ADC Therapeutics SA (ADCT) Earnings Call Transcript & Summary

. Thank you for holding. Good afternoon, and welcome to the ADC Therapeutics ZYNLONTA FDA Approval Conference Call. [Operator Instructions] Please be advised that this call is being recorded at the company's request. At this time, I'd like to turn the call over to Amanda Hamilton, Investor Relations Manager at ADC Therapeutics. Please proceed.

Thank you, operator. This afternoon, we issued a press release announcing the FDA approval of Lonca, which is now known as ZYNLONTA. This release is available on the ADCT website at ir.adctherapeutics.com under the Press Release's section. On today's call are Chris Martin, Chief Executive Officer; Jay Feingold, Chief Medical Officer; and Jennifer Herron, Chief Commercial Officer. In addition, Jen Creel, our Chief Financial Officer, will join for the Q&A session. As a reminder, this conference call may contain forward-looking statements. Such statements are subject to risks and uncertainties. We refer you to the section titled Cautionary Statement Regarding Forward-Looking Statements in our annual report on Form 20-F filed with the U.S. Securities and Exchange Commission for further information on forward-looking statements. Such statements speak only as of the date of this conference call, and we expressly disclaim any obligation or undertaking to update these forward-looking statements unless required to do so by applicable law. It is now my pleasure to pass the call over to our CEO, Chris Martin. Chris?

Thanks, Amanda, and thank you for joining us today. I'm truly delighted to be with you to discuss the significant milestone for oncology patients and for ADC Therapeutics. Today, a month before our PDUFA date, I'm very pleased to say that the FDA granted accelerated approval for Lonca, brand name ZYNLONTA, for the treatment of adult patients with relapsed or refractory large B-cell lymphoma after 2 or more lines of systemic therapy. In addition to accelerated approval for diffuse large B-cell lymphoma, not otherwise specified, ZYNLONTA was also approved for DLBCL arising from low-grade lymphoma and high-grade B-cell lymphoma, with the latter being an important point of differentiation. Jay will discuss our clinical highlights a little later in the call. ADC Therapeutics was founded on our strong commitment to improving the lines of patients with our next-generation ADC technology. In March 2016, the first patient was dosed in our Phase I trial of ZYNLONTA. Just over 5 years later, we have received FDA accelerated approval. I would like to take this opportunity to thank each and every one of our dedicated colleagues for their tireless efforts to bring ZYNLONTA to patients. I would also like to thank our investigators, collaborators, and most importantly, the patients who participated in the clinical trials and their families who helped us make this achievement possible. As we celebrate our first product approval, we mark our evolution from an R&D company to a fully integrated commercial organization. Jennifer Herron, our Chief Commercial Officer, has done a tremendous job in preparing the commercial team alongside our medical affairs team to ensure successful launch. Jennifer will share further details of our launch plan later in the call. I would now like to hand the call over to our Chief Medical Officer, Jay Feingold, who will review the clinical data supporting ZYNLONTA's approval. Jay?

