Earnings Call: Q4 2021

May 28, 2021

Hello, and welcome to Medicina Therapeutics Fiscal Year 2021 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. Earlier today, Medicina issued a press release providing financial results and corporate updates for the fiscal year ended March 31, 2021. If you have not 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-eleven, MDNA-fifty five and biscuits programs, the potential of the Super Kind 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 applicable securities regulators from time to time in Canada and the United States. The reader is 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'll turn the call over to Doctor. Fahar Merchant, President and Chief Executive Officer of Medicena Therapeutics. Fahar? Thanks, Dan, and thanks to all listening for joining us on the call today to discuss our fiscal year 2021 corporate update. In addition to that, I'm joined by Doctor. Manmousin, our Chief Medical Officer Doctor. Kevin Mulder, our Chief Scientific Officer Nina Merchant, our Chief Development Officer and Liz Williams, our Chief Financial Officer. Fiscal year 2021 was Medicina's strongest and most productive year yet despite the unpredictable environment caused by the pandemic. We achieved key clinical, scientific and corporate milestones that have left us well positioned for sustained success. On today's call, we will review some of these recent accomplishments, give an update on the current status of our pipeline programs, introduce the new members of our executive team and provide an outlook for fiscal year 2022 and beyond. So let us start with some of our accomplishments over the past year, beginning with our program focused on mDNA11, our long acting IL-two superagonist. Milestones in this program include the presentation of non human primate data showing that mGna11 selectively stimulates prolonged expansion of anticancer immune cells without causing unwanted side effects, such as the generation of antigleric antibodies, hypotension associated with vascular leak syndrome or cytokine release syndrome. We also presented additional preclinical data that further highlighted MDN11's best in class potential by demonstrating its durable and potent therapeutic efficacy both as a monotherapy and in combination with checkpoint inhibitors in urine tumor models. To prepare for the initiation of a clinical study in 2021, we completed our scientific advice meeting, which is similar to a pre IND meeting with the United Kingdom Medicines and Healthcare Products Regulatory Agency. During the meeting, the agency agreed that our CMC preclinical and Phase IIIa clinical plans would be appropriate for submission of an investigational medical product dossier for a first in human study with MDN-eleven in the U. K. In addition, we are on track to submit a clinical trial notification to the Australian Human Research Ethics Committee this quarter in order to commence the Phase IIIa clinical trial of mdna11 in the Q3 of calendar 2021. Man will provide more information on our mdna11 clinical plans in the next few minutes. I'd now like to turn our attention to mdna55, our IL-four guided toxin targeting recurrent glioblastoma or R GBM, the most common and uniformly fatal form of brain cancer. Throughout the past year, we presented updated data from our Phase IIb trial in RGBM that demonstrated MDN55's potential to change the treatment paradigm in a high unmet need indication. These data showed that amongst an all covered population, a single MDLF55 treatment resulted in a greater than 100% increase in 2 year survival compared to an eligibility matched external control arm and a greater than 100% improvement in progression free survival compared to what is achieved with approved therapies. Thanks in large part to the robust external control arm study we conducted, the substantial magnitude of the effect observed in the Phase IIb trial as well as the significant unmet medical need in RGPM, the FDA recommended we conduct a landmark Phase 3 trial to support MDN A55's approval in this indication. This planned trial has an open label hybrid design that allows for 2 thirds of the control subjects to be from a matched external control arm. This was truly pioneering recommendation by the agency and to the best of our knowledge, this groundbreaking design may be the first in oncology to include a substantial external control arm in a trial designed to support regulatory approval. I will talk more about this trial as well as a recent publication featuring our Phase IIb data in a short while, but we'll say now that we remain in active discussions with potential partners to facilitate MDN A55's advancement. While the details of these conversations need to remain high rated at this point, We look forward to providing a more thorough update on these activities when appropriate. On the discovery and preclinical front, we also recently unveiled our bispecific supertank platform, which we refer to as biscuits. These novel molecules, which are