Lite Strategy Inc (LITS) 2021 Q4 法說會逐字稿

Good afternoon, and welcome to the MEI Pharma 2021 Fiscal Year-End Conference Call. Please note that the call is being recorded. At this time, I would like to turn the call over to David Walsey, MEI's Senior Vice President, Corporate Affairs. Please proceed.

Thank you. Good afternoon, everyone, and thank you for joining us. After the market closed today, we filed our Form 10-K for the fiscal year ended June 30, 2021, with the Securities and Exchange Commission and issued our financial results and corporate highlights press release, both of which are available on our website at www.meipharma.com.

On our call today, we will provide a summary of financials from the fiscal year ended June 30, 2021, and then review progress in our programs and business over the last year. We will then open the call to your questions.

Before we get started, I want to call your attention to the fact that this conference call may contain certain forward-looking statements within the meaning of the safe harbor provisions of the Securities Litigation Reform Act of 1995. You should be aware that our actual results could differ materially from those contained in its forward-looking statements, which are based upon management's current expectations and are subject to a number of risks and uncertainties as discussed in our SEC filings, including our most recent annual report on Form 10-K filed earlier today. A replay of this call will be available on our website relatively soon after its conclusion.

I'd now like to introduce you to our speakers for today. With me are Dan Gold, our President and Chief Executive Officer; and Brian Drazba, our Chief Financial Officer. Additionally, David Urso, our Chief Operating Officer and General Counsel, is also with us today. Brian will start with a summary of our financial results before Dan shares remarks reviewing the year and comment on the coming quarters. After that, we will open the line for your questions. I'll now turn the call over to Brian.

Thank you, David. I'll provide a brief overview of financial results. For more detailed information regarding our financial results, I invite you to review our 10-K filed earlier today. I'm pleased to report that we finished fiscal year 2021 with about $153 million in cash, cash equivalents and short-term investments with no outstanding debt. For the year ended June 30, 2021, and net cash used in operations was $52.4 million compared to $45.3 million for 2020. Excluding upfront cash payments we received from Kyowa Kirin.

The increase primarily relates to increased costs associated with our clinical development programs. Research and development expenses were $69.4 million for the year ended June 30, 2021, compared to $34.1 million for 2020. The increase was primarily related to increased development cost associated with zandelisib, including start-up costs related to the Phase III COASTAL study, increased drug manufacturing costs and increased consulting fees to support clinical trial activities.

General and administrative expenses were $24.4 million for the year ended June 30, 2021, compared to $16.7 million for 2020. The increase primarily relates to increased professional services cost, increased personnel cost associated with increased headcount to support our activities, including preparation for commercial launch of zandelisib and general corporate expenses incurred during 2021.

We recognized revenues of $25.5 million for the year ended June 30, 2021, compared to $28.9 million for 2020. The decrease in revenue primarily related to the license agreement with Kyowa Kirin and included the recognition of fees allocated to research and development obligation. Revenues also includes recognition of fees allocated to performance obligations in accordance with the Helsinn License Agreement.

Net loss was $50.6 million or $0.45 per share for the year ended June 30, 2021, compared to a net loss of $46 million or $0.51 per share for 2020. The company had 112,614,643 shares of common stock outstanding as of June 30, 2021, compared to 111,513,689 shares as of June 30, 2020. The adjusted net loss for the year ended June 30, 2021, excluding noncash expenses related to changes in the fair value of the warrants, a non-GAAP measure, was $68.7 million compared to an adjusted net loss of $23.1 million for 2020.

With that, I'll turn the call over to Dan.

Thanks, Brian, and thanks to everyone for joining us this afternoon. This past fiscal year was successful on multiple fronts for MEI. I'm proud of the progress we have made across our pipeline to execute on our mission to develop and commercialize novel best-in-class cancer therapies intended to improve outcomes for patients.

Understandably, our main focus is currently on the clinical development and pre-commercialization activities for zandelisib. In particular, we are very focused on the top line results from TIDAL, our potentially registrational study for zandelisib expected by year-end.

