Participants

Chris Ogden; SVP, Finance and Accounting; CytomX Therapeutics, Inc.

Sean McCarthy; CEO and Chairman; CytomX Therapeutics, Inc.

Wayne Chu; Chief Medical Officer; CytomX Therapeutics, Inc.

Peter Lawson; Analyst; Barclays

Roger Song; Analyst; Jefferies LLC

Joe Catanzaro; Analyst; Piper Sandler

Etzer Darout; Analyst; BMO Capital Markets

Anupam Rama; Analyst; JPMorgan

Mitchell Kapoor.; Analyst; HC Wainwright

Presentation

Operator

Good day, and thank you for standing by. Welcome to the CytomX Therapeutics First. Quarter 2024 financial results conference call. (Operator Instructions) please be advised that today's conference is being recorded I would now like to hand the conference over to your speaker today, Chris Ogden, CytomX's Senior Vice President, Finance and Accounting. Please go ahead.

Chris Ogden

Thank you.
Good afternoon, and thank you for joining us.
Before we begin, I would like to remind everyone that during this call, we will be making forward-looking statements Because forward-looking statements relate to the future that 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. We undertake no obligation to update any forward-looking statements, whether as a result of new information, future developments or otherwise.
Earlier this afternoon, we issued a press release that includes a summary of our first quarter 2024 financial results and highlights recent progress at Cytokinetics. We also issued a press release today announcing positive initial Phase 1a dose escalation data for monotherapy CX nine oh four, which will be the primary focus of today's call. We encourage everyone to read today's press releases and the associated materials, which have been filed with the SEC. Additionally, the press releases or recording of this call and our SEC filings can be found under the Investors & News section of our website.
With me on the call today are Dr. Sean McCarthy, CytomX's, Chief Executive Officer and Chairman, and Dr. Wayne Chu CytomX's Chief Medical Officer. Sean will provide an update on the overall pipeline and also outlines the topics this broader strategy for mass T cell engagers. Wayne will then give an update on the CX nine oh four Phase one dose escalation study before Sean provide closing comments, and we'll open up the call for Q&A.
With that, I'll now turn the call over to Sean.

