Atomic Therapeutics at Jefferies Conference: Promising CRC Treatment

On Thursday, 05 June 2025, Atomic Therapeutics (NASDAQ:CTMX) presented at the Jefferies Global Healthcare Conference 2025, revealing promising clinical data for its Probody ADC, CX-2051, targeting metastatic colorectal cancer (CRC). The company highlighted strong response rates and a potential accelerated approval pathway, though challenges remain in navigating regulatory landscapes and expanding treatment lines.

Key Takeaways

• Atomic Therapeutics is focusing on CX-2051 for metastatic CRC, showcasing a 28% overall response rate.
• The company secured $100 million in financing, extending its cash runway to Q2 2027.
• Plans are underway to expand dose cohorts and initiate a potentially registrational study in 2026.
• Atomic Therapeutics is exploring partnerships, particularly for gastrointestinal cancers.

Financial Results

• Financing:

- Closed a $100 million financing in May 2025, extending the cash runway into Q2 2027.

• Market Opportunity:

- Fourth-line CRC represents a multi-billion dollar opportunity.

- Comparatively, Fruquintinib, a TKI for fourth-line CRC, generated $350 million to $400 million in its first year.

- The total addressable market for metastatic CRC in the U.S. is approximately 150,000 patients.

Operational Updates

• CX-2051 Development:

- Focused on enrolling expansion cohorts for a comprehensive dataset by Q1 2026.

- Developing Phase 2/3 strategy with a goal to initiate the next study in the first half of 2026.

- Exploring combination studies with bevacizumab in 2026.

• CX-801 Development:

- First patient treated with CX-801 and Keytruda combination for melanoma.

- Initial data update for monotherapy biomarker evaluation expected by the end of 2025.

Future Outlook

• Regulatory Strategy:

- Potential accelerated approval in fourth-line CRC due to unmet need and strong drug performance.

- Regulatory updates anticipated with the Q1 2026 data release.

• Expansion Plans:

- Aiming to replace systemic chemotherapy in earlier lines of CRC treatment.

- Considering combinations with bevacizumab and FOLFIRI in earlier lines.

- Exploring potential in other solid tumors beyond CRC.

• Corporate Strategy:

- Considering partnerships for CX-2051, especially with companies focused on GI cancers.

Q&A Highlights

• Protease Profile: Believed to be similar in CRC and other tumors.
• Linker Stability: Designed for moderate cleavage to balance efficacy and toxicity.
• CX-801 Masking: Double-masked to enhance safety and effectiveness.

For more detailed insights, readers are encouraged to refer to the full transcript below.

Full transcript - Jefferies Global Healthcare Conference 2025:

Roger Sung, Senior Analyst, Jefferies: All right. All right. Welcome, everyone, to Jefferies twenty twenty five Global Healthcare Conference. My name is Roger Sung, one of the senior analysts cover SMICHA Biotech in The US. It is my pleasure to have the next fireside chat with Atomic Therapeutics CEO, Sean.

Good. Yeah. Good to see you.

Sean McCarthy, CEO, Atomic Therapeutics: Pleasure to be here, Roger.

Roger Sung, Senior Analyst, Jefferies: Awesome. Maybe before we start, we know you just announced a very exciting data from your the clinical program for APKAN ADC. So maybe just give us a high level recap and then we’ll have a conversation.

Sean McCarthy, CEO, Atomic Therapeutics: Yeah, once again, great to be here. Thanks very much for the invitation. And we are super excited about the dataset we presented on May regarding CX-two 51, our Probody ADC targeting epithelial cell adhesion molecule, EpCAM. This is a drug that we believe has disruptive potential in the treatment of metastatic colorectal cancer and potentially many other cancer types. In addition to CRC, EpCAM is a target that actually was first described as a colorectal cancer antigen many decades ago.

It’s been of high interest to many in the oncology field for a very long time. It’s been a challenging target to drug because of its presence on normal tissue. It’s been of, as I said, high interest because it’s very highly expressed on many solid tumors including CRC. And we’ve always believed that it had the profile to uniquely benefit from our technology, our Probody masking platform and this first twenty five patients of data that we presented just a couple of weeks ago have we think shown that we’ve not only broken through on EpCAM for the first time with a systemic therapy, but we are able with this drug, we are making a very big difference for a very tough area of oncology to treat, which is late line metastatic CRC. So really happy to be here today, Roger, talk more about the data, what we’ve seen so far, what it means and where we’re headed with this drug candidate?

