MEI Pharma Inc
NASDAQ:MEIP
MEI Pharma Inc
NASDAQ:MEIP
Price:
3.14 USD
2.61%
Updated:
May 2, 2024
Section:
Earnings Call Analysis
Summary
Q4-2023
Q4-2023
MEI Pharma's Oncology Programs Show Promise
MEI Pharma is optimistic about their two clinical stage oncology programs: voruciclib, aimed to combat resistance in AML and other cancers, and ME-344, focused on limiting ATP in cancer cells. Voruciclib has shown promise in Phase 1 studies, while ME-344 will see data readouts in the first half of 2024. MEI Pharma targets large markets, with $2 billion in sales for venetoclax and $2 billion for Avastin in 2022, both forecasted to grow by 2028. They have $100.7 million to fund these operations for at least the next 12 months.
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Good day, and welcome to the MEI Fiscal Year-end Earnings Call. My name is Gary, and I will be the conference facilitator today. [Operator Instructions] Please note today's event is being recorded. I would now like to turn the conference over to David Walsey, Senior Vice President of Corporate Affairs at MEI Pharma. Please go ahead, sir.
Thank you, Gary. Hello, and thank you for joining the MEI Pharma conference call today. My name is David Walsey, and I'm Senior Vice President of Corporate Affairs for MEI. With me today on the call from MEI are David Urso, President and Chief Executive Officer; Jay File, Chief Financial Officer; and Dr. Richard Ghalie, Chief Medical Officer.Before turning the call over to David for opening remarks, I'd like to remind you that during today's call, we'll be making forward-looking statements. Certain information contained in this communication that are not historical in nature are forward-looking statements in the meaning of the safe harbor provisions of the Private Securities Litigation Reform Act of 1995, including, without limitation, statements regarding the potential safety, efficacy and regulatory and clinical progress of our product candidates, including the anticipated timing for the initiation of clinical trials and the release of clinical trial data and our expectations surrounding potential regulatory submissions, approvals and timing thereof, our business strategy and plans, the sufficiency of our cash, cash equivalents and short-term investments to fund our operations. You should be aware that our actual results could differ materially from those contained in the forward-looking statements, which are based on management's current expectations and are subject to a number of risks and uncertainties, including, but not limited to, our failure to successfully commercialize our product candidates, the availability of appropriateness of utilizing the FDA's accelerated approval pathway for our product candidates, final data from our preclinical studies and completed clinical trials may differ materially from reported interim data from ongoing studies and trials, costs and delays in the development and/or FDA approval or the failure to obtain such approval of our product candidates, uncertainties or differences in interpretation in the clinical trial results, uncertainty regarding the impact of rising inflation and the increase in interest rates as a result potential economic downturn, activist investors or inability to maintain or enter into and the risks resulting from our dependence upon collaboration or contractual arrangements necessary for the development, manufacture, commercialization, marketing, sales and distribution of any products, competitive factors, our inability to protect our patents or proprietary rights and obtain necessary rights to third-party patents and intellectual property to operate our business, our inability to operate our business without infringing the patents and proprietary rights of others, general economic conditions, the failure of any products to gain market acceptance, our inability to obtain any additional required financing, technological changes, government regulation, changes in industry practice and onetime events. We do not intend to update any of these factors or to publicly announce the results of any revisions to these forward-looking statements. Under U.S. law, a new drug cannot be marketed until it has been investigated in clinical studies and approved by the FDA as being safe and effective for the intended use.With that, I'll now turn the call over to David Urso.
