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ADC Therapeutics SA
NYSE:ADCT

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ADC Therapeutics SA
NYSE:ADCT
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Price: 3.44 USD -6.27% Market Closed
Updated: Jul 21, 2024
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Earnings Call Transcript

Earnings Call Transcript
2024-Q1

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Operator

Good day, and thank you for standing by. Welcome to the ADC Therapeutics First Quarter 2024 Financial Results Conference Call. [Operator Instructions] Please be advised that today's conference is being recorded.

I would now like to hand the conference over to your speaker today, Nicole Riley, Head of Communications. Please go ahead.

N
Nicole Riley
executive

Thank you, operator. This morning, we issued a press release announcing our first quarter 2024 financial results and business updates. This release is available on the ADCT website at ir.adctherapeutics.com under the Press Releases section. The event is being recorded, and the slides accompanying this call are available on the ADCT website at ir.adctherapeutics.com under the Latest Events and Presentations section.

On today's call, Ameet Mallik, Chief Executive Officer; and Pepe Carmona, Chief Financial Officer, will discuss recent business highlights and review our first quarter 2024 financial results. We will then open the call to questions when we will be joined by Kristen Harrington-Smith, Chief Commercial Officer; and Mohamed Zaki, Chief Medical Officer.

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 U.S. 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 the accompanying slide presentation on Slide 3 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?

A
Ameet Mallik
executive

Thanks, Nicole, and thank you all for joining us today. As you will have seen, we have shared some very exciting news items earlier this morning. But to begin with, I'd like to focus on key business updates for the quarter. Starting with our commercial performance. ZYNLONTA continued its return to sequential growth in revenues of $17.8 million in Q1. This represents a 7% increase over the fourth quarter of 2023. Importantly, we saw continued growth both in the community and in academic centers despite the intensified competitive landscape.

Turning next to our pipeline. We have made significant progress. Last month, we announced that our LOTIS-7 study of ZYNLONTA, in combination with bispecifics, successfully cleared the final dosing cohort in both arms with no dose-limiting toxicities, no ICANS and either no or low grade levels of CRS. We are now dose expanding at 120 and 150 micrograms per kilogram in the ZYNLONTA plus glofitamab combination arm in second line plus DLBCL. Today, we are delighted to share, for the first time, encouraging initial data recently presented from the University of Miami's Phase II investigator-initiated trial of ZYNLONTA in relapsed/refractory marginal zone lymphoma. Based on initial results from the first 15 evaluable patients, 13 achieved a complete response and 1 achieved a partial response with all patients maintaining response at the time of data cutoff.

Moving to ADCT-601, our novel AXL targeting ADC. We began enrolling pancreatic cancer patients and continue to enroll sarcoma patients, and we are in the process of optimizing the dose and schedule. Lastly, we shared a comprehensive update on our novel exatecan-based solid tumor platform, including early preclinical data on our 4 preclinical ADC candidates for the first time at our recent research investor event.

Finally, in terms of our corporate update, we maintained our disciplined capital allocation strategy and decreased operating expenses in Q1 by 16% year-over-year on a non-GAAP basis. This, in turn, enabled us to manage our cash burn, so that we ended the first quarter with cash of $234.3 million.

On top of this, we have just announced today that we have priced an underwritten offering to raise $105 million in gross proceeds. The offering at the closing price per share on Friday included common shares and prefunded warrants and is expected to close on May 8. We expect this will extend our cash runway into mid-2026, and provide the company with enhanced financial flexibility to execute our strategy. Given our strength and balance sheet, I would like to remind everyone of the strategy we are pursuing, which we believe will unlock the tremendous value we see in the company.

Our first pillar and primary focus remains 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 plus DLBCL indication and to pursue the substantially larger potential opportunity in earlier lines of DLBCL therapy and indolent lymphomas, such as marginals on lymphoma.

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. ADCT-601 is our most advanced asset. Behind this, we see the potential to advance a broad portfolio of differentiated ADCs against solid tumor targets of interest driven by our novel exatecan-based platform.

