Medicenna Therapeutics Corp.

Greetings, and welcome to Medicine and Therapeutics Corp. First Quarter Fiscal 2023 Earnings Call. At this time, all participants are in a listen-only mode. A brief question and answer session will follow the former presentation. If anyone should require operator assistance during the conference, please press star zero on your telephone keypad. As a reminder, this conference is being recorded. It is now my pleasure to introduce your host, Dan Ferry of LifeSci. Thank you. You may proceed.

Thank you, operator. And thank you all for participating in today's conference call. This morning, Medi-Sena issued a press release providing financial results and corporate updates for the quarter ended June 30, 2022. If you have not yet seen the press release, it is available on the investor page of Medi-Sena'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. All statements other than statements of historical facts shared during this call, and that 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 MDNA 11, MDNA 55, and the BISCUITS programs, the potential of the SuperKind platform, preliminary clinical data, partnering activities, cash runway, and the presentation of additional data and other milestones are forward-looking statements that are subject to risks and uncertainties. There can 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 may cause actual results to differ materially from the company's expectations include the risks detailed in the annual information form management's discussion analysis in Form 20F 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 good morning, everyone. During today's conference call, I'd like to focus on MediCenter's most recent presentation of exciting clinical data providing preliminary evidence of MDNA 11's single agent anti-cancer activity. This discussion will then be followed by comments from our Chief Financial Officer, Liz Williams, who will report our first fiscal quarter financial results and also provide you with an overview and rationale for our most recent financing. While we acknowledge that this financing was costly, it does bring with it a number of key positives. First, a selection of fundamental healthcare-focused institutional investors participated in this financing. Second, it removes the financing overhang for the foreseeable future in these very difficult markets. Third, it allows us to build momentum. on the back of positive clinical data that I will share with you shortly, and to complete the combination of the phase one to ability study. Fourth, it enables us to advance one of our novel biscuit candidates for IND readiness. And finally, and most importantly, puts us in a sound financial footing to pursue clinical collaborations in the combination arm of the Ability Study. As I mentioned, Liz will provide additional clarity later on. For those interested in hearing a broader update on recent progress made with MBNA 55 or our Preclinical Biscuit Program, please listen to the replay of our last earnings call which occurred on June 22nd and is available on our website at www.medicina.com. Getting back to our lead program, I will start by reminding everyone that MDNA 11 is a beta-only, long-acting IL-2 super agonist. It has been engineered specifically to overcome the shortcomings of native IL-2, which is FDA-approved and known as pro-lucid. Prolucan's shortcomings are mainly as a result of its severe toxicity, poor pharmacokinetic profile, and mediocre affinity for the key receptor found on cancer-fighting immune cells, namely the IL-2 receptor beta. These limitations necessitate dosing Prolucan every eight hours for five days continuously and at high doses to make up for its inability to stimulate cancer-fighting immune cells that rely on binding to the beta receptor, which in turn causes severe toxicity, requiring the treatment to be administered in the ICU. Other competing programs have attempted to overcome Prolucan's shortcomings through various techniques, such as pegylation, but these have been unsuccessful for a variety of reasons I will discuss later. In the design of MDNA11, we have taken a very rational but differentiated approach to overcome Proleukin's shortcomings. First, using directed evolution, MDNA11 was engineered with five mutations that confer a 30-fold improvement in affinity for the IL-2 receptor beta, allowing mRNA-11 to more potently stimulate the cancer-killing immune cells that subsequently drive clinical response to IL-2 therapies at low doses. Second, instead of using suboptimal masking technologies such as pegulation or steric hindrance, we inserted two additional mutations to abolish its affinity for the IL-2 receptor alpha, which is associated with both toxicity and immunosuppression of proleukin and other IL-2 agents that retain binding to the alpha receptor subunit. Finally, unlike any other IL-2 in development, we have incorporated an albumin scaffold into the molecule to improve its half-life while at the same time exploits our human's ability to localize in the tumor and tumor-draining lymph nodes. As you know, we are advancing MDNA 11's clinical development through the ongoing Phase 1-2 Ability Study. The primary objectives of this trial, as is the case with all first-in-human Phase 1-2 trials, are to evaluate MDNA11's safety, PK, PD, and establish the recommended Phase II dose required for the dose escalation portion of the trial. Once the recommended Phase II dose is established, the secondary objective of the trial would be to determine the potential antitumor activity of MDNA11 as a single agent and also in combination with a checkpoint inhibitor during the dose expansion portions of the trial. Key objectives of the trial are therefore to identify a recommended phase two dose during the dose escalation