Q4 2023 MEI Pharma Inc Earnings Call

Speaker 1: Good day and welcome to the MEI Fiscal Year End Earnings Call. My name is Gary and I'll 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.

Good day and welcome to the M E <unk> fiscal year end earnings call. My name is Gary and I'll be the conference facilitator today, all participants will be in a listen only mode. After today's prepared remarks, there'll be an opportunity to ask questions.

Speaker 1: To ask a question, you may press star, then one on a touch tone phone. To withdraw your question, please press star, then two. Please note, to the days of...

To ask a question you May press Star then one on a touchtone phone to withdraw your question. Please press Star then two.

Please note today's event is being recorded.

Speaker 1: I would now like to turn the conference over to David Walzy, Senior Vice President of Corporate Affairs at MEI Pharma. Please go ahead, sir.

I would now like to turn the conference over to David Walsh Senior Vice President of corporate Affairs that MDI pharma. Please go ahead Sir.

Thank you Gary Hello, and thank you for joining the <unk> Pharma conference call. Today. My name is David Vaulting, and I'm Senior Vice President of corporate Affairs for MAA with me today on the call me I or David or so President and Chief Executive Officer, Jay file Chief Financial Officer, and Dr. Richard Hawley, Chief Medical Officer before.

Speaker 2: Thank you, Gary. Hello, and thank you for joining the MEI Farmer Conference call today. My name is David Walzy, 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 Fial, Chief Financial Officer, and Dr. Richard Golli, Chief Medical Officer.

Speaker 2: Thank you for 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.

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 within the meaning of the safe Harbor provisions of the private Securities Litigation Reform Act of 1995, including without limitation statements regarding to.

Speaker 2: 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 other candidates.

The potential safety efficacy and regulatory and clinical progress of our product candidates, including the anticipated timing for 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 sufficient.

Speaker 2: 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.

Speaker 2: the sufficiency of our cash, cash equivalents, and short-term investments to fund our operations.

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 or.

Speaker 2: 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.

Speaker 2: the availability or appropriateness of utilizing the FDA's accelerated approval pathway for our product candidates.

Appropriate appropriate of utilizing the fda's accelerated approval pathway for our product candidates final data from our preclinical studies are completed clinical trials may differ materially from reported interim data from ongoing studies and trials cost and delays in the development <unk> FDA approval or the failure to obtain such approval for our product.

Speaker 2: 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.

Speaker 2: 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.

<unk> uncertainties are differences interpretation of clinical trial results uncertainty regarding the impact of rising inflation and the increase in interest rates as a result.

Speaker 2: potential economic downturn, activist investors are inability to maintain or enter into and the risk resulting from our dependence upon collaboration or contractual arrangements necessary for the development, manufacture, commercialization, marketing sales and distribution of any product.

Potential economic downturn activist investors.

Inability to maintain our entered into and the risks, resulting from our dependence on collaboration or contractual arrangements necessary for the development manufacture commercialization marketing sales and distribution of any products or competitive factors or inability to protect our patents are proprietary rights and obtain the necessary rights to third party patents and intellectual.

Speaker 2: competitive factors, our inability to protect our patents or proprietary rights, and obtaining 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.

Property to operate our business our inability to operate our business without infringing the patents and property proprietary rights of others General economic conditions, the failure of any products to gain market acceptance or inability to obtain any additional required financing technological changes government regulation changes in industry practice and one.

Speaker 2: 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. We do not intend to update any of these factors or to publicly announce the results of any revisions to these forward-looking statements.

Time 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, our 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.

Speaker 2: Under US 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.

With that I'll now turn the call over to David herself.

Speaker 3: Thank you, David, and thank you all for joining us today.

Thank you David.

Thank you all for joining us today.

Speaker 3: On today's call, I'll make some opening remarks and then turn the call over to Richard Golley, our Chief Medical Officer, to review our program.

On today's call I'll make some opening remarks, and then turn the call over to Richard <unk>, Our Chief Medical Officer to review our programs.

Speaker 3: 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 1st, so this is his first earnings call at MEI, and we're very happy to have him on the team.

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Our Chief Financial Officer will then provide some brief financial comments before moving into Q&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 MSCI and we're very happy to have one of the team.

Speaker 3: 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 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 upsell.

Upside of the Infinity merger was compelling for <unk> stockholders, we value the perspective of our stockholders with the proposed transaction behind US we are committed to pursuing our two promising clinical stage programs at the stand alone company.

Speaker 3: With the proposed transaction behind us, we're committed to pursuing our two promising clinical stage programs at the standalone company.

Speaker 3: Looking ahead over the next few quarters, we see important opportunities in the continued progress of our two clinical stage oncology programs, Voracyclib and ME344. 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.

Looking ahead over the next few quarters, we see important opportunities and the continued progress of our two clinical stage oncology programs Board cycle, and Ami 344, I would like to use this call to provide an update on the status of these programs and why we're optimistic.

<unk> about their potential.

Speaker 3: But of our access represent novel mechanisms of action. Forest cycloid is an oral CDK-9 inhibitor, and ME344 is a mitochondrial inhibitor that inhibits the oxfoss pathway. We're investigating the potential of these compounds to overcome resistance mechanisms to standard of care therapies. The BCL-2 inhibitor, the natoclaxid for forest cycloid, and the VEJF inhibitor, Bavicismat, in the case of ME344.

Both of our assets represent novel mechanisms of action for recycling as an oral CDK <unk> inhibitor and <unk> hundred four four is the mitochondrial inhibitor that inhibits the <unk> pathway. We are investigating the potential of these compounds to overcome resistance mechanisms to standard of care therapies.

The Bcl two inhibitor fanatical export board cycle, and the VEGF inhibitor Bevacizumab in the case of <unk> three four for the.

Speaker 3: The ongoing advancement of each program is based on non-clinical and in the case of ME344, clinical data supporting proof of principle for the respective combination.

The ongoing advancement of each program is based on non clinical and in the case of Ami 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.

Speaker 3: 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.

Speaker 3: We're 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 program.

We are working with some of the leading oncologists in the company in the country and both of our clinical studies and we are pleased with their level of engagement and interest in our programs.

Speaker 3: We expect data readouts from each program in the coming month.

We expect data readouts from each program in the coming months.

Yes.

With respect to fourth cycle as previously reported.

Speaker 3: With respect to the Vorocyclerb, as previously reported, we've seen promising data from our ongoing Phase I study. We're called at Vorocyclerb as a selective CDK-9 inhibitor, regulates the transcription of MCL-1, and through that mechanism, also potential to address the known Benenoclax resistance mechanism.

We've seen promising data from our ongoing phase one study recall that board cycle about the selective CDK <unk> inhibitor regulates the transcription of mcl, one and through that mechanism holds the potential to address a known <unk> resistance mechanism.

Speaker 3: The ongoing phase one study is evaluating borosite but at the single agent and combination with the NETA class, which is standard of care in AML and used in other hematwatch boygancies as well.

The ongoing phase one study is evaluating <unk>, but at the single agent and combination with <unk>, which is standard of care in AML and used in other hematologic malignancies as well.

Speaker 3: Ritual provide more detail shortly, but in brief, for a cycle of alone, and in combination with Venetoclacks, has been generally well tolerated in the Phase I study to date, with no significant mild suppression in patients with B cell bullying disease, or AML.

Richard will provide more detail shortly but in brief board cycle alone and in combination with <unk> has been generally well tolerated in the phase one study to date with no significant mindless depression in patients with B cell malignancies or AML.

Speaker 3: The results further demonstrate encouraging early clinical activity and heavily pretreat of patients that progressed on Venetoclacks who were administered for psychopmonotherapy and at the initial dose level in combination with Venetoclacks. The planned for psychoplock data readout in early 2024 is expected to include data from the dose-assending cohorts in the Phase I study evaluating for for psychoplus Venetoclacks and patients with AML.

The results further demonstrate encouraging early clinical activity in heavily pretreated patients that progressed on banana clacks, who were administered four-cycle mono therapy and that the initial dose level in combination with inadequate.

But planned for cyclic data readout in early 2024 is expected to include data from the dose ascending cohorts in the phase one study evaluating <unk> plus <unk> in patients with AML.

Speaker 3: Here are some of the leading KOLs we're working with. We're pleased with how the study is in the role.

Here are some of the leading Kols, we are working with.

We're pleased with how the study is enrolling.

Speaker 3: As for ME-344, we're pursuing a novel approach to cancer therapy with a combination of ME-344 and oxfos inhibitor that inhibits the production of ATP and monocondria and behecism at a Vegeph inhibitor, which inhibits the production of ATP through glycolysis.

As for MB 344.

We're pursuing a novel approach to cancer therapy with the combination of <unk> four four in Oxford <unk> inhibitor that inhibits the production of ATP in mitochondria and Bevacizumab.

Yes, Jeff inhibitor, which inhibits the production of ATP proved by colleges to.

Speaker 3: to deprived cancer cells of the energy needed to proliferate. Sevacism is an established standard of care in multiple solid tumors, including colorectal cancer. Our ongoing phase one of these studies evaluate metastatic colorectal cancer patients with ME-344 plus per sevacism.

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 one studies evaluating metastatic colorectal cancer patients with endometrial for core plus bevacizumab.

Speaker 3: This novel approach to treatment has also generated enthusiasm among our investigators in the ongoing study.

This novel approach to treatment has also generated enthusiasm among our investigators in the ongoing study.

Speaker 3: In earlier clinical studies, ME344 was generally well tolerated at the dose where currently investigating, and there was evidence of clinical activity as a single agent.

And early in earlier clinical studies <unk> hundred 44 was 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 and her two negative breast cancer patients waiting for mastectomy, Richard will discuss the decrease in pro in the proliferation and biomarker CAD 67 observed in that study.

Speaker 3: We had a first look at the potential for this combination and a 42 patient controlled window of opportunity clinical study in her two negative breast cancer patients waiting for mastectomy. Richard will discuss the decrease in the proliferation and biomarker, KIs-67 observed in that study.

We expect that the <unk> 34 for 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 <unk> study evaluating <unk> hundred 44 in combination with Bevacizumab in patients with metastatic colorectal cancer.