Sean McCarthy

Thanks, Chris, and good afternoon, everyone. It's a pleasure to be here today to share our considerable progress during Q1, including our initial findings from our Phase one study of our EGFR targeted Probody T-cell engager, CX nine oh four. Cytomx is highly focused on addressing major unmet needs in oncology using our Probody therapeutic platform, a proprietary antibody masking strategy designed to improve the therapeutic window from multiple antibody modalities through tumor localized activation. We are leveraging our Probody therapeutic platform to discover and develop new cancer therapies based on unmasked T-cell engagers, masked ADCs and masked cytokine is our broad and deep pipeline encompasses more than 15 active programs, including three clinical-stage molecules and SIGNIFICANT retain commercial rights.
Strategic partnering is a long-standing components of our corporate strategy, and we're proud to be working closely with Bristol-Myers Squibb, Amgen, Astellas, Regeneron and Moderna on multiple Probody therapeutic programs.
We continue to be in a strong financial position with $150 million of cash at the end of Q1, which provides cash runway to the end of 2025, not including any milestone payments under our existing collaborations or any potential new partnership funding CytomX is very strong organizationally with integrated R&D capabilities, continued investment in our core technology and a deeply experienced team dedicated to our vision of transforming lives with safer, more effective therapies Moving to Slide 6.
The CytomX X product design strategy using our Probody therapeutic platform is informed by more than a decade of experience and seeks to balance target selection, marketing strategy and effector function to make meaningful impact in key areas of unmet need in oncology. Ch nine oh four brings the EGFR target together with T-cell engagement via CD. three with the goal of T-cell mediated killing of EGFR positive tumor types, potentially including those for which conventional antibodies have not shown activity six two zero five one is unmasked conditionally activated ADC that integrates the high potential of EpCAM as a cancer cell target with the potency of a topo one inhibitor payload ideally suited, we believe to high EpCAM expressing tumors like colorectal cancer. CHAO.
one leverages the potent activity of the cytokine interferon alpha, which in this case is the effector mechanism itself. Amassed interferon is designed to locally activate the intra-tumoral immune microenvironment with potential to drive responses across multiple cancer types, including melanoma, renal cell carcinoma and head and neck squamous cell carcinoma.
Q1 was an extremely productive quarter for Cytokinetics we are executing to our plans and we're making progress across the full breadth of our pipeline. Today, we're announcing positive initial Phase 1a dose escalation data for monotherapy CX nine oh four REGFRCD. three T cell engager in solid tumors. And this is the main topic of our update here today.
In addition to our exciting progress with CX nine oh four. During Q1, the first dose cohort cleared in the Phase one clinical study of two oh five one, our ADC targeting EpCAM. This study is focused largely in colorectal cancer, and we anticipate initial data in the first half of 2025.
Also during Q1 Phase one study initiation activities continued for CX eight oh one. Our mass interferon alpha, including the execution of an agreement with Merck to supply Keytruda for combination with CX. 81. We announced that agreement last night initial data from the eight oh one program is also anticipated in 2025 for them.
We continue to make excellent progress across our collaborations, including earning $10 million of milestones under our T-cell engaging bispecific collaboration collaboration with Astellas. That was for preclinical progress on the first two programs in the alliance. We were also delighted to welcome Dr. Xu to our Board during Q1. So a really productive start to 2024 for CytomX is on all fronts. And our current clinical pipeline is really gaining momentum. And we have a very exciting 12 to 24 months ahead of us.
Moving now to our T-cell engager strategy. T-cell engaging bispecific antibodies, of course, have enormous potential for the treatment of cancer. And our first demonstrated meaningful clinical clinical benefit in hematologic malignancies and looking at the solid tumor landscape for T cell engagers. However, it's taken time to see meaningful clinical progress and for this modality to really breakthrough in solid tumors. There are some significant challenges to overcome. Notably T cell engagers bring very high potency, and this potency can lead to toxicities in normal tissues where the tumor actually have interests may also be present.
Another key limitation for T cell engagers in solid tumors is cytokine release syndrome resulting from systemic binding to CD3 on T cells and also neurotoxicity in the form of ICAT. at CytomX is we have a broad based program focused on masking T-cell engagers to decrease tumor antigen binding in normal tissues and also decrease CD3 binding in the periphery, thereby improving therapeutic index. In addition to our internal programs, we're working with partners, Amgen and Astellas, Regeneron and BNS. in this exciting space, CX nine oh four is our lead program in the T-cell engager area, and I'd like to spend a few minutes now walking through the history and structure of this molecule.
We've had a long-standing interest in EGFR Cytomedix. Our seminal publication of the first ever successful antibody masking was focused on on the EGFR binding antibody cetuximab, for which we showed a marked reduction in systemic skin rash for the mast antibody compared to the unmasked group. These findings set the stage for the evolution of the mono specific EGFR Probody into our CX nine oh four bispecific T-cell engager.
We reason that EGFR as a target has so much more potential to be realized and the realization of this potential would require a more potent effector mechanism, leading us to the concept of the mass EGFRCD. three strategy encompassed in CX nine oh four. We did actually publish an early lead molecule from this program in cancer research. I have to demonstrate preclinical proof of concept, and we subsequently refined the structure using the depth of our platform and in collaboration with our partner, Amgen.
The next slide shows the molecular architecture of nine oh four CX nine oh four has one CD3 binding domain and one EGFR binding domain. Both domains amassed with unique peptides. Furthermore, the protease cleavable substrate are different in each binding domain, reflecting our preclinical fine tuning strategy for optimization of therapeutic window. Series nine oh four also has an Fc region as would be expected to have an antibody-like half-life.
This overall structure is somewhat similar to Amgen's tocilizumab that has shown impressive results in small cell lung cancer, shown on the right of this slide is a recap of the therapeutic concept for CX nine oh four and for our platform, generally, the concept is that masking reduces drug binding to target in normal tissues where the tumor tissue, the master removed by activated tumor proteases. This tumor localization leads to the improvement or creation of a therapeutic window for the EGFR CD3.
As Jean-Pierre has been shown previously, that the unmasked bispecific is highly toxic in preclinical models. So our marketing strategy is, we believe, essential for creating a therapeutic window in terms of the toxicities, we're looking to mitigate EGFR antibodies are well known to cause rash and gastrointestinal side effects. And so we've been specifically looking at looking out for our masking strategy to really limit serious EGFR toxicities, particularly Grade three and above.
With regard to CD. three. Our marketing strategy is, of course, designed to limit CRS, and I can't before handing over to Wei away. Let me review the high-level goals and achievements to date for our Phase one study of CX. nine and four, given the really high potency of T cell engagers and the widespread expression of EGFR gone above one for this study has been to evaluate the safety of nine oh four and we've made excellent progress.
As you will see from Wayne's presentation, we've explored non step and step dosing. We were very pleased to see very limited CRS with nonstop dosing, we believe because of successful CD. three Mascot and in step dosing cohorts rather remarkably, we've seen no CRS at all. We've also seen no evidence of IKON's at any dose level or scheduled. Furthermore, while we have seen some EGFR toxicities, these have been manageable and have not limited us in achieving therapeutically active doses. Again, this shows the success we believe of our EGFR marketing strategy and the success of each of our marketing is consistent with our prior published work.
But I mentioned earlier Goal number two of our Phase one study has, of course, been to look for initial signs of antitumor activity. As we've said in recent months. Any evidence of tumor stabilization or tumor shrinkage in this first-in-man study will be very encouraging. I want to emphasize that the patient population we've enrolled to date in this Phase one study is heavily pretreated and is a range of tumor types and is unselected for EGFR mutant.
All that said, we're delighted to announce today very encouraging early signs of anti-cancer activity for nine oh four, including confirmed resist responses in pancreatic cancer, a very difficult-to-treat tumor type that is not typically responsive to EGFR inhibition or for that matter to immunotherapy. Moreover, our initial assessments of pharmaco dynamics are supportive of the mechanism of action of CX nine oh four as a mass T cell engager providing crucial platform proof of concept with read through, we believe, to the many other programs we're working on as Cytomedix.
Importantly, this Phase one study is ongoing. We're continuing to dose escalate and enroll multiple tumor types, but our next goal is to determine the recommended Phase two dose and to define plans for Phase Ib expansions. We see the data that we're sharing today as a very promising initial step in the development of CX nine oh four, and this work positions Cytomedix at the forefront of the T-cell engager field.
Now let me hand over to Wayne to review the data in some detail.