As you may know, zandelisib, formerly called ME-401 and is a selective PI3-kinase delta inhibitor being investigated as an oral treatment for patients with B-cell malignancies. Differentiated by its molecular structure and pharmacological properties, zandelisib is administered on an optimized dosing schedule consisting of once-daily administration for 2 28-day cycles as a response induction therapy, followed thereafter by intermittent dosing therapy, or IDT, the unique zandelisib IDT consists of once-daily dosing for the first 7 days of each subsequent 28-day cycle.

The IDT is intended to mitigate immune-related adverse events while providing continuous therapeutic benefit. To date, our data demonstrate that zandelisib administered on the IDT is associated with a low incidence of Grade 3 or greater adverse events of special interest. In addition, with longer follow-up, we've observed that the IDT continues to demonstrate durable responses and general tolerability of the regime.

We think this provides an exciting opportunity for zandelisib to deliver an improved clinical benefit and the opportunity to positively impact the standard of care for patients with B-cell malignancies. We currently, the standard of care for follicular lymphoma patients that have received 2 or more prior therapies is highly fractured treatment setting.

Despite this, our research suggests that PI3-kinase delta inhibitors are the most prescribed therapy in this setting where we are planning our initial submissions for marketing approval. To date, there does not appear to be a PI3-kinase inhibitor that can provide physicians and their patients an optimal risk/benefit ratio to make any agent the standard of care.

Consequently, we believe there's a significant opportunity to consolidate treatment in this patient population if a treatment can provide high response rate along with the tolerability profile that can maintain patients on therapy for an extended period and provide durable responses.

We believe that other therapies, which have been unsuccessful at consolidating treatment are challenged by clinical profiles that do not offer an efficacy and safety profile that meets this hurdle.

Later this year, we plan to report top line data from the Phase II TIDAL study, providing an opportunity to update zandelisib's emerging clinical profile. Enrollment in the follicular lymphoma primary efficacy population of 91 patients and enrollment in the full study population of 120 patients are now both complete.

TIDAL is evaluating zandelisib as monotherapy in adults with relapsed and refractory follicular lymphoma after failure of at least 2 prior systemic therapies, including chemotherapy and an anti-CD20 antibody. Subject to the results and discussions with the FDA, we plan to submit the TIDAL data to support an initial market approval by an accelerated approval marketing application.

Our results suggest -- our research suggests, excuse me, that the annual incidence of follicular lymphoma in the United States is about 14,000 individuals, while the prevalence is about 100,000 patients. We estimate that over 40% of patients with follicular lymphoma at some point will relapse after each remission. And that about 8,000 patients relapsed or refractory with follicular lymphoma are treated on an annual basis in the U.S.

Earlier this year, we also initiated COASTAL, a global Phase III study as part of our plan to expand zandelisib evaluation into earlier lines of follicular lymphoma therapy in cooperation with our global partner, Kyowa Kirin. For COASTAL, we are evaluating zandelisib in combination with rituximab in follicular and marginal zone lymphoma patients who received 1 or more prior lines of therapy.

The first patient in this study was enrolled last month. COASTAL is intended to support FDA approval for additional indications and act as the required confirmatory study for the potential accelerated approval of zandelisib in patients with relapsed or refractory follicular lymphoma or marginal zone lymphoma. COASTAL is also intended to support marketing application globally.

Because we are confident in the differentiation of the zandelisib profile and are committed to improving care in patients with relapsed and refractory follicular and marginal zone lymphoma, we initiated the COASTAL program at risk prior to seeing the results of TIDAL. We believe that the patient population is being evaluated in TIDAL and COASTAL represent a significant commercial opportunity upwards of $1.5 million in the underlying addressable relapsed and refractory follicular and marginal zone lymphoma populations.

Even with modest assumptions on potential zandelisib usage in the population of patients enrolled in the TIDAL study, this represents an important initial opportunity from which to build zandelisib's commercial value, subject to marketing approvals in new indications, particularly in combination with rituximab and other therapies.

Efforts to expand the zandelisib development program this year include initiation of a second arm in TIDAL evaluating zandelisib monotherapy in patients with marginal zone lymphoma, also after failure of at least 2 prior systemic therapies, including chemo and anti-CD20. Subject to the results, data from this arm are also intended to be submitted to the FDA to support an accelerated approval marketing application.

