ADC Therapeutics at Needham Conference: Strategic Expansion Insights

On Tuesday, 08 April 2025, ADC Therapeutics (NYSE: ADCT) presented at the 24th Annual Needham Virtual Healthcare Conference. The company outlined its strategic initiatives centered on its antibody drug conjugate technology and commercial strategy. While the outlook for its product ZYNLATA is promising, with potential revenue expansion, the company faces challenges in navigating regulatory pathways and competitive landscapes.

Key Takeaways

• ADC Therapeutics plans to expand the use of ZYNLATA beyond its current indication, aiming for peak revenue of $600 million to $1 billion.
• The company is advancing its solid tumor platform, seeking collaborations to fund its pipeline.
• Future milestones include data updates for LOTUS-7 in Q2 and H2, and top-line results for LOTUS-5 by year-end.
• ADC Therapeutics aims for profitability by the end of 2027, driven by ZYNLATA's expanded use and regulatory approvals.

Financial Results

• Current Sales: ZYNLATA sales range from $16 million to $18 million, ending the year at $69 million.

• Revenue Projections:

- Second-line ZYNLATA plus rituximab: $200 million to $300 million

- Bispecific combination: $500 million to $800 million (pending approval)

- Indolent lymphoma: $100 million to $200 million

- Peak revenue for ZYNLATA: $600 million to $1 billion

• Profitability Goal: Targeting profitability by end of 2027.

Operational Updates

• ZYNLATA:

- Approved for third-line plus DLBCL monotherapy.

- LOTUS-5: Phase 3 study with rituximab; results expected by year-end.

- LOTUS-7: Combining with bispecific glofitamab; ongoing dose expansion, updates in Q2 and H2.

- Indolent lymphoma studies: Pursuing regulatory and compendia strategies.

• Solid Tumor Platform:

- Four targets in IND enabling stage.

- Seeking research collaborations for broader portfolio financing.

Future Outlook

• LOTUS-7:

- 40 patients in dose expansion planned for Q2.

- Further data updates in Q2 and full data in H2.

- Regulatory engagement and compendia strategy evaluation later this year.

• LOTUS-5:

- Top-line results expected by year-end.

- BLA submission post-results, potential approval by end of 2026.

• Indolent Lymphomas:

- Data presentations at medical conferences.

- Pursuing regulatory and compendia pathways in parallel.

• Solid Tumors:

- Advancing compounds and seeking partnerships for early-stage pipeline funding.

Q&A Highlights

• LOTUS-5 Data: Anticipates maintaining a 50% complete response rate; a CR rate above 40% is competitive.
• LOTUS-7 Data: Potential for conversion from partial to complete responses; maintaining a CR rate over 70% is a goal.
• Compendia Listing Path: LOTUS-5 and LOTUS-7 data to be submitted to guidelines, following successful strategies of other combinations.

For a deeper dive into ADC Therapeutics' strategic plans and financial outlook, please refer to the full conference call transcript below.

Full transcript - 24th Annual Needham Virtual Healthcare Conference:

Ami Faria, Biotech Analyst, Needham: Good morning, everyone. Welcome to day two of the Needham Healthcare Conference. I'm Ami Faria, biotech analyst here at Needham. It's my pleasure to be hosting ADC Therapeutics for the first session of our day two. Amit Malik, welcome.

Thank you for taking the time to do this presentation. Just a quick reminder for our listeners, if you want me to ask any question on your behalf, feel free to send it over through the dashboard, and I'll turn it over to me.

Amit Malik, ADC Therapeutics: Thank you, Ami. I appreciate the opportunity, and welcome, everyone. So I look forward to, sharing with you a little bit about ADC Therapeutics. Nicole, if you can go to the next slide. So ADC Therapeutics is a commercial stage pioneer in the field of antibody drug conjugates.

We have specialized capabilities that are end to end with a variety of different technologies, whether they be pay payloads, linkers, conjugation chemistry, and we've been working a lot on next generation, highly potent ADCs. We have an approved product in XENLETA, as well as an early stage solid tumor portfolio. We've been delivering on our strategy with a very strong team, and we have a cash runway that goes, into the second half of twenty twenty six. If you go to the next slide. Our portfolio really is, as I mentioned, centered on two different pillars.

The first is on hematology, where we have an approved product, Xenlata, which is approved in the third line plus DLBCL setting as a monotherapy. It's already commercially profitable, meaning that the sales that we generate more than offsets all of the commercialization medical affairs, headcount, and cost associated with the product. But the much bigger opportunity as we as we as we move into earlier lines of DLBCL and into indolent lymphomas. We have our LOTUS five study, which is combined with rituximab. It's a phase three study.