fusions of 2 complementary superkines or a superkine and an antibody, such as a checkpoint inhibitor, have the potential to address critical unmet needs such as the treatment of cold tumors that do not typically respond to current immunotherapies. We recently presented some very exciting early data from this program at AACR, which Kevin will discuss later in this call. Now alongside our scientific and clinical accomplishments, we also achieved notable corporate milestones during fiscal 2021, such as our listing on NASDAQ and the strengthening of our Board via the addition of Doctor. Jack Zoltosky. This corporate momentum has continued into fiscal 2022 as we recently added Man and Kevin, 2 highly talented immuno oncology experts to our management team. As they will tell you in a few moments, our ability to recruit such ideal candidates was due in large part to the clinical and scientific milestones I just mentioned, which showcased the best in class and 1st in class potential of our assets together with the power and versatility of our Super Kind and biscuits platforms. I will now let you hear from these team members, starting with our Chief Medical Officer, Doctor. Maayan Moosin. Maayan, please go ahead. Thank you, Fahar, and good morning, everyone. Today, I'll be talking about the MDN-eleven program. First, I'd like to introduce myself and explain exactly why I'm so excited to be part of the Medicina team. I joined Medicina earlier this month and have deep expertise in immuno oncology and IL-two specifically. I've conducted more than a dozen clinical trials sponsored by multiple industry leaders including AstraZeneca, Hoffman LaRoche, Nerve, Novartis, Eli Lilly, Johnson and Johnson and Bayer. I've also designed, executed and led clinical development programs and oncology trials for a variety of biotech companies, most recently working at Nestor Therapeutics prior to joining Medicina. One of the primary drivers behind my decision to come on as Medicina CMO was MDN-eleven's robust preclinical data set, which demonstrates the molecules best in class potential and clearly differentiates it compared to approved therapies on competing IL-two variants in development landscape. As those of you familiar with IL-two space likely know, recombinant human IL-two while approved for the treatment of metastatic melanoma and renal cell carcinoma has some major shortcomings. These shortcomings stem from the fact that recombinant IL-two targets the primary receptor, which includes CD25. Emulation of CD25 leads to the activation of TRx, which inhibits anti tumor immune response and is associated with unfavorable prognosis in patients with various types of cancers as well as causing extreme toxicity, which necessitates the dosing of patients in intensive care unit. Additionally, the dosing is required every 8 hours for 9 days due to recombinant human IL-two's poor pharmacokinetic properties. Now what I find so exciting about the MDN-eleven is not only that it can overcome these shortcomings, but how it overcome these shortcomings. Using the superkines platform, Medicina has engineered MDN11 to have dramatically increased affinity for the CD122 subunit of the IL-two receptor, while having reduced affinity for the CD25. This is significant as stimulation of the CD122 is key for the activation of the cancer killing immune cells that are the target effectors of IL-two therapy. Additionally, the inclusion of human albumin in the molecule improves the molecules half life and bioavailability in the tumor tissue. Its fusion to a second protein, in this case albumin is a key point of differentiation for MDN-eleven compared to competing IL-two variants, many of which rely on pegylation to improve half life. In general, pegylation requires a complex manufacturing process that is well known to not only affect product consistency, but can also unintentionally mask the active site of the protein and reduce its efficacy. We have robust preclinical data set demonstrating how MDN11 enhanced affinity for CD122 and reduced affinity for CD25 positions it to be best in class. This data set shows that compared to competing IL-two programs, MDN-eleven is able to preferentially stimulate cancer killing effector P and NK cells as opposed to Tregs. Thanks to this high selectivity, Z molecule has also shown impressive efficacy, both alone and in combination with checkpoint inhibitors in preclinical tumor models. Additionally, nonhuman primate studies indicate that the molecule does not cause vascular leak syndrome or cytokine release syndrome as has been seen with other programs. It was these best in class properties of MDMA-eleven that led me to realize the power of the Supertank platform and ultimately drove my interest in joining Medicenna. So now that I've told you a little bit of how I got here, let me talk about the plan moving forward. We're currently in the process of advancing MDKNA11 into Phase IIIa clinical trial in Australia and the United Kingdom followed by expansion to the United States. We have chosen to begin the trial in these countries rather than United States for two reasons. 