Q1 2021 CytomX Therapeutics Inc Earnings Call

Is this a new section of our website at fatal makes dot com.

During today's call, we will be making forward looking statements because forward looking statements relates to the future. They are subject to inherent uncertainties and risks, including the incidents surrounding the COVID-19 pandemic that are difficult to predict and many of which are outside of our control important risks and uncertain.

Teeth are set forth in our most recent public filings with the S. E C. At S E C dot Gov, including a form 10-Q filed today we on.

On to take no obligation to update any forward looking statements with a as a result of new information future developments or otherwise with that I'd like to turn to call now over to Sean.

Second child and good afternoon, everyone. Thanks for joining us today for brief remarks on our progress during the first quarter of 2021.

Q1 was smart price focused execution by this italics team as we continue to drive towards initial day to read a house from ongoing studies to studies.

Of our lead programs the conditionally activated antibody drug conscious problems. That's on my breath, Tenzing, formerly 62009 and 62029.

I hope all of you had the opportunity to attend last month's investor event that we hosted during which we took a deep dive into the science behind our priorities therapeutic platform.

And also the phase two clinical strategies for our two lead assets.

We were delighted to be joined at the event by keeping your leaders doctors, Sarah Pilati, Melissa Johnson and John Lambert on.

On archived webcast is available on the events and presentations section of our website and I encourage everyone to review the presentations to learn more about early programs on our leadership in the field of conditional activation of biologic therapeutics.

[noise] I'd like to start today with our program evaluating problems that's about in patients with breast cancer.

As a reminder, the phase two study is enrolling patients with her to non amplified breast cancer into three parallel arms.

A is evaluating monotherapy in patients with hormone receptor positive breast cancer.

R B as evaluating monotherapy in patients with C. D 166 positive triple negative breast cancer.

[noise] RMC is evaluating products that a map in combination with Pac milam app or proprietary PDL one priority and this is in patients with both C. D 166 positive and PD on one positive triple negative breast cancer.

Yeah.

Ah first patients were treated in this study during Q1 and we continue to work towards initial data from arms NB by the end of this year and we anticipate initial data from RMC in 2022.

Now a notable development during Q1 relating to our process on my breast cancer program with the full approval by FDA of substitute on Madagascar, T can and the second and third line metastatic T NBC settings.

Based on data from the ascent phase three trial and this is obviously a terrific development for patients.

I want to emphasize here that C. D 166, the target of product automap, as a novel target and breast cancer and the router a candidate utilizes a different payload to substitute on that.

Furthermore, enough phase one evaluation that we've reported previously we saw a meaningful activity and a CNBC patient in the post attitudes on my upsetting, where we expect high unmet medical needs to remain.

Indeed, the anticipated unmet need in the post substitute from upsetting is underscored by the 5% response rate and patients randomized to to control chemotherapy arm and the ascent study.

And their median progression free survival, one seven months, a medium overall survival barely exceeding six months.

Accordingly, our development strategy empty NBC will continue to assess pathways to accelerated and full approval for profit lab on novel and potentially first thing cost treatment for this disease.

I'd like to now move on to see X 2029 are conditionally aggravated ADC targeting CD 71, the transfer interceptor.

Patients enrollment continue jerky one in the face to expansion study evaluating CX 2029, as a single agents and four cohorts squamous non small cell lung cancer had neck squamous cell carcinoma, esophageal and gastroesophageal junction cancers, and diffuse large be solid and firm.

As with problems that the map we continue to work towards initial data for 62029 in the fourth quarter of this year, most likely from the squamous lung and had net cohorts with initial data from the additional cohorts anticipated in 2022.

Turning now to our research at preclinical pipeline.

Another key development for Cytotechs in Q1 was the first presentation of our emerging work in the field of conditionally activates cytokines.

One of the defining advantages of our property platform that we discussed during our recent investor that is this versatility and tune ability.

And this has allowed us to continuously innovate across multiple biologic modalities.

Are interested cytokines stems from the fact that systemic toxicity and poor exposure have limited the clinical access clinical success of this important and highly potent class of immune modulators.

Chao: and news section of our website at Citomix.com. 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, including the uncertainties surrounding the COVID-19 pandemic that are difficult to predict, and many of which are outside of our control. Important risks and uncertainties are set forth in our most recent public filings with the SEC at SEC.gov, including our Form 10Q filed today. We undertake no obligation to update any forward-looking statements, whether as a result of new information, future developments, or otherwise. With that, I'd like to turn the call now over to Sean.

Industry interest in this area is understandably high at the moment given the landmark progress made in recent years on interleukin two a prototypical immune modulator currently the focus of many efforts to improve its therapeutic window.

Enormous room exists to optimize cytokines of cancer therapy as <unk> aims to be at the forefront.

By leveraging the depth of our expertise on protein engineering protease biology, and our understanding of to chew on microenvironment. We have now demonstrated our ability to be a meaningful player in this field leading.

Leading outside the card program is a protease activates will version of interfere on alpha to be to which we have directed our sophisticated protein engineering approaches to improve therapeutic window and unlocked potential and this powerful immunotherapy.