Speaker 3: We expect that the ME344 data readout planned in the first half of 2024 will include initial phase B and efficacy data from the first 20 patient cohort in the phase one B study evaluating ME344 in combination with that is a mass in patients with missed second colorectal cancer.

Speaker 3: We believe the potential value of both programs is notable given that the addressable market opportunities for Boris Vykliv and combination with Benadoclacks and ME344 in combination with Babathizamab are significant.

We believe that the potential value of both programs is notable given that the addressable market opportunities for Boris I believe in combination with <unk> and Ami 344 in combination with Bevacizumab are significant.

Speaker 3: The Netacrux is currently used across AML, CLL, and double-hit DLBCL, and generated approximately $2 billion in 2022 worldwide sales.

<unk> is currently used across AML, CLO and double hit <unk> and generated approximately $2 billion.

2022 worldwide sales.

Speaker 3: The NETACCIC sales are continuing to grow and are expected to generate $3.4 billion by 20. The NETACCIC sales are continuing to grow and are expected to generate $3.4 billion by 20.

<unk> sales are continuing to grow and are expected to generate $3 $4 billion.

By 2028.

Speaker 3: of asthenin-bevacism at bias simmores are used to treat a variety of cancers, including colorectal cancer and ovarian cancer.

The vast and Ambev and Bevacizumab biosimilars are used to treat a variety of cancers, including colorectal cancer and ovarian cancer.

Speaker 3: 2022 worldwide of Estonian Seventh-System App, I have similar sales reached $2 billion in 2022 and are expected to grow to $3.3 billion by 2020

2022 worldwide Avastin Bevacizumab Biosimilar sales reached $2 billion in 2022 and are expected to grow to $3 $3 billion by 2028.

Insured <unk> pipeline is promising and presents a substantial opportunity for delivering novel therapeutics for patients and creation and value creation for EMEA.

Speaker 3: In short, MEI's pipeline is promising and presents substantial opportunity for delivering novel therapeutics for patients and creation and value creation for ME.

Speaker 3: MEI stockholders. Both foresighted, global ME344 have the potential in combination with current standards care therapies to overcome known resistance mechanisms and improve patient outcomes.

<unk> stockholders.

Oh, sorry go ahead, then any 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 non clinical and in the case of <unk> hundred four for clinical data, demonstrating antitumor activity and mechanistic proof of concept.

Speaker 3: Each program is supported by non-clinical and in the case of ME344, clinical data demonstrating anti-tumor activity and mechanistic proof of concept for the combinations being evaluated. We anticipate reporting data for horse-likewood early in calendar 2024 and in the first half of 2024 for ME344.

The combination is being evaluated.

Anticipate reporting data for foresight, but early in calendar 2024 and in the first half of 2024 for 344.

Speaker 3: We look forward to these data readouts and the next steps these data will form.

We look forward to these data readouts and the next steps these data one four.

I'll now turn the call over to Richard <unk>, 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.

Speaker 3: I'll now turn the call over to Richard Galley, our chief medical officer, to provide additional details on our pipeline. Following Richard's remarks, J-File, our chief financial officer, will provide a brief financial overview before moving to Q&A.

Speaker 2: Thank you David and I will begin first by discussing what is likely a selective oral city cannot enter a drug candidate.

Thank you David and I will begin first by discussing by recycling a selective oral <unk> inhibitor drug candidate.

The mechanism of action of motorcycle just victim and this had to recycle a blog the transcription of Mcl, one and make at the pole 211, and DNA chips in that.

Speaker 4: The mechanism of action of the boris-saccharib is depicted in this cartoon boris-saccharib to block the transcription of MCL1 and make at the 122 level and DNA the transcription. In addition, boris-saccharib block the, the includes the stabilization of the NIC protein, which has the downstream effect on that pack.

In addition, Florida.

The Stebbins and includes the stabilization of the Nic protein, which has the balance sheet in effect on that in a moment I'll give more detail.

Speaker 4: And in a moment I would give more detail to the meaning of these two parts.

Meaning of these targets.

<unk> targets.

While <unk> had ebay has a favorable PK and PD profile.

Speaker 4: For a slightly had a very, as a favorable PK and PD profile, that allow its use or a link, because it's bioavailable, it is selective to CDK9 compared to other CDK, as shown to the table on the table to the right, where they are more binding affinity and longer residence time for CDK9 compared to the other CDK. In addition,

<unk> allow its used orally because it's available it is a selective to CDK nine compared to other CDK as shown to the table on the table to the right where they are more binding affinity add longer residence time for CDK nine compared to the other CDK. In addition.

Speaker 4: For recycling, have more selectivity to CDK compared to other kind mates.

We're excited to have more selectivity to CDK as compared to other teammates.

But is that this portends within IC 50, ranging from two to $1 seven micro molar and a variety of cell lines tested and interestingly in constant change in tumors other classes, which is rather than in patients with solid tumors or lymphoid malignancies with.

Speaker 4: For a saddest potent with an IC-50 raising from 0.2 to 1.7 micromolar in a variety of sen line tested and interestingly in constant rates in tumors over class which is rather than in pace with solid tumors or lymphoid maling speeds with tumors.

Tumors.

Speaker 4: Now let's focus on the two targets of interest. The protein MCL-1, it is known that it's increased is associated with poor prognosis in patients with acute myelid leukemia or AML and in a variety of these cell malignant.

Now, let's focus on the two targets of interest the protein Mcl. One it is now and that is this increase is associated with poor prognosis in patients with acute myeloid leukemia or AML and in a variety of b cell malignancies.

Gary: Good day, and welcome to the MEI fiscal year end earnings call. My name is Gary, and I'll be the conference facilitator today. All participants will be in a listen-only mode.

Gary: After today's prepared remarks, there will be an opportunity to ask questions. To ask a question, you may press star then one on a touch-tone phone. To withdraw your question, please press star then two. Please note, today's event is being recorded.

Speaker 4: In addition, up-regulation of MCL-1 is an established mechanism of resistant to Benarklax. As Benarklax inhibits ECL-2, it can lead to stabilization of MCL-1, leading to resistant to Benarklax over time.

In addition, upregulation of <unk> is an established mechanism of resistance to benefit flex as the Netflix inhibit ECL Julie can lead to stabilization of mcl, one leading to resistant <unk> overtime.

David Walsey: 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.

And defendants and separately. We also know that Mi is over expressed in a variety of cancers and tend to be associated with poor prognosis. In addition, make badly include K Ras mutation, which will be relevant for the discussion about the potential rollout for a site.

Speaker 4: independently and separately. We also know that a MIG is over-expressed with a variety of cancers and tend to be associated with puruprognotes.

David Walsey: With me today on the call from MEI or David Urso, president and chief executive officer, Dave File, chief financial officer, and Dr. Richard Ghalie, chief chief executive officer, Dave, for opening remarks, I'd like to remind you that during today's call will be making forward-looking statements. Certain information contained in this communication that are not historical in nature are forward-looking statements within 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 other 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 equivalent, and short-term investments to fund our operations.

Speaker 4: In addition, the Mick Bakley include care as a mutation, which will be relevant for the discussion about the potential role of horse fight.

David Walsey: 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 certainties, including, but not limited to our failure to successfully commercialize our product candidates, the availability or appropriateness of utilizing the FDA's accelerated approval pathway for our product candidates, final data from our pre-clinical 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.

Speaker 4: Let's begin first on the aspect of inhibition of MCL-1. As mentioned, it is relevant for AML and B-cellomethygneces and as a way to address the neglects resistance.

Let's begin first on the aspect of inhibiting mcl one as mentioned it is relevant for AML and B cell malignancies, and as a way to address that lacks resistance.

<unk> focus is initial development in hematologic malignancy, beginning with al <unk>.

Speaker 4: MEI focus is initial development in the hematologic malignistry beginning with A and L.

Speaker 4: The reason we selected AML is because the anatoclax based therapies are stator of care and approved and elderly patients who are unfit to receive intensive chemotherapy. In the NCCH guidelines, it's been established also as the stator of care in the body of market research, including the one cited on the right.

And the reason, we selected <unk> because of that <unk> based therapies are standard of care and approvals and elderly patients who are unfit to receive intensive chemotherapy.

CCH guidelines has been established also as the standard of care in a variety of markets, we serve including the one sided on the brands.

Speaker 4: In addition, ongoing studies are being conducted to establish the role of ventilats as part of the center of care in team at that being eligible patient.

In addition, ongoing studies are being conducted to establish the role of <unk> labs as part of this setup can and chemotherapy eligible patients.

Speaker 4: Our hypothesis is more precisely combined to vena clags as the potential to restore sensitivity to vena clags and therefore improve your elderly off-response.

Our hypothesis is for recycling combined to vantage labs has the potential to restore sensitivity to venetic class and therefore improve durability of response.

Okay.

Speaker 4: This slide summarizes the nonclinical data that support the combination of risk-active and better clacks in AML. This is a murine zinographed model. In panel A, it shows suppression of MCL well-level. In panel B, it shows that either a either agent alone has activity in AML, but the combination is synergistic with further increase in upper doses level. And that corresponds to an improvement survival in the model depicted here in AML.

This slide summarizes the non clinical data that support the combination of our recycling and Ben and blacks and AML listen in Marine Xenograft model and panel it shows suppression of mcl, well level and panel. The it shows that either a either agent alone has activity in AML, but the combination is synagis.

With further increases in that both doses level and that corresponds to an improving survival in the model depicted here in AML.

David Walsey: But certainties are differences interpretation in the clinical trial results, and certainly regarding the impact of rising inflation and the increase in interest rates as a result. Potential economic downturn, activists and investors, our inability to maintain or enter into and the risk resulting from our dependence upon collaboration or contractual arrangements necessary for the development, manufacture, commercialization, marketing sales and distribution of any products. Impeditive 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 property proprietary rights of others, general economic conditions, the failure of any products to gain market acceptance, our inability to obtain any additional required financing, technical hospital changes, government regulation, changes in industry practice and one-time events.