Roger Sung, Senior Analyst, Jefferies: Right. Let’s drill down this. And when I look at the data, obviously it’s a positive on the top line. But if you look into details, swim and plow and then the disease control and the durability all looks very good. And maybe just give us what are the key data point when you look at this data say, wow, this is giving me the confidence we should move forward this program, even we only have relatively small end and then still in early stage?

Sean McCarthy, CEO, Atomic Therapeutics: Yeah, absolutely. So, the drug has been very intentionally designed for the treatment of colorectal cancer. The target is broadly and highly expressed in just about every patient, if not all patients as far as we can tell. So it’s a terrific target for CRC. The payload that we’ve selected for this drug very intentionally is a topoisomerase one inhibitor.

Of course, we know that CRC responds to topoisomerase inhibition in earlier lines of treatment. It’s standard of care, arinotecan in various regimens. And we have applied our masking strategy in a very intentional way. And then the fourth aspect of very intentional aspect of our strategy has been to focus our Phase one study entirely in metastatic CRC, which was a big decision for us about a year ago, but it’s really we think paid off. The data set that we’ve shared so far, 25 patients treated through dose levels one to five in our dose escalation beginning at a dose of two point four milligrams per kilogram administered every three weeks up to and including the dose of ten milligrams per kilogram, which was dose level five also a Q3 week.

Twenty five safety evaluable patients across those five dose levels, 23 safety evaluable at dose levels three, four and five of seven point two, eight point six and ten mgs per kg. And within that dose range, 18 efficacy evaluable patients as of our April 7 data cutoff with a very impressive response rate. Twenty eight percent confirmed ORR across those 18 efficacy evaluable patients, including three out of seven patients treated at the top dose of ten mgs per kg, accounting for an overall confirmed response rate at that dose level of forty three percent. And just to put that in context, these patients had a median number of prior lines of therapy of four. So this is essentially a fifth line metastatic CRC patient population.

And we know that in the fourth line, current standard of care response rates are in the one percent to two percent range with PFS of about two to three months. We also had a very encouraging preliminary assessment of PFS in this initial 25 patient data set of five point eight months, which is a great start. So combined with disease control, a disease control rate of ninety four percent, so across all measures, ORR, disease control, PFS, this drug really has had a very strong start in the clinic. And I think our strategy of deciding very intentionally to not only design this drug for CRC initially, but do the right experiment first and really take on the challenge of late line CRC has really delivered. And the response that we’ve had from investors and others in recent weeks has been really, really exciting, including as we’ll probably talk about in a moment, a very successful $100,000,000 financing that we closed on the cusp of the data around May 12 as well.

Roger Sung, Senior Analyst, Jefferies: Excellent. Yes. Those dependence, very long duration of the response, and then there is control translate to the PFS as way higher than standard of care. And the safety, right? Because we look at the top one related safety and then also APKAN related safety, seems the masking technologies are working.

And you are not worsening or anything worse than the typical top one. So maybe you talk a little bit about the safety because that’s also very important for cancer therapy as well.

Sean McCarthy, CEO, Atomic Therapeutics: Yes, absolutely. So let’s break down the safety profile somewhat and there are really two main components to think about with 02/1951. First of course is the target itself, EpCAM. As I’ve already mentioned, EpCAM has been a very high interest to many in the oncology space for a long time, but it’s been a very difficult drug to target, to drug because EpCAM is present on most normal epithelial tissues, as the name suggests, epithelial cell adhesion molecule. Prior attempts to develop systemic therapies against EpCAM have quickly hit tox roadblocks in the clinic that include acute pancreatitis, liver enzyme elevation, and gastrointestinal inflammation.

And that’s across a range of modalities, antibodies and T cell engagers as an example. But there have been some interesting clues that actually if you can get EpCAM therapeutics to the target in a localized way, you can be quite effective in shrinking tumors. That’s been shown in bladder cancer. It’s also been shown in the treatment of malignant ascites in the peritoneum of patients with various gynecologic and GI tumors. So we’ve known for a long time that if you can get the drug to the target, you have the potential to shrink tumors, but the barrier has been the on target toxicity given how broadly expressed EpCAM is in normal tissues.

