Thank you for joining the MEI Pharma and Infinity Pharmaceuticals merger and clinical program overview webcast. My name is David Walsey, and I'm the Senior Vice President of Corporate Affairs at MEI Pharma. Presenting today to tell you about the potential of the pending merger are, from MEI, David Urso, President and CEO, and Dr. Richard Ghalie, Chief Medical Officer. From Infinity, we are joined by Dr. Robert Ilaria, Chief Medical Officer. Subject to the approval and closing of the pending merger of the two companies, David and Robert will be the CEO and CMO of the combined entity, respectively. Also joining today is Dr. Ezra Cohen, a leading medical oncologist and cancer researcher, recently the Chief of the Division of Hematology Oncology and Associate Director of Clinical Science at UC San Diego Moores Cancer Center. Joining for a Q&A discussion will be Dr. Nick Abbott. Nick brings over 35 years of biotech experience, including research as a bench scientist at both UK and US companies, and from Wall Street, where he was most recently a senior biotech analyst at Wells Fargo, covering over 20 stocks with an oncology focus. Before turning the call over to David for opening remarks, I'd like to remind you that during today's call, we'll be making forward-looking statements. Such statements are based on current expectations and assumptions that are subject to risks and uncertainties, and involve a number of risk factors that could cause actual results to differ materially from projected results. In particular, statements include, but are not limited to, the sufficiency of our cash and cash equivalents to fund operations, the anticipated timing of release of data of our clinical trials, our business and operations, and our future financial performance and expense levels. Forward-looking statements may include words or phrases such as "we expect," "we believe," "we intend," "we anticipate," "we plan," "may," "likely," "upcoming," and similar terms. For a discussion of material risks and other important factors that could affect actual results, please refer to the accompanying slide, as well as those risks contained under the risk factors in the latest 10-Q and 10-K reports filed by MEI and Infinity with the SEC, and the registration statement on Form S-4 that was declared effective by the SEC on June 6, 2023. Actual results may differ materially from today's forward-looking statements, MEI, Infinity don't assume any obligation or intent to update them, except as required by law. The statements in this discussion do not constitute an offer to sell, or the solicitation of an offer to sell, or the solicitation of an offer to buy any securities, nor shall there be any sale of securities in any jurisdiction in which such offer, solicitation, or sale would be unlawful prior to registration or qualification under the security laws of any such jurisdiction. No public offer of securities shall be made, except by means of a prospectus meeting the requirements of Section 10 of the Securities Act of 1933, as amended. This discussion relates to a proposed transaction between Infinity and MEI. In connection with the proposed merger, MEI and Infinity filed with the SEC a registration statement on Form S-4 that includes a joint proxy statement prospectus regarding the proposed merger. Investors in MEI's and Infinity's respective stockholders are urged to read the joint proxy statement prospectus in its entirety, and any other documents filed by each of MEI and Infinity with the SEC in connection with the proposed merger or incorporated by reference therein, because they contain important information about the proposed merger and the parties to the proposed merger. Investors and stockholders may obtain a free copy of the joint proxy statement prospectus and other documents containing important information about MEI and Infinity from the SEC website at www.sec.gov. MEI and Infinity make available free of charge at www.meipharma.com and www.infi.com, respectively, copies of materials they file with or furnish to the SEC. MEI, Infinity, and their respective directors, executive officers, and certain employees and other persons may be deemed to be participants in the solicitation of proxies from the stockholders of MEI and Infinity in connection with the proposed merger. Security holders may obtain information regarding the names, affiliations, and interests of MEI's and Infinity's directors and executive officers in the joint proxy statement prospectus, which may be obtained free of charge from the SEC website at www.sec.gov, MEI's investor website at www.meipharma.com/investors, and Infinity investors website at investors.infi.com. With that, I'll hand it over to David to start the presentation. Thank you, David. The pending transaction presents an exciting opportunity for MEI and Infinity to advance three promising clinical stage oncology candidates, each with the potential to be a transformative, first-in-class therapy in patients with advanced diseases and for which the standard of care is inadequate. MEI brings two attractive early-stage therapeutic development candidates, an experienced team, and a strong balance sheet to the combined company. We expect both of these candidates, voruciclib in combination with Venclexta, and ME-344 in combination with Avastin, to generate data around the end of this year, with the potential to demonstrate safety and preliminary evidence of efficacy for voruciclib in patients with acute myeloid leukemia, and for ME-344 in patients with colorectal cancer. Infinity's eganelisib program would provide a phase II candidate representing a potential first-in-class immunotherapy, a PI3K-gamma inhibitor designed to reprogram macrophages and reduce immune suppression in the tumor microenvironment, as well as an experienced drug development team. Each of these programs utilize understandings of biology to attempt to overcome resistance mechanisms of standard of care therapies, and has preclinical and clinical data showing potential anti-tumor activity and mechanistic proof of concept for the combinations being evaluated. We will review some of this data during this presentation, but I'd like to highlight the recently announced early data from the voruciclib program. Last month, we reported promising clinical activity in heavily pre-treated patients with acute myeloid leukemia, or B-cell malignancies, administered voruciclib alone and at the initial dose level in combination with venetoclax. Early safety data was also consistent with our prior experience. We view this as very encouraging and look forward to additional data. Beyond the diversification of our pipeline and supportive data generated to date, the pending merger leverages our company public infrastructures, builds a great team, and has projected starting capital of about $100 million at closing, which we expect funds operations through mid-2025. We anticipate that this funding would enable us to move each of these programs forward in clinical development and to clinical data over the next six to 18 months. The combined team includes significant industry experience between me, Rob, and Stéphane Peluso. As mentioned, Rob will serve as CMO and Stéphane, our CSO. Together, this provides a highly experienced and knowledgeable core team to lead the successful advancement of our programs and business. Rob joined Infinity as CMO in September of 2021 from BMS and Celgene, where he focused on immuno-oncology drug development, including leadership roles on CTLA-4 and PD-1 inhibitor programs. Prior to that, he was at Eli Lilly for over 12 years. His expertise in drug development, coupled with his familiarity with immuno-oncology, will continue to be invaluable as we shape the clinical programs. Stéphane, prior to re-joining Infinity in August of 2021 as its CSO, was at Ipsen Bioscience as VP, Global Head of Oncology, External Innovation. During his earlier work at Infinity, he held increasing roles of responsibility, ultimately leading the company's early discovery and pipeline expansion efforts through internal R&D and business development. As for myself, I was appointed MEI CEO earlier this month as part of our previously announced transition plan, replacing Dan Gold, who remains on the board. I joined MEI in 2014 as SVP, Head of Corporate Development and General Counsel. In 2018, I was appointed COO. Prior to that, I was COO and General Counsel at Tioga Pharmaceuticals, a privately held drug development company I co-founded in 2005 while I was Principal at the venture capital firm, Forward Ventures. Before that, I worked in corporate development at the genomics company, DNA Sciences, and was an attorney in the corporate securities and licensing groups at Wilson Sonsini Goodrich & Rosati. The composition of our board will change upon the approval of the proposed transaction. Importantly, Dan's experience and the experience of Adelene Perkins, the CEO of Infinity, will continue to be leveraged, and here you can see the co-composition of the remainder of the board with Norman Selby as chair. I'm very much looking forward to working with our new team, and we've already started to work together to ensure a smooth transition. Our integration planning has gone very well. As I've noted, the combined company will have three clinical-stage oncology drug candidates in development. We will go into more detail shortly on the programs, each of which addresses a clear medical need and represents significant market opportunity. Briefly, eganelisib is planned to be evaluated in combination with KEYTRUDA in a controlled phase II clinical study for the potential treatment of head and neck squamous cell carcinoma, starting in the third quarter of this year. Initial safety and PFS data from the planned phase II study is expected in the H2 of 2024. voruciclib is currently being evaluated in a phase Ib study, exploring dose and schedule in patients