Thank you, Chris. This is indeed a momentous day for the company and for the patients. As many of you know, I've been an oncologist for more than 30 years and have been involved in drug discovery and development for most of that time. While tremendous progress has been made treating hematologic malignancies, there remains a significant unmet medical need for patients not cured by first to subsequent lines of therapy. Today, I'm excited to be part of the team that is bringing ZYNLONTA to patients with relapsed/refractory diffuse large B-cell lymphoma, including those with very hard-to-treat forms of the disease. ZYNLONTA, the first and only CD19-targeted antibody drug conjugate approved for the treatment of this indication. The data from the LOTIS-2 trial establishes the significant activity of ZYNLONTA as a monotherapy for these patients. And I am very pleased that we have received a broad indication, including high-grade B-cell lymphoma. We believe that ZYNLONTA has the potential to be the standard of care in third-line and later patients, and look forward to continuing our work to study ZYNLONTA as part of combination modalities and in earlier lines of therapy. ZYNLONTA was granted accelerated approval on the priority review based on the LOTIS-2 trial, a single-arm, multicenter, open-label Phase II trial that enrolled a total of 145 patients with relapsed/refractory diffuse large B-cell lymphoma following at least 2 lines of prior systemic therapy. The trial included a broad spectrum of heavily pretreated patients with very-difficult-to-treat disease, including patients with high-grade B-cell lymphoma. The trial also enrolled patients who never responded to first-line therapy and patients who had not responded to any prior line of therapy as well as patients who had prior stem cell transplants and prior CAR-T therapy. While a portion of patients are cured in first-line treatment, approximately 40% either have refractory disease or relapsed. And of these patients, approximately 50% will require third-line therapy. This broad patient population is reflected in the LOTIS-2 trial, and represents the patients who remain in need of another treatment option. The overall response rate in the total patient population was 48% and an additional 15% had stable disease. It was also very encouraging to see compelling overall response rates, even in the high-risk category population that I mentioned earlier and even in the older patients. For example, patients who never responded to first-line therapy or never responded to any prior line of therapy had an overall response rate of 38% and 36%, respectively, in the LOTIS-2 trial. And while ages typically indicate our treatment outcome, ZYNLONTA was equally efficacious and had similar safety profiles in patients older and younger than 65. The median duration of response to the data package for the BLA submission was 10.3 months. As we continue to follow patients, this data has since matured and the median duration of response at the last analysis was 12.6 months for all responders and 13.4 months for patients who had a complete response. As expected, the ZYNLONTA label contains important safety information. Notably, the label reflects the manageable safety profile of ZYNLONTA with no black box warnings and no contraindications. You can see on the slide the warnings and precautions as well as the most common adverse events in the pooled safety population of our Phase I and Phase II trials of 215 patients. 19% of patients in the Phase II trial discontinued due to treatment-related adverse events. To put this safety information in perspective, it's important to consider the heavily pretreated patient population in the Phase II trial with a median number of prior lines of therapy was 3. We believe the recommended monitoring and management guidelines are clear and straightforward and that physicians will be able to adequately manage adverse events. ZYNLONTA offers a truly differentiated treatment option for relapsed/refractory diffuse large B-cell lymphoma patients. We also think this first approval is just beginning. As the slide shows, we continue to explore ZYNLONTA's potential in additional promising combinations, early lines of therapy and new histologies. With that, I will turn the call over to Jennifer to discuss the highlights of the commercial launch.

