MEI Pharma Q4 2023 Earnings Call Transcript

Quartr
Provided by Quartr
September 26, 2023

There are 7 speakers on the call.

Operator

Good day,

Speaker 1

and welcome to the MEI Fiscal Year End Earnings Call. My name is Gary, and I will be the conference facilitator today. All participants will be in a listen only mode. After today's prepared remarks, there will be an opportunity to ask questions. Please note today's event is being recorded.

Speaker 1

I would now like to turn the conference over to David Walsey, Senior Vice President of Corporate Affairs at MEI Pharma.

Speaker 2

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 With me today on the call from MEI are David Erso, President and Chief Executive Officer Jay Fyhl, Chief Financial Officer And Doctor. Richard Volley, 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.

Speaker 2

Certain information contained in this communication that are not historical in nature are forward looking statements within the meaning of the Safe Harbor provisions The Private Securities Litigation Reform Act of 1995, including without limitation, statements regarding the potential safety, 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 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 We commercialize our product candidates, the availability or 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, our 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 the 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 one time events.

Speaker 2

We do not intend to update any of these factors or to publicly announce With that, I'll now turn the call over to David Arceaupt.

Operator

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 Gauley, 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 and A. Before getting started, I want to welcome Jay. He was just appointed our CFO as of August 1st, So this is his first earnings call at MEI, and we're very happy to have him on the team.

Operator

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 Looking ahead over the next few quarters, We see important opportunities in the continued progress of our 2 clinical stage oncology programs, vorociclib and ME-three forty four. 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.

Operator

Vorasiclib is an oral CDK9 inhibitor And ME-three forty four is a mitochondrial inhibitor that inhibits the oxfos pathway. We are investigating These compounds overcome resistance mechanisms to standard of care therapies. The BCL-two inhibitor venetoclax for vorociclib And the VEGF inhibitor, bevacizumab, in the case of ME-three forty four. The ongoing advancement of each program is based on non clinical And in the case of ME-three forty four, 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.

Operator

We are working with some of the leading oncologists in the company 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 voraciclib, as previously reported, we've seen promising data from our ongoing Phase 1 study. Recall that vorcyclov as a selective CDK9 inhibitor regulates the transcription of Mcl-one and through that Holds the potential to address the known venetoclax resistance mechanism. The ongoing Phase 1 study is evaluating boracipa as a single agent In combination with venetoclax, which is standard of care in AML and used in other hematologic ointment disease as well.

Operator

Richard will provide more detail shortly, but in brief, boraciclib 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 Foraciclib data readout in early 2024 is expected to include data from the dose ascending cohorts in the Phase 1 study Evaluating furocycline plus venetoclax in patients with AML. Here are some of the leading KOLs we're working with. We're pleased As for ME-three forty four, we're pursuing a novel approach to cancer therapy with the combination of ME-three forty four and oxfos inhibitor That inhibits the production of ATP in mitochondria and bevacizumab, a VEGF inhibitor, which inhibits the production of ATP through 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 This novel approach to treatment has Also generated enthusiasm among our investigators in the ongoing study.

Operator

In earlier clinical studies, ME-three forty four 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 and biomarker Ki-sixty seven We expect that the ME-three forty four data readout planned in the first half of twenty twenty four We'll include initial safety and efficacy data from the first 20 patient cohort in the Phase 1b study evaluating We believe the potential value of both programs is notable, given that the addressable market opportunities for voraciclib In combination with venetoclax and ME-three forty four in combination with bevacizumab are significant. Venetoclax is Currently used across AML, CLL and DoubleFit DLBCL and generated approximately $2,000,000,000 in 20 22 worldwide Sales. Venetoclax sales are continuing to grow and are expected to generate $3,400,000,000 by 2028.

Operator

Avastin and bevacizumab biosimilars are used to treat a variety of cancers, Including colorectal cancer and ovarian cancer, 2022 worldwide Avastinin Bevacizumab biosimilar sales reached $2,000,000,000 in 2022 and are expected to grow to $3,300,000,000 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 for pauracyclobin and E-three forty four 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 non clinical and in the case of ME-three forty four clinical data demonstrating anti tumor activity And mechanistic proof of concept for the combinations being evaluated. We anticipate reporting data for vorcyclib early in calendar 2024 And in the first half of twenty twenty four for ME-three forty four.

Operator

We look forward to these data readouts and the next I'll now turn the call over to Richard Ghaly, our Chief Medical Officer to provide additional details on our pipeline. Following Richard's remarks, Jay Pfeil, our Chief Financial Officer, We'll provide a brief financial overview before moving to Q and A.