I'd like to expand now on the substantially larger potential opportunity 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 plus DLBCL. As a reminder, LOTIS-5 is our confirmatory Phase III study of ZYNLONTA in combination with rituximab. Here, we remain on track and expect to complete enrollment by the end of this year, with the potential for a headline readout by the end of 2025. If positive, we believe this trial will lead to full approval for ZYNLONTA and expand our indication into second line plus DLBCL in combination with rituximab, potentially as early as the end of 2026.

LOTIS-7 is our Phase Ib trial of ZYNLONTA in combination with bispecifics. We are encouraged by the initial safety and tolerability profile as well as the observed anti-tumor activity amongst the majority of patients in part 1 of the dose escalation. We are now enrolling in Part 2 dose expansion with ZYNLONTA plus glofitamab in second line plus DLBCL and expect to complete enrollment and plan to share additional efficacy and safety data before year-end.

We also see the potential to expand the uses ZYNLONTA into the second-line plus setting of follicular lymphoma and marginal zone lymphoma based on initial data from investigator-initiated trials at the University of Miami. Today, I want to focus on the marginal zone lymphoma data that we shared this past weekend at the Lymphoma Research Foundation's 2024 Marginal Zone Lymphoma scientific workshop by the trial's lead investigator, Dr. Izidore Lossos at the University of Miami. Relapsed/refractory MZL represents an unmet need, based on publicly available incidence data, there are an estimated 3,000 to 4,000 second-line plus MZL patients who are drug treated in the U.S.

Unmet medical need remains in relapsed/refractory MZL, less than 30% CR for second-line plus approved or NCCN preferred treatment. At present, there are 2 FDA approved regimens and several other preferred regimens for the treatment of MZL in second-line plus included in NCCN guidelines. Complete response rates are modest and sample sizes in the study supporting this data are relatively small.

As complete response rates are a strong predictor of time-related outcomes in MZL, clinicians continue to seek novel agents with higher and durable CR rates, a manageable safety profile and a fixed duration of treatment. The University of Miami is leading a multicenter Phase II IIT study in ZYNLONTA as a single agent fixed duration regimen to treat 50 relapsed/refractory MZL patients. Initial data from the first 15 evaluable patients showed 13 achieved a complete response and 1 achieved a partial response.

According to the lead investigator, ZYNLONTA was generally well tolerated, and safety was consistent with the known profile. There are 2 sites currently enrolling, University of Miami and City of Hope, and the lead investigator is currently expanding to 5 sites to accelerate trial enrollment. As soon as we have sufficient data, assuming it remains positive, we plan to potentially pursue our regulatory pathway and compendia strategy in parallel.

In terms of the opportunity based on our analysis, we believe the total addressable second-line plus NPL patient population has a potential peak market opportunity of approximately $500 million valued at ZYNLONTA price and expected average number of cycles. If successful, it means every 10% of market share captured represents $50 million in incremental annual peak sales opportunity.

While still early in the Phase II IIT, if this trial continue to yield similar results, the potential opportunity to expand into MZL could contribute to the overall ZYNLONTA growth strategy in NHL. The current standard of care an MZL includes CD20-based regimens online in addition to BTK inhibitors in second-line MZL. The data used for FDA approvals and inclusion in NCCN guidelines were based on either single-arm studies or a subset of larger indolent NHL studies and offer modest CR rates, which are below 30%.

Per the study protocol, all patients included must have failed 1 or more lines of systemic therapy, including at least 1 anti-CD20 antibody, under the protocol, patients receive a fixed duration of treatment of 6 cycles of ZYNLONTA across 18 weeks. The primary endpoint is CR rate at 6 and 12 months as patients will be followed for up to 3 years with progression-free survival and overall survival measured at 24 months.

The predetermined futility threshold for efficacy was set at 31% CR rate.

