Medicenna Therapeutics Corp.

Hello, and welcome to the Medicina Therapeutics Fiscal Q2 Earnings Call. All participants are now in a listen-only mode. There will be a question and answer session at the end of this call. Please be advised this call is being recorded at the company's request. I would now like to turn the call over to Dan Ferry of LifeSci Advisors. Please go ahead.

Thank you, Operator. and thank you all for participating in today's conference call. This morning, Medicina issued a press release providing financial results and corporate updates for the quarter ended September 30th, 2021. If you have not yet seen the press release, it is available on the investors page of Medicina's website. Before we begin, I would like to remind you that certain statements and information shared during this call constitute forward-looking information within the meaning of applicable securities laws and relate to the future operations of the company and other statements that are not historical facts, including statements related to the clinical potential and development of the MDNA 11, MDNA 55, and BISCUITS programs, the potential of the SuperKind platform, partnering activities, cash runway, and the presentation of additional data. All statements other than statements of historical fact included in this conference call, including the future plans and objectives of the company, are forward-looking statements that are subject to risks and uncertainties. There could be no assurance that such statements will prove to be accurate, and actual results and future events could differ materially from those anticipated in such statements. Important factors that could cause actual results to differ materially from the company's expectations include the risks detailed in the recently filed annual information form, management's discussion and analysis in Form 40F of the company, and in other filings made by the company with the applicable securities regulators from time to time in Canada and the United States. Listeners are cautioned that assumptions used in the preparation of any forward-looking information may prove to be incorrect. Events or circumstances may cause actual results to differ materially from those predicted. As a result of numerous known and unknown risks, uncertainties, and other factors, many of which are beyond the control of the company, you are cautioned not to place undue reliance on any forward-looking information. Such information, although considered reasonable by management, may prove to be incorrect and actual results may differ materially from those anticipated. Forward-looking statements contained in this conference call are expressly qualified by this cautionary statement, except as required by law, We do not intend and do not assume any obligation to update or revise publicly any of the included forward-looking statements, only as expressly required by Canadian and United States securities law. Now, I will turn the call over to Dr. Fahar Merchant, President and Chief Executive Officer of Medicina Therapeutics. Fahar.

