Medicenna Therapeutics Corp. (NASDAQ:MDNA) Q1 2023 Earnings Conference Call August 15, 2022 8:30 AM ET
Dan Ferry - IR, LifeSci Advisors
Fahar Merchant - President & CEO
Liz Williams - CFO
Conference Call Participants
Matt Biegler - Oppenheimer
David Martin - Bloom Burton
Catherine Novack - JonesTrading
Arthur He - H.C. Wainwright
Greetings, and welcome to the 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. [Operator Instructions] As a reminder, this conference is being recorded.
It is now my pleasure to introduce your host, Dan Ferry of LifeSci. Thank you. You may proceed.
Thank you, operator. And thank you all for participating in today's conference call. This morning, 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 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. 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, the presentation of additional data and other milestones 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 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 anti-cancer activity. This discussion will then be followed by comments from our Chief Financial Officer, Liz Williams, who will report our first fiscal quarter financial results and also provide you with an overview and rationale for our most recent financing.
While we acknowledge that this financing was costly, it does bring with it a number of key positives. First, a selection of fundamental healthcare-focused institutional investors, participated in this financing. Second, it removes the financing overhang for the foreseeable future in this very difficult markets. Third, it allows us to build momentum on the back of positive clinical data that I will share with you shortly. And to complete the combination arm of the Phase 1/2 ABILITY study. Fourth, it enables us to advance one of our novel BiSKIT candidates for IND readiness. And finally, and most importantly, puts us in a sound financial footing to pursue clinical collaborations in the combination of the ABILITY study. And as I mentioned, Liz will provide additional clarity later on.
For those interested in hearing and 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 22, and is available on our website at www.medicenna.com.
Getting back to our elite program, I will start by reminding everyone that MDNA11 is a beta-only long-acting IL-2 super-agonist. It has been engineered specifically to overcome the shortcomings of native IL-2, which is FDA-approved and known as Proleukin. Proleukin's shortcomings are mainly as a result of its severe toxicity for pharmacokinetic profile and mediocre affinity for the key receptor found on cancer fighting immune cells, namely, the IL-2 receptor beta.
These limitations necessitate those in 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, of 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, and 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 our albumin's ability to localize in the tumor and tumor-draining lymph nodes. As you know, we are advancing MDNA11's clinical development to the ongoing Phase 1/2 ABILITY study.
The primary objectives of this trial, as is the case with all first in-human Phase 1/2 trials, are to evaluate MDNA11's safety, PK, PD and establish the recommended Phase 2 dose required for the dose escalation portion of the trial. Once the recommended Phase 2 dose is established, the secondary objective of the trial would be to determine the potential anti-tumor 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 2 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 trials results to-date. Let me elaborate. First and foremost, we have not seen dose limiting toxicities in any of the 14 patients treated at each of the four dose levels. There have been no dose interruptions, dose de-escalation or treatment discontinuation in any of the patients due to safety issues with MDNA11 being administered via IV infusion, once every two weeks.
Furthermore, as expected, preliminary PK studies have shown dose-dependent increases in C-max and area under the curve, without any signs of immunogenicity upon repeated infusions. Also, fueling our optimism on the outlook of the ABILITY study, are encouraging pharmacodynamic data that provide strong mechanistic support for the tumor control results that I will share later.
Pharmacodynamic data have shown multi-fold increases in anti-cancer CD-8-positive T cells and natural killer cells that are greater than those achieved with competing agents administered at equivalent IL-2 doses. This was accompanied by limited or no stimulation of the eosinophil or Tregs, including ICOS-positive Tregs. This is significant as ICOS-positive Tregs are highly immunosuppressive and linked to resistance to IL-2 therapy.
In addition, high eosinophil counts are associated with vascular leak syndrome, which is one of Proleukin's most serious side effects. These pharmacodynamic results highlight what differentiates 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 maintained 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 anti-tumor 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 are 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 four, who had initially achieved stable disease at the first 12 week scan, subsequently showed additional tumor shrinkage at week 16, consistent with an unconfirmed partial response. This is significant.
Prior to entering the ABILITY study, the pancreatic cancer patient had surgery, followed by three systemic therapies, including first FOLFIRINOX, which is a combination of four different chemotherapies on which the patient progressed, followed by a second, a combination treatment with abraxane and gemcitabine, which the patient could not tolerate, and finally, treatment with an immune checkpoint inhibitor KEYTRUDA, which again, the patient could not tolerate.
