I-Mab at H.C. Wainwright: Strategic Shift Towards U.S. Operations

On Tuesday, 17 June 2025, I-Mab (NASDAQ:IMAB) participated in the H.C. Wainwright “HCW@Home” series, outlining a strategic pivot towards U.S. operations. The company highlighted its focus on a capital-efficient model while addressing both the potential and challenges of its lead candidate, givastomig, for gastric cancer treatment.

Key Takeaways

• I-Mab is focusing on its Claudin 18.2 targeting bispecific antibody, givastomig, for treating gastric cancer.
• The company is shifting its operations to the U.S., emphasizing a lean business model with 25 employees.
• A mini-oral presentation at ESMO GI on July 2nd will reveal Phase 1 study data on givastomig.
• The addressable market for Claudin 18.2-positive gastric cancer is estimated at $12 billion across the U.S., EU, and Japan.
• I-Mab has $168 million in cash, expected to fund clinical developments over the next 6-12 months.

Financial Results

• Cash Position: I-Mab reported $168 million on its balance sheet at the end of Q1, providing a financial runway for upcoming clinical readouts.
• Addressable Market: The company sees a $12 billion opportunity in the U.S., EU, and Japan for Claudin 18.2-positive gastric cancer treatments.

Operational Updates

• Company Transformation: I-Mab has divested its Chinese assets to concentrate on U.S. operations, operating with a streamlined team of 25 employees.
• Clinical Pipeline: The focus remains on givastomig, with a "bolt-on" strategy to complement existing treatments without altering them.
• Upcoming Presentation: I-Mab is set to present data from a Phase 1 study at ESMO GI, evaluating givastomig in combination with nivolumab and chemotherapy.

Future Outlook

• Clinical Development Strategy: The primary focus is on givastomig for frontline metastatic gastric cancer, with potential expansion into other gastrointestinal malignancies.
• Combination Strategies: Exploring combinations of givastomig with novel agents in HER2-positive gastric cancer is under consideration.
• Data Readouts: Anticipation of significant data readouts within the next 6-12 months, aligning with Project OPTIMAT guidelines.

Q&A Highlights

• Claudin 18.2 Biology: Claudin 18.2 is selectively expressed in tumors, making it a target for therapeutic interventions.
• Mechanism of Action: Givastomig's design aims to mitigate adverse effects seen with previous 4-1BB agonists.
• Differentiation: Givastomig targets a broad range of Claudin 18.2-positive patients and boasts a favorable safety profile.

In conclusion, I-Mab’s strategic focus on the U.S. market and its innovative approach to cancer treatment are set to capture significant market opportunities. For a detailed understanding, refer to the full transcript below.

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Full transcript - H.C. Wainwright “HCW@Home” series:

Andres Malvinato, Senior Health Care Analyst, HC Wainwright: Great. We'll get started now. I'd like to welcome everybody to HCW's at home series. Today, we're hosting EyeMed Biopharma. My name is Andres Malvinato.

I'm a senior health care analyst here at HC Wainwright, and it's my pleasure to host, you today. And it's my pleasure to introduce, IMAD Biopharma's chief executive officer, Sean Fu, and IMAD's chief medical officer, Philip Dennis. So the crux of our fireside chat will be to give you an overview of the Claudine 18.2 landscape in order to provide proper context ahead of the company's mini oral presentation that is expected at s at ESMO GI and scheduled for July 2. So I'd like to take the time now to welcome Sean and Philip. Thank you for joining us today.

Sean Fu, Chief Executive Officer, IMAD Biopharma: Thank you, Andres.

Philip Dennis, Chief Medical Officer, IMAD Biopharma: It's a pleasure to be here.

Andres Malvinato, Senior Health Care Analyst, HC Wainwright: Great. So I guess, you know, to kick things off for those who are getting up to speed on the I Mab name, you know, could you begin with a brief overview of the company's vision and the current clinical pipeline?

Sean Fu, Chief Executive Officer, IMAD Biopharma: Absolutely, Andre. Thanks for the invitation. We're very happy to have the opportunity to join the HCW fireside here. I Mab is a a company that went through significant transformations. So you can think of it as a new company, if you will.

Last year, we went through a divestiture. So we split it out to assets and operations and teams in China and really focus on The US side of operations. As a result, we have a new business model, which I believe is capital focused, capital efficient compared to the old model. And we have 25 full time employees, all of them in US. So you can see that we are much smaller company, which means we're much more focused.

Focused on what? Our clinical pipelines. We have three clinical stage assets. And the one that we're gonna be talking about spend most of the time today is the Clouding 18.241 b b bispecific. And we're very excited about these assets.