Thanks, Dan, and thanks to those who have joined us today to discuss our fiscal Q2. 2022 Corporate Update. In addition to Dan, I am joined by Dr. Man Musin, our Chief Medical Officer, Nina Merchant, our Chief Development Officer, and Liz Williams, our Chief Financial Officer. This is an exciting time for Medicina as our accomplishments over the past months have us advancing towards key positive inflection points with the potential to differentiate our IL-2 program and provide clinical validation of our SuperKind platform. Today, we will review some of these recent accomplishments, outline our clinical and corporate strategy, and set the stage for what to expect over the coming months by discussing the clinical, scientific, and corporate objectives we are working towards. So, let's start with some of our recent accomplishments, beginning with our MDNA 11 program. As a reminder, MDNA 11 is our beta-only, long-acting IL-2 super agonist that we believe is well-positioned to be a best-in-class cytokine in the immunotherapy treatment landscape. Last quarter, we initiated our Phase 1-2 ability study of MDNA 11, expanding our clinical pipeline. Patient dosing in the trial is currently underway in Australia. And we recently received IND clearance from the FDA to expand the trial to the United States. In addition, we are planning to further expand the study to sites in Canada and the United Kingdom and expect regulatory submissions for these jurisdictions to be complete before the end of the calendar year. While I let Matt speak in more detail about the trial, I will say now that we are very pleased with the progress being made and remain on track to provide a preliminary update on safety, PKPD, and biomarker data from patients in the early cohorts enrolled in the dose escalation phase of the study by the end of calendar 2021, as well as an initial efficacy data update from the dose escalation portion of the study by mid-2021. The update in calendar 2021 will be an important check to confirm that the best-in-class properties we see in our murine and non-human primate studies are being replicated in humans, which we believe will correlate for more efficacious drug when compared with other IL-2 variants in clinical development. Staying with our MDNet11 program, We also recently reported data from murine and IND-enabling non-human primate studies at the triple meeting. These data reinforce our belief that mDNA11 has the potential to be a best-in-class therapy and highlight the advantages of its differentiated beta-only approach to selectively target this key IL-2 receptor subunit. Non-human primate data indicate that mDNA11 may overcome the safety and PK challenges of recombinant human IL-2, which is known as proleukin, and approved for the treatment of advanced renal cell carcinoma and metastatic melanoma. They also show that by selectively targeting the IL-2 receptor beta subunit and avoiding the IL-2 receptor alpha unit, MDNA11 preferentially induced durable proliferation and expansion of anti-cancer immune cells with limited stimulation of pro-tumor Treg cells. We believe this beta-only activation of the IL-2 receptor will translate to enhanced efficacy in comparison to proleukin and not alpha IL-2 versions that are in the clinic. In a murine colon cancer model, data showed that MDNA11 alone or in combination with an anti-PD-1 checkpoint inhibitor led to tumor growth inhibition and dose-dependent durable complete responses in all mice, even though tumor growth rate was not inhibited by anti-PD-1 monotherapy. Additionally, initial treatment with MDNA 11 alone, or in combination with anti-PD-1, provided long-term protection against subsequent tumor re-challenge by inducing antigen-specific memory CD8 T cells. We believe these collective results, which mine will be discussing in more detail shortly, provide a strong scientific rationale for our ability study, and highlight the potential of MDNA11 to overcome the shortcomings associated with Prolucan and competing not-alpha IL-2s in the clinic. Shifting gears, I'd like now to briefly discuss MDNA55, which is our Phase III-ready, empowered IL-4 superkind being developed as a treatment for recurrent glioblastoma. As some of you may recall, our Phase IIb trial showed that a single treatment with MDNA55 led to a doubling in the overall survival when compared to a matched external control arm. Based on these and other data, we have aligned with the FDA on an innovative hybrid Phase III trial design that allows for two thirds of the control subjects to be from a matched external control arm. This trial design was recently featured in a peer reviewed manuscript published in the Lancet Oncology and in an oral presentation at the Society for Neuro-Oncology and American Society of Clinical Oncology's first annual conference on CNS clinical trials. We have recently secured the FDA's agreement on deferring any pediatric clinical trials with MdNA55 to occur only after the adult phase three trial is completed, instead of having to conduct a pediatric study in parallel with the adult study. This approach substantially de-risk the conduct of the registration trial in adults by the potential partner. In the interim, We continue to advance the required regulatory activities associated with MDNA55, GMP manufacturing, and future commercial supply for potential market launch so that the program can be advanced as efficiently as possible once a partnership is established. On the discovery and preclinical effort, last quarter we were pleased to announce a peer-reviewed publication in Frontiers in Immunology, featuring data on MDNA-109, which is our IL-2 supercrime platform and the precursor of MDNA-11. This paper, which was independently authored by researchers at the University of Helsinki and other