ADC Therapeutics SA (NYSE:ADCT) Q4 2023 Earnings Call Transcript

ADC Therapeutics SA (NYSE:ADCT) Q4 2023 Earnings Call Transcript March 13, 2024

ADC Therapeutics SA misses on earnings expectations. Reported EPS is $-1.03 EPS, expectations were $-0.47. ADCT isn’t one of the 30 most popular stocks among hedge funds at the end of the third quarter (see the details here).

Operator: Welcome to the ADC Therapeutics Fourth Quarter and Full-Year 2023 Financial Results Conference Call. My name is Norma and I will be your operator for today’s call. At this time, all participants are in a listen-only mode. Later, we will conduct a question-and-answer session. [Operator Instructions]. I will now turn the call over to Nicole Riley, Head of Communications. Nicole, you may now begin.

Nicole Preiss-Riley: Thank you, operator. This morning, we issued a press release announcing our fourth quarter and full year 2023 financial results and business updates. This release is available on the ADCT website at ir.adctherapeutics.com under the Press Releases section. On today’s call, Ameet Mallik, Chief Executive Officer; Kristen Herrington-Smith, Chief Commercial Officer; Mohamed Zaki, Chief Medical Officer; Patrick van Berkel, Chief Scientific Officer; and Pepe Carmona, Chief Financial Officer, will discuss recent business highlights and review our fourth quarter and full-year 2023 financial results before opening the call for questions. Before we begin, I would like to remind listeners that some of the statements made during this conference call will contain forward-looking statements within the meaning of the Safe Harbor provisions of the US Private Securities Litigation Reform Act of 1995.

These forward-looking statements are subject to certain known and unknown risks and uncertainties, and actual results, performance and achievements could differ materially. They are identified and described in today’s press release and the accompanying slide presentation on slide 2 and in the company’s filings with the SEC, including Form 10-K, 10-Q and 8-K. ADCT is providing this information as of the date of today’s conference call and does not undertake any obligation to update any forward-looking statements contained in this conference call as a result of new information, future events or circumstances after the date hereof, except as required by law or otherwise. The company cautions investors not to place undue reliance on these forward-looking statements.

Today’s presentation also includes non-GAAP financial measures. These non-GAAP measures have limitations as financial measures and should be considered in addition to, and not in isolation, or as a substitute for, the information prepared in accordance with GAAP. You should refer to the information contained in the company’s fourth quarter earnings release for definitional information and reconciliations of historical non-GAAP measures to the comparable GAAP financial measures. It is now my pleasure to pass the call over to our CEO, Ameet Mallik. Ameet?

Ameet Mallik: Thanks, Nicole. And thank you all for joining us today. 2023 was a year of prioritization and focus for the company. We made some tough decisions and firmly believe we are well positioned for success in 2024 and beyond. With enhanced talent in place, we implemented a new corporate and capital allocation strategy, focusing our resources and energy on our most advanced and highest potential clinical value drivers. As you can see here, we enhanced commercialization efforts, prioritized our pipeline, expanded our research platform and reduced organizational costs. This reset in 2023 was critical to enable our strategy moving forward. There are two core pillars to the strategy which we believe will unlock the tremendous value we see in this company.

Our first pillar, and primary focus, is hematology. Within this, we have a derisked asset in ZYNLONTA, the key product in our prioritized portfolio, which we expect to carry the company through to profitability. We are deploying the majority of our capital to the ZYNLONTA franchise to commercialize our existing third line and third line plus DLBCL indication and to pursue the substantially larger potential opportunity in earlier lines of DLBCL therapy and indolent lymphomas. We believe these potential opportunities will help expand the ZYNLONTA franchise and have the potential to generate annual peak sales in excess of $0.5 billion. The second pillar of our strategy is grounded in our emerging solid tumor pipeline. Our most advanced asset is ADCT-601.

And behind this, we have a number of exciting next generation antibody drug conjugates, which potentially address significant unmet patient needs. Driven by our novel platform, we see the potential to advance a broad portfolio of differentiated ADCs against solid tumor targets of interest. To capture this opportunity, our ambition is to progress multiple assets in parallel, internally and externally, supported by non-dilutive funding from partners. Across each of our presenters today, you will hear about how we are putting this strategy into action, whether through enhancing our commercial execution, prioritizing and accelerating our most promising pipeline assets, advancing high potential early stage research programs, or through our capital allocation strategy.

