we announced an important pipeline milestone in our foundational oncology collaboration with Bristol Myers Squibb.

The leading edge of this alliance is the ITC theater at full price body BMS 986 to four nine.

CBLI for the target it believing that is the prototypical checkpoint target and blocking this mechanism has proven highly effective both as monotherapy and in combination with PD pathway inhibitors in the bread treatments to patients with melanoma and in many other cancer types.

What a very important advance if limit can cause severe immune related toxicities, creating a clear opportunity for a pro body version of this agent to improved tolerability increased duration of treatment and potentially improve activity.

Sean A. McCarthy: BMS and CytomX have previously presented preclinical proof of concept for CTLA-4 pro-bodies at several major research conferences, and BMS has completed enrollment now in the Phase I clinical studies with BMS 986249, the results of which we expect to see presented this year. As we announced on Monday, BMS has now initiated a randomized phase 2 expansion study evaluating the tolerability and activity of BMS 986249 plus the PD-1 inhibitor nivolumab versus nivolumab with or without ipilimumab in metastatic melanoma. The advancement of BMS-986249 into this study has triggered a milestone payment of $10 million to CytomX from BMS. This is an important study that, if positive, has the potential to place the ipilimumab probody on a registrational path. Moreover, this work is a direct embodiment of exactly what we set out to do with our platform when it was first conceived of, and we are very excited about the potential for cancer.

BMS insights I mentioned previously presented preclinical proof of concept for seats you like for probably bodies. Several major research conferences and BMS is completed enrollment now in the phase one clinical studies with BMS nine it's six to four nine the results of which we expect to see presented this year.

As we announced on Monday BMS is now initiated a randomized phase two expansion study evaluating the tolerability and activity BMS nine at 64, nine plus the PD, one inhibitor nivolumab versus in the bottom out with or without equilibrium at investor Stasik melanoma.

The advancement of BMS nine six to four nine into this study is triggered a milestone payment of $10 million to be him to sites had mix from BMS.

This is an important study that if positive has the potential to place the upper limb about probably body on a registrational tough. Moreover, this work has a direct import image of exactly what we set out to do without platform. When it was first conceived of and we're very excited about the potential for cancer patients.

Additionally, recent progress within our foundational BMS Alliance includes the initiation of the dose escalation phase of a phase 128 clinical study for a second and he's he's got a for probably body BMS 986 to eight eight which is based on a modified version of Ipilimumab.

Sean A. McCarthy: Additional recent progress within our foundational BMS alliance includes the initiation of the dose escalation phase of a Phase 1-2A clinical study for a second anti-CCLA-4 probody, BMS-986288, which is based on a modified version of ipilimumab. This second clinical probody program demonstrates BMS commitment to our technology platform as a way to potentially unlock additional value in the CTLA-4 mechanism. As these CTLA-4 programs progress through clinical development, potential regulatory approval, and commercialization, CytomX is eligible to receive certain milestone payments and royalties. And it's important to note that we also continue to work closely with BMS to initiate new discovery programs under this broad-based alliance. In addition to this progress with VMS,

The second clinical property program demonstrates BMS commitment so our technology platform as a way to potentially unlock additional value in the CCRI for mechanism.

As these CCRI four programs progress through clinical development.

Potential regulatory approval and commercialization sites I missed that is able to receive certain milestone payments royalties.

And it's important to note that we also continue to work closely with BMS to initiate new discovery programs under this broad based the lives.

In addition to this progress with BMS 2019 was eight year old many achievements. This I'd say mix within a wholly owned lead programs. The anti PDL, one property Cxo seven too and the anti CD 166, probity drug conjugate CX teaser nine we also advanced a very unique.

Program in partnership with Abbvie, the Cdseventy, one targeting probity drug conjugate CX to zero Tonight.

Yeah. So seven two is a property therapeutic directed against the validated immuno oncology target PDL one.

Sean A. McCarthy: 2019 was a year of many achievements for CytomX within our wholly owned lead programs, the Anti-PD-L1 ProBody CX072 and the Anti-CD166 ProBody Drug Conjugate CX2009. We also advanced a very unique program in partnership with AbbVie, the CD71-targeting ProBody Drug Conjugate CX2029. CX072 is a pro-body therapeutic directed against the validated immuno-oncology target PD-L1. We believe that CX072 has the potential to become a differentiated foundation for combination anti-cancer therapies by increasing tolerability, achieving optimal dosing, and delivering increased anti-cancer activity to improve patient outcomes. We have shown previously that CX072 is active as a monotherapy in multiple tumor types and that the probody has the activity to be expected from a checkpoint inhibitor, providing the first clinical proof of concept for our unique platform.

We believe this year. So seven two has the potential to become a differentiated foundation for combination anticancer therapies by increasing tolerability, achieving optimal dosing and delivering increased anticancer activity to improve patient outcomes.

We have shown previously the six or seven two as active as a monotherapy in multiple tumor types and not the president. He has the activity to be expected from a checkpoint inhibitor, providing the first clinical proof of concept for our unique platform.

In the fourth quarter, we advance yeah. So seven two into a phase two clinical trial to further evaluates the activity and Tolerability of say, so 70, plus if it believer that.

In patients with relapsed or refractory melanoma.

Building on our encouraging phase one two data. This trial is evaluating six or seven two in combination with the full labeled monotherapy dose and schedule <unk> it'd be with a goal of driving meaningful anti cancer activity in this difficult to treat patient population.

We believe this combination has the potential to become a best in class regiment, not only for melanoma, but potentially other cancer types.

Initial data is anticipated from stage one off the phase two study during twentytwenty.

Now turning to our second holier drug candidate CX users are nine appropriately drug conjugate designed to target. The previously undruggable target CD 166.

Sean A. McCarthy: In the fourth quarter, we advanced CX072 into a Phase II clinical trial to further evaluate the activity and tolerability of CX072 plus ipilimumab in patients with relapsed or refractory melanoma. Building on our encouraging Phase I-II data, this trial is evaluating CX072 in combination with the full labeled monotherapy dose and schedule of IPPE with a goal of We believe this combination has the potential to become a best-in-class regimen, not only for melanoma but potentially for other cancer types. Initial data from Stage 1 of the Phase 2 study are anticipated during 2020.

C. D wants 66 is a unique to imagine that has expressed a high levels of most solid tumors, but there's also present on most normal tissues ruling it out as a target for typical antibody drug conjugate.

We're exploring the ability of a pro body drug conjugate to unlock the potential of this target by focusing anticancer activity to tumor tissue and not normal cells.

Based on encouraging phase one clinical data, we reported last year.

We initiated in Q4 2019, a phase two expansion study of C. S. Users are nine monotherapy in patients with hormone receptor positive hertwo negative breast cancer.

This study was initiated in the fourth quarter.

And he will provide more context on this program in a few moments.

Sean A. McCarthy: Now turning to our second wholly owned drug candidate, CX2009, a pro-body drug conjugate designed to target the previously undruggable target CD166. CD166 is a unique tumor antigen that is expressed at high levels on most solid tumors, but it's also present on most normal tissues, ruling it out as a target for a typical antibody drug conjugate. We're exploring the ability of a pro-body drug conjugate to unlock the potential of this target by focusing anti-cancer activity on tumor tissue and not normal cells. Based on encouraging Phase I clinical data we reported last year, we initiated a phase 2 expansion study of CX2009 monotherapy in patients with hormone receptor positive HER2 negative breast cancer. This study was initiated in the fourth quarter. Amy will provide more context on this program in a few moments.

Now turning briefly to our collaborations and specifically within our at the Alliance we continue to enroll patients in the dose escalation and refinement phase of the proclaims CX to zero to nine phase one two study evaluating monotherapies see excuse or two nine a first in class property drug conjugate targeting cdseventy, one and this is in patients with.

Solid tumors.

This is a very novel and ambitious program Cdseventy ones biological role is to function as what we call a professional internalize or as it moves iron from the extra cellular space to intercellular compartments and it does have an old inviting cells.

Cdseventy one is in fact, the gold standard internalize it used to assess ADCC activity in vitro.

Now, while an attractive targets of payload delivery to cancer cells. It has remained undruggable and in fact, we have showed an 80 season at 80 see the Cdseventy one is legally toxic in preclinical models.

The partnership would that be we've created a property drug conjugate cfptwos rights, United in which a mouse antibody to Cdseventy. One is conjugated to the size totally payload MME E.

Sean A. McCarthy: Now, returning briefly to our collaborations, and specifically within our AbbVie Alliance, we continue to enroll patients in the dose escalation and refinement phase of the Proclaim CX2029 Phase 1-2 study, evaluating Monotherapy CX2029, a first-in-class pro-body drug conjugate targeting CD71 in patients with solid tumors. This is a very novel and ambitious program. CD71's biological role is to function as what we call a professional internalizer, as it moves iron from the extracellular space to intracellular compartments, and it does so in all dividing cells.

Dose escalation in the clinic was initiated in mid 2018, I just ongoing as we progressed towards as we progress towards the selection of a recommended phase two dose.