Looking at the baseline characteristics of the patients enrolled so far in the study, there are a few things I want to point out. We believe this initial group of patients is representative of the overall MZL population, including MZL subtypes. In addition of the patients treated with ZYNLONTA so far, 10 of the 15 were Stage IV MZL patients with 8 of the 15 designated as POD 24, meaning they progressed within 24 months of initial treatment, a group that is typically harder to treat.

The median prior lines of therapy is 2 ranging from 1 to 4. And as you can see on the right side of the slide, included multiple currently available systemic treatment. As shared by Dr. Losses at the Lymphoma Research Foundation's 2024 Marginal Zone Lymphoma scientific workshop on May 4, these initial results showed 13 of 15 patients achieved a CR with 1 additional patient achieving a PR.

Of the 13 CRs, 9 were achieved after 2 cycles. In addition, all patients achieving responses and maintain them as of the data cutoff with the longest responder reaching approximately 20 months. And from an initial safety perspective, per the lead investigator in this study, ZYNLONTA was generally well tolerated and consistent with a known safety profile.

One patient discontinued after cycle 2, a second patient discontinued after cycle 4 due to a toxicity which fully resolved upon discontinuation of treatment. Both of these patients remain in CR at 10 and 6 months, respectively. Based on this initial data from University of Miami's Phase II trial, evaluating ZYNLONTA in relapsed/refractory MZL, we are encouraged by the potential opportunity in the second line plus setting for patients with this rare disease.

Moving on to LOTIS-7, we are sharing here additional safety data from the Part 1 dose escalation portion of the study. The important takeaways are that the majority of CRS events were grade 1 and that no CRS greater than Grade 2 is observed. Those patients who have experienced a Grade 2 CRS were managed with no requirement for ICU management or pressers.

On the left-hand side, you will see that the overall CRS rate with glofitamab was 33%, which is the combination of focus for Part 2 of the study. Important to note that current glofitamab label and third-line plus DLBCL includes a 70% CRS rate, including some higher grade events. We believe that dosing with ZYNLONTA 1 week prior to glofitamab may be debulking the tumor.

Turning to our research platform. We hosted a virtual investor research event on April 9, which provided a comprehensive overview of our solid tumor research strategy, our novel exatecan based platform and our 4 lead ADC candidates. Our focus is on advancing differentiated ADC candidates against prostate, non-small cell lung cancer, colorectal, endometrial and ovarian cancers.

For each tumor type, the combination of incidents and 5-year survival offers large potential opportunities and indicates that better treatment options are needed. Furthermore, in each case, chemotherapy remains a key part of the treatment armamentarium. Our 4 lead ADC targets are NaPi2b, Claudin-6, PSMA and ASCT2. We believe each offers the potential to improve the standard of care for cancer patients and each utilizes our novel exatecan based platform.

Preclinical work suggest that our 4 lead candidates each have a high therapeutic index, reflecting the proprietary design of the ADC. In terms of stage, our NaPi2b and Claudin-6 ADCs are in IND-enabling studies, and we are pleased to share exciting early data on these at AAGR last month.

Our PSMA and ASCT2 ADCs are in the drug candidate selection stage, which we expect to complete this year. Looking ahead, we plan to move forward with 1 candidate to IND and to seek research collaborations to advance a broad portfolio. Given the unmet medical need, coupled with the market opportunity, a successful outcome for one or more of our early research programs has the potential to transform the lives of patients and create significant value in the future. With that, I would like to turn the call over to Pepe.

J
Jose Carmona
executive

Thank you, Ameet. Before I discuss today's financing, I will take you through a brief summary of our first quarter results. As a reminder, we're now reporting our results under U.S. GAAP, we became a U.S. domestic filer as of January 1, 2024.

Starting with our balance sheet, at March 31, we had cash and cash equivalents of approximately $234.3 million. Moving to the P&L. As you already heard, ZYNLONTA net sales were $17.8 million in the quarter, a decrease of 6% versus prior year, primarily driven by higher gross to net deductions and lower volume, partially offset by higher gross price.