Thank you, David, and thank you all for joining us today.On today's call, I'll make some opening remarks and then turn the call over to Richard Ghalie, our Chief Medical Officer, to review our programs. Jay File, our Chief Financial Officer, will then provide some brief financial comments before moving to Q&A. Before getting started, I want to welcome Jay. He was just appointed our CFO as of August 1. So this is his first earnings call at MEI, and we're very happy to have him on the team.With that said, I'll make a brief statement regarding the termination of the merger agreement with Infinity Pharmaceuticals before moving on to review our business. Regarding that proposed transaction, while we believe the potential upside of the Infinity merger was compelling for MEI stockholders, we value the perspective of our stockholders. With the proposed transaction behind us, we're committed to pursuing our 2 promising clinical stage programs as a stand-alone company. Looking ahead over the next few quarters, we see important opportunities in the continued progress of our 2 clinical stage oncology programs, voruciclib and ME-344. I would like to use this call to provide an update on the status of these programs and why we're optimistic about their potential.Both of our assets represent novel mechanisms of action. voruciclib is an oral CDK9 inhibitor and ME-344 is a mitochondrial inhibitor that inhibits the OXPHOS pathway. We are investigating the potential of these compounds to overcome resistance mechanisms to standard of care therapies, the BCL-2 inhibitor venetoclax for voruciclib and the VEGF inhibitor bevacizumab in the case of ME-344. The ongoing advancement of each program is based on nonclinical and in the case of ME-344, clinical data supporting proof of principle for the respective combinations. We chose these combination approaches based on clear hypotheses to address known resistance mechanisms of each standard of care therapy, clear medical need and significant commercial opportunities. We are working with some of the leading oncologists in the country in both of our clinical studies, and we're pleased with their level of engagement and interest in our programs. We expect data readouts from each program in the coming months.With respect to voruciclib, as previously reported, we've seen promising data from our ongoing Phase 1 study. Recall that voruciclib as a selective CDK9 inhibitor regulates the transcription of MCL1 and through that mechanism, also potential to address a known venetoclax resistance mechanism. The ongoing Phase 1 study is evaluating voruciclib as a single agent and in combination with venetoclax, which is standard of care in AML and used in other hematologic malignancies as well. Richard will provide more detail shortly, but in brief, voruciclib alone and in combination with venetoclax has been generally well tolerated in the Phase 1 study to date with no significant myelosuppression in patients with B-cell malignancies or AML. The results further demonstrate encouraging early clinical activity in heavily pretreated patients that progressed on venetoclax who are administered voruciclib monotherapy and at the initial dose level in combination with venetoclax. The planned voruciclib data readout in early 2024 is expected to include data from the dose ascending cohorts in the Phase 1 study evaluating voruciclib plus venetoclax in patients with AML.Here are some of the leading KOLs we are working with. We're pleased with how the study is enrolling. As for ME-344, we're pursuing a novel approach to cancer therapy with the combination of ME-344, an OXPHOS inhibitor that inhibits the production of ATP in mitochondria and bevacizumab, a VEGF inhibitor, which inhibits the production of ATP for glycolysis to deprive cancer cells of the energy needed to proliferate. Bevacizumab is an established standard of care in multiple solid tumors, including colorectal cancer. Our ongoing Phase 1b studies evaluate metastatic colorectal cancer patients with ME-344 plus bevacizumab. This novel approach to treatment has also generated enthusiasm among our investigators in the ongoing study.In earlier clinical studies, ME-344 is generally well tolerated at the dose we're currently investigating and there was evidence of clinical activity as a single agent. We had a first look at the potential for this combination in a 42-patient controlled window of opportunity clinical study in HER2-negative breast cancer patients waiting for mastectomy. Richard will discuss the decrease in the proliferation in biomarker Ki67 observed in that study. We expect that the ME-344 data readout planned in the first half of 2024, will include initial safety and efficacy data from the first 20-patient cohort in the Phase 1b study evaluating ME-344 in combination with bevacizumab in patients with metastatic colorectal cancer.We believe the potential value of both programs is notable given that the addressable market opportunities for voruciclib in combination with venetoclax and ME-344 in combination with bevacizumab are significant. Venetoclax is currently used across AML, CLL and double-hit DLBCL and generated approximately $2 billion in 2022 worldwide sales. Venetoclax sales are continuing to grow and are expected to generate $3.4 billion by 2028. Avastin and bevacizumab biosimilars are used to treat a variety of cancers, including colorectal cancer and ovarian cancer. 2022 worldwide Avastin and bevacizumab biosimilar sales reached $2 billion in 2022 and are expected to grow to $3.3 billion by 2028.In short, MEI's pipeline is promising and presents substantial opportunity for delivering novel therapeutics for patients and value creation for MEI stockholders. Both both voruciclib and ME-344 have the potential in combination with current standard of care therapies to overcome known resistance mechanisms and improve patient outcomes. Each program is supported by nonclinical and in the case of ME-344 clinical data demonstrating antitumor activity and mechanistic proof of concept for the combinations being evaluated. We anticipate reporting data for voruciclib early in calendar 2024 and in the first half of 2024 for ME-344. We look forward to these data readouts and the next steps these data will be for.I'll now turn the call over to Richard Ghalie, our Chief Medical Officer, to provide additional details on our pipeline. Following Richard's remarks, Jay File, our Chief Financial Officer, will provide a brief financial overview before moving to Q&A.