We have our LOTUS seven study combining with bispecifics, and we have indolent lymphoma studies. In addition, we have our second pillar, which is our solid tumor, platform using our novel, exatecan based payload. It's a differentiated platform with using a very novel hydrophilic linker, and we have four different targets that are in the IND enabling stage. PON six, PSMA, which are the two most advanced, in that group, but also NaPi two b and a s e d two. We're in the process of advancing one of those candidates to IND, but more broadly looking for research collaborations to finance, a broader portfolio to move forward.

This is just an overview of the pipeline that I mentioned. As you can see, that the majority of the activity is really around ZYNLATA, coupled with this early stage pipeline I mentioned in solid tumors, which is beyond the DC stage and now progressing towards, IND. This is just some of the, leadership team that we have. It's a very experienced team with, you know, twenty to thirty years of experience both in pharma, and biotech, multiple, critical experiences that people have had, with very large scale leadership as well as kind of very agile leadership in biotech. So very excited about the team that we've been able to build, not only at a leadership team level, but across the whole organization with really proven expertise, all the way again from preclinical research through commercialization.

So let me dive into Xenlanta now. Xenlanta, as I mentioned, is approved right now as a monotherapy, in the third line plus DLBCL setting, and it really is ideally suited across care settings for patients in that relapsed refractory setting. So it's a c d nineteen directed ADC that's indicated, as I mentioned, as a monotherapy for treatments, for patients with, relapsedrefractory large B cell lymphoma with two or more prior lines of therapy. So it's really third line plus DLBCL. Now there's a few features of the product that are important to note because especially as we get into combinations.

These attributes really differentiate the product. First, it has really rapid, deep, and durable efficacy. So the immediate time to the CR is only one and a half months. You achieve a CR very quickly. Overall, as a monotherapy, even in this very late line setting, we have deep responses.

Forty eight point three percent overall response rate with a twenty four point eight percent complete response rate, and those CRs are very durable. Of course, getting deep response is important, but durability is key. And we have immediate duration of response that wasn't yet reached even with two years of follow-up, for those CRs. We've a very manageable safety profile, so we don't have any CRS or ICANS like you see with other therapies or cumulative irreversible toxicities like what you see again with chemotherapy and other therapies that are often used in this in this class. Very accessible because it's just a fixed duration dosing, q three week dosing with no ramps or inpatient stay requirement.

So it's very, very convenient, for physicians to administer the patients with a simple thirty minute infusion every three weeks. And, again, typically, what you're seeing in monotherapy is three to four cycles, and combination, can be up to eight cycles. Now here's the strategy. We're playing in a relatively small space today, which is that third line plus d l b s d l b c l setting as a monotherapy. But the strategy is really to expand the use of ZENLANTA.

First, we wanna expand into the second line setting in combination. So we have our LOTUS five study, as I mentioned, which is, looking at Zemlata plus rituximab. It's currently a phase three study that's fully enrolled, which we expect could read out, by the end of this year. We have just if you look at the safety run-in data because we were approved via accelerated approval. So we did a safety run-in before we went into the randomized portion of the study, and that 20 patient safety run-in data showed an overall response rate of eighty percent with a CR rate of fifty percent and no new safety signals versus the monotherapy.

We're also looking at the combination ZINLANTA plus the bispecific glofitamab. We've seen very promising initial efficacy data, ninety four percent overall response rate with a seventy two percent complete response rate in the initial eighteen efficacy evaluable patients. Also, very manageable safety profile. I'll go through more of the details in the twenty nine patients that were evaluable for safety. But beyond DLBCL, we're also expanding into indolent lymphomas, and so we've demonstrated very strong data in that setting as well.

So recently at the at ASH in December, data was presented, looking both at ZENLANTA plus rituximab in the high risk relapsed or refractory FL setting. In that setting, in the first thirty five patients evaluable, Zilanta plus rituximab demonstrated a ninety seven percent overall response rate and a seventy seven percent complete response rate. And then, also, there was a poster presentation with ZYNLATA monotherapy and relapsedrefractory MZL, Marginal Zone Lymphoma, wherein the first twenty three patients are viable. There was a ninety one percent overall response rate and a seventy percent complete response rate. So we've really seen consistently strong efficacy as we've been moving Xelanta both in combination as well as into different settings of care.

Now how does this translate into an opportunity? As I mentioned today, we're really playing in that third line plus monotherapy. It's really the smallest part of what the opportunity is. Typically, sales have been in the 16 to $18,000,000 range post the bispecific entry. We finished the year with 69,000,000 in sales, which was the same as what we had the prior year.

