Tshank you for standing by and welcome to the Zepzelca ASCO Data Webcast. At this time, all participants are in listen-only mode. After the speaker's presentation, there will be a question-and-answer session. To ask a question during the session, you'll need to press star one one on your telephone. If your question has been answered and you'd like to remove yourself from the queue, simply press star one one again. As a reminder, today's program is being recorded. Now I'd like to introduce your host for today's program, Jeff Macdonald, Executive Director of Investor Relations. Please go ahead, sir.
Thank you, Operator, and good afternoon, everyone. We are excited to have the opportunity to review the compelling clinical data presented at last week's ASCO annual meeting evaluating the use of Zepzelca in first-line maintenance treatment for small cell lung cancer. We'll also discuss our commercialization plans for this potential new indication. The slide presentation accompanying this webcast is available in the investors' section of our website. This call will feature commentary from Jazz Management, including Renee Gala, President and Chief Operating Officer; Dr. Rob Iannone, Executive Vice President, Global Head of Research and Development and Chief Medical Officer; and Sam Pearce, Executive Vice President, Chief Commercial Officer. We are also incredibly pleased that Dr. Stephen Liu, Associate Professor of Medicine at Georgetown University and the Director of Thoracic Oncology and Head of Developmental Therapeutics at the Georgetown Lombardi Comprehensive Cancer Center, is participating in today's call.
On slide two, I'd like to remind you that today's webcast includes forward-looking statements which involve risks and uncertainties that could cause actual events, performance, and results to differ materially. We encourage you to review the statements contained in our slide deck and the risks and uncertainties described in our SEC filings, which identify certain factors that may cause the company's actual events, performance, and results to differ materially from those contained in the forward-looking statements made on today's webcast. We undertake no duty or obligation to update our forward-looking statements. I'll now turn the call over to Renee.
Thanks, and welcome to those of you joining us today. I'll begin on slide three in our agenda for today's call. I'll start by providing a brief overview of the evolution of the Jazz Oncology portfolio, after which we have the privilege of being joined by leading small cell lung cancer expert, Dr. Stephen Liu, who will walk us through the current clinical practice for treating small cell lung cancer and review the exciting Zepzelca data presented in an oral presentation last week at ASCO. Dr. Rob Iannone, Global Head of Research and Development, will recap our plans to have these data potentially incorporated into NCCN guidelines and product labeling. Our Chief Commercial Officer, Sam Pearce, will discuss our commercial strategy for Zepzelca in light of these new data, which we view as practice-changing.
Zepzelca is currently indicated in second-line treatment of small cell lung cancer, and we're excited about the opportunity to bring a new treatment regimen to first-line small cell patients that has demonstrated a clinically meaningful improvement compared to the current standard of care. We'll then conclude with a Q&A session. Moving to slide five, we have spent the past several years diversifying our product mix across both neuroscience and oncology, and we're very excited about the direction of our commercial oncology portfolio. Currently, our oncology business is driven primarily by Zepzelca and Rylaze, with legacy products such as Defitelio and Vyxeos remaining important options for patients that also contribute to our top line. Late last year, we secured approval for Ziihera or Zanidatamab, and believe future development and new indications represent a $2 billion-plus opportunity.
Turning to slide six, I'm incredibly proud of the accomplishments that have advanced both our commercial and R&D capabilities in oncology. Our early investments in this area, such as bringing in Erwinaze, Vyxeos, and Defitelio, provided a platform for us to build out our medical and field-based teams as well as our in-house R&D capabilities. These early initiatives paved the way for us to significantly accelerate our presence in oncology over the past several years. Since 2020, we've successfully launched three oncology products, Ziihera, Rylaze, and Zepzelca, which generated combined revenue of more than $730 million in 2024. In total, our oncology therapeutic area generated over $1 billion in revenue last year, with meaningful growth potential.
Building on that momentum, our strategic investments in R&D should position us to expand the use of Ziihera and Zepzelca to additional patient populations that are in need of new treatment options. We also recently completed the acquisition of Chimerix, which added dordaviprone to our late-stage pipeline. With a PDUFA date of August 18th, we have the potential to deliver another important therapy to patients within this calendar year. In addition, while not shown on this slide, we are advancing a number of promising earlier-stage programs in our oncology pipeline as well. We view oncology as a vital component of Jazz's future, and we were pleased to present a number of data sets at this year's ASCO annual meeting that highlighted our progress across multiple clinical programs.
This included data from the phase III IMforte trial, which we believe will establish Zepzelca as a foundational treatment in the first-line maintenance setting for small cell lung cancer. Turning to slide eight, it is my pleasure to introduce today's expert speaker, Dr. Stephen Liu. Dr. Liu serves as an investigator on the IMforte trial and is an author on both the data presented at ASCO and the concurrent publication in The Lancet. Dr. Liu currently serves as the Director of Thoracic Oncology and Head of Developmental Therapeutics at the Georgetown Lombardi Comprehensive Cancer Center. He is a board-certified medical oncologist with a busy clinical practice in Washington, D.C. He leads the drug development program at Georgetown University and oversees thoracic oncology research at the Cancer Center. In addition to leading national and global clinical trials for the treatment of lung cancer, Dr.
Liu is also the co-host for the official International Association for the Study of Lung Cancer, or IASLC, podcast, Lung Cancer Considered. Dr. Liu?
