Q1 2025 CytomX Therapeutics Inc Earnings Call
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.
They're 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.
The SEC S D C dot Gov.
We undertake no obligation to update any forward looking statements, whether as a result of new information future.
Your developments or otherwise.
Earlier today, we issued a press release that includes a summary of our first quarter 2025.
Actual results and highlights we can progress that they tell me.
Additionally, this morning, we are excited to announce.
Positive interim phase one data for CX, 2051, and advanced colorectal cancer as.
As well as a $100 million financing with a leading group of healthcare investors.
The focus of our call today will be the phase one data for CX 2051.
For details on the company's financial results and pipeline updates, we encourage everyone to read today's press releases and the associated materials, which have been filed with the SEC.
Additionally, the press releases a recording of this call and our SEC filings can be found under the investors and news section of our website.
Speaker Change: With me on the call today are Dr. Sean Mccarthy, <unk>, Chief Executive Officer and Chairman.
Speaker Change: And Dr. Wayne Chu tectonics of Chief Medical Officer.
Speaker Change: Sean will provide introductory remarks regarding CX 2051 design and clinical strategy.
Speaker Change: Wayne will then walk through the CX 2051 phase one interim clinical results and next steps for the program.
Speaker Change: We will then wrap up with concluding remarks, before we move to Q and a.
With that I'll now turn the call over to Sean for opening remarks.
Sean: Thanks, Chris it's a real pleasure to be here today to share our exciting update on CX 2051.
Sean: This is a transformational moment for <unk>, we believe we've really broken new ground in colorectal cancer with this novel antibody drug conjugate.
Sean: It's been uniquely enabled by the cytogenetics probiotic therapeutic platform.
Sean: The results were sharing today represent the integration of years of learning about our technology and importantly, how to best direct it to the maximum benefit for cancer patients.
Sean: Before getting to 6051, we're of course delighted to have also announced today as Chris just mentioned $100 billion financing with a top tier syndicate of health care, especially as the investors that belief inside so it makes truly underscores the importance of what we have achieved with teaser of five one and the potential of this product.
Sean: It's been I think positions us extremely well to continue our determined and focused execution towards bringing transformational cancer therapies to patients.
Sean: Turning now to CX 251.
Sean: Colorectal cancer remains one of the biggest unmet needs in oncology today with approximately $1 9 million patients diagnosed each year on a global basis and this disease burden is expected to increase considerably over the next couple of decades to more than $3 million and is currently the second leading cause of cancer deaths worldwide.
Sean: This is a significant global health problem and despite many advances across many other cancer types in recent years.
Sean: Colorectal cancer has not seen very much impact at all from innovation over that period of time, resulting in our current five year survival rates in metastatic colorectal cancer of only five only 13%.
Sean: The current pad.
Sean: This situation is unfortunately really underscored by just having adequate options are for the treatment of late stage CRC and the third and fourth line setting or later.
Sean: Current standard of care therapies have core response rates unlimited survival benefit there is enormous room for improvement.
Sean: So I'd say it makes we have taken this challenge head on by designing a colorectal cancer targeting antibody drug conjugate CX 2051.
Sean: Antibody drug conjugates are transforming cancer care, making a really big impact in the treatment of many solid tumors accrued benefit for many many thousands of patients around the world.
Sean: This class a differentiated targeted oncology therapeutics continues to build very substantial value.
Sean: The adcs have yet to breakthrough however in colorectal cancer.
Sean: Our goal is to transform colorectal cancer care with CX 2051, a first in class antibody drug conjugate that we've carefully designed to target a protein called <unk> that is present at high levels in CRC.
Sean: We've been highly focused on running a phase one clinical trial over the past year entirely focused in CRC. This is a very tough cancer to treat but we really wanted to do the killer experiment to see what <unk> can do for these patients.
Sean: Okay.
Sean: Today, we are very excited to share positive phase one clinical data at <unk> 501.
Sean: And our first 12 months in the clinic, we have demonstrated robust.
Sean: Anticancer activity for CX 2051 in metastatic CRC with a 28% confirmed overall response rate at.
Sean: 94% disease control rate and five eight months of preliminary progression free survival.
Sean: This strong anticancer activity offers the potential to position <unk> as a new standard of care in late line colorectal cancer.
Regarding safety <unk> five one has shown a favorable safety profile to date, including no dose limiting toxicities during dose escalation.
Sean: We believe the safety profile, we've seen to date in late line CRC is strongly supportive of developing two or 501 in earlier lines of therapy, including in combinations.
Sean: Furthermore, our marketing strategy has succeeded in avoiding classic <unk> toxicities that have impeded the successful development of drugs against this target before additionally.
Sean: Additionally, we can say with some confidence that <unk> has the potential to be a pan CRC target. Since we have validated that the target is indeed present at high levels in all patients we have tested.