So we've kind of been stable in that range, but the real big opportunity comes as we move into different, lines of therapy in combination. So with our second line plus, Xelanta, plus rituximab opportunity, that will take the total opportunity for Zilanta to 2 to $300,000,000. When you think about it, you're doubling the number of patients. We're increasing the duration of therapy, by over fifty percent, and the efficacy we expect to get much better than the monotherapy. So all those factors start leading to an opportunity that can get into the 2 to $300,000,000 range.

Then when you look at bispecifics with both an approval and compendia listing, we could take this opportunity to 5 to 800,000,000 in total for the brand. Bispecifics will no doubt be the biggest segment of the relapsedrefractory segment, and we believe we have the chance to have best in class efficacy and safety profile, with our bispecific combination with glofitamab, and I'll review some of that data, in this presentation. Beyond DLBCL, also have an opportunity in the lymphomas where we're pursuing both regulatory strategy and compendia strategy. With that opportunity, that could be an additional 1 to $200,000,000 opportunity. So in total, we believe that the peak revenue opportunity for XENLETA will go from where we are right now, which is 69,000,000 last year, to roughly a 600,000,000 to $1,000,000,000 opportunity, again, depending on the clinical profile, and how the competitive landscape evolves over time.

Now as you dive deep into the competitive landscape, there really are four classes of drugs, that exist in that second line plus setting. First is cell therapy. These are really dominated by CAR T. There's still some transplant, but the majority is CAR T, which have really strong efficacy. Typically, you see CRH that are sixty five to seventy percent and with a long tail, so the durability is quite good with CAR Ts.

Now the safety profile is a little bit tougher, and they're less accessible because you only have about a 50 CAR T accredited centers in The US. And because of the need to be at or near the hospital for roughly a month with someone with you, it's it's not very accessible to many patients. So CAR Ts have about 20 share, and that share has actually remained quite flat over the last couple of years. On the other extreme, you should have chemotherapy, which is actually the least effective therapy. Only about twenty five percent CR rate.

Doesn't tend to be very durable either. The safety comes with some irreversible toxicities like neuropathy and others, you know, irreversible toxicities, but it's very easy to give. Physicians are comfortable with it, especially in the community. And so it's still actually used quite a bit, more than you would expect given the efficacy difference with some of the other therapies. Biospecifics are emerging and really expected to become the biggest class of drugs in that relapsed refractory setting.

Up to this point, they've only been approved as a monotherapy in the third line plus setting, but as they move into combination. In the second line setting, you see efficacy in that fifty eight to sixty two percent range from a CR standpoint. Durability, you know, as a monotherapy look good, so we'll see how that plays out in combinations. The safety is, of course, better than a cell therapy, but you still have CRS and ICANS, which oftentimes requires hospitalization. And so you see the penetration in the community, although it started much more limited than what you would see in the academic setting.

And that, of course, hamper some of the accessibility in that broader kind of community setting. Nonetheless, as they move into earlier lines with multiple combinations, this is projected to kind of grow the class. ADCs and monoclonal antibodies, which there are a number that have been approved in a second line setting, typically have efficacy up to forty percent CR rates. So there's, again, an opportunity here, not only as a class themselves, but across ADCs plus bispecific combinations to really, expand the opportunity. Today, the efficacy is worse than bispecifics, but, again, there's an opportunity to really improve that.

The safety, of course, is is is better than a cell therapy and a bispecific, and they're very accessible. So like chemotherapy, really any physician can administer these products. So that's a big advantage. You can see we're really playing in the two segments that are projected to grow, bispecific based combinations and ADC based combinations. And so with our LOTUS seven and LOTUS five trial, we believe we have a chance to really disrupt the treatment landscape and to lead in the two segments of the market that are projected to grow.

Ultimately, you know, physician treatment choices aren't just driven by efficacy, because if they were, CAR T should have a % share. At the end of the day, you know, physicians are always balancing the treatment of efficacy, safety, and accessibility based on those individual patient considerations. And and, you know, not only in terms of the clinical profile of the patient, but the accessibility that that patient has, to different centers. So if we go to the next slide, I'll dive a bit deeper now into LOTUS five, which is our confirmatory phase three study of ZYNLATA in combination with rituximab, again, in that second line plus DLBCL setting. So these are second line plus DLBCL transplant ineligible patients.

The primary endpoint is PFS, but, of course, a lot of other key endpoints like overall survival, ORR, CRR, duration of response, and and other key factors. As I mentioned, we did a safety run-in, given that the approval the accelerated approval is based on the monotherapy. We did an, safety run-in where the first twenty patients, showed an eighty percent overall response rate and a fifty percent CR rate. No new safety signals. We've now since completed the randomized portion of the study that was done by the end of last year, and now we're waiting for the events to happen.