Thanks, Renee. We'll start at slide nine. These data were shared as an oral presentation at the 2025 ASCO annual meeting. Lurbinectedin plus atezolizumab as first-line maintenance treatment in patients with extensive-stage small cell lung cancer are the primary results of the phase III IMforte trial. On slide 10, the key takeaway points: IMforte demonstrated a statistically significant and clinically meaningful improvement in both progression-free survival and overall survival with first-line maintenance therapy with lurbinectedin plus atezolizumab. Lurbinectedin plus atezolizumab was generally well tolerated, with no new or unexpected safety signals. This combination of lurbinectedin and atezolizumab maintenance has the potential to become the new standard of care in extensive-stage small cell lung cancer. On slide 11, our current standard of care for the treatment of extensive-stage small cell lung cancer is the combination of platinum-based chemotherapy and immunotherapy.
The addition of an immune checkpoint inhibitor, like the PD-L1 inhibitor atezolizumab, to front-line chemotherapy has improved survival for patients with small cell lung cancer and redefined the standard of care. Immunotherapy offers the potential for long-term survival, something we cannot achieve with chemotherapy alone. Unfortunately, this benefit is limited to a subset of patients, and most patients do experience disease progression. Despite the availability of several agents in the second-line setting, there is an extremely high rate of attrition in small cell lung cancer. Up to 60% of patients never receive any second-line therapy despite several agents being available. This is simply because the act of progression itself can render patients unable or unfit to receive any further therapy. In some cases, the act of progression is a fatal one.
With these high attrition rates, a maintenance approach is appealing, delivering active therapy before progression instead of waiting until progression has occurred, a proactive approach instead of reactive. There has never been a positive maintenance study for small cell lung cancer until this trial. Lurbinectedin is a transcription inhibitor that is approved in the U.S. and other countries for the treatment of small cell lung cancer after progression. In preclinical studies, lurbinectedin shows synergy with immunotherapy, and the combination has been well tolerated in the clinic. The global open-label randomized phase III IMforte study investigated the efficacy and safety of lurbinectedin plus atezolizumab versus standard atezolizumab alone for the maintenance treatment of extensive-stage small cell lung cancer in patients whose disease had not progressed after induction treatment with standard atezolizumab plus chemotherapy. Slide 12 shows the IMforte study design.
This trial included patients with no prior treatment for extensive-stage small cell lung cancer and no brain metastases. Eligible patients were treated with standard atezolizumab plus carboplatin and etoposide for four cycles. There was then a second screening event, and the patients who had no evidence of progression and an adequate performance status were then randomized to receive standard atezolizumab maintenance therapy or the combination of atezolizumab plus lurbinectedin at a dose of 3.2 milligrams per meter squared with primary prophylaxis using G-CSF. The primary endpoints were investigator-assessed progression-free survival and overall survival. Slide 13 shows the statistical analysis plan. One interim analysis and one final analysis were planned for overall survival. If the survival results were statistically significant at the interim analysis, they would constitute the primary analysis. On slide 14, we see the baseline characteristics. 483 patients were randomized into the maintenance phase.
Patient characteristics were well balanced, though there were slightly more patients under the age of 65 in the combination arm. As expected, most patients achieved a response to induction therapy. Only about 10%-12% of patients achieved stable disease. The median time from the start of induction to the time of randomization at maintenance was 3.2 months. On slide 15, we see the addition of lurbinectedin to standard atezolizumab maintenance significantly improved progression-free survival. Median PFS improved from 2.1 months with atezolizumab to 5.4 months with the combination of lurbinectedin and atezolizumab for a PFS stratified hazard ratio of 0.54. Recall, these median values do not include the 3.2 months from the time of induction. The six-month PFS rate improved from 18.7% to 41.2%.
On slide 16, we see a forest plot showing the PFS benefit with lurbinectedin plus atezolizumab was seen in all meaningful subsets, including age, sex, smoking history, and the presence of liver metastases at baseline. On slide 17, importantly, the addition of lurbinectedin to atezolizumab led to a meaningful improvement in overall survival. The median survival from the start of maintenance therapy was 10.6 months with atezolizumab, 13.2 months with lurbinectedin plus atezolizumab for an overall survival hazard ratio of 0.73. There was an improvement in the one-year survival rate from 44.1% to 56.3%. As slide 18 illustrates, when evaluating these median numbers, recall, they are measured from the start of maintenance therapy and do not include the median of 3.2 months from the start of induction treatment. Slide 19 shows subsets, and as seen with progression-free survival, the overall survival benefit extended to all meaningful subgroups of patients.
Slide 20 shows details of response rate. This measures response after randomization and maintenance, as most patients had already achieved a response during induction. From the start of maintenance therapy, 10.4% of patients went on to achieve a further objective response with atezolizumab. 19.4% achieved a response with lurbinectedin plus atezolizumab. The median duration of response was 5.6 months with atezolizumab, 9.0 months with lurbinectedin plus atezolizumab. Slide 21 details the follow-up systemic anti-cancer treatments. While the study did not have formal crossover, note that 22 patients in the atezolizumab arm, or 9.1%, did receive subsequent lurbinectedin therapy. Also note that in the control arm with atezolizumab, only 54.8% of patients who discontinued therapy received further systemic treatment. This rate of attrition is consistent with historical data over the years.