Sean: Taken together, we see this as a very strong start to the <unk> 501 development program.
Before I hand over to Wayne to walk through our exciting results I'd like to make a few comments on the molecular design of CX user of five one and our phase one clinical strategy.
Sean: First of all a few words on the target.
Pet Chem or epithelium cell adhesion molecule, we really believe is an ideal CRC target enabled by the <unk> platform.
Sean: <unk> has high and uniform expression across colorectal cancer and you can see here at immuno histochemistry image of a patient actually in our phase one clinical trial, showing just how Si <unk> expression is in this cancer type.
Sean: In fact, this patient has a maximum score a score of 300.
Sean: By this assay.
Sean: Now the challenge with that Tam in the past has been its expression in normal tissues and this has limited drug development due to toxicities that have emerged including acute pancreatitis.
Sean: So we have developed and designed CX 2051, as a first in class <unk> targeting antibody drug conjugate and we really believe with this molecule we have the right target the right payload and the right tumor type and it's really how these three design elements come together that underscore the progress that we are sharing.
Sean: Today with this really exciting program.
Sean: So 205, one is based on a high affinity anti <unk> monoclonal antibody that we have masked using our proprietary <unk> therapeutic platform and the masking is designed to reduce <unk> binding in normal tissues.
Sean: The masks, however are removed specifically and selectively within schuh with tissue by tumor associated proteases, resulting in anticancer activity within the tumor.
Sean: We have empowered this masked antibody with the <unk> one inhibitor cap 59, which is a cytotoxic payload designed to kill cancer cells.
Sean: The payload is linked to the antibody through a feasible peptide linker optimized for what we call bystander effect, which is the ability of the drug to kill neighboring cancer cells.
Sean: The drug antibody ratio for <unk> at 501 is eight.
Sean: Moving now to our clinical strategy. We commenced this phase one study just about one year ago.
Sean: And we really have made terrific progress we began dose escalation at the dose of two four milligrams per kilogram administered every three weeks and we have escalated through seven dose levels to date.
Sean: The focus of today's update will be the first five dose levels, where we have 25 safety evaluable patients across the doses of two four to 10 milligrams per kilogram we.
Sean: We have 23 safety evaluable patients at the doses of seven to eight six and 10 milligrams per kilogram and these three doses. We have already started to expand based on the exciting results we've already seen with 2051.
Sean: We have 18 efficacy evaluable patients across these three dose levels and we did anticipate once these expansions are completed towards the end of this year that our recommended phase II doses will come from among this this broad dose range.
Sean: I should also say that in this critical study every patient enrolled was the metastatic CRC patient.
Sean: We didnt enrolled any patients with any other tumor types. So this has been a highly focused study and.
We did not select for <unk> expression because of our expectation that the target will be highly expressed in all patients enrolled and Wayne will update you on that in just a moment.
Sean: So it's been a really.
Wayne Chu: Strong year of execution and I will now.
Sean: I'll hand over to Wayne to talk through our findings so far.
Wayne Chu: Thanks, Sean.
Wayne Chu: So as Sean mentioned.
Wayne Chu: We are exclusively focused enrollment of this study in patients with metastatic colorectal cancer or CRC. So summarized here are the key baseline characteristics of this patient population.
Wayne Chu: As typical for a phase one trial. This represents a very heavily pretreated advanced CRC population essentially a median fifth line patient population.
Wayne Chu: Evidenced by though median number of prior lines of cancer therapy of four.
Wayne Chu: Relevant to the mechanism of action of.
Wayne Chu: 2051, as a <unk> inhibitor. It is important to note that.
As expected for this late line population that CRC patients all received prior around it he can and in many cases.
Wayne Chu: Patients received multiple by I've already he can containing therapy.
Wayne Chu: Other key baseline characteristics that have not have been known to affect therapeutic selection and therapeutic outcomes.
Wayne Chu: Agents used in colorectal cancer, and cuda liver metastases and K Ras mutation status, which are observed in the majority of these patients.
Wayne Chu: Finally, virtually all patients were microsatellite stable had microsatellite stable disease.
Wayne Chu: Indicating that these patients are not.
Wayne Chu: Have tumors that are responsive to immune checkpoint therapy.
Wayne Chu: Okay.
Wayne Chu: Shown here is the waterfall plot.
Wayne Chu: Illustrating the objective responses in patients enrolled at the three relevant doses at seven two to 10 milligram per kilogram.
Wayne Chu: Only 18 efficacy evaluable patients are total of five or 28% had a confirmed partial response by resist one one criteria and this included three of seven efficacy evaluable patients at the 10 milligram per kilogram dose level.
Wayne Chu: You can see the depth of the responses in the waterfall plot, including one patient who had a 100% reduction and measurable target lesions.
Wayne Chu: Turning our attention to the table at the bottom of the waterfall plot, which indicates the specific baseline characteristics for each of these patients and you can see that 2051 had activity in patients who had many lines of prior systemic therapy.