1st, starting in these countries allows us to begin the dose escalation portion of the trial at doses that are closer to therapeutically effective doses. 2nd, the United Kingdom and Australia have a relatively higher prevalence of checkpoint inhibitor naive patients compared to the United States, which may help with study enrollment. We continue to make good progress towards initiation of our trial as we wind down our GLP toxicology studies and are in the process preparing their regulatory package for submission in Australian agencies. This submission is expected by end of June. Additionally, we have chosen a CRO for the trial and site selection is already underway in Australia. Initiation of the trial is expected in the Q3 of calendar 2021. With regards to trial design, we plan to begin with a dose escalation and DNA-eleven monotherapy phase, which will then be followed by a dose expansion phase. This dose expansion phase will evaluate both as well as MDN11 in combination with a checkpoint inhibitor. Another key element of the trial design is a planned collection of pre and on treatment biopsies, which will allow us to collect valuable biomarker data that may speak to the MDN-eleven's mechanistic activity in humans. Looking ahead, we expect to provide a preliminary update on any available safety PKPD and biomarker data by the end of this year. The first set of monotherapy efficacy signals from the trial are expected in the first half of twenty twenty two. Shifting gears now, I would like to ask Wahad to speak briefly about our Phase 3 Ready MDna-fifty five program. Thank you, Ivan. As I mentioned earlier, MDna-fifty five is an IL-four guided toxin targeting recurrent glioblastoma. Findings from the Phase 2b trial evaluating MDN55 in RGBM were recently published in the peer reviewed journal Clinical Cancer Research. These findings indicate that early determination of progression free survival with the modified RENO criteria employed in the study may be a strong surrogate for overall survival in RGBM. These results supplement previously presented findings showing an 81% tumor control rate based on modified renal and a median overall survival of 15.7 months, which represents a greater than 100% improvement when compared to a well balanced external control arm. As a reminder, the patient population included all mbna55 treated trial participants with high IL-four receptor expression and participants with low IL-four receptor expression that received a high dose of mbna55 treatment. We believe these positive modified RANO PFS and overall survival data bode well for the outcome of the PLANT Phase III trial, which has overall survival as a primary endpoint. As I mentioned earlier, this planned trial utilizes an innovative open label hybrid design that allows for 2 thirds of the control arm subjects to be from a well matched external control arm. This design will reduce the cost and timelines associated with completing the trial by reducing the overall number of subjects needed to achieve the primary endpoint, which will be based on a one to one analysis of the MDN55 treatment arm versus the pooled control arm. To ensure a near contemporaneous external control arm, we can include patients treated for RGBM over the past 5 years as there has been no substantive change to the RGBM standard of care during this time frame. We believe the FDA's recommendation to proceed with this first of its kind trial leaves MDN55 well positioned for success. The numerous benefits offered by the trial's hybrid design together with our robust clinical data set continue to drive our partnering discussions around the MDN55 F55 program. These discussions remain ongoing and we look forward to providing an update on their status at the appropriate time. With that, I will now hand it over to our Chief Scientific Officer, Doctor. Kevin Moulder. Thank you, Fahad. I'm very excited to be speaking on the call today and would like to start by introducing myself to those listening since I like Mann and also a recent addition to the Medicina management team. I joined Medicina with over 30 years experience in drug discovery and development in several fields such as protein design, antibody technology, autoimmune disease and immuno oncology. This includes my time at Biogen, where I ran a Predictive Medicine Department my time as CSO at Fstar Therapeutics, where I established the company's bispecific antibody technology and led the translational efforts to identify the program's 1st clinical lead. And my time as Chief Development Officer at Tusk Therapeutics, where I directed the development of an anti CD25 antibody. This antibody showed anticancer activity that stemmed from its ability to deplete Tregs while preserving IL-two activity on affected T cells and advancements in its development subsequently prompted the acquisition of TASK by Roche. At Menesina, I will be applying my knowledge from these