As Andres mentioned earlier, this asset is subject to a mini oral presentation at ESMO GI on July 2. And what about this asset? This isn't an asset that we are actively developing as a bolt on to the standard of care in frontline gastric cancer, which is IO chemo. And our strategy is unique compared to other competitors is that we are adding Giva to the standard of care without changing anything of the standard of care itself. And in the monotherapy studies, it's clear that Giva, which is the bispecific antibody, Giva is an active agent.

We have eighteen percent monotherapy heavily treated population ORR. And the safety was very well tolerated. We liked it a lot. Then we bring into combination. And this is the study data that we're going to share at ESMO GI.

In this study we looked at the 17 patient over three doses when we add Giva to the undulterated nivo chemo standard of care. And the ORR looks very, very exciting and the safety continued to look promising. We do not see any additional tox beyond and above small numbers, but above and beyond nivo chemo background. So this is a really exciting data. I also wanted to say that why are we focused on gastric cancer frontline?

This is still a very devastating diseases. The when someone is diagnosed unfortunately with a metastatic gastric cancer, the five year survival rate is only seven percent. So this is significant unmet medical needs where we believe Jeeva can add to the overall arsenal of the treatment options for patients around the globe. And because of the unmet medical needs and the relatively large population, this gastric cancer ranked number five in terms of frequency and number four in terms of the mortality. So this actually translates to significant commercial opportunities.

So we're talking about the frontline clouding positive patients represent 12,000,000,000 addressable markets just in US, EU, and Japan. That's where we have rights. Right? So I think this is a significant unmet medical needs, very exciting assets, promising data, and we are full steam pushing forward with the clinical studies. Now before I hand it over to Philip to talk about the data, let me just also say that I Mab is in a strong position when it comes to finance.

We have a $168,000,000 on balance sheet as end of the as of end of the first quarter, which means we are positioned to see through some of the important financial clinical readouts in the next six to twelve months. So with that, I would turn it over to Philip, and let's dive into the data.

Andres Malvinato, Senior Health Care Analyst, HC Wainwright: Great. So I guess the first question I have, very interesting bispecific, Jeeva, is and I wanna start with on the basic biology of the targeting of claudin 18.2 before we start incorporating the other arm, the four one b b. So maybe to start with, you know, how does clotting exposure, you know, enable you to target selective tumor types? Would be great to talk about its expression levels, its overall importance in, you know, tumorigenesis, and any implications given, you know, where, the cells that express 18.2, are, you know, given they're in the tight rich junction of the epithelial cells. Any high level thoughts there to kick off, or kind of encapsulating the biology of GLODIN eighteen point two?

Oh, Philip, I think you're muted.

Philip Dennis, Chief Medical Officer, IMAD Biopharma: About that. Thanks, Andreas. The 18.2 is a very good example of precision oncology. What do I mean by that? It alludes to what you just mentioned, which is we're looking for ways to maximize the therapeutic index to target cancer cells and not harm normal cells that lead to toxicities that patients experience.

Clon 18.2 is a component of tight junctions between gastric epithelial cells, and it's really GI epithelial cells. What happens with the transformation of a gastric epithelial cell is that the polarity is lost. The polarity that normally means that the blood 18.2 is tethered very tightly into junctions literally mean that that liquid can't get through. It is a tight junction impermeable to really anything other than ions, but even water is too big. So the idea here is that with transformation, the polarity is lost.

The Claude 18.2 is expressed on the cell surface where it can be identified by antibody based approaches such as bispecifics, ADCs, anything that uses an antibody to target claudin 18.2. Now even though and because it's selectively expressed in tumor versus normal, again, in normal, it's hidden. So if you look at cell membranous staining of 18 point two, you don't find it in normal cells. But there are a couple interesting features. In spite of the fact that it is selective for tumor versus normal, it's not an oncogenic driver.

It doesn't create it doesn't change the biology of the tumor cells. It's simply a homing address for the therapeutics that we develop. I will also say we're referring and we're focused on frontline gastric cancer, but the expression of clotting eighteen point two is very high in other GI malignancies as well, such as pancreatic adenocarcinoma and biliary tract cancer, where the majority of those tumor types also have high levels of clotting expression. So it's a feature of GI malignancies, the polarities lost with transformation, allowing clotting directed assets and medicines to get to the tumor.

Andres Malvinato, Senior Health Care Analyst, HC Wainwright: Great. No. Very helpful. So, you know, on one side of, we have the, Claudine 18.2 arm. And on the other side, oncology investors are very familiar with the four one b b, arm, you know, after a host of other utilizations of that target.

So I I guess the question becomes, you know, how does the conditional activation of four one b b via tumor localized spot in 18.2 binding, you know, really overcome the limitations that we've seen previously with four one b b agonists and particularly in avoiding those off off tumor, you know, hepatotoxicity that the class has previously seen.