We anticipate the presentation of initial data from this exploratory clinical work in 2020.

Just a study progress the cohorts expansions at the recommended phase two days, we anticipate the presentation of proof of concept data in 2021.

For this program. So I said mix has responsibility to advance it through initial proof of concept where phone if successful the program will transition to Abbvie for Registrational studies that ultimate commercialization such that makes retains profit split and certain co commercialization rights for this asset.

Before handing the call over to Amy for more detail on our lead programs I spend a few moments on two earlier stage programs that are emerging as potential as a potential second wave of ideal candidates in our pipeline.

Sean A. McCarthy: CD71 is, in fact, the gold standard internalizer used to assess ADC activity in vitro. Now, while an attractive target for payload delivery to cancer cells, it has remained undruggable, and in fact, we have shown that an ADC to CD71 is lethally toxic in preclinical models. In partnership with AbbVie, we created a pro-body drug conjugate, CX2029, in which a masked antibody to CD71 is conjugated to the cytotoxic payload, MMAE. Dose escalation in the clinic was initiated in mid-2018 and is ongoing as we progress towards the selection of a recommended phase 2 dose. We anticipate the presentation of initial data from this exploratory clinical work in 2020. Should the study progress to cohort expansions at the recommended phase 2 dose, we anticipate the presentation of proof-of-concept data in 2021. For this program, CytomX has the responsibility to advance it through initial proof of concept, whereupon, if successful, the program will transition to AbbVie for registrational studies and ultimate commercialization. CytomX retains a profit split and certain co-commercialization rights for this asset.

Starting with our collaboration with Immunogen from whom in Q4, we obtained exclusive worldwide development and commercial rights to an EPS cabin targeting property drug conjugate.

This program was developed utilizing sites have its probably technology and Immunogens drug conjugate technology under rose from my previous strategic collaboration between the parties.

At the 2018 European antibody Congress and also at Ace Yara 2019.

Immunogen presented encouraging preclinical data demonstrating that an Afghan property drug conjugate has posted sense it potent activity and it'd be better efficacy models as well as improved tolerability and exposure compared to an unmatched abcam antibody drug conjugate.

So tell me that was full development control and commercial rights for this promising programs.

Another promising preclinical program is our T cell by specific probably body targeting each fr. Cdthree. This program is part of with Amgen with sites embodies retaining development control and certain commercial rights.

We're really excited about the prospects for the T cell by specific application of properties to enable solid tumor targeting of this modality.

Solid tumor targeting with unbiased piece up by specifics has been very challenging for the field, she's a narrow or non existant therapeutic window.

Sean A. McCarthy: Before handing the call over to Amy for more detail on our lead programs, I'd like to spend a few moments on two earlier stage programs that are emerging as potential second wave IND candidates in our pipeline, starting with our collaboration with Immunogen, from whom we obtained exclusive worldwide development and commercial rights to an Epcam targeting pro-body drug conjugate in Q4. This program was developed utilizing CytomX ProBody technology and Immunogen's Drug Conjugate technology and arose from previous strategic collaboration between the parties at the 2018 European Antibody Congress and also at AACR 2019. Immunogen presented encouraging preclinical data demonstrating that an EPCAM pro-body drug conjugate has potent activity in in vivo efficacy models, as well as improved tolerability and exposure compared to an unmasked EPCAM antibody drug conjugate.

We anticipate advancing a lead clinical candidate for this program during 2020.

So now let me turn the call over to Amy Thanks, Sean I'm pleased to be here today to report on the great progress and continue to make with our lead wholly owned programs Cxos seven to NCS, two 009, including studies that set us up to answer important question over the next one to two years.

Let's begin with our lead program.

Seven too.

As previously reported patient enrollment is complete for the part D expansion cohort studying CFO seven two at the dose of 10 milligrams per kilogram administered intravenously every two weeks to patients with multiple tumor type and we expect to present, a summary of our finding from these expansion cohort this year.

Data presented at the date most recently at ASCO 2019 showed that Cxos seven two functions as a checkpoint inhibitor demonstrating encouraging activity were one would expect to see it was such agents, including triple negative breast cancer.

Sean A. McCarthy: CytomX now has full development control and commercial rights for this promising program. Another promising preclinical program is our T-cell bispecific probiotic targeting EGFR and CD3. This program is partnered with Amgen, with CytomX retaining development control and certain commercial rights. We're really excited about the prospects for the T-cell bispecific application of probiotics to enable solid tumor targeting of this modality. Solid tumor targeting with unmasked T-cell bispecifics has been very challenging for the field due to a narrow or non-existent therapeutic window. We anticipate advancing a lead clinical candidate for this program during 2020. So now, let me turn the call over to Amy.

I'll squamous cell carcinoma and titanium.

Carcinoma.

Yes, Oh, seven to Tolerability appears favorable as well and well numbers are too small to be clinically significant trends toward lower rate of immune mediated adverse events have been observed.

Michael Pharmacokinetic and biopsy data has shown that the cxos seven to pro body behaves as designed that is it remains man in the circulation and becomes unrest in tumor tissue, resulting an intra tumoral saturation of the target and anti tumor activity.

These findings provides an important clinical proof of concept for our platform and a strong rationale for differentiation of CX Oh, seven tail from other PD inhibitors and support combination strategies with other anti cancer agents.

Given that combination therapy is likely to be required to make continued significant improvements in patient outcome. We're focusing our efforts on CX 072 combination and any immediate term specifically on the combination of cxos seven to with its aluminum.

Amy Peterson: Thanks, Sean. I'm pleased to be here today to report on the great progress we continue to make with our lead wholly-owned programs CX-072 and CX-2009, including studies that set us up to answer important questions over the next one to two years. Let's begin with our lead program, CX 072. As previously reported, patient enrollment is complete for the Part D expansion cohorts studying CX072 at the dose of 10 milligrams per kilogram administered intravenously every two weeks to patients with multiple tumor types, and we expect to present a summary of our findings from these expansion cohorts this year. Data presented to date, most recently at ASCO 2019, showed that CX072 functions as a checkpoint inhibitor, demonstrating encouraging activity where one would expect to see it with such agents, including triple negative breast cancer, anal squamous cell carcinoma, and cutaneous squamous cell carcinoma. CX072 tolerability appears favorable as well.

During our last quarterly update I didn't multiple clinical trials evaluating regimen involving a PD inhibitor pluses CTL before inhibitor, where significant reductions in dose intensity of either agent, although more commonly with the T. Kelly for inhibitor have been required in order to maintain it.

Trouble safety profile for patients.

There are multiple studies demonstrating dose dependent anti cancer activity from if aluminum to date no. One has been able to combine full doses of CTL its or an impression with full day. This is a PD inhibition. We are interested to determine the extent to which are pro body platform can enable the combination of fold.

Yes, PD inhibition here in the form of Cxo seven to placeholder illumina.

Accordingly in Q4 2019, we advanced into an open label non randomized multicenter Simon two stage phase two trial I've see if it was seven two in combination with Ipilimumab in patients with advanced melanoma, who had previously.

Amy Peterson: And while numbers are too small to be clinically significant, trends towards lower rates of immune-mediated adverse events have been observed. Clinical pharmacokinetic and biopsy data have shown that the CX072 ProBody behaves as designed. That is, it remains masked in the circulation and becomes unmasked in tumor tissue, resulting in intratumoral saturation of the target and antitumor activity. These findings provide an important clinical proof-of-concept for our platform and a strong rationale for differentiation of CX072 from other PD inhibitors and support combination strategies with other anti-cancer agents. Given that combination therapy is likely to be required to make continued significant improvements in patient outcomes, we are focusing our efforts on CX072 combinations and, in the immediate term, specifically on the combination of CX072 with ipilimumab.

Congrats on a PD pathway inhibitor.

MS Phase two trial patients are receiving ipilimumab at its full approved monotherapy label dose and schedule of three milligrams per kilogram every three weeks for four cycles.

Yes, 072 at a fixed dose of 800 milligrams every three weeks for four cycles.

Upon completion of this combination patients can receive continued treatment with 800 milligram Cxos 17 monotherapy administered intravenously every two weeks.

The primary objective of this study is overall response rate with the secondary objectives being safety Tolerability and other markers of clinical activity, including progression free and overall survival as well as the duration of response in those patients achieving partial and who are complete responses.

Amy Peterson: During our last quarterly update, I cited multiple clinical trials evaluating regimens involving a PD inhibitor plus a CTLA-4 inhibitor, where significant reductions in dose intensity of either agent, although more commonly with the CTLA-4 inhibitor, have been required in order to maintain a tolerable safety profile for patients. Additionally, there are multiple studies demonstrating dose-dependent anti-cancer activity from ipilimumab. To date, no one has been able to combine full doses of CTLA-4 inhibition with full doses of PD inhibition.

Stage one of this trial aims to enroll up to 40 patients and we hope to have initial data from the stage of the study in 2020.