with AML and B-cell malignancies as a single agent and in combination with venetoclax. The ongoing phase Ib study is expected to report initial combination data around the end of this year. ME-344 is to be evaluated in a phase I study in combination with Avastin in patients with relapsed colorectal cancer, which is expected to begin enrollment imminently. Data from the phase Ib study to support opening enrollment in an additional cohort are also expected around the end of this year. By the end of next year, our plan calls for eganelisib to have initial safety and PFS data from a phase II study, and for voruciclib and ME-344 to have final data from their respective phase Ib clinical studies. We believe these studies will provide meaningful support for their potential in combination with KEYTRUDA, Venclexta, and Avastin, present the opportunity to create, with existing capital and resources, a compelling developmental oncology story in just the next couple of years. The summary of the proposed transaction. The stockholder votes for both companies are scheduled for July 14 at 10,00 AM Eastern Time. This is an all-stock transaction where Infinity stockholders will receive shares of MEI common stock. Upon approval of the transaction, Infinity will become a wholly owned subsidiary of MEI Pharma, with the outstanding equity ownership post-closing of about 58% being held by MEI stockholders and about 42% being held by Infinity stockholders. I'd now like to turn the call over to Rob, followed by Ezra, to provide an overview of eganelisib, including the mechanism of action, clinical development to date, plans to start a phase II study in patients with head and neck cancer, and the need for new therapies to treat this type of cancer. After remarks from Rob and Ezra, Nick will join in for some discussion about eganelisib and the plans for the continued clinical development. Thanks, David, and welcome everyone. Eganelisib is a first-in-class, potent, and highly specific PI3K-gamma inhibitor. It's a small molecule. It's taken as a capsule daily, and it has a at least two fold, two log fold selectivity over the other isoforms. Infinity's interest in this target was because it was shown to be a very important switch that controls immune suppression and also may play a role in checkpoint inhibitor resistance. The reason Infinity's been interested in this target is there's a lot of data showing that if you block this signalling pathway, you tend to bias the tumor microenvironment towards a more activated or M1-like macrophage environment, compared to the normal suppressive macrophage environment, which is M2-like. It's important to understand that PI3K-gamma is quite distinct from the other PI3K isoforms you may have heard of. For example, PI3K-alpha and PI3K-beta are expressed ubiquitously in the body and playing very, very important roles in metabolism. PI3K-delta is more limitedly expressed in B and T cells, and if you block that pathway, you tend to get a lot of autoimmunity. PI3K-gamma, on the other hand, is much more restricted. It's only expressed in myeloid cells, and the adverse event profile is also distinct from the delta, in that mainly blocking this pathway is associated with reversible hepatotoxicity, rash, and occasionally fever or pyrexia. Infinity has had a broad development program for eganelisib that includes two phase II studies, one, MARIO-275, in platinum-resistant urothelial cancer, and another, MARIO-3, with metastatic TNBC. Both of these phase II studies have had very encouraging data, which we presented previously. We've also provided eganelisib in a collaboration with Arcus, we saw some very interesting data in TNBC and ovarian cancer, both of which were in a chemotherapy-free regimen. Our focus today is based on the MARIO-1, where we had clinical experience and encouraging data in squamous cell cancer of the head and neck, in particular, patients that were resistant to checkpoint inhibitor treatment. I'll next hand it off to Dr. Ezra Cohen, who is an expert in head and neck cancer, to lead us through the patient experience and treatment landscape. Ezra? Thanks, Robert, thanks for allowing me to participate in this webcast. Squamous cell carcinoma of the head and neck is a locally advanced disease, it's important to note that for a couple of reasons. First of all, most patients are going to be treated with curative intent because they present with either local or locally advanced disease, that is to say, a tumor with or without lymph nodes. In fact, it's unusual for patients to present with metastatic disease. Despite the fact that we treat with curative intent, many patients, actually about 50%, will unfortunately develop recurrent or metastatic disease, and that's where currently immunotherapy is being utilized. This is a global health issue in that there are about 60,000 cases in the United States per year, and incidentally, that number is climbing, but about 10-20 times that worldwide, with almost half a million deaths estimated to occur from head and neck cancer this year. You can see that the graphic on the left illustrates the point I was trying to make with an increase in the annual incidence, and this is primarily driven by HPV-positive oropharynx cancer that we now recognize as an etiologic factor for squamous cell carcinoma of the head and neck. For patients with recurrent and metastatic disease, the current landscape really encompasses immunotherapy, cytotoxic chemotherapy, and some targeted agents. Here you see a summary of at least some of the approaches that one can take. In first-line, anti-PD-1 monotherapy is often used. These are for patients whose tumors express PD-L1 or have a lesser tumor burden. Anti-PD-1 and chemotherapy can also be used when PD-L1 status is either unknown or zero in the tumor, or for patients who have a greater tumor burden. Occasionally, patients in the first line will be treated with chemotherapy, with or without an EGFR inhibitor. That EGFR inhibitor, incidentally, is often almost exclusively cetuximab, a monoclonal antibody. In the second line, it really becomes an undefined arena that is dependent on what patients received in their first line and how preserved their performance status is. For anti-PD-1-naive patients, anti-PD-1 is often chosen. For chemotherapy-naive patients, a chemotherapy regimen will be used, and for anti-EGFR inhibitor-naive patients, cetuximab will often be administered. The third line, really here, the standard is completely undefined and very much dependent on what patients have received in the first and second line. Of course, molecular testing and clinical trials are heavy considerations as they may influence the therapeutic choices. I talked about anti-PD-1 in the first line, really that is based on the data using pembrolizumab. Here we see the results of pembrolizumab monotherapy with respect to progression-free survival and overall survival in the KEYNOTE-048 study. This is the study that really set the standard of care in first-line recurrent metastatic squamous cell carcinoma of the head and neck and established pembrolizumab, the anti-PD-1 antibody, in the use in these patients. What you see here is that in the 1-19 CPS-expressing group, an initial decrement in the progression-free survival and then eventually equilibration in the curves. In overall survival with the CPS 1-19 group, essentially parallel curves when compared to the triplet regimen of platinum, 5-FU, and cetuximab. There's a little bit of a different story when one looks at a higher CPS expression level in the tumor, that is CPS greater than or equal to 20. Again, you see that initial decrement in PFS, but then the overall survival clearly is improved in the CPS greater than or equal to 20 population with pembrolizumab monotherapy compared to the extreme regimen. With that in mind, we can see where MARIO-8 will fit into the landscape of recurrent metastatic head and neck cancer. Essentially, in the first line, one can combine eganelisib with pembrolizumab, yielding a potential IO/IO chemotherapy-free regimen in patients whose tumors express PD-L1 at CPS 1-19, but also in patients whose tumors express higher levels of PD-L1, that is, the CPS greater than or equal to 20. Here you see the study design for MARIO-8 is it is a randomized phase II in recurrent metastatic squamous cell carcinoma of the head and neck. Patients will be treated in the first line. Their tumors will have to express some level of PD-L1, and you can see the key stratification factors include PD-L1 expression by CPS, that is 1-19 versus greater than or equal to 20. The primary endpoint is overall survival, with key secondary endpoints being progression-free survival and safety. The other stratification factor is HPV status, which we now recognize as a strong prognostic factor in head and neck squamous cell carcinoma. You see that Part A will be a dose finding section with a randomization of two to two to one, two different dosing regimens. Upon optimization of the dose, that will be based on available efficacy and safety data from approximately 40 to 70 patients in Part A. Part B will be initiated that will randomize patients two to one to eganelisib-pembrolizumab versus placebo-pembrolizumab, and the final overall survival analysis will be undertaken. With that in mind, let me turn it over to Rob once again to discuss the basis for the MARIO-8 study, the phase I clinical side. Thank you, Ezra. MARIO-1 was our first in-human study of eganelisib alone or in combination with nivolumab in patients with advanced solid tumors. The first portion was a monotherapy dose escalation, where we explored various doses of eganelisib. The second was a dose escalation of eganelisib in combination with nivolumab in a variety of different solid tumor types, which included patients that were refractory to immediate prior checkpoint inhibitor treatment, including patients