Good morning, everyone, and welcome to the ArriVent BioPharma virtual webinar. At this time, all attendees are in a listen-only mode, and a question and answer session will follow the presentation. To our analysts joining us live, we kindly ask that you limit yourself to one question and one follow-up. As a reminder, this call is being recorded, and a replay will be made available on the ArriVent website following the conclusion of the event. I'd now like to turn the call over to Winston Kung, Chief Financial Officer at ArriVent BioPharma. Please go ahead, Winston.
Great. Thank you, Tara. Before we start the presentation, I want to make note that this webinar may include forward-looking statements under the PSLRA. Actual results may differ materially from those projected in the forward-looking statements. Additional information concerning factors that could cause materially different results includes forward-looking statements in our periodic reports filed with the SEC and available on our website. With that, I'd like to turn it over to our CEO, Dr. Bing Yao.
Thank you, Winston, and good morning, everyone. Thank you for joining us today. We are very pleased to host this investor call following the presentation of our phase I clinical data for ARR-217 at ESMO. We are particularly excited that this data was selected for late-breaking oral presentation. Before we dive into the clinical results, I would like to briefly put ARR-217 into the context of ArriVent's broad strategy and pipeline. Next slide, please. Next. As you can see on this slide, we have built a diversified oncology pipeline spanning targeted small molecule and antibody drug conjugates with multiple opportunities across indications and geographies. Starting with firmonertinib, we continue to advance our global phase III ALPACCA trial in patients with EGFR PACC mutant non-small cell lung cancer. Enrollment remains ongoing, and we believe this program represents an important opportunity to address significant unmet medical needs.
At the same time, we have made substantial progress in building a differentiated ADC portfolio, which has become an increasingly important part of our long-term growth strategy. We now have four ADC programs in our pipeline, including two in clinical development and two earlier stage programs. I'm also pleased to highlight that we recently enrolled the first patient in our phase I trial of ARR-002, our novel dual targeting ADC, directed against NaPi2b and MUC16. This represents another important milestone in the advancement of our ADC pipeline. Turning to ARR-217, the focus on today's call. This is our CDH17 targeted ADC being developed for gastrointestinal cancers, particularly colorectal cancer. Yesterday's ESMO presentation represent an important milestone for the program. We are very encouraged by the emerging clinical data, particularly the anti-tumor activity and the tolerability observed to date.
We believe these results provide a strong foundation for further development and reinforce our confidence in the potential of ARR-217. More broadly, our strategy remains on identifying and advancing differentiated oncology therapies with a goal of delivering meaningful benefits to patients and creating long-term value. With that, let me turn it over to Stuart to discuss our ADC strategy.
Yeah. Thank you, Bing. Next slide. Next slide, please. Our ADC strategy is to identify and develop therapeutically important ADCs based on the pattern of ADC target expression. For ADC targets that have high homogeneous tumor expression, such as CDH17, which we will discuss today, we pursue differentiated molecules with design features such as conjugation method, linker, and payload for best-in-class ADC potential in tumors with high unmet medical need, many of which are still treated with standard chemotherapy. For ADC targets that have a high but more heterogeneous expression, which is actually more common in solid tumors, we are developing a pipeline of novel tetravalent dual targeting ADCs. As Bing mentioned, we are very excited that our first tetravalent dual targeting ADC, ARR-002, is in phase I dose escalation in the United States.
These dual targeting ADCs are designed to overcome resistance that can arise from tumor cells present within the tumor mass that have lower expression and that can lead to resistance. In this way, dual targeting ADCs have the potential to more completely treat the entire tumor and all sites of disease, and also decreases the need for IHC-based companion diagnostic to select patients such as in folate receptor high ovarian cancer. The tetravalent ADC design also increases the binding and internalization of the ADC to tumor cells to provide superior drug delivery and enhance cytotoxicity over bivalent ADCs. Next slide. As I mentioned, CDH17 is an ideal target for single targeting ADCs as it has high homogeneous expression in colorectal cancer, which as you can see, the vast majority of colorectal tumors exhibiting greater than 75% of the tumor cells having high IHC 3+ staining. Next slide.