Speaker 3

Thank you, David. And I'll begin first by discussing voraciclib, 2 and vericiclib block the transcription of Mcl-one and MYC at the PAL2 level, DNA transcription. In addition, for sacib block, the includes the stabilization of BIMIC protein, which has a downstream effect on that pathway. In a moment, I will give more detail to the meaning of these two targets. For the second It has a favorable PK and PD profile that allow its use orally because it's bioavailable.

Speaker 3

It is selective to CDK9 compared to other CDK as shown to the table on the table to the right, With a more binding affinity and longer residence time for CDK9 compared to the other CDK. In addition, porisib had more selectivity to CDKs compared to other kinase. Porisib is potent with an IC50 Erasing from 0.2 to 1.7 micromolar in a variety of cell line tested and interestingly it concentrates in tumors oberplasma, which is relevant in patient with solid tumors or lymphoid malignancies with tumors. Now let's focus on the two targets of interest. The protein MCL1, it is known that Its increase is associated with poor prognosis in patients with acute mild leukemia or AML and in a variety of B cell malignancies.

Speaker 3

In addition, up regulation of Mcl-one is an established mechanism of resistant to venetoclax. As venetoclax inhibit BCL-two, it can lead to stabilization of MCL-one leading to resistance 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 poor prognosis. In addition, the MYC pathway include KRAS mutation, which will be relevant for the discussion about the potential role of uricylate. Let's begin first on the aspect of inhibition of MCL-one.

Speaker 3

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 NCCIH guidelines, it's been established also as the center 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 center This Slide summarize the non clinical data that support the combination of vericiclib and venetoclax in AML.

Speaker 3

This is a murine xenograft model. In panel A, it shows Suppression of MCL level. In Panel B, it shows that either agent alone has activity in AML, but the combination It's synergistic with further increase in apoptosis level, and that corresponds to an improvement in survival in the model depicted here in AML. We have similar data with a combination with venetoclaxin CLL and diffuse large cell lymphoma models. Now moving to describe the Phase 1 study.

Speaker 3

This is a typical Phase 1 dose escalation expansion study In patients with relapsedrefractory 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 said for Phase 1 studies, its endpoints consist of safety, pharmacokinetic. We are also collecting sample for biologic Corlett, primarily to look at BH3 profiling and MCL1 expression, as well as molecular mutation analysis, and we will also collect, of course, The monotherapy dose escalation component has been completed with 40 patient enrolled, and we are now 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.

Speaker 3

Once a dose that is confirmed to have Well tolerance as well as MSO activity, then we will proceed to expansion cohort. Currently, there is one contemplated and additional 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. Prominent data were presented at ASH 2021 And additional data and final data will present 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.

Speaker 3

2 dose schedule evaluating Initially, daily, continuously in 16 patients. And we have at that time pivoted to evaluate voriciclib on a 14 days on, 14 days off And the reason for this pivot is because we have seen in the daily dosing 2 patients pneumonitis That we felt were confounded by patient having developed differentiation syndrome, seen in AML Patient receiving targeted 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 dose 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 one patient with AML who has a morphology leukemia free stage achieved and 5 of 10 patients with AML at the 200 milligram dose who had stable disease.

Speaker 3

Importantly, we have seen in our collaborative laboratory studies done with collaboration at academic centers, a decrease in Mcl-one And Mick, using a single cell RNA sequencing from 3 patients with CLL and 2 patients AML. So overall, vorociclib 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.

Speaker 3

The PK analysis of the earlier dose levels do not Show drug drug interactions, and we are seeing evidence of clinical activity at the low dose evaluator today, manifested by a reduce in transfusions, Improved counts, response observed in some patients and over 85% of the patients continuing beyond cycle 1, the DLT windows. Keep in mind, this is observed in patients who have been heavily pretreated with the immediate acute prior therapy, including venetoclax. Now let's turn the focus to voriciclib effect on MYC. As mentioned, MYC is overexpressed in the variety of cancer And tend to be associated with poor prognosis. There is no current treatment approved for MYC mutated tumors.

Speaker 3

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 About the prior sponsor, 2 studies were conducted, 1 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 continuous schedule 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 SP MYC expression in 60% of the patient tested in that study. And here are shown only 2 illustrative examples of 2 patients, circles are the MYC gene that we evaluated showing a decrease in MYC Over time with each course of therapy.