To summarize there are now two important studies underway evaluating pro bodies in patients with melanoma. Each study is designed to show how these novel combinations could improved tolerability and lead to better outcomes for patients.

There's a lot to learn from each study most importantly, the ability. This platform offers to improve the risk benefit from Io based therapy in people with cancer were excited about these two studies and look forward to learning from each.

Amy Peterson: We are interested in determining the extent to which our ProBody platform can enable the combination of full-dose PD inhibition here in the form of CX072 plus full-dose ipilimumab. Accordingly, in Q4 2019, we advanced into an open-label, non-randomized, multi-center, Simon 2 stage phase 2 trial of CX072 in combination with ipilimumab in patients with advanced mel In this Phase 2 trial, patients are receiving ipilimumab at its full approved monotherapy labeled dose and schedule of 3 mg per kg every 3 weeks for 4 cycles, plus CX072 at a fixed dose of 800 mg every 3 weeks for 4 cycles. Upon completion of this combination, patients can receive continued treatment with 800 mg CXO72 monotherapy administered intravenously every two weeks.

I'd like to now turn attention to see exit two 009, our pro body drug conjugate targeting CD 166, an 80 see with a co body mass.

In the fourth quarter of Twain team, we initiated an open label non randomized multicenter phase two study of CX to 009 monotherapy in up to 40 patients with hormone receptor ERP are positive and hertwo negative breast cancer. This sub type of breast cancer remains uncertain.

Damsel area of unmet medical need and in this study Cfptwos years. Your line is being administered intravenously at seven milligrams per kilogram every three weeks to this population.

The initiation of this expansion say follows our presentation of encouraging dose escalation phase one data and E. R 20 thinking.

Amy Peterson: The primary objective of this study is overall response rate, with the secondary objectives being safety, tolerability, and other markers of clinical activity, including progression-free and overall survival, as well as the duration of response in those patients achieving partial and or complete responses. Stage one of this trial aims to enroll up to 40 patients, and we hope to have initial data from this stage of the study in 2020. To summarize, there are now two important studies underway evaluating pro-bodies in patients with melanoma. Each study is designed to show how these novel combinations can improve tolerability and lead to better outcomes for patients. There is a lot to learn from each study.

As you heard from Sean CD 166 is widely expressed both on tumor and normal tissue precluding the development of the CD 166 targeting antibody drug conjugate due to expected systemic toxicity.

We have leveraged our pro body technology to mitigate binding CX to 009 to normal tissue, thereby creating a therapeutic window for this novel target.

Our phase one dose escalation trial was designed to gain a comprehensive look at the safety profile of this novel drug Con, Canada as well as assess exploratory marker supporting the hypothesis behind this platform.

Amy Peterson: Most importantly, the ability this platform offers to improve the risk benefit from IO-based therapy in people with cancer. We're excited about these two studies and look forward to learning from each. I'd like to now turn attention to CX2009, our pro-body drug conjugate targeting CD166, an ADC with a pro-body map. In the fourth quarter of 2019, we initiated an open-label, non-randomized, multi-center Phase 2 study of CX2009 monotherapy in up to 40 patients with hormone receptor ERPR positive and HER2 negative breast cancer. This subtype of breast cancer remains a substantial area of unmet medical need, and in this study, CX2009 is being administered intravenously at 7 milligrams per kilogram every three weeks to this population.

Well not expected in a dose escalation study in the heavily pretreated and heterogeneous patient population preliminary signs of single agent anticancer activity were observed and presented a CR training team.

As a reminder, the payload conjugated to see X two 009 SDM for a may tanzim derivative.

Based on work conducted by Immunogen from whom we licensed the payload the toxicities associated with DM for our well documented and are predominantly okcular and our neuropathic in nature.

Payload toxicities typically define the MTD of drug conjugates and it's important to note that we would expect us to be the same for pro bodies as for antibodies since in the pro body. It has the antibody that as math not the payload.

Amy Peterson: The initiation of this expansion study follows our presentation of encouraging dose escalation phase 1 data at AACR 2019. As you heard from Sean, CD166 is widely expressed both on tumor and normal tissue, precluding the development of a CD166 targeting antibody drug conjugate due to expected systemic toxicity. We have leveraged our ProBody technology to mitigate binding of CX2009 to normal tissue, thereby creating a therapeutic window for this novel target. Our phase one dose escalation trial was designed to gain a comprehensive look at the safety profile of this novel drug candidate, as well as assess exploratory markers supporting the hypothesis behind this platform. While not expected in a dose escalation study in a heavily pretreated and heterogeneous patient population, preliminary signs of single-agent anti-cancer activity were observed and presented at AACR 2019.

Our pro body drug conjugate strategy is to drive and Druggable target.

By achieving the maximum tolerated dose of the payload, but with serious but without the serious on target off tumor toxicities.

Specifically the CD with PD 166, we're seeking to avoid on target toxicity is expected to occur in Oregon's worst TD 166 is highly expressed for example in colon pancreas and lung and indeed, we were able to escalate up to 10 milligrams per kilogram eight.

No that to our knowledge has never been previously been it has never been previously administered with any DC.

As we did as expected.

Observed payload toxicities, including care tighter and neuropathies.

Amy Peterson: As a reminder, the payload conjugated to CX2009 is DM4, a Maytanzin derivative. Based on work conducted by ImmunoGen, from whom we licensed the payload, the toxicities associated with DM4 are well documented and are predominantly ocular and or neuropathic in nature. Payload toxicities typically define the MTD of drug conjugates, and it's important to note that we would expect this to be the same for pro-bodies as for antibodies since in the pro-body, it is the antibody that is masked, not the payload.

Taken together these findings demonstrate clearly that our masking strategy was effective in protecting against on tumor often on target off tumor toxicities.

And what was even more encouraging as we reported a CR in 2019 was that in patients who received.

More than or equal to four milligrams per kilogram of T. X 200, 938% achieved tumor shrinkage and 74% achieved stable disease or better at the time of the first on treatment scan.

Observed anti cancer activity included seven unconfirmed partial responses in breast cancer, including Hertwo negative hormone receptor positive breast cancer, ovarian cancer and head and neck cancer.

Amy Peterson: Our pro-body drug conjugate strategy is to target undruggable targets by achieving the maximum tolerated dose of the payload, but without the serious on-target, off-tumor toxicity. Specifically, with CD166, we are seeking to avoid on-target toxicities expected to occur in organs where CD166 is highly expressed, for example, in the colon, pancreas, and lung. And indeed, we were able to escalate the dose up to 10 milligrams per kilogram, a dose that, to our knowledge, has never been previously administered with any ADC. And we did, as expected, observe paleotoxicities, including keratitis and neuropathies.

This risk benefit profile compares well to early phase one experience for other NBC is that have advanced into Registrational studies and supports the further development of this asset.

We anticipate announcing more complete data from the CX to 009 phase one dose escalation trial in 2020.

And we anticipate initial data from the breast cancer phase two expansion trial in 2021.

We're also very interested in the potential of CX to 009, plus Cxos seven two combination we think when we think about the types of therapies that have been most successfully combined with PD inhibitors in terms of improvements in risk benefit profile, we can't ignore the improved outcomes.

Amy Peterson: Taken together, these findings demonstrate clearly that our masking strategy was effective in protecting against on-tumor, on-target, and off-tumor toxicities. And what was even more encouraging, as we reported at AACR in 2019, was that in patients who received more than or equal to 4 mg per kg of CX2009, 38% achieved tumor shrinkage, and 74% achieved stable disease or better at the time of the first on-treatment scan. Observed anti-cancer activity included seven unconfirmed partial responses in breast cancer, including HER2 negative, hormone receptor positive breast cancer, ovarian cancer, and head and neck cancer. This risk-benefit profile compares well to early Phase I experience for other ADCs that have advanced into registrational studies and supports the further development of this asset. We anticipate announcing more complete data from the CX2009 Phase I dose escalation trial in 2020, and we anticipate initial data from the breast cancer Phase II expansion trial in 2021.

I've been observed in combination with cytotoxic agents. Furthermore, there is growing evidence that PD inhibition can be successfully combined with 80 fees. We therefore also plan to evaluate the tolerability of the combination of Cxos seven two plus CX to 009 to identify a combination dosing regimen to it.

Dancing indication, where both agents and demonstrated simulation activity.

Turning to our organization, we continue to strengthen the development capabilities of the company and most recently announced the appointment of Dr. Allison Hannah to the role of senior Vice President and Chief Medical Officer reporting directly into me.

Allison joins my team with 30 years of relevant experience in clinical drug development in oncology and malignant hematology prior to joining us she let her own consultancy, where she advise pharmaceutical and biotechnology clinical teams, resulting in successful filing of over 40 regulatory applications for first in human clinical testing well.

Also playing significant roles in the broad marketing approval approval of eight therapeutics, including extensive experience interacting with global health and regulatory authorities.

