Medicenna Therapeutics Corp (MDNA) 2021 Q4 法說會逐字稿

Hello, and welcome to Medicenna Therapeutics Fiscal Year 2021 Earnings Call. (Operator Instructions). 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, Medicenna 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 Medicenna'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 MDNA11, MDNA55 and BiSKITs programs, the potential of the Super kind platform, partnering activities, cash runway, in the presentation of additional data. All statements other than statements of historical facts 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 and Form 40-F 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 a Canadian and United States securities law.

Now I'll turn the call over to Dr. Fahar Merchant, President and Chief Executive Officer of Medicenna 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 Dan, I'm joined by Dr. Mann Muhsin, our Chief Medical Officer; Dr. Kevin Moulder, our Chief Scientific Officer; Mina Merchant, our Chief Development Officer; and Liz Williams, our Chief Financial Officer.

Fiscal year 2021 was Medicenna'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, introduced the new members of our executive team, and provide an outlook for fiscal year 2022 and beyond. So let me start with some of our accomplishments over the past year, beginning with our program focused on ending at 11 our long-acting IL-2 super agonist. Milestones in this program include the presentation of nonhuman primate data showing that MDNA11 selectively stimulates, prolonged expansion of anticancer immune cells without causing unwanted side effects, such as the generation of anti anticoagulant antibodies, hypotension associated with vascular leak syndrome or cytokine reduced symptom. We also presented additional preclinical data that further highlighted MDNA11's best-in-class potential by demonstrating its durable and potent therapeutic efficacy, both as a monotherapy and in combination with checkpoint inhibitors in nearing 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 I/IIa clinical plans would be appropriate for submission of an investigational medical product dossier for a first in Q1 study with MDNA11 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 I/IIA clinical trial of MDNA11 in the third quarter of calendar 2021. Mann 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-4 guided toxin targeting recurrent glioblastoma or rGBM the most common and uniformly fatal form of brain cancer. Throughout the past year, we presented updated data from our Phase IIb trial rGBM that demonstrated MDNA55's potential to change the treatment paradigm in a high unmet need indication. These data showed that amongst an all-comer population, a single MDNA55 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 rGBM, the FDA recommended we conduct a landmark Phase III trial to support MDNA55's approval in this indication. This client's trial has an open-label hybrid design that allows for 2/3 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 MDNA55's advancement. While the details of these conversations need to remain (inaudible) 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 Superkine platform, which we refer to as BiSKITs. These novel molecules, which are fusions of 2 complementary Superkines, oral 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 Dr. Jack Geltosky. This corporate momentum has continued into fiscal 2022, as we recently added Mann and Kevin, 2 highly talented immuno-oncology experts to our management team. As I 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 first-in-class potential of our assets, together with the power and versatility of our Superkine and BiSKITs platforms.

I will now let you hear from these team members. Starting with our Chief Medical Officer, Dr. Mann Muhsin. Mann, please go ahead.

Thank you, Fahar, and good morning, everyone. Today, I will be talking about the MDNA11 program. First, I'd like to introduce myself and explain exactly why I'm so excited to be part of the Medicenna team. I joined Medicenna earlier this month and have deep expertise in immuno-oncology and IL-2 specifically. I have conducted more than a dozen clinical trials sponsored by multiple industry leaders, including AstraZeneca, Hoffmann-La Roche, Merck, Novartis, (inaudible), Johnson & Johnson and Bayer. I've also designed, executed a medicinal development programs in oncology trials for a variety of biotech companies, most recently working at Nektar Therapeutics prior to joining Medicenna.

One of the primary drivers behind my decision to come on as Medicenna CMO for MDNA11's robust preclinical data set, which demonstrates the molecules, best-in-class potential and clearly differentiates it compared to approved therapies on completing IL-2 variance in development handicap. As those of you familiar with IL-2 space, likely know, recombinant human IL-2, 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-2 targets the trimeric receptor, which includes CD25. Simulation of CD25 leads to the activation of TRX, which inhibits antitumor immune response and its associated with unfavorable prognosis in patients with various types of cancers as well as closing extreme toxicity, which necessitates the dosing of patients in intensive care units. Additionally, the dosing is required every 8 hours for 9 days due to recombinant human IL-2 for pharmacokinetic (inaudible).

Now what I find so exciting about the MDNA11 is not only that it can overcome these shortcomings, but how it overcomes the shortcoming. Using Superkine platform, Medicenna has engineered MDNA11 to have dramatically increased affinity for the CD122 subunit of IL-2 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 targeted factors of IL-2 therapies. Additionally, the inclusion of human albumin in the molecule and prove the molecules half-life and bioavailability in the tumor. Its fusion to a second protein, in this case, albumin, is a key point of differentiation for MDNA11 compared to competing IL-2 variant, many of which rely on regulation to improve half life. In general, simulation requires a complex manufacturing process that is well known, not only affect product consistency, but can also unintentionally match the active side of the protein under dose efficacy.