ARR-217 is our novel CDH17-targeting ADC we are developing together with Lepu Biopharma. ARR-217 consists of a novel high-affinity humanized anti-CDH17 monoclonal antibody directed against the most exposed extracellular domain of CDH17, which includes a potent TOP1 inhibitor exatecan payload. Exatecan is less subject to drug efflux pumps such as P-gp than other TOP1 inhibitors. Site-specific conjugation is achieved through a stable glycan-based linkage utilizing a hydrophilic linker to improve the PK properties of the molecule. ARR-217 exhibits rapid internalization and enhanced bystander activity in tumor cell lines and robust anti-tumor activity in multiple xenograft models with a range of CDH17 expression. ARR-217 was well-tolerated in monkey studies at the highest dose tested, with minimal GI toxicity, conferring a favorable preclinical therapeutic index. Next slide.
To demonstrate the enhanced stability of glycan-based site-specific conjugation, ARR-217 and a control ADC consisting of the same antibody but with conventional cysteine-based conjugation to DXd were incubated in non-human primate plasma. As you can see, there was minimal release of the payload from ARR-217 during this 21-day period compared to the DXd control. Next slide. ARR-217 with DAR4 exatecan exhibited improved bystander activity compared to the DAR8 DXd control ADC, as you can see in this figure, with near complete killing of non-CDH17-expressing cells, here demonstrated utilizing two different cell line models. Next slide. ARR-217 induced tumor regression across a range of xenograft models with different CDH17 expression. The activity of ARR-217 was comparable or improved over ARR-217 DXd control. This is despite ARR-217 having a lower DAR. Together, this data demonstrates the best-in-class potential of ARR-217 in colorectal cancer.
I'll now hand things over to Preethi to discuss the clinical development of ARR-217.
Thank you, Stuart. Next slide. Colorectal cancer continues to represent one of the largest unmet needs in oncology today. Globally, nearly 1.9 million patients are diagnosed each year, and the incidence is expected to grow substantially, reaching approximately 3 million cases annually by 2040. Despite advances in treatment, colorectal cancer remains the second leading cause of cancer-related death worldwide, and outcomes are particularly poor for patients with metastatic colorectal cancer. The current five-year survival rate is only about 13%, underscoring the need for more effective therapies that can meaningfully extend survival and improve quality of life. Next slide. This slide highlights the current treatment landscape for metastatic colorectal cancer. Today, treatment selection is guided by molecular profiling with patients stratified across key biomarker-defined populations, including KRAS, RAS mutant, BRAF mutant, MSI-high, and HER2-amplified disease.
In the first and second-line setting, the majority of patients receive chemotherapy backbone such as FOLFOX or FOLFIRI, often combined with biological agents. Despite the increasing use of biomarker-directed therapies earlier in treatment, options become much more limited after progression, with treatments that generally provide modest clinical benefit. Next slide. Current third-line and later treatment options for metastatic colorectal cancer provide limited benefit. This slide summarizes the efficacy of the currently available standards of care for metastatic colorectal cancer after progression on earlier lines of therapy. While several agents are approved and commonly used, the overall outcomes are limited. Objective response rates are in the single digits and are generally only 1%-6%, highlighting the difficulty of generating meaningful tumor shrinkage in this setting. Progression-free survival is typically just two to five months, and the median overall survival remains under a year.
Even the best available regimens provide modest outcomes, highlighting the significant unmet need for more effective therapies. Next slide. ARR-217 is being evaluated in a multicenter phase I study in China and the United States in advanced solid tumors, including colorectal cancer. Eligible patients have locally advanced or metastatic solid tumors, have progressed on standard therapies, maintain a good performance status with an ECOG score of zero to one, and have measurable disease according to RECIST criteria. The phase Ia portion of this study focuses primarily on safety and dose escalation. Patients were enrolled across escalating dose levels, beginning at 2 mgs per kg and advancing through multiple dose cohorts to characterize the safety profile, identify dose limiting toxicities, and establish an appropriate dose range for further development. Additional backfill cohorts were included to evaluate safety and generate preliminary efficacy data at selected dose levels.