Upon entering in the 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 that week 16 showed that both tumors had further decreased in size, with a 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 MDMA11, an independent research group demonstrated that an oncolytic virus, armed with MDNA109, a first-generation version of MDNA11, showed remarkable anti-tumor effects in a hamster model of pancreatic cancer, with over 62% of monotherapy complete response in this highly aggressive model of pancreatic cancer. We believe 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 mid-stage dose escalation cohorts provide an early sign of MDNA11's single agent activity. They view this as a very encouraging finding, especially when considering several aspects of the trial's patient population. First, there's the tumor types, in which we have observed disease control. As mentioned, 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's studies patients. All 14 patients enrolled in the trial to-date has failed between one and four lines of prior systemic therapy, including 11, who relapsed on or what unresponsive to checkpoint inhibitor therapy.
And third, there is the information we can glean from baseline measurements of lymphocyte counts. Lymphocytes, sites include CD-8-positive T cells, and natural killer cells, which are the cancer killing effectors of IL-2 therapies. Importantly, high lymphocyte counts have been shown to correlate with response to Proleukin.
When looking at baseline lymphocyte measurements made in the ABILITY study to-date, we see that these counts are much lower than those seen in prior studies of Proleukin. This suggests that the majority of patients entering the ABILITY study have tumors that are highly immunosuppressive and extremely difficult to treat, consistent with what we'd expect, based on the types of patients enrolled, and the clinical histories.
Based on this information, we amended the trial protocol to ensure that subsequent patients will have baseline lymphocyte counts that are higher and more in-line with what we would expect to see MDNA11's dose expansion portion of the ABILITY study. This amendment went into effect with our fifth dose escalation cohort, which evaluates patients receiving two 30 microgram per kilogram priming doses of MDNA11, followed by 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 a step-up dosing protocol now being administered to patients, we are exploring higher doses during this portion of the study, and aiming to further increase our chances of improving patient outcomes in a single agent setting.
Next month, we expect to report additional anti-tumor activity data from the trials fourth dose escalation cohort. In the fourth quarter of calendar year, we expect to announce initial anti-tumor activity data from the trial's fifth dose escalation cohort. Looking ahead into calendar 2023, we expect to report anti-tumor activity data from ABILITY's single-agent expansion and combination phases, 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, to 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 called and unresponsive to immunotherapies, such as pancreatic cancer. A key goal of the ABILITY study's next readouts would be to generate additional evidence of MDNA11's single agent activity. Doing this will further derisk and inform MDNA11's development and may present a critical inflection point for the company and a better treatment paradigm for patients that have failed to benefit from other immunotherapies.
So with that clinical review complete, I will hand off to Liz, so she can run through our financial results from the fiscal first quarter, and provide an overview of the recent financing. Liz?
Thanks, Fahar. And thanks to all listening. Before I begin, I'll note that all references are in Canadian dollars unless otherwise noted that. 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 a position of having MDNA11 Phase 1/2 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, and 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 is current shelf prospective 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 perspective, 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 to 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 events of positive news catalysts, the valuation of the company will increase accordingly.
As of June 30, 2022, Medicenna had cash and cash equivalents and marketable securities of $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 in the calendar year 2024, leaving us well-capitalized through important upcoming catalysts.
Net loss for the quarter ended June 30, 2022 was $4.2 million or $0.07 per share, compared to a loss of $6.4 million or $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 $2.4 million, were incurred during the quarter ended June 30, 2022, compared with $4.3 million incurred in the quarter ended June 30, 2021. The decrease in research and development expenses in the current fiscal years' 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 $1.9 million were incurred during the quarter ended June 30, 2022 as well as during the quarter ended June 30, 2021. General and administrative expenses were consistent quarter-over-quarter. 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, 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 provide meaningful clinical benefit. However, its utility is hampered by 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, albumins 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 the proliferation of cancer fighting immune cells.
And 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 favorable safety profile, total stimulation of anti-cancer lymphocytes, without activation of pro-tumor immune cells and encouraging signs of anti-tumor 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 dataset, as we continue to dose escalate and hone in on the tumor types that we believe MDMA11 will have the strongest impact.
With that. I would now like to open the lines for questions. Operator?
Thank you. We will now conduct the question-and-answer session. [Operator Instructions] Our first question comes from Matt Biegler with Oppenheimer. Please proceed.