Now, I’d like to expand briefly on the substantially larger potential opportunity that I just mentioned for ZYNLONTA in earlier lines of DLBCL therapy and indolent lymphomas. Pending the results of the LOTIS-5 and LOTIS-7 studies, our goal is to expand usage of ZYNLONTA into second line and second line plus DLBCL. Furthermore, if data supports expansion into the second line and second line plus settings of follicular lymphoma and marginal zone lymphoma, we believe this would further increase the potential for this product. Now I’d like to share a snapshot of the business updates you’ll hear about today. I’m pleased to confirm that ZYNLONTA achieved double-digit sequential sales growth in the fourth quarter, with revenues of $16.6 million. Importantly, we saw a resumption of growth both in the community and in academic centers.

We are also delighted to share positive pipeline news at the start of this year. For our LOTIS-7 study of ZYNLONTA in combination with bi-specifics, we shared early data from the first dosing cohort. Since that time, we have successfully cleared the second dosing cohort in both arms, with no dose-limiting toxicities. We are encouraged by what we have observed with ADCT-601, our novel AXL-targeting ADC in sarcoma, and a recently initiated screening in pancreatic cancer patients. Lastly, we disclosed that we are advancing an early-stage portfolio of investigational ADCs, which utilize a novel exatecan-based platform. Turning to our financial position. We ended 2023 with close to $280 million in cash. Together with our business plans and strict cost discipline, this provides us with an expected cash runway into Q4 2025, which will support us through multiple value-generating catalysts this year and next.

So, taken together, we entered 2024 with great confidence, having repositioned and refocused the company, and with some encouraging early data emerging from our pipeline. With that, I would like to turn the call over to Kristen for a commercial update. Kristen?

Kristen Herrington-Smith : Thanks, Ameet. Today, our strategy is to grow ZYNLONTA in the community, where the third-line, third-line-plus DLBCL setting continues to be fragmented with no standard of care, and to maintain our position in the academic centers for patients who are not eligible for CAR-Ts or bi-specifics or who have progressed following treatment with these complex therapies. Our strategy is supported by real-world data as presented at the recent Tandem Meetings, which demonstrated ZYNLONTA’s efficacy pre and post CAR-T. Execution against our strategy was the fundamental driver for our commercial restructuring and resulted in higher ZYNLONTA demand in November and December, similar to the levels in the first half of 2023.

We delivered a 17% increase in net revenue in Q4 compared to Q3, with growth in both the community and academic settings. I am especially proud of our performance, given the competitive dynamic with the recent approvals of two bispecifics in the same third-line, third-line-plus setting as ZYNLONTA. We are confident we have the right team and the right strategy to maximize ZYNLONTA in the current approved indication. Now, I want to turn to the future market landscape and the important role we expect ZYNLONTA to play. Within the DLBCL market, a true standard of care only exists in the front line, with R-CHOP and recently pola R-CHIP, as well as in the academic setting in the second line with CAR-T and autologous stem cell transplant. However, accessibility to most patients treated in the community remains a challenge.

The market is evolving towards highly effective combinations with off-the-shelf agents as a cornerstone. As polatuzumab moves to the front line, we expect this will create an unmet need in the market as re-treatment in the relapse/refractory setting is unlikely. With our confirmatory Phase 3 trial, LOTIS-5, our plan is to expand the ZYNLONTA label to the second line, second line plus. We have a tremendous opportunity to build share in this broader patient population if this study continues to deliver the competitive efficacy that we have already observed with ZYNLONTA in combination with rituximab in the 20 patient safety run-in. These data, coupled with the potential advantages of accessibility, ease of use, and manageable tolerability, lead us to believe the results from LOTIS-5 will help to cement ZYNLONTA as a standard of care in the second line, second line plus among community centers where R-based regimens are commonly used across all lines of therapy.

In addition, these data have the potential to expand the use of ZYNLONTA in both the second line and third line, third line plus academic settings when an alternative to CAR-T and or bispecifics is needed. Moving to LOTIS-7, our Phase 1b trial evaluating ZYNLONTA in combination with bispecifics. As we progress this development program forward, our objective is to demonstrate that the combination can deliver enhanced efficacy compared to bispecifics alone, which could significantly expand ZYNLONTA use. In addition, we hope to demonstrate that ZYNLONTA when compared with bispecifics can reduce levels of CRS and eliminate the need for hospitalizations, expanding accessibility in the community. Ultimately, if successful, this combination has the potential to transform the treatment paradigm in the second line across both settings and substantially enhancing the patient and commercial opportunity for ZYNLONTA.