Wayne Chu: Anti tumor activity was observed in patients with K, Ras wild type tumors as well as K Ras mutated tumors and importantly.
Wayne Chu: Activity of 2051 was observed in patients whose disease has spread to other organs, specifically the liver.
Speaker Change: Finally, and importantly, as Sean mentioned.
Speaker Change: Supporting the hypothesis of high and uniform levels of <unk> expression at CRC, we tested baseline tumor biopsies for <unk> expression, using H score, which captured the proportion and the intensity of <unk> expression.
Speaker Change: In tumor cells and as you can see all tumors that have been evaluated had near maximal each scores supporting the fact that 2051 is a therapy that will not require patient selection based on <unk> expression.
Speaker Change: The Spider plot on the next slide shows that.
Speaker Change: Evolution of anti tumor responses over time and I wanted to highlight two important observations.
Speaker Change: First in addition to the confirmed partial responses you can see multiple examples of continuing evolution of anti tumor activity over time exemplified by our patients who had stable disease response assessment at the first tumor assessment.
Speaker Change: With continued treatment with 2051 had conversion of that stable disease to a resist partial response.
Speaker Change: The second important observation is the disease control. In addition to virtually all patients 17 out of 18 efficacy evaluable patients with disease control, which is resist stable disease or better. This disease control was durable there were no examples of patients with rapid disease.
Speaker Change: <unk> progression following an initial assessment are showing either stable disease or an objective response.
Speaker Change: And as durability of disease control.
Speaker Change: Highlighted by the individual patients treated at the $7 two milligram per kilogram dose level was able to maintain that disease control in excess of nine months on therapy.
Speaker Change: So when you take into account the objective responses and the durability of disease control.
Speaker Change: This has allowed a preliminary estimate of the median progression free survival of five eight months.
Speaker Change: 10 of the 18 patients.
Speaker Change: Who are efficacy evaluable continue on 2021 treatment, including three of the five patients who had a confirmed partial response, who continue on treatment.
Speaker Change: Importantly, there were no discontinuation for ongoing treatment related adverse events and while some patients have dose delays and our reductions for the management of adverse events.
Speaker Change: This has not precluded patients continuing to derive clinical benefit from 2051, nor has it in preventing patients from continuing 2051 treatment.
Speaker Change: I wanted to highlight an example, all of the activity that we've been observing with 2051.
Speaker Change: In this case study. This is a 46 year old male with metastatic CRC K Ras Wild type microsatellite stable disease and as is typical for patients with metastatic colorectal cancer.
Speaker Change: There are multiple lesions in multiple locations outside of the Gi tract, specifically for this patient.
Speaker Change: There were metastatic lesions in the lung.
Speaker Change: And as you can see by the example, <unk> get multiple lesions in the liver.
Speaker Change: This patient received three prior therapy and this represents the typical course of treatment for metastatic colorectal cancer comprised of combinations of monoclonal antibody and systemic chemotherapy and the last line of prior treatment. It was combination of Bevacizumab and long service.
Speaker Change: The patient came on study was treated at <unk> 2051 at a dose of seven quite two milligram per kilogram every three weeks.
Speaker Change: The patient tolerate in 2015 went extremely well and as you can see by the Cte scans underwrite at the first tumor assessment the patient had a significant reduction in tumor burden corresponding to a near 50% reduction in burden that far.
Speaker Change: Our response to a partial response by resist criteria.
Speaker Change: In addition to the measurable lesions as indicated by the Green Arrow to patient also had nodal support reductions in multiple liver metastatic lesions as indicated by the blue arrows.
Speaker Change: Importantly in addition to the radiographic response.
Speaker Change: Thank you Juan against patients matter of fact cancer. The patient also had significant clinical improvement.
Speaker Change: Highlighted by the discontinuation of multiple medications for the management of cancer related pain.
Speaker Change: This patient was able to maintain its partial response through six months of treatment.
Speaker Change: And this example, nevertheless highlights the fact that the patient derived significant clinical benefit were otherwise the patient would have received.
Speaker Change: Morris clinical benefit with standard of care therapies.
Speaker Change: Turning our attention to safety. This is a table of the treatment related adverse events observed.
Speaker Change: And more than one patient and as Sean mentioned earlier.
Speaker Change: Previous efforts.
Speaker Change: To develop systemically administered <unk> direct anti cancer therapies have been extremely limited by the by the evolution of dose limiting toxicities and the absence of compelling efficacy.
Speaker Change: So in that context, I want to mentioned multiple Knoxville observations on this table first what is no. Notable by its absence are number one there were no dose limiting toxicity observed on this trial to date number two there were no grade four or five treatment related adverse event.
Speaker Change: Yes.