We expect top line results could happen, by the end of this year once the 262 prespecified PFS events are reached. Of course, the timing is events driven. So the, you know, the exact timing is gonna depend on when we hit those events. And once we do, we plan to then submit to regulatory authorities, you know, soon after. When you look at the competitive landscape on the lower left, you can see that LODA's five, whereas a monotherapy, we have about roughly a twenty percent CR rate, which is, you know, more akin to chemotherapy.

Of course, more durable without all the side effects, but you can see how LOTUS five, you know, brings that can bring the therapy if the data holds at fifty percent to be really the best in class outside of the CAR T and bispecific combinations. And we know that not all patients are gonna have access to or be suitable to a bispecific or CAR T, and also many of them, unfortunately, will progress. And so for all those patients, having a best in class combination like LOTUS five really provides a great opportunity for us. You know, one of the things we did was to look at some quantitative market research because, as you know, there's a lot of different classes coming in. There's a number of bispecific combinations getting approved.

There's the ECHELON three data that came out. So there's a lot of new combinations coming out. And so we asked, independent market research companies to do quantitative market research. So really sort of anticipate where is this market moving, and where is it expected to go. So in the second line setting, you could see CAR Ts, which are just over 20% share, are expected to be roughly stable.

Within that 78% share today, you know, most of those are either ADC or antibody based therapies or or chemotherapy, which is still actually used quite a bit. What you could see is, you know, CAR Ts are expected to be roughly stable. Biospecific based combinations are expected to become the biggest part of the market. And together, you know, the the CAR Ts and bispecifics capture about 50% of the market. You could see this in Lanta as it would be if the if the if, again, the data holds at 50% with strong durability.

You can see that the physicians project, roughly a 14% share for XENLETA plus rituximab. Given that Xenlanta you know, not only do you have more patients in that second lab setting, what we're seeing is a higher duration of therapy. So, typically, instead of the three or so cycles that we get with Xenlanta monotherapy, we see about five cycles. We expect to see with Zilanta plus rituximab. When you couple the greater number of patients plus a longer duration of therapy, each of these share points is worth roughly $15,000,000.

So could see how 14% translates to a lot. Even if we only only got 10% share, that's a roughly $150,000,000 opportunity just in the second line setting. So it's a pretty significant opportunity for us. And, again, not all patients are gonna have access to bispecific CAR T. Not all are gonna have be suitable for them, and many are gonna also unfortunately progress.

And then so you get to the third line setting where we can plan the 50% in the second line where, you know, patients don't get access to or not suitable for CAR T or bispecific. But when you get to the third line setting, that also includes patients that have also progressed post them. In the third line setting, you could see that, again, bispecifics and CAR T will play a big role because these therapies can be sequenced. So you may get a CAR T second line and then a bispecific third line or vice versa. But nonetheless, you still see that therapy, Xenlanta combination really expected to take a lot higher share.

We're roughly 9% share, nine to 10% share, and it's expected to more than double, based on this market research. Because, of course, the efficacy going from twenty five percent CR rate to roughly fifty percent CR rate, you know, puts us from closer to chemo from a response rate of although, of course, more durable and safer, but to one in which you could be kind of best in class amongst those non CAR T bispecific therapies. Again, here, even if we took the share down and said, well, what if it was only, you know, 15% share, 14 share? That could still be, you know, a hundred, $50,000,000 another opportunity. So you could see how getting to 2 to $300,000,000, given that we have a better efficacy profile, we're doubling our patients, we're increasing the duration of therapy by more than fifty percent.

There's a real place for Zenlanta to play, not only in the second line setting, but in the later line settings as well and to gain share versus where we are today, as a monotherapy. So now I'm gonna turn to LOTUS seven. We're really excited about this. This is the combination that we look at with ZENLATA with, the bispecific based therapies. We did a dose escalation where we looked actually across, NHL patients, both at ZENLATA plus golifitamab and ZENLATA plus mozentuzumab.

We looked at the full doses of those bispecifics with three different doses of ZENLANTA, ninety micrograms per kilogram, hundred twenty micrograms per kilogram, and the approved dose of a hundred fifty micrograms per kilogram. We had cleared all the doses, no DLTs with any of the combinations. We decided to move forward with Zenlatta plus glufetamab since they're both approved agents in DLBCL and really two of the most potent agents that have been approved in DLBCL. We're looking at two different dose levels, the one hundred twenty microgram per kilogram and the approved a hundred fifty microgram per kilogram dose of XENLETA with the full dose of glufetumab. What you could see below is in terms of how they're dosed, obetuzumab as per the label of glufetumab is given on day one, Then ZENLATA is given on day two to debulk the tumor, and then you do the step up dosing of glufetamab.