And now, I would like to turn the call over to Mohamed for a clinical update.

Mohamed Zaki: Thanks, Kristen. It’s my pleasure to provide an update on our clinical stage pipeline. Starting with LOTIS-5, our Phase 3 confirmatory trial with ZYNLONTA and rituximab, we significantly accelerated the pace of enrollment in 2023, and we reported encouraging updated safety lead-in results in September. While we have been pleased with the increase in patient enrollment, our clinical team recently observed higher than expected sensory in the trial, which was confirmed with the IDMC. As a result, we may need to expand enrollment beyond the planned 350 patients to achieve the required number of pre-specified progression free survival events. Based on the current pace of enrollment, we do not expect this to affect our target to complete enrollment in 2024.

Importantly, the IDMC noted no safety concerns and recommended the study to proceed at its most recent meeting held on the 16th of January 2024. Moving to LOTIS-7, this is our Phase 1b study to explore ZYNLONTA in novel combinations. We are focusing on the combination in two bispecifics arm, Roche’s glofitamab and mosunetuzumab. Enrollment started in each arm in July 2023. Part 1 is a 3 plus 3 dose escalation and third line plus heavily treated patient, with ZYNLONTA doses starting at 90 microgram per kilogram, and then proceeding to 120 and 150 micrograms. As we discussed in January, we dosed the first three patients in each arm with the 90 microgram dose and cleared the dose limit to 60 period. Since that time, we have cleared the 120 microgram dose for both arms, with no DLTs and we are currently enrolling the 150 microgram dose.

Once dose escalation is complete, we plan to expand at the appropriate dose levels. After the first investigator assessment, we have seen evidence of antitumor activity among the majority of patients dosed at the first two levels, with mixed histologists, including DLBCL, follicle lymphoma and marginal zone lymphoma. We expect to share additional data once a larger and more mature data set is available. While we are excited, but what we have seen, we recognize that it is early. And once dose expansion in second line is complete and assuming data are promising, we plan to approach the regulatory agencies to discuss our strategy and potential path forward. Beyond our own studies, there is significant amount of interest from investigators to explore ZYNLONTA in additional indications and combinations.

At ASH in December 2023, there was an oral presentation from the University of Miami on their investigator initiated Phase 2 study of ZYNLONTA and rituximab in patients with high risk relapse or refractory follicular lymphoma. This is a unique population not served well by the current standard of care. Initial results from the 33 patients were very encouraging, including a best overall response rate of 96% and a complete response rate of 85%. In terms of safety, the majority of adverse events were primarily grade 1 and manageable. The presentation was extremely well received by the physician community and the trial is now being expanded to other centers with a target enrollment of 100 patients. The University of Miami is also conducting another investigator initiated Phase 2 study of ZYNLONTA in relapse or refractive marginal zone lymphoma, an indication with significant unmet needs.

The study is designed to enroll 50 patients and a futility analysis is expected to be conducted in the second quarter of this year. We anticipate the investigators will present the data from both studies at upcoming medical meetings. If these investigator initiated trials are positive, we would move quickly to determine the regulatory and or compendia path forward. I want to turn now to our solid tumor candidate ADCT-601 targeting AXL, which we are investigating in a Phase 1 study in sarcoma, pancreatic cancer, and non-small cell lung cancer. While others have explored AXL as a therapeutic target, we are especially excited by the potentially differentiated profile we see with the 601 D2, its innovative design incorporating a PBD toxin. AXL is expressed in multiple tumor types and it has been shown that high expression of AXL is correlated towards patients’ overall survival across many cancer types, including non-small cell lung cancer, pancreatic, and sarcoma.

Our Phase 1 trial includes monotherapy as well as combination arms with gemcitabine in sarcoma and pancreatic cancer. Given the high level of AXL expression, sarcoma is serving as the proof of concept. In January, we disclosed that we reached the recommended dose of 13 milligrams. In addition, we also shared that ADCT-601 was well-related at the doses tested and we have been encouraged by the early size of anti-tumor activity in both monotherapy and combination. The study is currently in part two which includes dose optimization and expansion. We plan to share additional data from the trial in a presentation at AACR next month for which abstract is now available online. With regard to the other indications, I am pleased to report that we have initiated screening in the pancreatic cancer monotherapy arm based on an enriched patient population.

We also plan to initiate dosing in the non-small cell lung cancer pre-selected patients once we have optimized the assay for non-small cell lung cancer. I am encouraged by the progress we are making with our pipeline and look forward to sharing more in the future. I would now like to hand over to Patrick.

