Greetings, and welcome to Medicenna 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 formal 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 Advisors. Thank you. You may proceed.
Thank you, operator, and thank you all for participating in today's conference call. This morning, Medicenna 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 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. 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 MDNA11, MDNA55, and the BiSKITs programs.
The potential of the Superkine 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 and analysis, and Form 20-F 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 Medicenna Therapeutics. Fahar?
Thanks, Dan, and good morning, everyone. During today's conference call, I'd like to focus on Medicenna's most recent presentation of exciting clinical data, providing preliminary evidence of MDNA11's single-agent anticancer 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. To complete the combination arm of the phase I/II ABILITY study.
Fourth, it enables us to advance one of our novel BiSKIT candidates for IND readiness. 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 MDNA55 or our preclinical BiSKIT program, please listen to the replay of our last earnings call, which occurred on June 22nd and is available on our website at www.medicenna.com. Getting back to our lead program, I will start by reminding everyone that MDNA11 is a beta-only, long-acting IL-2 superagonist. It has been engineered specifically to overcome the shortcomings of native IL-2, which is FDA approved and known as Proleukin.
Proleukin'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 Proleukin 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 Proleukin'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 MDNA11 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 sub-optimal masking technologies such as pegylation 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 albumin's ability to localize in the tumor and tumor-draining lymph nodes. As you know, we are advancing MDNA11's clinical development through the ongoing phase I/II ABILITY study.
The primary objectives of this trial, as is the case with all first-in-human phase I/II 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 II 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 Cmax 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 anticancer CD8+ 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+ Tregs. This is significant as ICOS+ 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 MDNA11 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 designed 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 antitumor activity from ABILITY's 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 a 30 microgram per kilogram dose. Finally, a patient with pancreatic cancer also achieved tumor control in the fourth dose escalation cohort, where MDNA11 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 $20 million financial raise, that the pancreatic cancer patient in cohort 4, 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 MDNA11 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 RECIST 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 the 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 antitumor 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 MDNA11 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. Collectively, the tumor response data from ABILITY's early and midstage dose escalation cohorts provide an early sign of MDNA11's single-agent activity. We view this as a very encouraging finding, especially when considering several aspects of the trial's patient population. First, there is the tumor types in which we have observed disease control.
As mentioned, this includes 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 ABILITY study's 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. Third, there is the information we can glean from baseline measurements of lymphocyte counts. Lymphocytes include CD8+ 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 and extremely difficult to treat, consistent with what we'd expect based on the types of patients enrolled and their 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 MDNA11'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 MDNA11, 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 MDNA11 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 antitumor activity data from the trial's fourth dose escalation cohort. In the fourth quarter of calendar year, we expect to announce initial antitumor activity data from the trial's fifth dose escalation cohort.
Looking ahead into calendar 2023, we expect to report antitumor 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 Proleukin 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 study's next readouts will be to generate additional evidence of MDNA11's 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.
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?
Thanks, Fahar, and thanks to all listening. Before I begin, I'll note that all references are in Canadian dollars, unless otherwise noted. Medicenna announced last week the completion of a $20 million unit offering in the midst of a very difficult financing environment for biotech companies. We were pleased to be able to attract a number of new healthcare-focused investors as part of this financing. We believe that it was important for Medicenna to raise capital this summer for a number of key reasons. Firstly, we wanted to be in the position of having the MDNA11 phase I/II ABILITY study funded to completion. This is particularly important as our existing funding was not sufficient to initiate the combination arm of the study. As previously disclosed, the combination arm of the study requires an anti-PD-1, a very expensive drug to purchase outright.
In order to establish a collaboration with a pharma company who can provide an anti-PD-1 to Medicenna free of charge, we need to demonstrate that we have sufficient capital to complete the ABILITY study, including the combination arm. Secondly, Medicenna's current shelf prospectus expires at the end of August. Due to the biotech market downturn and corresponding reduction in our market capitalization, we're not in a position to refile a similar shelf prospectus and will be caught by the Baby Shelf Rules, increasing the complexity of the process and limiting our ability to fund the company at a future point. Finally, with a number of key milestones, as Fahar discussed above, coming in the near future, we wanted to remove the financing overhang that was on the stock.