From cycles two to eight, you give both therapies concomitant, like, on the same day. They're both every three week dosing. So you they you know, Xenlonta can be given for up to eight cycles, glafitamab for up to 12 cycles, so cycles nine to 12. If the patient's still on therapy, we'd only get glafitamab. And so this was the design of the of of the study.

Again, we completed the dose escalation, and we're currently in dose expansion right now. I'll share some of the initial data that we shared, in December. This is where the data cut off as of November 20. We had twenty nine patients in the safety evaluable population because, of course, we can include some of those patients not only in the dose expansion, but in the dose escalation across the different histologies. And we could see you see base baseline patient characteristics, which are very similar to the other bispecific studies.

So you see whether whether it be the histology, the IPI scores, Ann Arbor stage, you see it's a good representation of risk status. There were immediate prior lines of therapy of two, and prior CAR T therapy was about 24. In addition, we see, you know, quite a few patients that were refractory to primary therapy or the last prior therapy. So this is, you know, a pretty tough patient population and very similar again to what you've seen with other bispecific based combination studies. If you look at the next page, this is just an overview of the safety.

Now what we know is most of the adverse events are actually not overlapping between glofitamab and Cinelanta. And so for most of the grade three, four adverse events of special interest, you see kind of one off events, which are, you know, all adverse events that are either attributable unknown with either glofitamab or with Cinlanta. So no surprises there. What we were pleasantly surprised by is where there is overlap in toxicities on some of the heme toxin. So each of the products, glafinamab, ZENLATA, have neutropenia with grade three or four higher roughly of thirty percent.

And you see we saw something very similar in the combination. So we didn't see additive heme tox so far, in this initial patient set. Also, the discontinuation rate was relatively low, which was good to see, within this trial so far. Now CRS and ICANS is obviously, you know, one of the downsides within the bispecifics. And so we're pleased that if you look at the CRS rate, overall, it was half the level of what you see with glofitamab monotherapy.

So we had thirty four and a half percent, which is roughly half of the seventy percent level that's in the label of glifidomab. Most of that was grade one and could be managed with acetaminophen. There was a couple grade two cases as well, which could be managed with Tosi, corticosteroids, and fluid bolus. We didn't have any requirement for ICU admittance or pressure support, which is which is important. Also, ICANS, there were two cases of of low grade ICANS.

Both patients had complete resolution of their symptoms. One patient resumed treatment and ultimately achieved a CR and still remained in a CR as of the follow-up that we shared, in December. And both patients could just be managed primarily just with corticosteroid. So this is the if this profile keeps playing out, this is really encouraging to make, you know, bispecific based combinations more accessible, you know, across the community setting. When you look at efficacy, we are really pleased to see the efficacy because as I mentioned, look at all the competitive bispecific data that ends up end up being in that fifty eight to sixty two percent range from a CR standpoint, obviously, not just response that matter, durability, and I'll show you some of that initial, data on the next slide.

But if you look at just the response rates, overall response rate, across the two dose levels of ninety four percent with a seventy two percent complete response rate. So this right now is really encouraging to see north of a seventy percent CR rate in these initial 18 patients. Again, if this data holds, we think it has a chance to really be a best in class bispecific combination and really to change the treatment paradigm in that relapsed or refractory setting. This is warmer spot. What you could see is, you know, really durable.

Twelve of the 13 CRs remained in CR as of the data cutoff, so only one patient progressed. Now most of those patients, about eight of those patients had CRs at the initial assessment, but five patients did convert from either a stable disease or a PR to a CR over time. And that's one of the phenomenons we know with ZINLANTA is when we're giving you these response rates, they're the best overall response as of the data cutoff. When I when I quote, like, other competitor data, it was the best overall response rate throughout the whole course of the study. So there's always a chance that you can have conversions.

We know it's in MANTA. Even in the monotherapy study, about twenty five percent of patients who started as a partial response ultimately converted to a complete response. And so you can still we should have those four partial responses that are all we're currently ongoing when we did this data cut off. So now turning to indolent lymphoma. So this is marginal zone lymphoma.

Marginal zone, there's about three to four thousand of the last refractory marginal zone patients in The US. Very few options for these patients, so there's only two approved therapies. A couple others that are in the compendia and NCCN preferred guidelines. You could see that if you look at the lower left, the response rates really only complete response rate only up to about twenty nine percent. Many you know, the biggest class of these drugs is really the BTK inhibitors, which are also not fixed duration.