And so going into this Phase I study, we were very interested to see the extent to which our masking technology could limit or eliminate these on target toxicities, and that seems very much to be what we’ve observed so far. The other component, of course, of the safety of a drug like this is the payload, and the payload is a novel topoisomerase one inhibitor, it’s called CAMP59. We licensed it from Immunogen, now AbbVie. And this is the first in human experience with CAMP59, but it is a topoisomerase and so we kind of knew what we were on the lookout for in the phase one study in terms of payload toxicity. And very important to underscore that with our technology we don’t mask the payload.

So we do anticipate that as we dose escalate and push towards MTD that ultimately payload toxicities would emerge, they are expected. And for TOPO-one inhibitors, they’re fairly well characterized for irinotecan and others. For example, upper GI toxicity, nausea, vomiting would be expected, heme toxicity in the form of anemia and neutropenia would be expected, and diarrhea, lower GI toxicity is also a hallmark of many of these Topol one agents. So the way the study has played out, first and foremost, we’ve seen very little if any evidence of on target toxicity giving us a high degree of confidence that our masking strategy is indeed unlocking EpCAM as a systemic therapeutic target for the first time. With regards to payload toxicity, as we’ve escalated, as expected, we have seen some of the anticipated TOPO-one payload tox, Actually, very low rates of cytopenias in the form of anemia and neutropenia, and what we do see is very manageable, and moderate levels of GI toxicity, nausea and vomiting, which is manageable with prophylaxis, and some incidents of diarrhea, including some grade three, but again, we believe for the most part attributable to the payload, given that this is the first in man experience.

So, taken together with the really impressive clinical activity that we’ve seen, again twenty eight percent ORR across all dose levels, forty three percent ORR at the highest dose level, ten mgs per kg, we really think this is a strong start with a very compelling efficacy profile and a very promising safety profile overall. Lot of us were taken pleasantly by surprise. Yeah, so let me just repeat the question. The question is to what extent does the protease profile in CRC differ from other tumors? And we believe it’s substantially similar based on everything we know about the tumor microenvironment.

I think in this case, the masking strategy that we’ve used is actually quite similar to strategies we’ve used with previous programs, all of which have shown quite compelling anti tumor activity across multiple cancer types over the years, whether it’s hormone receptor positive breast cancer, triple negative breast cancer, cutaneous squamous carcinoma, multiple tumors where we’ve seen activity with the platform. I think in this case where we’ve really broken through is by directing the technology to a very clear clinical problem, which is metastatic CRC, where the target is very highly and very uniformly expressed, allowing us to really see the full potential of what our technology can do.

Roger Sung, Senior Analyst, Jefferies: And also the linker is very stable, maybe because when I look at just side by side other top one kind of the ADC seems you are even less toxic in terms of the on target, the payload toxicity there. So maybe just that’s

Sean McCarthy, CEO, Atomic Therapeutics: Of the payload toxicity itself. Yes, I think it’s a key observation. The linker on 2051 that links the CAMP59 payload to the antibody is also a novel linker. It’s a tri alanine peptide linker that has been designed by our colleagues at Immunogen to be cleavable in the extracellular microenvironment in the tumor to promote bystander effect. But it is a novel payload that was selected to have a kind of a moderate level of cleavage compared to perhaps some other ADC linkers, which can tend to run into higher levels of systemic payload toxicity, particularly in the bone marrow.

So, we’re still characterizing the full profile of this trialanine cab 59 linker payload module, but we are very gratified by these initial findings and we think that the work, the foundational work that Immunogen did to build this particular approach to inhibiting TOPO-one is really looking very, very encouraging indeed.

Roger Sung, Senior Analyst, Jefferies: Awesome. All right, great. I think the data is appreciated by the investors community for sure. And then we are going to ask for more, right? So you are moving forward with that dose level three to five and then also you continue dose escalation.

So maybe just tell us the rationale you’re expanding three, five and then the six and seven, what should we expect from the next data update, I believe the 1Q next year?