When we promise patients they will receive the most active drug at the first signs of progression, about half the time we simply cannot keep that promise. Slide 22 is a safety summary. It's important to consider toxicity. Here, we're adding an active agent that improves progression-free survival and improves overall survival, but clearly we expect to see more toxicity. That is what we see if we look, for example, at the rate of grade 3- 4 treatment-related adverse events. It's higher with the combination of lurbinectedin and atezolizumab at 25.6% compared to 5.8% with atezolizumab alone. Many of these toxicities are paper toxicities or laboratory abnormalities. If we look at the rate of discontinuation of any study drug due to adverse event, it is only 6.2% with lurbinectedin plus atezolizumab compared to 3.3% with atezolizumab alone. Stopping treatment due to toxicity was very uncommon in this study.
Slide 23 is a tornado plot outlining the adverse events in the study: nausea, fatigue, decreased appetite. These are more common with the combination, but almost exclusively low-grade. Most of the grade 3 or higher adverse events were laboratory abnormalities and reflect myelosuppression seen with lurbinectedin. While 10.7% of patients experienced neutropenia, for example, the rate of febrile neutropenia was only 1.7%. On slide 24, in conclusion, the phase III IMforte trial demonstrated that the addition of lurbinectedin to maintenance atezolizumab in patients with extensive-stage small cell lung cancer improved progression-free survival with a hazard ratio of 0.54, and importantly, improved overall survival with a hazard ratio of 0.73. The benefit was consistent across the majority of subgroups. The safety profile was manageable with mostly low-grade adverse events and low treatment discontinuation rates reflecting a favorable tolerability profile and no increase in immune-related adverse events.
IMforte is the first phase III study to show PFS and OS improvement with first-line maintenance treatment for extensive-stage small cell lung cancer, highlighting the potential of lurbinectedin and atezolizumab to become a new standard of care for first-line maintenance therapy in patients with this aggressive and difficult-to-treat disease. Thank you for your attention. I'll now turn the call over to Rob.
Thank you, Dr. Liu. That was an excellent overview of the current small cell lung cancer patient experience and the IMforte data, which we believe will set a new standard in treating extensive-stage small cell lung cancer patients in the first-line maintenance setting. Turning to slide 26, on behalf of all of my colleagues at Jazz, I'd like to start by thanking the IMforte investigators, site coordinators, and other professionals involved in the trial. Their dedication, time, and expertise made this clinical trial and the advance it represents possible. We'd also like to recognize our partner, Roche, with whom we collaborated on the design and execution of this trial. Most importantly, we extend our deepest appreciation to all of the people with small cell lung cancer and their families who participated in this and other Zepzelca studies.
Facing a difficult disease, they made the brave choice to help contribute to finding better therapies. Since its approval in June 2020, our team has endeavored to communicate to the medical community about the clinical profile and benefits of Zepzelca treatment. Based on its efficacy, safety, and tolerability, Zepzelca has been rapidly adopted for the treatment of second-line small cell lung cancer. We felt there was more that Zepzelca could do to improve patients' lives in a disease area that has a very challenging prognosis. Looking at the current treatment landscape in the first-line treatment of small cell lung cancer, it was clear to us that there was a need for better therapies. The standard platinum plus etoposide chemotherapy is typically given for four to at most six cycles due to tolerability issues. Patients generally experience a good response to induction chemotherapy but rapidly progress thereafter.
We hypothesized that patients would benefit from the addition of Zepzelca to the post-induction maintenance therapy phase, given its favorable tolerability profile, in order to delay the expected rapid disease progression at this stage of treatment. Also, based on preclinical data, Zepzelca's mechanism of action could be synergistic with IO therapy, leading us to initiate a program exploring the use of Zepzelca as switch maintenance therapy in first-line for patients with extensive-stage small cell lung cancer who had not progressed after induction chemotherapy. As Dr. Liu just outlined, the IMforte trial was successful in validating this hypothesis, with positive results showing that adding Zepzelca to the current standard of IO maintenance therapy in first-line extensive-stage small cell lung cancer results in clinically meaningful improvements in patients. In the maintenance setting, median PFS for the Zepzelca plus atezolizumab combination was 5.4 months compared to 2.1 months for atezolizumab alone.
The combination of Zepzelca plus atezolizumab reduced the risk of disease progression or death from the time of randomization by 46% compared to atezolizumab alone. We also observed improvement in overall survival with a median OS for Zepzelca plus atezolizumab of 13.2 months compared to 10.6 months, reducing the risk of death by 27% compared to the atezo only arm of the trial. Please note that these estimates are from the time of randomization, such that this cohort of patients would have a median survival between 16 and 17 months from the time of initiating induction chemotherapy. The Zepzelca plus atezolizumab combination as maintenance therapy was generally well tolerated with no new safety signals identified. Neutropenia was manageable with routine prophylaxis, and the discontinuation rate was low, approximately 6% and 3% in the experimental and control arms, respectively.
Moving to slide 27, we believe these data are practice-changing, offering physicians an opportunity to improve patient care by incorporating Zepzelca as maintenance therapy for patients with extensive-stage small cell lung cancer who have not progressed after front-line induction chemotherapy. Small cell lung cancer treaters in both academic and community oncology centers are already familiar with Zepzelca. Given the results we observed in the IMforte trial, we believe adoption of this new first-line regimen should occur quickly, given the clear improvements in both PFS and OS over the current standard of care. Incorporating Zepzelca into the first-line regimen is relatively simple. It does not impact the current atezolizumab administration schedule, and Zepzelca was well tolerated in this regimen with manageable AEs similar to what can be experienced in second-line.
