Q3 2025 ALX Oncology Holdings Inc Earnings Call
Speaker #3: Greetings and welcome to the Al Oncology third quarter 2020 financial Results conference call and webcast . At this time , all participants are in a listen only mode .
Speaker #3: A question and answer session will follow the formal presentation . If anyone should require operator assistance during the conference , please press Star Zero on your telephone keypad .
Speaker #3: Please note this conference is being recorded . I would now like to turn the conference over to your host , Jason . Please go ahead , sir .
Speaker #4: Thanks everyone , and welcome to our Q3 2025 results . I appreciate everybody spending some time with us this morning , and I'm looking forward to this update on slide two here .
Speaker #4: Before we start our presentation . As housekeeping , here are our forward looking statements for your review . So on the next slide , slide three here here is the agenda .
Speaker #4: And our plan for today . We're going to be providing an update on our key accomplishments in the third quarter of 2025 . Most notably , we are very excited to share with you the data set that will be presented at STScI .
Speaker #4: This weekend . From a pre-planned analysis of our Aspen oh six trial that showed Cd47 expression as a key predictive biomarker for increasing durable clinical response with over in Her2 positive gastric cancer patients .
Speaker #4: So our goals for today are most importantly to share these detailed results with you as we believe this data set . Now clearly validates the role of Cd47 in Her2 positive cancers .
Speaker #4: We will then give you a sense of how this data now impacts our development strategy for Evorpacept going forward , we will also be providing an update on our novel , a 2004 EGFR targeted ADC , which is now in the clinic .
Speaker #4: Today , we are also excited to be joined by Doctor Peter Schmid from Barts Cancer Institute in the UK , who is a key opinion leader in breast cancer and investigator in our Evorpacept phase two Breast Cancer study .
Speaker #4: He will be presenting his views on a data and its potential within the current treatment paradigm for Her2 positive metastatic breast cancer . Then our CMO , Barb Quincy , will provide an update on our novel EGFR targeted ADC AOCs 2004 , which is currently dosing patients in our phase one trial .
Speaker #4: Now on slide four , in the third quarter , we made significant advances in both the Vorbis and AOCs 2004 clinical programs . We again , are excited to present the full data at Sitc .
Speaker #4: That is demonstrating the potential of Cd47 expression as a predictive biomarker and highlight a clear opportunity to now identify patients who are most likely to achieve the greatest benefit from Evo .
Speaker #4: As Barb will present in detail on our clinical section in this analysis , we saw that patients with high cd47 expression derived the greatest benefit across all key efficacy markers .
Speaker #4: Response rates , duration of response , median PFS , and overall survival from a prospective versus those with low expression . The data is very clear as the magnitude of benefit across many of these metrics was double or even triple those observed in the control arm , and also clearly compare very favorably with the large benchmark studies in second line gastric cancer .
Speaker #4: Most importantly , these results support the potential to pursue targeted oncology approach to additional tumor types . With Evo , and given the broad overall expression of Cd47 in both solid tumors and heme disease , it gives us a real opportunity to really focus Evo .
Speaker #4: Now , as a targeted IO therapy , our phase two clinical trial of breast cancer , which is designed to pursue a Cd47 and Her2 biomarker driven strategy based on this strong data , is on track to dose its first patient this quarter .
Speaker #4: And as we discussed , Evo has the potential to represent the first and only option for metastatic breast cancer patients who overexpress Cd47 , which we know can lead to worse outcomes in a poor prognosis for these patients .
Speaker #4: And with our second pipeline product , our novel EGFR targeted antibody , Alks 2004 , which is a highly differentiated ADC , we presented preclinical data and design of our phase one trial at the conference a few weeks ago .
Speaker #4: So we're excited to announce today that we are currently enrolling patients in the second dose core cohort, rapidly clearing the first dose cohort in this Phase 1 trial.
Speaker #4: Turning to our financials quickly . We reported a total cash balance of 67 million . And that cash is expected to provide US runway into the first quarter of 2027 , which positions us to achieve the value enhancing data milestones for both Alks 2004 and Evorpacept that we have coming next year .
Speaker #4: Now , turning to slide five . It has been very well established that Cd47 is widely overexpressed across almost every type of cancer , and it is also clear that CD cd47 overexpression matters as it is a clearly a negative biomarker for patients .
Speaker #4: So when you look at research in Cd47 over the last decade plus , it is a very strong foundation that Cd47 is clearly a negative prognostic biomarker .
Speaker #4: And what you can see here is a meta analysis of 38 cohorts across 17 publications , which includes over 7000 patients . And there really is no question that Cd47 is clearly associated with shorter survival and worse outcomes .
Speaker #4: And you can see on the right the wide range of tumor types where this has been established . Now turning to slide six .
Speaker #4: And as a reminder that during our Q2 call , just a few months ago in August , we presented the topline data , which support that cd47 overexpression is a clear predictive biomarker for response with Evorpacept in Her2 positive gastric patients .