stage of the trial and subsequently build a body of clinical evidence that demonstrates MDNA11's potential as a best-in-class IL-2 agonist during the dose expansion portion of the Ability study. Seeing promising clinical activity during the dose escalation portion of the trial is indeed very reassuring. We presented Ability's most recent data at the Cytokine-Based Drug Development Summit held in Boston in late July, and we were very pleased to show the trial's results to date. Let me elaborate. First and foremost, we have not seen dose-limiting toxicities in any of the 14 patients treated at each of the four dose levels. There have been no dose interruptions, dose de-escalation, or treatment discontinuation in any of the patients due to safety issues with mDNA11 being administered via IV infusion once every two weeks. Furthermore, as expected, preliminary PK studies have shown dose-dependent increases in C-max and area under the curve without any signs of immunogenicity upon repeated infusions. Also, fueling our optimism on the outlook of the ability study are encouraging pharmacodynamic data that provides strong mechanistic support for the tumor control results that I will share later. Pharmacodynamic data have shown multifold increases in anti-cancer CD8-positive T cells and natural killer cells that are greater than those achieved with competing agents administered at equivalent IL-2 doses. This was accompanied by limited or no stimulation of eosinophils or Tregs, including ICOS-positive Tregs. This is significant as ICOS-positive Tregs are highly immunosuppressive and linked to resistance to IL-2 therapy. In addition, high eosinophil counts are associated with vascular leak syndrome which is one of Proleukin's most serious side effects. These pharmacodynamic results highlight what differentiates MBNA11 from competing IL-2 variants. As we have detailed on prior earnings calls, these competing variants have reduced affinity for the IL-2 receptor beta compared to Proleukin, which further diminishes activation of the immune cells that drive clinical efficacy. In addition, some competing variants maintain residual affinity for the IL-2 receptor alpha, increasing the potential risk of toxicity and unintentional activation of pro-tumor regulatory T cells. As mentioned earlier, mDNA11 was designed to have enhanced IL-2 receptor beta affinity and no affinity for the alpha subunit. We believe our design approach is superior. With the Ability Study, we aim to gather clinical evidence showing mDNA11 has the intended biological effects and early signs of efficacy in patients that would not typically be expected to respond to immunotherapy. A very exciting result indeed. that we plan to verify with continued dose escalation. Moving on to therapeutic activity of MDNA11, we have seen encouraging early signs of anti-tumor activity from abilities low and mid-dose escalation cohorts. At this time, four of 10 evaluable patients achieved tumor control with MDNA11 monotherapy. Patients achieving tumor control included two receiving 10 micrograms per kilogram doses in the second dose escalation cohort. The tumor types for these patients were sarcoma and metastatic melanoma. An additional sarcoma patient achieved tumor control in the third dose escalation cohort, which evaluated mDNA11 at the 30 microgram per kilogram dose. Finally, a patient with pancreatic cancer also achieved tumor control in the fourth dose escalation cohort, where MDNA 11 is administered initially at 30 micrograms per kilogram for the first two doses, followed by a step-up dose of 60 micrograms per kilogram. We also just disclosed last week, in conjunction with our USD 20 million financial raise, that the pancreatic cancer patient in cohort four who had initially achieved stable disease at the first 12-week scan subsequently showed additional tumor shrinkage at week 16 consistent with an unconfirmed partial response. This is significant. Prior to entering the ability study, the pancreatic cancer patient had surgery followed by three systemic therapies including first, Folfirinox, which is a combination of four different chemotherapies on which the patient progressed, followed by a second, a combination treatment with Abraxane and gemcitabine, which the patient could not tolerate, and finally, treatment with an immune checkpoint inhibitor, Keytruda, which again, the patient could not tolerate. Upon entering in the MDNA 11 trial, the patient had two metastatic tumors that had spread from the pancreas to the liver, and both of those decreased in size at week 12. However, it was not enough to be considered a partial response. A second scan at week 16 showed that both tumors had further decreased in size, with the total reduction being more than 30%, for an unconfirmed partial response. According to the protocol and resist 1.1 criteria, a second scan on or after 28 days after the most recent scan is required to confirm a partial response. We expect the patient will have the second scan in the coming weeks. There is no assurance that the tumor will not progress or the patient will not have clinical signs of progression or new lesions will not appear prior to the next scan at week 20. A melanoma patient who progressed following two lines of immunotherapy also achieved durable, stable disease for over nine months, having entered the study at the low dose of only 10 micrograms per kilogram, which is the second dose cohort, and subsequently escalated to the 30 micrograms per kilogram and more recently to the 60 micrograms per kilogram dose levels. This patient has not achieved a threshold for a partial response and is also expected to receive the first scan next month after commencing the treatment at the 60 microgram per kilogram dose. We are eagerly awaiting the results of the next