Sean McCarthy, CEO, Atomic Therapeutics: Yes. So far in dose escalation, we’ve actually proceeded through seven dose levels. The data that we just presented was through dose levels one through five. Again, to recap doses of two point four up to ten milligrams per kilogram. Based on the really compelling profile of the drug at the seven point two, eight point six and ten mgkg dose levels, We’ve already started to expand at each of those doses.

And our goal is to increase each of those dose cohorts to 20 patients by the end of this year to gain additional experience of efficacy, safety, PK, exposure and such like. And we anticipate having that full expansion dataset and releasing that in Q1 of twenty twenty six. And so fast forwarding to that timeline, Q1 of twenty twenty six, I would expect our dataset to be in the 70 patient range including of course the first two patients that we treated in single patient cohorts at two point four and four point eight mgs per kg, a handful of patients at dose levels six and seven. We don’t have any plans at the moment to expand those dose levels. We do think at dose levels six and seven, we’re pushing up against our maximum administered dose.

Again, we’ll learn more in the coming months. So the majority of the data that will be the next update in Q1 of twenty twenty six will come from the dose levels that we’re expanding on those 60 patients. We fully anticipate that our recommended phase two dose or doses will come from within those three dose ranges and the selection of doses of course for the go forward study, which we’ll talk about in a minute, I’m sure will depend of course on how the data shows itself over the rest of this year.

Roger Sung, Senior Analyst, Jefferies: Excellent. Okay, great. I think, we obviously we have a couple of months to see the next data update. But before that, you may have some interaction with the FDA to think about what’s the next step, right? So I think the late line, so the plus line, metastatic CRC, no standard of care, potentially have some opportunity for accelerated approval, but your ambition can go even earlier line.

So just tell us the overall strategy for the CRC for 02/1951.

Sean McCarthy, CEO, Atomic Therapeutics: Yes. Well first thing to say there is that the profile of 2051 is just so interesting because we see the drug as having truly disruptive potential in the treatment of metastatic CRC and what we mean by that is that our clinical evidence to date shows activity independent of the typical clinical features that are used to manage and triage patients through their treatment course. For example, we have activity in KRAS wild type patients. We have activity in KRAS mutant patients. We have activity in patients with liver mets.

We have activity in patients without liver mets. We have activity in patients with left sided or right sided tumors. And as you all know, these features are used and have been characterized historically to direct patients down certain treatment pathways. EpCAM is expressed so highly and so consistently in CRC that once we, in hopefully the not too distant future, secure our first approval in late line metastatic, this drug should be able to come earlier and earlier in the treatment paradigm. And our vision for 2051 has always been to replace systemic chemotherapy in earlier lines of treatment.

So our development strategy right now we are obviously laser focused on enrollment of these expansion cohorts to get this more robust Phase one data set in Q1 of twenty twenty six. In parallel with that, we are actively developing our Phase twoPhase two, three strategy. I have not pinned that down yet, but it will there’s a number of ways we can go. Given the we believe, given the extraordinary unmet need in the fourth line in CRC, given the extraordinary activity that we’re seeing of the drug and given the very poor nature of the existing therapies in standard of care, this is a line of therapy where we do think we could go very, very quickly and it could potentially lend itself to an accelerated approval path. We have not yet spoken with FDA.

We don’t know that that’s the case, but there are a number of conversations we’ll be having to lock in that next step in development. And our goal is to initiate the next study potentially registrational in the first half of twenty twenty six. Looking earlier, we’re really excited to bring 2051 into the third line and potentially into the second line. In the third line, standard of care, as you know, has become bevacizumab and Lonsurf. That combination shows relatively modest ORR in the single digits, about five, five and a half months of PFS, the combination of BevLonsurf.

And as we learn more about the monotherapy profile of two thousand and fifty one, we’ll be able to evaluate the potential for two thousand fifty one to compete directly in the third line with the bevlonserv combination or whether or not we would need to combine with bev to do a head to head bev-two thousand fifty one versus bevlonserv. That will, as I said, depend upon how the data continues to shape up over the rest of this year with the monotherapy. Looking to second line, second line in The United States at least is dominated by the use of FOLFIRI, so Orenitikan being a key component of second line treatment and our ambition is to replace Orenitikan in that setting. So we will be initiating in the not too distant future the appropriate combination studies to begin to lay the groundwork for moving 2051 into the second line. And then looking even further ahead, as we’ve been seeing, including at ASCO just last week, ADCs continuing to progressively move earlier and earlier in the treatment paradigm, and I would cite Trodelvy as an example showing impressive activity in the frontline in combination with Keytruda in the ASCENT-four study in triple negative breast cancer, now presenting a new standard of care for first line treatment of TNBC.