In addition to evaluating zandelisib as a monotherapy and in combination with rituximab, we are evaluating other combinations, including with zanubrutinib, a BTK inhibitor developed and marketed by BeiGene. Clinical evaluation of the combination is currently under a clinical collaboration with BeiGene.

Initial results exploring the combination were presented at EHA earlier this year. The objective of our clinical efforts was to see if we could leverage dose and schedule to provide deeper and prolonged responses. We reported that we identified a unique optimized dosing regimen, which for zandelisib, was the IDT that we believe may capture the synergistic potential of this combination in a well-tolerated manner.

We believe the initial data from the run-in portion of the study in 20 patients is very encouraging. The optimized dosing schedule did not result in additive toxicity compared to each agent alone and we saw a 100% response rate in patients with relapsed and refractory indolent B-cell malignancies. Responses were durable as of the reporting of data, though follow-up was limited as of the data cutoff.

Currently, we are enrolling expansion cohorts evaluating follicular and mantle cell lymphoma patients using this combination. In addition to our COASTAL study, other company-initiated studies include a planned Phase II study evaluating zandelisib plus venetoclax and rituximab in patients with relapsed chronic lymphocytic leukemia as well as the ongoing Phase II pivotal study in Japan conducted by our partner, Kyowa Kirin, evaluating zandelisib in patients with indolent B-cell non-Hodgkin's lymphoma without small lymphocytic lymphoma, lymphoblastic lymphoma and Waldenstrom's. This study is intended to support a Japanese filing with PMDA.

Finally, our efforts also include the support of ongoing and planned investigator-initiated studies such as the study being conducted by the Cleveland Clinic evaluating zandelisib plus R-CHOP to treat patients with newly diagnosed diffuse large B-cell lymphoma. We look forward to announcing additional updates to the clinical development plan as we continue to build out our evaluation of zandelisib for additional indications, particularly in combination with other cancer therapies.

All of the zandelisib development activity I'm describing, and more to come, leverage what we believe is a very strong and promising data set generated to date. In addition to this zandelisib plus zanubrutinib data summarized above, at ASCO and ICML earlier this year, we reported updated data from a Phase Ib study exploring zandelisib as a monotherapy and in combination with rituximab.

Specifically, with respect to relapse and refractory follicular lymphoma, we reported a 95% overall response rate in patients treated with zandelisib plus rituximab in this Phase Ib study. It's interesting to note that the study subject population evaluated was similar to the study population in our ongoing COASTAL study. We also reported a 78% overall response rate in patients treated with zandelisib as monotherapy.

Response rates were high regardless of POD24 status, the line of therapy or tumor bulk. Median duration of response was not reached in any of these groups. Importantly, treatment was generally well tolerated with a low incidence of Grade 3 or greater adverse events, no cumulative toxicity over time and an 8% discontinuation rate due to adverse events.

We have been asked in the past if there was an impact of the ongoing COVID-19 pandemic on the zandelisib clinical program. I can say that we did our best to be proactive in taking steps consistent with guidance from the FDA and other regulatory authorities to communicate with sites and investigators and in making accommodations to patients in order to maintain patients on study and preserve the overall integrity of the study.

While the pandemic adds an element of uncertainty to our business, and the ongoing impact remains subject to further developments, we are confident in our ability to navigate challenges across our business in a manner that can continue to minimize disruptions to the extent reasonably possible. Given the broad opportunity presented, the progress in the zandelisib clinical program, the resources and expertise that we are bringing to bear, including our continued precommercialization activity and infrastructure build-out, we are excited about the potential we can bring to patients and the value that we can deliver to our shareholders with this program.

I would now like to briefly update you on some of our other pipeline programs. Voruciclib is our oral CDK9 inhibitor that we believe has the potential to improve treatment options for patients with hematologic and solid tumors. As you may know, CDK9 is a transcriptional regulator of the myeloid leukemia cell differentiation protein, or MCL-1, a member of the family of anti-apoptotic proteins, which when elevated may prevent the cell from undergoing apoptotic cell death.