We have robust preclinical data set demonstrating how MDNA11 enhanced affinity for CD122 and reduced affinity for CD25 positions this to be best-in-class. This data set shows that compared to competing IL-2 programs, MDNA11 is able to preferentially stimulate casting effector T and NK cells as opposed to TRX. Thanks to this high selectivity the molecule has also shown impressive efficacy, both alone and in combination with checkpoint inhibitor in preclinical tumor models.

Additionally, nonhuman primate studies indicate that the molecule does not go with vascular leak syndrome or cytokine release syndrome has been seen with other programs. It was the pet in class properties of MDNA11 that led me to realize the power of the Superkine 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 plans moving forward. We're currently in the process of advancing MDNA11 into Phase I/IIa clinical trial in Australia and the United Kingdom, followed by expansion to the United States. We have chosen to begin the trial in this country rather than United States for 2 reasons. First, starting in these countries allows us to begin the dose escalation portion of the trial at doses that are closer to therapeutically effective doses. Second, the United Kingdom and Australia has 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 to our initiation of our trials as we wind down our GLP toxicology studies and are in the process preparing their regulatory package for submissions 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 third quarter of calendar 2021.

With regards to trial design, we plan to begin with a dose escalation MDNA11 monotherapy phase, which will then be followed by a dose expansion phase. This dose expansion phase will evaluate both MDNA11 monotherapy as well as MDNA11 in combination with a checkpoint inhibitor. Another key element of the trial design is the planned collection of free and on treatment biopsies, which will allow us to collect valuable biomarker data that may speak to the MDNA11's mechanistic activity in humans.

Looking ahead. We expect to provide a preliminary update on any available safety, PK/PD 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 2022. Shifting gears now, I would like to ask Gohar to speak briefly about our Phase III-ready MDNA55 program.

Thank you, Mann. As I mentioned earlier, MDNA55 is an IL-4-guided toxin targeting recurrent glioblastoma. Findings from the Phase IIb trial evaluating MDNA55 in rGBM were recently published in the peer review journal, clinical cancer research. These findings indicate that early determination of progression-free survival with a modified renal 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 medium -- 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 MDNA55 treated trial participants with high IL-4 receptor expression and participants with low IL-4 receptor expression that received a high dose of MDNA55 treatment. We believe these positive modified renal PFS and overall survival data bode well for the outcome of the planned Phase III trial, which has overall survival as a primary endpoint. As I mentioned earlier, this plant trial utilizes an innovative open-label hybrid design that allows for 2/3 of the control arm subjects to be from a well matched external control on. This design will reduce the cost and time lines associated with completing the trial by reducing the overall number of subjects needed to achieve the primary endpoint which will be based on a 1:1 analysis of the MDNA55 treatment arm versus the cold 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-fit kind trial leaves MDNA55 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 MDNA55 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, Dr. Kevin Moulder.

Thank you, Fahar. I'm very excited to be speaking on the call today, I would like to start by introducing myself to those listening since I like Mann and also a recent addition to the Medicenna management team. I joined medicine with over (inaudible) and development in several fields of the protein design, antibody technology, autoimmune disease, anti-immuno-oncology. This includes my time at Biogen, where Avena predicted medicine department. My time as CSO at Star Therapeutics so I established the company's bispecific antibody technology. And led the translational efforts to identify the programs for a clinical need. And my time as Chief Development Officer at Tas Therapeutics directed the development of an anti-CD25 antibody. This antibody showed anticancer activity that stem from his ability to deplete (inaudible) while preserving IL-2 activity or effect of T cells and advancement in its development subsequently prompted the acquisition of Task by Roche. At Medicenna, I will be applying my knowledge from these experiences as we were to leverage the power of the Superkine BiSKIT platforms to advance first and best-in-class assets towards the clinic. These platforms are powerful and versatile drug development tools and my desire to work with them as a key factor behind my decision to join Medicenna.

I'd now like to give a brief overview as to how these platforms work. I'll start with the Superkine platform, which was by enabling the enhancement of natural interleukin-2 process known as dilated evolution. During this process, several changes are made to interleukin to modulate their desire properties, ultimately resulting in there might be 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 cells, specifically to cancer cells as in the case with MDNA55. The natural progression of our Superkine platform eventually led to the creation of our BiSKIT program, which we unveiled in March. BiSKITs are highly versatile and powerful molecules that consist of us super kind fee to a second anti-cancer proteins such as a checkpoint inhibitor or the second Superkine. By combining molecules in this fashion, we can create immunotherapeutic agents that incorporates 2 synergistic mechanisms of action and overcome the shortcomings of currently available therapies.