institutions, evaluated oncolytic adenoviruses that were either unarmed, armed to code for MDNA-109, or armed with wild-type IL-2 in a hamster pancreatic cancer model. Results showed that compared to wild-type IL-2, MDNA-109 was better able to reprogram the tumor microenvironment, which led to superior tumor growth inhibition with an MDNA-109-armed virus compared to an IL-2-armed virus in a pancreatic tumor model. These and other results from the paper externally validate the versatility of the MDNA-109 platform and its potential to overcome limitations associated with less active versions of IL-2, such as native IL-2, particularly in immunologically cold tumors, such as pancreatic cancer, where a great unmet need exists today. Going forward, we expect the versatility offered by our Superkind platform to continue to power our discovery and preclinical programs as we seek to develop next-generation Superkind-based therapies such as those derived from our BISCUITS platform. As a reminder, our BISCUITS platform enables the design of bespoke immunotherapeutic agents that incorporate two functionally non-overlapping mechanisms of action so as to potentially achieve synergistic therapeutic effects. This may allow for the treatment of more aggressive and recalcitrant tumors where a simultaneous two-pronged approach may be necessary to improve safety and efficacy. Biscuits comprise a super kind that is then fused to a second anti-cancer agent such as another super kind, an antibody, or a checkpoint inhibitor. An example of a biscuit comprising two super kinds is MDNA19-413, which is another promising long-acting therapeutic candidate that combines an IL-2 super agonist with an IL-4, IL-13 super antagonist to potentially overcome tumor resistance mechanisms to immunotherapies and can be a viable treatment option for immunologically cold tumors. Examples of biscuits include fusions of our IL-2 super kinds with checkpoint inhibitors such as an anti-PD-1 antibody in the cis mode or an anti-PD-L1 antibody in the CRANS orientation. These agents can potentially provide superior anti-tumor effect compared to traditional checkpoint inhibitors in monotherapy settings by enabling T cell activation while simultaneously stimulating pathways to suppress T cell exhaustion and inhibiting tolerance of the immune system to tumor cells and antigens. They may also offer important intellectual property advantages and crucial life cycle management and patent extension as first-generation checkpoint inhibitors begin to come off patent in the coming years and highlight one of the key advantages of our SuperKind platform. Unlike others who utilize inefficient chemical synthesis or conjugation techniques, such as pagulation to improve pharmacokinetic profiles of cytokines, our SuperKind platform is independent of such manufacturing challenges and instead uses protein scaffolds such as albumin, as is the case with MDNA11. Our highly selective and tunable super kinds and biscuits are generated using directed evolution, allowing them to be genetically fused with other biologics such as targeting antibodies, checkpoint inhibitors, other cytokines, or they can be used to arm oncolytic viruses, CAR T cells, and cell-based therapies to further enhance their efficacy. These versatile options are not available with pegylated IL-2s. Our manufacturing platform simplifies the scalability of the manufacturing process and leads to improved IL-2 receptor beta binding affinity compared to pegylated IL-2, further differentiating our superkind and BISCUITS platform from competing approaches. Finally, using albumin as a scaffold has the potential for localizing our superkinds to the tumor microenvironment and tumor-draining lymph nodes, which function as sites of T-cell invigoration required for immunotherapy and checkpoint blockade. Looking forward, we remain committed to our BISCUITS program, given its potential to create fusions with antibodies, other super kinds, and checkpoint inhibitors, and we are currently advancing multiple candidates through the discovery and optimization process. We plan to conclude the candidate selection and declare a lead candidate by the end of the calendar year. In addition to our recent clinical and scientific accomplishments, we also strengthened the intellectual property portfolio, protecting our SuperCAN platform with the issuance of a U.S. patent. This patent covers methods of treating a wide range of cancers with IL-2 variants, such as MDNA-11, and has claims that specifically focus on agents with enhanced affinity for IL-2 receptor beta, which, as I mentioned earlier, is a key point of differentiation for our IL-2 super kinds. This latest patent adds to a long list of issued and filed patents in major jurisdictions around the world, which collectively provide foundational composition type protection for MDNA 11 and our broader IL-2 super kind platform. Lastly, before handing the call off to Man, I'd like to highlight an important corporate accomplishment from last quarter, which was the appointment of Dr. John Sampson for our board of directors. John is an immunology expert who brings extensive experience in clinical trial design and execution to our board, as well as deep knowledge of the regulatory process. He is currently the Robert H. and Gloria Wilkins Distinguished Professor of Neurosurgery at Duke University, President of Duke's Physician Practice Private Diagnostic Clinic, and a member of the prestigious National Academy of Medicine. The insights he has provided have already proven to be valuable, and I look forward to his continued contribution to MediCenter's long-term growth and clinical strategy. And with that, I will hand the call off to Man to provide some more details on our MDNA 11 program. Man, please go ahead.

