Good afternoon, and welcome to the Bolt Biotherapeutics BDC-3042 Phase I dose-escalation study and clinical programs update conference call. [Operator Instructions] Please be advised that today's conference is being recorded.
I would now like to hand the call over to Sarah Nemec, Senior Vice President of Finance and Principal Accounting Officer. Please go ahead.
Thank you, and good afternoon, everyone. The slides for today's call are available under Events and Presentations in the Investors section of our company's website and are available on the webcast platform for those who are logged into the webcast for today's event. We suggest that you follow along with the slides at your own pace.
Before we begin, I'd like to remind everyone that during this call, we will be making forward-looking statements that are subject to a number of risks and uncertainties. These may cause our actual results to differ materially, and I encourage you to read our SEC filings for more details on these risks and uncertainties. You are cautioned not to place any undue reliance on these forward-looking statements, and Bolt disclaims any obligation to update such statements.
Earlier today, we presented our first quarter results, including cash, cash equivalents and marketable securities, totaling $58 million as of March 31. This is expected to fund multiple key milestones, including our Phase I dose-escalation trial for BDC-4182 through mid-2026. We continue to reduce costs while actively developing products to treat patients with cancer. With activities such as our recently announced sale of lab equipment for proceeds of approximately $1 million and our second sublease, which will help to reduce our operating costs going forward.
While we would be happy to entertain questions on our financials, the focus of today's call will be on the data from our Phase I dose-escalation clinical trial of BDC-3042, which was presented at the American Association for Cancer Research Annual Meeting in Chicago last week.
With this in mind, I'd like to introduce the presenters. We are honored to have Dr. Ecaterina Dumbrava, Associate Professor at the University of Texas MD Anderson Cancer Center, an investigator for the 3042 program join us today to further discuss the BDC-3042 data. Also joining us today are several members from the Bolt Biotherapeutics team, including Willie Quinn, our President and CEO; Justin Kenkel, Senior Principal Scientist; Grant Yonehiro, Chief Operating Officer and Chief Business Officer; and Jakob Dupont, Board Director and Senior Clinical advisers. We also have additional team members available for the question-and-answer session after our prepared remarks.
I will now turn the call over to our CEO, Willie Quinn, who will provide an overview of our topics for today.
Thanks, Sarah. I'll start my comments on the Slide 6, if you're following along with us. As background for those unfamiliar with Bolt, we are harnessing the power of the immune system to improve lives and eradicate cancer. We are developing several programs, including BDC-3042, a first-in-class dectin-2 agonist antibody. And BDC-4182, a next-generation Boltbody immune-stimulating antibody conjugates or ISAC, targeting claudin 18.2. BDC-4182 is the most advanced program using next-generation linker-payloads for our Boltbody ISAC platform, and I'm excited to announce that we have opened enrollment for the first-in-human Phase I study of BDC-4182 in gastric and gastroesophageal cancer. The Boltbody ISAC platform is the basis for our collaborations with Genmab and Toray and for our proprietary pipeline. In our Genmab collaboration, we have now advanced two product candidates into development and continue to research and develop additional programs.
Turning to the agenda on Slide 7. Today, we will walk through the background on BDC-3042, including an explanation of how this drug candidate works and the steps we took to prepare for our clinical trial. This section will be presented by Justin Kenkel, PhD, who started exploring the impact of dectin-2 agonism on tumor growth back when he was in the Engelman Lab at Stanford. Then Dr. Dumbrava will discuss the Phase I results from her perspective as an investigator in the clinical trial. Grant Yonehiro, our Chief Business Officer, will then discuss our plans for partnering BDC-3042. We'll then shift gears to discuss our claudin 18.2, targeting Boltbody ISAC BDC-4182 and its clinical development plan presented by our Board Director and Senior Clinical Adviser, Dr. Dupont. I'll then return for some concluding remarks, and we look forward to answering any questions you may have.
I'll now turn the call over to Justin Kenkel, Senior Principal Scientist here at Bolt Bio to discuss the mechanism of action for BDC-3042 and our preclinical development. Justin?
Thank you, Willie. I'm happy to be here today to go over some background on BDC-3042, our dectin-2 agonist antibody, which we view as a really unique and promising new approach to treat cancer.
So moving to Slide 9. Dectin-2 is a pattern recognition receptor that is normally involved in sensing and responding to foreign pathogens. But we have found is that the receptor expressed by tumor-associated macrophages or TAMs across a wide range of cancers. Now TAMs are known to typically be tumor supportive and immunosuppressive, but our goal with BDC-3042 is to engage and agonize dectin-2 receptor on TAMs and thereby, convert them into tumor destructive cells that promote antitumor immune responses.