Dose and frequency will be the same, and Zepzelca would be given until progression or unacceptable toxicity in first-line, just like second-line. We have submitted these data to NCCN for consideration. NCCN can discuss guideline updates via off-cycle reviews, and we are hopeful that they will be able to evaluate our submission in the near future. Inclusion in NCCN guidelines is generally a path for broader uptake and reimbursement. We are also pursuing inclusion of the IMforte data in the Zepzelca label with an expanded indication for first-line maintenance therapy in combination with atezolizumab. Our sNDA submission has been accepted by the FDA and assigned priority review with a PDUFA date of October 7th, 2025. I'll now turn the call over to Sam for a discussion of our commercialization plan.
Thanks, Rob. I'll start on slide 29. Here you'll see a schematic representing the commercial opportunity for Zepzelca as we potentially move into the first-line maintenance setting for extensive-stage small cell lung cancer. First off, I'll start with the breakdown of patient presentation. There are approximately 30,000 patients diagnosed with small cell lung cancer each year in the U.S. Of the 30,000 diagnosed small cell lung cancer patients, initial testing will determine if a patient has limited-stage or extensive-stage disease, with about 70% being extensive-stage. Around 90%-95% of patients elect to receive first-line treatment. Whilst not curative, there is a high response rate to chemo or chemo plus IO treatment. Now, there are differing treatment regimens for limited-stage and extensive-stage disease. I’ll reiterate what we’ve previously noted. The IMforte trial evaluated Zepzelca in extensive-stage patients, with limited-stage patients receiving a different regimen.
When we zoom in on the extensive-stage patients, approximately three-quarters are treated with chemotherapy plus immunotherapy in the induction phase, which is typically four rounds of treatment. These patients are then evaluated following induction, and if there is no disease progression, they're eligible for maintenance therapy with IO treatment. The majority of these patients are eligible and do move into the maintenance setting. In the IMforte trial, of the 660 patients who received chemotherapy plus atezolizumab as induction therapy, 483 or 73% were eligible for maintenance therapy and were randomized to either the active or control arm of the trial. As we think through the numbers of patients that we believe we can reach in first-line with Zepzelca, that's the general framework. We're very excited about the opportunity to help improve patient outcomes in small cell lung cancer.
Moving from second-line treatment to first-line maintenance therapy should increase the number of patients eligible to be treated with Zepzelca and increase the duration of therapy. For reference, in the IMforte trial, we observed a median PFS of 5.4 months in the first-line maintenance, and that compares to 3.5 months in the second-line small cell lung cancer trial that supported conditional approval of Zepzelca. I'll also call out that patients who do not receive Zepzelca in the first-line, whether that be because they have an initial diagnosis of limited-stage disease, they've progressed prior to going into maintenance stage, or they and their physicians elect not to incorporate Zepzelca in their treatment regimen, these patients will be eligible for Zepzelca therapy in later lines of treatment.
I'll also remind you that we would not expect patients to be rechallenged with Zepzelca once they have received it in a prior line of therapy. Moving to slide 30, small cell lung cancer patients are in need of more effective treatment options, and the IMforte data clearly demonstrates an improved survival benefit to extensive-stage patients in the first-line maintenance setting. We'll be able to provide promotional support once we have an approved indication for this setting. Given the positive experience with Zepzelca in second-line and these new compelling data, we believe that oncologists will be quite willing to adopt a data treatment regimen using Zepzelca in the first-line setting, which has been shown to improve survival outcomes.
While our goal is to establish Zepzelca as a standard of care in first-line maintenance in combination with atezolizumab, we will not lose sight of the opportunity for Zepzelca to continue to play an important role in later lines of therapy. We already have the right team and capabilities in place to deliver a successful launch of Zepzelca in this new indication, and we're positioned to initiate key launch activities immediately upon receiving FDA approval. With that, I'd like to now turn the call to our operator to begin the Q&A session.
Certainly. Ladies and gentlemen, we'd like to ask you, please limit yourselves to one question each, as we have a very full queue today. Our first question comes from the line of Jess Fye from JP Morgan. Your question, please.
Hey, guys. Good afternoon. Thanks for taking the question. Just a timing question as we think about the overall Zepzelca franchise and the outlook here. With the Imdelltra second-line data, also at ASCO, it seems like that product could continue to pressure Zepzelca second-line sales in the near term. Is it possible we could see a scenario where the franchise first shrinks due to second-line competition before it sort of grows and kind of finds a new level higher than it's been thus far as a result of this front-line maintenance opportunity being bigger than the second-line opportunity ever was? Thank you.
Yeah. Thanks, Jess, for the question. We will not give specific product guidance, but I will ask Sam if she can give you a feel for what we are expecting from a commercial perspective.
Yes. Thanks, Renee. Hi, Jess. Thanks for the question. Yes, I mean, Imdelltra had obviously data also presented at ASCO, and we believe that there's a place for both products. I think the answer to your question depends a little bit on how quickly we can secure NCCN guidelines. We do believe, given the strength of the data that you've heard about already, that we should see quite rapid adoption of Zepzelca into the first-line setting. Of course, those patients that receive Zepzelca in the first-line setting, it's good that they have another very valuable efficacious option in that second-line setting following the use of Zepzelca. We are optimistic that we should see Zepzelca continue to grow into that first-line setting in the coming months.
Thank you. Our next question comes from the line of Ami Fadia from Needham. Your question, please.