Speaker Change: And number three some of the key dose limiting toxicity, specifically severe pancreatitis that have hampered the development of other therapies were not observed in this study.
Speaker Change: Overall, the AE profile of 2051 is manageable and reversible.
Speaker Change: If you look at the hematologic adverse events of anemia and neutropenia. These have primarily been laboratory in nature and there were no significant clinical supply lines, such as Paypal neutropenia or sepsis observed on the study.
Speaker Change: And with respect to non hematologic adverse events.
Speaker Change: Profile is consistent with that of other top why summaries inhibitors and thats. The most frequently observed adverse events were gastrointestinal in nature, including diarrhea and nausea.
Speaker Change: Nevertheless.
Speaker Change: Again, these aes were generally manageable and reversible.
Speaker Change: And its overall profile combined with the compelling efficacy that we discussed earlier clearly indicates the presence of a robust therapeutic index.
Speaker Change: Few words on PK, we continue to evaluate.
Speaker Change: Pharmacokinetics and shown here is a summary of interim analysis or cycle, while PK <unk>.
Speaker Change: Overall, CX 2051 is behaving as expected for an antibody drug conjugate.
Speaker Change: Importantly, the rate of payload conjugation was low and in line with other topo one inhibitor adcs as you can see by the low levels of the free Blake our payroll.
Speaker Change: In addition, CX 2021 remain masked in circulation as evidenced by the Super implausible PK curves for intact, 2051, and totaled 2051, which represent masked and mass and unmatched 2051, respectively.
Speaker Change: Half life of 2051 is approximately six days.
Speaker Change: And based on its early analysis of cycle. One PK 2051 showed dose linearity with respect to both AUC and feedbacks.
Speaker Change: So when you take the clinical data together with respect to safety and with the efficacy having compare what we've observed with 2051 with other standard of care therapies in late line metastatic CRC.
Speaker Change: It is already evident based on this early dataset that with respect to key efficacy endpoints, including objective response rate disease control rate and median PFS that $2 51 compares very favorably with the standard of care, we are potentially potential to establish 2051.
Speaker Change: A new standard of care in the late line CRC setting.
Speaker Change: As the data continue to mature with respect to the number of patients and longer follow up.
Speaker Change: We are optimistic that this efficacy endpoints will continue to be maintained if not improve.
Speaker Change: As far as our plans going forward as Sean mentioned, we continued to expand.
The relevant dose levels of seven to eight 6% and 10 milligrams per kilogram, we are expanding each of the three dose levels towards haul of 20 patients.
Speaker Change: Such SaaS by the time of Q1 2026, we'll have a robust data set across these three dose levels correspond to approximately a total of 70 patients of summit phase one data that we will update. Furthermore, the data from these dose expansions what will be the basis.
Speaker Change: Although gulfport plan regarding phase III design, which we also anticipate to initiate in the first half of 2026.
Sean: So with that I will turn it back to Sean for concluding remarks.
Sean: Great. Thanks Wayne.
Sean: Well based on this really exciting data that we are absolutely thrilled to share with you. All today I believe we can say that <unk> 501 is functioning exactly as we have designed it.
Sean: We've broken new ground for <unk>, and colorectal cancer with our marketing strategy.
Sean: Looking at <unk> as a viable therapeutic target for systemic anticancer therapy for the first time.
Sean: This is a highly differentiated program and very consistent with our overall philosophy at <unk> over the years of making a difference by being different.
Sean: Looking ahead, we see a very broad development opportunity for <unk> 501.
Sean: We will be highly focused on advancing 2051 in late line CRC towards approval as rapidly as we can as fast as we can we see tremendous opportunities to advance the drug in the third line or later setting based on these.
Speaker Change: Groundbreaking results that we've shared today as I mentioned earlier the current standard of care is waning as Wayne just reviewed the current standard of care in the late line setting is highly inadequate and we believe we've got something really valuable that can make a big difference for patients.
Speaker Change: In addition to the late line setting of course, we see enormous opportunities to bring <unk> forward in the treatment paradigm for colorectal cancer.
Speaker Change: Indeed, our vision for 2051 has always been based on using a total one payload that we could bring it to earlier lines potentially replacing <unk> in earlier line regimens and perhaps even more broadly replacing chemotherapy in the treatment and management of earlier lines.
Speaker Change: So this drug has we believe transformational potential based on this early look at our phase one data showing just how.
Speaker Change: Effectively the drug is performing in the metastatic CRC setting.
Speaker Change: We of course are also.
We also note that in having.
Speaker Change: Doesn't the CRC experiment in a way we've done the hardest experiment first.
Speaker Change: Is not only very highly expressed in colorectal cancer, but it is an antigen that is present on most solid tumors at high levels.
Speaker Change: This presents a very large opportunity for expanding the 2051 program. It's a multiple other solid tumors over time, and we really believe that in addition to being a pan CRC target.