Speaker #4: In this analysis, patients with both confirmed HER2 positivity and CD47 high expression had a dramatic response to Evo. This was in contrast to those in the control group who did not receive Evo.
Speaker #4: And as you can see here on the IT population , we saw a strong response of a 41% RR in the Evo arm versus 27% RR in the control arm , and if you look at the data now in patients that clearly have cd47 high expression , there is a magnitude of benefit for those patients where we had an Orr of 65% in the treatment arm versus 26% in control , with a nominal p value of less than 0.05 .
Speaker #4: Now , as you can see on slide seven and what we're very excited to share with you now , and at later today , this strong RR benefit with a precept in combination with TRP and Cd47 high patients was also reflected in translated well to Dor , DFS as well as survival as it's clear that patients who overexpress Cd47 and retain Her2 expression is driving the effect here .
Speaker #4: This is very important as this clearly validates Evo's dual mechanism of action . And again , this is a second line plus gastric population , which has historically been a very tough cancer to treat .
Speaker #4: So in addition to the RR benefit which had a delta of almost 40% versus control , the median duration of response here for those patients is over two years , which is more than triple the control .
Speaker #4: The median PFS was over 18 months in the evorpacept arm versus just seven months in control with an impressive hazard ratio of 0.39 .
Speaker #4: And then we were also pleased to see these gains further translate to a benefit to overall survival , where we saw median OS of 17 months with Evo versus about ten months in control , and also a strong hazard ratio of 0.63 .
Speaker #4: Barb will walk you through this data and more detail and the full data set will be shared at stsi . Here soon . What is clear is that this data shows the potential for Bicep to drive really substantial benefit for these patients with high cd47 expression on the next slide , this just shows the focus set of milestones that we're driving to now .
Speaker #4: In summary , we're laser focused on these two programs . First , driving Evorpacept into Aspen Breast , which is our study investigating patients post Enhertu .
Speaker #4: And again focused on Cd47 high and understanding the impact of that biomarker . We continue to execute well against the milestones that we've communicated in the past .
Speaker #4: And are anticipating . First , patient and Q4 of 2025 with interim data expected Q3 2026 . Alex 2004 also remains on track and continues to proceed very well .
Speaker #4: We dosed our first patient in August of 2025 , and we continue to expect initial safety data first half of 2026 . Turning to the next slide .
Speaker #4: And in summary , before I hand the call over to Barb , we had a strong quarter , both in terms of execution , continued tight discipline around our capital and our excited about the key value catalysts for Alex in 2026 .
Speaker #4: And as you can see here on slide nine , this is a snapshot of our current clinical pipeline as we have communicated previously , we are pursuing a focused development strategy for Evo in combination with anti-cancer antibodies .
Speaker #4: Given the consistent proof of concept that we have seen in various clinical studies with different monoclonal antibodies , and this data here today , further builds on that .
Speaker #4: In addition to our Her2 positive breast cancer program with a cd47 biomarker driven approach , AOCs 2004 . Again , our EGFR targeted ADC continues to progress well , and we are also very excited about our partner program with Sanofi , Sarclisa and multiple Myeloma , which is now in dose optimization phase .
Speaker #4: So next we'll turn this over to Barb , who will take over and provide more details on the Evorpacept Cd47 biomarker data presentation coming here at CDC .
Speaker #4: Barb .
Speaker #5: Thank you . Jason , I will start by describing a process , mechanism of action . Cd47 is broadly overexpressed on cancer cells as a mean of means of evading the immune .
Speaker #5: Detection . And it does so by sending a don't eat me signal . Evorpacept is a fusion protein , and it's designed to block that signal for FC region is engineered to be inactive , and hence its particularly effective when given in combination with an anti-cancer antibody such as Herceptin .
Speaker #5: The active FC domain on the anti-cancer antibody can then trigger very effective phagocytosis , which otherwise would have been suppressed by the cd47 signal .
Speaker #5: Slide 12 shows that the aurora approach to blocking Cd47 is different from the conventional approach pursued by other cd47 targeted agents . While Cd47 is overexpressed in cancer cells , it is also expressed in healthy cells such as red blood cells .
Speaker #5: The conventional approach to block Cd47 with an antibody that can also binds to macrophages through an active FC has caused significant toxicities in some patients , and thus this approach has largely failed in contrast , overall approach using an inactive FC spares normal cells and our the safety database in more than 750 treated patients confirms the safety of this approach .
Speaker #5: Slide 13 shows the design of the Aspen O6 gastric study that Jason has introduced earlier . We enrolled 127 second line or third line Her2 positive gastric cancer patients , all of whom had received prior Her2 directed therapy patients were randomized to a evorpacept trastuzumab ramucirumab and paclitaxel , or the TRP alone .
Speaker #5: The primary endpoint was objective response . Importantly , because this can be loss of Her2 expression following prior Her2 directed therapy , we wanted to look beyond the Her2 status as diagnosed on archival tissue based on the known mechanism of action for evorpacept , our drug is not going to work as effectively if Her2 is not overexpressed on the on the cancer cell surface .
