All right. Well, hi, everyone. Thank you for attending. I'm Giselle with TD Cowen and I'm pleased to introduce ADC Therapeutics' CEO, Ameet, who will be presenting today. I'll pass it off to him. Thank you.
Thank you very much. Well, it's a pleasure to be here with all of you. Thanks so much for joining. I'm happy to speak about ADC Therapeutics today. We're one of the pioneers in the field of ADCs. We have specialized capabilities across development, technical operations, commercialization. We have a product that's already been approved via accelerated approval pathway with ZYNLONTA. It's approved in the third-line plus indication, but our strategy is really to move it into earlier lines of therapy in DLBCL in combination, as well as into indolent lymphomas, and we have multiple studies to do that. We also have a very well accomplished and multidisciplinary team and a cash runway that goes at least into 2028. There's three real horizons right now for the value creation of the company. This is a critical year because it's really a big year around data readouts.
We have our pivotal phase III reading out soon. We have other big readouts coming out later in the year. That will lead to approval and compendia inclusion for the product to expanded uses starting next year, ultimately to significantly more growth. Now, ZYNLONTA is a CD19-directed ADC with a PBD-based warhead. Some of the attributes of this product are really rapid, deep, and durable efficacy. We know that the product works extremely quickly. Typically, you're getting to a response, and most times a best response or the first disease assessment. When you get to a CR, which happens about 25% of the time in the third-line plus indication as a monotherapy-based therapy, those CRs tend to be very durable. The mean duration of CRs wasn't reached even two years after follow-up.
In addition to being rapid, deep, and durable, it also has a very manageable safety profile. No CRS, no ICANS, none of the inpatient REMS requirements that you see with other products, no cumulative irreversible toxicities like you see with chemotherapy, also very convenient, easy to deliver. Where we play today is in a field of mostly combinations. Outside of CAR-T and bispecific products, we're the only product that's ever been approved as a single agent in any line of therapy in DLBCL. We're playing as a single agent in that third line plus, the goal is to move into earlier lines with our LOTIS-5 and LOTIS-7 studies. LOTIS-5 is looking at the combinations in lota plus pertuzumab. LOTIS-7 is looking at the combinations in lota plus glofitamab, the approved bispecific product.
We also have two different indolent lymphoma studies going on in marginal zone lymphoma and follicular lymphoma, and we're happy that across all these studies, we see emerging, you know, very good data with the potential to be highly differentiating across all these different spaces. If you do dive deep into the DLBCL market, we know that frontline is pretty standard. You know, most patients are getting R-CHOP or Pola-R-CHP, whether you're treated in an academic institution or a community center. When you move into that second line of therapy, you start to see therapies break into two different categories. More complex therapies like CAR-Ts, transplant, bispecific-based products, which require more unique patient management and infrastructure requirements to administer. These are typically available in all academic centers and more sophisticated community centers.
Your broadly accessible therapies like chemotherapy, ADCs, and monoclonal antibody-based therapies, which are really accessible across all segments, including the whole community. We see this bifurcation, so where we play today is in the third-line setting. In third line, bispecific products have been approved for over 2.5 years now, and so they've already gained quite a bit of share. We see CAR-T and transplant has about 25% share. That's remained roughly stable for the last three years. Bispecifics over this period of time has gained about 35% share. Complex therapies as a whole have about 60% share in that third-line plus market.
The broadly accessible therapies comprise 40%, and we have about 10 of those 40 share points, which is in ZYNLONTA as a monotherapy, where we're playing only as a single agent, again, competing really against combination therapies. In that second line setting, the market looks a little bit different. You still have about that same 25% share that's between CAR-T and transplant, but bispecifics only have about a 10% share because no bispecific has been approved in the second line setting, but they were added into NCCN guidelines at the beginning of last year and gained about 10% share in that setting. You see complex therapies having about 35% share, broadly accessible, about 65% share.