Thank you, David, and I'll begin first by discussing voruciclib, a selective oral CDK9 inhibitor drug candidate. The mechanism of action of voruciclib is depicted in this cartoon, voruciclib block the transcription of MCL1 and MYC at the at the pol II level DNA transcription. In addition, voruciclib block the inclusive stabilization of the MYC protein, which has a downstream effect on that pathway. In a moment, I will give more detail to the meaning of these 2 targets.Voruciclib has a favorable PK and PD profile that allow its use orally because it's bioavailable. It is selective to CDK9 compared to other CDK as shown on the table to the right, where there is more binding affinity and longer residence time for CDK9 compared to the other CDK. In addition, voruciclib has more selectivity to CDK as compared to other kinase. Voruciclib is potent with an IC50 ranging from 0.2 to 1.7 micromolar in a variety of cell lines tested and interestingly, it concentrates in tumors over plasma, which is relevant in patients with solid tumors or lymphoid malignancies with tumors.Now let's focus on the 2 targets of interest. The protein MCL1, it is now that it's increase is associated with full prognosis in patients with acute myeloid leukemia or AML and in a variety of B-cell malignancies. In addition, upregulation of MCL1 is an established mechanism of resistance to venetoclax. As venetoclax-inhibited BCL2, it can lead to stabilization of MCL1, leading to resistant to venetoclax over time. independently and separately, we also know that MYC is overexpressed in a variety of cancers and tend to be associated with poorer prognosis. In addition, the MYC battery includes KRAS mutation, which will be relevant for the discussion about the potential role of voruciclib.Let's begin first on the aspect of inhibition of MCL1. As mentioned, it is relevant for AML and B-cell malignancies and as a way to address venetoclax resistance. MEI focused its initial development in hematologic malignancy beginning with AML. The reason we selected AML is because venetoclax-based therapies are standard of care and approved in elderly patients who are unfit to receive intensive chemotherapy. In the NCCH guidelines, it's been established also as the standard of care in a variety of market research, including the one cited on the right. In addition, ongoing studies are being conducted to establish the role of venetoclax as part of the standard of care in chemotherapy eligible patients.Our hypothesis is voruciclib combined to venetoclax has the potential to restore sensitivity to venetoclax and therefore, improve durably of response. This slide summarizes the nonclinical data that support the combination of voruciclib and venetoclax in AML. This is a murine xenograft model. And panel A, it shows suppression of MCL level. In Panel B, it shows that the either agent alone has activity in AML, but the combination is synergistic with further increasing apoptosis level. and that corresponds to an improvement survival in the model depicted here in AML. We have similar data with a combination with venetoclax in CLL and diffuse large cell lymphoma models.Now moving to describe the Phase 1 study. This is a typical Phase 1 dose escalation expansion study in patients with relapsed/refractory AML and B-cell malignancy in the first stage, which is the monotherapy dose escalation and in patients with relapsed and refractory AML for the combination with venetoclax stage. As for Phase 1 studies, its endpoints consists of safety, pharmacokinetics. We are also collecting sample for biologic correlate primarily to look at BH3 profiling and MCL1 expression as well as molecular mutation analysis. And we will also collect, of course, activity data.The monotherapy dose escalation component has been completed with 40 patients enrolled, and we are now currently enrolling in the combination with venetoclax group in patients with AML. As mentioned, this is a 2-stage component, first, a dose escalation going from 50 milligram every other day upward. And as of now, we have completed enrollment at the 150-milligram dose level. Once a dose that is confirmed to have well tolerance as well as evidence of activity, then we will proceed to expansion cohort. Currently, there is one contemplated and additional expansion cohort will be discussed with the FDA.In total, the study will enroll over 100 patients with hematologic malignancies, including approximately 70 patients in the combination with venetoclax. This is a brief summary of the data observed in the monotherapy dose escalation. Preliminary data were presented at the ASH 2021 and additional data and final data were presented at some subsequent scientific meeting. In total, 40 patients were enrolled, all heavily pretreated with a median of 3 prior therapy ranging from 1 to up to 8 therapies in 1 patient. 