with squamous cell cancer of the head and neck. On this slide, you can see the various doses that we explored in monotherapy, ranging from 10 to 60 milligrams a day. As you can see, doses from 10 to 40 milligrams daily were very near or above the EC90 of PI3K-gamma. Keep in mind, we want a very specific molecule. By the same token, all doses except the 60 milligrams, which was not taken forward, were below the EC50 of PI3 kinase. Here is some biomarker data in which we're looking at the impact of eganelisib monotherapy on immune activation in the peripheral blood. On the far left, you see as we go from day zero to day 28, we see a very nice increase in interferon gamma-responsive cytokines. In particular, we're showing here CXCL10. These are very important proteins that have been implicated as activated whenever you block the PI3 kinase gamma pathway. Importantly, associated with this upregulation of interferon gamma-responsive cytokines, we see evidence of T-cell reinvigoration in the peripheral blood as well. In addition, on the right, we see an increase in interferon gamma-responsive genes. All of these support that the eganelisib mechanism of action is established as a monotherapy in the peripheral blood. When we look to safety, we see that eganelisib monotherapy was very well tolerated, with no grade III treatment-related adverse events up through a dose of 40 milligrams a day. As you can see, as we dose escalated further to 60 milligram a day, we started seeing evidence of liver enzyme increase, in particular AST and ALT, in addition to some rash. For these reasons, we didn't bring the 60-milligram dose forward, but instead studied 30 and 40 milligrams. Here is showing you the safety profile of eganelisib when combined with nivolumab. Again, we don't see any grade III hepatic treatment-related adverse events up through a gram, the eganelisib dose. We do see some rash in combination with nivolumab, which we had also seen as a monotherapy. Interestingly, the grade III hepatic events that we did observe were very quick to resolve. Generally, hepatic adverse events like autoimmune hepatitis with nivolumab may occur two to four months into treatment. In this case, we saw it very early. Instead of taking weeks to resolve, interestingly, this hepatotoxicity we observed was quick to resolve, with a median duration of only about nine days. The overall grade III treatment-related hepatic event rate was about 18%. With this information, we moved forward to the randomized phase II study, MARIO-275. This phase II study was in patients who were resistant to platinum combination chemotherapy, which is the standard of care in patients with advanced metastatic urothelial cancer. Patients were randomized to eganelisib 40 mg daily in combination with nivolumab versus nivolumab alone. Here I show you biomarker data now comparing eganelisib and nivolumab, compared to nivolumab alone in the peripheral blood. As you can see on the left, we see a nice increase of interferon gamma responsive cytokines like we had seen in monotherapy. Interestingly, it's even greater than you see with nivolumab alone, which is shown in light green. Similarly, on the far right, we're looking at T-cell reinvigoration like we had done with eganelisib monotherapy. You can see in the dark blue, we see enhanced T-cell reinvigoration in the peripheral blood compared to nivolumab alone, which is in that light green on the far right. Looking at safety, these are the treatment-related adverse events that were associated with treatment discontinuation of eganelisib placebo and/or nivolumab. At the top, we show that hepatic TAEs were indeed more common as a reason for treatment discontinuation with the combination of eganelisib and nivolumab than nivolumab alone. Still, the overall treatment discontinuation rate was rather low, at approximately 21%. If we look at patients discontinuing due to other reasons, in other words, non-hepatic TAEs, you actually see it's fairly similar between eganelisib and nivolumab and nivolumab and placebo. Regarding the hepatic TAEs, there was no evidence of Hy's Law, which is a way of looking at severe hepatotoxicity. There were no grade V treatment-related adverse events, and all the hepatic grade III TAEs resolved, except in two patients who came off of treatment for other reasons. However, because we did notice this imbalance of treatment discontinuation due to hepatic events, we decided to reduce the dose of eganelisib in this study from 40 milligrams to 30 milligrams. We also added earlier monitoring of LFTs, since, as I mentioned earlier, we tend to see this hepatotoxicity, if we're going to see it, fairly early in treatment. Here is some efficacy that we had observed, in particular, the two year overall survival data in this study. This is for the entire population, in other words, the ITT. As you can see, at the two year landmark survival analysis, 45% of patients on the eganelisib plus nivolumab arm were alive, compared to only 24% of patients on the nivolumab control arm. Interestingly, we also saw the same profile even in PD-L1 negative patients. It turns out that in urothelial cancer, most patients have PD-L1 negative tumors, and you can see that we still saw an excellent two year OS landmark even in this population. Next, would like to hand this back over to Ezra Cohen again, who will review, in particular, the squamous cell head neck clinical data from the MARIO-1 study. Thanks, Robert. Really, you set the stage quite nicely for the design of the MARIO-8 and the rationale behind it, based on MARIO-1 and of course, the urothelial study as well. Here you see, eganelisib and nivolumab combination in patients having progressed on immediate prior checkpoint inhibitor therapy. Just to put this into a context, the study concept really examined the activity of adding eganelisib to an anti-PD-1 antibody in patients who were progressing on checkpoint inhibitors. Patients who had gotten first-line and second-line and now had a checkpoint inhibitor and then were eligible to receive eganelisib and in this case, nivolumab. Patients then were evaluated for response and by typical RECIST criteria. What we saw was that, in fact, in patients who had two or fewer lines of therapy, a clear indicator of activity. Here you see patients A and B, tracking the size of their tumor, prior to initiation of the MARIO-1 study. You can clearly see that there was a dramatic increase in tumor volume. The start of MARIO-1, that is the initiation of eganelisib and nivolumab, and a dramatic reduction in their tumor volume. In fact, patient A, a 63% tumor reduction with a progression-free survival of 11 months. Patient B, a 36% tumor reduction with a progression-free survival of seven months. Clearly, this would not have happened with simple continuation of the anti-PD-1 antibody. With respect to the safety from MARIO-1, specifically in the head and neck cancer cohort, there were really no signals that were different than what Rob had described in his earlier discussion. You see the most common treatment-emergent adverse events that occurred in greater than 15% of patients that were reflective of the larger population. The hepatic adverse events appear in about 20%-25% of patients. With respect to the grade III, the table on the right, that occurred in greater than or equal to 5% of patients. The hepatic events are at the top, but in general, a really well-tolerated combination with nivolumab, the anti-PD-1 antibody. Here you see the idea that in patients who had received two or fewer prior lines of therapy, we saw two partial responses yielding an objective response rate of 20%. Clearly, this was an indicator to us that there was activity, there was the opportunity to reverse resistance to anti-PD-1 antibodies. Our best signal was also in patients who were not heavily pre-treated, which intuitively makes sense. Of course, part of the rationale for the MARIO-8 study that, again, you see here. Patients now in the first-line with recurrent or metastatic disease, whose tumors express some level of PD-L1, undertaking the combination of eganelisib and the approved anti-PD-1 in first-line head and neck cancer, that is pembrolizumab. With that in mind, let me turn it back to Rob to discuss the timelines associated with MARIO-8. Thank you, Ezra. Yes, the study team is working hard, and we have an estimated study start to occur in Q3 of this year. Using the adaptive design that Dr. Cohen described for part A, we anticipate that we will have preliminary efficacy and safety data from approximately 40 to 70 patients sometime in the H2 of 2024. That decision, as Ezra mentioned, we will move from part A to part B to continue the randomized phase two study. In summary, we've shown you very encouraging data from heavily pretreated patients with advanced metastatic head and neck cancer, in particular, patients whose tumors had progressed on an immediate prior checkpoint inhibitor treatment. As you can see, this supported further investigation of eganelisib in combination with a checkpoint inhibitor. This is also why the design that Dr. Cohen went over, MARIO-8 study, is in first-line recurrent metastatic squamous cell cancer in combination with the standard of care, pembrolizumab. We've received FDA feedback on the study design, we plan to move forward with the randomized phase II study in squamous cell cancer of the head and neck. This study also includes dose optimization, as Dr. Cohen described. Again, the estimated study start will be in Q3 of 2023, with an anticipated dosing decision in the H2 of 2024, which will include preliminary safety and efficacy data on approximately 40 to 70 patients. With that, I'll hand it off to Dr. Nick Abbott, who will start the Q&A section. Thank you. Thanks, Dr. Ilaria. Maybe starting with Dr. Cohen. As an internationally recognized head and neck cancer specialist, you know, you have your pick of