I do expect over time that bispecific-based combinations will likely grow in the second line setting, given the strong efficacy with those combinations. Maybe not to the same degree as what they've seen in the third line setting, simply because they're not approved right now and can't be promoted. Our strategy is really to win in both segments with our combinations. Regardless of how the penetration of these markets evolve, we wanna be able to lead for both complex therapies as well as lead in the broadly accessible segment. We have, again, LOTIS-7. Our study was in ZYNLONTA plus glofitamab, where we think we have the potential to be the leading bispecific combination regimen for those patients that can get access to these complex therapies.
We also believe that LOTIS-5 is gonna play a very important role, the combination of ZYNLONTA plus pertuzumab, because we believe it has the potential to be the leading efficacy amongst broadly accessible therapies, and especially for those who either don't have access to or progress on a complex therapy. Now, when you look at the competitive set in these two different segments, starting with the left-hand side, the complex therapies, bispecifics, as I mentioned, have been approved as single-agent therapies. That was on the basis of roughly a 40% CR rate, which is actually quite good as a single agent in the third-line plus setting. When you look at bispecific combinations, there were three that are preferred in guidelines.
All of these three have a CR rate of anywhere between 51% and 61%, and typically either adding on with chemotherapy, GemOx, or with POLIVY, another ADC. CAR-Ts have roughly a 65% CR rate. Now, the benefit, of course, of CAR-T is the long tail, so you get long durability at 5 years out. Our LOTIS-7 data, which I'm gonna go through in more detail, we were able to demonstrate a 78% complete response rate in the first 49 patients. We believe if this data continues to persist, we have the opportunity to be the best bispecific combination in that second-line plus setting, which should be a big part of the second-line plus market. If you look at the right-hand side, the broadly accessible therapies, chemotherapy is still a mainstay. It works quickly.
Physicians are comfortable using it, especially in the community, so you still see a lot of chemo use. Our GemOx, as an example, has about a 25% CR rate. That's about where ZYNLONTA plays as a monotherapy. Again, we're competing against combination-based therapies, so if you look at the ADC and monoclonal antibody combination therapies, they're around that 40% CR rate. What we showed in our safety run-in data for our LOTIS-5 study is a 50% CR rate. Again, we think we have a chance to really significantly grow the product from where it is today to where it can be through three main drivers. First is you increase the patient population. Whereas there's roughly 6,000+ third line plus patients, you add another 12,000 that's in the second line population.
In addition, we expect to have higher market share. If you go from suboptimal efficacy to much more competitive or differentiating efficacy, we should have higher market share. Finally, what we see with a single agent is roughly on average 3 cycles of therapy. In our combo studies, we're seeing on average 5-6 cycles. All these 3 will help to drive to significantly more revenue growth opportunity for ZYNLONTA. I'm gonna deep dive into LOTIS-5. This is our pivotal phase III study. As I said, we were approved via accelerated approval pathway for the single agent with a phase II trial. Our phase III confirmatory study is looking at ZYNLONTA plus rituximab versus R-GemOx. It's a 1-to-1 randomized study with 420 patients randomized, 90% power, and the primary endpoint is PFS.
Again, a number of key secondary endpoints, including overall survival, ORR, and CR, as well as, of course, safety will be an important consideration. This is a large study that we, as I mentioned, in the safety run-in demonstrated an 80% overall survival overall response rate and a 50% complete response rate. The median PFS in that overall in those 20 patients is about 8.3 months. The way this study is powered is hazard ratio of 0.67. For example, if R-GemOx does four months, the treatment would have to show six months or more median PFS. We feel quite comfortable with the way we've designed the study. This is the pivotal phase III study that's gonna read out in the second quarter of this year.
We expect to report top-line results with full results available by the end of this year. We completed enrollment of the study at the end of 2024, statistically, we need to reach about approximately 262 PFS events to read out the study. We expect to hit that this quarter so that we can read the study out in the second quarter. Just diving deeper into the opportunity around LOTIS-5. You know, despite today as a monotherapy having, I would say, suboptimal, indicated population and CR rate, we're still getting quite a bit of use. Why are we getting the use that we do today? You know, one is we work really quickly. When you get to third line plus DLBCL, our patients are progressing quickly.