2 dose schedule evaluating initially daily continuously in 16 patients, and we have, at that time, pivoted to evaluate voruciclib on a 14 days on, 14 days off therapy in a 28-day cycle. And the reason for this pivot is because we have seen a daily dosing 2 patients pneumonitis that we felt were confounded by patients having developed differentiation syndrome seen in AML patients receiving target therapy as well as prior allogeneic transplant with graft versus host disease.When we switch to the 2 weeks on, 2 weeks off schedule, we're able to dose escalate up to 200 milligram without seeing DLTs. We stopped those escalation not because of safety reason but because we wanted to start pivoting to the combination with venetoclax, our target combination regimen. With the monotherapy, we have seen patients having evidence of antitumor activity, including 1 patient with AML, who has a morphology leukemia free state achieved and 5 of 10 patients with AML and the 200-milligram dose led stable disease.Importantly, we have seen in our curative library studies done with collaboration at academic centers, a decrease in MCL1 and MYC using a single cell RNA sequencing from 3 patients with CLL and 2 patients with AML. So overall, voruciclib as a monotherapy at a dose of up to 200 milligram on a 14 days on, 14 days off schedule was well tolerated, had no DLT. We did not see drug-related neutropenia. We did not see grade 3 or higher drug-related toxicity and no patients were discontinued due to drug-related toxicity. As mentioned, we are now enrolling in the venetoclax combination. Up to now, we have not seen DLTs. The PK analysis of the earlier dose level do not show drug-drug interactions, and we are seeing evidence of clinical activity at the low dose evaluated today, manifested by reducing transfusions, improved counts, response observed in some patients and over 85% of the patient continuing beyond cycle 1, the DLT windows. Keep in mind, this is observed in patients who have been heavily pretreated with a mean of 2 prior therapy, including venetoclax.Now let's turn the focus to voruciclib effect on MYC. As mentioned, MYC is overexpressed in a variety of cancer and tend to be associated with poor prognosis. There is no current treatment approved for MYC mutated tumors. CDK9 inhibition lead to reduced transcription of MYC and stabilization, thus can have a potential treatment effect. We have clinical data from initial studies conducted in patients with solid tumors by the prior sponsor. 2 studies were conducted, one using a 2 weeks on, 1 week off schedule and the other one using a daily continuously schedule. Relevant to the discussion today is in the daily continued scheduled study, samples were obtained from 25 patients with a variety of solid tumors and tested on a 10-gene biomarker with a sample obtained at baseline and with each subsequent course of therapy. We have seen a decrease in MYC expression in 60% of the patients tested in that study. And here are shown only 2 illustrative examples of 2 patients circled are MYC gene that were evaluated showing a decrease in MYC over time with each course of therapy.At MEI, we have further expanded the value of that effect on MYC and KRAS by evaluating a number of cell lines listed here, including colorectal cancer and other tumors that had a variety of KRAS mutation, G12C, but also others. And shown to the panel to the right is a dose response relationship between voruciclib dose and suppression of tumor growth and 3 different cell lines with different KRAS mutation. And lastly, enough interest is a combination of voruciclib with the KRAS inhibitor sotorasib. This experiment was conducted in a pancreatic tumor cell model. This is intralesional infusion of 1 or a combination of drug and the readout is shown to the panel to the right, where we see 2 type of analysis. One is the standard pathology with an HA staining that shows the control arm, either agent alone and to the bottom right panel of the combination, showing evidence of cell best [indiscernible] cells and also in the fluorescent staining an increased number of cells die. So that is my summary for the voruciclib program.Now I'm turning to the description of ME-344, a mitochondrial inhibitor drug candidate. This is a very interesting and novel mechanism of action, where the inhibition of the mitochondria is a dual effect. One on OXPHOS and 2 on purine synthesis, reminding that purine synthesis is made at the surface of mitochondrial cells. The relevance of that mechanism is illustrated in the panel to the right, which I will simplify by saying that mitochondria generate ATP, which are essential for producing energy for cells, and that is done through the OXPHOS pathway, blocking the OXPHOS with ME-344 would lead to a decrease in ATP source of energy and eventually by a cascade of event to potentially cell death. Separately, purine biosynthesis is done, as I said, at the surface of mitochondria, which ME-344 can block. Purine are essential to a cell proliferation and blocking purine biosynthesis could lead to a decrease in cell growth and proliferation.This is a simple panel of over 200 cell lines that were tested for ME-344 activity in vitro. And as one can see, ME-344 is potent at the nano molecular level and nearly all cell line tested except a few. MEI conducted 2 Phase I studies, one as a single-agent dose escalation to determine the safety, efficacy and PK and that study led to the determination that a recommended Phase 2 dose for further development is 10 milligram per kilogram. The next study evaluating ME-344 with the chemotherapy, topotecan in a couple of types of solid tumors. 