Sean: Thank you, Chao, and good afternoon, everyone. Thank you for joining us today for brief remarks on our progress during the first quarter of 2021. Q1 was marked by focused execution by the Citermics team as we continued to drive towards initial data readouts from ongoing phase two studies of our lead programs, the conditionally activated antibody drug conjugates, Pallazatamabravtanzin, formerly CX209, and CX2029. I hope all of you had the opportunity to attend last month's investor event that we hosted, during which we took a deep dive into the science behind our pro We were delighted to be joined at the event by key opinion leaders Dr. Sarah Talani, Melissa Johnson, and John Lambert.

We'll have more to say in the future as we advanced this exciting new frontier of cytokines.

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Another area of intense industry interests that present is by specific piece on engages we continue to work closely with our partner Amgen on indie enabling studies for six 900 for our conditionally activated T cells by specific antibody targeting Egfr on CD three.

Submission per six nine or force plan for late 2021.

Additionally, progress continue to be made in Q1 with drug discovery activities for this modality in our strategic collaborations with our newest partner or spouse.

During Q1, we also continue to evolve 62043 are conditionally activated antibody drug conjugate directed against the abundant tumor antigen Afghan.

Sean: An archived webcast is available in the events and presentations section of our website, and I encourage everyone to review the presentations to learn more about our lead programs and our leadership in the field of conditional activation of biologic therapeutics. I'd like to start today with our program evaluating Peralizatomab in patients with breast cancer. As a reminder, the Phase 2 study is enrolling patients with Hurt2 non-amplified breast cancer into three parallel arms

Int, enabling studied continue to progress although here, we have experienced some delays as a result of recent supply chain interruptions and based on a reassessment of the program timeline, we no longer expect to submit an int in 2021 and we're currently reassessing the timeline for this program.

Returning to the clinical pipeline our partner Bristol Myers Squibb continue to make progress.

Enrolling in the part to be evaluation of BMS 90, 6249 appropriately version of a preliminary in combination with and if all on that and a randomized study of patients with metastatic melanoma.

Sean: Arm A is evaluating monotherapy in patients with hormone receptor positive breast cancer, R&B is evaluating monotherapy in patients with CD166 positive triple negative breast cancer, and RMC is evaluating Pranazatamab in combination with Pekmimab, our proprietary PDL1 probot, and this is in patients with both CD166 positive and PDL1 positive triple negative breast cancer.

BMS also recently initiated three new cohorts testing this combination in patients with advanced hepatic cellular carcinoma, metastatic castration resistant prostate cancer and advanced Tmv's C.

With these updates I would like to turn on the call over to Carlos to review our financials.

Thank you Sean Thomas.

Sean: Our first patients were treated in this study during Q1, and we continue to work towards initial data from arms A and B by the end of this year, and we anticipate initial data from arm C in 2022. Now, a notable development during Q1 relating to our Peralizatomab breast cancer program was the full approval by FDA of Sassetuzumab Gavitikan in the second and third line metastatic TNBC setting, based on data from the Ascent Phase 3 trial, and this is obviously a terrific development for patients.

How much can be in an excellent financial position to drive beyond the key value, creating data readouts on the fourth quarter of this year and well into 2023.

As of March 31st 2021, we had $394 million in cash cash equivalents and short term investments.

This balance included the $108 million in net proceeds we right in January from morale received the follow on public equity offering.

<unk> Avenue was $16 million from the first quarter of 2021 compared to 50 million for the corresponding quarter and 2020.

Sean: I want to emphasize here that CD166, the target of Pralazatomab, is a novel target in breast cancer and that our drug candidate utilizes a different payload to Sassituzum. Furthermore, in our phase one evaluation that we've reported previously, we saw meaningful clinical activity in a TNVC patient in the post-Satutuzum phase, where we expect high unmet medical need to remain. Indeed, the anticipated unmet need in the post-Sacetuzuma setting is underscored by the 5% response rate in patients randomized to the control chemotherapy arm in the Ascent study and their median progression-free survival of 1.7 months, a median overall survival barely exceeding 60.

And decrease was due to research and development partnership payments that were recognized in 2020.

R&D expense or $22 million during the first three months of 2021 compared to 43 million in the first quarter of 2029.

The decrease is largely attributed.

Two one time line dancing expenses decreased clinical trials spend and timing of manufacturing Kennedys.

<unk> expenses were essentially flat for the first quarters on 2021, and 2020 amounting to 9.2 million and $9.6 million, respectively with that I'll turn on the call back to Sean.

Sean: Accordingly, our development strategy in TMBC will continue to assess pathways to accelerated and full approval for Pralazatamab, a novel and potentially first-in-class treatment for this disease. I'd like to now move on to CX2029, our conditionally activated ADC targeting CD71, the transfer in receptor. Patient enrollment continued during Q1 in the Phase 2 expansion study, evaluating CX2029 as a single agent in four cohorts, squamous non-small lung cancer, head-in-neck squamous cell carcinoma, esophageal and gastroesophageal junction cancers, and diffuse large B-cell lymphoma.

Great. Thanks Carlos.

So it makes we continue to dedicate ourselves to working towards making a meaningful difference for cancer patients.