Speaker #5: To this end , ctDNA was obtained at baseline in all patients and in addition , 48 patients underwent a biopsy either at study entry or at some point following their prior Her2 directed therapy .
Speaker #5: In total , 95 patients or 75% of the enrolled population were confirmed as having retained Her2 positivity by either the ctDNA or on fresh biopsy .
Speaker #5: 90 of these 95 patients were evaluable for Cd47 expression in tumor cells , using either archival tissue or , where available , fresh biopsy sample , high cd47 expression based on a cut point of IHC three staining in at least 10% of the tumor cells was present .
Speaker #5: In 48% . Of these , 90 patients , the expanded results of this pre-planned exploratory analyses of efficacy by Cd47 expression level in patients who retained Her2 positivity is the focus of the data that I will review with you today .
Speaker #5: Slide 14 shows the objective response rates in key subsets . As we've previously reported in the 95 patients who retained Her2 positivity , we see a robust response rate of 48.9% for the Evorpacept CRP arm , versus 25% in the control arm .
Speaker #5: And then the subgroup by Cd47 expression level Evorpacept produced a response rate of 65% , compared to 26% in the control arm . Amongst patients with the high Cd47 expression levels , the response rate in the control arm was consistent across Cd47 expression levels and lower than that in the evorpacept arm .
Speaker #5: In both the Cd47 and Cd47 in the Cd47 high and Cd47 low groups . Moving to slide 15 , I'm now displaying the duration of response in these same subgroups .
Speaker #5: Again , we see the potential of Cd47 expression as a powerful predictive biomarker for Evorpacept benefit . The duration of response in all Her2 positive patients , irrespective of Cd47 expression , was 15.7 months for Evorpacept plus TRP , compared to 9.1 months for responders in the control arm .
Speaker #5: In the Cd47 high Group , the duration of response was three times longer for patients in the Evorpacept trastuzumab arm compared to the control .
Speaker #5: The median duration of response of 25.5 months versus 8.4 months in the cd47 low group of TRP had a median duration of response of 11.2 months , compared to 12 months for TRP .
Speaker #5: In slide 16 , we're now showing the progression free survival in patients with confirmed Her2 positivity and high cd47 expression . The hazard ratio is 0.39 , with a median PFS of 18.4 months for the Evorpacept trastuzumab arm , which is more than double the seven months seen in the TRP alone .
Speaker #5: Arm . Again suggesting the potential for cd47 expression as a powerful predictive biomarker for Evorpacept benefit . Slide 17 shows a similar pattern of longer survival observed in the Her2 positive cd47 high evorpacept arm median overall survival was 17 months , compared to 9.9 months for the control arm , with a hazard ratio of 0.63 .
Speaker #5: All of these data being presented at the conference this week are based on mature follow up . The median follow up for survival , for example , was 25 months .
Speaker #5: Slide 18 shows some of the various cut points that we examined for for Cd47 expression based on the range and strength of IHC testing , as shown here .
Speaker #5: We looked at the median . We looked at medium or high intensity staining findings . IHC two and three plus in at least 10% and in at least 25% of tumor cells .
Speaker #5: And we also looked at high intensity staining or IHC three plus in tumor samples with 5% or more or 10% or more of cancer cells expressing that high intensity staining .
Speaker #5: The prevalence of cd47 high across these ranges from 40% to nearly 60% of Her2 positive patients , depending on the cut point . The key takeaway from this slide is that we see consistent improvements in response rate PFS and OS in the aurora and the Aurora treatment arm , irrespective of the cut point for Cd47 expression .
Speaker #5: On slide 19 , I'm showing a cross-trial comparison of our evorpacept efficacy data in patients with retained Her2 positivity and high Cd47 expression relative to benchmark trial data in Her2 positive gastric cancer , with the usual cross-trial comparison caveats in mind , Evorpacept data directionally compares favorably to recent Enhertu data from the Destiny gastric oh four study .
Speaker #5: In the second line , setting , in that trial of nearly 500 patients published earlier this year in the New England Journal of Medicine , those patients required confirmation of Her2 status by fresh biopsy following a trastuzumab containing regimen , and they very randomized these patients to enhertu or to HRP as a control arm as effective as Enhertu was .
Speaker #5: In the second line setting . In that trial , our second and third line of data generated in patients with high cd47 expression , a known negative prognostic biomarker appear much better .
Speaker #5: In our attention now from gastric cancer to Her2 positive breast cancer , slide 20 introduces a phase one two trial in Her2 positive breast cancer patients conducted by Jazz that evaluated the safety and efficacy of a evorpacept plus zanidatamab in patients who progressed on prior Her2 directed therapy .
Speaker #5: These patients were heavily pretreated with a median of six prior lines of therapy in nine patients confirmed to retain Her2 status by central assessment .