So our longer term vision for 2051 would be to bring this drug into the frontline treatment of CRC. And if you add that all up, you can see why we see 2051 as being really potentially disruptive in the treatment of metastatic colorectal cancer.

Roger Sung, Senior Analyst, Jefferies: Yes. And I believe the guidance is also you will give us some regulatory updates when you report a data next year and then the start of Phase II potentially pivotal first half next year.

Sean McCarthy, CEO, Atomic Therapeutics: That’s right. So in conjunction with our next data update in Q1 twenty twenty six, we very much would hope and plan to be announcing our go forward strategy at that time. So that should all be announced concurrent in the early part of next year.

Roger Sung, Senior Analyst, Jefferies: Is that possible you can do the third plus line versus fourth plus line as the initial indication because you seem to separate these two populations?

Sean McCarthy, CEO, Atomic Therapeutics: It’s a really good question. Quite honestly, the market opportunity in the fourth line is so compelling and the unmet need is so great and our drug is performing so well, we think that the probability of technical success in the fourth line is high and therefore the right study to do next. I think third line would follow, as I mentioned, depending upon how the profile of two thousand fifty one develops in terms of PFS in particular. The other thing about the fourth line to say is that there are about fifteen thousand treatable patients in The U. S.

Every year in fourth line CRC. And a very interesting commercial benchmark is presented by Fruquintinib, the TKI that is one of the components or one of the options for treatment of fourth line patients. Fruquintinib in its first year of sales first year on the market generated $350,000,000 to $400,000,000 of sales in CRC. So this is not a small opportunity and that was with relatively modest penetration of the market. So, we see the fourth line as a multi in and of itself as a multi billion dollar opportunity.

We currently own it. We control this drug. We have full rights to 2,051, full commercial rights, and we see the fourth line as a terrific place to start, even more so for a company of our size and shape and an opportunity that can help us drive cytomics to huge value creation as we drive towards potential commercialization ourselves.

Roger Sung, Senior Analyst, Jefferies: Okay. Maybe just since we’re on this market opportunity, first line 15,000 and then how about the third line, second line and then for the CRC opportunity that you move earlier line?

Sean McCarthy, CEO, Atomic Therapeutics: Well, you’re looking at about one hundred and fifty thousand patients across multiple lines of treatment in The U. S. In metastatic CRC. And of course, does evolve as you go from first line through to late line. But across the treatment paradigm, this is a very, very large market.

Roger Sung, Senior Analyst, Jefferies: And then right now, as you fully own this asset and then it’s in early development, what’s the corporate strategy in terms of move this into the later line? It seems it’s very doable in the later line kind of therapy, particularly if you can do this accelerated approval. But overall strategy, you want to do this by yourself or through the partner?

Sean McCarthy, CEO, Atomic Therapeutics: Well, as I’m sure we’ll discuss in a moment, EpCAM not just a sorry, two thousand and fifty one is not just a CRC drug. One of the really additional compelling features of EpCAM is that it’s expressed on just about every other solid tumor and in many of them at very high levels. So we see two thousand fifty one is really having pipeline in a product potential and we’re keen to begin work in certain non CRC indications. That could take a little bit of time because we’re having some having many capital allocation conversations at the moment, having just raised a successful round a few weeks ago. But we’re very excited to move over time two thousand fifty one into other tumor types where there remains significant unmet need.

Given the scope of the opportunity in CRC and also in those other tumor types, it’s not lost on us that CX-two thousand fifty one is a drug candidate that could benefit from a partner. We’ve always said at CytomX, we’ve done a lot of BD over the years, we’re all about doing the right deal at the right time. And we do anticipate high strategic interest in this program, not just from companies that are already decidedly in the GI space, but certainly from those who are looking hard at getting into it as one of the key areas of unmet need in oncology today. So, we’re in no hurry. We’re well funded.

We want to generate more data, but we do anticipate having partner conversations in the future.