Another important thing to note is that tumor PD-1 blockers like pembrolizumab and nivolumab has been shown to lead to an upregulation of dectin-2 expression in the tumor market environment, which when taken clinically suggest that tumors can be more responsive to BDC-3042 in the post checkpoint inhibitor setting and that combined 3042 with checkpoint inhibitors could be a particularly powerful combination.
Dr. Dumbrava will go over in more detail with you the results from our first-in-human study. But overall, we've been very encouraged with what we've seen, and believe the results strongly support further development.
To briefly summarize, 3042 has appeared safe and has been well tolerated at adults level tested. It is clearly biologically active. We are seeing evidence of target engagement and immune simulation, in line with our expectations based on the preclinical work. It has a good PK profile, which would enable more convenient dosing regimens, and we are seeing promising signs of antitumor activity with a single agent, in particular, in non-small cell lung cancer in the overlapping post checkpoint inhibitor setting and at the highest dose level tested. And again, Dr. Dumbrava will go over more of the clinical details with you later in the presentation.
Moving to Slide 10. BDC-3042 is the first clinical stage agent targeting dectin-2 which is a novel IO target that we consider to be well differentiated from other myeloid-directed programs. For one, 3042 is an agonist antibody targeting an activating receptor, which contrasts with many of the recent efforts at myeloid reprogramming which have often involved blocking antibodies targeting inhibitory receptors. As shown in the figure on the right, dectin-2 is known for its role in stimulating innate inductive immune responses against fungi and other microbes. And what we are doing in essence is trying to harness these activities to stimulate more potent immune responses against tumors.
And here we have shown preclinically that dectin-2 agonist can activate and reprogram TAMs leading to enhanced CD8 T cell responses, complete tumor regression in some cases and the induction of immunological memory. And while, of course, toxicity can be a great concern with immune agonists, dectin-2 has a very favorable expression profile with low expression in most normal tissues as well as on circulating immune cell populations, which we think are important factors underlying the safety of our approach.
Moving to Slide 11. We have found that dectin-2 is expressed on TAMs across many cancers. And as shown here, its gene expression is higher in tumors relative to normal tissues across virtually every type of cancer included in the analysis here. So we think there could be a large opportunity to ultimately treat many different types of cancer with the potential for broad applicability similar to checkpoint inhibitors. I would note as well the low expression of dectin-2 in most normal tissues, as shown in the blue, which again could help to explain the encouraging safety profile that we're seeing with 3042 in the clinic.
Moving to Slide 12. Now looking at dectin-2 expression at the cellular level, we find the highest expression on macrophages within tumors with little to no expression on non-myeloid cells or even on most other myeloid cell populations. On the left, we're showing that dectin-2 is expressed on macrophages in various types of human tumor samples, including cases of breast cancer, colorectal cancer, lung cancer and ovarian pancreatic cancer. On the right, we see a similar expression profile in the syngeneic mouse models that we use in our preclinical studies, including in this model of bladder cancer as shown here.
Moving to Slide 13. We developed an IHC assay for dectin-2, so we could conduct a broader survey of its expression across human cancers. We also analyzed over 600 samples using both tissue microarrays and whole tissue sections from 7 different tumor types. Notably, we detected dectin-2 expression in every whole tissue section that we examined. We also confirmed through this effort that non-small cell lung cancer looks like a promising indication on the basis of depth and expression with 40% to 50% of cases showing 1% or more total tumor area staying positive for dectin-2.
Slide 14. We pursued the development of BDC-3042 in part due to compelling preclinical results like those shown here. Note that 3042 does not cross-check with mouse dectin-2. So we're using here a natural ligand of the receptor, a fungal extract known as Mannan as a surrogate agonist for these studies. As you can see, systemic administration of the agonist shown in the blue curves, elicits tumor regression in these two syngeneic tumor models, including a model of bladder cancer, as shown on the left as well as the model of pancreatic cancer as shown on the right. And very importantly, the therapeutic effects of the agonist were blocked when mice were pretreated with the dectin-2 blocking antibody, confirming that engagement in dectin-2 is driving the antitumor activity that we see here.