Philip Dennis, Chief Medical Officer, IMAD Biopharma: Yeah. This is a really Jeeva's differentiated structurally in terms of its mechanism of action. The first word I'm gonna g I'm going to use is conditional activation of four one b being conditional activation of T cells. That's through the binding to clot 18.2. The binding to 18.2 is highly added.

The KD log lower for Giva than it is for zolvetuximab. It's very ab binding. But what's also critical is the Fc effector function is eliminated be through a mutation that we introduced. This allows two important things to, not happen, to eliminate. One is the induction of, processes such as antibody dependent cellular toxicity, and CDC as well that have been associated with the toxicity of other assets by due to the fact that ADCC and CDC are directed against normal gastric mucosal cells.

So the first thing is we lose VCC and CDC, which is a good thing because it's associated with toxicity. The second thing is that because we lose that Fc receptor function, we can no longer get imprecise clustering of four one b via the Fc receptor. So, basically, what we end up with is a precise targeting of 18.2 without getting ACC or CDC, and we activate T cells in the microenvironment only through four one b b. And this is that we've shown this preclinically in our preclinical data. We show in circulation that Giva by itself, if Giva encounters a T cell in circulation, it does not activate four one b because the Fc moiety again is is silenced, and there's no clustering of four one b.

So the clustering of four one b b, the activation of T cells, only occurs in the tumor microenvironment. And you can say, well, you know, this is a scientific hypothesis. It's mouse data, blah blah blah. But I think that our clinical data, the toxicity profile of Giva as monotherapy, which showed single digit grade three and above nausea and vomiting, which showed minimal hepatic toxicity, says to us that Giva, in fact, is acting in patients the way we showed in animals and the way we think it should act. This is all being borne out in our combination study that will be presented in just a few days at SGI.

Andres Malvinato, Senior Health Care Analyst, HC Wainwright: Very helpful. So you did touch upon, a little bit this next question, but I kinda wanna drill down, to really bring some clarity here. So, you know, with the role of the costimulation of four one b b, you know, in terms of T cell exhaustion and memory differentiation, you were just touching upon, you know, how does this differ? How should we be thinking about this signaling differences when it comes to Claudine eighteen point two low expressers versus 18.2 high expressers? Does it expand the the utilization of of of Jiva there?

Philip Dennis, Chief Medical Officer, IMAD Biopharma: Yeah. So, without a doubt. So our our monotherapy phase one data that's been presented previously shows that we have responders with claudin 18.2 expression as low as eleven percent of tumor cells being positive. So we can extend the range of expression very low, and you will also see in the ESMO GI presentation patients with very low levels of Claude lower than eleven percent also responding to the combination of Giva plus nivolumab plus chemotherapy. The the the conditional the conditional activation, in terms of, like, T cell subsets and function, what we have shown preclinically in our animal studies is that Giva monotherapy induced a localized immune activation, and that was shown by an increase of c d eight positive to regulatory t cells, increased memory t cells, and decreased exhausted T cells in the tumor microenvironment.

We also saw the a long lasting memory response against tumor rechallenge as well. So we're having kind of the the the types of effects on the immune system that you would want to provide long lasting benefit. But, again, we have this combination of a breadth of clot and expression that we can target, targeted expression of four one b b activation of that co two stimulatory signal in T cells in the tumor microenvironment leading to increased c d a positive t cells, a decrease in Tregs, and ultimately, tumor immunity such that if we rechallenge again, talking about mice now. If we rechallenge mice, we actually they successfully mount an immune response and do not develop new tumors with rechallenge.

Andres Malvinato, Senior Health Care Analyst, HC Wainwright: Great. Incredibly helpful. Thanks for that, you know, giving us a good basis for the scientific context of Jeeva. So one of the things I wanna move on to now is the true differentiation of givestomag. So, obviously, you know, we we spoke at ASCO.

We saw many different approaches to targeting Plot and eighteen point two that are up and coming and many historical ones as well. So I guess, you know, broadly speaking, before we get into the nitty gritty of, you know, one off one to one comparisons, just on a modality basis, you know, can you walk us through the key differentiation points for Jeeva versus other types of ADCs, c d other c d three bispecifics, or any type of modality that comes to mind, targeting Cloud and 18.2 to start?

Philip Dennis, Chief Medical Officer, IMAD Biopharma: The first thing I'll say as oncologist, I think this is a really exciting time for patients who have Cloud9 eighteen point two positive tumors. I think we're seeing a lot of progress in the field in general, and I think that's a great thing for patients. Jeeva is highly differentiated in this very crowded field. It it's differentiated for several reasons. The first, and I'm just gonna start with the basics here, which is the fact that it targets the broadest range of Claudine positive patients.