Inhibition of CDK9 blocks the production of MCL-1, which is an established resistance mechanism to B-cell lymphoma or -- to the B-cell lymphoma or BCL-2 inhibitor, venetoclax. CDK9 is also a transcriptional regulator of the MYC proto-oncogene protein, which regulates cell proliferation and growth. Upregulation of MYC is implicated in many human cancers and is frequently associated with poor prognosis and unfavorable patient survival.

With respect to the development for hematologic malignancies, we are currently conducting a Phase I study, evaluating the dose and schedule of voruciclib as a monotherapy in patients with relapsed or refractory B-cell malignancies and acute myeloid leukemia, or AML, after failure of prior standard therapies to determine the safety, preliminary efficacy and appropriate tolerated dose. We plan to provide an update on this portion of the development program later this year, perhaps at ASH in December.

Our plan now, subject to FDA agreement, is to evaluate the dose and schedule of voruciclib in combination with a BCL-2 inhibitor such as venetoclax and to assess synergies and the opportunity for combination treatments initially in patients with AML and subsequently across multiple B-cell malignancy indications. As mentioned above, this would address the MCL resistance mechanisms associated with BCL-2 inhibition.

Our voruciclib development plans also include evaluation of patients with solid tumors. In addition to regulating MYC transcription, CDK9 directly decreases phosphorylation of MYC protein, a property that is implicated in stabilizing MYC in KRAS-mutant tumors. Since KRAS-mutated tumors are frequently associated with overexpression of MYC, we believe voruciclib could be an attractive therapeutic target for KRAS-mutated cancers particularly in combination with a KRAS inhibitor.

This is supported by data we reported at the AACR 2021 meetings in preclinical models supporting voruciclib CDK9 activity, relating to MYC inhibition and degradation as well as showing that it synergistically inhibits KRAS G12C mutant cancer cell lines in combination with KRAS G12C inhibitors, both in vitro and in vivo. The research presented suggested that voruciclib could be an attractive therapeutic target for cancers driven by KRAS mutations.

Lastly, I'll update you very briefly on the ME-344, our novel and tumor-selective mitochondrial inhibitor targeting the OXPHOS complex. As you may recall, our clinical data demonstrates that ME-344 in combination with the anti-angiogenic antibody Avastin, reduces mean relative Ki67 levels in tumors of women with HER2-negative breast cancer compared to a control group of patients receiving Avastin alone.

Based on the output from an advisory board, we convened to review options that offer an efficient path forward for evaluating the combination of ME-344 and Avastin. We are planning to start a Phase II study of ME-344 plus Avastin in patients with relapsed colorectal cancer, perhaps around the middle of calendar 2022.

In sum, Fiscal 2021 was a successful year in advancing our business, particularly with respect to the zandelisib program. We look forward to continuing to provide updates as we advance towards potential commercialization. And as we move forward with both the voruciclib and ME-344 programs to further explore their potential to deliver benefit to patients with cancer.

We started the new fiscal year with approximately $153 million. This does not include the $10 million milestone payment payable to MEI from Kyowa Kirin that was triggered by the dosing of the first COASTAL patient last month. Receipt of the milestone payment is expected in the quarter ending September 2021.

We believe we have runway to see us into 2023. In terms of upcoming milestones, we expect top line title data by the year-end, updates on the zandelisib/zanubrutinib combination, including the follicular and mantle cell expansion cohorts, start of additional zandelisib clinical trials such as the CLL trial and other investigator-initiated studies, voruciclib data from our ongoing Phase I study, updates on potential timing of a study starting next year of voruciclib in combination with the KRAS inhibitor and the start of the Phase II ME-344 study in combination with Avastin in colorectal cancer patients. We look forward to keeping you updated as we work to deliver benefits to patients and value to our investors.

And with that, I think we are now ready for questions. Operator?

(Operator Instructions) Our first question today comes from Stephen Willey with Stifel.