Hi. Good afternoon. Thanks for taking my question. This is a question for Dr. Stephen Liu. Can you talk about the sort of development of Imdelltra plus durva, for which trials are ongoing in both first-line and first-line maintenance, and how that could potentially impact how you think about treatment in the first-line maintenance setting with Zepzelca plus atezolizumab? Also, maybe just talking about the second-line, how do you think about the adverse event profile of the combination impacting your decision on which patients will get that treatment in first-line maintenance? Thank you.
Yeah, thanks. It's hard to comment on data that's not out there yet. While there are a lot of strategies that are in development, we need to see the data. I think it depends on the specific patients included and what it looks like. I think there's space for all active drugs in small cell lung cancer. When I look at the data from IMforte, on paper, what I would expect from this would be, before the study started, you're adding an active drug, you're implementing it earlier. It's a very logical approach, one we've tried many times in small cell. What you expect is an improvement in progression-free survival, a deepening in some response rate, and more toxicity. The big question is, does that translate to people living longer? Up until now, it hasn't.
Clearly, the OS benefit we see in IMforte makes this something we can't ignore, and we have to implement. The toxicity numbers, if we look at the rate of grade 3 for adverse events, they are there. You see more adverse events clearly with lurbinectedin. It's mostly, though, myelosuppression, heme toxicity. The discontinuation rates today, I thought, were strikingly low. 6% stopping treatment due to adverse event. That's a very small number. I think it means that we're able to deliver this drug safely with a primary prophylaxis regimen, and we keep people out of trouble. The rate of febrile neutropenia is less than 2%. I think that this is a tox profile that we've become more comfortable with. They are largely paper toxicities. In the same session, we did see Delphi data presented with tarlatamab superior to chemotherapy. That was largely versus topotecan.
It was about 50% of patients who were chemorefractory. Where topotecan is not really an active drug, actually. I think it is refreshing to see that second-line data. That is in the second-line setting, not in the maintenance setting. How will this drug perform in the maintenance setting when we have a little bit more disease? It remains to be seen. It is a very different toxicity profile, and I think there are barriers to delivering T-cell engagers. We are still working out the delivery, but it is simply not available to everyone who might benefit as of now, just because of the infrastructure required to deliver this safely, to monitor for CRS and ICANS. I think that it is good to have many drugs available. The IMforte approach really is a maintenance one.
If patients do progress, do relapse, then I think reaching for an active second-line drug like tarlatamab makes a lot of sense. I think that my sequence for most patients will be to receive all of these drugs. That's at least my hope.
Thank you. Our next question comes from the line of Marc Goodman from Leerink Partners. Your question, please.
Hi. Good afternoon. This is Basma on the line for Marc. Thank you for taking our question. You mentioned that 37,000 new cases of SCLC are reported in the U.S. each year. Should we assume that the proportion of patients who are eligible for the maintenance therapy with the combination of Tecentriq and Zepzelca will be 70% in line with the data from IMforte, or is it something different? Also, regarding the long-term outcomes for the efficacy and safety, are you planning to track the patients longer with this maintenance therapy? That's it for us. Thank you.
Yeah. Thanks for the question. Maybe I'll ask Rob to comment on, in particular, the second part of your question.
Yeah. The epidemiology that we tend to quote is about 30,000 new diagnoses of small cell lung cancer, not all of whom get treated, but a great majority, about 27,000, and then extensive-stage being about 70,000. As you noted in the clinical trial, not everyone made it through the induction period to then be randomized to receive Zepzelca with atezo versus atezolizumab alone. I would caution about extrapolating the dropout in the clinical trial to the real world. I mean, there certainly were reasons for dropout that might not apply in the real world. Now we have data showing, as Dr. Liu very clearly laid out, showing the compelling case to use Zepzelca as front-line maintenance. I think that may not be quite as big a dropout in the real-world setting.
Thank you. Our next question comes from the line of Annabel Samimy from Stifel. Your question, please.
Hi. Just thanks for taking the question. This is actually for Dr. Liu. I guess just going back to the question about durvalumab and the extensive-stage first-line setting, I know they're looking at the maintenance setting. If there's a patient who had received durvalumab as part of their induction regimen, would you feel comfortable using Zepzelca as part of maintenance as well, or are they interchangeable, or is there something very specific to atezo that can only be used with Zepzelca? Maybe you can just sort of help us understand how you might see the interchangeability of the IO treatments.
Yeah. I'll acknowledge that there's not data in this setting, that the high level of data from the phase III trial is with atezo after atezo induction. I think scientifically, the drugs are pretty interchangeable. I think scientifically, they're very similar. They're more similar than different. I would not expect any differences there. I suspect clinical use, if I sort of look to my clinic, it would really depend on reimbursement and how strict payers would be with labels. If, for example, someone were receiving Durva in the front-line setting and I felt they were a good candidate for lurbinectedin, the options would be to switch to atezo and then give lurbinectedin with it or to add lurbinectedin to durva. I think scientifically, I wouldn't expect any difference between them.
I think that to avoid any possible problems with reimbursement, I probably would switch to atezolizumab and then continue and then add lurbinectedin to that. I think going forward, if my plan was maintenance from the beginning, that might influence the choice upfront since both drugs are approved, since both drugs have very similar numbers, overlapping Kaplan-Meier curves, since the schedules for both are there. In addition, now that I can give Atezolizumab as a subcutaneous injection, that's sort of even more reason to switch. I suspect it would shift me more towards Atezo in the front-line setting. Scientifically, I can't think of a reason why I would see different outcomes with one PD-L1 inhibitor versus another.