By being different and thinking differently, we've pioneered an entirely new way to design therapeutic categories that other biologic modalities and we've used our technology to purposefully go after high potential targets that were previously considered undruggable like CD 166, and 60 71.

Across our pipeline, we now have four assets in phase two studies in nine different tumor types.

I'm moving to the cytokine space, where many opportunities exist to take high potential immune modulators and widened or open therapeutic window is also consistent with a broad guiding philosophy, we believe that by taking on big challenges like these we increase our chances of really moving the needle for cancer patients and realizing our vision doesn't organization.

Sean: As with Peralazatomab, we continue to work towards initial data for CX2029 in the fourth quarter of this year, most likely from the squamous lung and head and neck cohorts, with initial data from the additional cohort anticipated in 2022. Turning now to our research and preclinical pipeline, another key development for Cytomics in Q1 was the first presentation of our emerging work in the field of conditionally activated cyto One of the defining advantages of our pro-body platform that we discussed during our recent investor event is its versatility and tunability.

So thanks for your time and.

Listening to that brief updates with that let's open on the call up for Q&A, Carlos and I will take your questions Amy Peterson, who usually join US on these calls is currently performing her civic duty on jury service. So we will.

I'd be happy to field vehicles operator.

As a reminder to ask a question you would need to <unk> to retire question. Please press okonski I have strength.

Sean: And this has allowed us to continuously innovate across multiple biological modality. Our interest in cytokines stems from the fact that systemic toxicity and poor exposure have limited the clinical success of this important and highly potent class of immune modulators. Industry interest in this area is understandably high at the moment, given the landmark progress made in recent years on interleukin 2, a prototypical immune modulator currently the focus of many efforts to improve its therapeutic window. Enormous room exists to optimize thertychines for cancer therapy, and Cytomics aims to be at the forefront.

Again as a reminder to ask a question really depressed I rang accounts on three diet crash on please.

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From that will be compiled.

Okay.

Alright first question is on the line of canceling from I'm, calling from from.

Yeah line Miss Hamilton.

Great. Thanks, so much for taking the questions. Maybe two for me was just wondering broadly Sean if you can comment on enrolment trends you're seeing in your trials you know given the pay per vaccinations and in the U S has obviously been picking up an infection that have been going down, but maybe just what have you seen at the at the enrollment level at your sites and then maybe one.

Sean: By leveraging the depth of our expertise in protein engineering, protease biology, and our understanding of the tumor microenvironment, we have now demonstrated our ability to be a meaningful player in this field. Leading our cytokine program is a protease-activatable version of interferon alpha-2B, to which we have directed our sophisticated protein engineering approaches to improve the therapeutic window and unlock potential in this powerful immunotherapy. We'll have more to say in the future as we advance this exciting new frontier of cytokines at Cytoma.

Carlos just on pacing on spend for the rest of the year is the first quarter of good baseline to think about or if they're gonna be upward pressure on that over the course of the year here as you as you continue to enroll. These these keep eight two studies. Thank you.

Great High tariff thanks for the questions first of all with regard to enrollment.

Of course, we're seeing across.

Across the country, a lot of great trends with vaccination.

Improving numbers across the board and that's great. We're looking to open up a bit more I would say that with regards to clinical execution still with a predominantly remote monitoring and.

Sean: Another area of intense industry interest at present is bispecific T-cell engagers. We continue to work closely with our partner, Amgen, on I&D enabling studies for CX904, our conditionally activated T-cell bi-specific antibody targeting EGFR and CD3. I and D submission for CX904 is planned for late 2021. Additionally, progress continued to be made in Q1 with drug discovery activities for this modality in our strategic collaboration with our newest partner, Estelle. During Q1, we will also continue to advance CX2043, our conditionally activated antibody drug conjugate directed against the abundant tumor antigen, Epcot.

Activities.

But we are seeing things steadily continue to improve and.

We remain.

On track with our guidance for.

The initial data for these studies by the end of this year.

Cancel on the standard Q1, it's a pretty good proxy, even though there will be fluctuations from quarter to quarter.

And we haven't really guidance for four.

Four year spend that there shouldn't be anything super out of the ordinary.

Sean: IND enabling studies continue to progress, although here we have experienced some delays as a result of recent supply chain interruptions, and based on a reassessment of the program timeline, we no longer expect to submit an IND in 2021, and we're currently reassessing the timeline for this program. Returning to the clinical pipeline, our partner Bristol-Myers Squib continued to make progress, enrolling in the Part 2B evaluation of BMS-986249, a pro-body version of epilumumab, in combination with nivolomab in a randomized study in patients with metastatic melanoma.

Our next question comes from the line of Peter Laughing from Bichrome.

Yeah line xylophone.

Hi, This is Mitchell on for Peter Thank you for taking our question today.

The first question on.

2009 could you comment on the size and scope of the day that we might see for the past two datasets and <unk>.

Yes, hi, thanks. Thanks for the question. So the the study design across the three arms arms, a BMC is to enroll 40 patients in each of those arms.

Sean: BMS also recently initiated three new cohorts testing this combination in patients with advanced hepatocellular carcinoma, metastatic castration-resistant prostate cancer, and advanced TMBC. With these updates, I would like to turn the call over to Carlos to review our financials. Thank you, Shadm.