This is Bonnie on for Steve Willey. I wanted to ask about your upcoming top line data for TIDAL in follicular lymphoma. Can you set the stage for us in terms of what we should expect? I'm not sure if you can give us an idea of what the duration of follow-up will be, but what do you think is important for us to pay attention to at that median follow-up time point?

Right. That's a great question. Thanks for asking. So to be clear, the primary endpoint of this study for regulatory approval is overall response. And that is the data that we are focusing right now, and that is what we will report for sure when the data are ready to report.

In terms of the median follow-up, I don't know what that is now. Obviously, it's related to the pace of accrual. We will be able to report with some clarity what the follow-up is at the time of the report. But obviously, that is an ongoing collection of data that will continue so that we can give a more precise durability answer probably more towards the second half of next year or the first half of next year.

So to be clear, the overall response will be in all patients who have had a minimum of 6 months of treatment. And certainly, many have had many more months of that. But precisely, I don't know where that's going to fall once we lock the data, but we'll give the best estimate we can at the time.

Okay. Great. And will you also be looking or analyzing the POD24 patients separately, similarly to how you've done in the past? And I'm not sure if you can give us an idea of like the proportion of patients that are POD24. Would it be similar to what was seen in the Phase Ib portion of the trial?

Right. Yes. So we are analyzing that. I don't know in terms of the proportion of patients in this particular study where it falls compared to the Ib. But clearly, we know that there are POD24s that have enrolled. And we will analyze that. That's just an exploratory analysis that we'll do. We probably won't have much to say about it at the top line data, but certainly, we'll have more to say down the road once we've cleaned all the data and unlock the database.

Okay. And my last question is ME-344. Can you discuss briefly like why have you chosen a CRC -- to target relapsed/refractory CRC patients and maybe some data that you have to support that choice?

Right. So based on the mechanism of action that we believe is operating for -- when you combine an anti-angiogenic with ME-344, we think that this is applicable across all -- potentially across all indications where anti-angiogenesis is important in controlling tumor growth.

As I mentioned, we did have an advisory panel of very prominent physicians in the U.S. who treat patients where anti-angiogenics are used primarily, which is really -- was included colorectal and a couple of other indications. It was the consensus from that discussion that colorectal in third line is the best place to look because Avastin is currently used in the third-line population. And the median durability or PFS of that is actually quite short and with very low response.

So the feeling was that if you were able to expand PFS regardless of response rate, that would be a very meaningful outcome to encourage further development. So that was the decision. We do have preclinical data in animal models, looking at in xenograft studies looking at breast cancer and colorectal and lung models. So again, we don't think it's anything particularly the tumor type. It's really how deprived of oxygen these tumors are and when they grow and how the anti-angiogenics can reverse that and make ME-344 more effective. So it's really a matter of most of these cancers become hypoxic and that's the mechanism action that we're going after with the combination.

Our next question comes from Yale Jen with Laidlaw & Co.

Okay. Great. Congrats reaching the underlying at this point. So first, just a follow-up from the previous question in terms of if you could have positive TIDAL readout, what may be the time line afterward for the filing and the preparation needed for that?

Yes. It's a really important question, Yale. Thanks for asking. So the time line is completely driven following our pre-NDA discussions with the FDA. As I'm sure most of you are aware, the primary endpoint for an accelerated approval in this disease setting is overall response. But clearly, the agency is also interested in the risk benefit. So safety is a primary concern.

And we know with this class of drugs with other drugs that late term -- later onset toxicities have been observed. So there is an interest as part of the agency, and they've given guidance to all companies to have sufficient follow-up as well as durability.

And in many of the cases of the prior PI3-kinases, the durability and the toxicity sort of went hand in glove because if patients are being -- are coming off study because of toxicities, then they get censored. So the ability to see a true durability measurement is somewhat obscure.

So we'll have that conversation. We will provide the agency with our follow-up and with our safety, and we'll gain insight from them on when is the appropriate time to file. And then it's just a matter of -- we're already doing the work. This is a long process, and we've gotten a good head start on writing some of the modules and being prepared so that when they tell us it's time, we'll be ready. But I can't give you a precise date until we have that conversation.