48-patient enrolled in the study, myelosuppression due to topotecan was observed, we had disease stimulation at 49% of the patients. However, MEI decided to pursue the development of ME-344 in a different direction on the basis of biology. However, before I go to that, this is a table summarizing the safety profile of ME-344 as a single agent in the Phase 1 study, pointing to the fact that neuropathy was seen only at doses higher than 10 milligram per kilogram was the dose limiting toxicity. It was not reported at lower doses.Now let's describe the new strategy that we would like to employ ME-344 in combination with the anti-angiogenic agents, primarily Avastin or bevacizumab. This stands for a simple observation that when Avastin is administered to patient, it blocks the glycolytic energy pathway leading to effect on cell growth. However, cells are [Technical Difficulty] ATP I mentioned earlier. Therefore, it is possible that combining [Technical Difficulty] I'll continue then. Combining ME-344 to block the mitochondrian energy and a VEGF inhibitor like Avastin would now have a possibility of synthetic lethality and therefore, improving antitumor control. This hypothesis was tested initially in animal model, of which I present 2, one, a colorectal cancer model, and one, a breast cancer model using ME-344 in combination with oral VEGF inhibitor, nintedanib and regorafenib. And seen on this slide is a decrease in tumor growth for the combination compared to either agent alone and improved survival in colorectal model. This led to a study by collaborated at the NCI Spain in Madrid, a multicenter study, a proof-of-concept study evaluating ME-344 and bevacizumab in patients with breast cancer. The reason breast cancer was selected because that is a window of opportunity for this type of mechanistic studies where patients between diagnosis and definitely surgery has a period of time where the study could be conducted.It was a randomized controlled study in 41 patients. Group A received bevacizumab with ME-344 just one cycle and Group B received bevacizumab alone. The readout was a PET scan to look at tumor vascularization and tumor biopsy looking primarily as the biomarker of tumor proliferation called Ki67. Results are illustrated on this slide. Group A, again, is the combination of ME-344 and bevacizumab in green, as you can see, looking at all patients enrolled in this study, there was a significant decrease of Ki67 compared to what observed with bevacizumab alone. Focusing now on the subset of patients in this study who had a tumor normalization, vascularization normalization by PET, this effect is further enhanced. This led us to the decision now to proceed in a clinical trial with clinical readout, and we selected colorectal cancer as the first study to evaluate the combination because it's an unmet need and Avastin is used in that setting.So this is a Phase 1/2 study in patient relapsed colorectal cancer after failure of all standard therapy. Primary objective is progression-free survival, secondary objective are survival and safety. The study is conducted in a separate cohort, beginning with Cohort 1 and using the same dose and schedule that was used in the breast cancer study. 20 patient will be enrolled, and the readout will be that 4 months after the last patient's enrolled and considered as a positive outcome is a PFS at 4 months of 20% or higher. Then that will lead to a valuation of a second cohort and subsequent dose cohort to be discussed with the FDA.With that, I conclude the clinical update, and we'll turn it to Jay File to talk about the financial overview.
Thank you, Richard. As reported earlier today, as of June 30, 2023, MEI had $100.7 million in cash, cash equivalents and short-term investments with no outstanding debt. We believe our cash balance is sufficient to fund operations for at least the next 12 months and through the reporting of clinical data readouts from the ongoing and planned voruciclib and ME-344 Phase 1 and Phase 1b clinical programs, respectively. I look forward to any questions on the broader set of financial information reported earlier today during the Q&A portion of the call. I'll turn that back to David.
Thanks, Jay. As you've heard today, I believe we have 2 exciting programs with expected data readouts beginning with voruciclib early in calendar 2024 and in the first half of 2024 for ME-344. With the promising pipeline and capital to support our near-term development plans, we're excited about the potential to create stockholder value and deliver improved therapeutic options for patients. Before we turn to Q&A, I'd like to briefly acknowledge that 2 of our stockholders, Anson and Cable Car have initiated a consent solicitation process and separately submitted 3 director candidates to stand for election at the company's annual stockholder meeting this year. We have had several conversations with Anson and Cable Car as part of ongoing efforts to resolve the situation and remain open to further discussions. We will appropriately address the actions of these stockholders in due course. For the purposes of this earnings call, we're here to discuss our programs and upcoming milestones. We ask that you please keep your questions to these topics.I'll now ask the operator to provide the instructions for asking questions and then open the call for Q&A.