Our cutoff in all of our clinical studies is one percent of those, one plus or greater intensity. The next part of the differentiation is an incredibly well tolerated asset as monotherapy, but with a discernible objective response rate in highly pretreated gastric cancer patients, namely an ORR to Sean's point of eighteen percent. So if you wanna develop, we know that in solid tumors, patients benefit most by getting the best therapies up front. So our strategy all along was to move Gvastomic into frontline therapy. And if you look across the entire 18.2 asset class, I daresay there's no better suited drug to be moved into standard of care without modifying the standard of care than givastomic.

And that's, again, what's what to be shown at ESMO GI, where we can add Giva to regular standard of care, regular doses, regular schedule of nivolumab plus FOLFOX Without modifying it, it's well tolerated, and the efficacy it's, you know, it's it's very notable, and you'll see that. But in comparison to other assets, there are other assets that will clearly have a role to play. ADCs, T cell engagers that activate T cells through c d three. You know, we just a very interesting presentation on on Claudine 18.2 CAR T cells that are being developed in China. These assets will have a role.

They have a high active response rate, but they also come burdened by a very high rate of toxicity. Now as monotherapy, you could say, okay. As an oncologist, second and third line, I'm willing to tolerate that toxicity profile. But what I'm thinking about benefiting the most patients by moving it into frontline therapy, I have to think about the existing toxicities of nivolumab plus FOLFOX. And I'm saying to myself, I don't see how this works.

How can you add something that has a fifty or sixty percent grade three and above treatment related adverse event incidents? How can you add that standard of care without taking something away from standard of care? We know health authorities don't that approach. Health authorities love additions to standard of care because in a in a study where you're comparing standard of care plus standard of care plus an experimental fit, everyone gets standard of care. So the development path is much easier when you have an asset that can just be added, and that's the situation that Jeeva's in because of its properties of being very well tolerated and having discernible clinical efficacy.

Andres Malvinato, Senior Health Care Analyst, HC Wainwright: That incredibly helpful. And, you know, it's a perfect lead in, to my next question. Again, you touched upon this, but kinda really wanna drill down again. So when investors, you know, are comparing, you know, whether it be the efficacy profile or the safety profile of Giva against, you know, the you know, one of the first monoclonal antibodies of rituximab, an ADC like CMG nine zero one or a TCE like IBI three nine eight. You know, can you just broadly speak about some of the caveats of those cross trial comparisons and how, you know, investors might get hooked up on maybe focusing too much on ORR without taking into account the holistic safety profile.

Any high level thoughts there would be helpful.

Philip Dennis, Chief Medical Officer, IMAD Biopharma: Yeah. This, I'm trying to thank you, Andres. I'm I will try not to get in the weeds too greatly here, but I will point out the differentiation of, again, givastomic. We have the widest, broadest range of eligibility for Claudine at a 1% cut. Zolbituximab, has an indication in frontline gastric cancer in combination with chemotherapy.

That indication is that it's seventy five percent of tumor cells, so it gives you a breadth of the exposure. Other assets such as, you know, AstraZeneca's ADC zero nine zero one, Innovence T cell engager, the the ADC XNW that was just presented at ASCO, again, variable levels of clotting 18.2 expression were the lowest. What you see again across these asset class, especially in sobetuximab and their phase one data with a cut point of fifty percent, their objective response rate was nine percent or 18. If you look at the ADC and T cell engager, it's twenty five to thirty percent. And with this ADC presented at ASCO, the ORR was of 60% or so.

So this is this is a way to compare. But, again, I go through the the toxicity profile for distinguishing these assets. One category that you can look are grade three and above treatment related adverse events. If we look at the monotherapy for all of these different assets, Gvastomic has grade three and above treatment related adverse events of thirty three percent. For, 09/2001, the percent was fifty seven percent.

For the Innovent c, T cell engagers, fifty eight, almost double of what we see. And for the ADC presented at ASCO, XNW, it was over sixty percent. So, again, if you have monotherapy activity, sure. But monotherapy toxicity where grade three and above are that high, it's just going to be prohibitive. And then if you hone down into the toxicities, for example, ADCs almost always have bone marrow toxicity because of premature release of the warhead.

No linker is perfect. Right? So the minute you have grade three and above neutropenia, anemia, thrombocytopenia, and you're looking at FOLFOX, which does the same thing, it's gonna be very hard to combine. Right? So in totality, we have these assets with different profiles, but Jeeva is arguably best suited to be combined because the other assets, whatever they come with with activity and toxicity, aren't well suited to move into frontline.