Patients have to keep taking the BTK inhibitors, for the duration of their treatment, so, that's another downside. Right now, there's a phase two IIT that's being conducted by doctor Losos at University of Miami. This is a 50 patient, multicenter study that of which 23 patients, were enrolled, and then evaluable for, this presentation that happened at ASH. Overall response rate of ninety one percent, CR rate of seventy percent. So this is really outstanding.

When we talk to physicians, let's say if you can get over forty percent and you maintain good durability with a good safety profile, given that this is an indolent lymphoma, that would be outstanding data. So we're excited about this. University of Miami and City of Hope are enrolled. Emory, recently, is on board too, and additional sites will be coming on board as well to enroll the full 50 patient, study. Once we have the results of this and data's published, we plan to pursue both regulatory pathway as well as compendia in parallel.

Once again, we have the data sufficiently available from these 50 patients. We turn now to follicular lymphoma. Again, really strong data. This is an oral presentation, the last two ASHs in a row. This data was also simultaneously published in Lancet Hematology this past December.

So if you look at the follicular lymphoma data, you look at the lower left, it's, I say, a lot more crowded segment than MZL where there's very few options. Here, you do have a lot of options. But, you know, CAR T therapies, which are have the highest efficacy, not always very accessible. Typically, typically given in later line settings and have relatively low share because, again, the safety profile that's acceptable in this indolent setting is much different than in a more aggressive lymphoma like DLBCL. These patients tend to progress slowly, oftentimes multiple years between lines of therapy, and many of these patients don't die of the disease.

So the safety profile really matters a lot. We're excited that, you know, even when we studied in the high risk population, including, you know, more than half the patients were POD twenty four, meaning patients that progressed within twenty four months where the average patient may only progress after five years, we saw an overall response rate of ninety seven percent with a CR rate of seventy seven percent. This study, is enrolling now a hundred patients. And then once we have that study completed, we again plan to pursue both regulatory compendia and regulatory pathway and compendia in parallel. Once again, the data is is available on the hundred patients.

Now beyond Xenontha, we also have a really growing toolbox with novel payloads, linkers, and conjugation chemistries. This has been built up over the last decade with, really strong end to end capabilities where we've been able to, with a high degree of success, translate, you know, technology and biological ideas into into novel compounds. So the most advanced of our platforms is a novel exatecan based platform. Go to the next slide. And our exatecan really has advantages over traditional topoisomerase based platforms like DXD, for example.

So, you know, one of the things with exoticon that's tough to work with is highly hydrophobic. And so because of that, you you need a very novel linker system that's hydrophilic enough to to create stability within the delivery of the molecule and to make sure that we could trace this and release exatecan into the cells. We know exatecan has a lot of advantages, so it has higher bystander effect and potency, has a lower risk of multidrug resistance. We don't see the interstitial lung disease in the monkey studies we've conducted, which you do see with DXD, and we've we've seen a much higher therapeutic index. We've tested our ADCs, you know, against DXD, and we see, you know, superior, you know, potency, efficacy, and and and so far, you know, better tolerability profile, especially when it comes to ILD.

So we're excited about the exatecan platform. Again, the the novel part is really the linker because of you have to offset that hydrophobicity, of the exatecan. We have four different molecules that are on that IND enabling stage. Clon six and PSMA are the most advanced and closest to the clinic. We're moving one of those forward to IND, and then we are seeking a research collaboration in order to advance our portfolio forward as we've only funded these programs up to a point, and then really require collaboration to, be able to continue beyond that as we're really allocating the majority of our capital right now to Zymanta.

Our strategy in hematology, we focus on The US where we commercialize the product. We have ex US partners to help commercialize the product as well to help fund some of the development expense with Xenlanta. And solid tumors, as I mentioned, the strategy is really to focus on more BD opportunities to unlock the value and to be able to, you know, resource and be able to fund a broader portfolio through partnership. These are some of the key milestones. So with LOTUS seven, we plan to enroll 40 patients, which are planned currently in the dose expansion, in the second quarter, so in this quarter, this year.

We'll also give be giving another update with additional patients, not all 40, but a a a good subset of the data as well as longer follow-up, in the second quarter of this year. We'll have full data on all those four p 40 patients with much more mature follow-up, in the second half of this year, and then we plan to engage with regulatory agencies and evaluate compendia strategy in the later part of this year and then as we get into 2026. With LOTUS five, we expect top line results by the end of this year. Again, that's events driven because this is a PFS events driven trial. So, yeah, we expect it could happen by the end of this year.