We will now begin the question-and-answer session. [Operator Instructions] Our first question is from I-Eh Jen with Laidlaw & Company.
Good afternoon, and thanks for taking the questions as well as providing us clear view of what's happening currently. Maybe I'll start with the housekeeping questions, you got about $100 million in cash. And in the press release input, you suggested that you have on 12 months or maybe a little bit longer runway. Given that you are still in Phase 1/2 study, should we anticipate it to be a more conservative estimate or the additional thoughts behind that in terms of the runway? And I have some follow-ups as well.
This is David. I would say it's conservative in the sense that we've got all the capital we need to do the Phase 1 programs as they're currently planned and as we have some ideas about augmenting them. But going into Phase 2 is really data-driven. And so it's really impossible to speculate about the next phase of development for these programs. So I think it's an appropriate guidance in that respect. Like we said, it's at least 12 months and covering the current work that we're doing. So you could characterize it as being, I guess, somewhat conservative, but we did say at least 12 months.
Sure. And maybe just in terms of, again, it's the housekeeping one, which is the top line. I understand the prior years are completed. So should we anticipate still some top line coming just because of the amortization? Or we should anticipate that to be stopped at least in the near term?
I'm sorry, can you repeat we were having a little bit of trouble following the question. Could you please repeat it?
Sure. In terms of the top line revenue that you have this quarter, my question is, would that will continue for the subsequent fiscal year? Or simply these revenue numbers, is just the amortization of the prior revenue received?
Yes. I mean all of the revenue we're recognizing is all KKC driven from our collaboration with them. So it's not anticipated to continue into the future.
Okay. Maybe the last question here is in the clinical side, on the [ voruciclib ] Phase 1 data readout, what should we anticipate specifically in terms of sort of type of data? Other than safety, would that be PK? And would there be any biomarker or other aspects? Could you provide a little bit more color on that?
Yes, this is Richard. Yes, it will be a combination of safety data, primarily since this is the prime endpoint of Phase 1 study, perhaps the recommended Phase 2 dose, there will be also PK data and biomarker analysis. All of them will be available.
What specific would you already have some biomarker in mind? And if so, what that might be?
Right? So I've mentioned it when I present the monotherapy dose escalation, the biomarker that we are evaluating are BHC profiling, particularly MCL1 expression. We are looking at multiple molecular biomarkers such as MYC, and we will be looking at potentially other biomarkers that are relevant directly the effect of CDK9 on the target. Okay. Great. Yes, I'll get back to the queue.
I mean I guess we could also say that just from a clinical perspective, for the cohort 1 from ME-344, we will be looking at PFS and for the voruciclib expansion cohort that's in our protocol right now, we'll be looking at ORS those are just standard clinical endpoints for the 2 respective diseases.
Actually, if I can maybe just follow up on that. You said a 20% or higher of the threshold for moving forward for them for the ME-344 cohort 1. What other factors determined that the 20% was the number as A cutoff?
Well, that was a requirement or a gate that we reached in collaboration with the clinicians. But we really need to dig into exactly what the patient population is before we can really know what the meaning of that threshold is it obviously depends on exactly the experience that each patient...
And maybe, again, one more question here, which is that if compared to what your prior study in the breast cancer or non-small cell lung. Was there any comparable number to that PFS?
Yes, this is Richard answering. So it's really 2 very different approach to therapy here. In the Phase 1 study in combination with chemotherapy, we were really looking at cytotoxic effect and looking at response as the primary endpoint. Here, we're really looking at a different approach where there is synthetic lethality by combining VEGF inhibitor with a mitochondrial inhibitor. And therefore, the response rate is less relevant, more relevant will be the time to progression. Again, it's a very different disease. So it will be hard to compare correctly test on one hand with a prior study, which was done in ovarian cancer and small cell lung cancer.
Mr. Willey, your line is open, or you have to, you haven't muted on yours.
So maybe just one on voruciclib, one on 344 and then just a modeling or financial question. So on voruciclib what's your expectations just around venetoclax retreatment post progression in the context of AML. And I guess I asked the question because there's not a lot of data that's out there in the public domain and the sort of retreatment experience and CLL that's shown that you can resensitize patients to venetoclax with venetoclax alone. And I'm just kind of curious, as you think about the data you're going to be generating, what's good, what's interesting, what is your working assumption around venetoclax retreatment response rates?