Moving to Slide 15. One of the main goals of 3042 and the dectin-2 agonist therapy more generally is to reprogram antigen-presenting cells like TAMs into cells that enhance and support T cell responses, which, of course, are critical for deep and durable antitumor immune responses. As shown on the left, we do find, in fact, that if we deplete CD8 T cells, as shown in the red curve, the surrogate agonist loses efficacy, confirming that in the induction of cytotoxic T cell responses is a major mechanism of action.
And importantly, we shown on the right that mice that experienced complete tumor regression following dectin-2 agonist therapy would reject those same tumors upon being rechallenged, indicating the induction of a strong adaptive immune response of immune memory against that tumor cell line, but not to an unrelated tumor cell line that the mouse had not been exposed to before, even in this case, the MC38 tumor cell line.
Now to Slide 16. Moving on to some key preclinical work with BDC-3042. We performed numerous studies evaluating the binding of the antibody to cells in human tumor samples in the cases shown here to colorectal cancer, non-small cell lung cancer and ovarian cancer samples and found as expected, that 3042 preferentially down to macrophages within those samples. And as shown on the right, we also looked at the ability of the antibody to activate the macrophages within those samples in ex vivo functional assays, and found that 3042 is able to elicit robust cytokine responses with some of the strongest responses that we noted in the lung cancer samples.
Slide 17. And finally, and again, because 3042 does not cross check with the mouse protein, we have to use mice with humanized immune systems to study 3042 in vivo. These models, of course, come with significant limitations, including a lot of donor variability. But as shown in the example on the left, 3042 inhibited tumor growth relative to active control antibody as well as to the PD-1 antibody pembrolizumab. And while pembrolizumab has demonstrated efficacy in this model in other published studies, as we show in the middle panel, we observed greater tumor growth inhibition with 3042 relative to pembrolizumab across 9 different cohorts of humanized mice generated using the distinct donors.
And finally, on the right, similar to what we've seen with the surrogate agonist in syngeneic models, 3042 modulated the tumor immune compartment in these mice in various ways, causing an increase in overall immune cell infiltration, a favorable shift towards CD8 T cells and changes in activation markers on TAMs that indicate a reprogramming toward a more immunosimulatory phenotype.
And so with that background on BDC-3042, I now turn the call over to Dr. Cathy Dumbrava, investigator for the BDC-3042 clinical trial and Associate Professor of Investigational Cancer Therapeutics at MD Anderson. Dr. Dumbrava?
Thank you so much, Justin, for the great introduction. It was an honor to present the preliminary results of this Phase I clinical trial with BDC-3042 at the AACR meeting earlier this year, just a few weeks ago. And just a quick reminder is that, as Justin said, this is a Phase I of first-in-human study evaluating the BDC-3042. And this is a first in class and it was tested in patients with metastatic solid tumors.
And here, you can see on Slide 19, you can see the dose escalation across 7 dose levels. In the first 3 years that had an accelerated titration with just 1 subject per cohort. And after that was following a BOIN or Bayesian Optimal Interval design. And a total of 17 patients were enrolled, including 2 patients with non-small cell lung cancer who are still continue to be on treatment.
If you go to the next slide, on Slide 20, you will see the demographics. And what I would really want to highlight is that these patients were heavily pretreated. You can see that the median patients had 4 prior lines of treatment and some of them had even 8 lines of prior treatment, 41% is the prior immune therapy. And you can see that almost half of patients enrolled were patients with colorectal cancer who were MS stable. And we had 3 patients with non-small cell lung cancer, including the 2 in cohort 7 that -- for which the treatment is still ongoing.
On Slide 21, you can see a quick summary of the safety, and what I can share is that this was very well tolerated. We have not seen Grade 4 or 5 drug-related AEs, we have not seen drug-related SAEs. And in fact, we have not identified any dose-limiting toxicities up to 10 milligrams per kilogram every 2 weeks. One patient had a drug-related infusion reaction that was well managed and did not reoccur. And we have no drug-related treatment discontinuation. For running Phase I trial, this is so important, safety, making sure that for our patients, especially that for this Phase I trial, the primary objective was to evaluate the safety and tolerability of the BDC-3042.
If you go to the next slide on Slide 22, you can see the treatment-related AEs that we only had two that were higher than Grade 3, and all of them were Grade 1 or 2 and this was very, very well tolerated. And the Grade 3 was increase in amylase and lipase and patients who had muscle weakness.
On the next slide, you can see a beautiful translational data. We can see that by increasing the dose, we can see increase in the cytokines. And these are cytokine that are pro-inflammatory and also chemokines that really support even more the further development and combinations.