Speaker 4: We have similar data with the combination with Venoclax and CLL and diffuse large cell lymphoma model.

We have similar data with the combination with <unk> and diffuse large cell lymphoma models.

Speaker 4: Now moving to describe the Phase I study. This is a typical Phase I dose escalation expansion study. In patients with relapse refractory AML and B-cell malignancy in the first stage, which is the monoterepidose escalation, and in patients with relapse and refractory AML for the compilation with Benachlax stage.

Now moving to describe the phase one study.

As a table typical phase one dose escalation and expansion study and <unk>.

<unk> with relapsed refractory AML and B cell malignancy in the third stage, which is the monotherapy dose escalation and in patients with relapsed and refractory AML for the combination with <unk> stage.

Speaker 4: As for phase one studies, it endpoints consists of safety, pharmacokinetic. We are also collecting sample for biology, correlates primary to look at BH3 profiling and MCL-1 expression, as well as molecular mutation analysis. And we will also collect, of course, activity data.

As.

Phase one studies and the endpoints consists of safety pharmacokinetics.

It also collecting samples for biologic correlate primarily to look at BHG profiling and mcl, one expression as well as molecular mutation analysis and we will also collect of course activity data.

David Walsey: We do not intend to update any of these factors or to publicly announce the results of any revisions to these forward-looking statements.

David Walsey: Under US 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.

Speaker 4: The monitor torpedoes' escalation component has been completed with 40 patient enrolled, and we are now currently enrolling in the combination with VEDACLACS group in patient with AML.

The monotherapy dose escalation component has been completed with 40 patient enroll anywhere now currently enrolling in the combination with <unk> <unk> and patients with AML.

David Urso: 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. J-File, our Chief Financial Officer, will then provide some brief financial comments before moving to Q&A.

Speaker 4: As mentioned, this is a two-stage component, first a dose escalation, going from 50 milligram every update upward. And as of now, we have completed enrollment at the 150 milligram dose level.

As mentioned this is a two stage components, firstly dose escalation going from 50 milligram every other day a port.

And as of now we have completed enrollment at the 150 milligram dose level.

Speaker 4: Once it does that is confirmed to have well tolerance as well as evidence of activity, then we will proceed to expansion cohort.

Once.

It does that it's confirmed to have well tolerance as well as evidence of activity. Then we will proceed to expansion cohort.

David Urso: 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.

Speaker 4: Currently there's 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 Van Averclap.

There is one contemplated an 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 <unk>.

David Urso: 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 two promising clinical stage programs as a standalone company. Looking ahead over the next few quarters, we see important opportunities in the continued progress of our two clinical stage oncology programs, VORS Cyclib and ME344.

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 presented at some subsequent scientific meeting.

Speaker 4: This is a brief summary of the data observed in the Monus at the Dolde Estilation. Birmingham data would present it at the <expletive> 2021, and at this little data and final data would present it at some subsequent scientific meeting.

Speaker 4: In total, 40 patients will enroll all heavily pre-treated with a need enough three prior therapy ranging from one to up to eight therapies in one patient.

In total 40 patients were enrolled all heavily pre treated where they need enough three prior therapy, ranging from one to up to eight therapies and one patients.

Speaker 4: Two of those scheduled evaluating, initially daily, continuously in 16 patients.

Two dose schedule evaluating initially daily continuously in 16 patients and we have at that time pivoted to evaluate where recycling on a 14 days on 14 days offset FTE and a 28 day cycle and the reason for this pivot is because we have seen in the daily dosing to patients pneumonitis.

Speaker 4: And we have at that time pivoted to evaluate or recycling on a 14 days on, 14 days off therapy in a 28 days cycle. And the reason for this pivot is because we have seen an adedi dosing two patients, pneumonitis, that we felt were confounded by patient having developed differentiation syndrome.

David Urso: 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. With our assets represent novel mechanisms of action. VORS Cyclib is an oral CDK-9 inhibitor and ME344 is a mitochondrial inhibitor that inhibits the oxfoss pathway. We're investigating the potential of these compounds to overcome resistance mechanisms to standard of care therapies, the BCL-2 inhibitor of the Natal clax IVORS Cyclib and the VEGF inhibitor, Bavicismat in the case of ME344.

That we felt was confounded by patient having developed differentiation syndrome.

Speaker 4: seen an AML patient receiving drug therapy, as well as prior aogenic transplant with graft versus cells disease.

Seen in AML patients receiving targeted therapy as well as prior allogeneic transplant with graft versus host disease.

When we switch to the two weeks on two weeks off schedule, we're able to dose escalate up to 200 milligram without seeing dlt's, we stopped dose escalation not because of safety reason, but because we wanted to start pivoting to the combination with Vannatter flex our target combination regimen.

Speaker 4: When we switched to the two weeks off schedule, we were able to dose escalate up to 200 milligram without seeing DLT.

Speaker 4: We stopped those escalation not because of safety reason, but because we wanted to stop pivoting to the combination with venetoclacks, our target combination regs.

David Urso: The ongoing advancement of each program is based on non-clinical and in the case of ME344, clinical data is supporting proof of principle for their respective combinations. We chose these combinations approach is based on clear hypotheses to address known resistance mechanisms of each standard of care therapy, clear medical needs, and significant commercial opportunities. We're 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.

Speaker 4: With the monitor, we have seen patient having evidence of anti-tumor activity, including one patient with AML who has a morphology in looking at free state, let's see.

There isn't a monotherapy, we have seen patient having evidence of anti tumor activity, including one patient with AML, who has a morphology leukemia free state achieved.

Speaker 4: and five of temptations with the ML and the 200 milligram dose with stable disease.

And five of 10 patients with AML at the 200 milligram dose less stable disease.

Speaker 4: Importantly, we have seen in our positive laboratory studies done with collaboration at academic centers, a decrease in MCL1N and MIG using a single cell RNA sequencing from three patients with CLL and two patients AML.

Importantly, we have seen in our qualitative laboratory studies done with collaboration academic centers, a decrease in mcl, one and and make.

Using a single cell RNA sequencing from three patient with cielo and two patients with AML.

Speaker 4: So overall, the recidivism on therapy added those up to 200 milligram on a 14 days on, 14 days off schedule was well-connerated. Had no deality, we did not see drug related metropenia. We did not see grade three or higher drug related toxicity and no patients were discontinued due to drug related toxins.

So overall the recycled as a monotherapy at a dose of up to 200 milligram on a 14 days on 14 days of schedule was well tolerated had no DLT, we did not see drug related neutropenia, we did not see grade III or higher drug related toxicity and no patients were discontinued.

David Urso: We expect data readouts from each program in the coming months. With respect to VORS Cyclib, as previously reported, we've seen promising data from our ongoing Phase I study. We're called at VORS Cyclib as a selective CDK-9 inhibitor, regulates the transcription of MCL-1 and through that mechanism, also potential to address the known Natal clax resistance mechanism. The ongoing Phase I study is evaluating VORS Cyclib as a single agent and combination with Natal clax, which is standard of care in AML and used in other hematology poignant disease as well.

<unk> due to drug related toxicity.

Speaker 4: As mentioned, we are now enrolling in the Benad Glass combination. Up to now, we have no not seen DLT.

As mentioned, we are now enrolling in Nevada glass combination up to now we have no doubt seen dlt's net.

Speaker 4: The PK analysis of the earlier dose levels do not show drug-right interactions, and we are seeing evidence of clinical activity at the low dose evaluate to today, manifested by reduced transfusions in proof counts, response observed in some patients, and over 80% of patients continuing beyond cycle one, the DLC window.

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 evaluated today manifested by reducing transfusions and probe counts response observed in some patients and over 85% of the patient continuing beyond.

David Urso: Richard will provide more detail shortly, but in brief, Borys cycle of alone and in combination with Venatoclacks has been generally well tolerated in the Phase I study to date with no significant myelose depression in patients with B-cell blowing disease, or AML. The results further demonstrate, encouraging early clinical activity and heavily pre-treat of patients that progressed on Venatoclacks who were administered 4-cycle of monotherapy and at the initial dose level in combination with Venatoclacks.

<unk> cycled one the LTE windows keep in mind. This is observed in patients who have been heavily pre treated when they need us to prior therapy, including <unk>.

Speaker 4: Keep in mind, this is observed in patients who have been haven't even retreated with the need of two prayers that are at the including venerable.

Speaker 4: Now let's turn the focus to the recycling effect on me.

Now, let's turn to focus two very stagnant effect on mix.

Speaker 4: As mentioned, Ming is overexpressant in a variety of cancer and tend to be associated with poor prognosis. There is no current treatment approved for Ming-Vitated Tumor.

As mentioned, making is over expressed in a variety of cancer and tend to be associated with poor prognosis. There is no current treatment approved for Mick mutated tumors CD.

David Urso: The planned Borys cycle of data readout in early 2024 is expected to include data from the dose-assending cohorts in the Phase I study, evaluating 4-cycle plus Venatoclacks in patients with AML. Here are some of the leading KOLs we're working with. We're pleased with how the study is in rolling.

Speaker 4: CDK-9 inhibition lead to reduce transcription of MIC and stabilization thus can have a potential treatment effect.

CDK inhibition lead to reduce transcription of snake and stabilization, thus can have any potential treatment effect.

We have clinical data from the initial studies conducted in patients with solid tumors by the private sponsors two studies were conducted one using a two weeks on one week off schedule and the other one using a daily continuously schedule.

Speaker 4: We have clinical data from initial studies conducted in patients with solid tumors by the prior sponsor. Two studies were conducted one using a two weeks on one week off schedule and the other one using a daily continuously schedule.

David Urso: As for ME-344, we're pursuing a novel approach to cancer therapy with a combination of ME-344 and Oxfos inhibitor that inhibits the production of ATP and monocondria and Bethacismat, a Vegeph inhibitor which inhibits the production of ATP for glycolysis to deprive cancer cells of the energy needed to proliferate. Vegephismat is an established standard of care in multiple solid tumors, including colorectal cancer. Our ongoing Phase I D study is evaluating metastatic colorectal cancer patients with ME-344 plus Vegephismat.