Amy Peterson: We're also very interested in the potential of CX2009 plus CX072 combinations. We think when we think about the types of therapies that have been most successfully combined with PD inhibitors in terms of improvements in risk-benefit profiles, we can't ignore the improved outcomes that have been observed in combination with cytotoxic agents. Furthermore, there is growing evidence that PD inhibition can be successfully combined with ADCs. We therefore also plan to evaluate the tolerability of the combination of CX072 plus CX2009 to identify a combination dose and regimen to advance an indication where both agents have demonstrated single-agent activity.

Been fortunate to have worked with Allison during my time at Beijing, and Medivation and look forward to her many contributions during this important time in the advancement of our pipeline assets I told me.

I will now turn the call on the call over to Robin for a review of financial. Thank you Amy I would like to review selected financial highlights for the year 2019, we ended the year with cash cash equivalents and investments totaling 296.1 million compared to 436.1 million as of December.

31st 2018.

Our strong balance sheet allows us to comfortably find operations into the second half of 2021, assuming no new collaboration and or financing.

Research and development expenses were 132 million for the year compared to 104 million the corresponding period in 2018.

Amy Peterson: Turning to our organization, we continue to strengthen the development capabilities of the company and most recently announced the appointment of Dr. Allison Hanna to the role of Senior Vice President and Chief Medical Officer reporting directly into me. Allison joined my team with 30 years of relevant experience in clinical drug development in oncology and malignant hematology. Prior to joining us, she led her own consultancy, where she advised pharmaceutical and biotechnology clinical teams, resulting in the successful filing of over 40 regulatory applications for first-in-human clinical testing, while also playing significant roles in the broad marketing approvals of eight therapeutics, including extensive experience interacting with global health and regulatory authorities. I've been fortunate to have worked with Allison during my time at Beijing and Medivation and look forward to her many contributions during this important time in I will now turn the call over to Robin for a review of the financials.

The increase was primarily attributable to additional costs related to our maturing pipeline, including personnel related expenses.

In 2019, we incurred approximately 16 million of nonrecurring charges related to the acquisition of Tech logical no license fees tcs be associated with entering into the amendment would be CSP and the license fee for the F. Cam program.

General and administrative expenses were 37 million compared to 34 million and the corresponding period in 2018.

Revenue for the year was 57.5 million compared to 59.5 million and the corresponding here.

The decrease was primarily due to a 13.1 million decreasing revenue from Abbvie under the CD 71, who development and licensing agreement leading to the 21 million dollar milestone payment net of the associated sub license fees.

In May 2018 of which the 11.7 billion was recognized in 2018.

Robin Nifson: Thank you.

Robin Nifson: I would like to review selected financial highlights for the year 2019. We ended the year with cash, cash equivalents, and investments totaling $296.1 million, compared to $436.1 million as of December 31, 2018. Our strong balance sheet allows us to comfortably fund operations into the second half of 2021, assuming no new collaborations or financing.

In addition, there's a slight decrease in revenue under our agreement with Amgen and decreases relating to the Pfizer any religion collaboration which concluded in 2018.

The decreases were partially offset by an increase in revenue from Bristol Myers Squibb due to the accelerated revenue recognition bleed into the cessation of research on certain targets under our agreement with Bristol Myers Squibb in the first quarter of 2019.

With that I will turn the call back over to Sean.

Robin Nifson: Research and development expenses were $132 million for the year, compared to $104 million for the corresponding period in 2018. The increase was primarily attributable to additional costs related to our maturing pipeline, including personnel-related expenses. In 2019, we incurred approximately $16 million of non-recurring charges related to the acquisition of technological know-how, license fees to UCSB associated with entering into the amendment with UCSB, and the license fee for the EPCAM program. General and administrative expenses were $37 million compared to $34 million in the corresponding period in 2018. Revenue for the year was $57.5 million compared to $59.5 million in the corresponding year. The decrease was primarily due to a $13.1 million decrease in revenue from AVDII under the CD71 co-development and licensing agreement relating to the $21 million milestone payment net of the associated sublicense fees earned in May 2018, of which $11.7 million was recognized in 2018.

Great. Thanks, Robin so in closing.

Let me briefly review our anticipated 2020 milestones.

For six or seven to our PDL one pro body, we anticipate presentation of final monotherapy data for the expansion arms and multiple selected tumor types building on our ESCO 2019 presentations of last year.

We also for the six or seven two if he combination and we're not refractory melanoma. We anticipate initial data from stage one of the ongoing phase two study.

For six 2009, or CD was 66 targeting property drug conjugate.

We anticipate presentation of updated phase, one dose escalation and dose ranging data to support the dosing indication selection for the ongoing phase two study you've heard about today.

And then for six to there are two nine or Cdseventy, one property drug conjugate. We anticipate initial data from the phase one dose escalation portion of the phase one two study with additional proof of concept. They said from expansion cohorts targeted for 2021, assuming that the program transitions to that stage.

Robin Nifson: In addition, there was a slight decrease in revenue under our agreement with Amgen and decreases relating to the Pfizer and Immunogen collaborations, which concluded in 2018. However, the decreases were partially offset by an increase in revenue from Bristol-Myers Squibb due to the accelerated revenue recognition related to the cessation of research on certain targets under our agreement with Bristol-Myers Squibb in the first quarter of 2019. With that, I will turn the call back over to Sean.

Also and as I mentioned earlier on in my remarks.

We do anticipate that BMS will present, the phase one data for the it'd be probity BMS 96 to four nine sometime this year.

And that of course would be the data that has supported the announcement that we made this week regarding their entry into the randomized phase two study of the it'd be probably bodies of rural very very excited about so.

So thanks, everyone for taking some time to join US today, it's obviously been a turbulent out there in the markets.

But we're very pleased with the broad progress we've made a slight time as last year and continuing into this year, both with our very unique technology platform, but also with our boxing and deepening clinical pipeline and all of us on the sites that we see more excited excited for an eventful 2020 ahead. So I think what that will then turn the call.

Sean A. McCarthy: Great, thanks Robin. So in closing, let me briefly review our anticipated 2020 milestones. For CX072, our PD-L1 probody, we anticipate presentation of final monotherapy data for the expansion arms in multiple selected tumor types, building on our ASCO 2019 presentations of last year. We also, for the CX072-Ipi combination in relapsed refractory melanoma, we anticipate initial data from stage 1 of the ongoing phase 2 study. For CX-2009, our CD166-targeting pro-body drug conjugate, We anticipate presentation of updated phase 1 dose escalation and dose ranging data that support the dose and indication selection for the ongoing phase 2 study you've heard about today, and then for CX2029, our CD71 pro-body drug conjugate, we anticipate initial data from the phase 1 dose escalation portion of the phase 1-2 study with additional proof of concept data from expansion cohorts targeted for 2021, assuming that the program transitions to that stage.

But to Chris for acuity.

Lee I think we're ready to open the call for questions.

Certainly well they just and gentlemen, if you have the question at this time. Please press star and then the number one key.

Such tone telephone if your question that's been asked or are you wish to remove yourself from the Q pressed to town key well pause for just a moment.

Your first question is from Christopher MRI from Nomura Instinet. Your line is still open.

Hi, Thanks for taking my question and congrats on all the progress.

I just wonder if you could touch upon having to see 166, two 009 pro body program.

Yeah, I guess, you update us on the path forward there, including.

Hurt her to negative HR positive breast cancer.

Yeah, and that would constitute youre expansion cohort in the phase two could you maybe elaborate a little bit on a potential path to approval that could emerge from that and how that might look.

Sean A. McCarthy: Also, and as I mentioned earlier in my remarks, we do anticipate that BMS will present the Phase 1 data for IPI ProBody, BMS 986249, sometime this year, and that, of course, will be the data that supports the announcement that we made this week regarding their entry into the randomized Phase 2 study of IPI ProBody that we're all very, very excited about. So thanks, everyone, for taking some time to join us today. It's obviously been a turbulent day out there in the markets, but we're very pleased with the broad progress we made at CytomX last year and continuing into this year, both with our very unique technology platform and also with our advancing and deepening clinical pipeline, and all of us on the CytomX team are excited for an eventful 2020 ahead. So I think with that, we'll turn the call back to Chris for Q&A.

Is there go no go decision maker or lift you're looking for and then how might this fit into the evolving.

Treatment paradigm here, obviously other therapies are looking for approval in this setting as well. Thank you.

Hi, Thanks classify this as Amy Thanks for your question.

Yeah. So this study just to recap.

The first part of this study will evaluate 40 patients with hormone receptor positive hertwo negative breast cancer, while we can't disclose the details around the eligibility criteria what I can say as we have taken a sharp eye for that to ensure that the patient population is one that would be something that we can take.

Forward to global health authorities should we see activity.

Commensurate with taking the molecule forward and it is in patients who have received hormonal based therapy, we recognize that.

Operator: Lee, I think we're ready to open the call for questions. All right. Ladies and gentlemen, if you have a question at this time, please press star and then the number one key on your touchtone telephone. If your question has been answered or you wish to remove yourself from the queue, press the pound key. We'll pause for just a moment.