Speaker Change: This is a potential pan tumor target with tremendous value creation opportunities for <unk> over time.
Speaker Change: So to summarize again, we are Super excited about this first look at 2051, we have shown today clinical proof of concept.
Speaker Change: At <unk> targeting total one ADC and this really is a big landmark for cytogenetics and the Pinnacle achievement for our technology platform to date. This first in class antibody drug conjugate represents a multibillion dollar annual sales opportunity on a global basis.
Speaker Change: First in late line CRC alone.
Top priority is to advance now towards the potential first approval in late stage metastatic colorectal cancer, while also advancing in parallel into combination regimens to bring 2051 earlier in the treatment paradigm, while starting to explore additional opportunities for this exciting drug.
Speaker Change: Now before opening up to questions I want to recognize and sincerely. Thank the patients who join our studies.
Speaker Change: Families are clinical investigators and our highly dedicated team at cytogenetics, including present and past employees.
Speaker Change: This team has been through many ups and downs, but to a person has stayed laser focused on execution for the benefit of patients.
Speaker Change: I want to also thank our board of directors for their continued belief and support.
Also our investors, including the new investors that were welcoming to the company in todays financing.
Speaker Change: We've never been more committed to our vision mission and values and we look forward to great things to come so with that operator, let's go ahead and open up the call for Q&A.
Speaker Change: To ask a question. Please press star one on your telephone and wait for your name to be announced to withdraw your question. Please press star one again.
Speaker Change: Please standby, while we compile the Q&A roster.
Roger Song: Our first question comes from Roger song with Jefferies. Your line is open.
Speaker Change: Excellent.
Speaker Change: Congrats for the data really impressive and then thank you for taking my question a couple of from US. So the number one is you have a very high disease control and then also a very meaningful.
Speaker Change: Partial response patient just curious about what do you see for those patient different between the stable disease versus responders in terms of the baseline maybe the response from the prior lines.
Speaker Change: First part of the question second par how likely this anti tumor activity and will deepen over time, given you have 10 of the 18 patients.
Kim: Kim ongoing thank you.
Speaker Change: Yeah, Thanks, Roger for that for the questions.
Speaker Change: So we're absolutely delighted with the overall profile of 2051. After this first year of work in the clinic.
Speaker Change: <unk>.
Speaker Change: Disease control rate is indeed impressive we believe that response rate across the dose range that we're advancing into expansion is also impressive in this very difficult to treat tumor type in terms of.
Speaker Change: Patient characteristics that could.
Speaker Change: Determine.
Speaker Change: Response versus stable disease.
Speaker Change: I think that's something we'll continue to look at but we just think this overall level of activity.
Speaker Change: An unselected patient population not just on selected for <unk>, but also unselected for other clinical characteristics like K Ras mutation or.
Speaker Change: Liver metastases.
Speaker Change: It's just really impressive and quite frankly is surpassing our expectations.
Speaker Change: In terms of.
Speaker Change: Improvement over time, I think I think on that point.
Speaker Change: I am sure why you would say the same that we would point to the.
Speaker Change: Emerging preliminary progression free survival, where we see.
Speaker Change: Five eight months so far there.
Speaker Change: There is of course, the confidence interval on that this is an early data set but we do have many patients still on study as of the data cutoff.
Speaker Change: We have good reason to believe that that PFS number will improve overtime.
Speaker Change: Great. Thank you.
Speaker Change: If I may just add one more question rates a next step.
Les: This is Les line, you say you will move this forward as quickly as possible.
Les: Is that what is the current development strategy in terms of what that pivotal.
Les: The endpoint and then also how you were moving to this early align with temporarily work along with that later line. Thank you.
Yeah, Thanks again Roger.
Speaker Change: Obviously, we've got a lot of work to do and now thinking through the mid and late stage development strategy.
Les: For <unk> 501 based on this very strong start.
Les: We are right now highly focused on generating data from the three expansion cohorts, we expect to have that data.
Les: In Q1 of 2026, we will be discussing.
Les: Towards the end of this year, we expect with the regulatory authorities to.
Les: I'll ask and answer that exact question as to what is the optimal path forward for phase III potentially phase III three to get this drug to patients who need it as quickly as possible we do.
Les: We will of course be exploring the fastest possible routes to the market in.
Les: In the context of the current regulatory landscape, but this will these will be data driven decisions, including generating additional data.
Les: Beginning in 2026 in the combination setting to enable to start to enable bringing the drug into earlier lines of therapy.
Speaker Change: Great Congrats again.
Speaker Change: Thank you. Our next question comes from <unk> Rama with JP Morgan Your line is open.
Rama: Hey, guys. Thanks, so much for taking the question and congrats on the data.
Speaker Change: Two quick ones for me.
Speaker Change: Just in the <unk>.