Thank you, Jay. I'm excited to be on this call today to provide an update on the preparations we have made to support a successful launch of ZYNLONTA. Before I get into the specifics of the ZYNLONTA launch plan, I would like to reiterate that relapsed/refractory DLBCL remains an area of significant unmet medical need, especially in the third-line-plus setting, where patients are heavily pretreated, and often have poor prognostic factors, creating unique challenges for treating physicians. One of the key aspects of the LOTIS-2 trial is the broad inclusion of these relapsed/refractory patients, including patients who did not respond to first line or any prior lines of therapy, patients who failed CAR-T therapy or stem cell transplant and patients with high-grade B-cell lymphoma, including those with double-hit and triple-hit genetics. These difficult-to-treat patients included in the LOTIS-2 trial and therefore, in the ZYNLONTA label, are representative of an oncologist's everyday practice population. As Chris mentioned, an important point of differentiation for ZYNLONTA is the broad indication in third-line-plus DLBCL, including DLBCL not otherwise specified, DLBCL arising from low-grade lymphoma and high-grade B-cell lymphoma as well as both transplant eligible and ineligible patients. In terms of the initial market opportunity, we estimate approximately 10,500 third-line-plus DLBCL patients in the U.S. and EU5 for a third-line-plus market opportunity in excess of $1 billion. And importantly, we have a number of ongoing and planned trials to potentially expand into additional histologies and earlier lines of therapy, representing additional business opportunities. With FDA approval in hand, our team will deliver on 3 launch imperatives to ensure a successful ZYNLONTA launch. First, we will effectively communicate the differentiated profile of ZYNLONTA. It's significant single-agent activity across a real-world patient population highlighted by our broad indication. With nearly half of the LOTIS-2 patients responding to ZYNLONTA, it's important to note that patient response to therapy was seen at a median of only 41 days. Uniquely, ZYNLONTA is delivered in a convenient 30-minute IV infusion every 21 days. Our second launch imperative is to ensure a positive first experience for physicians and patients to support trial and repeat use, through frequent engagement and education as we established ZYNLONTA as the third-line-plus standard of care. And finally, to ensure that any patient who may benefit from ZYNLONTA has the opportunity, we have a robust plan to support open access, affordability and patient support, and I will discuss the specific details in a few slides. As we launch into the relapsed/refractory DLBCL market, we are confident in our ability to establish ZYNLONTA as the third-line-plus standard of care and encouraged by our insights from extensive market research and our ongoing interactions with both academic and community thought leaders. Despite recently approved combinations, physicians still see significant areas of unmet medical need amongst their treatment choices. The ZYNLONTA product profile was very well received by treating [ hem/oncs ], where physicians indicated that the LOTIS-2 clinical trial population uniquely reflected their real-world practice to include a broad population of relapsed/refractory patients including heavily pretreated patients and patients with difficult-to-treat disease. Physicians were impressed with the robust single-agent efficacy, manageable side effect profile and convenient 30-minute infusion. This research also indicated a high willingness to prescribe ZYNLONTA when commercially available. And finally, physicians were interested to understand how ZYNLONTA would combine with other agents for application in earlier lines of therapy. We have built a world-class commercial team of seasoned oncology professionals to drive the launch of ZYNLONTA across marketing, sales and market access. The sales team has an average of 13 years of oncology experience and an average of 8 years of specific hematology expertise. Each hematology therapeutic specialist has a strong local network across their geography, has completed their business planning and with the final USPI is perfecting the communication of the ZYNLONTA value proposition for prescribers and other health care providers. Our market access team is equally impressive, including a field-based payer team with an average of 22 years of oncology experience and an average of 8 years of specific expertise in hematology. Our 70-plus, customer-facing team covers over 90% of the total DLBCL opportunity, and we are confident in our plans, in our seasoned commercial organization and our ability to establish ZYNLONTA as the third-line-plus standard of care. While we recognize the challenges of launching in a COVID environment, we have prepared for this reality, and the team has already begun executing this hybrid model as they've introduced ADC Therapeutics to the hematology, oncology community. Customer engagement has included and will include a range of options from purely digital to face-to-face interactions, and our teams are trained and well positioned to engage all of our customers with an individual approach while respecting local and institutional guidelines. We have developed multichannel communications to ensure that all key audiences, physicians, nurses, office managers, payers and patients receive the necessary information and support to ensure access to and safe administration of ZYNLONTA. Seamless distribution, patient access and support services are all critical to ensuring that every patient who may benefit from ZYNLONTA has the opportunity to receive it as soon as possible. To this end, we are on track to make ZYNLONTA commercially available next week. From a distribution perspective, we have commercial supply to support the launch and beyond. Third-party logistics are fully in place, and our specialty distributors are ready to fill orders. In terms of pricing, the wholesale acquisition cost, or WAC, for a 10-milligram vial of ZYNLONTA is $23,500, which reflects the differentiated value of ZYNLONTA and is consistent with payer stakeholder expectations reflected in our extensive market research. Based on the approved dosing regimen for ZYNLONTA, it is important to consider that like many oncology agents, ZYNLONTA uses weight-based dosing. As a result, some patients will require 2 vials for each of the first 2 consolidation cycles. In the LOTIS-2 trial, patients received a mean of 4.5 cycles of ZYNLONTA. Our account directors and MSLs have been actively engaging with payers and other key access stakeholders for many months now, discussing the unmet medical need in relapsed/refractory DLBCL. In addition, our MSLs have been responding to medical questions about the LOTIS-2 trial data. From these encouraging discussions, we expect ZYNLONTA to be readily covered and the preferred treatment of choice in the third-line-plus DLBCL setting. Finally, in support of our relapsed/refractory DLBCL patients, we are pleased to offer Advancing Patient Support, our comprehensive patient assistance program. The Advancing Patient Support Program includes access and insurance coverage support, reimbursement and financial support and nursing support to address and remove any potential barriers for patients and ensure that any patient who may benefit from ZYNLONTA treatment has the opportunity to do so. In summary, we are well prepared and very excited to launch ZYNLONTA. We have carefully laid the necessary groundwork leading up to this day. We have an exceptional team of top industry talent in a truly differentiated product, and we are confident in our ability to establish ZYNLONTA as the third-line-plus standard of care. With that, I will turn the call back to Chris for closing remarks. Chris?

Thanks, Jennifer, and thank you, Jay. I'm super excited about the future of ADC Therapeutics as we enter this next phase of transformation and growth. The company has built on a strong scientific foundation based on our proprietary next-generation ADC technology, which has been validated by our first FDA accelerated approval of ZYNLONTA, which is the first-ever approval of a PBD-based ADC. We have 5 assets in ongoing clinical development and another 7 preclinical research programs in both hematological and solid tumor indications. And most importantly, a fantastic team with the ambition to transform the lives of patients. I'm proud of our achievements to date and look forward to updating you on our progress. We'll now open our call for questions. Operator?

[Operator Instructions] You have a question from the line of Matthew Harrison with Morgan Stanley. [Operator Instructions] And there are no questions in queue at this time. I will now turn the call back to Chris.

Thank you, operator, and thank you, everybody, for listening to this call, and we'll be happy to talk to you and update you in future calls. So at the end of this very exciting day, just like to say thank you, good evening, and have a good weekend. Take care. Goodbye.