On a sequential basis, ZYNLONTA net sales grew 7% versus the fourth quarter of 2023. Our total operating expenses on a non-GAAP basis which excludes stock-based compensation, were down 16% compared to the first quarter of last year. This mainly reflected our focus on driving operating efficiencies, together with reduced R&D expenditures 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 capital. To confine the reconciliation of GAAP measures to non-GAAP measures in the compounding financial tables of the press release issued earlier today and in the appendix of this presentation.

Moving to the bottom of the P&L, GAAP basis, we reported a net loss of $46.6 million for the quarter or $0.56 per basic and diluted share. On a non-GAAP basis, adjusted net loss was $31.1 million, adjusted net loss of $0.38 per basic and diluted share. The decrease in both reported and adjusted net loss for the first quarter of 2023 was primarily due to lower operating expenses.

Today, we have announced the pricing of a registered direct offering, which included prefunded warrants. We expect to close by May 8, and the offering is expected to raise approximately $105 million of gross proceeds. We have been delighted by the response from rate to high-quality institutional investors, and we expect to proceed to extend our cash runway into the middle of 2026.

By strengthening our balance sheet, we believe we are now better finance to pursue our corporate strategy. As a reminder, hematology continues to be the primary focus of our capital allocation. And within this, our key objective is to create value by expanding the use of ZYNLONTA beyond the current indication. We expect to achieve this by fully supporting our commercialization effort in the U.S. directly and to our partnerships ex U.S. and by investing behind potential expansion into earlier lines of DLBCL and indolent lymphomas.

In solid tumors, our aim is to pursue multiple ADC candidates in parallel and increase our shots on goal, mainly through our novel exatecan based research platform. We will determine on a case-by-case basis, whether we wish to progress candidates internally or seek partner in order to share the development of financial costs. As Ameet mentioned earlier, we intend to take at least 1 candidate forward to IND and the new funds raise give us a strategic figure to do so.

My final slide highlights the multiple potential value-driving milestones, which we expect in the coming year. Importantly, we have delivered on our promises to date in 2024 with positive updates for ZYNLONTA in the LOTIS-7 study and MZL IIT trading. With the initiation of dosing of ADCT-601 impact credit cancer and with the disclosure of our existing new research platform at our virtual investor research event.

In the second half of this year, we have multiple potential value generating catalysts, including expected completion of enrollment in LOTIS-5, initial efficacy and safety data from LOTIS-7 Part 2 expansion and initial read of ADCT-601 in AXL in both sarcoma and pancreatic cancer.

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

A
Ameet Mallik
executive

Thanks, Pepe. To conclude my team and I are very proud of our performance in the first quarter of 2024. We achieved another quarter of sequential growth with ZYNLONTA. We delivered against each of the planned key research and development milestones, and we maintained our disciplined approach to capital allocation.

Looking ahead with the strengthened balance sheet and enhanced financial flexibility to execute our strategy, I am confident that ADC Therapeutics is well positioned to drive value creation for all of our stakeholders.

With that, operator, could you please begin the Q&A session.

Operator

The first question will be from Kelly Shi from Jefferies.

Y
Yun Zhong
analyst

This is Yun for Kelly, and congratulations on the marginal zone lymphoma data. I believe you reported very positive data from the follicular lymphoma program were investigator-initiated study at ASH and so can you remind us your plan for follicular lymphoma and compared to marginal zone lymphoma. And which one do you think could potentially be -- maybe reach the potential or enter sponsored study first? And have you received any feedback in terms of the safety, considering that it's into lymphoma patients?

A
Ameet Mallik
executive

Yes. No, thanks for the question. I think you're right to say that we were excited to share data in an oral presentation last ASH on the relapse/refractory follicular lymphoma population which showed that the combination of LOTIS plus rituximab had an overall response rate of 96% and a CR rate of 85% with a manageable safety tolerability profile.