Speaker Change: Adverse events that you saw the serious adverse events that you saw in five patients can you give us a little color on how do you sort of manage five dose reduction or dose holiday and then.
Speaker Change: I know that the phase one update is expected in the first quarter of 2026 are there any plans on presenting the data at a scientific or medical forum between now and the next data update thanks, so much.
Speaker Change: Yeah, Thanks, and let me just make a high level comment on the AE SAE profile.
As reported today I think as Wayne mentioned, our initial sense of the safety profile.
Speaker Change: <unk> 2051 is that we have a great start here with a.
Speaker Change: A safety profile that is.
Speaker Change: We think very encouraging.
Speaker Change: Supportive of moving into earlier lines of therapy and potential combinations.
Speaker Change: The SAE reported today are consistent with the overall adverse event profile.
Speaker Change: And we're not at Liberty right now to really dig in patient by patient as I'm sure you'll understand it.
Speaker Change: In terms of presenting at a major medical meeting the.
Speaker Change: The next update from <unk> right now is planned for Q1 of 2026 that will be data from the expansion that we would expect it to be about a 70, plus patient update including 60 patients across the dose levels of seven to eight 6% <unk>.
Speaker Change: Eric.
Speaker Change: We have not yet decided exactly the venue to present or share that data that will come over time.
Speaker Change: Thanks, so much for taking our question.
Speaker Change: Youre welcome.
Peter Lawson: Thank you. Our next question comes from Peter Lawson with Barclays. Your line is now open.
Peter Lawson: Great. Thank you so much thanks for taking the questions.
Speaker Change: Perhaps on the data.
Peter Lawson: Just I guess two other questions around the potential.
Peter Lawson: Phase two.
Peter Lawson: Is going to be a registrational study.
Peter Lawson: <unk> had discussions around.
Etc settlement of a breakthrough designations and then.
Peter Lawson: Yes, I guess the ability to include peripheral exit strategies.
Peter Lawson: Yes.
Peter Lawson: Reduce Gi toxicities.
Speaker Change: The other follow up around that was just around the components around whether it's a single arm study kind of how you're thinking about that phase two thank you.
Peter Lawson: Yes.
Peter Lawson: Thanks, Peter Let me, let me address a couple of those questions and then I'll hand over to Wayne to make a few comments on.
Peter Lawson: On prophylaxis on the on the <unk>.
Speaker Change: Hi, Syed.
Speaker Change: So obviously with this level of <unk>.
Speaker Change: Activity that we're seeing in this very late line patient population.
Speaker Change: It does.
Speaker Change: Should open.
Speaker Change: Avenues.
Speaker Change: Moving quickly.
Speaker Change: In mid and late stage development.
Speaker Change: Way too early to say exactly what they will be but we will be.
Speaker Change: Discussing with the regulatory authorities to.
Speaker Change: Make sure we can move forward in the most expeditious way possible, we have not yet had dialogue with FDA. We believe that the expansion data across these three active dose levels will be of course important and very useful in those in those discussions.
Speaker Change: At the right time.
Speaker Change: In terms of comparator arm.
Speaker Change: Moving into.
Speaker Change: The next stage of development, we are mindful of a number of things in that.
Speaker Change: In the regulatory environment.
Speaker Change: We are.
Speaker Change: Exploring multiple doses of course too.
Speaker Change: Optimists very much in mind.
And.
And we do see.
Speaker Change: A tremendous opportunities for demonstrating the the full power and potential of <unk> thousand 51 by potentially comparing it to.
One or more of the current standards of care in the third.
Speaker Change: Fourth line setting where I think we all agree there is substantial room for improvement.
In CRC.
Speaker Change: Just one comment on the overall tox profile before I had a its way.
Speaker Change: On the prophylactic side.
Speaker Change: Again, we're really encouraged by the.
The AE profile of 2051 I want to underscore that this is the first in human study for this payload cap 59. This is a novel Camptothecin based by.
Speaker Change: Somebody is one inhibitor that we licensed from Immunogen and we're very pleased with how this linker and payload.
Speaker Change: It's functioning.
Speaker Change: When we look at the AE profile overall.
Speaker Change: It looks to us very much like other.
Speaker Change: Total one inhibitors and we would've expected.
Speaker Change: I'm, asking working as well as well as it is.
Speaker Change: To prevent <unk>.
Speaker Change: Toxicities like pancreatitis, we would've expected the principal Aes would come from the payload because of course, we're not masking the payload.
Speaker Change: No.
Speaker Change: With that I'll hand over to Wayne to talk about you know of course that does leave us with some Gi talks to manage but we have a very good plan.
Speaker Change: Yes, so regarding the Gi tox as we continue to get more experience. Our 2051, we continue to optimize our management strategy and sell a lot of that.
Speaker Change: Actually all of the data that we presented today are just reflections of earlier.
Speaker Change: To manage tasks, but specific to the question of prophylaxis for for.