The ongoing phase Ib portion of the study in colorectal cancer, patients are being randomized one-to-one between 5 mgs per kg and the 6 mgs per kg dose with safety and ORR as key endpoints. Next slide. As of the August 5, 2026, data cutoff, 123 patients have received ARR-217, including 113 patients with colorectal cancer. The enrolled CRC population reflects a typical metastatic colorectal cancer population. The median age was 58 years, with approximately one-third of patients were female. The majority of patients were ECOG zero to one. This study enrolled a heavily pretreated metastatic CRC population. Patients received a median of three prior lines of therapy. Nearly all had received standard chemotherapy agents such as oxaliplatin and irinotecan. Over half of patients had liver metastasis, nearly 60% had RAS mutations, and most had microsatellite stable disease. Next slide. ARR-217 demonstrated predictable dose proportional pharmacokinetics and strong ADC stability.
The ADC and total antibody profiles closely tracked together, while free exatecan exposure remained extremely low. These data suggest efficient payload delivery with minimal systemic payload release. Next slide. Across the 123 patients, the majority of treatment-related adverse events were low-grade. The most commonly observed toxicities were hematological and gastrointestinal in nature, including anemia, neutropenia, diarrhea, nausea, and decreases in white blood cell and platelet counts. While Grade three or higher events were observed, they generally occurred more frequently at higher dose levels. Of note, at 6 mgs per kg, the safety was well-tolerated, with only 2% Grade three diarrhea and a low rate of hematological toxicities. In addition, there were only two dose reductions and no treatment discontinuations due to adverse events at the time of the data cutoff. During dose escalation, the maximum tolerated dose was not reached.
Only a single dose-limiting toxicity was reported at the 8 mgs per kg dose level, consisting of a Grade four platelet count decrease and Grade four neutropenia. No ILD events occurred. Next slide. At the time of this analysis, 75 treated patients had undergone at least one post-baseline tumor assessment with a median follow-up of just over four months. Across dose levels of 4 mgs per kg and above, ARR-217 demonstrated encouraging objective response rates, particularly given the pretreated nature of this population. The strongest signal emerged at the 6 mgs per kg dose, where the objective response rate was 44.8% with a disease control rate of 93.1%. The waterfall plot further illustrates the depth and consistency of tumor shrinkage. At the 6 mgs per kg dose, the majority of patients experienced reductions in target lesion burden, including seven confirmed partial responses.
An additional four responses pending confirmations have been subsequently confirmed, including the unconfirmed response at 7 mgs per kg. Next slide. This slide highlights the consistency of efficacy across key patient populations. At the 6 mgs per kg dose, ARR-217 achieved a 45% overall response rate, and the activity was maintained across clinically relevant subgroups. Response rates were similar in patients who had received irinotecan at 43.5%. Activity was also observed regardless of molecular subtype, with response rates of 50% in RAS mutant patients and 42% in RAS wild-type patients. Importantly, efficacy was maintained in later line disease with a response rate of 46.7% in second and third-line patients and 42.9% in fourth-line plus patients. We also see a highly consistent signal geographically, with response rates of 37% in U.S. patients and 35% in China across the 6-8 mgs per kg dose range. Next slide.
In this swimmers plot, we observe that many patients have been able to remain on treatment for extended periods of time, with several continuing beyond six months and some approaching or exceeding nine months of treatment. The durability of treatment is especially evident in the 6 mgs per kg cohort, which, as we've seen, demonstrated strong efficacy and tolerability. Next slide. As we conclude, this slide summarizes the key findings from the phase I experience with ARR-217 and colorectal cancer. From a safety perspective, ARR-217 was generally well-tolerated. Adverse events were primarily low grade GI and hematological toxicities. Only one patient discontinued due to an adverse event. Turning to efficacy, ARR-217 has generated a strong preliminary efficacy signal in metastatic colorectal cancer with a 44.8% overall response rate and 93.1% disease control rate at 6 mgs per kg dose.
Responses were observed regardless of RAS mutation, prior irinotecan treatment in fourth line plus treatments, as well as across the United States and China. These results support further development and ongoing phase Ib dose optimization. Next slide. I will turn it back over to Bing.
Thank you, Stuart and Preethi, for the presentation. As you have just seen, we are very encouraged by the emerging clinical profile of ARR-217, in particular, the combination of anti-tumor activity and the tolerability observed to date. Next slide, please. I would now like to spend a few minutes putting these results into a broader competitive context. You can see from this slide, it puts ARR-217 results into the context of other ADCs being developed for colorectal cancer. As you can see, several ADC programs have demonstrated encouraging activity in this very challenging patient population with a confirmed response rate generally ranging from mid-teens to approximately 30%. What is particularly encouraging to us is that ARR-217 has demonstrated a 44.8% of all objective response rates that's on your left side, with confirmed plus pending confirmation response rate of 38% at the 6 milligram per kilogram dose.