Possible that it goes into early next year depending on the timing of the events. And then as soon as we get those top line results, we plan to submit the BLA to the regulatory authorities, and then expect that we could have potential compendia listing and BLA approval by the end of, 2026. Indolent lymphomas, we expect to have more data presentations at medical conferences on the indolent lymphomas. And then with solid tumors, we're, as I mentioned, we're advancing the portfolio of compounds, and in in parallel, really pursuing business development right now to fund the early stage pipeline. So I wanna thank you very much and open any questions you may have.

Ami Faria, Biotech Analyst, Needham: Alright. Thank you, Amit. That was a great presentation. Maybe I wanna just dig into, the LOTUS five and the LOTUS seven, data updates, and perhaps we can start with LOTUS five, which is in Lanta combined with rituximab. You know, we've obviously seen that fifty percent response rate complete response rate previously.

How do you see that data evolving with kind of the top line data update? I mean, obviously, that was sort of a initial safety run-in. Help help me understand, like, you know, as investors think about what type of data update we could get, right, as we see more mature kind of data later this year, what's sort of the risk around, the response rate data that you've seen previously?

Amit Malik, ADC Therapeutics: Yeah. So, I mean, as you mentioned, Lozheim is an event driven study, so we expect to see results once we hit those prespecified number of events. And I think, you know, the fact that it's a nonsystemic chemo combination really offers ZIMMANTA and rituximab advanced, especially as there's still a lot of chemo use in this setting. The fact that it's fixed duration has a really strong safety profile and really convenient dosing, just a thirty minute infusion of Zemanta, makes it really kind of widely, I think will make it widely accessible across the different settings. Again, when you look at those nonparti, nonbispecific options today that are approved, and there's really no other anticipated that are not bispecific based combinations in the future.

In that second line setting, the CRH are between 2540%. So remember in that safety runner, we saw a 50% CRH. I think anything north of 40% makes us very competitive. And so we have some buffer, you know, even if we're in a slip, but not that we expect it to. We expect that we hopefully can maintain that CR rate of 50%.

Of course, durability of the CRs matters too. So we're gonna be reading out a lot of things, but the durability what we're really pleased is that even as a monotherapy in that third line setting with so later line setting, just as a monotherapy, we saw that we never even reached the duration of response for those CRs after two years of follow-up. So if we can see not only deep responses, but also durable responses with a manageable safety profile, I think it could be really highly differentiated, particularly as there's still a number of patients that either won't have access to be suitable for or will progress on a CAR T or a bispecific based therapy.

Ami Faria, Biotech Analyst, Needham: And remind us what's the standard of care, duration of response or or medium p PFS for kind of the chemotherapy or all other bucket?

Amit Malik, ADC Therapeutics: Yeah. So depends on line of therapy. And the PFS and the third line setting, honestly, for almost everything's in Lanta, bispecifics, almost everything's around four months, even CAR T. It's very, very, very short. PFS is not necessarily the best indicator because when you talk to most physicians, they say, I care about the depth of response and then the tail of the curve.

So you look at CAR T, for example. There's some CAR Ts even in the second half study that only have a nine month PFS. There's other target therapies that have a longer PFS. The key is can you get a really deep response, and can you maintain a good portion of them for a long period of of time? Even if it's only thirty percent of patients that can maintain, but for years, you know, that becomes almost like a functional cure that you see with CAR T.

So what we're really looking at is can we get a lot of patients in deep responses, and can you especially for those patients who can see or maintain a large portion of them for a long period of follow-up. I think that would be a very competitive efficacy profile.

Ami Faria, Biotech Analyst, Needham: Mhmm. And is there kind of a bogey for that that you're looking for?

Amit Malik, ADC Therapeutics: Yeah. I mean, I think if we get north of 40 CR and you have a substantial number of patients that kinda have you know, again, if we if we hadn't reached the median duration of response for CR like we saw with monotherapy after two years, I think that would be very, very good in terms of durability.

Ami Faria, Biotech Analyst, Needham: Okay. That makes sense. With regards to, Lotus seven, you kind of talked about, the data that we've seen so far. And, again, you know, I think I'm I'm just sort of, trying to play devil's advocate here and think, is there any reason to believe that the data would deteriorate from what you've seen before? Because it obviously, you know, looks competitive, based on what we've seen so far, and you're gonna provide kind of an additional update on the patients on which you've already reported data.

So as that data matures and you're folding in more patients into the, data reported, how do you sort of see that evolve?

Amit Malik, ADC Therapeutics: Yeah. Look. It's small numbers. So data can obviously go up or down, but I would just say just as much as it could deteriorate, it could also go up. Because remember, when I quote response rates of fifty eight to sixty two percent for the other competitive based therapies, that's with longer follow-up, and that means that a patient achieved a CR rate at any point of time.