Wayne Chu

Thanks, Sean, and thanks, everyone, for the opportunity to share our early clinical and translational observations in the ongoing dose escalation study. This slide summarizes the dose escalation scheme key eligibility criteria and study objectives. Patients with tumors with known EGFR expression were enrolled. However, patients were not selected based on EGFR expression.
Dose escalation was initiated using a non step dosing schedule in which CX. nine oh four was dosed once every two weeks. Doses starting from seven micrograms through six milligrams were tested. As we will discuss in the subsequent slide dose escalation of CX. nine oh four continued using a step dosing schedule with an initial target dose of five milligrams. Various dosing schedules were tested after which the target dose was administered every two weeks.
The data presented today represents safety and efficacy data from a total of 13 dose escalation cohorts through the 10 milligram target dose. And as Sean mentioned, dose escalation continues with the current enrollment testing 15 milligram target dose selected baseline characteristics for enrolled patients are shown in this slide.
The majority of patients enrolled in nonstop dosing escalation cohorts were those with microsatellite stable or MSS colorectal cancer, which I will from CRC from here on out, which has been demonstrated to be unresponsive to immune therapies such as checkpoint inhibitors with step dosing would step dosing escalation cohorts. We have begun to focus on patients with tumors with early evidence of clinical activity as well as other tumor types with known EGFR expression.
As is typical for a Phase one first-in-human dose escalation study, patients had advanced late-line disease enrolled. Patients received a median of four prior cancer therapies. Many were refractory to their last prior therapy and a considerable proportion received prior EGFR and our PD-1 and PD-L1 directed therapy. Early clinical pharmacokinetic data from the non step dosing schedule was consistent with the CX. nine oh four Probody T-cell engager design. The graph on the left shows that total CX nine oh four exposure increases linearly with increasing dose, indicating no apparent change in dose-dependent clearance or evidence of target mediated drug disposition.
The graph on the right shows the cycle one PK profile of CX nine oh four at the three milligram dose level the three curves shows circulating analyte concentrations of intact or mast CD. three, Intact EGFR and total Probody. Notably, the three curves are essentially superimposable indicating that CX. nine or four exists in circulation and predominantly intact or match form preliminary estimates of CX nine oh four half-life, our between 2.8 and 5.3 days.
This slide summarizes treatment related adverse events observed with CX nine oh four and the non step dosing schedule. It is important to mention that during this CX nano for escalation, no cortical steroids or other prophylactic medication was administered for systemic toxicities such as CRS. and I can's the safety and tolerability data shown here with non step dosing, therefore reflect the ability of the masking to mitigate CRS. And I can with that, the virtual absence of CRS. and I. cancer is quite striking through the three milligram dose level, no CRS or I can't of any grade were observed even at the six milligram dose level where two patients had dose limiting toxicity of grade three to sites to tennis synovitis and Grade three rash no patients experienced, I can't have any grade.
And only Grade one CRS characterized by transient fever without any other signs or symptoms associated with CRS was observed low grade musculoskeletal adverse events such as our Roger and arthritis were observed. In addition to the one grade three tenants synovitis at the six milligram dose level, musculoskeletal events overall appear to be associated with a dose-dependent increase in circulating IL-6. As shown in the graph.
This is in direct contrast with CRS, where the association with circulating IL-6 levels was much less evident. Similarly, except for the grade three rash observed at the six milligram dose level, only grade one rash was observed. Overall, the data presented here quite convincingly demonstrate the benefit of masking up on effectively eliminating CRS and I can't which constitute dose-limiting toxicities with many T cell engagers based on the observations during dose escalation on the non step dosing schedule, which demonstrated that CRS. and items are effectively mitigated by the masking of CX. nine oh four step dosing schedules and tocilizumab prophylaxis for you specifically to mitigate emerging musculoskeletal adverse events, maintain a broad therapeutic index and allow continuation of escalation to higher and potentially more efficacious target doses.
These measures enabled escalation to higher CX nine of our target doses while continuing to maintain an acceptable safety and tolerability profile. Impressively, no CRS or icons of any grade was observed. Moreover, the incidence and severity of musculoskeletal adverse events did not substantially increase with higher CX nine oh four target doses, no related grade three rashes were reported and no treatment related adverse events resulted in CX nine oh four treatment discontinuation. Overall, the safety profile of CX nine oh four continues to be favorable.
And importantly, enable CX nine afford administration and management of adverse events in an outpatient setting. In this regard per protocol, no mandatory hospitalization is required for monitoring a clear dose levels and the safety profile observed to date has not necessitated a change to this practice in the context of a favorable safety profile, we observed compelling signs of CX nine or for anti-tumor activity, highlighted by activity observed to date in patients with advanced pancreatic adenocarcinoma.
The responses observed with CX nine oh four are highly encouraging given that outcomes in patients with recurrent metastatic pancreatic cancer remain extremely poor with current available therapies. Shown here is the waterfall plot of six efficacy evaluable patients treated across a range of target doses on both nonstop and step dosing schedules confirmed partial responses per resist. 1.1 criteria were observed in two of the six patients, one was treated with six milligrams on a nonstop dosing schedule and had an 83% reduction in measurable tumor burden. And a second patient was treated on a step dosing schedule with a target dose of five milligrams had a 51% reduction in tumor burden. Furthermore, of note, all six patients had disease control of the six patients to remain on study treatment, and we will now discuss these patients in greater detail.