As Preethi mentioned, the pending confirmation has subsequently been confirmed. This data compare favorably with the response rate reported for other ADC programs. Next slide, please. Equally important, we are encouraged by the emerging safety and tolerability profile. Here we compare two important categories of adverse events across several ADC programs and standard of care in colorectal cancer, diarrhea, and hematologic toxicity. Starting with diarrhea, ARR-217 had a 39% incidence of all grade diarrhea, mainly lower grade. However, only 2% Grade three or higher diarrhea at a 6 milligram per kilogram dose. We believe this is particularly encouraging given that gastrointestinal toxicity can be a significant concern for patients with colorectal cancer. On the right side, on the top you can see we compare severe hematologic adverse events, including anemia, neutropenia, and thrombocytopenia.
Here again, ARR-217 has demonstrated an encouraging safety profile with relatively low rates of severe cytopenia compared with several other ADC programs and established treatment regimen. Of course, these are cross-trial comparisons. Differences in patient populations, treatment exposure, and adverse reporting must be considered. Nevertheless, we believe the emerging safety profile, together with the encouraging anti-tumor activity we have observed, positions ARR-217 as a potentially differentiated ADC in colorectal cancer. Importantly, this profile may provide greater flexibility for combination strategies and opportunities to move into earlier lines of therapy. Next slide, please. Looking ahead, we see significant opportunities to expand ARR-217 across multiple treatment settings and potentially additional gastrointestinal cancers. Our initial focus is on third-line and later colorectal cancer, where patients have limited treatment options and there remains significant unmet medical need.
Our ongoing phase Ib monotherapy study in the U.S. and China will help us further characterize the efficacy, safety, and the durability of responses and support our plans for later stage development. At the same time, we are exploring combination strategies to potentially expand ARR-217 into earlier lines of treatment. We have an ongoing phase Ib study evaluating ARR-217 in combination with bevacizumab, as well as combination studies with chemotherapy in China, which could support development opportunities in both second-line and first-line colorectal cancer. Beyond colorectal cancer, we also see potential opportunities in other CDH17-expressing gastrointestinal cancers, including pancreatic cancer. Overall, our strategy is to establish ARR-217 as a potential monotherapy and all combination treatment option in later-line colorectal cancer while building the clinical evidence to support broader opportunities in earlier lines and additional tumor types. Next slide, please.
Finally, let me highlight several important milestones we expect over the coming year. Starting with firmonertinib, we plan to provide a program update in the first quarter of 2027 following our ongoing evaluation of relevant data and a broader development strategy. For ARR-217, we anticipate a number of important clinical milestones throughout 2027. In the first half of the year, we expect to report additional phase Ib monotherapy data, which should provide further insights into the durability of response, progression-free survival, and overall clinical profile of ARR-217. In the second half of 2027, we plan to share initial phase Ib data from our combination study with bevacizumab, followed by initial data from our chemotherapy combination studies by year end. Importantly, we are targeting initiation of our phase III study by the end of 2027.
This represents a major potential next step for the program as we work towards bringing ARR-217 to patients. We recognize this has been a challenging period for ArriVent, but we remain focused on disciplined execution, making thoughtful development decisions, and advancing programs that we believe can make a meaningful difference for patients. Lastly, I want to thank our clinical investigators, patients and their families, our partners, and the entire ArriVent team for their contributions to the program. With that, we will be happy to take any questions. Back to you, operator.
Great. Thank you, Bing. Yes, at this time, we will be conducting a question and answer session with our speakers, so please hold for a brief moment while we poll for questions. Our first question comes from Michael Schmidt at Guggenheim. Please go ahead, Michael.
Yeah. Hey, guys. Thanks for taking my questions, and congrats. Really nice data update here yesterday at ESMO. I had just a quick follow-up on the data itself. Could you just confirm whether the remaining two unconfirmed responses at the 6 mg per kg cohort, can they still be confirmed? Are they off therapy at this point in time? The other question I had is just on future development plans. We have seen a few other companies now pursue accelerated approval strategies in late-line colorectal cancer, and I was just wondering if that is something that you have considered, in addition to the phase III, obviously, in the future.