And if it is suited to move into frontline, like zolbetuximab, it becomes very limited because the activity of zolbetuximab is limited to to tumors that really only express claudin 18.2 in almost all tumor cells at very intense staining of two to three plus. Very

Andres Malvinato, Senior Health Care Analyst, HC Wainwright: helpful. Then, you know, just to confirm. So, I guess, you know, as we think about, you know, the prior kind of CRS rates observed with, other c d three bispecifics and as we take into account the broad expressional coverage that Jiva affords, about an 18.2, targeting, you know, What is the strategy, I guess, in terms of or or what's the internal bar there for, you know, saying that, look. We can expand beyond, you know, the patient subset of, you know, zobetuximab and other competitors. So what I'm really trying to hone in on is, you know, as we're looking at through the dose escalation data and as you lock in the, you know, the the real real world dosage, you know, I guess, what are some of the puts and takes there for honing in on the patient population that benefits the most with the cleanest safety profile?

Philip Dennis, Chief Medical Officer, IMAD Biopharma: Yeah. I I I've been an oncologist a long time, and I will say that that the data that's going to be presented is is very interesting. It's very intriguing. Our primary endpoint in this dose escalation was safety. So we did not hit a maximum tolerated dose.

We the toxicity profile, as Sean mentioned, looks very much like Nivolumab plus FOLFOX. And, importantly, we're not seeing a large increase in, we're not we're really seeing no increase in immune related adverse events. Our follow-up for this cohort is almost a year, and one reason why we wanted to wait so long to present this data, I wanted to be assured as someone who has more than a decade experience of developing agents in pharma that I wanna be assured that we didn't have late onset IRAEs. We're not. We don't have it.

So success to me looks like a well tall tolerated regimen. And then to the next point as well, okay. It's tolerated. Who's benefiting? Well, we already talked about our clotting cutoff being most threshold possible.

We're also seeing we also know that the responses, nivolumab and two other checkpoint inhibitors that are that have indications in front of gastric cancer are limited now in The US to p d l one one percent or above. That says that there's a gradation of response to the standard of care of Olmap plus FOLFOX based on p d l one. Well, in our cohort, we have patients that are low p d l one. We have low claudin eighteen point two, and we have a small number that are actually low for both. And we have the majority of responders in that select group low for both.

We're we're observing objective responses. And so that to me says that that is it's it's a small number of patients. We don't wanna make too much of it, which is why we're doing a dose expansion that's ongoing as we speak, that this is very intriguing data. The other intriguing data that we wanna look for that everyone wants is duration of which response. This is IO.

We all want duration of response. The good and bad news is that the data's immature. We've had very few events. So you're going to see little in terms of progression, you know, median PFS, we do make an effort to look at PFS and present data that that we think is appropriate given the immaturity of it. But the image surety is a good thing.

If you don't have events, you can't have a median. Right? So this is a really it's kind of a it's a it's a very impressive, intriguing dataset, and it has the attributes and the unique features that I just described.

Andres Malvinato, Senior Health Care Analyst, HC Wainwright: No. Absolutely. You know, really interesting strategy. So, you you know, kinda continuing on the strategy portion of the clinical strategy of Jeeva. So, obviously, you know, the strategy was a bolt on to frontline.

But given the safety profile and these are early days, so take you know, context is key here. But given the safety profile so far, you know, is the door you know, are you excited to maybe explore alternative chemotherapy backbones? And if you decided to, you know, where would that kind of steer the Giva ship, whether it would be further within, you know, GI cancers or maybe even outside there?

Philip Dennis, Chief Medical Officer, IMAD Biopharma: We're, we're committed to develop Jeeva in frontline metastatic gastric cancer. So we are that is our mission is to get an indication there to have the greatest benefit for the greatest number of patients, and that's what we're focused on. So we are laser like focused on frontline metastatic gastric cancer. Having said that, know that with any good drug, we wanna make a good drug available to as many patients as we can. So where might we test Jeeva next?

I think there's some kind of obvious places, both within gastric cancer and outside gastric cancer. What do I mean? Within gastric cancer, we just heard presentation of the Matterhorn data from AstraZeneca combining durvalumab with FLOT. FLOT is a different, arguably more toxic chemotherapy regimen that is used for locally advanced resectable gastric cancer and gastroesophageal junction cancer. We saw positive data there.

It's likely they will get an indication there. So if we establish proof of concept with Giva plus a checkpoint inhibitor plus chemotherapy and metastatic, why not move into locally advanced? That's an obvious place to look. And then as I mentioned, two other tumor types, pancreatic cancer and biliary tract or cholangiocarcinoma, also have high levels of clotting 18.2. The standard of care for frontline pancreatic cancer is a chemotherapy doublet.

Why not why not test Giva in that setting, have established POC and frontline metastatic gastric? Well, same could be said for biliary tract cancer where the standard of care is, again, a checkpoint inhibitor plus chemotherapy. So there there's a tremendous upside to Jeeva. We are laser like focused on the development in frontline metastatic. That's what we wanna drive home.

We wanna add Jeeva as a standard of care to IO plus chemo.