Other treatments are emerging.

And we are always have an eye to that but at this point in time I can't really it's evolved further details around a specifics of eligibility criteria.

Okay, then in just a follow up perhaps a pit.

Expansion component of the trial I assume.

Not be registration directed.

At what point does I told me they could go no go decision on this and run out a phase three and and even the population that you may be a selecting a in this expansion cohort. Thank you.

Christopher W. Ogden: Your first question is from Christopher Marai from Nomura, Inc. Hello, thanks for taking the question and congratulations on all the progress. I was wondering if you could touch upon the CDE-166-2009 ProBody program. I guess you updated us on the path forward there, including... her two negative HR positive breast cancers. And that would constitute your expansion cohort in phase two. Could you maybe elaborate a little bit on a potential path to approval that could emerge from that and how that might look? Is there a go, no-go decision that you're looking for? And then how might this fit into the evolving treatment paradigm here? Obviously, other treatments are looking for approval in this setting as well.

Alright, Thanks, a follow on so you're right with 40 patients that's not registrational, however, depending on what we see and depending on our discussions with health authorities. It could potentially lead to something that is registrational. If we have the right sample size.

If that answers the question.

Yeah, and then just to go no go on on data here, what do you want to see in those 40 patients and I'll jump back into queue. Thank you.

I think Chris as I.

As I mentioned Oh goal there is to have initial data on this first 40 patients in 2021, obviously, we'll take a look about data inside the path forward.

Your next question.

Your next.

Your next question is from Mohit Bansal from Citi. Your line is now open.

Hi, This is James on a form of it.

Amy Peterson: Hi. Thanks, Christopher. This is Amy.

It looks like personal now has 96 to eight eight and 96 to four nine in trials can you remind us how these two futility force differ and any insight on BMS a strategy to explore both.

Amy Peterson: Thanks for your question. Yeah, so this study, just to recap, is the first part of the study will evaluate 40 patients with hormone receptor positive for two negative breast cancer. While we can't disclose the details around the eligibility criteria, what I can say is we have taken a sharp eye to that to ensure that the patient population is one that would be something that we can take forward to global health authorities should we see hectivity commensurate with taking the molecule forward. And it is in patients who have received hormonal-based therapy. We recognize that other treatments are emerging, and we always keep an eye on that. But at this point in time, I can't really divulge further details around the specifics of the eligibility criteria.

Yes, Hi, James I'm, absolutely. So 249 is the pro body version of it be itself and I think as we've laid out that's the that's the program. This thing advanced into the randomized phase two study.

And that was the first priority.

Targeting CCR before that we made with BMS and this alliance to eight eight is as we said a modified version of it'd be a that is designed to be a more active.

Than the parental antibody I'm expecting them to probably say a bit more about this program. This year is the new leadership within BMS got their arms around these programs. So we're not at Liberty to say too much about it but.

Amy Peterson: Okay, then, and just to follow up, perhaps the expansion component of the trial, I assume, would not be registration directed. At what point does CytomX make a go, no-go decision on this and run out of phase 3? And even the population that you may be selecting in this expansion cohort. Thank you.

But we've made a property version of that modified it'd be and that has no also going into phase one dose escalation. So as I said in my in my prepared remarks, the fact that they're putting both of the book one program knows in phase two the other is moving into phase one I think it really underscores a couple of things that underscores their continue commit.

Amy Peterson: Sure, thanks for the follow-on. So you're right, with 40 patients, that's not registrational. However, depending on what we see and depending on our discussions with health authorities, it could potentially lead to something that is registrational if we have the right sample size, if that answers the question.

But to see feeling for as a target and it very much underscores their interested and commitment to our technology.

Amy Peterson: And then just the go-no-go on data here, what you want to see in those 40 patients. And I'll jump back in the queue. Thank you.

Thank you got following a the press release mentioned easier far T cell by specific with Amgen is gonna be advancing in 2020 can you highlight what sort of developments have been made and it will be seen any preclinical data this year.

Sean A. McCarthy: I think Chris is a... As I mentioned, our goal there is to have initial data on these first 40 patients in 2021. And obviously, we'll take a look at that data and decide whether

We presented some preclinical data previously a as you may have seen in post the form so the basic concept in the basic proof of concept behind Egypt far Cdthree.

Mohit Bansal: Your next question, your next question is from Mohit Bansal from Citi. Your line is now open. Hi, this is James on behalf of Mohit. It looks like Bristol now has 986288 and 986249 in trials. Can you remind us how these two CTLA-4s differ and any insight on BMS's strategy to explore both?

He has been presented a what we've been doing with Amgen for the last couple of years is really working through the detailed protein engineering, a molecular biology of how to optimize that format and as well as I'm sure. You know, there's a lot to that there's a lot different formats to sort through a lot of geometry to got right.

In terms of the activity of the two arms of this type of by specific Oh, I can say that we've made good progress and we do expect to move towards a lead clinical candidate stage over the course of this year with Amgen one of them no is as I as I mentioned, we do a sites had makes much like in the alliance we retain.

Sean A. McCarthy: Yeah, hi, James. Absolutely. So 249 is the pro body version of IPI itself, and I think, as we've laid out, that's the program that's being advanced into the randomized phase two study. And that was the first pro-body targeting CTLA-4 that we made with BMS in this alliance. 288 is, as we said, a modified version of IPPE that is designed to be more active than the parental antibody. I'm expecting them to probably say a bit more about this program this year as the new leadership within BMS gets their arms around these programs, so we're not at liberty to say too much about it, but we've made a pro-body version of that modified IPPE, and that has now also gone into phase one dose escalation. So as I said in my prepared remarks, the fact that they're putting both of these programs now in It underscores their continued commitment to CTLA-4 as a target, and it very much underlines their interest in and commitment to our technology.

In development control for this program through proof of concept. So we'll be filing the eye in the once we get to the point is having a clinical candidate we agreed to move forward with a with a partner.

Hi, Patrick you with your question.

Thank you.

Your next question is from Terence Flynn from Goldman Sachs. Your line is though.

Hi, this holly on for Terry. Thanks, So much for taking my question to for US one so as we look towards the data from stage one of the phase two study of Cxcrseven too, which is especially later this year, what do you need to see in order to with that program and to teach to the phase two study and then secondly on C. access to zero zero.

Nine beyond the breast cancer indication that you outlined what other tumor types might be appropriate for this treatment considering that risk benefit profile its demonstrated thus far thanks.

Sean A. McCarthy: Thank you. I just got a follow-on question. The press release mentioned that the EGFR T-cell bispecific with Amgen is going to be advancing in 2020. Can you highlight what sort of developments have been made and whether we'll be seeing any preclinical data this year?

It's actually the questions Ali I'll be happy to turn this over to abbey, okay, great. So as far as the stage one of the phase two study for Cxo seven to what we would need to see to move forward I don't think we're actually giving guidance on what sort of response rates. We would we would need to see however, I will say that.

Sean A. McCarthy: We've presented some preclinical data previously, as you may have seen in poster form, so the basic concept and the basic proof of concept behind EGFR-CD3 have been presented. What we've been doing with Amgen for the last couple years is really working through the detailed protein engineering and molecular biology of how to optimize that format, and as I'm sure you know, there's a lot to that, and there are a lot of different formats to sort through. There is a lot of geometry to get right in terms of the activity of the two arms of this type of bispecific, and all I can say is that we've made good progress, and we do expect to move towards a lead clinical candidate stage over the course of this year with Amgen. One other note is, as I mentioned, we do at CytomX, much like in the AbbVie Alliance, retain development control for this program through proof of concept, so we'll be filing the IND once we get to the point of having a clinical candidate that we agree to move forward with our partner. Fantastic Thank you for your

From the data that is available in the public domain response rates have been around the twentyth and in some cases using immune to resist as high as 45%.

And we are well aware of though and looking to see where we benchmark to that.

For CD 166 program additional indications as I sort of alluded to in the transcript.

We saw a monotherapy activity with a patients in head and neck.

Triple negative breast cancer hormone receptor positive hertwo negative breast cancer.

And in the.

2019, a presentation there are other indications where tumor volume reductions were observed for example in over there in ovarian cancer and Ah what we might think about then are moving forward into those indications where are we at least observed activity with our Asia, but at this point in time.

We're focusing on the hormone receptor positive hertwo negative breast cancer population, which you probably know very well, it's about 60% of all of a patients but breast cancer and at this point in time. There is no AG see approved in this particular indication and then when it comes to see X T zero zero.

Sean A. McCarthy: Fantastic. Thank you for taking the questions. Thank you. Your next question is from Terrence Lynn from Goldman Sachs. Your line is now open. Hi, this is Holly on behalf of Terence. Thanks so much for taking the question. Two for us. One, so, as we look towards the data from Stage 1 of the Phase 2 study of CX-072, which is expected later this year, what do you need to see in order to move that program into Stage 2 of the Phase 2 study? And then secondly, on CX-2009, beyond the breast cancer indication that you outlined, what other tumor types might be appropriate for this treatment, considering the risk-benefit profile that's demonstrated thus far? Thanks.