Given that we had less than a year of cash, the market would expect a financing upon positive news, which often limits the impact of such news. Our hope is that now that we have sufficiently funded the company, the market will not be anticipating a financing, and in the event of positive news catalyst, the valuation of the company will increase accordingly. As of June 30, 2022, Medicenna had cash and cash equivalents and marketable securities of CAD 19.3 million. Based on the cash on hand, along with net proceeds from our recently closed offering, we have sufficient capital to fund our operations into calendar year 2024, leaving us well-capitalized through important upcoming catalysts.
Net loss for the quarter ended June 30, 2022 was CAD 4.2 million or CAD 0.07 per share, compared to a loss of CAD 6.4 million or CAD 0.12 per share for the quarter ended June 30, 2021. The decrease in net loss for the quarter ended June 30, 2022 compared with the quarter ended June 30, 2021 was primarily a result of reduced research and development spending. Research and development expenses of CAD 2.4 million were incurred during the quarter ended June 30, 2022, compared with CAD 4.3 million incurred in the quarter ended June 30, 2021.
The decrease in research and development expenses in the current fiscal year's quarter is primarily attributed to costs associated with the development of MDNA11 incurred in the prior year, including GMP manufacturing and IND enabling studies for which no comparable expenses were incurred in the current year. General and administrative expenses of CAD 1.9 million were incurred during the quarter ended June thirtieth, 2022, as well as during the quarter ended June thirtieth, 2021. General and administrative expenses were consistent quarter-over-quarter. For further details on our financials, please refer to our financial statements, management's discussion and analysis which will be available on SEDAR and EDGAR, respectively. With that, we will now move on to some concluding remarks from Fahar before beginning the Q&A session.
Thanks, Liz. I'd like to conclude by reiterating three key points that give us confidence as we move into fiscal 2023 and towards key updates from the ABILITY study. Prior studies with Proleukin have shown that when administered at a high dose, native IL-2 provides meaningful clinical benefit. However, its utility is hampered by its burdensome administration schedule and the need to dose in the intensive care unit, which are due to its poor pharmacokinetic and safety profiles. Second, we are taking a differentiated approach specifically designed to overcome Proleukin's shortcomings. With enhanced affinity for IL-2 receptor beta compared to Proleukin and competing agents and no affinity to IL-2 receptor alpha, MDNA11 has a unique binding profile that we believe will yield improved efficacy. Third, MDNA11 is the only albuminated IL-2 in clinical development.
In addition to half-life extension, albumin has the unique ability to localize in the tumor microenvironment and to accumulate in tumor-draining lymph nodes, both of which are crucial for effective antigen presentation and proliferation of cancer-fighting immune cells. Finally, each passing readout from the ABILITY study continues to provide additional evidence supporting MDNA11's best-in-class potential. We have thus far seen a favorable safety profile, potent stimulation of anticancer lymphocytes without activation of pro-tumor immune cells, and encouraging signs of antitumor activity in patients with difficult-to-treat tumors that have been unresponsive to prior therapies, including an unconfirmed partial response in a heavily pretreated pancreatic cancer patient. We look forward to adding to this data set as we continue to dose escalate and hone in on the tumor types that we believe MDNA11 will have the strongest impact. With that, I would now like to open the lines for questions. Operator?
Thank you. We will now conduct a question and answer session. If you would like to ask a question, please press star one on your telephone keypad. A confirmation tone will indicate your line is in a question queue. You may press star two if you would like to remove your question from the queue. For participants using speaker equipment, it may be necessary to pick up your handset before pressing the star keys. Once again, that's star one at this time. One moment while we poll for our first question. Our first question comes from Matt Biegler with Oppenheimer. Please proceed.
Great. Congrats guys on the early data, seriously. Fahar, maybe just speak more broadly to how IO therapies, including Keytruda, work in general in PDAC. I don't believe that it's actually approved or indicated there. Is this like a lightning strikes kind of event? Second, I just wanted to maybe ask about the safety and tolerability so far because it's not. I don't think we've seen too much from it on that end, at least from the cytokine conference. Would you say it's broadly consistent with, you know, our experience of IL-2 in general, or anything you can say on that? Because there seems to be a disconnect between the stock price and your current market cap, and the quality of these data.