They don't oftentimes have time to wait for a therapy to be available or for our therapy to work. The fact that you get to a CR really quickly is one of the reasons chemotherapy is still used to this day. It's one of the reasons physicians like ZYNLONTA. The median time to getting to a CR is the first disease assessment at six weeks. It works extremely quickly, and when you get to a CR, they tend to be very durable, as I mentioned before. That's an attribute that physicians really like about the product. Another thing they like about the product is it's safe and convenient, easy to do. If you look at all of our combination studies, they're fixed duration therapies, and typically once patients get to a CR, they're consolidating for a few more cycles.
As I said, we see, you know, a maximum of 8 number of cycles that we allow in our combination studies, but on average, patients are only getting 5-6. It's a short fixed duration therapy every three weeks, 30-minute infusion, so it's relatively easy to give. With our combination study with rituximab, we get to address, let's say, the two deficiencies we have today, plus keep the strengths that we have. We're now gonna be in a much broader population in second-line plus. Why is that important? When you get to the community, they're keeping most of their frontline patients and even the majority of their second-line patients before they start referring out heavily to academic institutions. When you get to the third-line plus setting, it just becomes less relevant.
The average community physician may be seeing a third-line patient once, twice, or three times a year. It's not a very relevant population when they're treating so many other types of cancer. When you get to second line, they're seeing those patients typically every month, it becomes a much more relevant conversation with the community physician. Similarly, our response rate, which has been less competitive at a 25% rate 'cause we're a monotherapy playing against combination therapies when we move into the realm of where we think we could be at or above where competitors are from a CR standpoint that has the chance to be competitive to highly differentiating, and we still maintain the rapid durable responses and the manageable safety and convenient dosing.
If you think of what does that mean from a revenue opportunity, today in the 6,000 patients we play with a roughly 10% share in three cycles, that translates to roughly $70 million. We finished last year with, you know, over $73 million of sales. If you look at LOTIS-5, you add an additional 12,000 patients in second line with even only a 5%-10% share and the five cycles that we are seeing with the LOTIS-5 study, that would translate to $200 million-$300 million of opportunity. Basically every five share points in second line is about $100 million. Every five share points in third line plus is $50 million. Now I'll turn to LOTIS-7, which is the combination of ZYNLONTA plus glofitamab.
We knew that this could be a very interesting opportunity 'cause as I mentioned, outside of CAR-T, only the bispecific products and ZYNLONTA have ever been approved as single agent drugs. We know they're highly potent. The question is, can we have additive or synergistic efficacy and can we demonstrate a favorable safety profile that allows these agents to combine? We knew that the mechanisms were complementary. We were combining a CD19-directed ADC with a CD20/CD3 T-cell engaging bispecific antibody. We're pleased that a lot of the hypothesis that we expected did come through, come true. The way we designed the study is first to do a dose escalation. We looked at multiple doses of ZYNLONTA, 90, 120 and our approved dose of 150 with the fully approved dose of glofitamab. We also looked at mosunetuzumab in the dose escalation.
There were no DLTs. We cleared all the doses and we went right into dose expansion. We focused again on second-line plus DLBCL with the combination of ZYNLONTA plus glofitamab, we looked at the two higher doses of ZYNLONTA with the full dose of glofitamab. Again, no issues. We saw safety. It was pretty similar, with actually better safety at the higher dose, which I'll explain why. We're continuing to expand at the full doses of both products, ZYNLONTA at 150, glofitamab at its approved dose, and we're currently enrolling up to approximately 100 patients, which we think will be sufficient to get into compendia. Now, if you look at the lower left, the way these drugs are dosed, obinutuzumab is in the label of glofitamab and is given a week before you do the step-up dosing of glofitamab.