experiences as we work to leverage the power of the Superkine and Biscuit platforms to advance 1st and best in class efforts towards the clinic. These platforms are powerful and versatile drug development tools and my desire to work with them was a key factor behind my decision to join Medocina. I'd now like to give a brief overview as to how these platforms work. I'll start with the super kind platform, which works by enabling the enhancement of natural interleukins through a process known as directed evolution. During this process, subtle changes are made to interleukins to modulate their desired properties, ultimately resulting in a library of tunable superkines designed to address the underlying mechanisms of a particular disease. Select superkines can then be engineered to further improve properties such as half life, as in the case of MDNA11 or to add new capabilities, such as the ability to deliver a payload of a cell killing toxins specifically to cancer cells as in the case with MDNA55. The natural progression of our supercom platform eventually led to the creation of our biscuit program, which we unveiled in March. Biscuits are highly versatile and powerful molecules that consist of a superkine fused to a second anticancer protein such as the checkpoint inhibitor or the second superkine. By combining molecules in this fashion, we can create immunosyserapeutic agents that incorporate 2 synergistic mechanisms of action and overcome the shortcomings of currently available therapies. At the AACR meeting last month, we presented data on one of these assets derived from our biscuit platform. The asset is designed to overcome the shortcomings of checkpoint inhibitors. As you may note, checkpoint inhibitors are designed to target tumors by enhancing the activity of cancer fighting immune cells. However, many tumors have immunosuppressive microenvironments that limit the efficacy of these therapies. Such tumors are referred to as being immunologically cold. And it was with these tumors in mind that we designed mdna19-four thirteen. As we discussed during our AACR presentation, MDN819-four thirteen consists of a super antagonist. It is designed to work via 2 complementary and synergistic mechanisms of action targeting both IL-two and IL-four thirteen signaling. I'll focus first on the IL-four thirteen mediated mechanism of action. The molecule is designed to modulate this signal activity by selectively binding the IL-thirteen receptor alpha subunit on the cells of its tumor microenvironment. This leads to a disruption in the IL-four thirteen signaling and ultimately the inhibition of an M2A polarization of tumor associated macrophages. This is significant as blockade of M2A macrophage polarization mitigates the protumoral effect of immunosuppressive microenvironments. Mitigating these effects can effectively turn a cold tumor hot, thereby making it susceptible to destruction by anticancer immune cells. Now with regard to IL-two's signaling, MDNA19,413 worked in a manner of very similar to MDNA11, preferentially targeting CD122 to enhance the activity of cancer killing affected C and NK cells. This IL-two driven agonist action complements the IL-thirteen driven antagonist activity I just mentioned, making MDNA19 413 a potential anticancer agent with the potential to effectively target cold tumors that are often resistant to current available therapies. But this potential was demonstrated in our recent AACR presentation. And while I won't go through the full data set, here are a couple of key points I'd like to highlight. First, the molecule will effectively enhance signaling in cancer, killing effect T and NK cells and reduce activation of protumor Treg cells. This was evidenced by a 209 fold and 90 fold enhancements in CD8 Treg and NK Treg ratios in vitro respectively when compared to native IL-two. 2nd, the molecules selectively bound and inhibited both IL-four and IL-thirteen signaling via the IL-thirteen receptor alpha-one subunits, which is normally associated with the protumal effects of M2A macrophages, while showing reduced affinity for the IL-thirteen alpha-two decoy receptors subunits. Compared to long acting Fc fusion of IL-thirteen, the molecule was approximately 2 40 times more selective for the alpha-one subunit compared to the alpha-two subunit. This selectively led to notable functional outcomes as MGNA19-four thirteen was able to potently inhibit IL-thirteen, IL-four signaling pathways and mitigate the polarization of M2A macrophages in vitro. Taken together, these results show how the biscuit platform can effectively combine the enhanced immune signaling properties of multiple cytokines into a single bifunctional compound. In the case of MDNA19-four thirteen, this resulted in the novel molecule with the potential to enhance the power of the immune system to address critical unmet need. Looking forward, I'm eager to lead the continued development of MDNA19-four thirteen as well as our Board of Biscuit program, we expect to declare our 1st lead