Speaker #5: The response rate was 56% . The median duration of response for that group ranged from five months , 5.5 months to nearly 26 months , with the median not reached and the median PFS being 7.4 months .
Speaker #5: These data compare favorably to benchmark data , including , for example , the Sophia trial , a predominantly second and third line Her2 positive breast cancer trial , which produced a response rate of 22% for Margie two toxin Mab .
Speaker #5: Moving to slide 21 , we've now demonstrated in these two studies the potential of a evorpacept to engage the innate immune response , validating the mechanism of action of the given in combination with anticancer directed antibodies in both Her2 positive breast cancer and in Her2 positive gastric cancer .
Speaker #5: This gives a strong conviction on a broad potential and its path forward in Her2 positive breast cancer setting , which we'll talk about next .
Speaker #5: Slide 22 describes briefly the opportunity that we see for evorpacept in breast cancer , which now has a high probability of success having been de-risked by the two positive data sets in two different Her2 positive settings , a cd47 Her2 positive , biomarker driven approach with a evorpacept enables a highly targeted strategy , potentially addressing the high unmet medical need in the evolving breast cancer landscape , which includes patients who have now progressed on an Her2 .
Speaker #5: It is now my distinct pleasure to introduce Doctor Peter Schmidt , a professor of cancer medicine and center lead at the center of Experimental Cancer Medicine at Barts Cancer Institute .
Speaker #5: He's a well-known global lead investigator on multiple ongoing phase three trials in metastatic and localized breast cancer . Just as two examples of trials with immunotherapy agents .
Speaker #5: He's a global lead investigator on the pembrolizumab KEYNOTE 52 study and the atezolizumab IMpassion130 study. With that, I turn this over to you, Peter.
Speaker #6: Thank you . Bob . And treatment options for patients with metastatic Her2 positive breast cancer are currently undergoing . I would almost say a dramatic change .
Speaker #6: We obviously have seen a very active drug moving initially into second or third line treatment with trastuzumab deruxtecan , but everyone is aware of the data that now placing t-dxd increasingly in the first line setting .
Speaker #6: And I think that's where where the drug will ultimately end up the that is fantastic from a patient perspective , we are very powerful .
Speaker #6: New first-line treatment option, but the challenge that comes out of this is that there is no standard of care for patients who have been treated with trastuzumab deruxtecan.
Speaker #6: The sequence we had previously was that patients would get a triple called TEAAA first line with trastuzumab and pertuzumab, second line T-DXd, and third line other options. However, this has just been turned upside down.
Speaker #6: So at the moment there are a number of options we can choose from, but none of those options have actually been specifically approved.
Speaker #6: And tested in patients with prior therapy . So the options we have to choose from is to cut . And if trastuzumab in combination with capecitabine t-dm1 is still an option .
Speaker #6: Some investigators and clinicians may give chemotherapy and just Her2 TKI play a smaller role and increasingly a less and less being used . But of course , we also hope we have other Her2 targeted therapies .
Speaker #6: So there is a significant unmet need for patients with Her2 positive breast cancer who have progressed on or after t-dxd . And I can see that it will present as as a possibly exciting role to play .
Speaker #6: It has demonstrated activity in patients post trastuzumab deruxtecan in combination with other Her2 targeted agents . Now , if you look at what we would hope to see in such a situation , our challenge is to to to to bring a new agents that could overcome the resistance to t-dxd the need for agents in the her two positive breast cancer space at this point is to define novel agents ideally that bring a different mechanistic approach to to to target her genes .
Speaker #6: And we can see for Evorpacept that it has a different mode of action by killing cells via enhanced adcp versus the classic payload based ADCs or other drugs .
Speaker #6: We are currently using . The second thing we want to achieve is we want to have a drug that obviously has demonstrated activity post Her2 directed treatment after ADCs and after monoclonal antibodies , and the elephant in the room here is always trastuzumab deruxtecan .
Speaker #6: And we've seen from the data in in the gastric study , but also in some of the Her2 pretreated breast cancer studies that that Evorpacept has shown activity post trastuzumab in gastric cancer and following up to four or more lines of patients with Her2 with Her2 positive breast cancer prior to treatment .
Speaker #6: We would like to have a treatment that can supplement and enhance the current standard of care , rather than replace the backbone treatment .
Speaker #6: And again , if you look at the way how it works , it is really designed to work statistically alongside the key therapies .
Speaker #6: The key backbone, obviously, for HER2 targeted therapy is just using antibodies. We are keen to have a drug that's safe and safer than ADCs.
Speaker #6: We have to learn over the years what ADCs have quite substantial possible toxicity , which is obviously driven by payload as it is ultimately targeted chemotherapy and the safety profile of Evorpacept is very different to to what we know and seems to be much more favorable compared to some of the ADCs .
Speaker #6: Finally , having immune therapy agents that can really drive for b c sometimes in Her2 positive breast cancer , this long tail we as clinicians often go on about that is what ultimately patients need to have a long term benefit in survival .