Thank you, Fahar, and good morning, everyone. It's my pleasure to speak today about our beta-only long-acting IL-2 super agonist, MDNA 11, and the advancements we have made in the last few months. As Fahar alluded to, This molecule was engineered to overcome the shortcomings of prolutin and other modified IL-2s in the development landscape that rely solely on the not-alpha approach. Prolutin shortcomings stem from a number of limitations, including its dismal pharmacokinetic profile and preferential affinity for IL-2 receptor alpha compared to IL-2 receptor beta. Stimulation of IL-2 receptor alpha leads to the activation of TRX, which is generally associated with unfavorable prognosis in cancer, can limit antitumor response and cause extreme toxicity due to cytokine release syndrome, pulmonary edema, or vascular leak syndrome. These safety issues, together with Proleukin's poor pharmacokinetic profile, necessitates dosing in the ICU every eight hours. In an attempt to overcome these limitations, others have modified Proleukin to be a pegylated, not alpha IL-2. While the pegylation of Proleukin does reduce IL-2 receptor alpha binding by steric hindrance and improve its half-life, it also considerably interferes with and reduces IL-2 receptor beta binding, which is crucial for activation of cancer-killing immune cells that are the target factors of IL-2 therapies. We believe this is the reason that these pegylated, not alpha IL-2 variants, have produced suboptimal clinical results to date when compared to Proleukin. Now, rather than utilizing pegylation to improve half-life and avoid binding to IL-2 receptor alpha, we took a completely new approach when engineering MDNA11. First and foremost, using directed evolution Five mutations in the core of IL-2 improved the binding affinity for the IL-2 receptor beta by up to 200-fold when compared to proleukin and is the basis of our MDNA109 molecule. Beginning with MDNA109, we fused this IL-2 superagonist to albumin to improve its half-life, as Fahar mentioned earlier. Using albumin rather than PEG allows for a simpler, more homogeneous manufacturing process with no batch-to-batch variations while maintaining potent IL-2 receptor beta binding affinity. Finally, two additional mutations further enhance selectivity towards the beta receptor and restricting binding to IL-2 receptor alpha. The next result of the design objective was to construct a differentiated and active beta-specific long-acting IL-2. that has the potential of tumor accumulation without multiple liabilities of regulation and achieve the optimal balance of safety and efficacy as demonstrated in the data generated thus far. The results presented at the triple meeting that Fahar previewed earlier demonstrate how this meticulously engineered design confirms MDNA11 with best-in-class potential. Pharmacokinetic analysis from the IND enabling non-human primate studies showed dose proportional increase in exposure as measured by both CMAX and AUC with corresponding increases in durability of key PD markers. MDNA11 was detected in the serum of non-human primates up to four to five days after dosing with pharmacodynamic effects lasting more than eight days post-dose. As Fahar mentioned, these pharmacodynamic effects included the induction of anti-cancer immune cell proliferation and expansion with limited stimulation of protumoral T-ray. Importantly, MDNA-11 also exhibited a favorable safety profile in these non-human primate studies as its administration did not lead to any of the non-safety issues associated with proleukin that I mentioned earlier. Collectively, these results indicate that mDNA11 can overcome the limitations of Prolucan and other IL-2 variants in the development landscape, thanks to its enhanced beta targeting approach and its potentially superior safety, PK, and PD profiles. We are now working to clinically validate these findings through our ongoing Phase I-II Ability Study. This study is designed to assess safety pharmacokinetics, pharmacodynamics, and antitumor activity of various doses of MDNA-11 administered intravenously every two weeks in patients with advanced amygdastatic solid tumors in frontline as well as relapsed refractory settings. The study will enroll around 80 patients and will include a monotherapy dose escalation phase as well as combination arm to evaluate MDNA-11 with a checkpoint inhibitor. During the dose escalation phase, alternative dosing schedules can be examined, and options for intra-patient dose escalation will be included. This should allow us to gain a wealth of information to establish an optimal recommended phase 2 dose and treatment regimen. Following the trial's dose escalation phase, we plan to conduct a dose expansion phase that will enroll patients with various solid tumors in monotherapy and combination settings. Two tumor types included in these cohorts that will be of particular interest are advanced renal cell carcinoma and metastatic melanoma. These tumors are known to respond to proleukin, but to date have not shown comparable responses to new long-acting IL-2 variants currently in the clinic. We therefore believe evaluating MDNA11 in these tumor types will present an opportunity to demonstrate single-agent activity and best-in-class potential. Other tumor types that will be included in the trial are non-small cell lung cancer, both squamous and non-squamous non-small cell lung cancer, some GI tumors, triple negative breast cancer, and other selected tumors with unmet need to exploit the pan tumor potential of mDNA11. Looking ahead, the trial remains on track for a preliminary update on safety, PKPD, and biomarker data from the early dose escalation cohorts of the study by the end of calendar year. All patients enrolled to date in early dose escalation cohorts remain on treatment with no discontinuations, no reported DLTs or SAEs thus far. In addition to the favorable safety and tolerability profile, it's our goal to show by year end that it's PKPD profile, could facilitate dosing every two or three weeks, consistent with extended pharmacodynamic effects following biweekly dosing in the non-human primate studies. We hope to demonstrate that MDNA11's profile as the drug of choice when combined with a number of checkpoint inhibitors, irrespective if they have two, three, or six-week treatment cycles. We also plan to analyze peripheral blood biomarkers and immune cell markers. Immune profiling performed by epigenetic analysis will assess markers such as CD3, CD4, CD8B, FOXP3, GNLY for NK, CXCR3, CCR6, CCR7, PD1, LAG3 to further confirm drug activity. Immunophenotyping will include markers such as CD45, CD3, CD4, CD8, CD19, CD56, CD25, KI67, PD1, ICOS, CD11C, X40, CTLA4, and FOXP3. As part of this study, we intend to collect paired biopsies to assess changes in the tumor microenvironment. Gene expression profiles will be assessed using a panel of 770 cancer-related genes. Furthermore, specific markers such as granzyme B, perforin, interferon gamma, expression, and others that are indicative of cell activation will be assessed using nanostring analysis. The nanostring IO360 panel on immunofluorescence will be used for CD4, CD8, FOXB3, CD56, CD25, BDL1, and others. With these comprehensive set of analyses, we hope to observe signs of anti-tumor immune cell activation, a lack of activation of Treg cells, and a pro-inflammatory and more sensitive tumor microenvironment, which would confirm clinically that mDNA11 is making the tumor microenvironment more responsive, less resistant, with elevated immunogenicity characteristics. This will provide further clinical validation of our promising non-human primate data and would bode well for subsequent clinical data readouts. Speaking of subsequent data readouts, we expect to report an initial update on efficacy data and tumor response results from the trial mid-2022, which will be followed by additional updates throughout the year. As efficacy data are reported and mature throughout the calendar 2022, we are aiming to see objective responses rate that meet or exceed those generated with agents in the same drug class, along with deeper responses, improved durability of response, and a more favorable safety profile for comparable patient populations. When coupled with a more convenient dosing regimen compared to Proleukin, Results such as these would position MDNA11 as a based-in-class agent that could potentially have a broad therapeutic impact and clinical utility across multiple tumor types across a wide immunogenicity spectrum addressing high unmet needs. With the US FDA IND clearance, FPI for MDNA11-01 trial, and other objectives achieved, we believe we are making good progress towards achieving key goals of the MDNA 11 program, and we look forward to the Ability Studies' continued advancements. With that, I'll now hand the call off to our CFO, Liz Williams, to discuss our recent financial results. Liz?