The first case describes a confirmed partial response in a 49 year old patient with metastatic pancreatic adenocarcinoma. Prior therapies included surgery, radiation therapy and three lines of prior chemotherapy. Patient received CX nine oh four on a STEP dosing schedule with 1.5 milligrams administered on day one and the target dose of five milligrams administered one week later and then two weeks thereafter, every two weeks thereafter, patients had not experienced cytokine release syndrome or I can't the patient experienced grade three related arthralgia but this resolved to Grade one after one cycle delay and administration of cortical steroids.
As shown in the CT scan images, the patient achieved a partial response with deeper reduction in tumor burden to serve as the confirmatory CT scan. And as I mentioned, this patient remains on CX nine oh four treatment having received over three months of treatment to date. This next case illustrates durable stable disease with CX. nine oh four and a 59 year old patient with metastatic pancreatic adenocarcinoma who have received three prior lines of systemic chemotherapy patient received CX nine oh four on a stepped dosing schedule with 1.5 milligrams administered on day one five milligrams on day eight and 10 milligrams on day 15. Every two weeks thereafter.
Patient tolerated CX nine oh four treatment well with no CRS, I can't or musculoskeletal events and only grade one popular pustular rash, which resolved with topical treatment patient was able to maintain stable disease with no evidence of measurable tumor growth and additional information supporting continued clinical benefit included a greater than 50% reduction in serum CA 19 levels and overall improvement of performance status from baseline. This patient remains on CX nine oh four treatment having received over 3.5 months of treatment to date.
Preliminary translational data indicates T-cell pharmacodynamic activity that is consistent with the mechanism of action of CX nine oh four and pancreatic adenocarcinoma figure on the left is an immunofluorescence image from a biopsy obtained prior to CX nine for treatment in a patient with pancreatic cancer who achieved a deep partial response. The colors indicate T cell markers in red, dark blue and Magenta and cancer cells in light blue.
And as you can see, the pretreatment biopsy showed a high level of CD8 positive T cells within the tumor microenvironment, indicating their contribution to T cell engagers anti-tumor activity. The figure on the right shows the reduction of peripheral CD8 positive T cells as it relates to resist 1.1 response, both pancreatic patients with confirmed partial response had among the greatest reduction of peripheral CD8 positive T-cells following CX nine oh four treatment, consistent with the trafficking of T cells from the periphery to tumor sites as a mechanism of action of T cell engagers, taking a step back from the early but compelling activity of CX nine oh four in patients with pancreatic adenocarcinoma shown here is the waterfall plot for efficacy evaluable patients treated with CX. nine oh four target doses greater than or equal to 0.75 milligrams.
While no objective responses were observed in patients with other tumor types. Reductions in measurable disease burden were observed in a total of eight patients, including the two pancreatic cancer patients with partial responses. Reductions in measurable disease burden were also observed in patients with CRC, esophageal carcinoma and non-small cell lung cancer. We believe that the early signals of CX nine oh four activity in pancreatic cancer are compelling and that currently tested target doses are efficacious. As a result, study enrollment moving forward, in addition to continuing to enroll patients with pancreatic cancer will focus on patients with other EGFR-positive tumor types, including lung cancer, upper GI cancers and head-and-neck cancer.
This slide summarizes the time on study treatment for patients treated with CX nine oh four, again, highlighting the patients with pancreatic adenocarcinoma that continue to derive clinical benefit with ongoing CX nine oh four treatments. Importantly, while CX Sino-Forest has had minimal clinical activity to date in patients with CRCCX. nine oh four retains its pharmacodynamic activity as illustrated in this slide, which are immunofluorescence images of biopsies taken from a patient with MSS CRC at baseline.
And while on CX final four treatments as you can clearly see at baseline, the tumors tumor is notable for the almost complete absence of CD8-positive T cells within the tumor. In contrast, the on-treatment biopsy showed a substantial increase in the number of CD8 positive T cells within the tumor. This observation is a clear demonstration of the CX. nine oh four mechanism of action and demonstrates potential combinations strategies for the treatment of CRC.
In summary, we are very encouraged by this early clinical data of CX nine oh four in the ongoing Phase one dose escalation CX nine oh four has a favorable safety profile, which given the broad expression of EGFR in normal tissues in addition to cancers is indicative of the ability of masking to maintain a meaningful therapeutic index. Second, CX nine oh four has promising early efficacy and pharmacodynamic activity, highlighted by the confirmed partial responses in patients with metastatic pancreatic adenocarcinoma and early demonstration of CX nine oh four mechanism of action, including in colorectal cancer, clinical and translational observations have been extremely valuable in demonstrating not only the early clinical activity of CX. nine oh four, but also provide clear direction to plans to ultimately determine the recommended Phase two dose. And this includes continued enrollment in pancreatic cancer and enrollment in other EGFR positive tumor types. Data also is more responsive to immune therapies paid based on prior clinical experience. Together, these data will inform future development of CX nine oh four, which include considerations of combination strategies. And with that I will now turn it back to Sean for concluding remarks.