Speaker 3

At MEI, we have further expanded the evaluation 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 mutations, G12C, but also others. And shown to the panel to the right It's a dose response relationship between vorasacute dose and suppression of tumor growth and 3 different And lastly, and of interest is Combination of vorasaclib with the KRAS inhibitors, sotiracic. 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. 1 is the standard pathology with an staining that shows the control arm Either agent alone and to the bottom right panel of the combination showing evidence of cell death, spixotic cells And also in the fluorescent staining, an increased number of cells dying. So that is my summary for the vorsaklib program.

Speaker 3

Now I'm turning to the description of ME-three forty four, a mitochondrial inhibitor drug Candidate. This is a very interesting and novel mechanism of action where the inhibition on the microcardia Is a dual effect, 1, on oxfos and 2, on purine synthesis, reminding that purine synthesis is made at the Surface of MYCOMIOL cells. The relevance of that method is illustrated depending on 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 oxfos pathway. Blocking the octos with ME-three forty four would lead to a decrease in ATP source of energy And eventually, by a cascade of event to potentially sell death. Separately, Purine biosynthesis is done, as I said, at the surface of mitochondria, which ADME-three forty four can block.

Speaker 3

Purina is essential to cell proliferation and blocking Purina biosynthesis could lead to a decrease in cell growth and proliferation. This is a simple panel of over 200 cell line that were tested for ME-three forty four activity in vitro. And as one can see, ME-three forty four is potent at the nanomolecular level and nearly all cell line tested, except a few. MEI conducted 2 Phase 1 studies, 1 at a single agent dose escalation to determine the safety efficacy and PK, and that Study led to the determination that our recommended Phase 2 dose for further development is 10 milligram per kilogram. The next study evaluating ME-three forty four with the chemotherapy topotecan in a couple of type of solid tumors, 48 patients enrolled in the study, myelosuppression due to trochotegan was observed.

Speaker 3

We had disease stimulation at 49% of the patients. However, MEI decided to pursue the development of ME34 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-three forty four 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 me describe the new strategy that we would like to employ ME-three forty 4, in combination with the anti angiogenic agents, primarily Avastin or bevacizumab.

Speaker 3

This is stands for a simple observation that when Avastin is administered to patient, it blocks the glycolytic energy pathway, So I will continue then. Combining ME-three forty four to block the mitochondrial energy and a VEGF inhibitor like Avastin We now have a possibility of synthetic lethality and therefore improving antitumor control. This hypothesis was tested an animal model of which I present 2, 1 a colorectal cancer model and 1 a breast cancer Using ME-three forty four in combination with oral VEGF inhibitor, entinib and engraftinib. And seen on this slide is a decrease in tumor growth with the combination compared to ELAP agent alone and improved survival in colorectal model. This led to a study by collaborated at the NCI, Spain in Madrid, a multicenter A proof of concept study evaluating ME-three forty four and bevacizumab in patients with breast cancer.

Speaker 3

The reason Breast Cancer was selected is 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 abacizumab with ME-three forty four just one cycle, and Group B received abacizumab alone. The readout was a PET scan to look at tumor vascularization and tumor biopsy looking primarily Add the biomarker of tumor proliferation called Ki-sixty seven. Results are illustrated on this slide. Group A again is the combination of ME-three forty four a bevacizumab in green.

Speaker 3

As you can see, looking at all patients enrolled in the There was a significant decrease of Ki-sixty seven compared to what observed with belacizumab 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 III study in patient relapsed colorectal cancer after failure of all standard therapy. Primary objective is progression free survival.

Speaker 3

Secondary objective are survival and safety. The study is conducted in separate cohort beginning with Cohort 1 and using the same dose and schedule that was used in the breast cancer study. When the patient will be enrolled and the readout will be that 4 months after the patient's last patient is enrolled. And considers a positive outcome as a PFS at 4 months of 20% or higher. Then that will lead to a valuation of a second cohort and subsequent cohort to update and we'll turn it to Jay Fife to talk about the financial overview.

Speaker 4

Thank you, Richard. As reported earlier today, as of June 30, 2023, MEI had $100,700,000 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 voraciclib and ME-three forty four 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 and A portion of the call.

Speaker 3

I'll turn that back to David.

Operator

Thanks, Jay. As you've heard today, I believe we have 2 exciting programs with expected data readouts beginning with voraciclib early in calendar 2024 and in the first half of twenty twenty four for ME-three forty four. 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 and 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.

Operator

We've 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.

Speaker 1

We will now begin the question and answer session. Our first question is from Yale Jen with Laidlaw and Company. Please go ahead.