Great. Congrats, guys on the on the early data, seriously. Fahar, maybe just speak more broadly to how IL therapies including KEYTRUDA work in general, and PDAC I don't believe that it's actually approved or indicated there. So is this like a lightning strikes kind of event? And then 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, and at least from the cytokine conference.
So was it -- would you say it's broadly consistent with our experience of IL-2 in general, or anything you can say on that? Because there just -- there seems to be a disconnect between the stock price and your current market cap and the quality of these data. So I'm just interested, if you have any thoughts why, and I know you talked a little bit about market dynamics, but anything else that maybe could help investors would be great. Thanks.
Great. Thanks, Matt, and thanks for your question. So 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, was -- as we have 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, the first dose generally had a tendency to have a higher fever threshold, which would last longer.
And then as patients receive the second and subsequent doses, you will 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.
So 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. And that's why we sort of employed -- proactively decided to proceed with an approach, where we'd enroll the patients, administer a dose of which we found was kind of 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.
So we needed to make sure first and foremost, we started at a dose that was clinically benefit -- 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. And 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 we 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.
So 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 Alkermes' Phase 3 trial, where although they were administered a rather low dose of, say, six micrograms per kilogram, which is the dose that they administered in the Phase 3 trial. We are already at the 60 micrograms per kilogram, we have a dose which is double that of nectar, or BEMPEG, despite the fact that our molecule is so much more potent.
And we've also seen that in the BEMPEG study, patients, when they saw well 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. So 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.
So that's basically where we are with the safety profile. Our safety review committee has agreed and enrolling patients now at a 90 micrograms per kilogram dose, so that is encouraging from a safety profile as well. And I think based on current data that we see at the 60 micrograms per kilogram, it seems like we're 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. The old treatment regimens of FOLFIRINOX, as well as a combo with abraxane and gemcitabine tend to be the standard of care for pancreatic cancer patients. And there's been very little out there that has been innovative for these patients. So 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. Remind you, it's just one patient. So obviously, we want to see more or 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. Are you 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 going to be looking at going forward? Thanks, again.
Thanks for that question as well, Matt. Yeah, so 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 BEMPEG, et cetera. 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 to 800 counts per microliter, which is, in some cases, less than half of the normal range.
So what we have done, as we'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. And this is something that we've implemented in our revised amended protocols. So cohort five 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 of baseline, is what we're seeing with Proleukin bearing out in your trial as well?
Not necessarily. It's just been that -- the lymphocyte counts is obviously one parameter. We have seen, as I mentioned, in the first three dose cohorts, where we did see, three out of eight patients have stable disease, their baseline lymphocyte counts were generally quite low. Certainly not down to 300 counts per microliter, but they're generally in the 800 or so, which is sort of closer to the threshold that we want to accomplish. And we have seen one of those patients with melanoma, for instance, just under the threshold of 1,000 lymphocyte counts per microliter who is stable -- has stable it is now for well over nine months.
And therefore, it might imply that we certainly do need a higher lymphocyte counts, particularly post-treatment with Proleukin. And there's 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 benefits.
And generally, they started about 1,000 or 1,500 to begin with Proleukin, increase the counts to 3,000 or so and these patients tend to benefit. And we're seeing now, at cohort four, as we disclosed this data at the conference, at the end of July, was that the baseline lymphocyte count in this cohort four 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, are they're still on trial, had they all stepped up to the 60 microgram per kilo dose?
Yes, they've all -- all the four patients are on study. They're all now receiving the 60 micrograms per kilogram dose. Yes.
And have any of the patients in cohort five stepped up to 90 yet.
Cohort five just started. So we've just started enrolling patients in cohort five. As you know, there'll be two doses, at the priming dose of 30 micrograms per kilogram. So it will be another month or so before get to the 90 microgram dose.
Okay. And 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 don't have that information handy with me. So cannot specifically mentioned what happened patient [indiscernible]. Of course, if patient responds differently to the therapy, depends on their baseline characteristics and so on. But certainly, we'll be able to share more data as we have ability to conduct further analysis of adverse events, if they've 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 up 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? Has the positioning of various parties change because you did raise the 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, and those discussions remain ongoing. I take --
Yes, they are. Yes.
Okay. Thank you.
[Operator Instructions] Our next question comes from Catherine Novack with Jones Research. Please proceed.
Hi. Thanks so much for taking my questions. I 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? With tumor progression, are you seeing commensurate increases in lymphocyte counts a proliferation? And then will we be seeing paired tumor biopsies in this cohort or it will be waiting for further cohorts to see those?