Thanks, Man, and good morning, everyone. Before I begin, I would like to note that all references are in Canadian dollars unless otherwise noted. I'm pleased to report that Medicina maintained its strong cash position over the last quarter, as we had cash equivalents and marketable securities of $26.7 million as of the quarter close. Based on our current projections, we believe this will be sufficient to fund our operations through to the end of calendar 2022, including through preliminary updates on biomarker, PKPD, safety, and efficacy data from our Phase 1-2 ability study of MDNA11. We noted increased cash burn in the current quarter due to cash outflows associated with completing the manufacturing and IND enabling studies for MD&A 11 during the quarter, as well as paying our annual directors and officers liability insurance premiums. We've projected a lower quarterly cash burn in the next few quarters as these one-time high-cost activities are now complete. Net loss for the quarter ended September 30th, 2021 was 8.2 million or 15 cents per share compared to a net loss of 3.8 million or 8 cents per share for the quarter ended September 30th, 2020. The increase in net loss for the quarter ended September 30th, 2021 compared with the quarter ended September 30th, 2020 was primarily a result of increased research and development expenditures related to the MD&A 11 program as well as costs associated with the NASDAQ listing, in particular, directors' and officers' insurance premiums in the current period. Research and development expenses of $6.3 million were incurred during the quarter ended September 30, 2021, compared with $2.2 million incurred in the quarter ended September 30, 2020. The increase in R&D expenses in the current year's quarter is primarily attributable to higher CMC costs associated with GLP and GLP manufacturing of MDNA11, which is now predominantly complete. Increased preclinical expenses associated with GLP-compliant MDNA11 IND enabling studies, which are also now predominantly complete. as well as discovery work on the Biscuits platform and higher salary and benefit costs associated with a larger headcount necessary to support increased activities. General and administrative expenses of $2 million were incurred during the quarter ended September 30th, 2021, compared with $1.7 million during the quarter ended September 30th, 2020. The increase in expenditures in the current year quarter are primarily attributable to increased directors and officers' liability insurance premiums due to three months of amortization in the current year versus two months in the prior year, increased stock-based compensation expense due to the timing and value of option grants, and an increase in salary and benefit expenses due to a higher headcount to support ongoing operations. For further details on our financials, please refer to our financial statements and management's discussion and analysis which will be available on CDAR and EDGAR, respectively. With that, I'll now turn the call back over to Fahar.