Speaker #6: And we feel that there is an immune component to that . We know already that there's a small percentage of patients who have very , very long survival on how to target therapy , but enhancing that immune effect by giving a cd47 targeted drug can possibly increase the tail .
Speaker #6: For patients that at least that is at least my hope . If you look at Cd47 as a selection strategy . And again , I think that is really important for this program is that we're not going into this blindfolded .
Speaker #6: We actually have a very powerful biomarker . And as you have seen from the gastric data , it's it's a very clearly better signal for this concept .
Speaker #6: And patients with with high CD4 47 expression , as you can see , there's a number of breast cancer studies that have looked into this .
Speaker #6: And I'm not going to go into each of those trials . And the scoring methods in too much detail . The bottom line is about 1000 patients and they're relatively consistently showing a CD 47 high expression rate of around 50% .
Speaker #6: So 54% is the average . If we go through those trials . And that's a substantial proportion of patients . And actually allows us to drive that program forward without having a target group that is ultimately to to too small to to select for clinical trials .
Speaker #6: Now , there are a couple of preclinical data , I think are really interesting . Now , preclinical data , you may say it's a little bit nerdy , but I think it's really helpful for us to understand the biology .
Speaker #6: So if you look at this slide on the left side , you see the cd47 expression in Her2 positive breast cancer cells compared to Her2 negative cells .
Speaker #6: Green means low expression , red means high expression . This black or blue color is moderate . Expression and it's very obvious to see that we have a higher percentage of CD of cd47 expression in Her2 high disease .
Speaker #6: If you move to the right side of the slide again , probably even more important for what we're aiming for is this is this compares the the the cd47 expression in primary disease on the right side and in recurrent disease .
Speaker #6: So pretreated disease on the left side . And again it's very obvious that we have more positivity CD 47 positivity in tumors . And therefore in patients who have prior to treatment and have recurrent Her2 positive breast cancer .
Speaker #6: And this is exactly the target population we're aiming for . If you then look at emerging data again , cell line based data for cell lines that were treated with trastuzumab deruxtecan .
Speaker #6: And as I said earlier , this is the new standard of care in the first line setting . So our prediction for the future is all patients will have t-dxd pre-treatment .
Speaker #6: And we have to focus on patients who are resistant to t-dxd . As you can see here in orange , these are the these are cells that have been t-dxd pretreated in purple dm1 .
Speaker #6: And then and then in white is ultimately controlled . And it shows the percentage or the number of of cd47 positive cells . And as you can see , very I think impressively , is that we have a markedly higher expression of cd47 in cell lines that were prior exposed to , to trastuzumab deruxtecan , and that is the target group we're aiming for .
Speaker #6: So the target population is very clearly a substantial population of patients with Her2 positive breast cancer . The population is probably even bigger in patients who have prior CD4 47 pretreatment , but it also may be one of the ways these tumor cells evade the ADC .
Speaker #6: The ADC treatment effect , therefore , may be a really fantastic opportunity for us to target this clinically . Now , the clinical trial that is ongoing , the trial , we're very much aware of is , in my opinion , is one key key focus .
Speaker #6: So as a clinician , I've asked that question before . I'm keen to see this move forward into phase three as quickly as possible because we know it works .
Speaker #6: We know what the target population is and we know there's a huge need . Post t-dxd , but what we don't know exactly is how to do the statistics for a phase three trial by having the exact response rate and PFS and other endpoints , which we obviously need to do to size up and design the phase three trial properly .
Speaker #6: So this trial , therefore , is a non-randomized phase two trial in patients with Her2 positive metastatic breast cancer with measurable disease with prior treatment with trastuzumab deruxtecan and and are then offered treatment with evorpacept in combination with trastuzumab and patients of physician's choice chemotherapy .
Speaker #6: Very pragmatic design . This is the out there . But what we want to learn from this trial is really how what the response rates are in patients who are ctDNA positive for her two , but also what the duration of response DFS overall survival is .
Speaker #6: And in in patients with cd47 high . But also cd47 low tumors to get further confirmation from the biomarker data , we have already obtained from gastric cancer , which ultimately allows us to fine tune the phase three design going forward .
Speaker #6: Thanks everyone . I would like to pass back to Bob , please .
Speaker #5: Thank you . Peter . Well , let me wrap up this section with a brief breakdown of the addressable patient numbers in the core markets .
Speaker #5: As you can see , there are roughly 48,000 breast cancer patients in the second line setting who are Her2 positive . Of that , we believe that at least 60 to 80% of these patients will retain Her2 positivity following prior therapy of that group , 50 to 70% will have high Cd47 expression , as Peter highlighted , there are a number of publications to support that Cd47 overexpression in Her2 positive breast cancer patients will be upregulated post enhertu treatment .
Speaker #5: We believe that this represents approximately 20,000 addressable patients who are both Her2 positive
Speaker #5: and cd47 high . If you boil this down and you conventional estimates on pricing , you get real world roughly a 2 to $4 billion market opportunity .