Thank you. Our next question comes from the line of Troy Langford from TD Cowen. Your question, please.
Hi. Thanks for taking our question and congrats on the data. Maybe just one for the company. Can you also provide a little bit of additional color around if you think you could expand the commercial sales team at any point in the future in order to support the first-line indication? If so, can you just talk a little bit about what the cadence of that might look like?
Yeah. Thanks for the question. I'll turn over to Sam in just a second. I would say with respect to having entered the solid tumor space with Zepzelca a few years ago, it allowed us to establish a footprint to support this product, which we've now also expanded to be able to support our initial launch with Zani. Sam, do you want to comment further?
Yeah. I think we're pretty well scaled for this opportunity. As Renee said, we've been established in this market for some time, good relationships with those customers. There are no immediate plans to increase the size of that team further. Of course, that is something that we will continue to evaluate to ensure that we've optimized the full opportunity.
Thank you. Our next question comes from the line of Andrea Flynn from Goldman Sachs. Your question, please.
Hi, everyone. This is Moniart for Andrea. Congrats on the news today, and thanks for taking our question. Just one more on the competitive dynamics. Would you anticipate any headwinds to Zepzelca's uptake in the front-line setting, assuming the approval, just given the availability of insulin being the limited stage setting? Is there any reason to think the same challenges that were observed in the second line with the delayed disease progression might impact the extensive stage setting? Thank you.
Yeah. I'll jump in there, and then I'll ask Rob to also comment further. Yeah, what we have been seeing in the first quarter was twofold. We did see some impact from tarlatamab, but also a slowing in progression of patients from the first line into the second line. I do think as we look forward, it's important to step back and appreciate that we have both a first-line opportunity in extensive stage, but also for patients that progress into the second line that have not received Zepzelca before, we still have the opportunity to treat those. Rob, any other comments you want to make?
Yeah. Just reinforce that these are, in fact, different subsets of patients. We do not expect the Adriatic results to impact uptake of Zepzelca in the front-line maintenance setting as it was studied in the extensive-stage population. I will point out, though, that once patients with limited-stage disease progress, they are eligible for second-line therapy. To Dr. Liu's point earlier, one thing that IMforte has taught us is that being proactive rather than reactive can be very important for this aggressive disease. For those patients with limited stage, remember we said it is about 7 to 3, 7 extensive stage, 3 limited stage. For those patients with limited stage who have not gotten Zepzelca at the earliest signs of progression on their standard therapy, they would have Zepzelca available to them. The same principles apply.
Thank you. Our next question comes from the line of Ash Verma from UBS. Your question, please.
Yeah. Great. Thanks for bringing that question and congrats on the progress here. Maybe just one question for the Q&L. Just looking at the slides of the team here, wanted to understand how you interpret this landmark PFS Kaplan-Meier curve. Seems like the hazard ratio at the median is pretty impressive at 0.54. We're seeing clear separation of the curves early on. By a 12-month time period, the PFS curves start to get pretty close between the drug arm and the control arm. If you can talk about what could potentially be driving that, that'd be great. Thanks.
Yeah. When we think of the different types of benefit we see, there's certainly a cytotoxic benefit, which might be a bit more transient. And then there's the long-lasting immune benefit. I think a drug like lurbinectedin has the potential to contribute to both. It'll be important to follow this up long-term. When we think of atezo alone, we think of a 5-6 year survival rate around 11%-12%. Will that tail be elevated by the addition of lurbinectedin, which could interact with tumor-associated macrophages? I think that's certainly our hope. There's also the possibility that the benefit we'll see will be more transient in terms of progression-free survival. Importantly, that does translate to people living longer. The treatment may not be curative, and it may be delaying progression rather than outright stopping it.
That's what most of our agents do, is they delay them. I think there's still value there. We'll need to continue to follow these as they mature. If you look at the numbers, when you get out past that far, they are a bit lower. We'll want to continue to follow this, let this mature a little bit, get past some of the censoring. You're right. The curves start to come a little closer as time goes on for PFS, not for OS. Those OS curves do not kiss. They do not cross. They remain separate. I think that's the real value of this early treatment.
I'd like to add to that, if possible. Thank you, Dr. Liu, for your answer. I do think it will be important to follow the OS curves. Hopefully, it will have a lasting impact on OS. I do want to point out that, again, being proactive in this setting rather than reactive is really very important. The fundamental hypothesis we had was that at the end of standard induction platinum etoposide induction chemotherapy, many patients were deriving some benefit but had active residual disease and are only stopping their chemotherapy because they cannot tolerate longer-term platinum therapy. That is the point to intervene. We are able to do that with a very well-tolerated drug that can be given in a sustained fashion through the time of progression in Zepzelca.
Being proactive, certainly, we think creates an improvement for these patients during that period of time and may potentially make subsequent therapies more available.
Thank you. Our next question comes from the line of Joon Lee from Truist Securities. Your question, please.
Hey, thanks for the updates and for taking our question. As you continue to invest in Zepzelca, what's your strategy for extending patent exclusivity? What's the latest on the Zepzelca patent lawsuit with the ANDA filers? Thank you.