Okay. Great. That's very helpful. Maybe 2 quick follow-up questions here. First one is that in terms of the CLL trial, you are scheduled to start it soon. Do you have a time line for when to start the one TIDAL study?

Yes. Well, we're -- we definitely will start in the first half of the year. We're working as hard as we can. I'm sure you appreciate that it's here, it's all hands on deck with everything and where TIDAL is the main focus. But this is an important study for us, and we're working our best. We already have a CRO. We're already working on contracts. So we're hopeful we can get that study up and running in the first quarter.

Okay. Maybe the last 1 is in terms of TIDAL, you do have the full patient set of 120 recruited. So is there any time we should anticipate an update on this more -- the data once they are mature?

Yes. Right. So if you recall, the primary endpoint efficacy analysis will be done on the first 91 patients. The remaining 30 patients or so we're adding to increase the safety for the agency. And so of course, we will be analyzing the response rate, but they won't be part of the label presumably to be negotiated. So we do think -- we're hopeful that perhaps around midyear, like the ASCO time frame, we'll be able to give a much more robust update of the current TIDAL data.

Okay. Great. And congrats on reaching the important milestones.

Thank you, Yale.

Our next question comes from Robyn Karnauskas with Truist Securities.

This is Kripa on for Robyn. Congratulations on all the progress this year. I know there were a couple of questions about what to exactly expect in data release. My question is, have you made a decision of what you expect to release Obviously, we're going to see ORR. But is there anything else? Or will you look at the data and then decide also depending on when you expect to present the data later? Can we expect to see any durability data at all?

And then for COASTAL, can you provide any granularity in terms of how the trial is progressing? You initiated the trial. Can you remind us how many sites you expect to run the trial in and how many are open for enrollments? Are you seeing any hurdles with the sites due to the delta variant?

Sure. All great questions. I think in terms of your first question about TIDAL and data reporting. I mean please appreciate that the overall response is based on 6 months of treatment. So if the patient responded after the first measurement, which is at 2 months, the durability of that -- that clock starts. So the durability is 4 months at that point, right?

So I think that our feeling is that whatever we have to say about durability is probably -- should be taken with a bit measured because a lot of that -- there will be a lot of noise on the right side until there's been sufficient follow-up. So I don't think even if we told you a durability number, I don't think it would necessarily be as informative as if we were able to follow the patients for, let's say, another 6 months or so, so that we have a lot more confidence in that number.

And as I said, we will continue to follow all the patients for durability as well as for safety because we know that those are both time events potentially and certainly durability is. And so rather than misleading about anything, we just -- we need the time in order to give a more accurate estimate for both of those outcomes.

So I don't -- we haven't really -- I don't think we're focusing as much as on the durability as probably the Street is and you. But obviously, it's something that is critically important. Our experience is with every study we've run with this drug that the durability and the way we use it is quite considerable, and we have no reason to believe that won't be the case. But clearly, when we see the data, we'll know.

So I don't have much more I can say about that. And again, durability is also related to the pace of enrollment. And with COVID, the enrollment was rather protracted, a lot more patients were enrolled later in the trial than early in the trial. So the durability is probably quite immature in -- when we're finally locking the response data.

You asked a question about COASTAL.

Where you are in terms of...

Yes. That's right. So what we have said, I think the trial itself is about 500 plus or minus patients in that ballpark. And I think we -- our estimate is somewhere close to 200 clinical sites globally. As you may know, it's probably more in the weeds than you care to hear. But the biggest push one does at the beginning of opening a study is getting all the sites contracted. I mean, you're literally -- we're building an army of lawyers here just to deal with the contracting because every site is a new contract.

And so that's where we spend all our energy trying to get as many sites as we can open as quickly as we can. And that's going fine. We're not really seeing a lot of issues who they are related to COVID, again, being global is helpful because the impact of COVID is definitely different amount -- around the world.

Because this is a large study and the patient population is very well defined. All the sites that are open can begin looking through their records at patients who are potentially or will be potentially -- could be included in such a study and they can start creating their list, and that's happening. Some of these patients may not have progressed yet or may not want to go on to a clinical study and all those factors. But we are building a large data set of patients who are potentially available to the study, and we're working as quickly as we can, as hard as we can to open as many of those 200 sites as we can. And that's about all the color I can really give you, and that's about all I really know.