scan for the pancreatic cancer patient with the unconfirmed partial response to determine if it is confirmed. along with the scans of four additional patients from dose level four in the 60 microgram per kilogram dose cohort that have yet to receive their first scan at 12 weeks. We expect to obtain scans from up to six patients over the next few weeks, and we shall be able to provide an update on all these patients by the end of September. These include three patients with melanoma, one with renal cell carcinoma, one with esophageal cancer, and one patient with pancreatic cancer. Though unconfirmed, we believe clear evidence of monotherapy efficacy in a challenging immunotherapy-resistant tumor type is a major achievement for MDNA11, which validates the best-in-class pharmacodynamic profile potential observed throughout dose escalation. To the best of our knowledge, there is no published data showing systemic administration of IL-2 monotherapy effectiveness in pancreatic cancer. Pancreatic cancer is one of the most deadly cancers out there, with a five-year survival of less than 10%. We have what we are looking for, an unconfirmed PR as preliminary evidence that MDNA11 is viable as a monotherapy. Although we have not conducted any preclinical studies in models of pancreatic cancer with MDNA11, an independent research group demonstrated that an oncolytic virus armed with MDNA109, a first-generation version of MDNA11, showed remarkable anti-tumor effects in a hamster model of pancreatic cancer with over 62% of monotherapy complete response in this highly aggressive model of pancreatic cancer. We believe MDNA 11 could deliver additional responses as we continue to push dosing higher, followed by a comprehensive update from dose escalation in the fourth quarter of this year. the tumor response data from abilities early and mid-stage dose escalation cohorts provide an early sign of MDNA 11 single agent activity. We view this as a very encouraging finding, especially when considering several aspects of the trial's patient population. First, there's the tumor types in which we have observed disease control. As mentioned, These include sarcoma and pancreatic ductal adenocarcinoma, two cancers that are historically very difficult to treat and highly resistant to immunotherapies. Second, there is the treatment history of the abilities studies patients. All 14 patients enrolled in the trial to date have failed between one and four lines of prior systemic therapy including 11 who relapsed on or were unresponsive to checkpoint inhibitor therapy. And third, there is the information we can glean from baseline measurements of lymphocyte counts. Lymphocytes include CD8 positive T cells and natural killer cells, which are the cancer-killing effectors of IL-2 therapies. Importantly, high lymphocyte counts have been shown to correlate with response to proleukin. When looking at baseline lymphocyte measurements made in the ability study to date, we see that these counts are much lower than those seen in prior studies of proleukin. This suggests that the majority of patients entering the ability study have tumors that are highly immunosuppressive an extremely difficult retreat, consistent with what we'd expect based on the types of patients enrolled and the clinical histories. Based on this information, we amended the trial protocol to ensure that subsequent patients will have baseline lymphocyte counts that are higher and more in line with what we would expect to see MDNA 11's dose expansion portion of the Ability Study. This amendment went into effect with our fifth dose escalation cohort, which evaluates patients receiving 230 microgram per kilogram priming doses of MDNA 11, followed by a step-up to a fixed 90 microgram per kilogram dose. Given the early signs of clinical activity we've seen with lower doses of MDNA 11 in patients with highly immunosuppressive tumors, we are very much looking forward to data from this and subsequent cohorts where we hope to see more meaningful signs of efficacy. Looking ahead, we are currently enrolling patients in Ability's fifth dose escalation cohort with no dose-limiting toxicities reported in the trial to date. With the step-up dosing protocol now being administered to patients, we are exploring higher doses during this portion of the study and aiming to further increase our chances of improving patient outcomes in a single agent setting. Next month, we expect to report additional anti-tumor activity data from the trial's fourth dose escalation cohort. In the fourth quarter of calendar year, we expect to announce initial anti-tumor activity data from the trial's fifth dose escalation cohort. Looking ahead into calendar 2023, we expect to report anti-tumor activity data from Ability's single-agent expansion and combination phases in the middle and second half of the year, respectively. For enrollment into the expansion phases, we intend to hone in on patients with a select number of tumor types to better inform future studies. Two tumor types that will be of particular interest will be metastatic melanoma and renal cell carcinoma for which Prolucan has received FDA approval, and potentially other tumor types known to be cold and unresponsive to immunotherapies such as pancreatic cancer. A key goal of the Ability Studies next readouts will be to generate additional evidence of mDNA11 single agent activity. Doing this will further de-risk and inform mDNA11's development and may present a critical inflection point for the company and a better treatment paradigm for patients that have failed to benefit from other immunotherapies. So with that clinical review complete, I will hand off to Liz so she can run through our financial results from the fiscal first quarter and provide an overview of the recent financing. Liz?