At the AACR meeting last month, we presented data on 1 of these assets derived from our BiSKIT platform. The assets 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 in these calls. However, the 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 MDNA19-413. As we discussed during our AACR presentation, MDNA19-413 consists of a super antagonist. It is designed to work via 2 complementary and synergistic mechanisms of action targeting both IL-2 and IL-413 signaling.

I'll focus first on the IL-413 mediated mechanism of action the molecule was designed to modulate this signal activity by selectively binding the IL-13 receptor alpha subunit on the sales of its tumor micro environment. This leads to a disruption in the IL-413 signaling, and ultimately, the inhibition of an M2A polarization of tumor-associated microphages. This is significant as blockade of M2A microphage polorization that mitigates the protumoral effect of immunosuppressive microenvironments. Mitigating these effects can effectively turn a cold tumor hot, thereby making it susceptible to destruction by anti-cancer immune cells.

Now with regard to IL-2 signaling MDNA19-413 worked in a manner fairly similar to MDNA11, preferentially targeting CD122 to enhance the activity of cancer-killing affected T and NK cells. This IL-2 driven agonist action complements the IL-13-driven antagonist activity I just mentioned, making MDNA19-413 a potential anticancer agent with the potential to effectively target cold tumors after the resistance of current available tapes. But this potential was demonstrated in our recent AACR presentation. And while I'm going to go through the full data set here, a couple of key points I'd like to highlight. First, the molecule effectively enhanced signaling in cancer killing effect T and NK cells and reduce activation of provisional tumor CVEC cells. This was evidenced by a 209-fold and 90-fold enhancement in [CD8 TVEC and NK TVEC] ratios in vitro, respectively, when compared to native IL-2. The second, the molecules selectively found and inhibited both IL-4 and IL-13 signaling via the IL-13 receptor alpha-1 subunit, which is normally associated with the protumoral effects of M2A macrophages, while showing reduced affinity for the IL-13 alpha 2 receptor subunits.

Compared to long-acting FC fusion of IL-13, the molecule was approximately 240x more selective for the alpha-1 subunit compared to the alpha-2 of units. This selectively led to notable functional outcomes as MDNA19-413 was able to potently inhibit IL-13, IL-4 signaling pathways and mitigate the polarization of M2A macrophages in vitro. Taken together, these results show how the BiSKIT platform can effectively combine the enhanced immune and signaling properties and multiple Superkines into a single bifunctional compound. In the case of MDNA 19-413, 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- 413 as well as our broader BiSKIT program, we expect to declare our first lead candidate for the program in the fourth quarter of calendar 2021.

With that, I'd like to hand over 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, Medicenna was able to establish and maintain a strong financial foundation while advancing our pipeline of cytokine-based immunotherapies. Medicenna had cash, cash equivalents and marketable securities of $40.4 million 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 $17.3 million, or $0.35 per share compared to a net loss of $8.3 million 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 MDNA11 program as well as costs associated with the NASDAQ listing. In particular, directors and officers of insurance premiums as well as no reimbursement under the grant from the center Prevention and Research Institute of Texas in the current year period.

Research and development expenses of $10.9 million were incurred during the year ended March 31, 2021, compared with $5.9 million incurred in the year ended March 31, 2020. The increase in research and development expenses in the current year is primarily attributable to higher D&C costs associated with GMP manufacturing of MDNA11 for the planned Phase I/IIa clinical trial increased discovery and preclinical expenses associated with GLP-compliant MDNA11 IND-enabling studies as well as discovery work on the BiSKIT platform, increased regulatory costs associated with preparation for the end of Phase II meeting for MDNA55 as well as regulatory activities associated with preparation for the initiation of a Phase I/IIa clinical trial for MDNA11.

And finally, no reimbursement of expenses with respect to the (inaudible) grant in the year ended March 31, 2021, compared with $1 million in the year ended March 31, 2020. General and administrative expenses of $6.5 million were incurred during the year ended March 31, 2021, compared with $2.4 million 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 which health perspective in both Canada and the United States, qualifying our commentaries 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 and 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&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 enables 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?

(Operator Instructions). Our first question is from Matt Biegler with Oppenheimer.

Thanks, thanks for the questions, and welcome to the new members of the C-suite. Fahar and Mann, I appreciate the details on the planned Phase I. Maybe if we could just get a little bit more granular. Have you actually nailed down or agreed upon with Australia, U.K. a start dose yet? And based on preclinical models, 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. I appreciate the question that you've asked. Clearly, as I'll pass it on to Mann, 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 dosing that we are preparing right now. With respect to dosing and et cetera, I 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 human dose or give you projections regarding how many escalations would we need before getting into a recommended Phase II dose and heading 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.

Okay. And -- yes, and I'll also add to it 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 to be much better able to disclose the dosing plan in subsequent disclosures that come by.