Nine in combination with O seven to what I alluded to in the transcript as we would look to indications where either have had single agent activity and think about bringing the combination forward in those indications that we haven't disclosed what those indications are ya.

We I think we're ready for the next question.

Thank you. Your next question is from Terence Flynn.

Oh, it's from Marigold seen from Mizuho. Your line is now open.

Great. Thanks, so much for taking the question. Thanks for the additional color on did you hear a canine program I just had a question with respect to the biomarker arm in that study and if you can provide a little bit more insight into that and when you might have that information.

Holly: Thanks for the questions, Holly; I'll be happy to turn those over to Amy.

Amy Peterson: Okay, great. So, as far as the Stage 1 of the Phase 2 study for CX072, what we would need to see to move forward, I don't think we're actually giving guidance on what sort of response rate we would need to see. However, I will say that from the data that is available in the public domain, response rates have been around the 20s, and in some cases, using immune resistance, as high as 45%. And we are well aware of that and looking to see where we benchmark against that.

And as well Yeah, you know given this the novelty of this particular target how should we think about it in terms of the sort of focus of tumor types, even though I certainly respect it's a solid tumor study and then secondarily I know you've spoken to Bristow, a having data into Q4 nine.

Amy Peterson: For the CD166 program, additional indications, as I sort of alluded to in the transcript, we saw monotherapy activity with patients in head and neck, triple negative breast cancer, hormone receptor positive, HER2 negative breast cancer, and in the 2019 presentation, there are other indications where tumor volume reductions were observed, for example, in ovarian cancer. And what we might think about then is moving forward into those indications where we at least observed activity with our agent. But at this point in time, we're focusing on the hormone receptor positive HER2 negative breast cancer population, which you probably know very well is about 60% of all patients with breast cancer. And at this point in time, there is no ADC approved for this particular indication. And then when it comes to CX2009 in combination with 072, what I alluded to in the transcript is that we would look at indications where either of them have had single agent activity and think about bringing the combination forward in those indications, but we haven't disclosed what those indications are yet.

Program sometime this year do you have any particular.

Insight as to what venue that might be [noise].

[noise] Amer, thanks for the questions. So your second question.

The second question first can't comment on that unfortunately, they're they're working through.

But appreciate the question.

Regarding 2029 so.

So our guidance at this point so the.

This is a is a big idea. This target is it's a it's a very exciting target and you know as I've said before what we're doing is a pretty careful thoughtful dose escalation.

With a target that as we've demonstrated preclinically. If you don't mascot is actually.

Extraordinarily talking about lethal so so we would take it it carefully to learn about this molecule in patients.

And what we're working towards presenting this year its initial safety data from phase one dose escalation.

The.

Biomarker biopsy data would come from a little later in the study.

Operator: Lee, I think we're ready for the next question.

Terrence Lynn: Thank you. Your next question is from Terrence Flynn. Oh, it's from Mary Goldstein from Mizzou, Hawaii. Your line is now open. Great, thanks so much for taking the questions.

As we move.

She is.

Not quite to expansion stage, but at the upper upper range of that dose escalation, so probably know biomarker data this year.

Okay. Thank you.

Your next question is from Robert Burn from H.C. Wainwright Your line is that.

Mara Goldstein: Thanks for the additional color on the 2029 program. I just had a question with respect to the biomarker arm in that study and if you could provide a little bit more insight into that.

Hi, guys. Thanks for taking my questions. So I just wanted to circle back on the six or seven two plus your voice a phase two studies. So considering that Idera pharmaceuticals is currently running a phase three for their asset IMO 21, 25, plus Yervoy first yervoy and anti PD, one or all one refractory melanoma patients after achieving a 24 per.

Sean A. McCarthy: [inaudible]

Sean A. McCarthy: Types, even though I certainly respect it's a solid tumor study. And then secondarily, I know you've spoken to.

Sean A. McCarthy: Bristol, I will have data on the 249 program sometime this year. Do you have any...

<unk> objective response rate in their phase two could you comment about these sort of Africa C bench Mark do you believe you would have to hit in your phase two trial.

Sean A. McCarthy: Any particular insight as to what venue that might be?

Sean A. McCarthy: Hey Mara, thanks for the questions; take the time to answer the questions. Hit the second question first.

Sean A. McCarthy: Can't comment on that. Unfortunately, they're working that through. But I appreciate the question.

For six or seven two plus yervoy in order for the your phase two trial to potentially be registrational in nature.

Sean A. McCarthy: Regarding 2029, so, So our guidance at this point is that this is a big idea, this target. It's a very exciting target. And, you know, as I've said before, what we're doing is a pretty careful, thoughtful dose escalation with a target that, as we've demonstrated preclinically, if you don't mask it, is actually extraordinarily toxic and, in fact, lethal. So, you know, we're taking it carefully to learn about this molecule in patients. And what we're working towards presenting this year is initial safety data from phase one dose escalation. Um, the, um... Biomarker biopsy data would come from a little later in the study as we move to, not quite into the expansion stage, but at the upper range of those escalations, so probably no biomarker data this year.

And then I've one follow up after.

Yeah, Hi, Robert Great question and Yeah. We've also noted that data and I'll hand over to Amy Okay.

Right, so as far as what we would need to see him a phase two single arm.

Study, what what we would need to see to make it registrational in in of itself.

Yeah, it's hard to it's hard to pinpoint obviously, they went forward with a phase three with a response rate of 24% and we're encouraged certainly by that.

And so.

For a registrational standalone, we probably looking at something upwards of 24% right. However, when you see that it certainly gives us a justification to move forward into larger randomized studies as they did and we'll see what happens with their data, which I think.

Robert Burns: Okay, thank you. Your next question is from Robert Burns from HC Wainwright. Your line is now open. Hi guys. Thanks for taking the time to answer my questions. So, I just want to circle back on the CX072 plus Urovoy Phase 2 study. Considering that Idara Pharmaceuticals is currently running a Phase 3 for their acid IMO 2125 plus Urovoy versus Urovoy in anti-PD-1 or L1 refractory melanoma patients after achieving a 24 percent objective response rate in their Phase 2, could you comment about the sort of efficacy benchmark you believe you would And then I have one follow-up appointment afterward.

We're expecting a in 2022.

From the phase three.

Okay. Thank you for that and then a one more for me. So I just I'm curious as to how you see that sort of indication the anti PD, one refractory melanoma patients setting evolving over time, when we consider something to assets in combinations, where we see moving into that space.

Thanks.

Well, let me make sure I understand your question. So how does the anti PD, one refractory patient population evolve and other agents are moving into the space, Yeah, I'm sort of curious as to how you see that sort of treatment pattern sort of evolve considering all the data we're seeing from from.

Oh from multiple different assets.

Just from a landscape perspective your thoughts on it.

Robert Burns: Yeah, hi Robert, great question. And yeah, we've obviously noted that data, and I'll hand it over to Amy.

Yeah, I guess first nothing's, yet approved and so while there might be a lot of people dabbling in this space and testing in this space.

Amy Peterson: Okay, great. Right. So, as far as what we would need to see in the Phase II single-arm study, what we would need to see to make it registrational in and of itself, it's hard to pinpoint.

I think until we have approvals the spaces open.

And I'm not I guess I'm not quite sure what additional flavor, you're you're looking to get from us on that.

Amy Peterson: Obviously, they went forward with Phase 3 with a response rate of 24%, and we're encouraged certainly by that. For a registrational standalone, we're probably looking at something upwards of 24%, right? However, if we do see that, it certainly gives us justification to move forward into larger randomized studies as they did. And we'll see what happens with their data, which I think we're expecting in 2022 from phase three

Yeah, maybe just wondered if there's no sorry go ahead, no I'm, sorry, I'm starting off to go ahead.

I I was just going to add that you know we've moved into this patient population in large for of course because of the substantial unmet medical need.

Yeah that could shift over time right. If some of these other approaches or a successful and if they move a lot faster than us and we have to carefully monitor that but we see this this this particular patient population as an opportunity to run a study reasonably quickly in an area of unmet medical need.

Whereby the way the combination that we're evaluating you know may may afford.

Robert Burns: Okay, thank you for that, and then one more for me. So, I'm curious as to how you see that sort of indication, the anti-PD-1 refractory melanoma patient setting, evolving over time when we consider some of the assets and combinations we see moving into that space. Thanks.

Advances over others, because we know for example, the depth and durability of response that can be afforded with is still the already Io Io combination has been approved that can be very impressive and very meaningful for patients and so.

Robert Burns: Let me make sure I understand your question. So it's, how does the anti-PD-1 refractory patient population evolve as other agents are moving into the space?

I think we'll just have to see how it unfolds we haven't.

As.

As you as you well no we havent committed at this stage to a large randomized study we wanted to take a ticket one step at a time, but we'll closely monitored the field and see how it unfolds.