And we are working hard towards that as I mentioned the goal is for initial data from from arms AMB towards the end of this year RMC in 2022 and that remains.

Carlos: Thank you, Sean. Cytomics continues to be in an excellent financial position to drive beyond the key values creating data readouts in the fourth quarter of this year and well into 2020. As of March 31, 2021, we had $394 million in cash, cash equivalence, and short-term investments. This balance included the $108 million in net proceeds we raised in January from a well-received follow-on public equity offering.

Our objective at this point is to drive enrollment is.

Expeditiously as we carry on across those three hours.

<unk>.

Carlos: Revenue was $16 million for the first quarter of 2021, compared to $50 million for the corresponding quarter in 2020. The decrease was due to research and development partnership payments that were recognized in 2020. R&D expenses were $22 million during the first three months of 2021, compared to $43 million in the first quarter of 2020. The decrease is largely attributed to one-time licensing expenses, decreased clinical trial spend, and timing of manufacturing activity. GNA expenses were essentially flat for the first quarters of 2021 and 2020, amounting to $9.2 million and $9.6 million, respectively. With that, I'll turn the call back to Sean.

Sean: So at Cytomics, we continue to dedicate ourselves to working towards making a meaningful difference for cancer patients by being different and thinking differently. We've pioneered an entirely new way to design therapeutic antibodies and other biologic modalities, and we've used our technology to purposefully go after high-potential targets that were previously considered undruggable, like CD166 and CD71. Across our pipeline, we now have four assets in Phase 2 studies in nine different tumor types.

Clinically significant and the hormone receptor positive setting triple negative different much more aggressive disease of course these patients.

Progress on much more rapidly so here or are.

Sean: Our move into the cytokine space, where many opportunities exist to take high-potential immune modulators and widen or open the therapeutic window, is also consistent with our broad guiding philosophy. We believe that by taking on big challenges like these, we increase our chances of really moving the needle for cancer patients and realizing our vision as an organization. So thanks for your time and listening to that brief update. With that, let's open the call up for Q&A. Carlos and I will take your questions. Amy Peterson, who usually joins us on these calls, is currently performing her civic duty by serving on jury service. So we will... be happy to field your calls. Operator?

There's going to be more important and of course likely in the post substitutes on upsetting.

So on the ascent study for SASSA to somatic Cup of tea can.

Of our 35% PFS five to six months overall survival at 12 months.

Really a terrific outcome for patients and that's what's on underpin the approval in the second and third line settings.

In the post attitudes from upsetting I think what we've heard from talk to tell on he wasn't or are of 20 per cent or both would be clinically meaningful.

With a relatively short duration of PFS you know two to two to three months would be meaningful for these patients I would underscore my comments earlier on that.

Operator: As a reminder, to ask a question, you will need to press Sarva on your telephone. To withdraw a question, please press the pound key or hashline. Again, as a reminder, to ask a question, you will need to press Sarbonne on your cell phone. To read, direct a question, please press the Pound Key. Please send by will we compile his career in your office. Our first question comes from the line of Terrence Flynn from Golden Sack.

If you look in the ascent study the chemo arm.

These patients are on overall response rate of 5% so.

There's going to be significant unmet need remaining in this patient population, where the disease can progress very very rapidly. So.

So those are some of the benchmarks that where we're thinking about for the combination just to round out and talk a little bit about RMC.

Which is the combination with our PD L. One per body pack Miller map.

You know the the Kate to study here has been reported previously by Roche Taser plus Tdm one.

Terrence Flynn: Great. Thanks so much for taking the questions.

Sean: Maybe two for me. I was just wondering, broadly, Sean, if you could comment on enrollment trends you're seeing in your trials, given the pace of vaccinations and the U.S. has obviously been picking up, and infections have been going down, but maybe just, you know, what are you seeing at the enrollment level at your sites? And then maybe one for Carlos, just on pacing on spend for the rest of the year. Is the first quarter a good baseline to think about, or is there going to be upward pressure on that over the course of the year as you continue and roll out these key phase two studies? Thank you. Great.

<unk> was able to show a significant shift in the <unk> monotherapy from about 30% into the <unk>.

With PFS of greater than eight months.

So of course, we would be looking for the combination here to do.

To do more than the monotherapy and we've shown previously we've reported.

Pretty robust monotherapy activity, if a patent on a map in triple negative as well. So we know both of these agents.

009.

Problems, that's a map and putting them on a map both have single agent activity on oversee ware.

Sean: Great. Hi Terrence, thanks for the questions. First of all, with regard to enrollment, of course, we're seeing across the country a lot of great trends with vaccination and improving numbers across the board, and that's great. We're all looking to open up a bit more. I would say that with regard to clinical executions, still, you know, predominantly remote monitoring and remote activities. But, you know, we are seeing things steadily continue to improve, and, you know, we remain, you know, we remain. you know, on track with our guidance for initial data for these studies by the end of this year. Karen on the spend two.

Excited to see what this combination can do in this patient setting as well so I hope that helps.

Yes. It helps a lot. Thank you very much.

Our next question comes from the line that's true that's on zero from Piper Sandler.

Your line is now open.