Thanks, Liz. Before we move on to the Q&A, I'd like to take a moment to again commend Medicina's employees, partners, and investigators for their accomplishments over the past months. Their ability to execute on our stated milestones and bring MDNA 11 to the clinic despite working amid the ever-evolving pandemic, is a testament to their talent and dedication. It also gives me confidence in our future outlook and ability to successfully achieve the goals we have set for ourselves on the call today. We believe accomplishing these goals will enable us to grow a robust pipeline of novel super kinds and versatile biscuits which in turn will generate value for shareholders and bring us closer to delivering visionary immunotherapies to patients. We are excited for what lies ahead and will be sure to keep you updated on our progress along the way. And with that, we will now open the lines for questions. Operator?

Thank you. If you would like to ask a question, please press star 1 on your telephone keypad. A confirmation tone will indicate your line is in the question queue. You may press star 2 if you would like to remove your question from the queue. For participants using speaker equipment, it may be necessary to pick up your handset before pressing the star keys. Our first question today is from Matt Beigler of Oppenheimer. Please proceed with your question.

Hey, good morning, guys. Congrats on all the progress. Really looking forward to that first in human data later this year. Fahar, I wanted to ask you for your thoughts on the importance of NK cells relative to T cells. Obviously, we've seen really robust expansion in both NK cells and T cells preclinically, as you would expect, I think, from MDNA 11 mechanism of action. But there's some that speculate, or at least that I'm hearing, that that might not be ideal for optimal safety and efficacy for an IL-2 agonist. Can you just comment on that? Thanks.

Thanks, Matt. Thanks for being on the call and this question. You're correct. The issue about NK cells has been controversial, particularly recently. Nevertheless, we feel that NK cells are really important components of immune surveillance mechanism, and that has evolved to protect against tumor progression. We believe the importance of NK cell expansion to modulate the tumor microenvironment and to achieve therapeutic effects in tumor models without eliciting toxicity has already been established. and provides the basis for many different treatment paradigms that are currently using NK cells in different modalities. So we believe that the stimulation of NK cells is not detrimental. We believe it is essential for a holistic approach to having the most potential benefit for treating a patient with cancer, I think you need multiple attempts and multiple mechanisms to have a best outcome for the patient. To date, we don't see a potential for toxicity, et cetera, that seems to be claimed by others. So we will see how this pans out. Clearly, when we did our non-human primate study, we showed that administration of MDNA11 not only substantially increase the population of NK cells, but also naive CD8 T cells. And we know that increases in naive CD8 T cells are not associated with any toxicity, etc. So we feel that the proliferation of NK cells, naive CD8 T cells that are antigen inexperienced, are not cytotoxic, and therefore we believe those are also essential to boost therapeutic efficacy. Finally, we've also shown in our mouse studies that MDNA11 not only enhances the proliferation of naive CD8 T cells, but also activated effector CD8 T cells as well. So we're seeing multiple activities of MDNA11 in the tumor microenvironment where we see an expansion of effector CD8 T cells naive CD8 T cells and NK cells, and I think we believe that's probably the best approach. Mahan, do you want to add anything to this?

Thank you, Fahar. I think you covered it well. Generally speaking, as we know, NK cells nowadays representing a new strategy for cancer immunotherapy, and most of the new research emphasizing on the NK cell roles. NK cell based therapy become promising and advanced scientific topic and scientific approach to be applied in clinic. NK cells innate lymphocytes holding the spectrum of functional effect on anti-neoplastic and anti-cancer and the foremost effector cells against tumor and the innate immunity and greatly heterogeneous tumor microenvironment would require NK activity. As we know, there are NK cell therapy in the form of chimeric antigen receptor. And with reference to safety, we haven't seen those claims actually in clinic having a detrimental safety effect on those patients. the activity of NK cells and the surveillance and completion of the immunity cycle does indeed require NK activity to prevent recurrence and to have a durable immune response.

Yeah, that makes sense to me. Just one quick follow-up. How are you planning on unveiling the year-end update? Should we expect a press release and a conference call or just a press release? Any thoughts around that? Then I'll hop back into the queue. Thanks.

Yeah, there isn't any major conference coming up before the end of the year, so most likely it will be in the form of press release. Man, any thoughts? I believe that would probably be the best way for us to communicate those data.

Yes, I think we need to gather as much information, as much data, and we'll look into a number of ways of communicating it either via email company updates or preliminary papers to be submitted in the subsequent conference. Par, do you have anything else to add?

No, I think that's good enough. We might even, you know, based on that, following the press release, we might just have a a call similar to the one we've got right now so that there are questions that could be asked at that point. Okay. Thank you, Matt.