And on the next slide, you can see that the BDC has a very similar profile that what we see in preclinical model. It is so beautiful to see the preclinical and mirrored after that in humans really seeing -- and really proving our hypotheses.
And on the next slide, on Slide 25, you can see that this has a typical PK characteristics of an antibody with a half-life that is about 20 days. And we have not observed any ADAs to date in any of the patients.
And the most exciting slide is, on Slide 26, is that you can see that the waterfall plot in patients with -- especially with lung cancer, the 3 patients that they are here in green, all of them had some reduction in the tumor size. These are patients with lung cancer who had 4 prior lines of treatment or more, and they still respond to this. And you can also see that 4 out of the 5 patients who had prior anti-PD-1 or PD-L1 inhibitors, they still have reduction in the tumor size.
And if you look carefully at this waterfall plot, you can see that most patients they have -- they are in the range of stable disease. However, for the patients who achieved the partial response, the patient with the non-small cell lung cancer, that is still ongoing at 18 weeks, and I will give you a little bit more update in the following slides.
If you go to Slide 27, you can see the duration of response. And even if some patients did not achieve a PR, being stable is very meaningful for patients. And you can see that, for example, the first patient was on treatment for 18 weeks. That is really significant for patients for colorectal cancer. And you can see that all the non-small cell lung cancer patients had more than 2 prior lines of treatment.
And on Slide 28, in the patient who had a partial response. And you can see her history. She had a very aggressive non-small cell lung cancer, a lung adenocarcinoma with a KRAS mutation and also with PD-L1 50%. She had from the beginning, brain metastasis and the right adrenal gland metastasis. And she has chemotherapy and immunotherapy. She has radiation in November 2023. And after that she started the second-line treatment with another chemotherapy and immunotherapy. She had another retroperitoneal radiation because there was a significant tumor growth in that area. She started on a targeted therapy for KRAS and had progression in the brain and received radiation.
And in November 2024, she will be involved in this study. I do want to mention that the adrenal gland lesion was growing even if it was in an area that was previously radiated, it was growing. And she had a Grade 1 infusion reaction and the Grade 1 increase amylase, but all those are really manageable. And she had in February, at restaging, she had on the brain MRI, there was a questionable lesion that was still considered determinate, but the consensus was to go ahead and treat. And so that's why she had the brain radiation without really developing new brain metastasis. It was more a discussion between her and the radiation oncologists as she was just telling us that she cannot live with the idea that she has something in the brain that is not treated.
And -- but it was not really progression in the brain. And now we have -- when we presented this, it was an unconfirmed partial response. And I can share that we now since the presentation at AACR, we have the confirmation of the partial response and the patient is doing a fabulous, she's telling me that she is able to live and that she feels normal. She has no side effects. And that's what we really want to hear from our patients is that we develop better treatment that help with their survival, but also that we give them a good quality of life.
And so the next slide is really a summary of everything that I have mentioned is that, this is a well-tolerated drug up to 10 milligrams per kilogram every 2 weeks. We are seeing an early clinical support for the mechanism of action. It has a favorable PK profile. And I truly believe that this is showing the promising signs of efficacy in non-small cell lung cancer, especially in anti-PD-1 refractory setting. And so both our patients with non-small lung cancer, they are still continue treatment.
And with that, I will hand it over to Grant to be able to further discuss about partnering.
Thank you very much, Dr. Dumbrava. I appreciate that.
And if you go to Slide 31, I just wanted to briefly mention Bolt's effort to find a partner to rapidly develop and optimize the commercialization of 3042. We initiated this process with our disclosure at AACR on April 25, and we have multiple parties in both confidential and non-confidential discussions. Our goal is to get a nonbinding term sheet by June 6, so in a fairly rapid time frame. And any interested party should feel free to contact me for this effort, and we look forward to parties' interests.
With that, it's my pleasure to introduce Bolt's Senior Clinical Adviser, Dr. Jakob Dupont, Dr. Dupont has deep experience in developing oncology therapeutics, and he's an executive partner at Sofinnova Investments and on our Board. So turning it over to Jakob here.
Thanks, Grant. It's great to be with you all today. And now I have the great pleasure of speaking to you about BDC-4182, which is Bolt's next important drug in the pipeline.
So if we turn to Slide 33. You can see here a representation of BDC-4182. It is a first-in-class claudin 18.2 Boltbody ISAC program. It's next generation. So we're very excited to bring this into the clinic. And as Willie mentioned, the trial is now open on Australia. So really looking forward to bringing patients on to that trial.