experimental therapies, just remind us again, you know, what excites you about eganelisib? Yeah, thanks, Nick. I think there's a few factors that we really need to keep in mind when we think about eganelisib in this context. First of all, we've seen the preliminary data that formed the rationale for the MARIO-8 study, that ability to reverse resistance to checkpoint inhibition. When we think about the first line, we're certainly encouraged that pembrolizumab has shown efficacy and a long-term survival in about 20% of patients, but that means that 80% of these patients are unfortunately still dying of their disease. You can clearly see that there is room for improvement in this patient population. When we think about that, we begin to think about, well, what's the biology of squamous cell carcinoma of the head and neck, especially with respect to the tumor microenvironment, and how can we influence that? That's where eganelisib really is the right drug to use in this disease. Our group and others have shown the importance of the immunosuppressive effect of macrophages and myeloid cells in the tumor microenvironment. Eganelisib clearly reverses that effect to go from immunosuppressive to immunostimulatory, recruiting T-cells to the tumor, so the mechanism makes sense. In addition to that, what we've seen in all the data so far is that eganelisib can be readily combined with anti-PD-1 antibodies to deliver a well-tolerated IO/IO combination. Safety is likely not going to be an issue in that combination. Moreover, we have an opportunity to increase effort, especially or perhaps specifically, in that CPS 1-19 population, where pembrolizumab was good, but not better than the older standard therapy. Eganelisib can be readily added, hopefully improve efficacy in all levels of CPS PD-L1 expression, 1-19 and greater than 20, offer a chemotherapy-free regimen with two immunotherapy-acting agents. Certainly, we're quite encouraged about the prospects of MARIO-8 when you think about it in that context. All right. Thank you. Dr. Ilaria, I know you treat patients, but now putting your drug developer hat on, is there anything else you'd like to add? I mean, I think a lot of investors, were a little surprised about the choice of head and neck cancer versus, you know, continuing in urothelial bladder or triple-negative breast. Yes. Well, I think, you know, now that we've presented this data, you know, showing what critical activity we had in the checkpoint inhibitor refractory space, I hope this provides additional enthusiasm for why we chose this. You know, in addition, as Dr. Cohen alluded to, we had encouraging data in a mostly PD-L1 negative tumor type, urothelial cancer. We've also presented data in MARIO-3 and TNBC, in which we saw pretty similar signs of efficacy, even in PD-L1 negative tumors in that as well. You know, we're very optimistic. This is a very macrophage-rich tumor, and in addition, you know, we believe that patients, there's still room for improvement, particularly in the low CPS score range. We think our data in the other tumor types supports this. The other thing we like about head and neck cancer is that we think we'll be able to. You know, unfortunately for patients, the PFS and OS timelines are relatively short. You know, the patients have been benefited from PD-1-based treatments, but still we have a lot of room to go. We believe that we'll be able to get answers about the potential benefit in this patient population earlier than perhaps some other tumor types. Great. Let's just sort of follow up on that. I think you said, expect top-line data H2 of next year. Dr. Cohen, in your opinion, what is the hurdle for success in a, you know, frontline population? I think Robert made, first of all, some terrific points about the finer issue of PD-L1 expression and potential efficacy. Nick, to answer your question, really, we're looking for improvements in long-term survival. Again, what we saw with pembrolizumab, either monotherapy or in combination with chemotherapy in the five year data from KEYNOTE-048, is that about 20%, maybe a little bit more than that, are alive at five years. That's fantastic, because prior to anti-PD-1, that number was essentially zero. We've made, you know, definitely some progress. I think what we want to do now is further increase that, and especially where those patients in the... Whose tumors express CPS at 1-19, where there is still controversy on whether to use pembrolizumab monotherapy, pembrolizumab chemotherapy, or some practitioners don't even use anti-PD-1 in that setting because they're not completely convinced that immunotherapy works well for those patients. It's so interesting to me that in urothelial cancer, and Rob mentioned TNBC, that eganelisib appeared to be effective even in those tumors that don't express PD-L1 at high levels, and in fact, in some tumors that don't express PD-L1 at all. Here's a great opportunity to really bring immunotherapy to the forefront, addressing an important mechanism in squamous cell carcinoma of the head and neck, and that is macrophages or MDSCs with eganelisib. Just to push you a little bit, as you noted from the 48 trial, you know, there was a decrement of PFS for pembro versus standard of care. Are you looking to see sort of a reversal of that? I know this is just pembro placebos. There is no active control, there's no chemo control. Is that what you sort of need to see really to push forward is, "Okay, we're having some benefit on PFS, acknowledging that OS is the gold standard? Well, I think, Nick, that you put it quite well. We'd like to see that initial signal of an improvement in PFS over pembrolizumab alone. I think that would give us a lot of confidence. Ultimately, it is going to be overall survival that's going to drive the most important decisions on development and, of course, ultimately, patient care. We'd love to see, and in fact, are anticipating, that we will see a PFS that is numerically comparable to what we see with pembrolizumab chemotherapy or chemotherapy alone. That would really, I think, strengthen the position for eganelisib anti-PD-1 combination in all PD-L1 expressing tumors, irrespective of what that CPS is, as long as it's greater than one. We'll see what the data show, but that's exactly the hope. In fact, from what we see in the preliminary data so far, it's quite conceivable that we'll see that encouraging early PFS signal. Well, let's hope for patients and the drug. In terms of moving forward from the phase II, how do you think about registration and beyond? I mean, you know, you use multiple modalities to treat this disease, and maybe as an aside or an add-on to that, do you think there's a faster market opportunity in the CPS less than 20% population? I think so. I think that, again, based on the data that we've seen so far, that there really is an opportunity in that low-ish PD-L1 expressing cohort, that CPS 1-19, where pembrolizumab alone is approved, but by no means widely accepted. There are a lot of patients who are still receiving chemotherapy in that low-ish PD-L1 expressing tumor-expressing cohort. A IO/IO combination that works in that tumor type, I think, would be incredibly welcome for these patients. Moreover, in the grand scheme of things, eganelisib so far, be it in combination with anti-PD-1 or with cytotoxic chemotherapy, has been very well tolerated. There's every reason to believe that as agents come into play and other agents get developed in head and neck cancer, eganelisib would be able to combine very well with other mechanisms, other targets. What we have here is an agent that can essentially modify the tumor microenvironment, and augment whatever its partner will be in terms of activity and efficacy. One could see that it would be applicable to first-line recurrent metastatic and eventually, maybe even a locally advanced disease where the great majority of patients present. Terrific. You mentioned partners and obviously, you know, MEI and Infinity are not the only company who are interested in head and neck cancer. You know, do you see the standard of care changing substantially over the next few years? You know, what potential partners would you think might end up being combined with eganelisib? Certainly. We're seeing some encouraging data from other clinical trials. For instance, we know that a phase III study combining lenvatinib with pembrolizumab has completed accrual. We have yet to see the data. We anticipate those data will likely emerge in probably eight to 12 months. That may set a new standard of care for patients whose tumors express PD-L1. Again, I'll emphasize the ability to combine eganelisib with really almost anything else, including a potential pembrolizumab/lenvatinib combination, and even further augment the efficacy of that combination. There are a newer generation of EGFR antibodies that are being developed, building on some of the success that we've had with cetuximab. These are primarily bispecifics that have EGFR as one of the arms in the bispecific antibody. Again, these are agents that one could readily combine with eganelisib if they become part of the standard of care. Moreover, when we think about locally advanced disease and the potential for some newer agents to enter the spectrum there, such as the SMAC mimetic xevinapant, which just completed accrual of a phase III study in locally advanced disease. Again, the potential to add eganelisib to that combination exists and could be readily explored. Great. Thank you. Dr. Ilaria, coming back to you. You mentioned some encouraging data in urothelial bladder. We have some data in TNBC. How do you think about potential of utility of eganelisib beyond head and neck cancer? Well, you know, and I think Dr. Cohen mentioned this as well, that, you know, the tumor microenvironment is very macrophage-rich in a lot of solid tumors. You know, we believe that if we have compelling