Speaker 4: relevant to the discussion today is in the daily continuous schedule study samples were obtained from 25 patients with a variety of study tumors and tested on a 10 gene biomarker with a sample obtained at baseline and with each subsequent course of theta.

Relevant to the discussion today is in the daily continuous scheduled study samples 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 quarter et cetera.

Speaker 4: We have seen a decrease in steemake expression in 60% of the patient tested in that study. And here are shown only two illustrative examples of two patients. Circles are the make the gene that we evaluated showing a decrease in make overtime with each course of therapy.

We have seen a decrease in <unk> expression and 60% of the patients tested in that study and here are shown on the two illustrative example of two patients circles are the mic.

David Urso: 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 her two negative breast cancer patients waiting for mastectomy. Richard will discuss the decrease in the proliferation in biomarker K-67 observed in that study.

The gene that retaliated, showing a decrease and make overtime was each quarter Eric.

At <unk>, we have further expanded the evaluation of that effect on make and K Ras by evaluating a number of cell lines listed here, including colorectal cancer and in other tumors that had.

Speaker 4: At MER, we have further expanded the evaluation of that effect on MIG and Keras by evaluating a number of cell lines listed here, including Correctum Cancer and other tumors, that had a variety of Keras mutation, G12C, but also other.

Variety of K Ras mutation G 12, C, but also others and show to the panel to the right dose response relationship between <unk> dose and suppression of tumor growth and three different cell line with different K Ras mutation.

Speaker 4: and shown to the panel to the right is a dose response relationship between Boris Akip and suppression of tumor growth and three different cell lines with different care aspects.

David Urso: We expect that the ME-344 data readout planned in the first half of 2024 will include initial phase B in efficacy data from the first 20 patient cohort in the Phase I D study evaluating ME-344 in combination with Bethacismat in patients with second colorectal cancer. We believe that the potential value of both programs is notable given that the addressable market opportunities for borrower cyclists in combination with Benadoclis and ME-344 in combination with Bethacismat or significant.

Speaker 4: And lastly, enough interest is combination of forestry with the K-RAS inhibitors sotaricic. This experiment was conducted in a pancreatic tumor cell model. This is an intralesional infusion of one or a combination of drug. And the readout is shown to the panel through the right where we see two type of analysis.

And lastly, and of interest is combination of recycling with the K Ras inhibitors. So terracing. This experiment was conducted in a pancreatic tumor cell model. This is intra lesion of infusion of one or a combination of drug and the readout is shown to the analyst day.

Right, where we see two types of analysis, one is standard pathology with an H a sustaining that shows.

Speaker 4: One is the standard pathology with an H.A. staining that shows the control arm, either age of a long and to the bottom right panel of the combination, showing a evidence of cell death, picnotic cells, and also in the fluorescent staining, an increased number of cells died.

All are either agent alone and to the bottom right panel of the combination showing.

David Urso: Benadoclis is currently used across AML, CLL, and double-hit DLBCL and generated approximately $2 billion in 2022 worldwide sales. Benadoclis sales are continuing to grow and are expected to generate $3.4 billion by 2020-A. Of Aspen and Bethacismat bias similars are used to treat a variety of cancers including colorectal cancer and a varying cancer. 2022 Worldwide Abastanian Sevesism at Biosimilar Sales reached $2 billion in 2022 and are expected to grow to $3.3 billion by 2020 A.

Evidence of cell death exotic cells.

And also in the fluorescein staining and increased number of cells die.

Speaker 4: So that is my summary for the Vorsakib program. Now I'm turning to the description of ME344, a mitochondria inhibitor drug candidate.

So that is my summary for the <unk> program now I am turning to the description of Ami 344, <unk> inhibitor drug candidate.

This is a very interesting and novel mechanism of action, where date inhibition on the micro <unk> is a dual effect one on ox sparse and two on Purion synthesis reminding that fewer incentives is made.

Speaker 4: It's a very interesting and novel mechanism of action where the inhibition on the mitochondria is a dual effect, one on oxfoss and two on curing synthesis reminding that curing synthesis is made at the surface of mitochondria itself.

Surface of mitochondrial yourselves.

Speaker 4: The relevance of that is that the mechanism is illustrated the panel to the right, which I will simplify by saying that my Deconjria generate ATP, which are essential for producing energy for cells. And that is done to the Oxfauce pack.

The relevance of that mechanism is illustrated the panels to the right, which I will simplify by saying that.

David Urso: In short, MEI's pipeline is promising and presents substantial opportunity for delivering novel therapeutics for patients and value creation for MEI stockholders. Both foresighted global ME-344 have the potential in combination with current standards care therapies to overcome known resistance mechanisms and improve patient outcomes. Each program is supported by non-clinical and in the case of ME-344, clinical data demonstrating anti-tumor activity and mechanistic proof of concept for the combinations being evaluated. We anticipate reporting data for foresight books 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 form.

<unk> generate ATP, which are essential for producing energy for ourselves and that is done so the <unk> pathway.

Speaker 4: blocking the autofas with ME344 with lead to a decrease in ATP source of energy and eventually a by a cascade of event to potentially sell death.

Blocking the sauce with any 344 with linked to a decrease in ATP source of energy and eventually a by the cascade of events to potentially sell that.

Speaker 4: Fetrically, purine biospendence is done as I said at the surface of mitochondria, which M-E-344 can block. Purine are essential to cell proliferation, and blocking by purine biospendence could lead to a decrease in cell growth and proliferation.

Separately hearing in biosynthesis is done as I said at the surface of the mitochondria, which at least 344 can block <unk> essentially to a cell proliferation and blocking buyout peering biosynthesis could lead to a decrease in cell growth and brought exploration.

Speaker 4: This is a simple panel of over 200 cell lines that were tested for ME344 activity in vitro and as one can see, ME344's coaching at the nanomolicular level and nearly all cell line tested except if you...

This is a simple panel offset over 200 cell line that were tested for <unk> III for activity in vitro and as one can see.

Richard Ghalie: I'll now turn the call over to Richard Ghalie, our chief medical officer, to provide additional details on our pipeline.

Three four floors potent at the nano molecule level and nearly all cell lines tested except a few.

Richard Ghalie: Following Richard's remarks, J-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 Borersight lip, a selective oral CD-Canon in a drug candidate. The mechanism of action of Borersight lip is depicted in this cartoon, Borersight lip blocked the transcription of MCL-1 and made at the PAL-21 and DNA the transcription. In addition, Borersight lip blocked the, includes the stabilization of the NIC protein, which has the downstream effect on that path.

Amy I conducted two phase one studies, one as a single agent dose escalation to determine the safety efficacy and PK and that study led to the determination that order commended phase II dose for further the loss development is 10 milligram per kilogram.

Speaker 4: MEI conducted two phase one studies, one as a single agent, those escalation, to determine the safety, efficacy, and PK. And that study led to the determination that the recommended phase two dose for further development is 10 milligram per kilogram.

Richard Ghalie: In a moment, I'll give more detail to the meaning of these two targets. Borersight lip had a very, as a favorable PK and PD profile, that allow its use orally because it's bioavailable. It is selective to CD-Canon compared to other CD-K as shown to the table on the table to the right, where they are more finding affinity and longer residence time for CD-Canon compared to the other CD-K. In addition, Borersight had more selectivity to CD-K as compared to other timings.

Speaker 4: The next study evaluating ME344 with the chemotherapy to put the can in a couple of types of solid tumors.

The next study evaluating <unk> hundred 40, <unk>, where the chemotherapy <unk> and a couple of type of solid tumors.

Speaker 4: 48 patients are on the study. Myelose depression due to platycin was observed. We had disease revelation at 49% of the patients.

48 patient enrolled in the study myeloid suppression.

Keegan was observed we had disease simulation at 49% of the patients.

Speaker 4: However, NTI decided to pursue the development and E3-4 in a different direction on the basis of Spalag.

However, <unk> decided to pursue the development of <unk> four in a different direction on the basis of biology. However, before I go through that this is a table summarizing the safety profile of <unk> and a 344 as a single agent in the phase one study pointing to the fact that neuropathy was seen.

Speaker 4: However, before I go to that, this is a table summarizing this safety profile of ME-344 as a single agent in the Phase I study, pointing to the fact that neuropathy was seen only at doses higher than 10 milligram per miculogram was the dose limiting toxicity. The state was not reported at lower dose.

Only had doses higher than 10 milligram per kilogram was the dose limiting toxicity was not reported at lower doses.

Speaker 4: Now let us try the new strategy that we would like to employ any 344 in combination with the anti- and geogenic agents primarily a vast and orbital exosimap.

Now let me describe the new strategy that we would like to employ any 344 in combination with the anti angiogenic agents, primarily avastin or bevacizumab.

Speaker 4: This is for a simple observation that when a vestin is administered to patient, it blocks the glycolytic energy pathway.

Richard Ghalie: Borersight is potent with an IC-50 raising from 0.2 to 1.7 micromolar in a variety of cell line tested and interestingly, it concentrates in tumors over class, which is rather than in patient with solid tumors or lymphoid malinds leads with tumors.

<unk> stands for it's simple observation that when a vast and is administered to patients it blocks the glycolytic energy pathway.

Speaker 4: leading to effect on stalled roads. However, stalled are...

Leading to effect on cell growth however cells are.

Okay.

Richard Ghalie: Now, let's focus on the two targets of interest. The protein MCL-1, it is known that its increase is associated with poor prognosis and patients with acute mild leukemia or AML and in a variety of cell malignancies. In addition, a regulation of MCL-1 is an established mechanism of resistant to benaclax. As benaclax inhibited ECL-2, it can lead to stabilization of MCL-1, leading to resistant to benaclax over time. Independently and separately, we also know that MEI is overexpressing a variety of cancers and tend to be associated with poor prognosis. In addition, the MEI pathway includes care-aspectation, which will be relevant for the discussion about the potential role of horse-fighting.

Speaker 4: courses, the ADP I mentioned earlier. Therefore, it is plausible that the body... Thank you.

Versus the ADP I mentioned earlier.

Therefore, it is a plausible that the body.