Speaker 5

Good afternoon, and thanks for taking the questions as well as providing a clear view of what's Currently, maybe I start with a housekeeping question that you got about $100,000,000 cash. And in the press release, you suggested that you have on 12 months or maybe a little bit longer runway. Given that you are still in Phase III, should we anticipate To be a more conservative estimate or just additional thoughts behind that in terms of the runway? Can I have some follow-up as well?

Operator

Thanks, Yale. 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 we're currently 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.

Operator

So I think it's an appropriate guidance in that respect.

Speaker 5

Okay. Great. Yes, like we

Operator

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.

Speaker 5

Sure. And maybe just in terms of, again, the housekeeping one, which is the top line, I understand the The prior deals are completed. So should we anticipate still some top line coming just because of the amortization Well, we should anticipate that to be stopped in the early say in the near term.

Operator

I'm sorry, could you repeat? We were having a little bit of trouble following the question. Could you please repeat it? Sure.

Speaker 5

In terms of the top line revenue that you have this quarter, my question is that would that will Continue for the subsequent fiscal year or simply these revenue numbers, just the amortization of the prior Revenue received?

Operator

Yes, I mean, all of the revenue we're recognizing is all KKC driven from our collaboration with So it's not anticipated to continue into the future.

Speaker 5

Okay. Maybe the last question here In the clinical side, there were CRUCIDCLID's Phase 1 data readout. What should we anticipate specifically in terms of sort of type of data? Other than the safety, would that be PK? And would that be any biomarker or other aspect?

Speaker 5

Could you provide us a little color on that?

Speaker 3

Kelly, this is Richard. Yes, it will be a combination of safety data primarily since this is the Endpoint, the primary endpoint of Phase 1 study. Perhaps they recommended Phase 2 dose. There will be also PK data and biomarker analysis. All of them will be available.

Speaker 5

What specific would you already have some biomarker in mind? And if so, What that might be?

Speaker 3

Right. So, I've mentioned it when I present the monotherapy dose escalation, The biomarker that we are evaluating are BHG profile, in particularly Mcl-one expression. We are looking at multiple molecular biomarkers such as MYC, and we will be looking at potentially other Biomarkers that are relevant directly is the effect of CDK9 on the target.

Speaker 5

Okay. Okay, great. Yes, I'll get back to the queue,

Operator

I mean, I guess, we could also say that just from a clinical perspective For the cohort 1 from ME-three forty four, we will be looking at PFS and for The vorasiclib expansion cohort that's in our protocol right now, we'll be looking at LR. So those are just standard clinical Endpoints for the 2 respective diseases.

Speaker 5

Actually, let me if I can, maybe just follow-up a little on that. You said a 20% For higher threshold for moving forward for the ME-three forty four study Caller 1. What are the factors determining that 20 And what's the number as of the cutoff?

Operator

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

Speaker 5

And maybe again one more question here, which is that If compared to what your prior study in the breast cancer or not small cell lung, Was there any comparable number to that PFS?

Speaker 3

Yes. This is Richard answering. So it's really a 2 very different approach 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 are really looking at a different approach where there is synthetic lethality by combining VEGF inhibitor with a mitralgony inhibitor And therefore, the response rate is less relevant, more relevant would be the time to progression. Again, it's a very different disease, so it will be hard to compare breast cancer Rather, I'm sorry, colorectal cancer on one hand with the prior study, which was done in ovarian cancer and small cell lung cancer.

Speaker 5

Great. That's very helpful, and thanks a lot. I appreciate it.

Speaker 1

Mr. Willey, your line is open on our end. Perhaps you have it muted on yours?

Speaker 6

No. Thanks for taking the questions. So maybe just one on verusoclib, 1 on 344 and then just a modeling or financial question. So On verusoclib, 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 In the public domain, there's some retreatment experience in 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?

Operator

Yes, I mean, the initial experience with venetoclax in the relapsedrefractory AML population was pretty limited. I think it was like 19 patients and they saw about a 20 But that was in a as you know, that was in a venetoclax naive population. Now everybody's getting Venetoclax, but I think when we talk to our advisors, it's still around the same threshold is what they would be excited 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 that in this relapse population, I think would get everybody excited.

Speaker 6

Okay. And then on 344, I think per clintrials dot 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 Lonserf and regorafenib naive?