data in head and neck cancer, in a robust randomized phase II setting, there's, you know, very good reason to believe this, a combination similar to that, could work in other solid tumors. We don't have a lot of evidence that solid tumors are that different as far as being macrophage-rich. We think, you know, robust data in a tumor type like squamous cell cancer of the head and neck, really provides potential opportunities for other indications and other tumor types, such, you know, as lung cancer or other tumors, particularly ones that tend to have lower PD-L1 expression. Maybe just following up on that, you know, we saw in the urothelial bladder data, the ability of a eganelisib essentially to neutralize that, you know, negative PD-L1, poor prognostic indicator. Dr. Cohen, what, you know, and putting a broader hat on, you know, how problematic are these low PD-L1 patients? How common are they in solid tumors, and, you know, what do you do with those patients? Certainly, it depends on the tumor type. We know that some solid tumors tend to express high levels of PD-L1 in the tumor. Head and neck cancer is one of those, others tend to express very low levels or zero PD-L1. Now that the checkpoint inhibitors have become such an important part of cancer therapy, showing that for some patients with metastatic disease, treated with the anti-PD-1 antibody or PD-L1 antibody alone, we can have a long-term survival measured in years. For some of these patients, we were even thinking they may be cured of metastatic disease, something that was unimaginable even, you know, a short time ago. With anti-PD-1s being so important, the ability to augment their efficacy with an IO/IO combination, especially in patients who are less responsive and less likely to benefit, that is the tumors that don't express PD-L1 or express it at low levels, I think would be an incredible advantage for not only head and neck cancer, but across all of oncology. Here's really a strategy that could be applied to multiple tumor types, and the potential is really profound. Great. Thank you very much. Well, with that, I'll wrap it up, and we look forward to data from MARIO-8 in the H2 of next year. Thanks, gentlemen. Thank you. Thank you. Thank you, Ezra, Rob, and Nick. I'd now like to turn the presentation over to Richard to provide an overview of the Voruciclib and ME-344 programs, after which he will be joined by Nick for some additional discussion on each program. Thank you, David. I'm delighted to be able to introduce MEI pipeline, both v oruciclib and ME-344. Beginning with v oruciclib, our oral CDK9 inhibitor. For each of the two product, I'll follow the same logic, beginning by the scientific rationale, why we're exciting about the asset, the clinical data from past and present studies, as well as where we see the development going forward. For v oruciclib, we are very excited about this asset because it targets a important target that impacts cell proliferation called a CDK9. V oruciclib is a CDK9 inhibitor, and the relevance of that target is it can decrease the production of two proteins, MCL-1 and MYC. MCL-1 is a protein that is important for cell survival. The relevance of it clinically is that it is a poor prognostic factor in patients with acute myeloid leukemia, or AML, and patients with chronic lymphocytic leukemia, or CLL. In addition to that, MCL-1 overexpression is a known mechanism of resistance to venetoclax, which is a member of the BCL-2 family of protein that actually lead to stabilization of MCL-1. voruciclib, by inhibiting MCL-1 via CDK9 inhibitor, could make venetoclax more active and prevent resistance to this product. A completely separate mechanism is inhibition of MYC. The MYC gene is an important oncogene that is expressed at higher value in many cancers, including tumors that also express KRAS mutation. voruciclib, by inhibiting CDK9, can also inhibit MYC, and we will talk about it a little bit later. As I mentioned, voruciclib is CDK9. What are the CDK or cyclin-dependent kinase? Those are a set of enzymes that are essential for cell cycle regulations. There are a variety of CDKs, and CDK9 is the one relevant to that discussion. Voruciclib has a specificity for CDK9 compared to other CDK, and as important, it does not impact other kinase at the dose and concentration we are using in the clinic, as can be seen on the kinome scan to the right. Our focus, our early development focus, is now on the effect of voruciclib on MCL-1. The hypothesis is the one we touched on it a moment ago, that increased MCL-1 is an established mechanism of the resistance to venetoclax, and in addition, is also associated with poor outcome in AML and CLL. We know, and there have been several publications that effect, that venetoclax inhibit BCL-2, but that, in its turn, increase stabilization of MCL-1. Combining voruciclib to venetoclax may counteract the effect on MCL-1, decrease MCL-1 production, and therefore return the sensibility to venetoclax activity. I have a couple of slides to show you non-clinical data supporting that hypothesis. Beginning in AML xenograft model in mice, where we have three panels here. To the top shows decreased MCL-1 production with voruciclib. It doesn't decrease with MCL-1, with venetoclax rather. However, the combination also shows a decrease in MCL-1 production. The impact on that is the combination increase apoptosis, meaning cell death. These are the bars to the right in panel B, and that leads to improved survival, the panel C to the right, where you see in green the survival curve with the animal treated with a combination significantly superior to the one showing a single agent therapy with venetoclax or voruciclib. Now that I presented the AML murine xenograft model, I'm going to work and present to you another preclinical model, this one in an aggressive form of B-cell lymphoma called diffuse large cell lymphoma. Here we have data on six different DLBCL cell lines, and what I would like to show on this experiment is, one, a decrease in MCL-1 that was dose-dependent, as can be seen on the panel A to the left. Again, six cell lines. Then the panel to the right is an assessment of a decrease in tumor growth in these six cell lines. Single agent Voruciclib, single agent venetoclax, and the combination in red. As you can see, in all cases, the combination was synergistic, more effective than either agent alone, both in decreasing tumor growth and bottom right slide is effect on animal survival. Now, let's turn our attention to the clinical development program. With the earlier studies conducted by a prior sponsor, Piramal, in which they conducted two phase I studies in patients with advanced solid tumors. They investigated two different dosing schedule. One, where voruciclib is given daily, continuously, and the other one, where it's given for 14 days on and seven days off. As you may know, other CDK inhibitor are given on an intermittent schedule, such as 21 days on or off in a 28-day cycle. The take-home messages of these two phase I trials is that the maximum tolerated dose was 600 milligrams when voruciclib was given on, rather, twp weeks on, one week off, and 350 milligrams when given daily, continuously. Those are important numbers because we at MEI believe that Voruciclib dose in combination with venetoclax in the range of one to 200 milligrams will be sufficient to inhibit the target and result in clinical benefit, way below the MTD defined in the dose escalation studies in solid tumors. Important findings from these studies also is there were no evidence of neutropenia in these patients with solid tumor. There were no primary toxicity and no effect on the heart. As far as efficacy, as expected in those studies in very advanced stage disease, we have had some patients who have achieved disease stabilization and one or two patients who achieved a partial response, and some of these disease stabilization lasted for up to four months. I want to point to that set of experiments that was conducted in one of the two Phase I studies. That relates to the MYC inhibition that I had mentioned earlier. Blood samples were obtained from patients in this study at baseline before starting voruciclib. At every cycles for several cycles of therapy. Those are example from blood sample from two patients in which 10 genes were evaluated. The one of interest to us today is the MYC, circled in green in these two patients' panels. As you can see, at baseline, MYC was overexpressed. With therapy, MYC levels decreased from baseline. Indicating from these earlier trial that we do see an effect on MYC with voruciclib treatment. Let's pivot to MEI-conducted studies. When we acquired the asset, we saw that there is value in moving the development of voruciclib first in patients with hematologic malignancies, taking an advantage of the effect on voruciclib on this MCL-1. That was driven by two factors, one, the realization that voruciclib is primarily a CDK9 inhibitor, and two, the fact that we had data from patients' sample with CLL, as well as preclinical study shows the synergy with a combination with venetoclax. Our initial focus has been on enrolling patients with acute myeloid leukemia and B-cell malignancies, including CLL. This summarize the phase I study. It had two phases or two stages. The first stage with a monotherapy dose escalation, meaning escalating voruciclib as a single agent from a low dose up to a dose of 200 milligram, as shown in the middle. This was conducted in patients with both AML and B-cell malignancies, enrollment and the readout of that phase of the study is completed with 40 patients enrolled. We are currently enrolling in the second stage of this study, evaluating voruciclib in combination with venetoclax in patients with AML, beginning at a low dose of 50 milligram every other day and intending to go all the way to approximately 200 milligrams. We have presented