Our next question comes from Adam Evertts with LifeSci Capital.

Great. I hate to keep pushing this point, but maybe just to clarify 1 thing on the TIDAL readout. I mean it's pretty clear we'll see response rates next quarter durability of response will take some more time. But just again on what you might share on the safety side, given how important that component is for the class. I mean, for example, will we see like a preliminary rate of discontinuation due to adverse events, something like that?

Yes. Understood, Adam. We will do our best to be a transparent. I mean we -- obviously, we understand the issue, the durability and the safety and the response. All 3 of those legs of that stool have to come in line. And we will be as transparent as we can be. I just don't -- I don't want to promise right now because a lot of that -- I mean our goal right now is to have a 100% clean data for response. And in order to make sure that when we say a patient has progressed, I mean, it has come off study for safety, we have to be 100% confident on the quality of the data.

And we're doing that actively now. We have a whole army of people who are working on getting the data in and cleaning the data. So if we're ready to tell that -- if we're ready to tell you that we will tell you. But I don't -- I just can't promise right now because I just don't know the answer. We're still several months away and the data are continually coming in and the queries are going out. So we do understand the importance of those metrics, and we absolutely want to be as transparent as we can be with reason. And when we say what we say, we want to make sure it's absolutely rock solid information.

Totally understand. I appreciate that. And Dan, maybe 1 quick question on CLL. I think the venetoclax/rituximab combo is given as a fixed duration. Just curious, maybe it's too early to think about how you'll dose zandelisib there, but have you thought about whether you would use a fix duration there as well?

Yes. So we'll be -- very soon, Adam, we'll put out -- the trial will go up on clin trials, and we'll give you exactly the dosing regimen. I think my understanding, and again, I hate to speak out of school here. I think we'll be following MURANO on the venetoclax/Rituxan regimen. And then zandelisib will be given for a fixed amount of time.

Our next question comes from Justin Zelin with BTIG.

Team, congrats on all the progress this year and very much looking forward to results later this quarter on TIDAL. Maybe if you could just walk us through as far as the development plan, once you have enhanced your monotherapy follicular data, kind of how you are thinking about the strategy of expanding to other indications? And of course, you have your ongoing studies. But if you could just maybe walk us through when we should expect the cadence of releases?

Right. So I mean just more of a general comment. I think over the years, we've tried to be pretty consistent with our view on how you -- the cancer is treated. And we really -- we have taken a fairly strong opinion that the most effective therapies are generally in combination. And I think it's been clear to the field that there have been challenges in accomplishing combination therapies with prior PI3-kinases. And that's why, obviously, we're so excited about the profile of zandelisib and the way we're able to use it that we can really now explore these combinations like we're doing with zanubrutinib, like we're doing with Rituxan, like we plan on doing with venetoclax and Rituxan and CLL.

So I think going forward, what you should be looking for from us is a number of studies in addition to the ones we've spoken about in other indications in earlier lines of therapy where we're using the drug in combination with other standards of care. Again, and what we've said in the past is one of our goals is whenever possible to see if we can bring a non-chemotherapy combination regimen to patients to give them and the alternative and get the physicians an alternative.

So I think we've been pretty clear about our near-term plans, in terms of COASTAL, TIDAL, the zanubrutinib combination CLL study, the marginal zone study. Zanubrutinib is being studied in mantle as well as follicular and the R-CHOP. I mean there is a situation where we are employing chemotherapy. So I think we do have other studies that will be of interest to you and to the investors as time goes, and we're going to try and roll those out as quickly as we can. Many of these are with investigator study. Some of those will be our own studies. But I think that is -- we really do feel that zandelisib has that potential to kind of form the backbone around which one can combine other therapies, and that's kind of how we're approaching its development.

(Operator Instructions) Our next question comes from Matthew Cross with Alliance Global Partners.

Thanks for taking a couple of questions from me. I will not ask you about the TIDAL data in Q4.

How about the durability?