candidate for the program in the Q4 of calendar 2021. With that, I'd like to hand off the call now to our CFO, Liz Williams, who will present our financial results for the fiscal 2021. Thanks, Kevin, and good morning, everyone. Before I begin, I would like to note that all references to dollar amounts are in Canadian dollars, unless otherwise noted. I'm pleased to report that over the past fiscal year, Metasana was able to establish and maintain a strong financial foundation while advancing our pipeline of cytokine based immunotherapies. Svetafana had cash, cash equivalents and marketable securities of $40,400,000 as of March 31, 2021. These funds provide the company with sufficient capital through late 2022 based on its current plans and projections. Net loss for the year ended March 31, 2021 was $17,300,000 or $0.35 per share compared to a net loss of $8,300,000 or $0.26 per share for the year ended March 31, 2020. The increase in net loss for the year ended March 31, 2021 compared with the prior year was primarily a result of increased research and development expenditures related to the MD and A-eleven program as well as costs associated with the NASDAQ listing, in particular directors and officers' insurance premiums as well as no reimbursement under the grant from the Cancer Prevention and Research Institute of Texas in the current year period. Research and development expenses of $10,900,000 were incurred during the year ended March 31, 2021 compared with $5,900,000 incurred in the year ended March 31, 2020. The increase in research and development expenses in the current year is primarily attributable to higher CMC costs associated with GMP manufacturing of MD and A-eleven for the planned Phase IIIa clinical trial, increased discovery and preclinical expenses associated with GLP compliant, MD and A11 IND enabling studies as well as discovery work on the biscuit platform, increased regulatory costs associated with preparation for the end of Phase 2 meeting for mdna55 as well as regulatory activities associated with preparation for the initiation of a Phase IIIa clinical trial for mdna11. And finally, no reimbursement of expenses with respect to the CPRIT grant in the year ended March 31, 2021 compared with $1,000,000 in the year ended March 31, 2020. General and administrative expenses of $6,500,000 were incurred during the year ended March 31, 2021 compared with $2,400,000 during the year ended March 31, 2020. The increase in the expenditures year over year is primarily attributable to increased directors and officers liability insurance premiums due to our NASDAQ listing as well as higher legal fees and listing expenses in the current year period due to activities associated with the NASDAQ listing, filing a shelf prospectus in both Canada and the United States, qualifying our common shares of the depository trust company and other current corporate initiatives. For further details on our financials, please refer to our financial statements and management's discussion analysis, which will be available on SEDAR and EDGAR, respectively. With that, I'll now hand the call back over to Fahar. Thanks, Liz. Before we move on to the Q and A, I'd like to emphasize how proud I am of our team for all that they have accomplished over the past fiscal year. They showed a tremendous amount of talent and dedication amid the pandemic, which enabled us to generate strong clinical and preclinical data across our pipeline. This has left us poised to achieve a steady cadence of value creating milestones over the next year as we work to drive our sustained growth and most importantly improve the lives of patients. With that, we'll now open the lines for questions. Operator? Thank Our first question is from Matt Felder with Oppenheimer. Please proceed. Hey, thanks guys. Thanks for the questions and welcome to the new members of the C suite. Farhar and Man, appreciate the details on the planned Phase 1. Maybe if we could just get a little bit more granular. Have you actually nailed down or agreed upon with Australia or U. K. A start dose yet? And based on preclinical model, how long do you think into dose escalation it might take us until we get into a therapeutically active range? Right. Thanks, Matt. Thanks for calling in. Appreciate the question that you've asked. Clearly, as I'll pass it on to Man, so he can elaborate a bit more. But suffice it to say that, as I mentioned earlier on that we had positive meetings with the MHRA regarding the CMC, the preclinical as well as the clinical plan. And therefore, that has been reviewed and we've received comments and incorporated those in our dossier that we're preparing right now. With respect to dosing and etcetera, I'll pass it on to Mann. Perhaps you can elaborate a bit more. Mann? Thank you, Fahar. So at this point in time, we won't be disclosing our first in human dose or give you a projection regarding how many escalations would we need before getting into recommended Phase II dose and hitting an MTD level. But we