Okay. So hi, thanks, Catherine. And thanks for the question. So 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, and the post treatments and so when they sort of increase the day eight or 11, you'll see that their counts increased up to over 4,000 counts. And this is consistent with what we saw in the pancreatic cancer patient as well.
So in general, it seems like the pancreatic cancer patient who had a healthier baseline immune system seems to have benefited. So 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. So 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've seen 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 increase is continue, but they're not as dramatic as the first dose.
So I think there was some other question, but I might have forgotten if you can repeat that, please.
I wanted to ask about status of paired tumor biopsies, any -- which cohort we'll see.
Yeah. So 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 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 pretreatment biopsies, but on-treatment, as I said, we just have about three paired biopsies. We hope to get more of them as we go and more patients and the dose escalation, but we likely are going to get more patients willing to contribute their period 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. And then I just wanted to double check plans to conduct a sixth dose cohort. Obviously, at this time, you're only guiding to seeing data from the fifth cohort by the end of the year. What are the plans for additional cohorts beyond that? Will we see data next year or is that still to be determined?
Yeah. Cohort six is going to be to be determined. I think we've seen plenty in sort of quite a robust patient benefit response PDK -- PD data that are consistent with what we were hoping for what we're 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.
And we feel that it's unlikely we'll need to go higher than the fifth cohort, but we'll see, I think we played by year. And at the moment, we are assuming that the 60 and or 90 microgram per kilogram dose might be getting as close to the recommended phase two dose.
And can you remind us in terms of IL-2 concentrations, where 60 to 90 put you compared with other modified IL-2s that are being evaluated in the clinic?
Yeah. So it's -- obviously the dosing regimen is different. I think the only one comparison that I might have is BEMPEG, and also a nemvaleukin which is our Alkermes' 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 MPEG. 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 MDMA11 be adjusted high or possibly at 90 micrograms, maybe double the dose of Alkermes' molecule. So 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. So 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 Farah and Liz. This is Arthur on for RK. Thanks for taking my question. I had a two questions regarding the upcoming combination cohort study. So correct me, if I'm wrong. So my understanding is, are you going to dosing the MDNA11, with the CPI both at every three weeks regimen? Or if that's the case, could you tell us what how's your strategy to tweak the dose level for the MDNA11? Or you are going to just dose as the Q2 week as of right now and just using the Q3 week dose interval for the CPI?
Yeah, it's 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. And during that safety running portion, will 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 being used as well as what the safety running informs us before we proceed with the actual dosing and when we do the dose expansion during the combination part.
Got it. That's helpful. And regarding the starting of the combination dosing, will be a collaboration forged we see big pharma to provide a checkpoint inhibitor need to be completed before you guys started the combination phase? Thanks.
Yeah. So certainly, we are looking at different options with respect to collaboration. But 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. So it will be carefully evaluated before we proceed with that portion of the study together with the pharma company.
Thank you. Thank you for taking my question. And congrats on the progress.
Our next question comes again from David Martin with Bloom Burton. Please proceed.
Thanks for taking my follow-up. You mentioned earlier that was Proleukin baseline lymphocyte count also determined responsiveness to the drug. The label for the drug indicates a 15% to 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? And are there other biomarkers that are emerging from your study that you think confers responsiveness to MDNA11?
Right, thanks, David. So 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. So that was the baseline lymphocyte counts on both studies.
And in those, is also the responders generally were patients that had post-treatment or on-treatment lymphocyte counts increasing from 1,500 to 2,000, or more. So that was basically the sort of the take home message is, we need 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. So 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 than having a [Indiscernible].
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 -- ICOS-positive Tregs, those patients did not benefit. And whereas those patients that did not see an increase in ICOS-positive Tregs had reached.
So we're seeing something similar here with MDNA11. We are now monitoring ICOS-positive Tregs as well as CD-8 T cells that are ICOS-positive. And 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 it did all of them have high baseline counts, and the response rate was 15% to 16%? Or just among the patients who responded they have the higher baseline counts?
No, I don't think, 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 did they sounds were. But when they reported response rates, they did say that the response did occur in patients with lymphocyte counts during treatment to be above the 1,000. So, so that's the only information that we have that was published in that two or three different publications in melanoma and renal cell carcinoma.
But from baseline out, 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. Okay, got it. 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. And thank you for your participation. And have a great day.