I'm just interested if you have any thoughts why, and I know you talked a little bit just about market dynamics, but anything else that maybe could help investors, would be great. Thanks.
Great. Thanks, Matt, and thanks for your question. Let me answer the second question first, namely from a safety perspective. Clearly, first and foremost, we are not altering the dosing regimen in terms of continuing with the treatment every two weeks, so that's encouraging.
However, as I mentioned earlier, as we've been moving on to the higher doses, what we had observed, not only in non-human primate studies but also in studies that we conducted in mice and also when we look at the early dose escalation cohorts, even at the low early doses, what we did find is that the first dose generally had, if a patient had fever, for instance, a tendency to have a higher fever threshold which would last longer and then as patients received the second and subsequent doses, you would generally see that those adverse events of, let's say, fever or anything similar or chills, for instance, would be of a shorter duration and also would generally find that with subsequent treatments, these adverse events would not show up eventually.
We were proactive in the sense that we said, "Okay, if that is the case, how do we get MDNA11 so that the dose escalation proceeds unhindered by what we might see in the first treatment for a patient?" That's why we sort of employed proactively decided to proceed with an approach where we'd enroll the patients, administer a dose which we found was therapeutically active. That is important because remember, patients in this clinical trial are patients who are end-stage patients. You do not want them to receive doses for a couple of weeks or even four weeks where the patient is not likely to benefit.
We needed to make sure first and foremost we started at a dose that was clinically beneficial or was potentially of benefit to the patient as we've seen at the 10 and 30 microgram per kilogram dose, and subsequently escalate to the higher dose. The trends seem to be consistent with what we're seeing. We're seeing that as we escalate the third, fourth doses subsequently, even if they are at a higher dose, tend to be much better tolerated and therefore allows us to leverage all the benefits of MDNA11 without prematurely creating a situation that the first dose essentially makes the patient ineligible for additional treatments. I think we've been cautious. It's been important.
As we all know, IL-2 is a really potent drug, and we've seen also from data and results from Nektar's phase III trial, where although they were administered a rather low dose of, say, 6 micrograms per kilogram, which is the dose that they administered in the phase III trial. We are already at the 60 micrograms per kilogram. We have a dose which is double that of Nektar or bempegaldesleukin, despite the fact that our molecule is so much more potent. We've also seen that in the bempegaldesleukin study, patients, when they received the first dose, the subsequent doses were less well-tolerated, and therefore they had dose de-escalation, et cetera, taking place. This is something we did not want to occur in our patients in our trial.
Again, this approach of step-up dosing allows us to proceed in a manner that avoids patients to be administered the drug in an intensive care unit or having to stay in hospital for prolonged periods of time. All of that is important as we move the project along. That's basically where we are with the safety profile. Our safety review committee has agreed and in enrolling patients now at the 90 micrograms per kilogram dose, so that is encouraging from a safety profile as well. I think based on current data that we see at the 60 micrograms per kilogram, it seems like we are well in that therapeutic activity range that we would like to be in, but it's best for us to try higher doses and see what additional benefits we can provide without causing safety issues.
With respect to pancreatic cancer, it's true, pancreatic cancer, the checkpoints, none of the checkpoints have been approved for pancreatic cancer. All treatment regimens of FOLFIRINOX as well as a combo with Abraxane and Gemcitabine tend to be the standard of care for pancreatic cancer patients. There's been very little out there that has been innovative for these patients. It's a challenging disease and we are happy to see that MDNA11 on its own was able to generate such promising results in this one patient. Mind you, it's just one patient, so obviously we want to see more patients in this tumor type.
Understood. Okay. I just had a follow-up about you talked a little bit about the baseline lymphocyte counts and how that seems to correlate with outcome. But I didn't totally catch it. Going forward, are you going to restrict treatment to those only with higher lymphocyte counts or counts over some threshold? Or is this just another biomarker you're gonna be looking at going forward? Thanks again.