Andres Malvinato, Senior Health Care Analyst, HC Wainwright: Great. No. Very helpful, for giving us a prospective context. But I guess in a in a in a current state context, would be great, you know, ahead of the ESMO GI presentation on July 2 that we will all be tuning into. Would be great to just, you know, touch base with you on walking us through the dose escalation logic of this study, you know, and what you're evaluating pharmacodynamic wise and, you know, as a guide to, you know, really honing in on that, r p t two r p two d selection.

Philip Dennis, Chief Medical Officer, IMAD Biopharma: Correct. Yes. So our design of the combination with the standard of care biochemo was on our monotherapy analyses. So in our monotherapy dose escalation study, we know the doses where responses occur. We know that the pharmacokinetics for exposure are dose dependent, but we also know something very interesting, which is if we look at a pharmacodynamic marker, namely release of soluble four one b b by T cells that are stimulated through Jiva, what we find is that there's actually even though there's linear PK, there's a plateau of the pharmacodynamic number above five milligrams per kilogram in the monotherapy study.

So the doses that we chose that we will reveal at ESMO GI were based on that PK and PD data that we saw from the monotherapy data. We also have observed very similar data in combination. So we observe linear pharmacokinetics in terms of exposure, but we also observe a plateau of the pharmacodynamic marker suggesting that the three doses we chose were were really well chosen because we have a low, a middle, and a high dose, and we felt as though that is perfectly adequate because, again, based on the monotherapy data with the plateauing of the pharmacodynamic marker, dose level three is probably as high as we wanna go. So we have a very we're in a very good position now to choose the dose moving forward. In terms of the recommended phase two dose, we're gonna be able to make a much more informed decision after the completion of our dose expansion data.

Again, we're going to be enrolling, 20 patients each in each of the top two doses. This allow us this will allow us to validate the objective response rates we've seen in escalation, which, again, are very notable. Very notable, very much above the phase three ORRs that were reported for CheckMate six four nine as well as Spotlight, leading to approvals of nivolumab or zolvetuximab, respectively. So we we want to validate what we saw in escalation. We'll have a total of anywhere 25 to 30 patients at each of the two doses that we're testing in an expansion.

We'll be able to make a choice, we think, after that. And we'll also obviously be able to have more patients in those defined subsets. Right? So the it's a question. Does dose matter if you have really low levels of clotting?

Right? We don't know that. We don't you know, that's one of the things that we're trying to figure out. So the dose expansion for us is very important, but we're well suited to we're well suited to choose a dose, and we also have great confidence based on some consultations we've had that the approach we've had for dose expansion will satisfy Project OPTIMAT. We haven't spoken to the FDA.

I don't wanna overstate it, but I think the experts that we talked to have experience with OPTIMAT. I have experience with OPTIMAT as well in in prior positions. This will satisfy Project OPTIMIS. So I think we're in a very good position to be choosing a dose to move forward.

Andres Malvinato, Senior Health Care Analyst, HC Wainwright: Very helpful. So then, you know, ahead of the ESMO data, you know, probably, you know, as investors are trying to formulate what they view as successful dose escalation data, could you talk about not so much the internal bars for success because I think you've covered them, you know, and what we need to see, But can you speak more to some of the cross trial, you know, comparison caveats, you know, that are that may be over interpreted here? So if you could speak to any maybe internal safety thresholds that you guys have, you know, that could help frame, you know, the you know, a more stringent and and real world kind of assumptions of what to expect as just defined as good data.

Philip Dennis, Chief Medical Officer, IMAD Biopharma: So I I do think that we we've laid some of this out. I would say that when looking at the data, if I'm looking at this as an investor or as an attendee at ESMO GI, if I'm looking at the safety, I wanna know is there a dose limiting toxicity. There's not. I wanna know does the toxicity profile look different than the standard of care of Novo plus chemotherapy, and it it it looks very similar. And I'd like to know, is there a sign that because of your act because of activation of T cells through four one b b, you're exacerbating what already know what is already known about nivolumab, in this regimen.

And and, again, we're not seeing any notable increment above that. So I think those are the things that I would look for. I would look for in the escalation. Again, I I think that what we have and what you'll see are confirmed responses in everyone. You will have a sense if you keep in mind check rate six four nine and Spotlight and the objective response rates, the fact that zolbetuximab doesn't increase objective response rate but improves PS and OS, I think you'd wanna look at our ORR and think about the date from those two phase three studies and say, how does this is this a is this all increment of improvement, or is it a very large increment incremental improvement?

And I think you'd wanna know, does it look like, patients are staying on study? So those are those are the parameters I think that we would, I would certainly look at as as an oncologist, and I'm sure investors will be doing the same thing. I will say that with the objective response rates that you will see, and we present this for the whole cohort, and then we will also present data on the upper two doses that we are moving forward in expansion. And what I'll simply say is when the objective response rate is so high and it's so high using an IO agent, not a small molecule, this a tyrosine kinase inhibitor where you might get a deep response and the tumor evolves, and develops resistance. That certainly happens with IO, but it doesn't happen rapidly.