Sean McCarthy

Great.
Thanks, Wayne.
So I'm staying with CS 94 for a moment.
We're excited by our progress to date, developing this very novel drug candidate.
Egfr is such a high potential target with expression of many tumor types. And we're just at the beginning of learning what six nine zero four can do for patients. We clearly have a drug candidate with confirmed monotherapy activity, and we're redoubling our efforts to generate data in additional tumor types as we more broadly explore nine or four ideas also unlocks potential strategies for future combinations.
As we mentioned, focusing for a moment on pancreatic cancer, this is one of the greatest areas of unmet need in oncology today, and it's notoriously difficult to treat. Second line response rates are in the single digits and PFS and overall survival just a matter of months to reiterate the importance of our data shared today, pancreatic cancer does not respond to either anti EGFR antibodies or to immunotherapy alone. What we have shown today is that when we combine these two powerful strategies in bispecific form enabled by our Probody masking technology.
We can elicit meaningful responses in late-stage pancreatic cancer patients since 94 brings these two mechanisms together into an integrated and unique pharmacology that could impact this very difficult-to-treat disease showing how mast Probody T-cell engagers can be a new frontier in the war on cancer. These results are the embodiment of exactly what CX nine oh four was designed to do and we plan to aggressively pursue this signal for the better for the benefit of people afflicted with this devastating tumor type.
Now, zooming back out to our full pipeline and looking ahead to the rest of this year and also into 2025, we anticipate a great deal of additional progress at Cytokinetics. We see the data we're sharing today are known for as a promising initial step in developing this asset and also our T cell engager portfolio. Overall T-cell engagers are starting to break through in solid cancers and is exciting to be playing our part here at Cytomedix in this highly promising field, not only with NATO for, but also the many T cell engager programs. We're advancing through preclinical discovery and development, and we look forward to providing an additional C NATO for updates later this year.
Now, of course, today's update has been very low for focus but before I wrap up, I'd like to remind everyone to also keep our other programs in mind. We're making a lot of progress on multiple fronts. CX. two zero five one and CH. eight oh one, our wholly owned assets, and we anticipate Phase Ia data for both in 2025. We're already in our second Phase one cohort with 2051 must and yet can ADC and clinical initiation for six eight zero one Ahmass interferon is imminent.
I'd like to close by thanking everyone involved in this work for their commitment to our vision. The Cytokinetics team is intensely focused on delivering an innovative pipeline for the benefit of people living with cancer, and it's truly a privilege to work with such a talented team. I also want to sincerely thank the patients who join our studies, their families and our investigators. And with that, operator, let's go ahead and open up the call for questions.

Question and Answer Session

Operator

(Operator Instructions)
Peter Lawson, Barclays.

Peter Lawson

Thank you so much. Thanks for sharing the data. I'm really excited the mask and benefit you've seen. Do you think that can also extend to other T cell engagers and then the responses you've seen so far and do you think is something special about pancreatic cancer? Or do you think you can get deeper responses in other tissues as well?