But given that you, I guess, mentioned, if I heard you correctly, that now the whole primary endpoint population TIDAL's enrolled, including MZL...

Sorry, just to be clear, we did -- yes, that is incorrect. With the entire 120 safety population for follicular is in fully enrolled. The marginal zone study just opened earlier this past year. So that still has room to go.

Got it. Okay. That kind of reframes my question a little bit, but nevertheless, I was kind of curious to get your updated thinking on the MZL cohort. And it's been asked about what kind of your filing strategy would be for FL. I wanted to get kind of the latest thinking based on what you're now seeing as MZL enrolls, whether you would opt to wait for MZL's ORR data in the interest of collecting longer-term safety as you alluded to? Or if we should kind of expect a staggered multi-filing strategy for those 2 indications?

Right. Yes. No, I think it's the latter, Matt. I think that -- I mean, we have pretty -- been pretty clear that we plan on getting the follicular arm in front of the FDA and begin the filing if appropriate as quickly as we can. And then the marginal zone would be an additional indication as soon as that trial enrolls. I mean, obviously, those -- there are fewer of those patients. Although the trial is smaller, it's something like 61 patients or something for the efficacy evaluable.

So -- and the upside for us is that we didn't have to get the sites up and running as we did for the follicular study because we're using the same sites. So we hope that the enrollment will go a bit faster than it did for the follicular even though there are less patients. It's a rare population. So that will be a separate filing based on the outcome of the data.

Got it. Okay. That's helpful. And then the second that I had was just around the Phase II in CLL for zan plus ven plus rituximab. I was just kind of curious to get the rationale for the inclusion of ven in that combo given what we saw, I think, a near 100% response rate, certainly small numbers, but for zan plus rituximab in the Phase Ib in CLL. I was just curious about the inclusion of ven, especially given some of the dosing considerations that were brought up by Adam. Just curious to get your cent -- take on that triplet and whether we should be inferring anything about that in terms of the line of therapy and then general positioning that you might be pursuing at CLL?

Right. So yes, I think it's an important question, and it's -- probably needs a lot more time to answer than we have on this call. But we have spent a lot of time with our advisers, and we said this over -- in the past, we've had multiple advisory meetings with our key opinion leaders, both here and in the EU on really the landscape around CLL. I don't think there is a 100% response rate, by the way, plus Rituxan.

But what does appear to be clear is that the physicians are looking for time-limited therapy, and that is something that all -- many companies are pursuing. The MURANO data was very impressive, but clearly could get, better, especially for minimal residual disease in a time-limited basis. So I think that is all of our goals is to get the patients into a good, strong, deep remission and allow them to stop therapy.

If you look back on the history in CLL, the B-cell receptor engaging agents like PI3 or BTK are very effective in inducing remission and the remissions are actually pretty reasonable. But the level of CRs are quite low, and the feeling was in the advisers that if you really want to get into an MRD negativity, you do have to combine a venetoclax -- add venetoclax as part of the regimen. And so that's kind of the rationale of adding venetoclax because clearly, you are able to get into MRD negativity, which isn't really seen with either other -- the other classes of drugs.

And again, these other classes of drugs do have very good durability as long as you're taking the drug. But I think the real world experience, especially with the BTKs, is that patients don't continue to take drug, and then they need something else because they will relapse. So that's kind of our thinking and why we're going down that road.

Sure. Okay. No, that makes quite a bit of sense. And sorry, if I mumbled, the 100% response rate I was referring to was your own with -- thereabouts for zan plus ven (inaudible).

Ours, Yes. Well, yes. Of course.

But looking forward to seeing what you can do in terms of MRD negativity adding and then that makes a lot of sense.

Right. Exactly.

This concludes our question-and-answer session. I'd like to hand the call back over to Dan Gold for any closing remarks.

Thanks again for joining us today. We began our new fiscal year in a very strong position, and we definitely will look forward to reporting our progress to you across our entire portfolio in the coming quarters. Enjoy the long Labor Day weekend and be safe, and we'll look forward to catching up with you in the near future.

The conference has now concluded. Thank you for attending today's presentation. You may now disconnect.