Robert Burns: Yeah, I'm sort of curious as to how you see that sort of treatment pattern sort of evolving considering all the data we're seeing from all different sources. Just from a landscape perspective, your thoughts on it.

Awesome. Thanks, guys.

Your next question is from at dessert their routes from Guggenheim. Your line is that okay.

Great. Thanks for taking the question just a couple of questions for me first on six to nine just wondered if you could talk a little bit about the population that this study is you're going into the hormone receptor positive her to.

Amy Peterson: Yeah, I guess first, nothing's yet approved, and so while there might be a lot of people dabbling in this space and testing in this space, I think until we have approvals, the space is open. And I'm not, I guess I'm not quite sure what additional flavor you're looking for.

Ah nurture negative population as far as sort of.

A response rate expectations in how we can think about what what sort of the clinical hurdle is in that setting and then secondly, just wonder given that you know we've seen opdivo see Chile for a combinations be successful beyond melanoma, if if there's any expectations that.

Sean A. McCarthy: Yeah, maybe just one additional. Sorry, go ahead. No, I'm sorry, Sean, for cutting you off.

Sean A. McCarthy: Go ahead. I was just going to add that, you know, we've moved into this patient population, in large part, of course, because of the substantial unmet medical need. But that could shift over time, right? If some of these other approaches are successful and if they move a lot faster than us, then we have to carefully monitor that. But we see this particular patient population as an opportunity to run a study reasonably quickly in an area of unmet medical need, where, by the way, the combination that we're evaluating may afford advantages over others. Because, for example, the depth and durability of response that can be afforded with this, still the only IO- And so I think we'll just have to see how it unfolds. We haven't, as you well know, committed at this stage to a large randomized study. We wanted to take it one step at a time, but we'll closely monitor the field and see how it unfolds. Awesome, thanks.

So could take programs for beyond just the melanoma expansion. Thanks.

Let me answer the second question first and thanks very much so for the questions I'm sure I'd be happy to take the the second on the 2005 patient population.

So.

You know.

Obviously be of estimated pretty substantial commitment to that melanoma, the randomized melanoma study.

I can't comment on what that thoughts might be in terms of other indications, but as we've said with our combination of over seven Super Iffy.

We do see opportunities beyond melanoma, a that we could potentially move into and the team Amy and some of the team are very actively working those through.

So no specific update at this point, but we certainly see additional opportunity on our side.

Right and then I'll address your first question, which was I think trying to better understand what response rate we might be benchmarking to a in this patient population given given the.

Terrence Flynn: Your next question is from Ed Zurderoth from Guggenheim. Your line is now open. Great, thanks for taking the question. There are just a couple of questions for me. First, at CX2009, just wondered if you could talk a little bit about the population that the study is going into, the hormone receptor-positive HER2 negative population as far as sort of response rate expectations and how we could think about what sort of the clinical hurdle is in that setting. And then, secondly, just wondered, given that, you know, we've seen Optivo CTLA-4 combinations being successful beyond melanoma, if Thanks.

And given the competitive landscape.

So I can't give guidance on what response rate went benchmarking to there are I mean, it's known that hormone receptor positive hertwo negative breast cancer responses are not as easy to I'm happy with chemotherapy or with other agents, which doesn't mean that these patients.

Getting benefits. So we will be looking at a couple of things. In addition to response rate clinical benefit Ray for example, at a 24 weeks as often often used to assess whether or not the drug is doing anything and when it comes to other drugs moving in the in the area. There are certainly drugs moving out and their drugs.

Moving out and CDK for six inhibitors for example, or possibly moving to add human spaces Sacituzumab were interested to see what ultimately happens without that we don't anticipate that data oh for for quite sometime.

Sean A. McCarthy: Let me answer the second question first, and thanks very much, Esther, for the questions. And I'm sure Amy would be happy to take the second on the 2009 patient population. So, you know... Obviously, BMS has made a pretty substantial commitment to the randomized melanoma study. I can't comment on what their thoughts might be in terms of other indications, but as we've said with our combination of 072 plus IFI, we do see opportunities beyond melanoma that we could potentially move into. And the team, Amy and Allison on the team, are very actively working those through. So no specific update at this point, but we certainly see additional opportunity on our side.

So I can give you a number.

That's fair thank you.

Your next question is from during Allen from Jefferies. Your line is now open.

Yeah, Hi, guys. Thanks for taking my questions, maybe I guess, one more Sean on the refractory melanoma trial.

I think on this call you talked about 20% to 24% or ours, a good benchmark how do you position that if we look at you know the 14% or our that was presented by F.D.A. I think they publish this data in Lance and 27 team and about 2500.

Chance that fail PD, one, but well continue to be treated with PD. One pros progression. So essentially you know you're getting a 40% or are on PD one after they progressed.

Amy Peterson: Great, and then I'll address your first question, which was, I think, trying to better understand what response rate we might be benchmarking to in this patient population given the and given the competitive landscape. So I can't give guidance on what response rate we're benchmarking to.

So do you think of 20% to 24%.

Amy Peterson: There are, I mean, it's known that hormone receptor positive, HER2 negative breast cancer responses are not as easy to achieve with chemotherapy or with other agents, which doesn't mean that these patients aren't getting benefits. So we will be looking at a couple of things in addition to response rates, for example, at 24 weeks, which is often used to assess whether or not the drug is doing anything. And when it comes to other drugs moving into the area, there are certainly drugs moving in, and there are drugs moving out. And CDK4-6 inhibitors, for example, are possibly moving into adjuvant spaces. Sasitizumab, we're interested to see what ultimately happens with that, but we don't anticipate that data for quite some time, so I can't give you a number. That's fair. Thank you.

Or are in that population with the combo, which would be a differentiator. Thanks.

Yeah, Hi, there and a good question.

I want to be clear, though I mean, where no, but we're not guiding to it.

I don't think we did specifically guide to a 20% to 24% response rate.

On this call and what we said is when we look at the.

And by the way that that that data that you site is of course interesting intensive continue P.D. therapy in failures, but what we're saying let me try disturbances I can be is that if we look at the the published evidence or the publicly available evidence for how patients.

To have been pretreated treaty by Treaty previously with the PD and it was there how they are.

How they fair on.

TD CRD four combination those response rates are in the 20% to 40% range.

And the landscape is shifting as as Robert Austin, others Abbas right with other combinations in this patient setting. So the bar is probably getting higher not lower so yeah. We'll do the best we can do and we're obviously looking for the best response rate, we can get but we're not specifically guiding to 20 to 24 just to be clear.

Bering Amin: Your next question is from Bering Amin from Jeffery East. Your line is now open. Yeah. Hi guys.

Bering Amin: Thanks for taking my questions. Maybe I can guess one more, Sean, on the refractory melanoma trial. I think on this call you talked about a 20 to 24% ORR being a good benchmark. How do you position that if we look at the 14% ORR that was presented by FDA? I think they published this data in Lansing 2017 in about 2,500 patients that fail PD-1 but continue to be treated with PD-1 post-progression. So, essentially, you're getting a 14% ORR on PD-1 after they progress. So do you think a 20 to 24 percent, you know, RRR in that population with the combo would be a differentiator? Thanks.

Oh, we have to do better and then.

Yeah. Okay. That's helpful and then on the up how can you just talk about yeah. This is a target. That's also expressed on normal cells and.

Can you just talk a little bit about what you're seeing in the animal data and whether that'll all way in terms of off target toxicity.

This is on its own outcome. Yeah. So we're really interested in this target and you know immunogen has been for some time as you know and it just.

The program became available as it is a comp in the context of computer strategic Reprioritization last year. So we were able to negotiate to bring it back in into interest I'd say the target is it's been sort of for very long time is a very good cancer target is actually a reasonably well.

Bering Amin: Yeah, hi, Darren. Good question. I want to be clear, though, I mean, we're not guiding you to it. (inaudible)

Sean A. McCarthy: Let me try and be as clear about this as I can be: if we look at the published evidence or the publicly available evidence for how patients who have been pre-treated previously with a PD inhibitor fare on a PD-CTLA-4 combination, those response rates are in the 20 to 40% range. And the landscape is shifting, as Robert asked and others have asked, right, with other combinations in this patient setting. So the bar is probably getting higher, not lower. So, you know, we'll do the best we can. And we're obviously looking for the best response rate we can get. But we're not specifically guiding to 20 to 24, just to be clear. We hope to do better next time.

Halliday to target and that there is data out there.

For this phase two data for a.

Fusion protein an outcome targeting fusion protein, which actually is a a different kind of a tall soon as a recombinant talks infusion that is quite effective in in phase two so so we know this target can can work.

The the preclinical data showed that the and that you're gonna munitions presented this that the AIDC is quite toxic induces a range of toxicities, including in the skin. The pro body is protected in that regard and and yet the property retains the anticancer activity of the underlying 80.

Sean A. McCarthy: Okay, that's helpful. And then on the EpiCam, can you just talk about, you know, this is a target that's also expressed on normal cells, and can you just talk a little bit about what you're seeing in the animal data and whether that'll correlate in terms of off-target toxicity?