Three four.

Stockholders' nightmare.

Yeah.

Speaker 4: So how can you then combine ME344 to block the mitochondria energy and a Vegas inhibitor like a vastness with now have it possibly obstinetically Dallotty and therefore improving and fat tumor control.

So I would continue then combining I need 344 to block the microphones and energy and <unk>.

Jeff inhibitor like <unk> with now have a possibly authentic lithology and therefore, improving anti tumor control.

Speaker 4: This hypothesis was tested initially in animal model, of which I present two, one, a colorectal cancer model and one, a breast cancer model, using ME344 in combination with oral, vegetin inhibitor, intenidib and agroethanin. And, seen on this slide is a decrease in tumor growth with the combination, compared to either agent alone, and improved survival in colorectal model.

This hypothesis was tested initially an animal model of which are presented to one eight colorectal cancer model and won a breast cancer model using and new 344 in combination with oral VEGF inhibitor.

<unk> and seen on this slide is a decrease in tumor growth with the combination compared to either agent alone and improve survival in colorectal model.

Richard Ghalie: Let's begin first on the aspect of inhibition of MCL-1. As mentioned, it is relevant for AML and B-cell immun diagnoses and, as a way, to address the neglects resistance. MEI focuses its initial development in the hematologic malignancy, beginning with AML. The reason we selected AML is because the anatoclax-based therapies are standard of care in approved and elderly patients who are unfit to receive intensive chemotherapy. In the NCCH guidelines, it's been established also as the federal care in a variety of market research, including the one cited on the right.

Speaker 4: This led to a study by collaborative at the NCI Spain in Mendered, a multi-center study. A proof of concept study evaluating ME344 and the Vesizumab in patients with breast cancer. The reason breast cancer was selected is because that is a window for opportunity for this type of mechanistic studies where patients between diagnosis and definite surgery has a bit of time where the study could be conducted.

This led to a study by collaborators at the NCI.

Pain in Madrid, a multicenter study and proof of concept study evaluating <unk> and bevacizumab in patients with breast cancer. The recent 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 beautiful.

Time, where it is.

This study could be conducted.

Speaker 4: It was a randomized control study in 41 patients, group A received the vizimab with ME344, just one cycle, and we'll be receiving the vizimab alone. The readout was a PET scan to look at tumor vascularization and tumor biopsy looking primarily at the biomarker of tumor proliferation, called KI67.

It was a randomized control study in 41 patients group and received Bevacizumab with at <unk> hundred four for just one cycle.

Richard Ghalie: In addition, ongoing studies are being conducted to establish the role of Venoclax as part of the center of care in chemotherapy eligible patients. Our hypothesis is more precisely combined to Venoclax as the potential to restore sensitivity to Venoclax, and therefore improved your elderly off-response.

And we will be received bevacizumab alone.

The readout was a pet scans to look at tumor vascularization and tumor biopsy looking primarily at the biomarker of tumor proliferation Cole <unk> 67.

Speaker 4: Results are illustrated on the slide.

Results are illustrated on this slide.

Richard Ghalie: This slide summarizes the nonclinical data that supports the combination of obstaclet and Venoclax and AML. This is a murine zinographed model. In panel A, it shows suppression of MCL well-level. In panel B, it shows that either a either agent alone has activity in AML, but the combination is synergistic with further increase in apoptosis level. And that corresponds to an improvement survival in the model depicted here in AML. We have similar data with the combination with Venoclax and CLL and diffuse large cell lymphoma models.

Speaker 4: Group A, again, is the combination of ME344A vellisismab in green. As you can see, looking at all patients around the study, there was a significant decrease of KI67 compared to what observed with vellisismab alone.

Group again is the combination of <unk> hundred 40, <unk> Bevacizumab in Green as you can see looking at all patient enrolled in this study there was a significant decrease of <unk> 67, compared to observe with Bayliss with Bevacizumab alone.

Speaker 4: focusing now on the subset of patient in this study who had a tumor normalization, vascular vascularization, normalization by PET, this effect is further enhanced.

Focusing now on the subset of patients in this study who had a tumor normalization of vascular.

Vascularization organization by Pet this effect is further enhanced.

Speaker 4: This led us to the decision now to proceed in a clinical trial where clinical readout. And we selected the colorectal cancer as the first study to evaluate the combination because it's an unmet need and a vastness is used in that study.

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.

Richard Ghalie: Now I'm moving to describe the Phase I study. This is a keyable, typical Phase I dose escalation expansion study. In patients with relapse refractory AML and B-cell malignancy in the first stage, which is the model of the libido-descalation. And in patients with relapse and refractory AML for the combination with Venoclax stage. As Phase I studies, it endpoints consists of safety, pharmacokinetic. We are also collecting sample for biologic correlates, primary to look at BHC profiling and MCL-1 expression, as well as molecular mutation analysis, and we will also collect of course activity data.

Speaker 4: So this is a phase one to study and base relapse directly cancer of the failure of all standard therapy. Primary objective is progression free survival. Secondary objective are survival and safe.

So this is a phase one two study in patient relapsed colorectal cancer. After failure of all standard therapy primary objective is progression free survival.

The objective our survival and safety.

Speaker 4: The study is conducted in separate cohort beginning with cohort one.

The study is conducted in separate cohorts beginning with cohort one.

Speaker 4: And using the same dose and schedule that was used in the breast cancer study, one patient will be enrolled, and the readout will be that four months after the patients, last patients enrolled. And considering the positive outcome is a TFS at four months of 20% or higher. Then that will lead to a evaluation of a second cohort and subsequent to a cohort to be discussed with the FDA.

And are you using the same dose and schedule that was used in the breast cancer study <unk> patients will be enrolled and the readout will be that four months.

After the patients last patient is enrolled.

Consider it as a positive outcome as a PFS at four months of 20% or higher.

Richard Ghalie: The monotapido-descalation component has been completed with 40 patient enrolled, and we are now currently enrolling in the combination with Venoclax group in patient with AML. As mentioned, this is a two stage component, first a dose escalation, going from 50 milligram every update 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 venetoclux.

Then that will lead to an evaluation of a second cohort and subsequent dose cohort to be discussed with the FDA.

Speaker 4: With that, I conclude the clinical update and will turn it to a J5 to talk about the financial overview. Thank you, Richard.

With that I conclude the clinical update and we'll turn it to Jay to talk about the financial overview. Thank.

Thank you Richard.

Speaker 2: As reported earlier today, as of June 30, 2023, MEI had 100.7 million in cash cash equivalents in short-term investments with no outstanding debt.

As reported earlier today as of June 32023, <unk> had $100 7 million in cash cash equivalents and short term investments with no outstanding debt.

Speaker 2: 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 plan for a cycle of the ME-344, phase one and phase one B clinical programs respectively. I'll 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.

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 <unk> $3 40 for phase, one and phase <unk> 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.

Speaker 3: Thanks Jay. As you heard today, I believe we have two exciting programs with expected data readouts beginning with Forest Vycliffe, early encounter 2024, and in the first half of 2024 for ME344.

Thanks, Jay as you've heard today I believe we have two exciting programs with expected data readouts beginning with Pharmacyclics early in calendar 2024, and in the first half of 2024 4344.

Richard Ghalie: This is a brief summary of the data observed in the monopathy dose escalation. For me, a data was presented at the ASH 2021 and additional data and final data were presented at some subsequent scientific meeting. In total, 40 patients will enroll all heavily retreated with a need enough three prior therapy ranging from one to up to eight therapies in one patient. Two of those casual evaluating initially daily, continuously in 16 patients.

Speaker 3: 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.

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.

Speaker 3: Before we turn to Q&A, I'd like to briefly acknowledge that two of our stockholders, Anthony Cablecar, have initiated a consensualization process and separately submitted three director candidates to stand for election at the company's annual stockholder meeting this year.

Before we turn to Q&A I'd like to briefly acknowledge that two of our stockholders Anson and cable car have initiated a consent solicitation process separately submitted three director candidates to stand for election at the Companys annual stockholder meeting this year.

Richard Ghalie: And we have at that time pivoted to evaluate or recycling on a 14 days on, 14 days off therapy in a 28 days cycle. And the reason for this pivot is because we have seen in a daily dosing two patients, luminitis that we felt were confounded by patient having developed differentiation syndrome, seen in AML patient receiving therapy, as well as prior allogenic transplant with graft versus cells disease. When we switched to the two weeks off schedule, we were able to dose escalate up to 200 milligram without seeing DLTs.

Speaker 3: We've had several conversations with Anson and CableCar as part of ongoing efforts to resolve the situation and remain open to further discussion.

We have had several conversations with answering cable car as part of ongoing efforts to resolve the situation and remain open to further discussions with you.

Speaker 3: We will appropriately address the actions of these fuckholders in Duke Court.

We will appropriately address the actions of the stockholders in due course for the purposes of this earnings call. We are here to discuss our programs.

Speaker 3: For the purposes of this burning's 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 and A. We will...

Coming milestones, we ask that you. Please keep your questions to these topics I'll now ask the operator to provide instructions for asking questions and then open the call for Q&A.

Richard Ghalie: We stopped those escalation not because of safety reason, but because we wanted to start pivoting to the combination with venetoclux, our target combination region. With the monopathy, we have seen patient having evidence of anti-tumor activity, including one patient with AML who has a morphology looking at free state achieved, and five of temptations with AML at the 200 milligram dose were stable disease. Importantly, we have seen in our collective laboratory studies done with collaboration at academic centers, a decrease in MCL1NNMIC using a single cell RNA sequencing from three patients with CLL and two patients AML.

We will now begin the question and answer session to.

Speaker 1: To ask a question, you may press star then one on your telephone keypad.

To ask a question you May press Star then one on your telephone keypad if.

Speaker 1: If you are using a speaker phone, please pick up your handset before pressing the key.

If you were using a speakerphone please pick up your handset before pressing the keys to withdraw your question. Please press Star then two.

Speaker 1: If you would draw your question, please press star then two.

Speaker 1: At this time, we will pause momentarily to assemble our roster.

At this time, we will pause momentarily to assemble our roster.