Speaker Change: For diarrhea.
Speaker Change: We have implemented.
The use of prophylactic medication, specifically prophylactic loperamide.
Speaker Change: Four to prevent the onset.
Speaker Change: <unk>.
Speaker Change: But to prevent the onset of severe diarrhea.
Speaker Change: This was only recently implemented.
So a lot of the data that we showed today was actually all patients were not were in patients who are not prophylaxis loperamide.
Speaker Change: As you probably are aware the experienced a prophylactic loperamide was explored with other adcs, namely <unk> in the context of a clinical trial.
Speaker Change: They were able to demonstrate a notable reduction in the incidence of grade three diarrhea with loperamide prophylaxis. So moving forward, we will implement similar strategies for patients coming onto 2051 studies, our expectation and then we're very optimistic.
Speaker Change: Those rates of diarrhea, well will change and change for the better.
Speaker Change: Great. Thank you so much.
Speaker Change: Thank you as a reminder to ask a question. Please press star one on your telephone again that is star one.
Speaker Change: Ask a question.
Speaker Change: Our next question comes from Robert Driscoll with Wedbush. Your line is open.
Robert Driscoll: Thanks, Good morning, guys and congrats on the data here and just a couple of questions from us.
Speaker Change: Very high expression of <unk> come here in late line patients.
Speaker Change: Is that kind of evidenced similarly kind of high end robust expression of that comment earlier stage patients.
Speaker Change: Thank you concept as you go to those earlier lines next year potentially and then anything about the biology of upcoming you think may be particularly attractive here in colorectal cancer.
Speaker Change: And then potentially in other solid tumors.
Robert Driscoll: Hi, Robert Thanks for the questions.
Speaker Change: So.
Speaker Change: At Cam was first described.
Speaker Change: Quite some time ago.
Speaker Change: CRC antigen, so it's Ben.
Speaker Change: Well established for decades actually to be.
Speaker Change: CRC target and it is expressed on.
Speaker Change: Throughout the.
Speaker Change: The.
Throughout the natural history of the disease.
Speaker Change: So we feel confident about bringing <unk> earlier in the treatment paradigm based on target expression and other other.
Speaker Change: There are aspects that we've discussed today.
Speaker Change: Terms of the biology of that cap.
Speaker Change: Although it's been around alongside its actual biological function is still not that well characterized and.
Speaker Change: We haven't really.
Speaker Change: Focus on that as anything that relates to the design of <unk> 2051.
Speaker Change: Simply so there's just so much at all.
Speaker Change: On CRC tumor cells that we've always thought of it as an <unk>.
Speaker Change: The address to target with this with this ADC and then you just to put that in context, the expression level of outcome in CRC is similar to Tahira too.
Speaker Change: In breast cancer so.
Speaker Change: Now we can't rule out that there is some biology here that blocking at Cam is contributing to this really exciting clinical activity that we're seeing but it's never been something that we've relied on or needed to invoke.
Speaker Change: For the drug to work.
Speaker Change: Got it thanks, and maybe just one more in terms of the doses selected go forward any plans to go higher and dosing just kind of given that emerging signal with maybe a higher response at the time.
Speaker Change: The correct dose.
Speaker Change: Yes. Thanks.
Speaker Change: I'll start by saying, we're already pretty excited about the response rate that we have across these three dose levels.
Speaker Change: In this patient population that really is we think a really significant.
Speaker Change: Difficult achievement.
Speaker Change: Have escalated.
Speaker Change: <unk>.
Speaker Change: I mentioned in my in my presentation.
Speaker Change: Two.
Speaker Change: Through seven dose levels to date in the clinical study.
Speaker Change: We do anticipate that.
Speaker Change: We haven't seen any dose limiting toxicities in the execution of the study.
Speaker Change: To date, but.
Speaker Change: But we do anticipate that at these upper dose levels, we will find our maximum assessed dose.
Speaker Change: So we are not currently expanding those dose levels, we will present data from them.
Speaker Change: When we present the overall update on the expansions in Q1 of 2026, but right now we feel like the dose range that were expanding seven to $8 six and 10 gives us a lot of room to maneuver.
Perfect. Thanks, very much and congrats again guys.
Speaker Change: Thank you.
Speaker Change: Thank you once again to ask a question. Please press star one on your telephone.
Speaker Change: Our next question comes from Mitchell Kapoor with H C. Wainwright. Your line is now open.
Speaker Change: Okay.
Speaker Change: Good morning. This is Dan on for Michel Thanks for taking our questions and congratulations on the data. So the data appears to be a very clear indicator that the providing asking technology that work, especially slide 20.
Speaker Change: Why do you believe youre, providing asking work most optimally with the <unk> strategy versus the prior strategies in the past and is there anything that's being done to enhance the probiotic platform to where future pipeline candidates may have better odds of success and I would like to ask a follow up if I could.