Yeah. Thanks for the question. While we do not typically go into details on our strategy, the way I'd frame this is we do have ODE through June 2027 and composition of matter patent that extends through December 2029. It's important to note we have additional patent applications that could extend our IP as far as 2040. That's something that we will have to wait to see how that plays out. With respect to our ANDA filers, we have filed suit against all five of the ANDA filers. We're currently in the 30-month stay, and that runs through December 15th of 2027.
Thank you. Our next question comes from the line of David Amsellem from Piper Sandler. Your question, please.
Hey, thanks. In terms of looking beyond the current indication and the eventual approval in first-line maintenance, can you talk to potential development beyond that, both in small cell lung and potentially other solid tumor malignancies? I know there's a lot of investigator-sponsored studies that show up in clinicaltrials.gov, as one would expect for a novel agent. Maybe talk to how you're thinking about trying to expand the footprint beyond small cell lung. Thanks.
Rob, you want to jump in there?
Yeah. I'm happy to. It's probably premature for us to lay out any additional development plans as we are still thinking through that. As you point out, these results are highly encouraging, reinforce the activity, the high level of activity that Zepzelca has, and the potential significant benefit, again, here, an overall survival advantage when Zepzelca is used sort of in the optimal way. We certainly are actively thinking through other ways to improve outcomes. As Dr. Liu has said multiple times, small cell lung cancer has such a dismal prognosis that finding a way to ensure all active agents are used in all patients is an important priority. We are looking at different combinations, whether that be in the front line or in subsequent lines of therapy. We are now looking at other ways to improve small cell lung cancer.
Thank you. Our next question comes from the line of Mohit Bansal from Wells Fargo. Your question, please.
Great. Thank you very much for my question, taking the question, and thanks for hosting this. My question is for Dr. Liu as well. Dr. Liu, I mean, there is a lot of chatter about Zepzelca versus DLL3. As I understand and speaking with your colleagues, it seems like the convenience of using this drug is probably more important given these patients are treated at community centers. In that context, how do you think about Zepzelca versus a DLL3? Long-term, you are probably going to see a lot of ADCs like SCZ6 and B7S3. All of them, could you help us paint a picture where Zepzelca fits in in the broader paradigm here? Thank you.
Yeah. Thanks. It's nice, I think, to see a lot of new drugs in this space. It does leave us with some questions about what is the optimal sequence of these treatments? Which one should we prioritize? Also, is there a sequence that kind of makes sense biologically as well? One, I think the strategy here, first-line maintenance and then second-line, is important. We don't want to wait until progression. We really want to identify patients that can benefit from treatments earlier. I think keeping people on therapy will be important for this disease. It's something historically we haven't been able to do because of the toxicity and the diminished return on investment over time. I think that with this maintenance strategy, it really does add a new dimension. There are practical barriers to delivering a T-cell engager.
These drugs have not been compared head-to-head. We are comparing across studies, which is challenging to do because they are very different trials and they are very different populations. When we look at a study with a T-cell engager, everyone that enrolls in the trial is someone that is a potential candidate for T-cell engager. It is a very different population because not everyone who goes on a front-line therapy will be a candidate for T-cell engager or would agree in principle to a T-cell engager and to the commitments that are involved with it. It is a very different population from the jump. It makes it very difficult to extrapolate and to interpret and to compare across studies, even more so than usual. That said, if I look at a given patient who is a candidate for everything, lurbinectedin is very easy. It is once every three weeks.
It's chemotherapy. It's a cytotoxic agent that we're very familiar with. While the adverse event numbers might be high relative to other drugs, they're toxicities we're very comfortable with and largely toxicities we ignore. The patients don't really notice. Patients don't notice neutropenia. They notice neutropenic fever. A high rate of neutropenia itself, if it recovers without consequence, is really not something we worry about and something we're very comfortable with and something we're used to seeing. I think the types of toxicities we see—I don't know that we'd say the same thing for cytokine release syndrome or ICANS, which is something that I think is very scary—you're right, there are a lot of partners, collaborators, community doctors, referring physicians that simply are not able to deliver the treatment for various reasons. They either don't have access to the hospitals for overnight stays.
They might be worried about the reimbursement. It's an expensive drug. If a 23-hour observation, which in the label is recommended for cycles day one, day eight, and day 15, if that sort of flips over to a full admission, do you then eat the cost of the drug? That's a real financial concern and something that could wreck a practice. A lot of times, they're relying on tertiary centers to deliver it. We do. Not everyone is also on board with sort of staying overnight for the first several. Even cycles two and cycle three, these are six to eight-hour observations. I think there's something to be—you have to consider, can you tie up a chair for eight hours to treat one patient? A lot of practices need to turn that chair over three times.
There are a lot of practical barriers to delivering T-cell engagers, I think, across the board that will require some changes in infrastructure. I think lurbinectedin fits with the current paradigm of delivering drugs, whereas T-cell engagers really are a different thing. You need to look more towards hematologic diseases and such as to having the infrastructure to deliver those drugs. The antibody-drug conjugates, I think, are very exciting. We are involved in a lot of those agents as well. I think that they fit similar paradigms pretty early. We have to see exactly how they will be approved, where they will be approved, and what that therapeutic window will be. Will there be biomarker selection for them? Will they show an OS benefit? There are some that wonder whether they will. Certainly, ADCs have captured the narrative.