Great. I will direct that question to Preethi.
The two unconfirmed will not be confirmed and are off study. The second part of the question was? Can you repeat it?
Whether an accelerated approval strategy
in colorectal is something that you have considered, just given the high response rates. Durability looks great, and so I'm just curious, since we've seen it in the industry now, being pursued by other companies as well.
We're continuing to evaluate the data. We're excited by the efficacy, continue to follow for durability, and as the data evolves, I think we will consider all development options on the table.
Thanks.
Great. Thank you, Michael. Our next question comes from Gaurav Maini at LifeSci Capital. Please go ahead, Gaurav.
Hey, good morning. This is Gaurav on for Sam. Nice update here, everyone. Just one from us on the data itself. On the kind of a bell-shaped response curve you see with the 6 mg per kg performing the best, then we have the 7 mg per kg performing a little lower, and 8 performing a little lower than 7 mg per kg. I guess just with this, is there anything you can point to on dose intensity and dose reductions as a cause for this? Then following this, as we think about dose reductions, what did the protocol look like for where these 7 mg per kg and 8 mg per kg patients would typically dose reduce down to?
Mm-hmm. I'll take that. In terms of at our higher doses, we did see increased toxicity, primarily cytopenias and diarrhea, that did lead to some limited efficacy at those higher dose levels. In terms of dose reductions, the 7 mgs per kg, the first dose reduction was to 5.4 mgs per kg, and the second dose reduction level was at 4 mgs per kg . Then for 8 mgs per kg, the first dose reduction was at 6 mgs per kg , and then the second dose reduction, 4 mgs per kg .
Sorry, the second dose reduction, so 8 mgs per kg to 6 mgs per kg . You just cut off.
So 8 mgs per kg to 6 mgs per kg , then 6 mgs per kg to 4 mgs per kg .
Okay.
Then if you start at 7 mgs per kg , you went from 7 mgs per kg to 5.4 mgs per kg , then to 4 mgs per kg .
Gotcha. Thank you.
Yeah.
Thanks for the question, Gaurav. Our next question comes from Yigal Nochomovitz at Citi. Please go ahead, Yigal.
Hi, Bing and team. Thank you for taking the questions, and nice to see a very strong data set. I had a few questions with respect to the response rate. Obviously very strong, whether you do the 45% or the fully confirmed number. My question is, how do you think about what you could get in terms of an additional boost on response adding bevacizumab? Obviously, if you looked at the LONSURF approval trial, they got about a 5% boost off a very low 1% response rate. Then I think with the AbbVie molecule, with the c-Met, they got about another 10% or so by adding bev on top of the monotherapy. Just curious about that. Then secondly, how do you think about the translation of the response to PFS number?
Because I think the discussant was alluding to the fact that it wasn't necessarily clear if a higher response rate would flow through to higher PFS. It would seem that it would, but she wasn't sure. I'm just curious how you think about all that. Thank you.
Great. I'll direct that question to Bing.
That first one.
The first part was the additional boost that you might be able to receive from bev, and the second part was translating response rates to PFS.
Yigal, we do have phase Ib ongoing now, and the dose optimization is testing the monotherapy, then combination with bevacizumab. If you look at the past data by other companies, bevacizumab actually would be mainly extend the PFS. It remains to be seen. We have two studies ongoing that will inform us of that. We do anticipate adding bev will add to potential benefit, either ORR or PFS.
Great. Thanks for the question, Yigal. Our next question comes from Nabeel Nissar at Jefferies. Please go ahead, Nabeel.
Hey, team. Good morning. Congrats on the data. Thanks for taking our question. This is Nabeel on for Roger. Again, encouraging to see the 6 mg per kg data consistency across the sub-cohorts. What is your take on that, specifically the RAS wild type RAS mutant? Again, we do have an N of almost 10 in each. Thoughts on that and how you think about the pivotal design. Would you ever be sharing IHC data expression of CDH17 in the future? Thank you.
Great. I will direct that question to Bing for the RAS wild type mutant and then also the IHC data.