will continue to provide frequent updates and progress towards initiation of the trial in Australia, dosing the first patient. And as indicated earlier, we will be communicating earlier results from the available patient population dosed throughout this year by end of 2021. Thank you, George. Okay. And yes, and I'll also add to that, of course, the discussions with MHRA, for instance, they were keen to make sure that the first cohort would get a dose that was close to therapeutically active and that is remains our plan. And once we have shared the protocols with the regulators and ethics committees and those have been approved, we'll be much better able to disclose the dosing plan in subsequent disclosures that come by. Okay? Got you. Okay. Maybe I could just sneak one question in then about the safety profile. Obviously, the IL-two space in general, safety is a potential concern and kind of striking that right balance between safety and efficacy is kind of the Holy Grail, I think, as we see it. So are you using any as you think about your Phase 1 trial, are you using any lessons learned from your competitors, such as prophylactic hydration to reduce the risk of hypertension? Anything that you can kind of incorporate into the Phase 1 trial that you think could lower any safety risks? Thanks. Well, first, I'll just give my brief comments. Suffice it to say that, of course, all the regulator agency ethics committees who are familiar with the ongoing studies with different IL-two programs that are in the clinic at the moment would always want to ensure that we had appropriate language and procedures, protocols, etcetera, to address those. So that would be expected from any ethics committee, but I'll sort of also let Maan supplement that. Yes. Thank you, Fahad. It's a good question. So, yes, absolutely, all the above. We will use all the lessons learned from agents in the IL-two landscape. All the lessons learned, all the adverse events seen with this drug class myself worked on IL-twelve, high dose IL-two, pegylated IL-two. And as you know, there is a cluster of adverse events that we typically see with this drug class anticipated for all those agents and we will typically follow the usual institutional guidelines and specific guidelines in managing toxicities seen with this drug class and IL-two in specific. Thank you. Thanks guys. Looking forward to the next 12 months. Thank you. Thanks Matt. Our next question is from RK Ramakanth with H. C. Wainwright. Please proceed. Thank you. Good morning, Fahar and team. A couple of questions here. So, Doctor. Meechan, if you could help me kind of compare and contrast the MD and A11 program here versus the programs that have been are being run by Nektar, especially like Nektar-two fourteen, So we understand how these programs here are situated against what's out there in the competition? Thank you. Well, great. Thanks really. Sort of from a mechanistic point of view, let me just bring and then I'll let the further clinical aspects to be presented by Mann. But just from a structural perspective, the way the molecule has been designed is such that we have, as you know, engineered into the molecule 2 different key characteristics. The first one being that we have knocked out the binding or inserted mutations that would block binding to CD25. And second of all, we have inserted mutations that dramatically increase the affinity for CD122 and therefore selectively stimulating affected T cells, NK cells and naive T cells as well. So that's the key aspect that's differentiated. And then of course, the way we have approached this molecule with respect to how we extend the half life is to use albumin fusion instead of pecretive approaches that you mentioned was the case with NKTR-two fourteen. And we believe that that's a big differentiator because we know that albumin does extend half life as we've shown in our non human primate data, but also that albumin tends to accumulate in the tumor as well as draining lymph nodes. And that by itself also allows us to better localize our engineered IL-two at the tumor site. And I'll pass it on to Man, who's obviously got a lot more experience with NKTR-two fourteen. Man? Thank you, Fahar. So on top of what Fahar indicated from mechanistic from drug design and MOA, I cannot disclose much or anything to you about NKTR-two fourteen, but I can tell you about our compound. Of course, given that we don't have yet clinical data, but based on the preclinical data and animal models, we've seen the drug being utilized and dosed in those animal models. It doesn't look like we will have issues related to cytokine release syndrome, vascular release syndrome or other toxicities seen in this drug class and become dose limiting toxicities in some patients. Based on the data available so far, it doesn't look like it will be an issue that similar to agents in this drug class that have this issue based on mechanistic and pathway drug class effect. Obviously, the data, the clinical data will trump everything