Patrick van Berkel: Thanks, Mohamed. It’s a pleasure to update you all on our research activities. As we disclosed at the start of this year, as part of our broad toolbox, we’re now developing ADCs utilizing a differentiated payload based on the topoisomerase I inhibitors, exatecan, together with a novel hydrophilic linker. Compared with commercially available toxins such as the DXD platform, our innovative and proprietary approach has shown evidence in preclinical studies for greater potency, stronger bystander activity and excellent tolerability. Initially, we are conducting research utilizing our exatecan-based platform against four highly attractive targets and indications with high unmet needs. The first is Claudin-6, which is a novel target that is highly expressed in ovarian, endometrial, testicular and non-small cell lung cancer.

The second target is NaPi2b, a validated ADC target, which is also highly expressed in ovarian, endometrial, and non-small cell lung cancer. The third is PSMA, which is a validated ADC target, highly expressed in metastatic castrate-resistant prostate cancer. We intend to select a clinical candidate based on a novel optimized PSMA-specific antibody. Lastly, we are applying this platform to an undisclosed target. What I can say is that the target is a novel transporter protein, which is highly expressed in multiple hematological and solid tumor malignancies. For Claudin-6, NaPi2b, and the undisclosed target, we have completed in vivo pharmacology and dose range-finding studies in cynomolgus monkey. In each case, we’ve seen strong antitumor activity with an attractive therapeutic index and no evidence of interstitial lung disease.

Based on the encouraging initial data from these three investigational candidates, we believe we have a differentiated ADC platform that can be applied to multiple tumor targets of interest. In terms of next steps, we will share data for Claudin-6 and NaPi2b at AACR next month. The abstracts are available on the AACR website, and I would encourage you to review them. Following AACR, we plan to share additional information on our differentiated research platform at an investor event in the second quarter. With that, I would like to hand over to Pepe.

Jose Carmona : Thank you, Patrick. Before I get into the financials and outstanding catalysts, I want to remind everyone of our corporate business development strategy. Hematology continues to be our primary focus. And within this, our key objective is to drive the value of ZYNLONTA. We will achieve this by fully supporting our commercialization effort in the US directly and through our partnership ex-US. In solid tumors, our aim is to pursue multiple ADC candidates in parallel and increase our shots on goal. We will determine on a case-by-case basis whether we wish to progress candidates internally or seek to partner in order to share the development and financial risk. Turning to our fourth quarter performance, we’re now reporting our results under US GAAP as we became a US domestic filer starting January 1st, 2024.

Starting with our balance sheet, as of December 31st, we had cash and cash equivalents of approximately $278.6 million or a $32 million decrease from the end of Q3. Moving to the P&L, as you already heard, ZYNLONTA net sales were $16.6 million in the quarter, a decrease of 16% versus prior year, primarily driven by higher gross-to-net due to discounted drug rebate and slightly lower volume, partially offset by higher gross price. Our total operating expenses on a non-GAP basis, which excludes stock-based compensation, were down 24% compared to the fourth quarter of last year. This mainly reflected our focus on driving operating efficiencies, together with reduced R&D expenditure due to focused investment in our clinical studies and lower selling and marketing expenses.

For 2024, we will continue to take a very disciplined approach to our operating expenses. This is crucial to funding the development of our key pipeline programs and maintaining our expected cash runway into the fourth quarter of 2025. You will find the reconciliation of GAAP measures to non-GAAP measures in the accompanying financial tables of the press release issued earlier today and in the appendix of this presentation. Moving to the bottom of the P&L, on a GAAP basis, we reported a net loss of $85 million for the quarter or $1.03 per basic and diluted share. This took our full year 2023 net loss to $240 million or $2.94 per basic and diluted shares. My final slide highlights the multiple potential value driving milestones which we expect in 2024.

With that, I will turn the call back to Ameet.

Ameet Mallik : Thanks, Pepe. To close, we entered 2024 with a clear strategic roadmap and the capabilities to drive value creation for all our stakeholders. My team and I are excited about the company’s prospects and look forward to keeping you updated on our progress. Now we will be available for questions. Operator?

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Q&A Session

Operator: [Operator Instructions]. Our first question will come from the line of Naureen Quibria with Capital One Securities.