If you remember, I talked about conversion that can happen with with ZINLANTA, from PRs to CRs. We've already seen it in the trial. We've seen it with monotherapy. And so it's also possible that some of those PRs convert. So it could go either way.

Obviously, that's why we need larger data sets in terms of more patients and longer follow-up. But, I mean, so far, what we've seen is very encouraging because to get over seventy percent, if we are able to maintain that over that seventy percent CR rate I think over sixty percent is already competitive because, you know, typically, if you look at the bispecific combinations, they're either combined with chemotherapy, which has an unfavorable toxicity profile, lot of irreversible toxicity like neuropathy, of which many patients have already been exposed to in the frontline, or polatuzumab, which is also used more and more in the frontline setting, and physicians tend to not wanna recycle it. So the fact that we're not polo, not chemo, is already an advantage. So if you're with a similar efficacy range, but you actually are a novel mechanism, there's already an advantage. If we maintain the over seventy percent CR rate with a competitive durability and safety profile, I think it has a chance to be not only highly differentiated, but to really fundamentally change the treatment paradigm.

So we have let the data play out, obviously, with more patients and more durability, and that's you know, ultimately, the data is gonna tell us the answer. But I think we can maintain it. It's you know, at least this initial data is very encouraging for us.

Ami Faria, Biotech Analyst, Needham: Okay. You've talked about pursuing, sort of both regulatory filing and compendia listing. Can you help us understand sort of the path to compendia listing based on kind of the data readouts that you have laid out for LOTUS five and seven?

Amit Malik, ADC Therapeutics: Sure. Well, with LOTUS five, obviously, you know, we have a full phase three study. And so the basis of that phase three study would obviously get presented at Medical Congress, be published. The publication would be submitted right away to compendia. Typically, that happens a little bit before the approval just because it, you know, happens a little bit quicker.

You typically see, you know you know, phase three studies getting into compendia and then, you know, soon after than after regulatory approval. With LOTUS seven, what we've seen with the bispecific based combinations and really almost all the bispecific based combinations have have pursued the strategy, whether it lofinumab, mosintuzumab, or epritamab, all of those are now currently in guidelines with different combination partners based on roughly a hundred patients, from a phase one, two study. And so we see an opportunity with our LOTUS seven to potentially expand up to a hundred patients at the chosen dose level to be to submit to guidelines. That'll also form the basis for additional safety data, and a larger sample set for us as we kind of then engage with the FDA, a potential path forward for a regulatory strategy. So we think there's a faster path forward potentially with LOTUS seven in the compendia as we've seen with all the other competitor bispecific trials as we engage with the FDA and other regulatory agencies on a potential, phase three path forward.

Ami Faria, Biotech Analyst, Needham: Okay. I'll try to squeeze in one last question in the time that we have left. Obviously, within ZYNLOTA, you have a lot of opportunities for meaningful growth over the next couple of years with what we've discussed. You also have a very interesting ADC platform, and, you know, you mentioned, you're looking for, sort of a potential partner to sort of help fund some of the work, moving forward. Just maybe down the line, five years out or or so, do you intend to sort of keep some of the ADC portfolio internally and kind of, take it to the point of commercialization yourself, or is that something that you think about as, you know, a a source of partnership and, sort of revenue generation through that?

Amit Malik, ADC Therapeutics: Yeah. I think it all depends. I mean, we certainly have the capability to do it, but I think, you know, in this environment with the cost of capital, I think it's also just, you know, being focused and understanding where you think you can have the greatest chance to win is important. You know, prioritizing how we allocate precious and expensive capital is really critical. And so we really made that choice to to do most of that towards Enlanta.

Over time, of course, as the company gets towards profitability, which we think we can start to do as soon as the end of twenty twenty seven. Because, you know, in 2027, you start having not only LOTUS five opportunity, potentially LOTUS five in the guidelines, potentially the indolent lymphomas and guidelines. And, of course, we're not gonna promote anything off label, but all those opportunities start to create a bigger opportunity for XENLETA, which can help to fund also the next set of molecules. So it's certainly in the, I'd say, short to medium term, partnership's gonna be key for solid tumor. Over time, I think, you know, we may have the ability to invest more on our own, as the company gets profitable.

Ami Faria, Biotech Analyst, Needham: Okay. Alright. Looks like we are out of time. Thank you so much, Amit, for taking the time to be with us today, and thanks to all our listeners.

Amit Malik, ADC Therapeutics: Yeah. Thank you so much. I appreciate it.

Ami Faria, Biotech Analyst, Needham: Alright.

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