The next question is from David Martin of Bloom Burton. Please proceed with your question.

Thank you for taking my questions. So back to the safety question in NK cells and other things. What doses have you started to date and how many patients are in the trial? And you mentioned that there'd be no DLTs or SAEs. Do you have commentary on how well the patients are tolerating the drug?

We will provide all that information at the end of the year. So we'll sort of compile the full set of results. from the patients that have enrolled in the early cohorts so that we can provide context within not only the patient data, but also provide additional data that we collect from blood analysis, et cetera, so that we can provide a comprehensive set of results at the end of this year. So we are in that phase of dose escalation. You mentioned how many patients we plan to enroll. It's going to be approximately 80 patients. We estimate about 20 patients in the monotherapy dose escalation phase.

And how many patients have enrolled to date?

We provide that update at the end of this year.

Okay. Okay. Okay. Um, switching over to MDNA 55, uh, you talked about things that were underway so that once a partnership secured, uh, it can move quickly. Um, that sounds like you are still negotiating for MDNA 55, but I'm wondering if you can provide some color on that or there are multiple parties, one party, um, What's the profile of the interested parties and what are you expecting as far as a partnership in as much as you can answer any of that?

All right. Yes, good question. I have to basically say that we are in active discussions with companies that are covering various geographic areas. So with that said, if we complete a partnering deal, we will make an announcement and be in a position to comment further with respect to the type and company that we are working with. So generally, we can say that the partnering process for MDNF55 is progressing well. We are confident that a transaction would be completed. However, we cannot at the moment provide specific timelines, but we'll update the shareholders as soon as we're able to do so.

Okay, and just a quick housekeeping. When Liz says you have enough cash to the end of 22, that's calendar 22, and does that require some partnership dollars, or can you get there with what you have on the balance sheet?

Yeah, that's... Sorry, Fahar.

Go ahead. No, go ahead, Liz. I was going to ask you to answer that.

Okay. Yeah, that's calendar 2022, and it does not factor in any cash proceeds other than what we currently have on the balance sheet.

Okay, thanks. That's it for me. Thank you.

The next question is from Kumar Raja of Brookline Capital. Please proceed with your question.

Thanks for taking my questions and congratulations on all the progress. With regard to the clinical trial sites in Australia, how many sites do you have on board and when do you expect additional sites to come on board? And with regard to the U.S., when do you think you'll be able to start recruiting patients here?

Right. So with Australia, as you know, that's the geographic location where we first started enrolling patients. We have set a target of having at least four to six sites in place. Most of them are in place or nearing being in place and ready to enroll. We certainly have the enrollment currently underway. in Australia, as far as US is concerned. As you know, we just received the approval from the FDA for the IND submission. And as we go through the IRB process or the ethics review at different centers, we are proceeding with those activities as well. We expect to have about eight to 10 sites in the US also enrolling patients. We think the first patient we are expecting will be soon after New Year, will be the first patient in the U.S.

And the expectation is that the patients in U.S., they can potentially directly go to the monotherapy expansion phase?

Depending on how far we are, but it will be mostly, we will expect that there will be dose escalation continuing at that time in January. So we expect U.S. patients to also, on U.S. sites, to be also enrolling in the escalation phase as well.

Okay. And finally, in terms of your efforts in autoimmune diseases, are you doing anything in that front? Sorry, can you repeat that question? I'm talking about focus on autoimmune autoimmune diseases. You used to have some preclinical programs in autoimmune diseases earlier. Right.

Yes.

Yeah.

Right. So yes, there is ongoing activity currently where we are using or exploiting the different IL-2, IL-4, and IL-13 assets or super kinds that we currently have in the currently in discovery phases looking at different autoimmune diseases as well as neuroinflammation as the activities that are currently being evaluated from a discovery perspective. Yes, those activities are actively underway.

Thanks so much.

You're welcome. The next question is from David Botts of Zach's Small Cap Research. Please proceed with your question.

Hey, good morning, everybody. So you've previously indicated that for the dose expansion phase of ability, you're going to focus on renal cell, carcinoid, and melanoma patients. And I'm just wondering if there is a limitation for these early patients as far as tumor type goes.

Yes. Well, I'll pass it on to Man. Maybe you can elaborate a bit more on that, the dose expansion phase.