Hey, guys. Thanks, so much for taking my question, maybe one quick one from me. So Sean you had mentioned IL, two and I think.

Many of US are familiar with the historical data that made a recombinant IL two which generated on why there's so much interest for that target, but maybe you could just speak to the.

Carlos: Karen, on the spend, Q1 is a pretty good proxy, even though there will be fluctuations from quarter to quarter. And we haven't really guided for a full year spend, but there shouldn't be anything super out of the ordinary.

The historical single agent profile of interferon Alpha.

Are there specific tumor types that have shown some interesting activity and why you see it as a great assets for conditionally activated version.

Yeah, Hey, Joe Great question.

So.

It is.

It's the cytokine cytokine sort of had a long time right interferon.

No not really.

Peter Richard Lawson: Okay. Our next question comes from the line of Peter Lawson from Barclay. Your line is now open. Hi, this is Mitchell. I'm on behalf of Peter. Thank you for taking our questions today. On the first question about 2,009, could you comment on the size and scope of the data we might see for the phase two data sets in 4Q?

<unk> pursued.

Bye Bye bye.

Let me just say that we're kind of blazing a trail here. We think this is a terrific opportunity for our technology.

On the.

The clinical activity.

On to too.

Two indications in particular, where.

Interferon Alpha has shown.

Sean: Yes, hi, thanks for the questions. So the study design across the three arms, arms A, B, and C, is to enroll 40 patients in each of those arms. And we are working hard towards that. As I mentioned, the goal is for initial data from arms A and B towards the end of this year, and arm C in 2022. And that remains our objective at this point: to drive enrollment as expeditiously as we can across those three arms.

Particularly impressive clinical activity.

Sean: Great. And then could you just talk about what the bar would be to be kind of like on efficacy for TMBC and HR positive or two negative breast cancer? It's kind of how far above the bar would you need to show to be considered positive data?

One is.

In the non invasive non.

Non muscle invasive bladder cancer area, where our interferon alpha to be gene therapy approach given by installation into the bladder.

As shown robust clinical activity and actually that product candidate is in registration.

Moment, so it's pretty clear that on the right setting.

Luckily delivered Inc.

Fair on could have a potent anticancer effects.

And then there's a study.

BMS showing combination with PD, one in melanoma, which showed up.

Significant or arb about 60% grade three four adverse events of 49% so.

Sean: Yeah, I think this was covered in some level of detail by Dr. Salani at our investor events on April 7th. And, you know, I would say just a high level to recap her remarks.

Wide ranging toxicities.

Of an immune nature from the administration of interferon and a systemic manner. So.

So I think it's and there are several other indications besides that where.

Sean: You've obviously got two quite different diseases here with hormone receptor positive and triple negative. In the hormone receptor positive setting, you know, ORR tends to be less. of a driver and less of an objective, given the natural history of these patients over extended periods of time, it's really more about the duration of response, as evidenced in our phase one data, actually, where we showed a promising clinical benefit rate at both 16 and 24 weeks.

Interferon.

Has potential so.

It's still early days for our program. Some of this has been about just the basic protein engineering too.

Take on.

Our growth factor cytokine, where we.

We know there's significant room for improvement, but we think there are a lot of places we could potentially go with this.

But at the moment that the program is serving.

Actually as a proof of concept for some pretty sophisticated masking approaches that.

We've been doing including dual masking that we've reported at the cytokines summit.

Which we think is a particularly.

Sean: So, you know, Dr. Talani said, you know, in this setting, an ORR, you know, you're looking for greater than 10%, and you're looking for something in the range of three to four months of PFS. Obviously, we'll be looking to do even better than that, but that would, in her words and those of our other steering committee members, be clinically significant in the hormone receptor positive setting. Triple negative, different, much more aggressive disease, of course. These patients, you know, they progress much more rapidly. So here, ORR is going to be more important.

On innovative approach that may be extendable to other cytokines as well.

Okay, great. Thanks for taking my questions.

My pleasure.

Our next question comes from the line of Rogers from from Jefferies.

Your line is now open.

Yeah.

Great. Thank you.

Sean maybe a quick one.

Steve on your early pipeline.

So given the versatility of the debt pro body platform.

And then you are going to say, it's thinking about there.

Sean: And, of course, likely in the post-Sastatuzumab setting, we saw in the Ascent study for Sassetuzumab a TECAN, an OR 35%, PFS 5 to 6 months, overall survival of 12 months. So really, a terrific outcome for patients, and that's what underpins the approval in the second and third line settings. In the post-Lastatustatuse setting, I think what we heard from Dr. Talani was an ORR of 20% or above would be clinically meaningful, with a relatively short duration of PFS, you know, two to three months would be meaningful for these patients.

Mortality any other particular modality.

On may seem appropriate for the pro body like are they on.

That's like antibody conjugates.

And Andy I mean kind of a modality you're thinking.

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Yeah, Hi, Roger Thanks for the question.

Yeah.

Commented during during my remarks here.

I do think one of the defining features of our company is really the breadth and depth of the science that we've been able to prosecute over the last several years.

Sean: I would underscore my comments earlier on that if you look in the Ascent study at the chemo arm, these patients had an overall response rate of 5%. So, you know, there's going to be significant unmet need remaining in this patient population where the disease can progress very, very rapidly. So those are some of the benchmarks that we're thinking about.