Speaker 1: Our first question is from Yale Gen with Layla on Company. Please go ahead.

Our first question is from Yale Jen with Laidlaw <unk> Company. Please go ahead.

Speaker 5: Good afternoon and thanks for taking the questions as well as the providing.

Good afternoon, and thanks for taking the questions as well providing a.

Richard Ghalie: So overall, the recycling as a monotapy at a dose of up to 200 milligram on a 14 days on, 14 days off schedule was well-honored, had no DLT. We did not see drug related metropenia, we did not see great three or higher drug related toxicity, and no patients with discontinued due to drug related toxicity.

Speaker 5: clear view of what happened currently. Maybe I start with a housekeeping question that you've got about 100 million.

Clear view of what's happening currently.

Maybe I'll start with a housekeeping question that you got about 100 million cash and in the press release, you suggested that the.

Speaker 5: And in the press release, it's just that you have on 12 months, maybe a little bit longer runway. Given that you are still in phase one, one, two, study, should we anticipate it to be a more conservative estimate or additional thoughts behind that in terms of the runway? And I have some follow-up as well.

You have.

On a 12 month, Amit may be a little bit longer runway give.

Richard Ghalie: As mentioned, we are now enrolling in the venetoclux combination. Up to now, we have no not seen DLTs. The PK analysis of the earlier dose levels do not show drug right interactions, and we are seeing evidence of clinical activity at the low dose evaluated today, manifested by reduced transfusions, improved counts, response observed in some patients, and over 85% of patients continuing beyond cycle one, the DLT windows. Keep in mind, this is observed in patients who have been heavily pre-treated with the need of two parts that have been including venetoclux.

Given that you are still in phase one two study.

We anticipate it to be a more conservative estimate or additional thoughts.

Behind that in terms of the runway and I have some follow up as well.

Speaker 3: Thanks, you know, this is David. I would say it's, you know, conservative in the

Thanks, Joe This is David.

I'd say.

It's.

Conservative in the sense that.

Speaker 3: You know, we've got all the capital we need to do the phase one programs as we're currently, they're currently planned and as we, you know, have some ideas about augmenting them. But going into phase two 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 and that's in that respect.

We've got all the capital we need to do the phase one programs.

As you are currently.

There are currently planned and as we have some ideas about augmenting them.

Richard Ghalie: Now, let's turn the focus to the recycling effect on me. As mentioned, MEI is overexpressing in a variety of cancer and tend to be associated with poor prognosis. There is no current treatment approved for MEI Pharma Inc. CTK-9 inhibition lead to reduce transcription of MEI 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. Two studies were conducted one using a two weeks on one week off schedule and the other one using a daily continuously schedule.

We're going into phase two 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.

Okay.

Speaker 3: Yeah, like we said, at least, it's at least, you know, 12 months and, and you know,

It's at least its at least 12 months.

No.

Speaker 3: 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.

And covering the current 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, the housekeeping, one which is the top line I understand.

Speaker 5: Sure, and maybe just in terms of again, let the housekeeping one, which is the top line. I understand.

Richard Ghalie: Rather than 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 biomarkter. With a sample obtained at baseline and with each subsequent course of therapy. We have seen a decrease in steemake expression in 60% of the patient tested in that study. And here are shown only two illustrative examples of two patients. Circles are the gene that we evaluated showing a decrease in make over time with each course of therapy.

Speaker 5: The prior years are completed, so should we anticipate through some top line coming just because of the amurization or we should anticipate that to be stopped?

The prior deals.

Completed so should we anticipate some topline coming just because of the amortization or we should anticipate that to be stopped and the early sale of near term.

Speaker 3: I'm sorry, can you repeat, we were having a little bit of trouble following the question, could you please repeat it?

I'm, sorry could you repeat we were having a little bit of trouble. Following the question could you please repeat it.

Speaker 5: Sure. In terms of the top line revenue that you have, until this quarter of my question is, would that continue for the subsequent fiscal year, or simply this revenue numbers, is just the amortization of the prior revenue.

Sure in terms of the topline revenue that you have this quarter.

My question is would that contain will continue for the subsequent fiscal year or simply these revenue numbers just the amortization of the prior.

Richard Ghalie: At MEI we have further expanded the evaluation of that effect on MIG and KERAS by evaluating a number of cell lines listed here including colorectum cancer and other tumors that had a variety of KERAS mutation, G12C but also others. And shown to the panel to the right is a dose response relationship between Boryslachib dose and suppression of tumor growth and three different cell lines with different KERAS mutation.

<unk> revenue.

Revenue.

We received.

Speaker 3: Yeah, I mean, all the revenue we're recognizing is all KKC driven from our collaboration with them. So it's not anticipated to continue into the future.

Yes, I mean, all of the revenue were recognizing as all key Casey driven from our collaboration with them. So it's not anticipated to continue into the future.

Okay, maybe the last question here.

Speaker 5: Okay, maybe the last question here is in the clinical side over crucifix phase one data readout. What should we anticipate specifically in terms of sort of type of data with that? Other than the safety, would that be PK and would that be any biomarker or other aspect could you provide as a little color on that?

In the clinical side of or close the clubs.

Phase one data readout.

What should we anticipate that typically in terms of sort.

So the type of data with the.

Other than the safety would that be PK and would that be any biomarker or other aspect could you provide a little bit more color on that.

Richard Ghalie: And lastly and of interest is combination of Boryslachib with the KERAS inhibitors sulfuric. This experiment was conducted in a pancreatic tumor cell model. This is a traditional infusion of one or a combination of drug and the readout is shown to the panel to the right where we see two 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 a evidence of cell death, the kinetic cells and also in the fluorescent staining an increased number of cells dying.

Yes. This is Richard yes, it will be a combination of safety data primarily since this deep endpoint and the primary endpoint in phase one study.

Speaker 4: Kelly, that's a richer. Yes, it will be a combination of safety data primarily, since this is the end point, the prime end point that phase one study. Perhaps they're recommended phase two dose. They will be also PK data and biomarker analysis. All of them will be available.

Perhaps the recommended phase two 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 fire marker in mind? Yeah, it's still...

What specific.

You already have some biomarker in mind.

So what that might be.

Speaker 4: Right. So I've mentioned it when I present a monoterectodosolation, the biomarker that we are evaluating are the VAC profiling, particularly MCL-1 expression.

Alright, So I've mentioned it when I presented a monotherapy dose escalation the biomarker that we are evaluating.

Richard Ghalie: So that is my summary for the Boryslachib program.

Bac profiling, particularly mcl one expression.

Richard Ghalie: Now I'm turning to the description of ME344, a mitochondria inhibitor drug candidate. It's a very interesting and novel mechanism of action where the inhibition on the mitochondria is a dual effect one on oxfoss and two on curing synthesis, reminding that curing synthesis is made at the surface of mitochondria cells. The relevance of that is the mechanism is illustrated 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 oxfoss Blocking the autofas with ME-344, with lead to a decrease in ATP, source of energy, and eventually by a cascade of events to potentially sell death.

Speaker 4: where I look at multiple molecules by a market such as me.

Look at the multiple.

Molecular biomarkers such as Mitch.

Speaker 4: And we will be looking at potentially other biomarkers that are rather than directly the effect of CDK9 on the chart.

And we will be looking at potentially other biomarkers that are relevant directly to the federal CDK nine on the targets.

Speaker 5: Okay, great. Yeah, I'll get back to the queue and

Okay, Okay great.

I'll get back to the queue.

Thanks.

Speaker 3: I mean, I guess we should also say that it's just from a clinical perspective for the cohort one from ME344, we will be looking at PFAS and for the Forest Bike Lib expansion cohort that's in our protocol right now, we'll be looking at LR, so those are just standard clinical endpoints for the two respective disease.

For the colors.

I guess, we should also say that just from a clinical perspective for the cohort one from 344, we will be looking at.

PFS and for the water cycle expansion cohort thats in our.

In our protocol right now we'll be looking at <unk>. So those are just standard clinical endpoints for the two respective diseases.

Actually let me if I can maybe just follow up with one that you said that 20% or higher.

Speaker 5: Actually, let me, if I can, maybe just follow up as well, that you set up 20% or higher of the threshold for moving forward for them.

Threshold for moving forward for them.

Richard Ghalie: Fetrically, purine biosynthesis is done, as I said, at the surface of mitochondria, which ME-344 can block. Purine is essential to cell proliferation, and blocking by 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's potent at the nanomolecular level, and nearly all cell line tested except if you.

Speaker 5: for the ME344 study, CO-1. What sort of, what are the factors determining that the 20% was the number of the cutoff?

Uh huh.

And the repo or the cohort one.

What sort of.

What other factors determine that 20% number.

As of the cutoff.

Speaker 3: Well, you know, that was a requirement or a gate that we, you know, reached in collaboration with the clinicians. But we really need to dig into exactly what the patient population is before we can, you know, really know what the meaning of that threshold is. It obviously depends on exactly the experience that each patient.

That was a that was.

A requirement or a key 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 those that threshold as it obviously depends on exactly the experience that each patient.

Richard Ghalie: MEI conducted two phase-1 studies, one as a single agent, those escalation, to determine the safety, advocacy, 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 to puttiken in a couple of type of solid tumors, 48 patient role in the study, myelose depression due to puttiken was observed, we had disease revelation at 49 percent of the patients.

Speaker 5: And maybe again, one more question here, which is that if compared to what your prior study in the breast cancer, oh no, no, no.

And maybe again, one more question here, which is that it.

Compared to what your prior study in breast cancer.

Oh.

Non small cell lung.

Speaker 5: Was this, was there any, any comparable number to that?

Or was this.

Was there any any.

Comparable number to that.

Yes.

Speaker 4: Yeah, this is Richard answering. So it's really a two very different approach to therapy here. In the phase one study in combination with chemotherapy, we were really looking at cytosoxic effects.

Yes, yes. This is Richard answering so it's really two very different approach to therapy here in the phase one study in combination with chemotherapy, we are really looking at satisfactory effect.