Right. Thanks for that question as well, Matt. Yes. When we look at previous data, published results from Proleukin's clinical trials and as well as other therapeutic agents, including other IL-2s, including bempegaldesleukin, etcetera, we generally found that the baseline lymphocyte counts in these patients was about 1,500 counts per microliter. In the earlier dose cohorts, we did not have a threshold. We allowed patients with any kind of baseline lymphocyte counts to be in the study. That meant we had patients largely with baseline counts in the 300-800 counts per microliter, which is in some cases less than half of the normal range.
What we have done, as you've seen in other IL-2 programs, including Proleukin, is a requirement that the baseline lymphocyte count has to be above 1,000, which is consistent with what we've seen with Proleukin. This is something that we've implemented in our revised amended protocol. Cohort 5 onwards, that's going to be our minimum threshold for enrollment requirement.
Got it. Thank you.
Our next question comes from David Martin with Bloom Burton. Please proceed.
Yes, good morning. First question is kind of a follow-up to the last one. The patients that have done the best so far in the dose escalation have they had higher lymphocyte counts at baseline? Is what was seen with Proleukin bearing out in your trial as well?
Well, not necessarily. It's just been that, the lymphocyte count is obviously one parameter. We have seen, as I mentioned in the first three dose cohorts, where we did see 3 out of 8 patients have stable disease. Their baseline lymphocyte counts were generally quite low, certainly not down to 300 counts per microliter, but they were generally in the 800 or so, which is sort of closer to the threshold that we want to accomplish. We have seen one of those patients with melanoma, for instance, start just under the threshold of 1,000 lymphocyte counts per microliter, who is stable, has stable disease now for, well over nine months. Therefore, it might imply that we certainly do need higher lymphocyte counts, particularly post-treatment with Proleukin.
There is data to show that, during treatment regimen of Proleukin, when lymphocyte counts exceed 3,000 or 4,000 lymphocytes per microliter, these patients tend to have responses or treatment benefit. Generally, they start at about 1,000 or 1,500 to begin with Proleukin, increase the counts to 3,000 or so, and these patients tend to benefit. We are seeing now at cohort 4, as we disclose this data at the conference at the end of July, that the baseline lymphocyte count in this cohort 4 was about 1,500 or 1,600, and we saw that the increase in lymphocyte counts went up to 3,000 and 4,000, which is encouraging, and we hope that translates into better outcomes for the patient.
Okay, great. Next question. The four patients that you're waiting for first scans in cohort four, they're still on trial. Have they all stepped up to the 60 microgram per kilo dose?
Yes. They have all the four patients are on study. They're all now receiving the 60 micrograms per kilogram dose. Yes.
Have any of the patients in cohort 5 stepped up to 90 yet?
Cohort 5 just started, so we've just started enrolling patients in Cohort 5. As you know, there'll be two doses at the priming dose of 30 micrograms per kilogram. It'll be another month or so before we get to the 90 microgram dose.
Okay. Last question. When you did the step up to 60, what happened with fever and chills? Did they spike up a bit again when you went from 30 to 60, or did it completely blunt off that fever and chills effect?
Yeah, I sort of don't have that information handy with me, so cannot specifically mention what happened patient by patient. Of course, each patient responds differently to the therapy, depending on their baseline characteristics and so on. Certainly, we'll be able to share more data as we have the ability to conduct further analysis of adverse events if they have occurred. Did they increase in frequency or decrease in frequency over time? I think this will be a useful bit of study that we'll be conducting and reporting those data when we finish the escalation part of the study.
Okay. Sorry, I did have one other quick question. With regards to the financing and the stronger balance sheet, how does that impact your negotiations for MDNA55? Have the positioning of various parties changed because you did raise some money?
Well, we have not specifically discussed those with potential partners, but it certainly puts us in a stronger position to negotiate a transaction with a healthier balance sheet.
Okay. Those discussions remain ongoing, I take it?
Yes, they are. Yes.
Okay. Thank you.
Once again, ladies and gentlemen, to ask a question, please press star one on your telephone keypad. Our next question comes from Catherine Novack with Jones Research. Please proceed.
Hi. Thanks so much for taking my questions. You know, just wanted to ask another question about lymphocyte counts, specifically for the pancreatic cancer patient. Can you talk about any pharmacodynamic or biomarker data that can give us further information about MDNA11's activity in this tumor? You know, with tumor regression, are you seeing commensurate increases in lymphocyte counts or proliferation? Will we be seeing paired tumor biopsies in this cohort, or we'll be waiting for, you know, further cohorts to see those?