Naureen Quibria: Congrats on the progress. Actually, I was just curious about LOTIS-7. Can you talk about the safety data with bispecifics in combination to date, and what’s been seen with other therapies? And relative to that, can you speak to your expectation for LOTIS-7, your level of confidence for this combination? And just on the same topic, you mentioned on the press release that you have a larger data set. You present – I mean, you have a larger data set. Can you just talk about sort of the size and scope of that data set that you would expect to release if it’s after the 120 microgram data? Appreciate some granularity.

Ameet Mallik: Maybe I’ll turn it over to Mohamed to answer both those questions on the safety profile and what we’re hoping for and what we’ve been seeing as well as on – yeah, so, Mohamed, do you want to take it?

Mohamed Zaki: With regard to LOTIS-7, as you know, it’s a dose escalation study of combination of the ZYNLONTA plus two different bispecification, glofitamab and mosunetuzumab in three different disease types, marginal zone, DLPCL, and follicular in third line plus. We are very encouraged by the fact that we have cleared the first dose levels, the 90 microgram per kg and the 120 microgram with no DLTs. And all we have seen so far is either no CRS or low-grade CRS that resolves very quickly. We are very encouraged by the anti-tumor activity we keep seeing in the study to date. It’s an open-label study and we see things live. However, it’s early days, and we would like to wait until we have more mature data to be able to share more mature cohorts later this year. I think that pretty much answers your question.

Ameet Mallik: Maybe just one thing to add. We’re now currently dosing the 150 microgram per kilogram dose in both the glofitamab and the mosunetuzumab arm. Once those are cleared, we’ll move right into the dose expansion in second line plus DLBCL with glofitamab. And that’ll be the focus. That’s where I think we’re going to get a better representation of efficacy when we have a broader number of patients, longer follow-up, and in a single histology. And that’s really the focus of part two of the study, which we will start as soon as we clear the dose escalation.

Naureen Quibria: I guess I have one for Kristen, and then I’ll hop back in the queue. Just curious in terms of the penetration levels with the ZYNLONTA in the academic and community settings, what are those? Can you comment on that, number one? And number two, can you talk about what you saw in terms of how were you able to increase growth in academics, just out of curiosity?

Kristen Herrington-Smith: We don’t share exact numbers of penetration. What I can tell you is that we had a strong foundation in the first couple of years of launch and within the academic setting. In 2023, starting in Q2, we really refined our strategy to focus more on the community. Our strategy of driving adoption with the community played out well, and we started to see the impact of that in Q4 2023. So not only did we see more community sites adapt ZYNLONTA, but actually, we also saw an increase in volume in the academic centers as well, post the entrance of two bispecifics. So we see this increased demand, and I would say in November and December, we started to see our demand levels come back to what we saw in the first half of 2023, and we look forward to driving progressive growth with ZYNLONTA with this refined strategy.

Operator: Our next question comes from the line of Brian Cheng with J.P. Morgan.

Brian Cheng: Just a couple. On LOTIS-5, can you talk about a little bit more about the censoring that you mentioned on the call? Specifically, what is the reason for the higher than expected censoring in LOTIS-5? And how much of that is due to safety-related withdrawal? And I have a couple questions left.

Mohamed Zaki: Mohamed, do you want to talk about LOTIS-5 and censoring?

Mohamed Zaki: Just want to highlight that it is not uncommon for initiate the need for increased enrollment in a global open label Phase 3. It’s also not uncommon to see a little bit higher censoring when you are dealing with the relapsed/refractory diseases. The main reason we believe, or for the higher than ever censoring, is the lack of convenience from physicians and patients with relation to the control arm, possibly. And that’s usually because the physicians usually want to be in the active arm, of course. So, you can expect to see a little bit higher than usual. And there was no concerns by the DMC that met in January with regard to any safety issue that is not related to any safety reason or anything related to do. But it is very important, this is simply replacing possibly missing events to reach the required number of events, clear the [indiscernible] to reach the end of the study.

So, it’s a replacement procedure that many Phase 3s do in order to make sure they get that on time. The good news is that, even with possible increase in the size of this trial, we do not anticipate to have a delay on finishing enrollment, which we have communicated to be within 2024. The reason for that is, recently, we have observed an acceleration of enrollment and we’ve seen really a quite high number of enrollments per month compared to month before.

Brian Cheng: Going back to your comment related to commercial branded profitability later this year, what does that actually entail? Can you talk about the gross-to-net we should expect in our model? And related to SG&A expenses, how should we model that for the rest of the year?

Ameet Mallik: Pepe, do you want to take that in terms of gross-to-net evolution? What commercial brand profitability means and the evolution of SG&A?