Richard Ghalie: However, MEI decided to pursue the developer ME-34 in a different direction on the basis of spiraling. 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 me strive, the new strategy that we would like to employ ME-344 in combination with the end time genetic agents, primarily Avastin or Bavisusumap.

Speaker 4: and looking at response at the primary endpoint. Here we're really looking at a different approach where there's syntactically talisman by combining you know, Jeff and Hibber with a mitochondria 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, corrective cancer on one hand, with a prior study which was done in ovarian cancer and small cell lung cancer. Okay, great, that's very helpful and thanks a lot for sharing that.

Looking at response as the primary endpoint here, we are really looking at a different approach where there is synthetic modality by combining that Jeff inhibitor, where they might have gone 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 breast cancer, rather I'm sorry.

Cash on one hand with a prior study, which was done in ovarian cancer and small cell lung cancer.

Okay, Great that's very helpful and thanks I appreciate it.

Okay.

Richard Ghalie: This is there for a simple observation that when Avastin is at misstupation, it blogs this glycolytic energy pathway, a leading to effect on cell growth. However, cells are... ...forces BADP, I mentioned earlier. Therefore, it is plausible that the body...

Mr. Willey. Your line is open on our end wherever you have so you have it muted on yours.

Speaker 6: No, thanks for taking the questions.

No thanks for taking the questions.

Speaker 6: Maybe just one on VerusaClib, one on 344, and then just a modeling or financial question. So on VerusaClib,

So maybe just one on <unk>.

<unk> went on 344 and then just.

For modeling our financial question, so on Verrucae glib.

What's your expectations just around.

Richard Ghalie: [inaudible] This led to a study by collaborated at the NCI Spain in Madrid, a multi-center study.

The net of clocks re treatment post progression in the context of AML.

And I guess I asked the question because theres not a lot of data that's out there in the public domain.

Re treatment experience and CLO, that's shown that you can re sensitize patients coming out of the clocks.

With Vanadic locks alone and I'm, just kind of curious as you think about.

The data youre going to be generating what's good what's interesting what is your working assumption around venetic clocks retriever and response rates.

Speaker 3: Yeah, I mean, the initial experience with the Venaticlacks and the Relapse Referector AmL population was pretty limited. I think it was like 19 patients and they fell about a 20% response. But that was in a, as you know, that was in a Venaticlacks naive population. Now everybody is getting Venaticlacks, but I think when we talk to our advisors, 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 Venaticlacks and 20 to 30% response rated that in this Relapse population, I think would get everybody excited.

Yes, I mean, the initial experience with <unk> in the relapsed refractory AML population was pretty limited I think it was like 19 patients and they saw about a 20% response, but that was as you know that was.

<unk> naive population now everybody's getting fanatical X, but I think when we talk to our advisers. It's still around the same threshold is what they would be excited by it.

Richard Ghalie: A proof of concept study evaluating ME344 and the Vesizumab in patients with breast cancer. The reason breast cancer was selected because that is a window for opportunity for this type of mechanistic studies, where patients between diagnosis and definite surgery has a bit of time where the study could be conducted. It was a randomized control study in 41 patients, group A received Vesizumab with ME344, just one cycle, and will be received Vesizumab alone.

I think it's a big deal if you can bring back responds to a patient that progressed on vanadic clerks, and 20% to 30% response rate in that.

This relapse population I think we'd get everybody excited.

Speaker 6: And then on 344, I think per Clint Trials deck.

Okay and then.

344, I think per Quinn trials dock it doesn't list.

Speaker 6: Any of the approved salvage, salvage regimen.

Any of the approved salvage rather.

Salvage regimens as allowable prior therapy. So are we to assume that these patients are going to be.

Speaker 6: So are we to assume that these patients are going to be

Richard Ghalie: The readout was a PET scan to look at tumor vascularization and tumor biopsy looking primarily at the biomarker of tumor perforation called KI67. Results are illustrated on this slide. Group A, again, is the combination of ME344, a Vesizumab in green. As you can see, looking at all patients around the study, there was a significant decrease of KI67 compared to what observed with Vesizumab alone. Focusing now on the subset of patients in this study who had a tumor normalization vascular vascularization or normalization by PET, this effect is further enhanced.

Lawn surf and rigor after the naive.

Speaker 4: This is Richard. So you're right, this is not listed on to your trial, but the protocol is really about it with the FD1. So patients should have received and progressed on or did not tolerate standard chemotherapy.

This is Richard So you are right. This is not listed on that trial the protocol.

Really a body with the FDA wanted so patient should have received.

Progressed or did not tolerate standard chemotherapy.

Speaker 4: which is, you know, pleasant-based and cheek-in-base, private view.

Which as you know plasma based and chicken base private phew.

Speaker 4: In addition, if they have a mutation that is addressable, like B-RAP, they have to receive it. If they are eligible for check on a heavy, they should have received it or not, or it is. And only then they could alone the study. So we may have patients who haven't received regular AFN and or LONSER or not. So it's not a requirement that we anticipate that some patient any, in fact, would have received and then this study.

In addition, if they have a mutation that is addressable like be arrived to receded.

If they are eligible for checkpoint inhibitor should have receded or not.

And only then they could enroll in this study. So we may have patients who have received <unk>.

Richard Ghalie: This led us to the decision now to proceed in a clinical trial where clinical readout, and we selected the colorectal cancer as the first study to evaluate the combination because it's an unmet need and a vastness is used in that study. So this is a phase I want to study and face relapse directly cancer of the failure of all standard therapy, primary objective is progression free survival, secondary objective are survival and safety.

And our long served or not so it's not a requirement but we.

We anticipate that some patients.

<unk> would have received amendments.

Okay, and then maybe just a follow up on the 20% four month PFS rate that's required to get the enrollment of stage two I.

Speaker 6: And then maybe just to follow up on the 20% for month, PFS rate, that's required to gate the enrollment of stage two. I guess when you look at, I think it was what the sunlight study that was just published. I think they saw a six month.

I guess when you look at it.

I think it was what.

The sunlight study that was just published I think they saw.

A six month PFS with a vast and launch of <unk>.

Richard Ghalie: The study is conducted in separate cohort beginning with cohort one and using the same dose and schedule that was used in the breast cancer study. One patient will be enrolled and the readout will be that four months after the patients, last patients enrolled and consider as a positive outcome is a GFS at four months of 20% or higher. Then that will lead to a evaluation of a second cohort and subsequent cohort to be discussed with the FDA.

North of 40% and then I think with one circle loan 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 <unk>.

Some of the historical data that's out there.

Speaker 4: But you're absolutely right about this report, the face restarting, in fact, that was reported at ASCO GI came in when we were just launching the study. So just let me explain where the 20% threshold came, and then also what it means for us going forward. The 20% threshold was driven by the monotherapy, high-maintenance, so the regraftinate face restarting.

But youre absolutely right about this.

The phase III study in fact that was reported at <unk> Gi came in when we were just launching this study. So just let me explain why that 20% threshold pain, but then also what it means for us going forward. The 20% threshold was driven by the monotherapy kinase inhibitor <unk> phase II study.

Justin File: With that, I conclude the clinical update and will turn it to a J5 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 borers cycle of the ME344, phase one and phase one B 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.

Speaker 4: And the our advisors, which as you may know, was the academic GI, cancer consortia, who goes around the trial, said that they would like to see something upward of maybe double what we see in what were graphitic alone in the spatial population. So that's where the 20% case is not how...

And our advisors switches as you May know is the academic Gi cancer consortia, who is running that trial said that they would like to see something upwards of maybe double of what was seen with <unk> alone in this patient population. So that's where the 20% Kate this is not our <unk>.

Speaker 4: See, this is the floor. We need to get at least something better than we have to go to face to the cohort too.

Steven This is that the floor, we see at least something better than that to go to phase two cohort two.

Speaker 4: A separate question that you're asking is, you know, if we just get 20% only, it is enough. Would we get excited knowing that Loser has a 40% PFF that month?

A separate question that you're asking is if we just get 20% only.

David Urso: I'll turn that back to David. Thanks Jay. As you've heard today, I believe we have two exciting programs with expected data readouts beginning with borers cycle of early encounter, 2024 and in the first half of 2024 for ME344, 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 and preventive options for patients.

Would we get excited knowing that <unk> has a 40% PFS at months four to six and you're right I think the answer to that is going to be it depends who we enroll safely enrolled patients had failed long cerner for long serve beds or another then.

Speaker 4: four to six and you're right. I think the answer to that is going to be it depends who we enroll. If we enroll patient at failed launcher for launcher, that or another TPI, then the that that would get us excited would be very different. Then if we have patients who really fail, prior chemo, even though that I'm sorry, prior chemo that he will with with bed, and then they come on that study.

Can we get US excited we'll be very different than if we have patients who really failed prior chemo immunotherapy I'm sorry, Brian he might that went bad and that may come in that study. So I'm not trying to Dodge the I'm trying to say it will be determined by the kind of patiently enroll not unlike what David mentioned about very site, if we see responses.

David Urso: Before we turn to Q&A, I'd like to briefly acknowledge that two of our stockholders, Anthony Cablecar, have initiated a consensus solicitation process and separately submitted three director candidates to stand for election at the company's annual stockholder meeting this year. We have had several conversations with Anthony Cablecar 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.

Speaker 4: So I'm not trying to do it, yes, I'm trying to say it will be determined by the kind of patient we enroll. Not unlike what David mentioned about Boris Feich.

Speaker 4: If we see a response and for a slightly patient progress on respect, there will be the excitement level will be very different if we see response on patient response whether it clacks and then progressed and went back on the combination responded. It's primarily driven by the patients who enroll as is often the case in face-on-spot. With enroll, we look at the data we analyze and we make inclusion based on what we see.

In addition, a progression over a cycle that will be the excitement level will be vetted isn't it we send we see response on patient respond to various lags and then progress then went back on the on the Covenant responded. So it's primarily driven by the patients. We enroll as is often the case in phase one studies will enroll we look at the data.

We analyze them.

Based on what do we see.

David Urso: 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.

Speaker 6: Okay, that's helpful. And then just lastly, I guess when you look at the 4QR&D number implied from what you reported year end, it looks to be demonstrably down sequentially, I think.