And I would be surprised as a clinician that if our objective response rate that will be reported doesn't translate into improved p s PFS. Again, it's not a randomized study, but the fact is I think that our patients are going to do quite well long term, and that's what I'd be looking for as well.

Andres Malvinato, Senior Health Care Analyst, HC Wainwright: Great. And as the dataset continues to mature at ESMO and beyond ESMO, you know, I guess, what kind of evidence should be we be we we should be looking for to really confirm that activity of geostomax four one b b arm in delivering localized postimulation? You know, can you point us to what p PKPD signatures or immune signatures you're really honing in to confirm that there's a true I don't know if synergistic is the right word, but a true kind of additive effect there, you know, that goes beyond just trying to suppress the caveats of some of the older safety signals that some of those strategies have had?

Philip Dennis, Chief Medical Officer, IMAD Biopharma: So we will not be presenting biomarker data at in the escalation study other than in other words, biomarkers for T cell activation that that we we will have data forthcoming subsequently on that, and we will be presenting the dose expansion data. We've recruited quite well into those dose expansion cohorts, and we anticipate being able to present, that data, early next year. So what I will say is what to look for would be, I think because, you know, the clinical surrogate of t cell activation precise in the tumor microenvironment versus imprecise in circulation are cytokine release syndrome would be hepatic toxicity that's commonly observed with four one b b. You'll see very, very low incidence. We have no CRS, and you'll see a very low incidence of hepatic toxicity.

So that's the kind of thing that we would look for. What we know and one reason we weren't we weren't lazy or or kinda confident about not doing biomarkers, but what I'll say is we are doing them. But we showed preclinically that in in mouse studies that the only changes in T cell sub that's were in the microenvironment of the tumor once the tumor was excised and digested. If we look in the periphery of the circulation in the months treated with Giva, we saw no changes. So so it it's really we don't expect to see changes in humans, but we are looking.

But we will not be presenting this data at you know, in a few days at ESMO GI.

Andres Malvinato, Senior Health Care Analyst, HC Wainwright: Great. No. That that was very helpful context. Obviously, the biomarker strategy takes a long time and, you know, always chopping at the bit for more and more data here. So I I guess, you know, the next logical question is, you know, given the, you know, the very positive data package you have presented for Jeeva thus far, and you've touched upon kind of, you know, Jeeva's potential maybe outside of GI or other you know, in other tumor types.

So kinda wanted to hone in on your opinion on across tissue types, you know, how much does the experience of Giva in gastrointestinal cancers, really set a threshold for what other tumor types you can target? So let's say for pancreatic cancer, does the threshold hold up for the threshold of clotting expression, and do you expect a similar activity? If you can give any high level kind of macro view there on the translatability of this dataset to potentially inform, you know, activity and other, you know, tumor types would be very helpful.

Philip Dennis, Chief Medical Officer, IMAD Biopharma: A great question. I love thinking more broadly about this. I will say that if you look at databases that have looked at claudin 18.2 expression, the three tumor types that have the highest levels of expression are indeed gastric, pancreatic, and biliary tract. But there are other rare tumor types that have subsets that are very positive for claudine 18.2 expression. Right now, we're not pursuing a tumor agnostic indication.

I think if Jeeva were incredibly successful, it would be very much a lifestyle man a a life cycle management, you know, project to actually look at other tumor types agnostically to look for clotting 18.2. But I I I so I do think that the focus again is on gastric, then the obvious places would be the solid tumors that that I've mentioned. Now the challenge is so for the bar for success for Jiva, again, I'm a pretty cautious oncologist. One of the about pancreatic cancer is well, IO doesn't work in pancreatic cancer. Right?

So if we establish a proof of concept combining Jeeva with a traditional checkpoint inhibitor and a chemotherapy regimen, one of those drugs doesn't work well in pancreatic cancer. So the question is, one of the things we would want to understand is, does Jiva have activity absent the checkpoint inhibitor? Right? And that's something that I think is a very important question that we're considering. The next question, if you're thinking about biliary tract cancer, could we apply the lesson learned in gastric to biliary tract cancer?

Well, the first thing you wanna think about is biliary tract cancer is in the liver. Right? So whatever we've seen with gastric cancer, even though it's very well tolerated in gastric, one of the things we need to think about very carefully is, would the toxicity profile be very different adding Jeeva to IO and a chemotherapy regimen in biliary tract cancer. So I think these are all opportunities. They all make sense to explore, but I think each of them, the lessons learned in gastric are important, but they need to be applied to the specificity of each of these other tumors that we're thinking about.