Roger Sung, Senior Analyst, Jefferies: Yes, that makes sense. And then you mentioned earlier line likely going to be the combination. So when you will start to do some combo work in?

Sean McCarthy, CEO, Atomic Therapeutics: I think we’ll be in combinations by 2026 or sometime in 2026. Like I said, we’re right now super focused on getting this expansion data, but we do want to move the combinations. And the ones that’s most likely that we would start with would be with bevacizumab. We’re highly incentivized to get that combination moving as quickly as we can.

Roger Sung, Senior Analyst, Jefferies: Yes. And how about beyond the CRC? That’s probably I know you have some bandwidth, you will start to think about beyond the CRC?

Sean McCarthy, CEO, Atomic Therapeutics: Yes, not quite ready to put a timeline on that. Let’s just say we have high enthusiasm, but we’ve got a lot of things on our plate right now.

Roger Sung, Senior Analyst, Jefferies: Yes, absolutely agree. Okay, maybe a couple more minutes because you do it is a platform, right? So you take a long way to get here and then you get this seems a couple of things altogether in the right place and then you get this very promising data. But you have some a couple other early pipeline and your Probody platform. So give us some highlights, updates from your early pipeline and the platform and then we’ll talk about the partnership as well.

Sean McCarthy, CEO, Atomic Therapeutics: Yes, so the second drug we currently have in the clinic that we began Phase one for last year is also we believe very compelling and it’s in a way another old friend in the way that EpCAM is and it’s interferon alpha. Interferon alpha was, as many of you I’m sure know, actually the first immunotherapy to be approved way back in 1986. It has established anti tumor activity. Interferon is a very, very powerful modulator of the immune system. It drives multiple immune pathways in the tumor microenvironment, including broad and diversified antigen presentation.

It’s fallen out of use over the last couple of decades because its single agent activity is relatively modest in tumors like melanoma or renal, it’s also quite poorly tolerated by patients in terms of its peripheral side effects. But it is just from an immunobiological standpoint, it is an ideal mechanism to combine with checkpoint inhibition. And since we’ve in the field, we’ve kind of hit the of the limits of checkpoint inhibitor utility in tumors, particularly cold tumors, we’re very, very interested to see what eight zero one as we call our mass interferon can do in combination with PD-one inhibition. We have access to Keytruda from Merck. We actually announced just a couple of weeks ago the treatment of our first patient with the combination of CX-eight zero one with Keytruda and we are on track to have an initial data update for our initial biomarker evaluation of monotherapy by the end of this year, building a foundation for an evaluation of the KEYTRUDA combination in 2026.

I should also say that the study of eight zero one is following similar principles to the study of 2051 in that we’re very, very focused in a single tumor type. Every patient that we’re enrolling for eight zero one is a melanoma patient. It’s obviously a highly immunogenic tumor. It’s where we know interferon works. And there’s very, very good evidence from a study completed by Merck not too long ago that PD-one inhibition and interferon can synergize very effectively in early line melanoma treatment.

The problem was that there’s significant toxicity just not tolerated without our masking strategy. So very excited about eight zero one. It’s coming to you soon and we think another great example of the versatility of our technology platform.

Roger Sung, Senior Analyst, Jefferies: All right, great.

Sean McCarthy, CEO, Atomic Therapeutics: Double masked versus a single It’s double masked it’s masked in a very unique way. The question was what’s the masking of the cytokine? The cytokine itself is masked with a peptide mask and then we also have an FC mask, which is protease cleavable as well, which actually helps with half life modulation.

Roger Sung, Senior Analyst, Jefferies: Got it. Just last minute for the cash runway and then you recently did the financing and then it seems that you are well capitalized at this point. So what’s the runway guidance right now?

Sean McCarthy, CEO, Atomic Therapeutics: Yes. So really, really thrilled to have completed a financing concurrent with our data release in this rather challenging market that puts us in a very strong cash position with cash into Q2 of twenty twenty seven. So we’re well funded to execute through the expansion phase of 2051 to share that data in early the early part of next year and to initiate our Phase two study.

Roger Sung, Senior Analyst, Jefferies: Excellent. Thank you, Sean, for being with us this afternoon, and then thank you, everyone, for listening.

Sean McCarthy, CEO, Atomic Therapeutics: Thank you, Roger, and thanks, everyone.

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