Speaker #5: Again , just in patients that are cd47 high and Her2 positive , representing a opportunity for evorpacept . On slide 31 , I now want to provide a quick update on Alks 2004 .
Speaker #5: Our EGFR antibody drug conjugate program , as shown on slide 32 . Our company's first ADC , the Alks 2004 molecule , was a result of rigorous internal drug design process .
Speaker #5: Our goal was to create a best and potentially first in class drug designed to maximize the therapeutic window and to overcome the historic toxicity challenges that others have encountered in targeting EGFR with an ADC significant .
Speaker #5: With Al 2004 , we have optimized all three components to do this , including the payload , the linker , and the antibody to create a truly novel molecule against a very well validated target .
Speaker #5: Al 2004 uses Matuzumab derived EGFR antibody selected to minimize skin toxicity and to maximize the therapeutic window . Its binding epitope is distinct from the US , FDA approved EGFR antibodies such as cetuximab and panitumumab .
Speaker #5: Additionally , Al 2004 has a proprietary linker payload and total one inhibitor payload engineered to offer improved linker stability for on target delivery of payload and enhanced bystander effect at the recently concluded triple meeting in Boston in October , we presented preclinical data highlighting these elements in greater detail .
Speaker #5: Moving to slide 33, here are the preclinical data highlights. Both in vitro and in vivo animal models support impressive dose-dependent activity and a differentiated safety profile.
Speaker #5: Importantly , non-human primate toxicology studies did not demonstrate EGFR related skin toxicities at clinically relevant doses , and there was no evidence of payload related ILD in the animals .
Speaker #5: This overall profile supports our conviction that this molecule could potentially demonstrate efficacy with a manageable safety profile in patients . Slide 34 shows a snapshot of the efficacy data from our in vivo models .
Speaker #5: Al 2004 showed regression and tumor suppression across a panel of xenograft models representing a broad spectrum of cancer types and EGFR expression levels , notably , Al 2004 was effective in models harboring Kras , Braf , and p53 mutations .
Speaker #5: Al 2004 shows excellent tumor suppression activity at doses as low as 1mg/kg . Given either once or once . Weekly times three , leading to complete tumor eradication in several of the models .
Speaker #5: These results confirm the broad applicability of Al 2004 . In targeting EGFR positive cancers . Slide 35 shows the key findings from our six week repeat dose with six week recovery period in the GLP .
Speaker #5: Nonhuman primate Tox Study . All findings were minimal to moderate and fully recoverable . Thus , these data support the design of the Al 2004 study and the likely safety margin for clinical use .
Speaker #5: Slide 36 highlights our clinical development plan . We are targeting EGFR , expressing tumor types , namely lung , colon , head and neck , and esophageal squamous cell carcinoma .
Speaker #5: In this dose escalation and dose expansion trial , we dosed our first patient in August , and we have completed our first dose cohort at 1mg/kg without any DLT .
Speaker #5: We are currently dosing patients in our second dose cohort at 2mg/kg . We are on track to provide an initial safety data from a phase one portion of the study .
Speaker #5: In the first half of 2026 , our goal in this phase one , a phase one trial is to identify the dose that optimizes safety and activity in tumor types , which we believe have the highest potential for success .
Speaker #5: These data will then set up the program well to advance into a future registration study . With that , I turn the call back over to Jason .
Speaker #4: Thanks , Barb , and thanks again to Doctor Schmid for sharing this perspectives on the program . As a coal in the field .
Speaker #4: Again , Q3 was a strong quarter , both in terms of execution and new data . What we're most excited about now is driving a targeted IO breakthrough in a first in class drug with Evo , as well as our very encouraged by AOCs 2004 fast start in the clinic and building momentum , and some are Cd47 blocker has been successful where no other has , both in terms of its manageable toxicity profile as well as activity .
Speaker #4: As we've now demonstrated , efficacy in a randomized study , and we've identified an actionable and predictive biomarker for response to Evo in our gastric cancer study .
Speaker #4: This further reinforces the benefit we have seen in terms of Dor , PFS , and OS . And again , this biomarker is on mechanism .
Speaker #4: Going forward . We're developing a cd47 biomarker . And therefore it is really of no surprise to see that Cd47 overexpression shows such a strong impact on our data .
Speaker #4: So what this allows us to use is cd47 to select for patients in both current and future trials , with the goal of replicating the results we have seen here with gastric cancer and demonstrating the same significant and transformational benefit for patients and our Her2 positive breast study .
Speaker #4: Again , there are no approved therapies for patients overexpressing Cd47 and no options in late development . To address this , known path of evasion .
Speaker #4: So we remain focused on delivering for them . In 2004 . There are also no approved EGFR targeted ADCs , and although clearly a validated target that remains a substantial unmet need for these patients as well .
Speaker #4: Al 2004 is off to a very strong start in the clinic and we believe also as a potential to redefine standard of care across a range of EGFR , expressing cancers .