If we look at non-small cell, a little disappointing when compared to standard chemotherapy. I think it does need to show an OS benefit to really change practice. Some of the newer drugs you mentioned, CEZ6, I think it is a great target. I think it is a very logical target. It is very early. This is something that we will not really see affecting practice for years. I think there are a lot of unanswered questions. I think we still need to think of toxicity. IVXD is probably the furthest along from an ADC standpoint. The pneumonitis rate, it is not one that we can ignore. That is certainly something we worry about in this population as well. These drugs, I think, will come, will make an impact. I think for the foreseeable future, it is still going to be front-line maintenance and then second-line.
My own practice would be chemoimmunotherapy, lurbinectedin, IO maintenance, and then tarlatamab with T-cell engagers, my preferred second-line option at the first line of progression.
Thank you. Our next question comes from the line of Sean Laaman from Morgan Stanley. Your question, please.
Good afternoon, everyone. Hope everyone's well. Yeah, I just want to go back to the epidemiology just to be crystal clear. I think it's slide 29. Just in terms of patient numbers, the opportunity in first-line versus current second-line, and how quickly or what would the cadence be? How do you think about that with making first-line potentially the dominant uptake for patients? Will you provide that guidance or split going forward?
Sam, you want to jump in on this one?
Yeah. Hi. Thank you for the question. Yeah. I think as you see on that slide that you referenced, slide 29, we have 30,000 patients, and that's already been mentioned. Around 90% of those get treated, that's 27,000. We have our focus as we move that cell into the extensive-stage segment, which is around 70% of that total market. Our focus will be there. That leaves us with about 18,900 or so patients in that segment. What we do know and what we would expect is that the majority of those patients will receive the chemo plus immuno-oncology agent in the induction phase. Most of those will flow through into the maintenance and be eligible for maintenance therapy. That's where we're really focused.
I think one thing that we need to remember is that there is quite a significant proportion of patients that will not receive Zepzelca in that first-line segment, and they will flow through, therefore, into the second-line segment. There will be Zepzelca naive patients, and they'll be eligible to receive Zepzelca in that second-line segment. Our focus will be with submitted for NCCN guidelines. We're awaiting the label. We expect, given the results that we've seen from the IMforte study, to see quite rapid adoption for all the reasons that you've heard about from Dr. Liu and others on this call of Zepzelca in that first-line segment. Those patients that aren't eligible for Zepzelca in that first-line, we will certainly be looking to ensure that they can benefit in the second-line segment.
Thank you. Our next question comes from the line of Dennis Resnick from Raymond James. Your question, please.
Hi everyone. This is Dennis Resnick on for Gary Nackman. Congrats on all the data, and thanks for taking our question. Can you just remind us of the current split within second-line of where most of these patients are located, whether that be in the community or the academic setting? If you expect that split to be different when you move to the first-line. Thanks so much.
Yeah. Thanks for your question. Sam, do you want to jump in on that one?
Yes. Thanks for the question. Yes. I mean, we've already talked about the fact that many of these patients are treated in the community setting. That's certainly one of the strengths of Zepzelca, that it does allow for that treatment in that community setting. Obviously, that differs from what we see with Imdelltra, which requires more special monitoring requirements. We don't expect to see a significant difference between the newly diagnosed treatment and the second-line treatment. The focus, whilst we're covering both those two parts of our business, we would expect to continue to have that similar profile in the first-line segment.
Just to add there, just as a reminder as well, we do expect the duration of therapy to be longer in the first-line versus the second-line. That is also something to keep in mind relative to where our focus is and also in the prior question about the epidemiology.
Thank you. Our final question for today comes from the line of Leonid Timashev from RBC. Your question, please.
Hey. Thanks for squeezing me in. I just had a question on how you're thinking about read-throughs to the LAGOON study. Are you thinking that this is going to increase the likelihood there? I guess, do you still need that study to read out positively as a confirmatory study and to support the second-line opportunity? Thanks.
Rob?
Yeah. So that'll ultimately be a determination that the FDA would make. I mean, what I can say is that the IMforte trial is a randomized trial, and an earlier line of therapy provides definitive evidence, especially given the survival advantage, provides definitive evidence for Zepzelca as an active and appropriate therapy in small cell lung cancer. In many cases, the FDA will, in fact, allow only a front-line trial to be confirmatory of an accelerated approval in the second-line. That's, in fact, our situation with Zanidatamab in biliary tract cancer, where we have an accelerated approval in the second-line, and the only confirmatory trial is in the front-line. Of course, we'll need to look at the data from LAGOON and consider all the information. But I think Zepzelca is in a very strong position now in terms of its approval and recommendations from guidelines, etc.
Thank you. This does conclude the question-and-answer session of today's program. I'd like to hand the program back to Renee Gala for any further remarks.
Great. Thank you, operator. Thank you all for joining our call today. We hope this overview of the IMforte data and the Zepzelca commercial planning has conveyed our excitement about these results, as well as the potential to improve the standard of care in first-line small cell lung cancer with the addition of Zepzelca to maintenance therapy. This is a great outcome for patients. It provides a new growth opportunity for the brand. As we have mentioned, we are pleased with the priority review on October 7th, PDUFA, and hopefully being placed on guidelines in the much nearer term. Thank you to Dr. Liu for joining us today to provide his expert commentary. Thank you to all the patients that took part in this study. We look forward to keeping everyone updated on our regulatory and commercial progress. Have a good evening, everyone.
Thank you, ladies and gentlemen, for your participation in today's conference. This does conclude the program. You may now disconnect. Good day.