That's typically where patients are hospitalized 'cause that's where the CRS or ICANS can occur. That was initially intended to be a debulking agent, but obviously glofitamab on its own when you look at the label has about a 70% CRS rate, mostly low-grade, but there are some small percentages of higher grade CRS and ICANS that can occur with the therapy. The goal was could we debulk the tumor further by giving ZYNLONTA? You give obinutuzumab day one, ZYNLONTA day two, you do the step-up dosing of glofitamab, and these are both every three-week therapies given subsequently on the same day to the patient. ZYNLONTA for up to eight cycles, glofitamab for up to 12 cycles. The goal there is can we improve the CRS profile both in terms of rates and grades versus glofitamab on its own.
We were pleased that with the safety data in our first 49 patients that we reported this last December, that if you look at the grade three or higher events, we know that the only known overlapping toxicities of these compounds is hematological toxicity. Particularly neutropenia is the highest grade three or higher adverse event that's seen across both agents. What we saw in this trial is about 33% grade three or higher neutropenia. Each of the products in the label has about 30% grade three or higher neutropenia on its own, so we didn't really see additive heme toxicity. When you look at the other toxicities, they're very similar, not only in terms of the type, but rates as either product alone.
We didn't see any new toxicities, nor did we see additional toxicities in terms of rates versus what you see with the monotherapies alone. There were two grade five events occurred in about 4.1%. You look at other bispecific trials, they, the grade five events range anywhere from 5%-13%, so this is reasonable. two patients, one was treatment-related per the investigator, one was not treatment-related. CRS, which as you remember for Glofit on its own has about 70% of the label. At the 150 dose, which is the dose that we're selecting of ZYNLONTA to move forward with this combination, we were able to drop to 25%, all of which was grade one and grade two at that dose. At the 120 dose, there was one grade three.
ICANS was about 4.1%, all low-grade again, grade one and two. We're able to see a quite a good safety profile with this combination. From an efficacy standpoint, 90% overall response rate, 78% complete response rate. We were able to see of those 38 patients that achieved a CR, 33 remained in CR at the time of the data cut off. All these patients had a minimum of six months follow-up. The longest patients were about two years out after follow-up. Now, while the majority of patients achieved a CR at the first disease assessment, 14 of those 38 patients who got a CR converted over time, mainly from from PRs.
Of the eight patients that were treated previously with a CAR-T therapy, six of those eight achieved a CR. Now, one thing that's interesting is if you look at the difference between relapse and primary refractory, because we started to get some questions around, well, the difference in efficacy between these two doses that we looked at, but also between these populations because we know if you're primary refractory, these are the toughest to treat patients. These are patients that are progressing on frontline therapy within six months. That's the definition. Everyone else is considered relapsed. The primary refractory are very tough to treat population. I'll just send you on the 150. If you look at the 150 where we had a 78% overall response rate...
I'm sorry, if you look at the relapsed refractory at the 150, you can see the complete response rate was 90% for the relapsed population and 67% for the primary refractory. Most trials don't break this out, but when you look at trials that have, this substantially is better both for relapsed and for the primary refractory population. We were really pleased to see this difference. If you look at the difference between the 150 and the 120, we saw slightly better efficacy in that primary refractory population. At the 150 dose, it was very similar, the CR rates between the relapsed population. Overall, when you look at the total population, 92% relapsed, 92% CR in the relapsed population, 64% in the primary refractory.
Again, even in the toughest to treat patients, primary refractory post-CAR T, we're seeing very strong CR rates that look so far to be quite durable. When you look at the swimmer's plot, the green are the CRs. You can see, although these are fixed-duration therapies, where patients are stopping the therapy, you know, again, with a maximum of eight cycles of ZYNLONTA, maximum of 12 cycles of glofitamab, on average, what patients were getting is six cycles of ZYNLONTA so far, what we've seen. You're seeing that the majority of these CRs are remaining in CR as of the data cutoff. 33 of the 38 patients remained in CR. Two patients progressed. Two patients, as I remember, had grade five events, and one was censored because they had a solid tumor and had to be treated for that.