Speaker #4: So with that , I'll open up the floor to Q&A . Again , thank you for the time this morning .
Speaker #3: Thank you . We will now be conducting a question and answer session . If you would like to ask a question , please press star one on your telephone keypad .
Speaker #3: A confirmation tone will indicate your line is in the question queue . You may press star two . If you would like to remove your question from the queue for participants using speaker equipment , it may be necessary to pick up your handset before pressing the star keys .
Speaker #3: And again , that is star one . If you would like to ask a question . And our first question will come from Lee Wasek with Cantor Fitzgerald .
Speaker #7: Good morning Alex . Team , this is Daniel Bronner on for Lee . This is an exciting update . And we're curious to hear your thoughts on how to correlate the Cd47 positivity that you showed on slide 30 with the kind of cd47 expression cutoffs that you showed in the gastric data on slide 18 .
Speaker #7: What would you say is the high in this context ? And how should we think about the patient population ? That would be matching that in your in your trial ?
Speaker #4: Thanks , Daniel . Appreciate the question . So so thirsty . Just thinking about what we saw in breast or what we've observed in the literature versus versus gastric .
Speaker #4: Is that the that the question .
Speaker #7: Yeah . Basically , yeah .
Speaker #4: Okay . Yeah . Well yeah it's a great question . I think it's one we've looked into . I think what's really what we're really fortunate to have is a strong scientific basis behind Cd47 .
Speaker #4: And so what we see is , is , is really promising concordance across the , across the two indications . So if you look at gastric , it was roughly 50 over 50 in terms of the cd47 high group .
Speaker #4: And I think then if you turn to the benchmarks and again , this is where the strength of the the science comes in .
Speaker #4: It's we see we have five different publications looking at the question of of cd47 and specifically Her2 positive cancer . And again , what we see is strong concordance there to and if you add those numbers up , it's roughly half again .
Speaker #4: So five different studies supporting that around 50% of the patients will be cd47 high . And interestingly , those different publications use different clones , different methodologies , etc.
Speaker #4: . And so yeah , I think that that's what gives us such conviction that this is , you know , translatable not only to breast , but frankly , a broad range of , of tumor types .
Speaker #4: .
Speaker #7: And if I may, can I ask a follow-up question?
Speaker #4: Yeah , sure .
Speaker #7: How should we think about your companion diagnostic development ? Are you doing that yourself and how are you using the same kind of evorpacept construct , or are you using an independent antibody ?
Speaker #7: Do you can you shed any light on that ?
Speaker #4: Yeah , sure . I mean , I'll take it at a , at a high level and then maybe ask Barb to weigh in on , on the path to , to a seed .
Speaker #4: You know , we've we've done the testing with , with a partner for , for the gastric study plan to do , do the same in breast and then of course , as this data builds and I think as we , you know , continue to understand the right cutoff and how this , this translates , we'll pursue further work .
Speaker #4: But, Barb, do you want to add to that?
Speaker #5: I would just say that the assay is an IHCC. It's a research-use assay that was applied to the gastric data.
Speaker #5: Are ongoing or soon to be enrolling trial in breast cancer . The 80 patient single arm trial will use the same research based assay and then we are working already with partners to think about the operationalization of the process prior to the initiation of a phase three trial .
Speaker #5: So that we will be ready for a companion diagnostic . But again , via a partner .
Speaker #7: Great . Thank you so much for your time and answering my questions .
Speaker #4: Great . Thanks , Daniel .
Speaker #3: And our next question comes from Roger song with Jefferies .
Speaker #8: Great . Thanks for taking the question . And I'm very data . Thank you for hearing sharing this maybe related to the efficacy in the heart , the CD Cd47 high population .
Speaker #8: Do you have any data in your breast cancer trials with jazz and any any new data you can maybe give some comments on the Cd47 high versus low and then in terms of historical breast cancer , do we have any evidence for the Cd47 high population ?
Speaker #8: The traditional or the standard of care is performing less than the cd47 low population ? Have you done any retrospective study as well ?
Speaker #8: Because I know the the benchmark is using the Sophia or any other CD for the Her2 chemo combo , but that's in the broad Her2 positive , not cd47 cutoff .
Speaker #8: Thank you .
Speaker #4: Yeah . No , that's those are both great , great questions . Roger . So number one , in terms of the high versus low comparisons and the zany study .
Speaker #4: And frankly broadly , I think those are great questions . So this data and you know the the the way in which it's rippling through our development plan is relatively new as , as you know , Roger .
Speaker #4: So I think , you know , we're really excited about what we're seeing . It's incredibly strong in terms of cd47 high and gastric .
Speaker #4: There's no question it's driving the effect in that study . And so the natural question is where else is this ? This working .
Speaker #4: And I think whether it's the the study with jazz or our work with Sanofi or the other studies , we have going with anticancer antibodies , we're very keen to understand that .