Okay. Hi, thanks, Catherine, and thanks for the question. Very quickly, as per our data that we presented at the conference, you will see that in cohort four, the baseline lymphocyte count of these patients was around 1,500-1,600. The post-treatment scans, or when they sort of increased at day 8 or 11, you'll see that their counts increased up to over 4,000 counts. This is consistent with what we saw in the pancreatic cancer patient as well. In general, it seems like the pancreatic cancer patient who had a healthier baseline immune system seems to have benefited. It's difficult to generalize, of course, from just this handful of patients, but it seems consistent with the kind of data that has been reported with Proleukin itself.
That's one question. With respect to the sort of breaking it out patient by patient, we'll be able to provide that more during a medical conference. And finally, your other question was related to the baseline lymphocyte counts and the increase, if I'm not mistaken. We see continuous increases as we administer the drug. The first dose, you'll see that the lymphocyte count increases quite dramatically and that subsequent doses, the increases continue, but they are not as dramatic as the first dose. I think there was some other question that I might have forgotten. If you can repeat that, please.
Oh, I wanted to ask about status of paired tumor biopsies and?
Yeah, right.
which cohort we'll see.
Mm-hmm.
-those.
During the dose escalation, it's difficult to convince patients to participate in sort of contributing their biopsies pre- and on-treatment. As it is, they are, you know, not the healthiest of patients, but then again, also part of a dose escalation portion of the trial. We have two or three biopsies or paired biopsies so far. We do have several biopsies that are pre-treatment biopsies. On treatment, as I said, we just have about three paired biopsies. We hope to get more of them as we enroll more patients in the dose escalation, but we likely are going to get more patients willing to contribute their paired biopsies during the dose expansion phase, so that when we have data, we can have some more meaningful comparisons pre- and on-treatment.
Got it. Then I just wanted to, you know, double-check plans to conduct a sixth dose cohort. You know, obviously, at this time you're only guiding to seeing data from the fifth cohort by the end of the year. You know, what are the plans for additional cohorts beyond that? You know, will we see data next year, or is that still to be determined?
Yeah. Cohort 6 is gonna be to be determined. I think we've seen plenty in sort of, quite a robust, patient benefit response, PK, PD data that are consistent, with what we were, hoping for, what we are hypothesizing. Also, based on, the data, when we sort of, use the data from the non-human primates, the 60 microgram per kilogram, 90 microgram per kilogram tend to be the ones that would be, potential threshold doses. We feel that it's unlikely we would need to go higher than the fifth cohort, but we'll see. I think we'll play it by ear. At the moment we are assuming that, the 60 and or 90 microgram per kilogram dose might be, getting us close to the recommended phase II dose.
Can you remind us in terms of IL-2 concentration, where 60-90 puts you compared with other modified IL-2s that are being evaluated in the clinic?
Yes. It's obviously the dosing regimen is different. I think the only one comparison that I might have is Bempeg and also nemvaleukin, which is Alkermes's drug. In both cases, based on an IL-2 equivalent dose, at the 90 micrograms per kilogram, we are already three times higher dose than Bempeg. I would say we are, if you add the daily doses for nemvaleukin, which is five days of daily administration, we would, again, here with MDNA11, be adjusted higher or possibly at 90 micrograms, maybe double the dose of Alkermes's molecule. In both cases we are substantially higher. With respect to others, it's not quite clear as to whether they're reporting the dosing in terms of IL-2 equivalent or not. I wouldn't want to make a comment there.
Got it. That's very helpful. Thanks so much.
You're welcome. Thanks.
Our next question comes from Arthur He with H.C. Wainwright. Please proceed.
Hey, good morning, Fahar Merchant. This is Arthur for RK. Thanks for taking my question. I had two questions regarding the coming combination cohorts study. Correct me if I'm wrong. My understanding is, are you going to dose the MDNA11 with the CPI both at the every three weeks regimen? Or, if that's the case, could you tell us how your strategy to tweak the dose level for the MDNA11? Or you are going to just dose that as the Q2 week as right now and just using the Q3 week dose interval for the CPI?