Speaker 3

This is So the you're right, this is not listed on clinical trial, but the protocol is really abiding with what the FDA wanted. So patients should have received And progress on or did not tolerate standard chemotherapy, which is platinum based, interchicken based, 5FU. In addition, if they have a mutation that is addressable like BRAF, they had to receive it. If they are eligible for checkpoint inhibitor, they should have received it or not are eligible. And only then they could enroll in the study.

Speaker 3

So we may Have patients who have received regorafenib and or LONSRV or not. So it's not a requirement, but we anticipate that some patient And in fact would have received them in this study.

Speaker 6

Okay. And then maybe just to follow-up on the 20% 4 month PFS Great. That's required to date the enrollment of Stage 2. I guess when you look at, I think it was what The SUNLIGHT study that was just published.

Speaker 5

I think they

Speaker 6

saw a 6 month PFS With Avast in LawnSurf of north of 40%, and then I think with LawnSurf 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.

Speaker 3

You're absolutely right about this report, the Phase 3 study, in fact, that was reported at ASCO GI came in when we were 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 inhibitors, say, the rigrafinib Phase III study. And our advisors, which is, as you may know, is the academic GI cancer consortium who's running the trial, Said that they would like to see something upward of maybe double of what was seen with rigrafinib alone in this patient population. So that's where the 20% came.

Speaker 3

This is not our ceiling. This is the floor. We need to see at least something better than get to go to Phase To the Cohort 2. A separate question that you're asking is, if we just get 20% only, is this enough? Would we get excited knowing that monserbaab has a 40% PFS at month 4% to 6% and you're right.

Speaker 3

Think the answer to that is going to be, it depends who we enroll. If we enroll patient who had failed long serve or long serve bev Or another TKI, then that would get us excited would be very different than if we have patients who really failed prior chemotherapy I'm sorry, Right. Hemotherapy 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 enroll, Not unlike what David mentioned about voracycline.

Speaker 3

If we see a response in voracycline, patient progress on voracycline, there will be The excitement level will be very different if we see response on patient who respond to venetoclax and then progress then went back So it's primarily driven by the patients we enroll as is often the case in Phase 1 study. We'll enroll, we look at the data, we analyze and we make

Speaker 6

Okay. That's helpful. And then just lastly, I guess, When you look at the 4Q R and D number implied from what you reported year end, it looks To be demonstrably down sequentially, I think sub $3,000,000 How should we think about that number just Going forward, and is that somehow impacted by the KeyWatt 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 do more clinical development here. Thanks.

Speaker 4

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 and D into the next fiscal year, but I will tell Of that about 52.5 percent of R and D, about 26 percent of that was specifically related to zandalesib. We do know that that trial continues to wind down.

Speaker 4

We do expect that to run out right about October timeframe and probably not incur Expenses any more than $1,000,000 less than that most likely. The Q4 activity is just seeing the continued wind down of Coastal and Title 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 and D, yes, you're right. It will be down significantly from the prior year.

Speaker 6

Okay. Thanks for taking the questions.

Operator

Sure. Thank you.

Speaker 1

This concludes our question and answer session.

Speaker 5

I would

Speaker 1

like to turn the conference back over to David Erso for any closing remarks.

Operator

Thank you for joining the call today, and we appreciate your participation.

Speaker 1

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

Powered by Quartr

Key Takeaways

  • Strong Balance Sheet: MEI closed the fiscal year with $100.7 million in cash and no debt, providing at least 12 months of runway to fund ongoing and planned clinical programs.
  • After terminating the Infinity merger, MEI is focused on two novel oncology assets: voruciclib, an oral CDK9 inhibitor designed to overcome venetoclax resistance, and ME-344, a mitochondrial inhibitor paired with bevacizumab to induce synthetic lethality.
  • In the Phase 1 study, voruciclib alone and in combination with venetoclax was generally well tolerated with no significant myelosuppression and showed early activity in heavily pretreated, venetoclax-resistant AML and B-cell malignancy patients; data are expected early 2024.
  • ME-344 has demonstrated preclinical synergy with VEGF inhibitors and, in a window-of-opportunity breast cancer trial, produced a significant reduction in the Ki-67 proliferation marker; Phase 1b colorectal cancer data are anticipated in 1H 2024.
  • Both programs address large commercial opportunities—venetoclax sales of ~$2 billion in 2022 (forecast to $3.4 billion by 2028) and bevacizumab biosimilars of ~$2 billion (forecast to $3.3 billion)—by targeting known resistance pathways to standard therapies.
AI Generated. May Contain Errors.
Earnings Conference Call
MEI Pharma Q4 2023
00:00 / 00:00