and we'll keep you updated based on the clinical data obtained in the dose escalation portion of the program. Thank you for asking. Thank you all. The one additional question, this is on the biscuit program. So this from what I understand, this is a balancing act between inhibiting a pro tumor activity and activating a pro inflammatory response. So in such a program, what sort of safety signals should we be looking out for, especially in your preclinical work and also when you get into the clinic in the Phase I study? Yes. So again here, clearly, if it all depends on what components or what 2 bifunctional molecules become part of the candidate that goes into the clinic. And as we said, we are currently conducting research to identify the best candidate and we will disclose the best candidate towards the end of this year as a lead candidate. So it's a bit difficult for us to predict as to which molecule will be the one that goes into the clinic at this time. And based on the key components of the molecule, for instance, if it contains the IL-two superagonist, then of course, we will need to incorporate the safety issues that are consistent with the IL-two space. And with respect to any other fusion partner, whether it's a checkpoint inhibitor, a targeted antibody or an IL-four, IL-thirteen antagonist, that will then be based on those molecules characteristics and potentially we will obviously know a lot more once we've done some initial screening in non human primate studies as to what safety signals we need to look at. So it'd be premature for us to say anything at this time. And one last question, this is on the MD and A55. I understand you can't really talk too much about ongoing discussions. But obviously, this has been a subject for you folks for a while now. So what I mean, what exactly are you looking for in the partnership? And what are the major discussion points at this time that you need to get through before you can sign an agreement? Yes. It's difficult for us present anything with respect to what the discussion points are. Of course, those, as you say, remain private. And therefore, I can only say that we are in active discussions, and we will be able to provide an update as soon as the timing is appropriate. So that's the plan going forward. And suffice it to say that we do have discussions going on. So that's all I can say for now. Thank you, Fahar. Thanks. Thanks. Our next question is from Jason McCarthy with Maxim Group. Please proceed. Hi, everyone. It's Dave on the line for Jason. Thanks for taking my question. So with respect to MDNA11, would the ex U. S. Trials help guide in direction of U. S.-based trials? And do you think it's possible that data gathered from these trials could possibly help expedite the development process change to MD and A alignment in the U. S? Sorry, I didn't quite get the question. Could you sort of repeat it once more, please? Sure. So the trials that are initiating outside of the U. S. For MD and A11, I was just asking if those trials would help guide the future direction of U. S. Based clinical trial. And if you think data gathered from the ex U. S. Trials could help expedite the development process of fdna11 here in the U. S. Yes, of course. So any data we gather from outside the U. S. Will be part of the same protocol. And therefore, if any submissions that we make to the regulatory agency and as part of the protocol itself, we will make sure that there is a unified protocol that can be used globally. So I will let Maayan also supplement that, please. Maayan? Yes, Maher. It's confirmed the data that we will be gathering from Australia will contribute to the overall program and will be combined with the data generated in U. S. And other regions ex U. S. And that will constitute the total efficacy, safety data, the total sample size for the Phase I and the Phase II portions of the probes. Thank you. Great. Thanks for the additional color. I appreciate it. Our next question is from Kumar Raja with Brookline Capital Markets. Please proceed. Thanks for taking my questions and congratulations and welcome Doctor. Mulder and Doctor. Mukherjee. So first maybe with regard to the characteristics of the patients you plan to enroll in the Phase I trial, are there any particular histologies you guys are planning to target? And also looks like initially you are looking at checkpoint inhibitor naive patients. But how are you guys thinking about patients who are resistant to checkpoint inhibitors as well as progressing on those? And what are your thoughts on combinations with checkpoint inhibitor? At what time point do you think you will be able to move into that? Right. Thank you, Kumar. Good to talk to you today. I will ask Man to respond to that question. Man? Yes. Thank you, Fahar. Thanks for asking. So the histologies and the patient population to be included in the Phase I and the Phase II portions of the program, we will be including patients who are resistant, who failed prior lines, failed checkpoint inhibitors