You see just like our property drug conjugates too. So it's a it's interesting and exciting program. We've just brought it back into the company. So were in the process of a evaluating the data to decide.

Sean A. McCarthy: Yes, so we're really interested in this target and Immunogen has been for some time, as you know, and the program just became available in the context of Immunogen's strategic reprioritization last year, so we were able to negotiate to bring it back into CytomX. So the target has been thought of for a very long time as a very good cancer target. It's actually a reasonably well-validated target in that there is data out there, there's phase two data for a fusion protein, an Epcam-targeting fusion protein, which is actually a different kind of a toxin. It's a recombinant toxin fusion that is quite effective in phase two. So we know this target can work. The preclinical data has shown that the ADC is quite toxic, it induces a range of toxicities, including in the skin. The pro-body is protected in that regard, and yet the pro-body retains the anti-cancer activity of the underlying ADC, just like our pro-body drug conjugates do.

What a timeline is gonna be for moving that program forward, but we think it's a really interesting Morgan.

Okay, great. Thank you.

The indications where it is clinically valley validated it's been bladder cancer and there are actually up moving it they moved into a pivotal study.

Additionally, can as a naked antibody is used for the treatment of a sadie's in ovarian cancer in certain regions of the world. So there are two clinically validated areas, where abcam has demonstrated actual activity.

Resulting in it.

Continued progress forward your registration studies or approval.

Great. Okay. Thank you.

Your next question from Joe Catanzaro from Piper Sandler Your line is that.

Hey, guys. Thanks for taking the questions as a couple of quick ones for me would you be able to say how many patients enrolled into the dose ranging portion of the 2009 phase one study.

And whether we should expect that cohort of patients to be less heavily pretreated, then you know six or seven prior lines of therapy for the initial dose escalation cohort.

Amy Peterson: So it's an interesting and exciting program. Okay, great. Thank you.

Amy Peterson: are the indications where it is clinically validated. It's in bladder cancer, and they're actually moving it. They moved into a pivotal study. Additionally, Epcam, as a naked antibody, is used for the treatment of ascites and ovarian cancer in certain regions of the world. So there are two clinically validated areas where Epcam has demonstrated activity resulting in it. Continued progress forward to registration studies or approval.

Hey, Joe Sean I'm, just let me make sure I understand the question so you're asking about the the the phase one study enrollment.

Right.

So yeah, so like the dose optimization that you had done in implementing the prophylactic measures for ocular toxicity.

Joseph Michael Catanzaro: Great, okay, thank you. Your next question is from Joe Catanzaro on behalf of Piper Zandler. Your line is now open. Hey guys. Thanks for taking the questions. Those are a couple of quick ones from me. Would you be able to say how many patients enrolled in the dose-ranging portion of the 2009 Phase 1 study and whether we should expect that cohort of patients to be less heavily pretreated than, you know, six or seven prior lines of therapy for the initial dose escalation cohort?

Right, Yes. So again our goal is to present, a pretty comprehensive update on on all of that work sometime this year. What I can say is that the patient population pretty throughout the the work that we did a that led to the selection of dose and an indication was was all done in pretty late stage patients and so now.

As we're moving into the phase two expansion of the team is has a revised our enrollment criteria and is working hard to.

Joseph Michael Catanzaro: Hey Joe, Sean, just let me make sure I understand the question. So you're asking about the phase one study enrollment, right?

Joseph Michael Catanzaro: So, yeah, like the dose optimization that you had done in implementing the prophylaxis measures for ocular toxicity.

Tighten up the patient population to yeah relative to the phase one so I don't want to comment on specific numbers at this point, but it but it should become clearer as the year goes on.

Sean A. McCarthy: Right. Yeah.

Okay got it and then maybe following up along those lines and those kind of asked earlier, but with phase one dose escalation and optimization complete what triggers the expansion of additional cohorts beyond the initial hormone receptor positive cohort that you just kicked off.

Sean A. McCarthy: So, again, our goal is to present a pretty comprehensive update on all of that work sometime this year. What I can say is that the patient population really throughout the work that we did that led to the selection of dose and indication was all done in pretty late-stage patients. And so now, as we're moving into the Phase 2 expansion, the team has revised our enrollment criteria and is working hard to tighten up that patient population relative to Phase 1. So I don't want to comment on specific numbers at this point, but it should become clearer as the year goes on.

Yeah, No no one thing really I think it it could be additional data it could be thinking about priorities across the portfolio.

Of course, it would be data that we've already seen from the phase one so something that we're looking at in real time, and particularly baby at Allison that there that here in the firmly on board looking at very closely.

Sean A. McCarthy: Okay, got it. And then maybe following up along those lines, I know it was kind of asked earlier, but with phase one, you know, dose escalation and optimization complete, what triggers the expansion of additional cohorts beyond the initial hormone receptor positive cohort that you just kicked off?

Okay, Great. That's all I have thanks for taking my questions.

You bet.

Your next question is from Berlin Kumar from Cantor Fitzgerald Your line is though.

Sean A. McCarthy: Yeah, no one thing really. I think it could be additional data. It could be thinking about priorities across the portfolio. Of course, it would be data that we've already seen from phase one. So something that we're looking at in real time, and particularly Amy and Allison, now that they're here and firmly on board, are looking at very closely. OK.

Hey, good evening, everyone and thanks for taking the questions.

Well on the AG two zero to nine I understand the talks in use and this one is and then maybe versus the m. for being used in two 009.

Can you provide some context, that's how should we think about some off and they may you did talk all when we see the fourth data and some of the all I could talk so we should expect combination data.

Joseph Michael Catanzaro: Thanks for taking my...

Joseph Michael Catanzaro: Thanks for taking my questions.

Varun Kumar: Your next question is from Varun Kumar from Kantor Fitzgerald. Your line is now open. Hey. Good evening, everyone, and thanks for taking the questions. First, on CX-2029, I understand the talks in use in this one are MMAE versus CM4 being used in 2009. Can you provide some context as to what we should think about some of the MMAE-related talks when we see the false data and some of the off-target talks we should expect from the initial data?

Well.

Thanks to the question Brian.

If I could paraphrase your question to some extent it it might be would we expect to see ocular toxicities with them and they are they also there is that we probably wouldn't expect it based on the.

The wealth of clinical experience with that payload.

Sean A. McCarthy: Well, thanks for the question, Varun. If I could paraphrase your question to some extent, it might be, would we expect to see ocular toxicities with MMAE? The answer there is that we probably wouldn't expect it based on the wealth of clinical experience with that payload. You know, ocular toxicity is a particular consideration with DM4 and the metanazines. So the toxicities with MMAE that are best characterized are hematologic in nature, neutropenia, anemia, and then also neuropathy. So those would be the kinds of things that we'd be looking out for in the Phase 1 study.

Yeah.

Okay. That's obviously is a particular.

A particular consideration with the enforce it many times means soon.

The toxicities with M&A, either best characterized our hematologic in nature.

Neutropenia in EMEA and then also neuropathy. So those would be the kinds of things that we'd be looking out for in a in the phase one study.

Okay. So on and just maybe one question on 072 combo any color on inclusion criteria being you based on Uruguay prior years I tend to be indication.

Sean A. McCarthy: Thanks, Sean. And just maybe one question on 072 combo. Any color on inclusion criteria being used based on earvoi, prior ear surgery therapy in the patient?

Okay. When you say the zero seven to calm, though you're referring to the Ipilimumab combo and why we are not allowing prior CTL Lee for exposure.

Amy Peterson: Okay, when you say the 072 combo, you're referring to the ipilimumab combo, and right, we are not allowing prior CTLA-4 exposure.

Amy Peterson: Okay, so all the enrolled patients will be CTLA-4-naive in the enrolled cohort. Correct. Okay, great. Thank you, Sean, and thank you, Amy. Congratulations on the program.

Okay. So all the enrolled patients will be PD L. M naive and then Oh.

[music].

Correct.

Okay. Thank you Sean and thank you Amy.

Okay.

So we're reaching the top of the hour and I don't see any more questions I'm going to turn the call back over to Sean.

Operator: You're welcome. So we're reaching the top of the

Operator: I don't see any more questions. I'm going to turn the call over to you.

Great. Thanks, Chris well once again.

Well you know team was a very big here for the company very important advancements across the pipeline and ER. We think we're off to a great start and 2020 so I'm.

Sean A. McCarthy: Yeah, great thanks Chris. Well, once again, 2019 was a very big year for the company, with very important advancements across the pipeline, and we think we're off to a great start in 2020, so thanks for your time, and we'll talk to you next time.

I am and what's what's your nicely.

Ladies and gentlemen. This concludes today's conference. Thank you for participation and how the wonderful day you may all disconnect Goodbye.

Operator: Ladies and gentlemen, this concludes today's conference. Thank you for your participation and have a wonderful day. You may all disconnect. Goodbye.

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