Speaker #4: So I'd say what we know is we're seeing a 56% overall response rate in patients post in that have seen a whole lot of Her2 directed therapy .
Speaker #4: And to your point around the Margetuximab comparator , it's it's well north of what you'd expect . And actually there was recent data at ESMO that supports , again , you know , a relatively low response rate .
Speaker #4: There was a real world study that was sub 20% in patients in terms of or post and Her2 . So to see 56% , that's very strong .
Speaker #4: And I think , you your question on cd47 high versus low is one where in the process of of understanding and then your second question on just benchmarking the data and what we see , you know , Barb had laid out the the comparator with , with and Her2 in the destiny gastric oh four study .
Speaker #4: Certainly , if we were to line up the rainbow studies , to the best of our knowledge , the control arm is performing at par with with benchmarks across a number of different studies .
Speaker #4: And to your question , which again , is a good one , you know , those benchmarks we think are the best they're going to be .
Speaker #4: Right . Because we know Cd47 High is a negative prognostic . And we know that those patients should do do more poorly . And so , you know , to clear those benchmarks and compare well , and then also be armed with the knowledge that that those patients probably if we were to select from those studies , the cd47 high only patients , they would do even worse .
Speaker #4: Certainly I think builds our conviction .
Speaker #8: Yeah . Makes sense . Thank you .
Speaker #4: Thanks , Roger .
Speaker #3: And as a reminder , if you'd like to ask a question , please press star one and we'll go next to Sam Slutzky with Lifesci Capital .
Speaker #9: Hey good morning everyone . Thanks for taking my questions . Just on the interims next year , if the EGFR , ADC and the Breast cancer program , the Procept curious on how many patients you're hoping to have in each of those data sets , and then just how you view a win as you think about safety on the EGFR side , and then just the delta of efficacy on the Evorpacept side ?
Speaker #4: Yeah , both both great questions . Thanks , Sam . I'll take 2004 . I'll ask Barb to weigh in on on the breast front .
Speaker #4: I think 2004 , as you know , targeting EGFR , one of the most well trodden targets in in oncology , there's just no question that EGFR is effective .
Speaker #4: So I think it's led to a natural question from investors and partners . And that's , you know , can you can you target this target with an ADC when you have a payload involved ?
Speaker #4: And as a reminder again , I think we're very encouraged by what we see in the primate work . That tends to translate very well .
Speaker #4: And so far so good . Right ? To clear one MiG per kg quickly . I think is a strong start and already a relatively high dose .
Speaker #4: And now on to the next cohort , which again , I think is moving fast , is is what you want to see .
Speaker #4: So as we go into to the next year , early next year , in terms of what we'll share , I think it's , you know , it depends .
Speaker #4: Right . Which is is the reality of a dose escalation study . I think our goal is to answer the safety question as best we can in a phase one .
Speaker #4: And then put up data that will will answer that . And again , the study is , is marching very well here . And I think we feel , you know , we feel real confident that if this continues , of course , we'll be able to share something going into early next year .
Speaker #4: And then on the breast front , in terms of benchmarks , Barb , do you want to weigh in on that one ?
Speaker #5: Yeah , I think , Sam , thank you . I think you were asking what might our expectations be both for number of patients as well as the bar .
Speaker #5: The bar I'll start with there's a lot of data with trastuzumab and chemotherapy , which really is the backbone upon which we add a precept in our trial .
Speaker #5: Chemotherapy . Trastuzumab at best , will have about a 20% response rate . Interestingly , there was a new data coming out of Esma looking at the post enhertu setting and response rates continue to drop , not unexpectedly and as we noted , our trial will enroll all patients post enhertu where we do anticipate that Cd47 overexpression becomes part of the mechanism of resistance .
Speaker #5: We attack that directly, and we anticipate having good outcome data in our Evorpacept trial. So, I think the benchmark is going to be in the range of 15% response rates.
Speaker #5: Again , 20% might be the upper bound , but with the combination of the two things , the poor prognostic effect of Cd47 , as well as the evolving standard of care and the fact that there really isn't anything that has shown up well in really bodes well for us .
Speaker #5: What do we expect in our bar ? I think , you know , doubling that would be nice . 35% to 40% . We certainly in our gastric data that I showed you did in the gastric setting , did even better .
Speaker #5: And we anticipate that , you know , the the opportunity is there to do quite well . But I think we would be very happy with a 35 to 40% response rate in our in our breast trial .
Speaker #9: Okay . Thanks .
Speaker #4: Thanks , Sam .
Speaker #3: In this now concludes our question and answer session . I would like to turn the floor back over to Jason Lettmann for closing comments .
Speaker #4: Great . Thanks everybody . Really , really excited to share this data with you . We've continued good progress across both Evo and 2004 .
Speaker #4: So real positive update today . And again appreciate the engagement and and support and look forward to future updates . Thanks so much .
Speaker #3: Ladies and gentlemen , thank you for your participation . This does conclude today's teleconference . You may disconnect your lines and have a wonderful day .