Sean McCarthy

Hi, Peter. Great. Great questions. Thanks. And regarding that the extension and the read through to other programs, we're obviously very optimistic that that will be the case. You got to start somewhere in nine oh four, I think is a very strong start for us. We've learned a lot with this one in the clinic and as we mentioned, both internally and with our with our partners, we're doing a lot of work in T-cell engagers. We've got multiple programs. In fact, the majority of our partnered work is in T cell engagers so we would expect to make substantial additional progress here over the next few years.
In terms of pancreatic, I think it's a great question. It's been interesting to see them.You know, we've done a lot of thinking about this. Obviously, in pancreatic is typically thought of as an immunologically cold tumor or an immunologic desert, if you like. But actually evidence is beginning to mount suggesting that that might not be the case.
If you look at the Roche BioNTech on the vaccine data, most recently updated at ACR is really interesting. It suggests that there are some neoantigens in pancreatic cancer that there is some immunologic microenvironment. It looks like with this combination of each well, there's also EGFR, of course there, but no one's been able to break through with an anti EGFR directed therapy. So we think that could be something very unique about EGFR and CD3 in this particular tumor type.
But absolutely, it does not indicate that others would not respond to nine oh four. We're still very early in this study. As Wayne mentioned, the the colorectal data is interesting is it is there or MSS. patients that we've shown today.Does it does it does another cold tumor? Some not a lot of progress has been made with T-cell engagers yet in CRC so we would be looking to combination strategies there.
As far as the other tumor types are concerned, it's just very, very early days, for example, like outside lung, where we had two patients in the dose escalation study to date, one of those was treated at a very low dose. So probably not relevant. We really just haven't done the experiment yet. So we're going to keep enrolling across multiple tumor types in Phase 1a as we continue to pursue both the pancreatic signal and and define the activity of the drug across hopefully multiple tumor types over time.

Peter Lawson

Thank you. And then, Steve, the depth of the responses is that correlated with EGFR expression was it tumor microenvironment?

Wayne Chu

So one thing we have not shown was up this shown in this presentation, but we continue to evaluate is the level of EGFR expression as assessed by immunohistochemistry assay, and we've been doing this on a retrospective basis for all the patients that have enrolled to gauge based on our early data with EGFR by this IHC assay, we have not seen a clear association between EGFR expression and the left and the depth of the response. And just as an example, on the two patients in pancreatic cancer, whilst we had a confirmed partial response, one patient had a moderately high level of EGFR expression by IHC. But then the other the other patient had a very low level of EGFR expression. And it's actually the patient who had the 83% reduction and measurable tumor burden that had the low level of EGFR expression.
Interesting, but a more more word, yes, more work to be done there, but some that, Peter, a lot of it depends also on the assay itself. So we'll continue to look at that relationship.

Peter Lawson

I'll get back into the queue.
Thank you so much.

Operator

Roger Song, Jefferies.

Roger Song

Great. Congrats for the data and thank you for taking my question and a few questions from us on the first one related to that, those relationship seems the are the efficacy or antitumor PBT is not clearly collared with the dose level. My question is how do you think about as you dose higher even beyond TIM AG. Now you're at the 15. How do you think about the balance between the efficacy and the?
Not? Yes, I can't say more. These three are EGFR related tolerability profile. How how confident you are you can keep dosing higher? Thank you.

Sean McCarthy

Yes, thanks, Roger. Let me kick that one off year. I'd say I think that there is a dose response in the that the responses that we're seeing, the confirmed resist responses. We've seen a five and six milligrams of remember that we began this dose escalation at seven micrograms. So, you know, the range of doses where we're seeing activity is actually really consistent with our from our predictions and for modeling of where the biologically effective range would be. So we think we're in the zone.
We do believe, however, because of the safety profile, we can dose higher and whether that will help or not, I don't think we know, I think all of us in the T-cell engager field are kind of trying to figure this out. And if you look at Amgen's tireless I-Mab, I mean, they were all the way to 100 and concluded in the end that 10 milligrams was the dose to move forward because 100 didn't give significant additional efficacy. So I think we want to learn more, but we're ready. I'm very encouraged that we have this clean safety profile with EGFR, I guess, exceeded our expectations. It will allow us to dose escalate further and we will do that and we'll see where it takes us.

Roger Song

Got it. And my follow-up question is related to your partner and Jim, so this data have you share with them with the partner and if so, any initial feedback? And also understanding you well on giver it update by the end of the year, what you are looking for in order for both of you two parties to make the Phase Ib study design decision.

Sean McCarthy

Yes, great questions at. So with Andrew and let's take a little step back and talk about just recap the the of the agreement that we have with Amgen. So we're obviously running Phase Ia study and we do share data with them as it emerges. And we are also responsible for running the Phase Ib once we get that up and running. And the transition from Phase one to Phase Ib is a decision that we'll take jointly with Amgen and of course, the goal would be to in Phase Ib to enroll specific EGFR positive tumor types or which one now quite obviously would be pancreatic.
We would resume based on this very exciting signal that we've seen. And so we because we are on the way that enrollment has unfolded yet, we still have just not enrolled many patients in lung or head and neck. For example, we do want to bring in a few more patients, get some additional experience in those tumor types before we have the conversation with Amgen later in the year about what the Phase Ib strategy would be. So the update later this year could be a couple of things that could be done additional data from which we would ballpark we should have by end of year another 10 or so patients of data. And it could also be an operational update that we've agreed with Amgen on the next steps and we just have to have that dialogue with them. But in terms of their perspective on the data, I think has a question best asked of them at this point in time. But obviously, we're we're really excited by our progress.
Excellent.