As you know, claudin 18.2 is a clinically validated target, and this is really illustrated by the approval of zola -- zolbetuximab for gastric cancer. And that particular antibody, naked antibody does target the very highest expressers of claudin 18.2 gastric cancer. So that really provides validation for the target.
But with Bolt's BDC-4182, we think there's -- with a unique mechanism of action there is potential to bring better options for patients, not only as monotherapy but also in combination with other therapies as well. So the opportunity we see here is to expand the market and to improve the outcomes for patients.
Now over the next few slides we're going to be speaking to you about the profile of BDC-4182 where we believe we've created a best-in-class profile for this drug and the target product profile to expand the market beyond tumors that are merely -- that are just the high expressers. So we want to capture the moderate and the lower expressers as well. We want to have a profile of a drug that outperforms some of the ADCs that are in clinical development now. And we believe we have some pretty interesting mechanistic studies about the unique characteristics of this particular therapeutic candidate.
And so over the course of this year and the next few months, we think there's some key inflection points for this program. On the one hand, we do anticipate the initiation of enrollment of the clinical trial and then also some early clinical data as soon as the early part of next year.
So if we go to Slide #34, we'll jump in now to some of the preclinical data that the research team here at Bolt was able to create and really careful efforts here. But as described, we really wanted to make a therapeutic candidate that has the potential to be superior to antibody drug conjugates, specifically ones that had an MMAE payload or TOPO1 payload. And so in this particular set of experiments on Slide 34, the MC38 colorectal cancer cell line was modified to express low levels of claudin 18.2. And you can see here in the experiment on the left, the Bolt ISAC outperformed the claudin 18 (sic) [ claudin 18.2 ] MMAE ADC, especially in that low expressing population. At higher expression levels, the ADC and the ISAC performed at similar levels. On the right-hand side, you can see once again that the ISAC against claudin 18.2 outperformed TOPO1 ADC in that low expressing tumor model.
So if we move to Slide #35, another piece of preclinical data here that really set the IND filing up and really made us feel like we had target product profile that brought something unique potential to patients. Here, we're looking at the induction of immunological memory and epitope spreading in our preclinical experiments. So here, on the left, you see a similar type of experiment as you saw in the previous slide, where moderate doses of the claudin 18.2 ISAC really led to tumor regressions. And these mice were actually tumor-free. And so what was done here is the patient or the mice were allowed to remain treatment-free for 26 days to assure that they were cured, and then they were rechallenged and those are the panels on the right-hand side.
So on the upper panel, you could see rechallenging with the MC38 tumor expressing low levels of claudin 18.2, there was no ability for the tumor to regrow, especially when the T cells were present as opposed to or T cell depletion occurred, where, again, there was regrowth of the tumor. So this really speaks to immunological memory that's induced by the claudin 18.2 ISAC. Interestingly, in the lower right-hand panel, here the cured mice were rechallenged with MC38 tumors that did not express claudin 18.2. And here, again, the T cell memory was able to keep those mice in a cured state, speaking to epitope spreading here, which we think is quite important to the mechanism of action.
So if we move to Slide #36. This is the clinical trial -- the BDC-4182 clinical trial, and as I mentioned, this is open to enrollment. So this is open in Australia, and it's enrolling patients with claudin 18.2 expressing tumors. So that is advanced gastric and gastroesophageal tumors as well. So we expect that we'll be within the therapeutic range when we get up towards cohort #3. And again, we look to forward to providing you with clinical updates towards the beginning of next year.
So it's now my pleasure to hand back to Bolt CEO, Willie Quinn, for a few concluding thoughts. Willie?
Thank you, Jakob, and thank you all again for joining our call today.
I'll start on Slide 38 with a review of our pipeline. We are pleased by the promising Phase I data for BDC-3042, including its favorable safety profile dose-dependent biologic activity and monotherapy antitumor activity. We believe this program is best suited for partnering, and we look forward to working with a collaborator who can help accelerate its development and bring this promising treatment to patients.
We've made great progress with our claudin 18.2 ISAC BDC-4182 opening the trial for enrollment in April. We continue to be on track to treat our first patient this quarter and look forward to updating the investor community on our progress.
At AACR, we also presented posters on our two proprietary ISAC programs targeting CEA and PD-L1. After a period of relative neglect for the ISAC mechanism, it was gratifying to see strong interest in our posters and to note that Pfizer also presented a poster on a PD-L1 ISAC program at AACR.