So I think that was really encouraging data, of course, now seeing the marginal zone lymphoma data and then another into lymphoma with again, high overall response rate, higher CRs and again, a manageable safety profile. We're really encouraged. Both of these trials have been expanded. So the follicular lymphoma patient study will now be 100 patients. Marginal zone will be 50 patients, both are multicenter studies as well.

And with both of them, we plan to pursue both our regulatory strategy as well as a compendia strategy in parallel based on the outcome of the data. The one thing to note about the follicular data that's important is that it's really just going after the high-risk patient population. We know that when you go after all comers in follicular lymphoma, there is a precedence for randomized Phase III studies with long follow-up.

We're focused on a narrow population, which is a high-risk population, most of which were POD24. And we think that if the data looks good, there may be a faster pathway potentially either through a regulatory pathway or through guidelines in that more narrow patient population.

MZL is probably even more straightforward because if you look at the majority of -- if you look at everything that's been approved either by the FDA or in guidelines they've been approved based on either single-arm studies or subsets of larger randomized studies in indolent lymphoma studies and typically with somewhere between 40 to 70 patients.

So we think the 50-patient study we're running is an appropriate size. And based on the data maturity from this study, we again will pursue guidelines and a regulatory pathway in parallel. So that, I would say, is the even more straightforward pathway because there's so much precedent in MZL, but we also think just given the strength of the data, have a really interesting opportunity in follicular as well.

Operator

And our next question will come from Michael Schmidt from Guggenheim.

M
Michael Schmidt
analyst

Yes, super interesting update here at MZL. Obviously, I think you said all of the patients are still in response. Could you just help us contextualize the duration a little bit? What do we know about the duration clinical benefit for other drugs in MZL and then how do we compare to that? And then, yes, I think you did have this 1 patient discontinued due to toxicity. Can you just comment on what that was? And then I had a follow-up.

A
Ameet Mallik
executive

Yes. Thanks, Michael. We're -- yes, as you said, we're really encouraged by the data as well. And also in MZL, confirming what we've seen in follicular or what we've seen in other areas, the safety profile has been really good. We haven't seen any new safety signals in any of these studies. So that's been encouraging.

But I'm going to turn it to Mohamed to talk about both the duration that's seen in other treatments and what we would want to see here.

M
Mohamed Zaki
executive

Yes. Thanks, Michael. First, I want to highlight that one of the patients that we see are already in 20 months. Many of the patients have currently are more than 10 months and all are ongoing. You are correct at the time of account. What has been reported in literature, it's smaller trials and range between possibly 15 and 18 months. Those are the kind of PFMs that have been reported on their ability within either single agents or in combination.

So if the data maintains the way it is and responses are continuing for all the patients that we have seen, you've heard 13 [indiscernible] [ 16 CR AND 1 BR], we believe we will be in a very good place in terms of the ability, but again talk about durability a little bit too earlier to talk about.

A
Ameet Mallik
executive

Yes. And then, Michael, your second question was around the 1 patient with toxicity. We don't have more details. The investigators planning as there is the sample size increases and the duration and follow-up increases to do a much bigger presentation at a more major medical congress where he will share all the data. It doesn't want to compromise that. So what we know from the investigator is 1 patient had a toxicity discontinued after cycle 4, that patient was already in CR.

Once the patient was discontinued, the toxicity fully resolved and that, that patient still remains in CR. Now that patient is 6 months out, so that's what we know. The other thing we understand from the investigators, everything they've seen across all 15 patients, the safety profile is consistent with the known safety profile of ZYNLONTA.

M
Michael Schmidt
analyst

Great. Awesome. Yes, super interesting. And then a question on LOTIS-7. I know you had some really early Phase I data at AACR and I just wanted to know if you could provide some visibility on the next update. I think you have another look at data in the second half of this year and then more in the first half of next year as well.