Probably, I think first, I think Stuart, definitely please add in. I think from MOA point of view and ADC to ADC, that should not make that much difference regardless what RAS wild type mutations. Our data actually confirms that, it works in both. Probably I think Stuart can add to that.
Yeah, I think it is pretty balanced. The RAS status really dictates what prior therapies a patient has received, more than whether they respond to an antibody drug conjugate. But we are seeing activity in both groups. In regards to the expression of CDH17, we are evaluating CDH17 levels in these patients and need to have a large data set to see whether there is any correlation. But as I pointed out in that slide during the intro, there is high homogeneous expression using that 75% tumor cell, 3+ in mid 70%. So we are looking whether we need a diagnostic for further development, but most tumors are very high to start with.
Thank you. That is helpful. Regarding the enrichment in the 6 mg per kg versus the other dose groups, 8 mg per kg, do you see a similar pre-treated irinotecan, similar baselines as well there?
For that question, I'll turn it to Preethi.
Yes. These are small numbers, so a little bit difficult to piecemeal, but generally similar across the dose levels.
Okay, great. Thank you.
Yep.
Thanks for the questions, Nabeel. Our next question comes from Li Watsek at Cantor Fitzgerald. Please go ahead, Li.
Great, guys. Very encouraging data. A clarification question from us. The 6 mg per kg dose, we noticed that there is a little bit of difference in the patient number included in the safety data versus the efficacy data. Can you just share a little bit of information here? Second, just wondering if you used prophylactic growth factor in a dose escalation portion, any mitigation plan in the phase Ib trial to potentially reduce neutropenia?
Great. I will turn those questions to Preethi.
Okay. I will answer the second one first. We did not use growth factor prophylaxis in this trial, and do not plan to in the 1b portion either. The first question, so the safety numbers is really anybody who received a single dose is in the safety denominator versus efficacy is anybody who had measurable disease and at least one post-baseline disease assessment. So that accounts for the differences in the numbers between safety and efficacy. That is across all of the dose levels.
Thank you.
Thanks for the question, Li. Our next question comes from Jeff Jones at Oppenheimer. Please go ahead, Jeff.
Good morning, guys, and congrats on the really exciting data set here in Madrid. I guess two from us. Can you just comment on the patient mix between U.S. and China, both in terms of how you are looking at dose expansion in colorectal for the monotherapy study, and then as you move into some of these combination studies. I guess I have to ask, any commentary you can make on next steps and how you are thinking about the FURVENT readout?
Great. For the first part on patient mix to Preethi, and then FURVENT for Bing.
Geographically, we tend to be pretty well-balanced in the phase Ib portion. We are enrolling patients in China and in the U.S. And right now, I think over across the study is probably two-thirds, one-third. But in the phase Ib, we will probably be closer to 50/50. For FURVENT, I will hand that over to Bing.
Yeah. For FURVENT, we continue to evaluate, mainly looking into the differences between the BICR and the investigator on the control arm. You probably saw that where the firmonertinib performed pretty well as expected. In terms of PFS, in terms of the ORR, good trend with the overall survival too. But the main difference is in the chemo arm between BICR and the investigator assessment. So we are looking into that, and we plan to have an update by the Q1 of 2027.
Thank you, guys.
Great. Thanks for the questions, Jeff. Our next question comes from Mayank Mamtani at B. Riley. Please go ahead, Mayank.
Yes, team. Thanks for taking my questions, and let me add my congrats, too. So just maybe to understand the 5 mg versus 6 mg per kg dose selection on a go-forward basis, if you could just comment on what you learned from dose optimization, but also from maybe the bev combination and also, I think, the chemo combination that you are starting to work on. What dose levels are you looking at there? If you are able to also help us understand what your base case thinking for initial phase III. Again, you have a history of going very fast in earlier line settings, as we learned from FURMO. So was just wondering how you are thinking about I understand it is prematurely, but what are you thinking your initial phase III study design would be?
Great. Preethi, you want to start us off on the 5 mg question?
Yes. So we are evaluating the 5 mg and 6 mg cohorts for monotherapy. Those are similar doses that we will also explore with bevacizumab. In terms of chemo combinations, I think we are still evaluating the dose. Obviously, with combined toxicity with chemo, we expect to start at probably a bit of a lower dose and escalate upwards. So that data, I think, as Bing mentioned, will be available closer to the first half of the year.