Finally, I'll once again mention our collaboration programs and note that we're now working with Genmab to advance two development programs, and also have additional R&D programs in development. The Genmab ISAC programs and the Toray Caprin-1 ISAC program are all paid for by our collaboration partners through early clinical proof of concept, providing a cost-efficient way for us to continue to develop our pipeline and platform.
I'll move to Slide 39 for some final thoughts. Our team at Bolt looks forward to updating you on our progress on our preclinical and clinical programs. For BDC-4182, we expect to have some near-term updates on recruitment as we start treating patients. For BDC-3042, the next big milestone for the program will be partner selection which we expect by the fall. In today's biotech financing environment, our watchword continues to be efficiency as we work to efficiently develop product candidates that could improve lives and eradicate cancer.
With that, I thank you all for joining us today. We will now open the call for Q&A. In addition to those who spoke on our call today, we're also joined by additional Bolt Bio team members and we can introduce them as we go. We look forward to your questions. Operator?
[Operator Instructions] Our first question comes from Daina Graybosch with Leerink Partners.
Maybe two for me. One, I wonder if you can talk about the dose escalation of the dectin-2 agonist. And I realize you're done escalating. And I wonder if you think you've maximized out this dose or whether with a partner, you think that further dose exploration, I mean this is for Dr. Dumbrava is warranted given the chemokines, cytokine safety and efficacy you've seen thus far? And then I'll ask another one after the answer here.
Great. Dr. Dumbrava, do you want to go ahead and tackle that one for us?
Sure. Thank you so much for that question. Of course, I want to explore this in more patients. And I will start by answering that dectin-2 expression was available in all available patients tumor biopsies. And when we looked at large data sets, we also -- we have seen that mRNA expression of dectin-2 was present in nearly all solid tumors. And so I will answer your questions in two parts, saying that, one is that we do believe that this could be investigated in order tumor types than non-small cell lung cancer. And also if we do a partner, then or possibly with a run-in design that we would look at different schedules. And given that the BDC-3042 has a 20-day half-life in this trial in the dose escalation, it does potentially allow for a less frequent dosing that in this way for a partner that, for example, has schedule of every 3 weeks, I think that would be possible as well. And so yes, to answer your question.
And then my second question is, I hear you that it has potential potentially across solid tumors, but the signal is strong in lung cancer. And I wonder, Justin, if you can tell us maybe why? Do you have any hypothesis for why the TAMs are expressing it higher herein lung and what they could tell us about the potential for this mechanism to be more effective, I guess, than we've seen with prior TAM-targeted therapies ultimately in clinic.
Daina, thanks. I think one key thing is, as we noted, that the lung patients all had seen prior anti-PD-1 therapy within 12 months. So they may have been particularly well primed for a dectin-2 agonist because they may been shown further upregulation dectin-2 expression on the macrophages and those tumors. I think another key thing is that especially as we were seeking single-agent efficacy signals, lung obviously, is a bit more of an immunogenic tumor. There probably is some better pre-existing T cell response in those tumors that we were able to further enhance with our antibody. And so I think those are two key features, I think, we hope, obviously, to be able to see similar things in other tumor types, maybe in particular in combination with checkpoint inhibitors or other therapies. But I think those are maybe part of the reason for the stronger signal in lung cancer in this case.
And maybe Dr. Dumbrava, if you have anything to add, I know the clinical perspective could be really helpful here, too.
Yes. No, I agree with you. And just as a reminder, these patients were refractory. My patients had two different rounds of chemo and immunotherapy and she progressed on all that. And so to see a response after that to any treatment is so exciting from the clinical standpoint. And so I think exploring that with a combination would even deepen these responses.
Our next question comes from Stephen Willey with Stifel.
Maybe one for Dr. Dumbrava. I appreciate the additional information regarding the post AACR confirmation of the partial response that we've seen. I was wondering if you could also maybe provide an update of the second 10 mg per kg lung cancer patient who had stable disease and was still on therapy. I think as week 15 or so. Is that patient still on drug?
I believe that, that patient is still on treatment. Now we'll have some the data that we presented at AACR, both of these patients were on treatment. And I am just so excited for my patient that I disclosed that if we had a confirmed partial response, that it's something that, again, as I mentioned previously, her heavily pretreated and complicated history and to see a prolonged response with such a good quality of life is something that I was very pleasantly surprised and to see this -- the preclinical data really the hypothesis proven in patients. I don't know the answer for the other patients, but I believe that at the time when we presented, which was just 2 weeks ago, she was on treatment.