A
Ameet Mallik
executive

Yes. So we are now in Part 2 dose expansion right now. We were quite pleased, I think, with the dose escalation, how smoothly it went and now we're in dose expansion looking at ZYNLONTA plus glofitamab and second line plus DLBCL patients. We're looking at it at 2 different doses of ZYNLONTA, 150-microgram per kilogram dose as well as the 120-microgram per kilogram dose, both in combination with the full doses of glofitamab.

We are expect to complete the enrollment of roughly 20 patients in each of those dosing cohorts by the end of this year, and then we will share the safety and efficacy data that's available for all evaluable patients. What we mean by that is patients that have had at least a 12-week scan because obviously, any responses we want to make sure are confirmed. So that will be likely a subset of those 40 patients that are actually available at that time. We will share all the data available by the end of the year and then provide an even more comprehensive update in the first half of next year when we have data from all 40 patients including longer follow-up.

M
Michael Schmidt
analyst

Great. Super helpful. And then lastly, on LOTIS-5, it sounds like you're well on track to complete enrolling here later this year. And just curious if you had any additional visibility on the event rates as they're coming in and sort of the timing of the primary analysis?

A
Ameet Mallik
executive

Yes. I mean as you said, and I'll turn it to Mohamed, to comment further. But we're on traffic, we decided the enrollment pace has picked up quite a bit over the course of this past year and even this year, in particular, has picked up quite a bit. So we're confident in completing the enrollment of the study this year. It's an event-driven trial, so you can never predict the -- once it's going to exactly read out. But based on our current thinking, we believe it may read out as soon as the end of 2025, which if that's the case, and it's positive, could lead to an approval as soon as the end of 2026. But Mohamed, do you want to comment more on the enrollment and what you're seeing with LOTIS-5?

M
Mohamed Zaki
executive

Yes. We're very pleased with the current enrollment. It picked up strongly during 2023 and 2025 release. We are still -- and I believe that we will be able to build all the study this year, things are doing very well. Also, we have a DMC that meets regularly that have cleared the study multiple times, no changes. So that's a very positive sign. In addition, I would like to say that the events are being reviewed by independent sensor review. So that's another very key element for us to make sure that those are confirmed. And then completely independent, as you know, we're blinded, but it's an event-driven study and stick until next year, that's a positive thing. And hopefully, that would remain the case. So that's pretty much all about good sign at the moment.

A
Ameet Mallik
executive

Yes, I think all on track with LOTIS-5. We feel good about the progress and we're well on track to complete it this year.

M
Michael Schmidt
analyst

Great. Congrats on the update today.

Operator

And our next question will come from Gregory Renza from RBC Capital Markets.

U
Unknown Analyst

This is [indiscernible] on for Greg. Congrats on the progress. I have questions on the competitive dynamics from CD20 bispecifics. Number one, has the impact being fully realized the impact of the competition from CD20 bispecifics on ZYNLONTA, has it been fully realized in a third-line setting. And now the Roche recently announced that the trial in the second line hit the timing endpoint and it could potentially be ahead of ZYNLONTA combination from LOTIS-5. I'm just curious how should we think about the competition from that CD20 bispecifics combo to LOTIS-5.

A
Ameet Mallik
executive

Yes, that's a great question. Yes, the bispecifics, both of the approved bispecifics in the third line plus DLBCL setting are definitely getting uptake, primarily in the academic center. We see much more limited use in the community. So in the academic center, there is quite a bit of use of bispecifics post CAR-T. I think importantly, we still have seen some modest growth, though, in the academic centers overall in our volume when you look at Q4 to Q1.

What that's been driven with is while you have some lower level of depth in some centers that we're using ZYNLONTA quite a bit in that setting, we've actually seen a higher amount of breadth of centers and academic centers that are using the product. And so in essence, we've been able to basically compensate for a lot of that competitive impact, although it's real. I mean bispecifics are definitely being used quite a bit, and you can see that their growth rates a lot in that third line plus post CAR-T in the academic setting.