at ASH 2021, the initial readout of the dose escalation monotherapy. Key highlighters are shown here for safety. There were two groups, as you can see. Group one is when we dosed voruciclib daily continuously, we pivoted to administer voruciclib on an intermittent schedule of 14 days on, 40 days off. That is the schedule that we took in further development, the one we are evaluating in combination with venetoclax. As you can see on the table, on the intermittent schedule, which is called the group two, there were no grade III or higher adverse event related to the product. In fact, the tolerability was generally good. There were no significant myelosuppression in patients with B-cell malignancies and no grade III/IV neutropenia in patients with B-cell malignancies. We have not seen tumor lysis syndrome, and there were no fatal toxicity due to the drugs. Let me go into more detail, both on safety and efficacy. During the dose escalation, we initially evaluated voruciclib on a daily continuously dosing schedule. At the 100-milligram dose level, two patients developed pulmonary toxicity. It is unclear if this was due to the drug or to the fact that these patients had undergone prior stem cell transplant, had graft-versus-host disease, and during therapy may have developed a differentiation syndrome that can be seen in AML patients receiving active treatment. In collaboration with our investigator, we decided to evaluate another dosing schedule, administering voruciclib on a 14 days on, 14 days off schedule. With this schedule, we went to dose from 100 to 150 to 200 mg without observing dose-limiting toxicities. We stopped dose escalation at 200 mg because we believe these doses are sufficient to inhibit the target, and there were no need to continue dose escalation just for the purpose of defining the MTD in hematologic malignancies. We have seen in these patients who were heavily pretreated, in fact, the median prior therapy was three and up to eight in one patient, some clinical activity, including one patient with follicular lymphoma who had a near partial response lasting six months, a patient with diffuse large B-cell lymphoma that has disease stabilization lasting for four months, and one patient with AML who achieved what is called a morphologic leukemia-free state. Overall, at the 200-milligram dose level in patients receiving the two weeks on, two weeks off schedule, about half of the 24 patients achieved some disease stabilization or a response. We can move to the ongoing stage of this study, which is the combination of voruciclib with venetoclax. We are starting at a very low dose at the requested of FDA because we have introduced a new formulation in this combination that has several advantage. Far, we have completed enrollment at this first dose level, and we have not seen any additive toxicity from the combination. In fact, we have seen two interesting efficacy observation in patients with AML who have been very heavily pretreated. One of these patients achieved a partial responses, and that patient had received prior stem cell transplant, prior venetoclax, and prior combination chemotherapy. Another patient who had relying heavily on transfusion prior to starting voruciclib and venetoclax, went for several weeks without any transfusions. Overall, we are very encouraged by this very primary data and look forward to continuing enrollment and accumulating data with the combinations. Now, let's look toward the future and where the clinical development of voruciclib can be. First, initially, it will be in patients with acute myeloid leukemia. AML is primarily a disease of elderly patients or patients who are unfit to receive intensive chemotherapy. In this population, venetoclax, in combination with a hypomethylating agent, such as azacitidine or with low-dose cytarabine, is the standard of care based on multiple phase III studies. While this has been an improvement in response rate and survival compared to a single-agent hypomethylating agent, the median survival remained short at about 15 months. Therefore, there is a need to improve response rate and survival in these patients. Voruciclib in combination with azacitidine and venetoclax could lead to improve in response rate and ultimately survival, and represent a path for development of this compound. In addition, one should not discount the possibility to see benefit in patients with relapsed AML after having failed standard treatment, in which the median overall survival today with current therapy is very short, typically less than 6 months. Therefore, adding voruciclib to venetoclax in this setting could also potentially be an improvement in patient care. Another approach is in patients with chronic lymphocytic leukemia, where venetoclax, in combination with an anti-CD20 antibody, like rituximab, is currently approved as a frontline treatment or in the relapsed setting. There is a possibility that voruciclib can enhance the activity of venetoclax with anti-CD20 in patients with CLL and could be developed either in the relapsed setting as a triplet or substituting the anti-CD20 with voruciclib, leading to a completely oral regimen in patients with CLL. With that now, I will go to summarize overall what we know on voruciclib. It's an oral CDK9 inhibitor. The pre-clinical data we have today demonstrating downregulation of MCL-1 and synergy with venetoclax in multiple hematologic malignancies model. We know that increased MCL-1 is an important target to effect to improve on venetoclax activity since it is the main mechanism of resistance to venetoclax. Early clinical data shows encouraging results, both in terms of tolerability, where we do not anticipate overall toxicity, overlapping toxicity between venetoclax and voruciclib, and we already seen some clinical activity that is encouraging. The current phase I study is enrolling in the combination of venetoclax plus voruciclib, and we anticipate seeing the primary results of the dose escalation stage toward the end of the year. With this proof of principle of the combination being established, one can evaluate the combination with venetoclax in other disease where venetoclax is the standard of care. Now, I will turn to the other MEI compound, ME-344. I am very excited about this asset because it has a very unique mechanism of actions. In fact, that is also what exciting our investigators who are currently participating in our ongoing study in colorectal cancer. Let me step back a moment and explain to you the mechanism of action of ME-344. With that, we have to talk about cell energy. Why and how does a cell, normal cell or malignant cell, obtain their energy? Primarily, cells obtain their energy through the mitochondria, a small molecule called ATP. ME-344 inhibit the production of ATP by blocking a pathway called the OXPHOS pathway. However, as we know, as I mentioned it, cells also have other ways to get their energy, and one of it is through use of glucose or sugar. That's called the glycolytic energy. In cancer cells, there is a big reliance on the glycolytic energy. There's a class of drug, anti-angiogenic drugs like Avastin, that block the production of this pathway, of the glycolytic pathway, making cells switch to rely more on the mitochondrial energy. And here we can imagine that by adding ME-344 in combination with Avastin, now you're blocking completely the pathways that cells depend on it to get their energy, and that can lead to cell death. We can see synthetic lethality by combining these two class of agents, and that is what excites me about this compound. Let's give you a background about ME-344 preclinical data. This is the effect on 200 different cell lines, the panel to the left, and the waterfall plot shows a decrease in inhibition of cell proliferation with ME-344 alone. You can see in the very large majority of the cell tested, there is a significant decrease in proliferation. I picked one example of that, which is the panel to the right, in cell line from ovarian cancer, where you can see a dose-dependent decrease in proliferation with ME-344, these are the lines to the bottom, compared to the control arm, which is the top line going upward. This is single agent activity. More relevant to the discussion about the combination of ME-344 and Avastin is this animal model. This is a colorectal cancer model where ME-344 was combined with an oral anti-angiogenic, a kinase inhibitor called regorafenib. This is two panels, one to show to the left an improvement in survival when ME-344 was combined with regorafenib, and to the right, this was due to a decrease in tumor growth. Again, in red is a combination of the two drugs. Let's turn to update you on the clinical data with ME-344, beginning with the earlier trial conducted by MEI. First, a single agent, phase I dose escalation study that's been published, and next was a phase I/II study in combination with a chemotherapy called Topotecan. Let me give a quick snapshot information of these two studies. The first one was a standard dose escalation study by the 3+3 design that enrolled 30 patients from the lowest dose of 1.5 mg/kg all the way to 20. The important information learned from that trial is dose up to 10 mg/kg were well tolerated, and that was the dose that was selected for further development. The dose limiting toxicities at higher dose than 10 mg was neuropathy. It is no surprise that one can see neuropathy with mitochondrial inhibitor. Nerves, the nervous system, require a lot of energy to communicate the signals, blocking the energy by decreasing the ATP production could lead to neuropathy. Again, we only see it at the higher dose of 15 and 20 mg, which we do not intend to use in our current studies. In these very heavily pre-treated patients, one of the patient achieved a partial response, a patient with small cell lung cancer, another patient achieved stable disease with a disease control rate a little bit over a third of the patient. It is that patient with lung cancer who had achieved a partial response that led to the conduct of the next study, combining the chemotherapy topotecan that is approved for lung cancer, small cell lung cancer, with ME-344. 