Okay. Got you. Okay. Maybe I could just sneak 1 question in then about the safety profile obviously, the IL-2 space in general, safety is a potential concern in kind of striking that right balance between safety and efficacy, kind of the holy grail, I think as we see it. So are you using any -- as you think about your Phase I trial, are you using any lessons learned from your competitors such as prophylactic hydration to reduce the risk of type attention anything that you can incorporate into the Phase I trial that you think could lower any safety risk?

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 2 programs that are in the clinic at the moment. Would always want to ensure that we had appropriate language and procedures, protocols, et cetera, to address those. So that would be expected from any ethics committee, but I'll sort of also let Mann supplement that?

Yes. Thank you, Fahar. It's a good question. So yes, absolutely, all the above. We will use all the lessons learned from agents in the IL-2 landscape, all the lessons learned of the adverse events seen with this drug last myself worked on IL-12, high dose IL-2, pegylated IL-2. 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 and drug class and a rating specific.

Our next question is from RK Ramakanth with H.C. Wainwright.

Couple of questions here. So Dr. Muhsin, if you could help me kind of compare and contest the MDNA11 program here versus the programs that are being run by NKTR, especially like NKTR-214 so we understand how these programs here are situated against what's out there in the competition?

Great. Well 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 man. 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 1 being that we have knocked out the binding or inserted mutations that would block binding to CD 25. And second of all, we have inserted mutations, but dramatically increase the affinity for CD 122 and therefore, selectively stimulating effected T cells, NK cells and (inaudible) 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 pegylated approaches that you mentioned was the case with NKTR-214 and we believe that, that's a big differentiator because we know that argument does extend half-life as we've shown in our nonhuman primate data. But also that agreement 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-2 at the tumor site. And I'll pass it on to Man, who's obviously got a lot more experience with NKTR-214, Mann?

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-214. But I can tell you about our compound. And 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 on dose in those animal models, and it doesn't look like we will have issues related to cytokine release syndrome, vascular leak syndrome and 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 had 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 dose escalation portion of the program.

The one additional question. This is on the BiSKIT program. So this -- from what I understand, this is a balancing act between inhibiting a protumoral 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 we get into the clinic in the Phase I study?

Yes. So again, here, clearly, it all depends on what components are what to by functional 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 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-2 super agonist, then of course, we will need to incorporate the safety issues that are consistent with the IL-2 space. And with respect to any other fusion partner, whether it's a checkpoint inhibitor, a targeted antibody or an IL-4, IL-13 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 nonhuman primate studies as to what safety signals we need to look at. So it would be premature for us to say anything at this time.

And one last question. This is on the MDNA55. 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 find an agreement?

Yes, it's difficult for us to 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.

Our next question is from Jason McCarthy with Maxim Group.

It's a (inaudible) on the line for Jason. So with respect to MDNA11, would the ex U.S. trial help (inaudible) of U.S.-based trial? And do you think it's possible that a to gather from these trials could possibly help expedite the development process that pertains to MDNA11 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 MDNA11. I was just asking if those trials would help guide the future direction of U.S.-based clinical trial. And if you think data gather from the ex U.S. trials to help expedite the development process on MDNA11 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, 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 Mann also supplement that, please, Mann?

Yes, Mark, 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 at the total sample size for the Phase I and the Phase II portions of the prop.

Our next question is from Kumar Raja with Brookline Capital Markets.

Congratulations, and welcome Dr. Moulder and Dr. Mohsin. 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, it looks like initially, you're looking at Checkpoint inhibiting 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 Mann to respond to that question. Mann?

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 types that have highest likelihood of response and have higher probability of success based on the high dose IL-2 based on the pro leukin based on what we know about the IL-2 activity in the immunogenecity spectrum wise. Patient population will be naive as well as previously treated, but we won't be accepting heavily pre-treated patient population. As you know, this is a safety -- first part of the study is the 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 the 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, PD1 and PD-L1. Thanks for.

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 up 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? Mann, 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?

So as far indicated, and we also articulated in the call, we will not be starting from subtherapeutic doses or no doses. It will be an accelerated sequential dose escalation that will allow us to choose intermediary doses, deescalate, and in some cases, also we could skip adders 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 II dose relatively quickly. And I'm confident the drug will deliver a favorable safety profile, superior efficacy profile to completing agents in the landscape and certainly compared to high-dose IL-2.

Our next question is from David Bautz with Zacks Small-Cap Research.

Good morning, everyone. Thanks for the update this morning. Thinking about the development pathway for the MDNA19-413 bispecific molecule, do you eventually think you'll end up testing that and combination with like a PD-1 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 MDNA19-413 as a potential candidate. So that's not really (inaudible) as that being the molecule that will take ahead. It could be a molecule that has an infusion 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 -- still 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 BiSKIT 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 MDNA11. 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.

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 MDNA55 partnering activity as well, and we 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.