Yes. I mean the initial experience with venetoclax in the relapsed/refractory AML population was pretty limited. I think it was like 19 patients, and they saw about a 20% response. As you know, that was in a venetoclax naive population. Now everybody is getting venetoclax. But I think when we talk to our advisers, it's still around the same threshold as what they would be excited by. I think it's a big deal if you can bring back response to a patient that progressed on venetoclax and a 20% to 30% response rate in this relapse population, I think, would get everybody excited.
Okay. And then on 344, I think per clintrials.gov, it doesn't list any of the approved salvage regimens as allowable prior therapy. So are we to assume that these patients are going to be LONSURF and regorafenib naive.
This is Richard. You're right, this is not listed on clinical trial, but the protocol is really a body what the FDA wanted. So patients should have received and progressed on or did not tolerate standard chemotherapy, which is platinum-based [indiscernible] based 5-Fu, in addition, if they had a mutation that is addressable, like BRAF, they had to receive it, if they are usable for checkpoint inhibitor they should have received it or not tolerate it. And only then they could enroll in the study. So we may have patients who have received regorafenib and/or LONSURF or not. So it's not a requirement, but we anticipate that some patients and in fact, would have received them in the study.
Okay. And then maybe just a follow-up on the 20% 4-month PFS rate that's required to get the enrollment of Stage 2. I guess when you look at, I think it was what the Sunlight study that was just published. I think they saw a 6-month PFS with Avastin Lonsurf of north of 40% and then I think with Lonsurf alone close to 20%. So I'm just trying to, I guess, maybe think about the threshold that you're establishing here in the context of some of the historical data that's out there.
You're absolutely right about this report. The Phase 3 study, in fact, that was reported at ASCO GI payment when we were just launching the study. So just let me explain where the 20% threshold came, but then also what it means for us going forward. The 20% threshold was driven by the monotherapy kinase inhibitor, so the regorafenib phase 3 study and our advisers, which is, as you may know, is the academic GI cancer consortium who is running the trial, said that they would like to see something upwards of maybe double of what we've seen with regorafenib alone in this patient population. So that's where the 20% came. This is not our ceiling. This is the floor. We need to see at least something better than to go to Phase 2 cohort 2.A separate question that you're asking is, if we just get 20% only, is it enough? Would we get excited knowing that Lonsurf had the 40% PFS at months 4 to 6. And you're right. I think the answer to that is going to be it depends who we enroll. If we enroll patients that failed Lonsurf or Lonsurf bev or another TKI, then that would get us excited will be very different than if we have patients who really failed prior chemotherapy with bev and then they come on that study. So I'm not trying to dodge the answer, I'm trying to say it will be determined by the kind of patient we enrolled. Not unlike what David mentioned about voruciclib. If we see response in voruciclib, patient progress on voruciclib, the excitement level will be very different that we see response on patient response to venetoclax and then progressed and went back on the combination responded. So it's primarily driven by the patients we enroll as is often the case Phase 1 study. With enroll, we look at the data, we analyze and we make conclusion based on what we see.
Okay. That's helpful. And then just lastly, I guess, when you look at the 4Q R&D number implied from what you reported year-end, it looks to be demonstrably down sequentially, I think, sub $3 million. How should we think about that number just going forward? And is that somehow impacted by the Kyowa transaction some true-up there? Or is that just a true number per the quarterly report, and that's just going to accelerate as you guys see more clinical development here?
Yes, it's Jay. I'll take that. So yes, you're correct in your assessment. We're not giving specific guidance as to R&D into the next fiscal year, but I will tell you, of that about 52.5% of R&D, about $26 million of that was specifically related to zandelisib. We do know that, that trial continues to wind down. We do expect that to run out in about October time frame and probably not incur expenses any more than $1 million, less than that most likely. The Q4 activity is just seeing the continued wind down of COASTAL and TIDAL in Q4. And like I said, we expect that to go ahead and wind down. Then in addition to some of the other cost reductions that we've made throughout the second half of the year, overall R&D, yes, you're right. It will be down significantly from the prior year.
This concludes our question-and-answer session. I would like to turn the conference back over to David Urso for any closing remarks.
Thank you for joining the call today, and we appreciate your participation.
The conference has now concluded. Thank you for attending today's presentation. You may now disconnect.