46 patients were enrolled, and what we have noticed is there was significant myelosuppression with this combination. I believe in part due to the fact that we have used a higher dose of topotecan than typically used in this disease. In addition to that, we have seen patients with ovarian cancer achieve a partial response and an overall disease stabilization rate of about half of the patients. This is kind of a brief summary of the safety profile. This table is directly from the published paper. As you can look in the grade III toxicity, the only one of relevance is the one that relates to neuropathy that I mentioned to you, and it was only at the higher dose, and as well as fatigue and dizziness. As you can see, there were no other significant toxicities as a monotherapy. This is briefly re-summarizing the efficacy data with the disease control rate, about a third of the patient as a monotherapy. To the right, the bars in blue are patients on the ME-344 regimen and how long they had stayed on treatment. As you can see, their duration on therapy for many of these patients was much longer than it was on their prior regimen, indicating a biologic activity. Let's pivot to the interesting combination of ME-344 and Avastin, the anti-VEGF inhibitor. The initial proof of concept for that was done in animal novel, conducted with a collaborator in Spain, who then, with our agreement, decided to take the next step, which is evaluating the combination in patients. Not so much to look at evidence of clinical efficacy, but more as a proof of concept of biologic activity. That is called a window of opportunity study. It was conducted in 40 patients with breast cancer. The reason he selected breast cancer is women with breast cancer tend to have to wait several weeks to get their scheduled surgery appointment and get prepared for it. During that time, there's a possibility to do a very brief experiment to evaluate drugs and see whether there's a biologic effect, both before starting treatment and after starting treatment. This is exactly what was conducted in that trial. That has been since published, and I will give you the top-line results. In this study, these women who are have a breast cancer that was HER2 negative, again, planned to undergo surgery, underwent initial biopsy, received 1 dose of Avastin on day one, then three doses of ME-344 once a week for three weeks, and then they underwent another biopsy at the end of the treatment. The purpose of that trial is to look at biologic effect, and the readout was through the biopsy. Highlighted on this slide, the key readout that was used in this study is something called Ki-67. It's a well-established marker of cell proliferation and has been used in many studies as a way to determine whether a drug or a combination of drugs can be effective in breast cancer. That is what was used in that study. The panels in the middle and to the right shows the treatment effect. In green is the combination, and going downward shows a decrease in Ki-67, which is a desired outcome. As you can see, the combination in green has a significant improvement and decrease in Ki-67 compared to the control arm, who received bevacizumab alone in gray. That's in all patients, the panel to the middle, and in a subset of patients who have normalization of vascularization, which is more prominent, in fact, the treatment effect. Based on these data, we have decided to launch a clinical study now with a clinical readout, and we decided to run this study in patients with metastatic colorectal cancer, because this is a group of patients who have failed all standard therapy and for which there is really no very active treatment today. In addition, the readout in these diseases tend to be relatively short. The current study is designed as a standard phase I/II study, where we enroll patients with metastatic colorectal cancer after failure of standard therapy. Patients are administered ME-344 and bevacizumab like it was done in the prior study, but now with cycle repeated until disease progression or toxicity. The goal is to enroll first 20 patients, assess safety and efficacy, and then enroll another set of 20 patients in its second stage. The study now is open to enrollment, and hopefully, we will have data to present on this time, on this study at some time in the near future. Overall, where does this take us? Clearly, there remains an unmet need in patients with colorectal cancer. Currently approved drug in the third or later line of therapy are the oral kinase inhibitor and a chemotherapy. However, with this agent, the response rate is less than 5%, and the median progression-free survival remain very short. Any improvement in both the response rate and/or PFS with a combination with ME-344 and bevacizumab will be a significant advantage to patients in this setting. Next, we can envision other scenario where Avastin is approved as a single agent or in combination, where addition of ME-344 could enhance the efficacy of bevacizumab alone or Avastin alone, and or the combination with other agents. There are a number of disease where Avastin is currently approved, where this approach can be conceived. Now that I present to you our thoughts about future potential development of ME-344, I would like to kind of bring all together conclusion remark. ME-344 is a very exciting because it's unique mechanism of action, inhibit mitochondria. We have pre-kill data showing synergy with anti-angiogenic inhibitor, whether Avastin or oral TKI, in several preclinical model. We have a study that was conducted as a window of opportunity study in patients with breast cancer, in which we have demonstrated an effect on Ki-67, a biomarker of cell proliferation, in which the combination in a placebo-controlled study showed a significant decrease in Ki-67 compared to what was observed with Avastin alone. With this, we have now launched a phase I/II study, or phase Ib study, in patients with relapsed metastatic colorectal cancer. phase I, stage I, rather, of cohort I, will have its initial readout toward the end of the year. That will then take us to evaluate the combination in stage II next year. With that now, at the conclusion of the prepared remark, I would like to invite Nick Abbott to join me here to have a discussion on the program. Nick has over 35 years of experience in the biotech space. First, as a bench scientist at companies both in the UK and in the US Then after that, he had spent a lot of time at Wall Street, most recently as a senior analyst at Wells Fargo, where Nick covered over 20 biotech company, primarily in the oncology space. Nick, I'm delighted to see you and welcome you. Dr. Ghalie, appreciate the overview of those two exciting clinical programs. Moving back to voruciclib first, maybe from a clinical investigator perspective, what differentiates voruciclib from other CDK9 inhibitors that are in development? Right. Nick, that's a very good question, I'm really excited about voruciclib for a variety of reasons. Some are related to the pharmaceutics of the compound. It is oral, clearly an advantage when a drug needs to be given frequently to patients, or at least it enable that versatility if needed. It also has a long, long half-life, it's over 24 hours, which allows us to give it only once a day. Again, advantageous for patients. It also has a high volume of distributions, which I know we didn't discuss in the formal presentation. That means it can go to tissue. If in disease where it's primarily a tissue disease, that certainly would be an advantage. There's also several attributes from the biology of the compound that make it very attractive, and primarily the fact that it is at the dose used in the patient, our study, it is highly specific to CDK9, avoiding the off-target toxicity that could have been seen in the earlier generation CDK9. That certainly make it an advantage for use as a single agent, but primarily also when used in combination. A lot of attributes that makes it, in my view, a differentiated and hopefully a better CDK9. Thank you. Maybe from a slightly different perspective, but sort of getting at the same question, you know, given competition for patients in early-stage clinical trials, can you characterize how enthusiastic investigators have been and are to enroll patients onto the trial? Right. It's actually been very rewarding to see that interest from our investigators to be part of the trial. In fact, we really have a top-tier investigators from top-tier academic institutions that are participating in this study. When we approach them to see if they would be interested in the trial, their first answer is, "Yes, we would like to be part of it because we like the target." CDK9 is very important today in the hematology space, they wanted to sign up in a study looking at a new CDK9 inhibitor. We did the phase I monotherapy dose escalation. They liked what they have seen, primarily the fact that it can be given orally once a day, and also, perhaps more importantly, the safety profile of the compound. When we decide to open the combination with venetoclax, they certainly were very excited to be part of that phase of this study. I think what made them even more interested now than even just the class, is the fact that we haven't seen myelosuppression with voruciclib to date, which certainly this is an advantage when thinking about combination venetoclax and maybe at later time with other agents. I think there's a lot of interest and support from our investigators to be part of that trial and lead it to actually where we can see and publish the data. Thank you. You described elegantly, you