Both ourselves and with our partners, we've really built a significant research capability.

We are working across multiple modalities already checkpoint inhibitor antibodies.

Adcs bi specifics now moving into the cytokine space. We've also.

Sean: For the combination, just to round out and talk a little bit about RMC, which is the combination with our PDL1 probody, Pachmimimab. You know, the K2 study here, which has been reported previously by Roche, Atazzo plus TDM1, was able to show a significant shift in the ORR of monotherapy from about 30% into the 50s with PFS graded in eight months. So, of course, we would be looking for the combination here to do more than monotherapy.

<unk> got a growing interest.

Early though it may be in.

Applying the <unk>.

Direct the weapons, if you like to.

To cell therapies, such as car Ts.

Even car NK is where we did some work some years ago with MD Anderson so.

So really anything that looks it looks like on an antibody we can apply our technology to we think and that's really it.

And in no small part the depths of the protease biology expertise that we have developed over the over the years on the.

Sean: And we've shown previously, we've reported a pretty robust monotherapy activity for Pac-Millomab in triple negative as well. So we know both of these agents, CX2-009, Pactamase 2.009, Pachmulamab, and Paralizatamab both have single agent activity, and obviously, we're excited to see what this combination can do in this patient setting as well.

Tune ability of the.

Sean: So I hope that that helped. Yes.

The systems, which is a little different in each case right. Because he is the devil is really on the details here across each of these different modalities.

On the tune ability on the control if you like of the systems.

That will.

Allow us to move into these different modalities.

I'd refer you to.

Again the work.

Joseph Michael Catanzaro: Yeah, it helps a lot. Thank you very much. Our next question comes from the line of Joe Katanzaro from Piper Sandler. Your line is now open. Hey, guys, thanks so much for taking my question. Maybe one quick one for me.

The initial work that we've we've shown on on interferon.

You can see from that first preclinical data that we've shared that we we have very nice control over the system in terms of being able to activate.

Sean: So, Sean, you mentioned IL2, and I think many of us are familiar with the historical data that native recombinant IL2 has generated and why there's so much interest for that target. But maybe you could just speak to the historical single agent profile of interferon alpha. Are there specific tumor types that have shown some interesting activity? And while you see it as a great opportunity for a conditionally activated version. Thank you.

Both are singularly ended June masked version of interferon in a protease dependent manner. So this type of tight control that we've got we've been able to develop over this particular cytokine and I'm very confident others.

We will be very important for the future. So we're super excited about the science and continuing to explore all of these modalities, both ourselves and with our partners.

That's great thanks for that or the color on that.

Sean: Yeah, hey Joe, great question. So, you know, it's a, it's a, it's a cytokine, it's been around a long time, right, interferon, not, not really being pursued, you know, by, by, by. Um, let me just say that we're kind of blazing a trail here. We think this is a terrific opportunity for our technology. The clinical activity, I point to two indications in particular where Interferon Alpha has shown particularly impressive clinical activity.

It's all for me thank you.

Yeah.

Our next question comes from Dan I have on you.

From Rama from J P. Morgan.

Your line is now open.

Hi, guys. Thanks, so much for taking the question I just had a really quick one on CX 2043.

In terms of what are the ongoing from clinic preclinical activities here and the gating factors to an R&D filing and getting that program into the clinic. Thanks, So much.

Yeah, Hi, thanks for the question.

So.

We're at that point where were.

Doing all the things you do to get something into the clinic, and enabling studies, including getting GOP tox.

Sean: One is in the non-invasive, non-muscle invasive bladder cancer area where an interferon alpha-2B gene therapy approach, given by installation into the bladder, has shown robust clinical activity, and actually, that product candidate is in registration at the moment. So it's pretty clear that in the right setting, locally delivered interferon can have potent anti-cancer effects. And then, you know, there's a study from BMS showing combination with PD1 in melanoma, which showed a very significant ORR of about 60%, but grade 3-4 adverse events of 49%.

Getting to GOP talks.

It's a little bit of an unfortunate hiccup.

Yeah that I mentioned earlier on in terms of.

A delay on the supply chain.

These things are happening all over the place at the moment with.

On.

Biologics manufacturing as you know.

Given the.

The pressure on the system.

Understandably.

Brought by Vac.

Vaccine or other biologic.

Capacity being utilized for COVID-19, so and on other other COVID-19 related delays that are kind of out of our control, but so we're just we're doing the usual things and as I said the bad debt.

Sean: So, you know, wide-ranging toxicities of an immune nature from the administration of interferon in a systemic manner. So I think it's, and there are several other indications besides that where interferon has potential. So, you know, it's still early days for our program. Some of this has been about just the basic protein engineering to take on a growth factor of cytokine where we know there's significant room for improvement, but we think there are a lot of places we could potentially go with this.

This manufacturing.

Timeline change it's just.

We're just at that place right now where we're taking another look at the overall program timeline.

Does that help.

Thanks for taking our question.

My pleasure.

Our next question comes from the line of Mara Goldstein from Luca.

Your line is now open.

Great. Thanks, so much I apologize.