Great. Thanks for the question, Mayank. Our next question comes from Jeet Mukherjee at BTIG. Please go ahead, Jeet.
Great. Thanks for taking the question, and congrats on the impressive data. It is nice to see the combination strategies with bev and chemo being pursued, but just wanted to get your take on any thoughts around combinations with EGFR inhibitors and/or RAS inhibitors, as we are seeing these combinations really grab attention in the space as well. As a second question, just any comment on responses observed in other tumor types outside of colorectal in this data set? Thank you.
Great. I will direct that question to Preethi.
I think we are interested in exploring a variety of combinations. We are excited by our initial monotherapy efficacy and safety profile and think it is probably combinable with a variety of agents. We are definitely open to that. The second question was, just remind me, sorry.
Just the responses in tumor types outside of colorectal.
Oh, yes. We have not analyzed that data for the other tumor types. The majority of these patients were colorectal, and so those are the tumor types that we are focusing on.
Great. Thanks for the question, Jeet. Our next question comes from Supawat Thongthip at Truist. Please go ahead, Supawat.
Hi. Congrats on the data, team. Really exciting data. I was just wondering if there's anything you could say about perhaps the consistency between efficacy and safety data that we've seen between the China data versus the U.S. data. Just wondering if you have done any analysis on that.
Great. I'll turn that to Preethi.
Yes. I think we presented in our main deck that we have similar efficacy geographically, with response rates of about 30% in U.S. patients and 35% in China across the 6 mgs per kg to 8 mgs per kg dose range. And that has been consistent in terms of efficacy.
Got it. Maybe just a quick follow-up. It seems that ARR-217 is active across both RAS wild type, RAS mutant. I am just curious if you are thinking of exploring potential combination beyond chemo and bev, maybe with KRAS agents or even EGFR agents. Is that on the plan?
Yeah. I think similarly, I think we are exploring a variety of combination agents. Right now we are focused on bev and chemo, but we are exploring, looking at other potential combinations.
Okay, thanks.
Great. Thanks, Supawat. Our next question comes from Boris Peaker at Jones. Please go ahead, Boris.
Great. I'd like to add my congratulations to the exciting data. A question on CDH17. You've mentioned that it's high across all these colorectal patients. I'm just curious, are you collecting IHC data for patients post-treatment, particularly the patients that fail therapy, just to understand whether CDH17 loss is a potential resistance mechanisms? What is your thought of potential resistant mechanism? How would that impact your thoughts on the combination therapies?
Great, Preethi?
I'll pan the second part maybe to Stuart, but I think for the first part, yes, we are evaluating CDH17 expression throughout the trial. Stuart, would you like to speak to the resistance piece?
Yeah. In regards to collecting biopsies at progression, if a patient has a biopsy done, we do request that tissue, but it's not mandated in the study. In regards to resistance to these ADCs, it likely will be multifactorial, but we'll have to do further studies on that.
Great. Thanks for taking my question.
Thank you, Boris. Our final question comes from Kaveri Pohlman at Clear Street. Please go ahead, Kaveri.
Yes. Good morning. Congrats on excellent results, and thanks for taking my questions. I just want to put things in a broader perspective. What feedback you have received from physicians involved in the studies? How do they view the safety and efficacy profile relative to approved therapies and other clinical stage drugs? What would they most like to see from the next year's dose optimization data beyond durability? My second question is just if you could discuss the overall IP strategy for the drug. Thank you.
Great. Maybe the first part of the question, I will turn to Preethi, and then the second one to Bing.
Yes. We are very interested and engaged investigators on this trial that are very excited about the initial preliminary safety and efficacy data, particularly at the 6 mg per kg dose. I think they are interested in both exploring this drug as a monotherapy, as well as exploring various combinations because of the initial efficacy and safety profile that we've seen. That includes treatment in the late line settings with bev, as well as in earlier line settings with chemo and potentially other novel combinations.
Sorry, yeah. Can you repeat the question?
IP strategy for 217.
IP strategy? Yeah. Clearly, we have filed IPs on the molecule, and as we get more data, there'll be more filings to cover. We believe we have a comprehensive strategy to generate and also secure the IPs.
Great. Thank you for the question, Kaveri. This concludes today's virtual webinar. You may now disconnect.