Roger Song

Thank you.
You're welcome.

Operator

Joe Catanzaro, Piper Sandler.

Joe Catanzaro

Thanks for taking my questions and exciting data here. I guess maybe first one on the EGFR mediated tox that you're seeing. I guess my question is like what do you think is happening? Is that some small amount getting unmasked in periphery or maybe a small amount getting unmasked in the tumor and then reentering circulation? And is that tox that you're seeing typical of sort of historical EGFR experience a cetuximab? Or is there anything indicative that it's T cell targeting of EGFR on normal tissue? Thanks. And I may have one follow-up?

Sean McCarthy

Yes, Joe, thanks for the question, um, the um, what first of all, let me say that we're really, really pleased with the very low incidence of Grade three rash in this study, we only have one patient over the 35 patients with a grade three treatment-related rash, and that's a significant achievement. We think come because this unlocks the opportunity to use this mechanism. It just requires that otherwise couldn't be sure exactly whether the Gevaert. So we're very, very pleased about that.
Obviously, early days more work to do. But but we're encouraged and, you know, with any drug, you're going to see some you're going to see AB's. It's very hard to say what are they where they're coming from? Is that local is a systemic, we don't know. And we may never know in a way, might not matter that much because it's all about the risk benefit profile. And we're obviously delivering something we think we have very important if it did at least initially for patients with very late-stage pancreatic cancer. I would say it on the type of rash that we see in cetuximab. Rashes is typically the acne form rash.
We are we see some of that grade one grade two there also, as Wade mentioned, macular popular rashes, which we have maybe more T cell evolve T cells and deciding we're going to have to learn more about it, but we're not worried about it because it's mostly grade one two, if I look across the entire study. The incidence of rash across the entire 35 patients was 40% on OpEx, just about all grade one, two and manageable. So we're really encouraged by the AE profile here, not to mention the CRS profile, which really quite frankly surprises to the upside.

Joe Catanzaro

Yes, I think that that's helpful like me and my follow-up for the pancreatic cancer patient that had that deep response and and then subsequent progression, wondering if you could maybe elaborate a little bit more on that progression event on? Was it a new lesion growth of a target lesion? And if it was a new lesion, maybe you're able to sort of profile it and see what's going on. Just anything you could say there?
I guess would be would be interesting.

Wayne Chu

Yes, I can provide some details on that on. This is a patient that dumb, but with the six milligram not SubQ dosing, had a confirmed partial response does present a strikingly with over 80% reduction in measurable tumor burden. The patient did progress based on growth of the target lesion from the nadir as well as the appearance of, I think of one new new target lesion, a non sorry, one new lesion. So that was the nature of the progression on that particular patient. But all through that frame, Tom McCourt, the patient did quite well clinically. It was just based on the radiographic progression there.

Joe Catanzaro

Okay, thanks. And maybe if I could just squeeze in one more quick one. Maybe going back to an earlier question, just if you could maybe speculate more on what you think it may be going on in MSS CRC. It seems mechanistically like you're seeing T cell infiltration, but that's not translating to tumor reduction. So I'm wondering if you have any other sort of hypotheses of what may be going on in those patients?

Sean McCarthy

Yes.
I think mechanistically, it's really interesting when we think about how T cell engagers work overall, right? The CD. three arm, CD. three, combined with the tumor antigen, we think at these typically is being MHC. non-restricted mechanisms that may very well very well be what's going on, but that could be they could be more than necessary to really mount an antitumor response.
I think we're in again in the field. I think there's more to be learned about specifically how CD. three T cell engagers kill cancer cells. Clearly we're doing it in pancreatic cancer. We're getting the T-cells there in CRC, but it draws one's attention to thinking about what combination strategies could get you to actual objective tumor responses so I think more work to do there and some of the basic science and then also clinical work that we can do in terms of clinical combinations is quite intriguing.

Joe Catanzaro

Yes, okay. Thanks.
Thanks for the update, and thanks for taking my question.

Sean McCarthy

You bet.

Operator

Etzer Darout, BMO Capital Markets.

Etzer Darout

Thanks for taking the question. Just, Dan, if you could maybe talk through on your current thoughts on sort of the STEP versus the nonstop dosing, particularly in the pancreatic arm, Coca-Cola patients that sort of had a response and how you're kind of thinking about potentially moving one or the other option forward as you sort of expand on the patients. And then I don't know if you said this specifically, but about sort of the EGFR expressions across sort of the patients and that that you've seen so far is it that you're going to moving forward, you will look at EGFR expressions? Or is there an opportunity to kind of look at EGFR expression across the folks that you have already sort of enroll in the study. I don't know if I caught that correctly. Thank you.