Sure. Yeah. Thanks for the question. So for the dose expansion, and as the study design, which is also on clinicaltrial.gov, what we will have, we'll have one-to-one-to-one ratio of melanoma to RCC to other selected tumors. Now, the other select tumors I'm going to go over them quickly include sarcoma, triple negative, breast cancer, pancreatic, as indicated earlier, non-small cell, both variant squamous and non-squamous, non-small cell lung cancer, colorectal gastric, biliary tract, basal cell carcinoma, bladder, Merkel cell carcinoma, squamous cell carcinoma of head and neck, cutaneous, and OBGYN tumors, namely uterine, ovarian, and cervical cancer. So those are included in the expansion in the one-to-one-to-one ratio between melanoma RCC and this select tumors. In the escalation, all those patients with all those tumors are actually entering those escalation portion of the study as we speak. So we don't only have melanoma or RCC, we have also additional tumor types from the cluster tumors I've just mentioned. With the expansion combination, the same ratio is maintained, 1 to 1 to 1 ratio of melanoma to RCC to other selected tumors as well. Hopefully that addresses your question, and thank you very much for the question.

Yes, that's very helpful. Thank you. And as far as the BISCUITS program goes, I'm wondering if you could go over Maybe what are the most important considerations or what are the things that you're looking at that are most important for selecting a lead candidate from that program?

Well, thanks for that. What we are working on is a number of different potential fusion partners as part of the BISCUITS platform. And these two different bifunctional molecules really we have, I think, previously indicated different strategies where we have looked at two different super kinds of being part of the biscuit. We've had a opportunity to share with you data on a antibody, which is a targeting antibody together with a super kind, as well as data on a checkpoint inhibitor fuse to our super kind. So these are different various potential fusion partners. We are screening these and of course the focus as far as oncology is concerned to identify two distinct functional activities that would allow us to then subsequently create a molecule or test a molecule that has providing synergistic effect, very much being based on clearly different tumor types. So we are looking at that very, very closely. At the moment, it's difficult to specifically mention what is our preference. We'll definitely be able to share a lot more data and more information towards the end of the year.

Okay, thanks for that, and thanks for taking the questions. You're welcome.

The next question is from David Martin of Bloomberg. Please proceed with your question.

Yeah, thanks for letting me have the follow-up. Man, in his earlier comments, contrasted your approach to the not alpha approach. I'm wondering if you have some comments on the not gamma approach.

Right. So the not alpha approach, I think, as you know, has been a focus of others at the expense of of losing out also on the beta approach. And we've seen that with the pegylation approaches that have been perceived by others, where an attempt to create a not alpha IL-2 unfortunately has also resulted in a molecule that has a weaker beta. That therefore, not surprisingly, has not shown promising single agent activity so far. Our approach, as you know, is very distinct in the sense that although we are proceeding with a not-alpha approach, we also have dramatically improved the binding affinity towards beta. So that beta-only strategy is crucial. We feel that the beta-only approach would subsequently require an active gamma-based signaling approach so that they are able to fully take advantage of the selectivity for binding to beta and signaling through gamma. And this way, you are able to create a molecule or our molecule is such that it's not only stimulating your effector CD8 T cells, but to engage your naive CD8 T cells, your NK cells, you also require signaling through gamma. Because by blocking signaling through gamma, you're not going to be able to engage your naive CD8 T cells and therefore not build a population of inexperienced CD8 T cells that is essential. You're not going to be able to benefit from any potential activity that is required for NK cell activation. So we believe that engagement of both beta and gamma is essential. We certainly believe in gamma blockade in an autoimmune setting, which is something that has been demonstrated by work that has been done by Chris Garcia's lab and for which we already have a program of our own where high binding to beta subsequently with reduced binding to gamma clearly shows potential in autoimmune disease. So I feel that the approach that we've got here with beta binding and gamma signaling is absolutely essential to get a full spectrum of activity from an anti-tumor perspective so that we are engaging naive CD8 T cells, effective CD8 T cells, as well as NK cells. So that's what we believe is the best approach.

Okay, thank you. There are no additional questions at this time. I would like to turn the call back to Fahar Merchant for closing remarks.

Thank you all for being on the call today. Really appreciate the calls and questions and answers that we received. We will certainly keep you all updated as we progress to the end of this year with respect to any updates, any new results, et cetera, over the coming weeks and months. Thank you again for joining the call and look forward to giving you more updates in the coming weeks. Thank you. Operator?

Ladies and gentlemen, this concludes today's presentation. Thank you once again for your participation. You may now disconnect.