know, the rationale for combining voruciclib with venetoclax in AML. Venetoclax has an approved indication in chronic lymphocytic leukemia as well. How do you and your KOLs think about expansion into B-cell malignancies? Right. You know, as you mentioned in the presentation, currently our focus is on AML in combination with venetoclax and eventually perhaps moving to frontline in combination with venetoclax and azacitidine. Nevertheless, as you mentioned, venetoclax is a key drug for the treatment of patients with chronic lymphocytic leukemia. venetoclax in combination with anti-CD20 antibody is approved in frontline treatment in all the patients and all patients in the relapse setting. we would like to enhance the activity of venetoclax plus anti-CD20, primarily in a relapse setting. We know that CLL is a rapidly evolving landscape with the BTKi venetoclax now. Therefore, we think the better position at present would be in the relapse setting, either in combination with venetoclax and rituximab, or perhaps, and that will be data-driven, using only an oral combination regimen of venetoclax and voruciclib without the rituximab. That's something, of course, we will need to investigate before we go into later kind of decision about that combination. Sure. In your prepared comments, you mentioned that Piramal started evaluating voruciclib in solid tumors. Obviously, you know, that those studies were done prior to us really, you know, having a good handle on KRAS, on MYC amplify tumors. What are your thoughts about moving voruciclib into solid tumors, perhaps in a more selected setting than has been looked at previously? Right. I'm very excited about that possibility. For a variety of reasons. One, because it opens multiple opportunities in different solid tumors that either express MYC or the KRAS mutations. In fact, Piramal had provided us some of the data that actually supported the idea of going into a MYC or KRAS mutated. You may recall, when I did the formal presentation, I present data from patient sample from one of the earlier phase I studies in solid tumor that showed, in patients who were tested, a reduction in MYC in about two-thirds of the patients. We already have that evidence in patients, and we have conducted and already presented at AACR in 2022, data on the combination with KRAS inhibitor and voruciclib, that shows activity in cell line. Our focus now is to build the non-clinical package, a set of experiments that kind of guide us in the next step to decide where and when we will move into the clinic in solid tumor. Clearly, the potential opportunity would be in KRAS-mutated tumors, and it doesn't have to be only this, you know, the current drugs, but also potential new drugs that are being developed to target different mutation in the KRAS pathway. Great, thanks. Let's move to ME-344, novel mechanism of action. How is this resonating with clinicians you speak with, and particularly in the context we've had a lot of failures in, you know, targeting metabolic pathways in cancer? Right. Actually, the process of determining how and in which disease to evaluate ME-344 with bevacizumab originated an advisory board meeting we had not too long ago. The first reaction from the advisor we had at the meeting, and this advisory board had representation from different therapeutic and cancer expertise. The common theme that we heard at the meeting is, We like what you present to us on ME-344 because it has a different mechanism of actions. They particularly understand the science behind the combination of a VEGF inhibitor and ME-344, where really we're blocking completely, in at least rapidly proliferating tumor cells, the source of energy. They like the new mechanism of action. They like the science. They like the fact that we have data from the window for produced studies in patients, showing that the biology is translating to a positive readout in a biomarker, Ki-67. They're really exciting now to test it in patients. Great, thank you. You've mentioned, obviously, that the wind of opportunity study was done. Mm-hmm. In breast cancer. You know, remind us again, why switch to colorectal cancer? When could investors expect top-line data? In what, in your view, is the hurdle for efficacy for moving to stage two? Right. All good question, like, why was the window of opportunity studies performed in breast cancer? Why pick that specific disease? The reason is relatively simple. Patients with breast cancer need some time to have their surgery schedules, and typically, at least in Spain, where the study was conducted, it's usually about a month. It was really a perfect opportunity to slot a study like the one that was indeed conducted to look at bevacizumab and ME-344. That give the time to do the initial biopsy, administer the drug, and look at the readout four weeks later. The intent was really to study whether the biology support that combination. When we looked at now which disease to evaluate for now safety and efficacy data, the advisory coalesced, and we agree with them, to the concept of studying it in colorectal cancer. Two main reasons. One is there aren't many drug approved in the relaxed setting, and the currently approved drug aren't sufficiently effective, at least to the extent that investigators and their patients want. That was the right place to study a new combination. Also, unfortunately for the patient, but certainly it helped, the readout is relatively quick. We will have, you know, over a short period of time, some assessment on whether the combination is providing the outcome we're looking for. Now, you asked me what is that outcome that we would consider favorable? Again, that was discussed with our advisors, and essentially, they point to the data, not our data. The data currently observed with TKI and chemotherapy in third or later line of regimen. The response rate is very low, less than 5%, and the durability of response or PFS is still very short, you know, measured in only a few months. Anything that can improve on that will be considered positive. We'll think about a response rate, if possible, that is in a double digit instead of single digit. That'll be certainly a positive outcome, and/or an improvement in PFS, say, by doubling, to just give an example. That's kind of what we're aiming at as far as outcome, but of course, it's going to be data-driven. Finally, you asked me about when would we have the data from that study. As I mentioned, we're running the trial in 2 cohort. The initial cohort, we anticipate to have the initial readout toward the end of this year. After that, will be data for the next cohort next year. Great. Thank you. you know, you had this, high-powered group of experts come together. obviously, Avastin is used in other diseases. you know, as they prioritize the list, where do you go next after colorectal cancer, and how many places do you think you might be able to evaluate the combination of ME-344 with a VEGF inhibitor? Right. An excellent question, Nick. Is the first step is colorectal cancer, and of course, with positive readout, we're going to focus on colorectal cancer as in a development path. It doesn't mean that it has to be the only development path. Other disease that were, you know, discussed would be potentially in renal cancer, renal cell cancer, in combination with oral TKI. Certainly, in my view, there is still a huge unmet need in glioblastoma, where, you know, bevacizumab is approved with or without lomustine, but the results are still not sufficient to what we would like to have for our patients. Another opportunity will be in glioblastoma, for example. That's only a few, and of course, they'll be driven by, you know, where we see the current data take us. Also, we're considering some preclinical studies to conduct that may help orient us to what other diseases we could go to. Great. Beyond other diseases, how about other combinations? Obviously, checkpoint inhibitors are a backbone of cancer therapy. Chemotherapy remains part of that backbone. How do you think about combining ME-344 beyond the VEGF TKIs? Right. At least for one combination, we've already presented non-clinical data with collaborator MD Anderson and Wayne State. It's in combination with venetoclax in AML, it's been presented at AACR, I think, one year ago, 1.5 years ago. The manuscript now is accepted in a peer-reviewed journal, where we see a synergy with the combination in AML. That is one example of a combination that it goes beyond the TKI. Certainly, we're interested also with checkpoint inhibitor and that would be an attractive approach, but need to be tested first in preclinical model before we go into the clinic. Certainly, it's an interest to us. Great. Well, thank you, Dr. Ghalie. We've run out of time, so look forward to data sets emerging this year and into next year, and good luck to you and the team. Thank you. Thank you, Nick. We really appreciate your good questions, and we'll look forward to present data, as I mentioned, when they're available. With that, now I would like to turn it to David Urso to take it and conclude the meeting. Thank you. Thank you for joining this presentation that shares an overview of why we believe the pending transaction presents an exciting opportunity for MEI and Infinity to advance three promising clinical stage oncology candidates, each with the potential to be a transformative, first-in-class therapy that could advance the standard of care and the indications being evaluated. Together, we have a promising and diversified pipeline of oncology candidates, each with a differentiated mechanism intended to address known resistance mechanisms of commonly used therapies and enhance outcomes for patients with inadequate treatment options. I expect the combined company to be well-positioned to make a difference in cancer care and to deliver near and long-term value for patients and stockholders. Thank you.