Sean McCarthy

Yes, thanks. Thanks answer.
In terms of moving forward, which type of loans that we obviously haven't made a decision on that yet.
But I would say based on our experience to date, we are more likely that our fees, 1B doses will be set as strategies because it's allowing us to get to significantly higher target doses. And we do think there's a dose response here of sorts. So more to be learned, there will also likely take when you think about Project Optimus considerations will likely want to take more than one dose and schedule into Phase Ib to gain further experience of the drug candidate, not only in pancreatic, but also at other in other tumors as well in terms of EGFR and is surprising actually how on earth, how should I put this the available assay for EGFR assays to EGFR.
But I see let's just say it's not perfect.
And so we're not sure how much one would want to rely on it moving forward, particularly because it doesn't seem from our early data that this is a straightforward yield, ADC type thing where you have high target is required for activity, yes, these drug drugs like T cell engagers just up would be predicted to be active at low target levels because of the mechanism of the amplified mechanism of tumor killing one T cell can kill multiple GMSL. So I think we've got more to learn there.
And that's why we're where we may not be needing or leveraging EGFR selection on a go-forward basis based on what we've seen so far.

Etzer Darout

Got it. Thank you.

Sean McCarthy

You're welcome.

Operator

Anupam Rama, JPMorgan.

Anupam Rama

Hey, guys. How are you and thanks so much for the data update. Can you comment was there anything in the baseline characteristics, number of prior treatments?

Wayne Chu

I think the PDX case study that you said was three lines of therapy or otherwise that might be predictive of a response. I think based on the first question, EGFR expression didn't correlate.

Anupam Rama

And then can you comment in I'm sorry, if I missed this, the other three stable disease patients, what was their duration? Thanks.

Sean McCarthy

Thanks, Annabel. I'll take the first question in terms of, um, you know, but right, which I think was there anything in the patient characteristics that could have been predictive of response? And I'd say no, not really does. Again, these are all pretty late-line patients and And aside from EGFR.
Yes, we did show on that. That said, we showed a slide of on a pretreatment biopsy of a patient where with pretty high levels of pretreatment, CD8-positive cytotoxic T cells, which is intriguing that it certainly could have contributed to the risk to the response. And so on that, that's a that's something that we have observed. We don't have that data systematically across the whole study. That's difficult data to get for every patient, but it is intriguing on in terms of the stable disease on when could address that question, real quick?

Wayne Chu

Yes. So as we showed in the swim lane plot during the presentation, there were a number of patients who were able to maintain a stable disease for at least one of tumor response. And a smattering in that include a smattering of patients that had durable stable disease through tumor two tumor responses for the four otherwise, patients were able to achieve stable disease and then it was followed by progressive disease.

Sean McCarthy

I do think it's important to reemphasize that these these again impact pancreatic separate. As you as everyone knows, it's a very rapidly progressing disease. These these are patients who, for the most part, have had three or four priors and so on this side. So yes, we think this is really exciting data.

Anupam Rama

Thanks so much for taking your questions.

Operator

(Operator Instructions) Mitchell Kapoor, HC. Wainwright.

Mitchell Kapoor.

Hi, everyone. Congrats on the positive data. I wanted to ask about the total eight patients with tumor reductions. The other so well, I guess if you could just broadly comment on what a spider plot to these patients might look like. Are you seeing a trend and depth of response over time? Or how are we seeing those tumor reductions evolve?
Yes.

Sean McCarthy

But I mean, it's early days.
I think that those that those eight patients that were treated with pancreatic patients and you can see them in the waterfall plot. I think there's encouragement there in terms of the fact that escalation continues here. We'll keep pushing the dose here. And so at this point, I think it's fair to say the spider plot would be relatively immature.

Mitchell Kapoor.

Okay, thank you.
And could you just comment on the other confirmed partial response patient and how much duration of follow-up that patient had.

Wayne Chu

So that patient on again was treated at the six milligram non step dosing schedule had confirmed partial response. And that patient remained on study about eight of on-study treatment approximately 18 weeks before having progressive disease.

Mitchell Kapoor.

Okay, great.
Thank you for taking my question.

Sean McCarthy

You're welcome.

Operator

Thank you. And I'm showing no further questions. I would now like to turn the conference back to Dr. Sean McCarty, cytometers, Chairman and CEO, for a closing remark.

Sean McCarthy

Great. Thank you very much, and thanks, everyone, for listening in today. Service has made terrific progress so far in 2024, and we look forward to providing additional updates as the year proceeds and as we continue to build our company for the long term to make the biggest difference we can for patients. And so thank you very much, everybody.

Operator

This concludes today's conference call. Thank you for participating, and you may now disconnect.