Sean: But at the moment, the program is serving initially as a proof of concept for some pretty sophisticated masking approaches that we've been doing, including dual marvelous that we reported at the cytokine summit, which we think is a particularly innovative approach that may be extendable to other cytokines as well.

Proverbial I missed the beginning of the call, but I'm busy earnings day, So I'm just wondering.

Maybe if you could just give us a little bit of a kind of high.

High level understanding of the differences and the engineer.

Engineering production aspect of creating pro body for cytokine biology as opposed to for a specific antigen targeted biology that'd be awesome.

Sean: Okay, great, thanks for taking my question. My pleasure. Our next question comes from the line in Roger's song from Jeffreys. Your line is that open. Great, thank you. Sean, maybe a quick one still on your early pipeline.

Yeah, It's a really good question and you know.

When we talk about the field of cytokines is.

It's easy to do.

Think of it as one bucket is it's obviously a bucket with a long very complicated things on it.

So many different.

Roger Song: So given the versatility of the pro-body platform, and you obviously are thinking about the cytokine modality, any other particular modality may seem appropriate for the pro-body, like the immunosimitory antibody conjugate conjugate. And any kind of modality.

Families different.

Three dimensional structures different multi merrick structures. There are often multiple receptors receptor complexes receptor families that different cytokines interact with so.

I really think here, it's going to be.

Cytokines by cytokine the field.

Really breaks down the challenges in that that's why we why are we seeing so much effort in IL, two well because it's a complex system.

Sean: Yeah, hi Roger, thanks for the question. As I commented during my remarks here, I do think one of the defining features of our company is really the breadth and depth of the science that we've been able to pursue over the last several years, you know, both ourselves and with our partners. We've really built a significant research capability. We are working across multiple modalities already, checkpoint inhibitor antibodies, ADCs, BISPICs, and now moving into the cytokine space.

So.

I would say that when we think about our technology again, I would I would reiterate that the experience that we've been able to gain over the years with.

On the generation of.

Mm wave upon wave of protease cleavable linker is a lot of which we haven't talked about yet.

On the not available in the literature.

There's still sort of know how to <unk> gives us a very unique opportunity to to tune conditional cytokines in ways that we think can could allow us to really control the activity on the marketing strategies are.

Sean: We've also got a growing interest early on, though it may be, in applying the, you know, directing the weapons, if you like, to cell therapies such as Cartes, and even Carr NKs, where we did some work some years ago with MD Anderson.

Similarly, we typically work when it comes to antibody based marking our approach has been and continues to be to us.

Sean: So, you know, really anything that looks like an antibody, we can apply our technology too, we think, and it's really, in no small part, the depth of the protease biology expertise that we have developed over the years. The tunability of the systems, which is a little different in each case, right? Because the devil's really in the details here across each of these different modalities.

Peptide masks, which we screen for on an antibody by antibody basis, but as you saw on the work that we presented on interferon Alpha.

Combine that with a steric masking strategy as well and it offers up some really interesting opportunities.

For that and potentially other cytokine classes as well.

At the end of the day, you know success in the cytokine field is going to depend upon.

Sean: The tuneability and control, if you like, of the systems that will allow us to move into these different modalities. And I would refer you to, again, the work that we've shown on interferon alpha. You can see from the first preclinical data that we've shared that we have very nice control over the system in terms of being able to activate both a singly and a dual-mast version of interferon in a protease-dependent manner.

As I've already mentioned very sophisticated protein engineering and I'm very proud of our team at <unk> and they continue to do some really interesting things.

Yes.

Thanks, I appreciate the color.

My pleasure.

Our next question comes from the line of Sarah <unk> from Guggenheim.

Your line is now open.

Oh, great. Thanks for taking my question just one quick one for me just you know.

That's been made about sort of the efficacy profile right.

Okay, four six hosted Teekay forsake setting for hormone receptor positive, but wondering if you could talk a little bit about sort of tolerability safety.

Sean: So this type of tight control that we've got, we've been able to develop on this particular cytokine, and I'm very confident others will be very important for the future. So we're super excited about the science and continuing to explore all of these modalities, both ourselves and with our partners.

For potential for 2009, and the ability to kind of move up sort of the treatment paradigm. Thank you.

Yeah, that's a great question.

A fair amount of time spent on on that.

Roger Song: That's great. Thanks for all the color.

During our Investor event got Atlantic talking about the the principle.

Anupam Rama: That's all from me. Thank you. Our next question comes from the lineup, Anupam Rama from J.P. Morgan. Your line is that open. Hi, guys. Thanks so much for taking the question. I just had a really quick one on CX2043 in terms of what are the ongoing preclinical activities here and the gating factors to an I&D filing and getting that program into the clinic. Thanks so much.

Adverse event that we are watching the phase II study, which is.

Of course ocular toxicity that.

It is a function of the tier four payload.

As she mentioned we agree I mean, we feel pretty good about our ability to manage that seven make per kit Q3 <unk>.

Schedule and.