Although they were still in the CR, that patient had to be censored. Overall, we see so far with this follow-up really good data. We're encouraged by the durability that we're seeing so far. The next step is to have all 100 patients enrolled and reported out with data with a minimum of six months follow-up by the end of this year, where we think we'll have a really good sense of both the efficacy, the durability of that efficacy, and the safety profile of this combination. At which point, we'd publish and also then send for consideration to compendia inclusion early next year. Turning to marginal zone lymphoma. This is a Phase II- IIT. Marginal zone lymphoma is an area where there's still high unmet need.
There's about 3,000-4,000 patients that have relapsed refractory marginal zone lymphoma with very few treatment options. The BTK inhibitors are really the mainstay here. There's only outside of CAR-T, which was recently approved in that third-line plus setting, the majority of patients are getting, again, a BTK inhibitor. There's two products outside of CAR-T that have been approved, two others that are in guidelines. These are all based on relatively small sample sizes, though, of anywhere from 36-68 patients when you look at the patients that are in these studies. They're generally pretty small studies. You don't see large randomized studies in MCL, given the small patient population. Again, outside of CAR-T, you see the highest CR rate is only about 29%.
With ZYNLONTA single agent, what we showed, through this IIT study, back in ICML in June, this data was presented. When you look at the first 26 efficacy-evaluable patients, the CR rate was 69%, so really substantially better than what we see with other therapies. Again, a fixed-duration therapy where patients on average are getting about 5-6 cycles. The safety profile was consistent with our known profile of ZYNLONTA. The goal is to complete the trial with 50 patients, then we're gonna be assessing regulatory pathways for this, especially given the how good this efficacy data is and the fact that there may be novel ways to get towards regulatory approval, but also a compendia pathway that we plan to submit once we have the 50-patient data published.
With the combination of ZYNLONTA rituximab, the same combination that we're using in LOTIS-5, we're also studying in relapsed refractory follicular lymphoma. This is a phase II- IIT that's currently ongoing from the University of Miami, and again, data has been outstanding. Follicular, unlike MCL, has a lot more options. There are a lot of phase III studies and multiple CAR-T bispecifics and targeted therapy options available. Nonetheless, the data we've seen so far has been really outstanding. We're only studying this in the high-risk FL patients, and so far, the initial data in the first 55 efficacy-evaluable patients has showed an 84% complete response rate with a manageable safety profile that's consistent with the known label of ZYNLONTA. Again, we think this combination data is really compelling.
We're also in the process of assessing both regulatory and compendia strategies for this combination in follicular lymphoma. When you take a step back and say, "Well, what's the opportunity we have across this molecule?" We start with where we play today, which is roughly a $70 million opportunity that we've been stable at, which is in the third-line plus monotherapy. I showed with you that with even only 5%-10% share in the second line and maintaining our existing share in third line, you could take the ZYNLONTA plus rituximab combination to $200 million-$300 million. If you add on the glofitamab combination, again with regulatory approval and compendia, this could grow the total opportunity to $500 million-$800 million.
The indolent lymphoma opportunities can add another $100 million-$200 million, and that's where we think the peak opportunity across all these different indications can be $600 million-$1 billion. We think the potential is significant, and the key data unlocking event is really gonna be the LOTIS-5 readout that's gonna happen in the second quarter of this year. That's really the key next expected milestone. We're gonna enroll for LOTIS-7 all 100 patients in the first half of this year. We expect to be able to have data by the end of this year, and we're also in parallel assessing different regulatory pathways for potential phase III as well as compendia strategies for that LOTIS-7, which we expect could happen in the first half of next year, inclusion into compendia.
For LOTIS-5, we expect to share top-line results in the second quarter of this year, full results by the end of the year. In parallel, we'll be following the sBLA, and we expect that we could have approval by mid-next year. For the indolent lymphoma data, we're continuing to progress those studies forward with our independent investigators, and as they finish those studies, we expect that the data will be published and potentially into compendia anytime between the end of this year and the first half of next year. We have a number of expected milestones coming right now for this molecule. With that, I wanna thank you very much. Appreciate it.