Okay. That's helpful and then.

Just lastly, I guess when you look at the four Q R&D number implied from what you reported year end looks to be demonstrably down sequentially I think sub $3 million.

Gary: 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. To ask a question, you may press a star then one on your telephone keypad. If you are using a speaker phone, please pick up your handset before pressing the keys. To withdraw your question, please press star then two. At this time, we will pause momentarily to assemble our roster.

How should we think about that number just going forward and is that somehow impacted by.

The keywords transactions some true up there or is that.

Is that just a.

A true number per.

The quarterly report and that's just.

To accelerate as you guys.

Two more clinical development here. Thanks.

Yes, Jay I'll take that.

Speaker 2: Yeah, it's Jay, I'll take that. So yeah, 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, you know, of that about 52 and a half of R&D, about 26 of that was specifically related to Zadilusim.

Yes, you are correct in your assessment, we're not giving specific guidance as to R&D into the next fiscal year, but I will tell you.

Yale Gen: Our first question is from Yale Gen with Leyla on company. Please go ahead. Good afternoon and thanks for taking the questions as well as providing a clear view of what happened currently. Maybe I start with a housekeeping question that you've got about 100 million cash and in the press release that you suggested that you have on 12 months or maybe a little bit longer runway. Given that you are still in phase one, one, two, study, should we anticipate it to be a more conservative estimate or additional thoughts behind that in terms of the runway?

Of that about 52, and a half of R&D about 26 of that was specifically related to adolescent.

Speaker 2: We do know that that trial continues to wind down. We do expect that to run out.

We do know that that trial continues to wind down we do expect that to run out.

Speaker 2: I'm about October timeframe and probably not incur expenses anymore than a million less than that most likely. The Q4 activity is just seeing the continued wind down of coastal entitle 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, yeah, you're right. It'll be down significantly from the prior year.

October timeframe, and probably not incur expenses any more than $1 million less than that most likely the Q4 activity is just seeing the.

The continued wind down of coastal entitle and Q4 and like I said, we expect that to go ahead and wind down.

In addition to some of the other cost reductions that we've made throughout the second half of the year overall R&D, yeah, Youre right it will be down significantly from the prior year.

Yale Gen: And I have some follow-up as well. 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 one programs as they're currently planned and as we have some ideas about augmenting them. But going into phase two 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 and that's in that respect.

Okay. Thanks for taking the questions.

Sure.

Thank you.

Speaker 1: This concludes our question and answer session. I would like to turn the conference back over to David Erso for any closing remarks.

This concludes our question and answer session I would like to turn the conference back over to David or so for any closing remarks.

Speaker 3: Thank you for joining the call today and we appreciate your participation.

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

Speaker 1: The conference is now concluded. Thank you for attending today's presentation. You may now disconnect.

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

[music].

Speaker 7: Yeah.

Speaker 7: The.

Yale Gen: 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, let the housekeeping one, which is the top line, I understand the prior views that are completed, so should we anticipate through some top line coming, just because of the amurization, or we should anticipate that to be stopped, at least in the near term.

Yale Gen: I'm sorry, do 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 until this quarter of my question is, would that continue for the subsequent fiscal year, or simply these revenue numbers, just the amurization of the prior revenue receipt? Yeah, I mean, all the revenue we're recognizing is all KKC driven from our collaboration with them, so it's not anticipated to continue into the future.

Yale Gen: Okay, maybe the last question here is in the clinical side, there were crucifix phase one 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, could you provide us a little color on that? Kelly, that's a richer, yes, it will be a combination of safety data, primarily since this is the end point, the prime end point of phase one study.

Yes.

Yale Gen: Perhaps there were commendant phase two dose, they will be also PK data and biomarker analysis, all of them will be available. What specific would you already have some biomarker in mind, if so, what that might be? Right, so I've mentioned it when I present a mono-therapydo distillation, the biomarker that we are evaluating our VHC profiling, particularly MCL-1 expression, where I look at multiple molecular biomarkers such as MIG, and we will be looking at potentially other biomarkers that are rather than directly the effect of CDK-9 on the target.

Yes.

[music].

Yale Gen: Okay, great, yeah, I will get back to the queue and thanks for the colors. I mean, I guess we should also say that it's just from a clinical perspective, for the cohort one from ME344, we will be looking at PFAS, and for the Forest Bike Globe expansion cohort that's in our protocol right now, we'll be looking at LR, so those are just standard clinical end points for the two respective diseases. Actually, let me, if I can, maybe just follow up as well, that you said that 20% or higher of the threshold for moving forward for the ME344, the cohort one.

Yale Gen: What other factors determine that the 20% was the number of the connobs? Well, you know, that was a requirement or a gate that we, you know, reached in collaboration with the clinicians. But we really need to dig into exactly what the patient population is before we can, you know, really know what the meaning of that threshold is that 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 not supposed, or not supposed to long.

Speaker 7: I.

Yale Gen: Was this, was there any, any comparable number to that PFS? Yeah, yeah, this is Richard answering. So it's really two very different approach to therapy here in the phase one study in combination with chemotherapy. We were really looking at South Atlantic effect and looking at response at the primary endpoint here. We're really looking at a different approach, whether it's synthetically talented by combining, you know, Jeff and Heather with the mitochondria inhibitor.

Yale Gen: 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 would be hard to compare breast cancer rather. I'm sorry, directly cancer on one hand with a prior study, which was done in ovarian cancer and small cell lung cancer.

Yale Gen: Okay, great. That's very helpful and thanks for sharing it.

Willie: Mr. Willie, your line is open on all right. Perhaps you haven't muted on yours. No, thanks for taking the questions. Maybe just one on, on varusoclib, one on three, four, four, and then just a modeling or financial question. So on varusoclib, what's your expectations just around the neticlacks, retreatment, post progression in the context of AML? And I guess I asked a question because there's not a lot of data that's out there in the public domain and some retreatment experience and CLL that's shown that you can re-sensitize patients to the neticlacks with the neticlacks alone.

Willie: 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 the neticlacks, retreatment response rates? Yeah, I mean, the initial experience with the neticlacks in the relapse refractory AML population was pretty limited. I think it was like 19 patients and they thought about a 20% response. But that was in a, as you know, that was in a neticlacks naive population.

Willie: Now everybody's getting neticlacks. But I think when we talk to our advisors, 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 neticlacks and 20% to 30% response rate in this relapse population. I think we get everybody excited.

Willie: Okay. And then on 344, I think per Clean Trials.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 lawn surf and regaraffinib naïve? Yeah, this is Richard. So, you're right, this is not listed on people's trial, but the protocol is really about it with what the FDA wanted. So, patients should have received and progressed on or did not tolerate standard chemotherapy, which is, you know, platen-based and chicken-based type of few.

Willie: In addition, if they have a mutation that is addressable, like BRF, they have to receive it. If they are eligible for check-on inhibitors, they should have received it or not tolerate it. And only then they could alone this study. So, we may have patients who have received regaraffin and or lawn surf or not. So, it's not a requirement that we anticipate that some patient and in fact would have received them in this study.

Willie: Okay, and then maybe just to follow up on the 20% form on PFS rate, that's required to get the enrollment of stage two. I guess, when you look at, I think it was what the sunlight study that was just published. I think they saw a six month PFS with the vast and lawn surf of north of 40% and then I think with lawn surf 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.

Willie: You're absolutely right about this report, the Phase 3 study in fact that was reported at ASCO GI came in when we were just launching the study. So, just let me explain where the 20% threshold came and then also what it means for us going forward. The 20% threshold was driven by the monotherapy and it's inhibitor. So, the regaraffinate Phase 3 study and the our advisors, which is, as you may know, was the academic GI cancer consortium was running the trial, said that they would like to see something upward of maybe double of what was seen with regaraffinate alone in the patient population.

Willie: So, that's where the 20% came. This is not how ceiling this is the floor. We need to get at least something better than get to go to Phase 2 to this cohort too. A separate question that you're asking is, you know, if we just get 20% only, is it enough? Would we get excited knowing that lawn surf had the 40% PFS at month for just six and you're right? I think the answer to that is going to be it depends who we enroll.

Willie: If we enroll patient that failed lawn surf or lawn surf bath or another TPI, then the one would get us excited would be very different than if we have patients who really fail prior chemo immunotherapy. I'm sorry, prior chemo therapy with bath and then they come on that study. So, I'm not trying to do it. Yes, I'm trying to say it will be determined by the kind of patient we enroll. Not unlike what David mentioned about Boris Pike.

Willie: If we see a response in Boris Pike, the patient will progress on respect. There will be the excitement level will be very different than if we see response on, you know, patient will respond to whether it clacks and then progress then went back on the combination responded. It's primarily driven by the patients who enroll. As is often the case in Phase 1 spread, you know, with enroll, we look at the data we analyze and we make inclusion based on what we see.

Jay: Okay, that's helpful. And then just lastly, I guess when you look at the 4QR and 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 KIOA transaction some true up there? Or is that just a true number per quarterly report? And that's just going to accelerate as you guys do more clinical development here.

Jay: Thanks. Yeah, that's Jay. I'll take that. So yeah, 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, you know, of that about 52 and a half of R&D, about 26 of that was specifically related to the adolescent. We do know that that trial continues to wind down. We do expect that to run out by about October timeframe and probably not incurred expenses any more than a million less than that most likely.

Jay: 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, yeah, you're right. It'll be down significantly from the prior year. Okay.

Willie: Thanks for taking the questions. Sure. Thank you.

David Urso: This concludes our question and answer session. I would like to turn the conference back over to David or so for any closing remarks. Thank you for joining the call today and we appreciate your participation.

Gary: The conference is now concluded. Thank you for attending today's presentation.

David Urso: You may now disconnect. David Urso, Stephen Willey, David Urso, Richard File, MEI Pharma Inc David Urso, Stephen Willey, David Urso, Richard File, MEI Pharma Inc David Urso, Stephen Willey, David Urso, Richard File, MEI Pharma Inc David Urso, Stephen Willey, David Urso, Richard File, MEI Pharma Inc.