Yeah, it's a good question. Difficult to predict at this moment. As you know, the combination portion of the trial includes a safety running portion of the trial. During that safety running portion, we'll likely, as we are conducting the dose expansion monotherapy portion of the trial, we'll be looking at at least one if not two different treatment schedules. So that'll be pretty much dependent on which checkpoint we use, as well as you know, what the safety running informs us before we proceed with the actual dosing and when we do the dose expansion during the combination part.
Gotcha. Yeah, that's helpful. Regarding the starting of the combination dosing, will it be a collaboration forged with the Big Pharma to provide a checkpoint inhibitor, is need to be completed before you guys start the combination phase? Thanks.
Yeah. Certainly we are looking at different options with respect to collaboration. At the same time, we are not particularly wedded to a particular dosing regimen. We'll establish that as we work together with the collaborator and finalize that, of course. We need to make sure that any protocol that we put together for the combination arm is such that it's consistent with the safety PK/PD profile of the checkpoint inhibitor in addition to that of ours. It will be carefully evaluated before we proceed with that portion of the study together with the pharma company.
Oh, thank you. Thank you for taking my question, and congrats on the progress.
Thank you.
Our next question comes again from David Martin with Bloom Burton. Please proceed.
All right. Thanks for taking my follow-up. You mentioned earlier that with Proleukin, baseline lymphocyte count also determined responsiveness to the drug. The label for the drug indicates a 15%-16% objective response rate. Was that before they started measuring baseline lymphocyte counts and now assuming they do to make a patient eligible for Proleukin, what type of response rates do you get when you use that as an inclusion criteria? Are there other biomarkers that are emerging from your study that you think confers responsiveness to MDNA11?
Right. Thanks, David. Going back to your first question regarding the baseline lymphocyte count for Proleukin, these are actually the data of 1,500 or 1,600 lymphocyte counts per microliter are based on that, the large studies that were conducted where we saw 15% and 16% response rates. That was the baseline lymphocyte counts on those studies. In those studies also, the responders generally were patients that had, post-treatment or on treatment lymphocyte counts increasing from 1,500 to 2,000 or more. That was basically, the sort of the take-home message is, you need to start a patient with reasonably healthy baseline lymphocyte count, at least the lower limit of normal. If you're below 1,000, you are well below normal already.
I think you need to have some a reasonably healthy baseline lymphocyte count. Second of all, the increase to 3,000 or more was consistent with patients then having a benefit. Now with respect to our own study in terms of biomarkers, we're seeing again from Proleukin that patients that had increases in ICOS positive Tregs, those did not benefit. Whereas those patients that did not see an increase in ICOS positive Tregs had response. We're seeing something similar here with MDNA11. We are now monitoring ICOS positive Tregs as well as CD8 T cells that are ICOS positive. Let's see. I mean, obviously it's early for us right now. We don't have enough data on ICOS positive Tregs and its potential impact on tumor response, but we'll certainly be looking at that as a good marker as well.
Okay. Just to confirm, the study that you talked about for Proleukin, were all the patients in that study, did all of them have high baseline counts and the response rate was 15%-16%, or just among the patients who responded, they had the higher baseline counts?
No, I don't think, you know, it's sort of difficult because they only provided an average or the mean of those patients at baseline, so I can't say what the base counts were. When they reported response rates, they did say that the response did occur in patients with lymphocyte counts during treatment to be above 3,000. That's the only information that we have that was published in that two or three different publications in melanoma and renal cell carcinoma. From a baseline count, we don't know what their individual groups was. That was not a way of determining if responded. It was not on baseline lymphocyte counts. It was mostly on what the expansion of the lymphocyte count was post-treatment.
Okay. Got it. Thanks.
Thank you. At this time, I would like to turn the call back over to Dr. Fahar Merchant for closing comments.
Thanks operator. In closing, I will reiterate our excitement for the ABILITY study's continued advancement and upcoming results from the trial as we continue to dose escalate. I would like to thank the investigators and the patients who have enrolled in the study to date. I will also extend one last thanks to all those participating in today's call and wish everyone a good day. Thank you and goodbye.
Thank you. This does conclude today's teleconference. You may disconnect your lines at this time. Thank you for your participation and have a great day.