Okay. And then maybe for the company on 4182, can you just maybe talk a little bit about how you're gating enrollment with respect to claudin expression within the dose escalation portion of the study? Do you have any guardrails or I guess, any eligibility criteria that's established? And do you hope to, whether it's prospectively or retrospectively be able to recapitulate some of that activity in lower claudin 18.2 expressing tumors relative to what we've seen with the naked antibodies?
Yes, it's a great question, Steve. I'm going to ask Dr. Dupont to take that one as we think about balancing the probability of success and the expansion of the market.
Yes Absolutely. So the study is open, as we discussed, we're going into gastric and gastroesophageal cancer where, again, that's where you find high prevalence of claudin 18.2 expression in those tumor types. Obviously, there are other tumors that also have claudin 18.2 expression, but we've really gone to where the money is, so to speak.
And there, obviously, the approved drug is just going after that, the very highest expressers we are asking for expression of claudin 18.2, but it's not excluded to just the very highest expressers. And we're also doing backfill patients on the various cohorts to get a more robust clinical experience there. But the intent of the protocol is definitely to enroll patients with claudin 18.2 expression. And then there will also be capture of tumor tissue from patients on the study so that we can do further analysis and do our own confirmation of level of expression and so forth. But I do think we see the opportunity certainly is to broaden the market in patients that have varying levels of claudin 18.2 expression.
[Operator Instructions] Our next question comes from Chad Messer with Lake Street.
Great. I really appreciate the update on the call. Just on 3042, super exciting results in lung. I know my colleagues have already asked why you think lung might have sort of popped to the top of the list. But can you remind us like you guys had specific tumor types that you were looking at, TNBC, RCC, CRC, melanoma, was that based on dectin expression and dectin expression on the tumor cells or in the macrophage? Can you just remind us why you are interested in that subset to begin?
Yes, Chad, it's a great question. I'm going to hand this over to Justin to take us back at kind of decision heading into the IND and structuring the trial?
So I'd say a large part of it was due to the dectin-2 expression as far as we could glean at the time. Obviously, we eventually developed an IC assay for dectin, but prior to that, we're mainly relying on gene expression data that was out there publicly available. And those tumor types you listed did generally show some good expression with one being the highest expresser generally of the tumor types that we looked at. We note as well that there was some expressions in some of the tumor types, I would say, triple-negative breast cancer, in particular, looked like an attractive one based on some kind of subtype analysis that we have been doing as well.
I'd say, in our earliest studies on dectin-2. We were looking at various tumor types as well in our mousing models, looking at some additional types like blader cancer and pancreatic cancer, ultimately made a decision to focus on the ones that we did because of the potential large markets for those tumor types as well as some of the initial considerations as far as it relates to immunogenicity of the tumor and the like. So again, expression was the main factor, but there were other considerations as well in terms of the market opportunity as well as just kind of what's known about immunogenicity of the certain tumor types like lung cancer and melanoma.
One additional comment on the non-small cell lung cancer. We also note that 2 of those 3 were at the 10 mg per kg. And those were the only ones we had at 10 mg per kg. So we also think we're getting to a dose as you can see by some of the peripheral biomarkers that might have influenced more in those patients, too.
All right. Yes, I appreciate that color. And then maybe just one on 4182, the claudin. So you've got an approved drug out there that's -- it's indicated for, call it, I think it's 38% or something of the gastric cancer market out there. How low do you guys think you may be able to get -- what I really want to get a handle on is how much of the market do you think you can get based on what you know now? Obviously, we'll learn more over time. Are we talking 75%, 80%, 90%? How much past that 38% do you think that you can address with your ability to go after lower claudin expression?
Maybe I'll start with that one, and then I'll hand it off to the rest of the team if they want to add color. But I think you're laying it out really well, Chad. The approved label for at least 75% expression, IHC2+ is about 38% of the market. And ultimately, we are hoping we can capture all of the expressing patients. But I think as you consider development pathway, you don't want to go for everything and swing for the fence from the very, very beginning. So we want to make sure we characterize the drug appropriately, emphasize well it does in higher expressing patients and then explore how low we can go. So I think that's what we're going to see in our trial is a mix of different expression levels, and we will learn how it does. Certainly, preclinically, we were able to go quite low, IHC1+ and outperform all of the ADCs we compared against, including MMAE and TOPO1.
So anything to add on the...