Andres Malvinato, Senior Health Care Analyst, HC Wainwright: Great. Very helpful. And and then I guess a subsequent question to that. You know, would it be fair to say that one of the most, differentiated features of Giva, if we look beyond, you know, combinations with IO or chemo, do you think given the safety so far, do you see potential other combinations with maybe other small molecule targets, really being really adding to Jeeva's defensive position specifically against, let's say, CAR Ts, other ADCs, or other bispecifics?

Philip Dennis, Chief Medical Officer, IMAD Biopharma: Yes. So one of the one of the other opportunities I didn't mention is that, again, focusing on gastric cancer, the claudin eighteen point two positive tumors we're targeting are all HER two negative. Right? So if you're thinking about other combinations, right, so for HER two positive gastric cancer, the standard of care is typically a HER two agent combined with chemo plus minus a checkpoint inhibitor. So I think it would also you know, I think that that is something that is, I think, worthwhile to think about, to consider, right, in HER two positive.

We know that there's, there's an FGFR two antibody being developed that is currently in phase three studies in frontline, either in combination with chemo or IO chemo. I will say that we have data that suggests that the Claudine 18.2 expression is very similar in the FGFR two positive tumors versus the all gastric cancers. So could we, in fact, combine with other assets such as f g an FGFR two antibody? I think we'll need to see what the toxicity profile looks like. I think the the phase two data from that antibody suggests there's a high rate of discontinuation, a high rate of ocular toxicity that we need to think about.

But I do if I think about what are the combinations, I'm not I'm not thinking as much about small molecules. I'm thinking about positioning Jiva into additional sectors within gastric cancer, the HER two positive, the FGFR two positive. And then, you know, we'll have to see there's so much excitement about the p d one VEGF bispecifics. We know that there's, you know, there's a lot of excitement in lung cancer, but the fact is is that VEGF is a validated target in gastric cancer in second line with ramucirumab. But the fact is is that, you know, could these bispecifics ever move into gastric cancer?

Would they move into frontline, second line? And knowing that are you enhancing the IO response, a natural question would be, could Jeeva be potentially combined there? I think we need to let that mature. We need to see where those bispecific end up going.

Andres Malvinato, Senior Health Care Analyst, HC Wainwright: Very helpful. Great. So, you know, we've heard from, you know, Sean and Philip about, you know, the biology of claudin 18.241 b b, the clinical landscape of 18.2, the clinical strategy, and the future strategy for Jeeva. So at this time, I think it would be great to maybe, you know, wrap it all together for our audience here in terms of, you know, if you wanna just give a brief summary overview of what Jiva has done, what to expect in ESMO, and, you know, kind of a quick footnote summary of, you know, wrapping all of our very specific deep dive questions together. I'll leave it to you, Sean and Philip, to divvy that up, you know, as you see fit.

Sean Fu, Chief Executive Officer, IMAD Biopharma: Yeah. I I I think that the way I look at Jira's data flip in ESMO GI, I think it's the beginning of a series of important and exciting data readouts in the next six to twelve months. We went through a lot of the biologies and clinical datas in the last forty minutes also with Philip. I think those are the things that we've been thinking about day in and day out. The more we look at it, the more we like the profile of Jeeva.

It's highly differentiated, very promising early data, but very promising, very exciting. Our execution on our clinical development strategy is robust. Our recruitment is strong, and we're looking forward to seeing through some of those important data flips and, be able to, benefit patients, across the world.

Andres Malvinato, Senior Health Care Analyst, HC Wainwright: Very good. And, Philip, if you wanted to add, any closing remarks?

Philip Dennis, Chief Medical Officer, IMAD Biopharma: I'll just say Jeeva has properties that are truly The phase one data show that it has clinical activity and heavily pretreated patients with a very impressive, very safe profile, and successful in being able to add it to the standard of care nivolumab, FOLFOX, and dose escalation. You're gonna see much more data to Sean's point next year with the dose expansion data. We really think that it plays out. This has great potential to help patients with Claudine eighteen point two tomb first in gastric cancer and potentially later in other tumor types. It's a very exciting time.

Andres Malvinato, Senior Health Care Analyst, HC Wainwright: Absolutely. And just as a reminder for the investors that, you know, join later on, I Mab will be presenting a mini oral presentation at ESMO GI scheduled for 07/02/2025, so stay tuned. That's all our questions. We're gonna wrap this up on behalf of the entire HCW family. You know, we would like to thank IMAD CEO, Sean Fu, and their CMO, Philip Dennis, for joining us today, and we look forward for the data card flip.

Really excited about this new target, and thank you so much for your time.

Philip Dennis, Chief Medical Officer, IMAD Biopharma: Thanks, Andres. My pleasure.

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