and in certain cases, they're resistant. The tumor types are yet to be fully disclosed, but I can tell you in general, we will follow the tumor type that has highest likelihood of response and have higher probability of success based on the high dose IL-two based on the protein based on what we know about the IL-two activity in the immunogenicity spectrum wise. Patient population will be naive as well as previously treated, but we won't be accepting heavily pretreated patient population. As you know, this is a safety first part of the study is a safety focusing arm that will evaluate the dose and toxicity. So we have to be mindful of that. In regards to the checkpoint inhibitor part, yes, we will be having a checkpoint inhibitor arm in this study, but of course, after clearing the dose testing monotherapy part of the program as well and seeing the activity before combining it with the checkpoint inhibitor, ideally PD-onePD L1? Thanks for asking. And in terms of the U. K. Trial, when do you think it will come on board? And how do you plan to coordinate with the Australian trial? So just to let you know, we will as you know, we will be starting off in Australia and the same protocol will apply to U. K. From a timing perspective, of course, as we generate some initial data and prepare the IMPD dossier for submission to MHRA, those will be sequential. And also filing and submitting the package to the FDA as part of an IND package, these will all follow after we have started enrollment in Australia. So timing is not confirmed per se, but we will provide guidance as we advance with the enrollment in Australia first. Okay. And maybe finally in terms of dose escalation based on the animal models, how are you thinking that how quickly can you dose escalate? Thanks. Ma'am, maybe you can answer that. Sorry, if you could repeat the question. I didn't get the second part of the question. No, I'm asking how quickly you think you can dose escalate based on the data from the animal models? Thank you. Thank you. So as far indicated and we also articulated in the call, we will not be starting from sub therapeutic doses or low doses. It will be an accelerated sequential dose escalation that will allow us to choose intermediate doses, deescalate and in some cases also we could skip a dose level based on the availability of safety PK data and others. I don't anticipate we will have multiple escalations. I do anticipate that we will get into our recommended Phase 2 dose relatively quickly. And I'm confident the drug will deliver a favorable safety profile, superior efficacy profile to competing agents in the landscape and certainly compared to high dose IL-two. Thanks for asking. Okay. Thanks so much. Our next question is from David Bautz with Zacks Small Cap Research. Please proceed. Hey, good morning, everyone. Thanks for the update this morning. And thinking about the development pathway for the MDN A19-four thirteen bispecific molecule, do you eventually think you'll end up testing that in combination with like a PD-one molecule or that more likely say as a monotherapy? Right. Good question, David. The key aspect is that, of course, as you know, we have different modalities with respect to the biscuits program itself. And one of them we demonstrated was the M and A19-four thirteen as a potential candidate. So that's not really echtenstone as that being the molecule that will take ahead. It could be a molecule that has a fusion to a checkpoint inhibitor, for instance. So until we have done some additional studies, identified the lead candidate and studied these molecules either in a monotherapy setting or also in a combination setting. Once we have that data, we'll be able to judge further as to what will be appropriate combination partner or if we even need a combination partner. So that's still not to be determined. So that's a bit too early at this moment. Okay. And then do you foresee the company presenting any additional preclinical data on either MDNA11 or the biscuit program later this year? We are obviously looking forward to certain conferences that are on our horizon as to potential places where we would present additional data on MDN-eleven. This will be preclinical as well as additional data on our biscuits pipeline. So we look forward to updating these different programs that we have ongoing and hopefully there will be those presentations before the end of the year. Okay, great. Thanks for taking the questions. Thank you, David. We have reached the end of our question and answer session. I would like to turn the conference back over to management for closing remarks. Well, thanks again to everyone for joining us on the call. We look forward to the continuous advancement of our pipeline and discussions along the MBN-fifty five partnering activity as well and we'll keep everyone updated along the way. Thank you very much and goodbye. Thank you. This does conclude today's conference. You may disconnect your lines at this time and thank you for your participation.