Speaker Change: Yeah, Thanks, Dan Thats a terrific question.
Speaker Change: Yeah.
Speaker Change: This.
Speaker Change: This data is obviously super exciting and.
Speaker Change: Right.
Speaker Change: Absolutely is showing that.
Speaker Change: The power.
Speaker Change: Our pro body therapeutic masking platform.
Speaker Change: Many of you. Many of you will be aware of course that <unk>.
Speaker Change: <unk> is the company that really originated the whole concept of antibody marking to increase therapeutic index.
Speaker Change: In terms of.
Speaker Change: Why it's working so well.
Speaker Change: <unk>.
Speaker Change: On this target.
Speaker Change: I've kind of always believed us most.
Speaker Change: Most of you will know that our platform has always worked.
Speaker Change: And in the clinic with multiple programs we've shown.
Speaker Change: A lot of really interesting clinical results over the years.
Speaker Change: I think we've come to the view that it's it's all about where you direct the power of the technology and in this particular case.
Speaker Change: We have come to learn that and I think what we've really got right is the combination of the.
Speaker Change: The tumor type of interest and the clinical problem that we're trying to solve the target which of course the CRC.
Speaker Change: At least initially the target, which is which is at Cam and.
Speaker Change: Effector mechanism, which in this case is the cytotoxic payload.
Speaker Change: Type one inhibitor to <unk> 59, and I think you've got to get all three of those things right.
Speaker Change: And I think we have.
Speaker Change: To really nail it in terms of the underlying technology, the protease cleavable substrates.
Speaker Change: On the marketing strategy, which is a.
Speaker Change: Tight marketing strategy that we've always employed and continues to employ.
Speaker Change: This is this is a strategy that has been validated previously in our previous clinical work. So.
Speaker Change: We're not surprised to see it doing so well in the clinic as work before it's just in this case, we really think we've got that combination of the tumor the target and the effector. We've got it right and that's just really exciting and of course that opens up now many new opportunities to.
Speaker Change: Go back and design the next generation of priority therapeutic candidates across our pipeline as we build the company for the long term, but thanks for the question. It's a terrific question.
Speaker Change: Yes, I can answer thank you and thinking about on the PR for the Pan tumor phase one study expected in 2026, you intend on registering at the basket study or are you thinking of targeting those indications piecemeal and given the exceptional levels of that <unk> <unk> expression NTIC versus other solid tumors, which they still have.
Speaker Change: High levels of Trc is Hyatt would.
Speaker Change: Would you lean towards identifying Hyatt <unk> positive patients in the other solid tumors or are you thinking of going into diagnostic approach there. Thank you.
Speaker Change: Yes, well clearly a lot of ground to explore with 2051 across so many.
Schumer types, where there continues to be so much unmet medical needs. So.
Speaker Change: We.
Speaker Change: Yes, we are working through our strategy for moving into those additional cancer types at the moment we've been.
Speaker Change: As I mentioned, we've been really really focused on CRC for the last year and thus that's been very intentional and we really wanted to do as I said in a way kind of the hardest experiment first really put this drug through its paces now that is delivering it opens up a multitude of opportunities across other <unk>.
Speaker Change: And the specific design.
Speaker Change: That phase.
Speaker Change: Phase <unk> study, if that's what we call it.
Speaker Change: As a basket or looking in a more targeted way specific tumor types.
Speaker Change: It's something we continue to discuss internally.
Speaker Change: In terms of selection of patients.
Speaker Change: Again, one of the great features of CRC as we don't have to select patients, but I think we're going to need to and we think ultimately commercially that's going to be a huge advantage for 2051.
Speaker Change: As we get this drug to the market but.
Speaker Change: But we have a terrific IAC assay you have seen some of the results in this study we showed one of our patients.
Speaker Change: In our presentation today.
Speaker Change: And it.
Speaker Change: It may be helpful to select patients in the <unk>.
Speaker Change: And these other tumor types, but I would say we're also early.
Speaker Change: In very early actually and understanding any relationship between target level. In response, we don't actually know how much target as necessary. So theres just a lot more to be learned about this drug and obviously a ton of potential but thanks for the question.
Speaker Change: Thank you so much and congratulations again.
Speaker Change: Thank you.
Speaker Change: Thank you.
Speaker Change: As a reminder to ask a question. Please press star one on your telephone again that is star one to ask a question.
Speaker Change: Thank you I'm not showing any further questions in the queue. At this time I would now like to turn it back over to Dr. Sean Mccarthy, Chairman and CEO for closing remarks.
Speaker Change: Well thanks, everyone for joining us today is obviously, a very exciting day for all of US here at <unk> has done a very important day for cancer patients. So thank you for your time and we look forward to keeping you updated on our progress in the future.
This concludes today's conference call.
Speaker Change: Thank you for participating you may now disconnect.
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