Sean: Yeah, hi, thanks for the question. So, you know, we're at that point where we do all the things you do to get something into the clinic in I and dwindle studies, including getting GLP talks, getting through GLP talks. It's a little bit of an unfortunate hiccup that I mentioned earlier in terms of a delay in the supply chain. These things are happening all over the place at the moment with biologics manufacturing, as you know, given the pressure on the system understandably brought by the vaccine and other biologic capacity being utilized for COVID.

Requiring ocular prophylaxis mandating it in this study.

The combination of a steroidal and Vasoconstricting eyedrops cold compresses.

And if we look at the experience of others, including Immunogen with move it talks about.

We start to tell on you also refer to you know we feel we feel reasonably good about being able to manage that toxicity.

How that will help us move forward, obviously, we're optimistic one step at a time.

But we don't we don't see.

On the ocular toxicity being.

A really substantial barrier.

For 2009 in the long run.

Great. Thank you.

Yeah.

Sean: So, and other COVID-related delays that are kind of out of our control. But so we're just, we're doing the usual things. And as I said, this manufacturing timeline change is just, we're just at the point right now where we're taking another look at the overall program timeline. So does that help?

Youre welcome.

At this time I would now like to hand, the conference back over to counsel them for his closing remarks.

I on behalf of the executive team I'd like to thank you all very much for joining us. This afternoon, we look forward to updating you in the future on that.

Ongoing progress.

Yeah.

Great. Thank you everybody. Thank you for your time.

Sean: Thanks for taking our question. My pleasure. Our next question comes from the line of Marigold's team from Missou. Your line is now open. Great, thanks so much. I apologize to say the proverbial; I missed the beginning of the call on a busy earnings day. So I'm just wondering, maybe if you could just give us a little bit of a sort of high-level understanding of the differences in the sort of engineering production aspect of creating pro-bodies for cytokine biology as opposed to for specific antigens in targeted biology, that'd be awesome.

Okay.

Ladies and gentlemen. This concludes today's conference call. Thank you all for participating you may now disconnect and have a great day.

[music].

Marigold: Yeah, I'mara. It's a really good question. And, you know, when we talk about the field of cytokines, it's easy to, you know, think of it as one bucket. But it's obviously a bucket with a lot of very complicated things in it.

Sean: You know, there are so many different families, different three-dimensional structures, different multimeric structures; there are often multiple receptors, receptor complexes, receptor families that respond to different cytokines in Dracquids. So I really think here it's going to be, you know, cytokine by cytokine, that the field really breaks down the challenges. And that's why we have, why are we seeing so much effort in IL2? Well, because it's a complex system.

Sean: So I would say that when we think about our technology, Again, I would reiterate that the experience that we've been able to gain over the years with the generation of wave upon wave of protease cleavable linkers, a lot of which we haven't talked about yet and are not, you know, available in the literature, but still know-how to cytomics, gives us a very unique opportunity to tune conditional And the masking strategies, similarly, we typically, we typically, when it comes to antibody-based masking, you know, our approach has been and continues to be to use peptide masks, which we screen for on an antibody by antibody basis.

Sean: But as you saw in the work that we presented on Interferon 2 Alpha, we've combined that with a steric masking strategy as well, and it offers up some really interesting opportunities for that and potentially other cytokine classes as well. At the end of the day, you know, success in the cytokine field is going to depend upon, as I've already mentioned, very sophisticated protein engineering. I'm very proud of our team at Phytomics, and they continue to do some really interesting things. Thanks. I appreciate it.

Sean: Thanks, I appreciate her calling her. My pleasure. Our next question comes from the line of Ed Surrey-Dorough from Guggenheim. Your line is now open.

Ed Surrey-Dorough: Oh, great. Thanks for taking the time to ask a question. Just one quick one for me.

Sean: Yeah, hi, that's a great question. Again, a fair amount of time spent on that during our investor event, Dr. Talani talking about the principal adverse event that we are watching in the Phase 2 study, which is, of course, ocular toxicity that is a function of the DM4 payload. As she mentioned, and we agree, I mean, we feel pretty good about our ability to manage that at the 7-Mig-Pa-KGQ3 schedule. And, you know, we are mandating ocular prophylaxis mandating it in this study, a combination of steroidal and vasoconstrating eye drops, and cold compresses.

Sean: Just, you know, lots have been made about sort of the efficacy profile, right, and sort of the CDK-4-6 setting for hormone receptor positive. But I wonder if you could talk a little bit about sort of, you know, tolerability, safety for, you know, potential for 2009, and the ability to kind of move up sort of the treatment paradigm. Thank you. Yeah, that's a great question.

Sean: And if we look at the experience of others, including immunogen with myrotoctomab, which Dr. Talani also referred to, you know, we feel reasonably good about being able to manage that toxicity. How that will help us move forward, obviously, we're optimistic, one step at a time, but we don't see the ocular toxicity being a really substantial barrier for 2009 in the long run.

Chao: At this time, I would now like to hand the conference back over to Chow Tang for his closing remarks.

Chao: Hi, on behalf of the executive team, I'd like to thank you all very much for joining us this afternoon. We look forward to updating you in the future on our ongoing progress.

Operator: Great, thank you, everybody. Thank you for your time.

Operator: Ladies and gentlemen, this concludes today's conference call. Thank you all for participating. You may now disconnect. Have a great day.

unknown: Then and so on. I don't know.