Yes. This is Jakob Dupont. And just I think what Willie said is correct. It was -- the preclinical data did capture those IHC1+, and those are the experiments that we went through earlier in the slides. And I do think that we will get more information on the expression level. And in the clinical patients. But again, the target product profile that the research team was really going after here was to really go down on the level of expression and try to help more patients that had a broader range of expression. And I do think about the example of Enhertu, where they were able to capture the moderate, the low and the ultra-low patients. And a lot of it just has to do with how good is the technology. And we do think that this has a very robust efficacy profile at least preclinically, which is why we're excited to test it in the clinic.
And of course, we're going to -- this is Grant. We also are aware of what cutoffs other competitors have been using. And so we will consider that as we think about how to differentiate our drug relative to competitors, whether that's efficacy in the same level of expression or efficacy at lower levels of expression.
All right. Well, it will be exciting to hear how you go after that as you get into the clinic and looking forward to seeing how low you guys can go.
Our next question comes from Daina Graybosch with Leerink Partners.
I have two more. Dr. Dumbrava, I wonder if you could characterize your patient with the adrenal lesion that has a confirmed partial response. Can you help us understand how big that lesion was? And relative maybe to some of the stable diseases that you've seen some shrinkage, have you seen any shrinkage in large lesions?
And then on the claudin 18.2 ISAC, can you remind us why this ISAC is different from the first-generation Bolthead -- Boltbody with HER2? And also more broadly, the other HER2 ISACs out there that either failed for lack of maybe strong efficacy, but also for a lot of toxicity. Why should we be expected that this was going to work when the others multiple companies did not targeting HER2?
We'll let Dr. Dumbrava answer that question about her patient, and then we can jump in here with the team to answer the question about next-gen ISAC.
Thank you for that question. And that is true that for certain treatment, the size of the tumor is important. She -- the target lesion is about 2 centimeters. So it is a real reduction of partial response in a lesion that was growing after in an area where she had radiation. So very, very aggressive.
Great. And on the next-gen question, I think it's a really good one. I'm going to ask Grant to talk that question because in our partner discussions, he's routinely asked that exact question.
Yes. So we improved it across the board. And we looked for antibodies that work better with our mechanism of action. So certainly driving ADCP as the first stage step in our mechanism of action was important. So we tested a variety of antibodies, instead of just taking trastuzumab to demonstrate that on the antibody front. We did look at various different bioconjugation methods and found some that we felt worked better. And so we used a more optimal bioconjugation method for this.
And then our linker payload was more active and more potent. And certainly, we've been working on this since our 1001 days, and we've been working on this with Genmab, certainly to get better linker payloads. And so we are using these next-generation linker payloads that are different than the competition. So when you look at Novartis, they certainly had a lot of immunogenicity with their linker payload. We haven't seen that with ours, and we have various methods that we use to minimize the risk of immunogenicity and assess that as best we can preclinically. And we have had linker payloads that we have deprioritized because of concerns about immunogenicity.
And then when you look at safety, we also have managed to increase the activity of our ISACs while maintaining an attractive safety profile as demonstrated by our non-GLP and GLP tox studies with those that look better than ADCs in terms of toxicity that we've seen in those studies. And that is something that we have been thoughtful about and actually found ways where we could increase activity on fronts that we think drive efficacy without increasing activity on assays that we think might be safety related.
And so we combine all that in what we've referred to as our next-gen ISAC platform. And hopefully, that addresses that question sufficiently full.
Can you just -- maybe the very last point you made, can you clarify that a little bit more? So it sounds like you were screening and you had some assays that predicted what you thought were potency in humans and assays that you thought predicted toxicity in humans in the past ISACs, let's say, if you screening...
We have historically had a lot of assays to evaluate and select ISACs as well as linker payloads that are precursors to our ISACs on down the road. We have screened over 1,000 different linker payloads and generated probably many more than that in terms of certain chemistry to evaluate. And we've come up with a number of novel structures that we have intellectual property filed on that we think are favorable. And it's not just obvious that it's more TLR7 or more TLR8 or something like that, that I think a lot of people look at.
So that is correct. We do have screening that we use in getting to next-gen ISAC payloads.
I'm showing no further questions at this time. I would now like to turn it back to Willie Quinn for closing remarks.
Thank you again for joining us today and for the good questions and engagement. We continue to believe in the long-term potential of our product candidates to improve lives of patients with cancer, and we look forward to continuing to keep you updated on our progress. Goodbye.
This concludes today's conference call. Thank you for participating. You may now disconnect.