So we've felt the competitive impact. I think, importantly, though, we've been able to largely offset it in active center, and we see continued growth in the community as well. So we think our strategy is working. In terms of the data, around the glofitamab plus [ Genmab ] combination. We'll have to look, we have to wait and see the data. Obviously, it hasn't been published. They give top line results. I mean one thing of note, I think, is just that they said that the -- I think that we'll have to pay attention to is what's the toxicity profile. We don't know. But obviously, using systemic chemo with a bispecific, you'll have to see what the toxicity profile looks like.

I think there -- we feel quite confident, I think, in our combinations both of ZYNLONTA plus rituximab as well as ZYNLONTA plus glofitamab given the toxicity profiles we've seen there. So I think as we move into the second line, it's important to have strong efficacy and manageable safety tolerability profile. We feel confident in both of our approaches.

K
Kristen Harrington-Smith
executive

I don't have much to add, Ameet. Yes, we're excited to see this star load data that will be out at EHA. And as Ameet said, we've been able to hold share pretty much in the academic centers. We see that despite the bispecifics, we have strong advocacy in the academic centers. And what we also hear is that these advocates recommends ZYNLONTA to the community treaters, which is critical. Once we see the data from LOTIS-5, the racing is that rituximab is probably one of the most commonly used agents out there with a lot of familiarity, so between LOTIS-5 and LOTIS-7, we offer great optionality with ZYNLONTA.

A
Ameet Mallik
executive

Yes. It's a really, really important point that Kristen just made, one of the most predominant use is, we know that CAR-T is only used in about 20% of patients second line really in the academic center. The majority of patients in academic centers are getting it. In the community though, our base chemo regimens are very, very commonly used. So we think in our based ADC approach is going to fit really well better.

Operator

And our next question will come from Brian Cheng from JPMorgan.

L
Lut Ming Cheng
analyst

Maybe just the first question on LOTIS-7. Can you talk a little bit more about the strategy beyond those expansion in LOTIS-7. Will there be a need to run a larger second-line pivotal study to get you officially move into the bispecific -- move in of the bispecific combo? And if yes, how do you think about the study design and the timing? And I have a follow-up.

A
Ameet Mallik
executive

Okay. Yes. Thanks, Brian. Great question. I'm going to hand it to Mohamed to answer the question on LOTIS-7.

M
Mohamed Zaki
executive

Yes. Thanks, Brian. This is a stick-wise approach. First, I would like to see how the efficacy in the combination second line plus looks like and how it compares in the competitive environment. And definitely, we are looking to see how the safety profile is looking like. We're very pleased that we cleared all doses and see that. When we get to that point with the 2 doses that we're expanding, if the data persists, we're definitely planning to have a conversation with the regulators about the possibility of a Phase III approval there.

At that time, we will see what the comparator are -- would be. However, there could be investigated best choice, as you should be aware of because they're multiple agents and many things could be available at that time. But of course, it's going to be a data-driven approach and the conversation with the agency is going to tell us more about that.

L
Lut Ming Cheng
analyst

Okay. And then maybe a second one on -- for Pepe. Can you give us a better sense on how you define commercial brand profitability this year? Is it factoring in only cost of goods sold and selling and marketing expense? Or is there additional consideration coming from G&A expense as well.

J
Jose Carmona
executive

Yes. Thanks for the question, Brian. So this year, as in long term, we'll be able to pay for all the direct commercialization effort. That includes all the sales force, MSLs, the A&P that we're investing in the drug the IITs that we have been executing. And on top of that, obviously, cost of goods and rolls and whatsoever. So it doesn't -- what it doesn't include is the pipeline. So our LOTIS-5 and 7 trial and corporate G&A. That is not included.

Operator

And I am showing no further questions from our phone lines. And I'd like to turn the conference back over to Ameet Mallik for any closing remarks.

A
Ameet Mallik
executive

Thank you very much for joining our call today, and thank you for your continued support. We look forward to keeping you updated on our progress. Have a very nice day, everyone. Thank you.

Operator

This concludes today's conference call. Thank you for your participation, and you may now disconnect. Everyone, have a wonderful day.

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