Greetings, and welcome to the Q Biopharma Second Quarter 2021 Earnings Call. At this time, all participants are in a listen only mode. A brief question and answer session will follow the formal presentation. As a reminder, this conference is being recorded. It is now my pleasure to introduce your host, Doctor.
George Zavoic. Thank you, George. You may begin.
Thanks, Paul, and good afternoon, everyone. Thank you for joining us. On today's call are Dan Pasari, Q Biopharma's CEO Doctor. Anish Suri, President and Chief Scientific Officer Doctor. Ken Pienta, Acting Chief Medical Officer Doctor.
Matteo Lovasetti, Senior Vice President of Clinical Development And Cary Millar, Chief Financial Officer. Before I begin, I I would like to remind you that various remarks that the company makes during this call about the company's future expectations, plans and prospects constitute forward looking statements For purposes of the Private Securities Litigation Reform Act of 1995, actual results may differ materially from those indicated by these forward looking statements As a result of various important factors, including those discussed in the Risk Factors section of the company's annual report on Form 10 ks filed with the SEC on March 9, 2021 as well as other filings made by the company with the SEC from time to time, which can be accessed on the EDGAR database at atwww.sec.gov. In addition, any forward looking statements represent the company's views only as of today, August 17, 2021, and should not be relied upon as representing the company's views as of any subsequent date. While the company may elect to update these forward looking statements at some future point, the company specifically disclaims any obligation to do so even if the company's views change. Please be advised that today's call is being recorded.
Live and archived versions of the event can be accessed via the company's website for the next 30 days. With that, I would now like to turn the call over to Dan Fiserie, Q BioPharma's CEO. Dan?
Thanks, George. Good afternoon, everyone, and thank you for joining us today for a review of our ongoing progress as well as the Q2 2021 financial results, which are available in more detail in our Form 10 Q filed with the SEC on August 9. Our agenda for today's call is shown on the next slide, Slide 3. I'll provide first a brief overview Of ongoing progress since our last earnings call, highlighting recent developments with an emphasis upon Our lead clinical program, Q101 and strategic implications for the Q100 series regarding our competitive positioning and potential value creation for our shareholders. After the introductory update, I'll turn the call over to Doctor.
Nees Suri, Our President and Chief Scientific Officer will provide a synopsis of our approach for selective targeting of IL-two. After Anish provides an overview with Background context, Doctor. Ken Pienta is our acting CMO and Doctor. Matteo Levisetti, our Senior Vice President of Clinical Development will provide an overview of our ongoing Q101 clinical trial, our first and representative program from the IL-two base Q100 series. Ken and Mateo will then turn the call back over to Anish, who will provide further details on the expansion of our pipeline With the premise that Q101's development progress has essentially derisked and enhanced the value proposition of programs due to the platform's modularity.
Carey Millar, our Chief Financial Officer, will then provide a summary of our financial results for the past quarter, And I'll close with a summary prior to opening the call for questions. All right. To begin, I'd like to remind you of our foundational goal and that's Stated here on Slide number 4, which in essence is to design, develop and bring to patients in need Rationally engineered biologics with the aim of restoring immune balance by harnessing nature's own cues, Hence our name, a selective and specific modulation of disease relevant T cells directly in the patient's body. So we believe we're well underway to realizing our vision of leading the next wave of disruptive Breakthrough immunotherapies addressing the specificity and diversity of the human immune system to cure complex human disease. I'd first like to begin with Q101, our lead development program, which is representative of the IL-two based Q100 series.
On the previous earnings calls, we reported results pertaining to a refractory heavily pretreated patient that had a confirmed partial response or PR From the monotherapy Phase 1 dose escalation part of the Q101 trial, this patient remains on study And as Ken and Matteo will discuss momentarily, has demonstrated a durable PR after multiple scans with the latest scan evidencing additional tumor Reduction. We view this durable and ongoing resist confirm partial response as an important derisking event, confirming the ability of Q101 to selectively engage and continually modulate T cells in a challenging patient population. While still early in development, we believe that the growing body of clinical data is encouraging and supports the promise and potential of Q101 having a registrational path forward as a monotherapy and third line and beyond HPV positive Furthermore, as Anish will discuss, we also view the data as supporting the premise That our IL-two based Q100 series represents a potential breakthrough development in the clinical application of IL-two for As the drug candidate's mechanism of action is based upon activating cancer specific T cells Directly in the patient's body, in the case of Q101 that's HPV E7 specific T cells, We believe this growing body of data supports our position that not only could Q101 have a possible registration path as a single agent, but may also enhance patient reach and therapeutic benefit for frontline HPV positive head and neck cancer patients in combination With Pembrolizumab, which is currently standard of care for these patients, the combination trial referred to as Keynote A78 is presently enrolling patients in the 2nd dose cohort as Ken and Matteo will momentarily discuss during the clinical update section.
So in summary, we believe the ongoing data emerging from the monotherapy trial to be transformative for Q Biopharma As it provides preliminary objective evidence of clinical activity as a single agent monotherapy in a late stage prior treatment refractory patient Population and clearly differentiates our drug candidate Q101 as well as our IL-two based Q100 series from Competing IL-two modalities and vaccine programs. As we continue to observe supportive data in our ongoing Phase 1 dose and expansion trial. It's important to recognize that these data could not only provide potential risk reduction and validation for Q101, but also by implication the entire IL-two base Q100 series. The underlying framework for the IL-two base Q100 series remains essentially the same across programs with the only primary difference, for example, between Q101 and Q102, Being the 9 to 10 amino acid antigenic epitope in the MHC or HLA binding group, The key features underlying our ability to target selected cancer relevant T cells is based upon engineering a molecule that builds upon Fundamental Principles of T Cell Activation. Anish will now elaborate upon these characteristics and features of The Q100 series and the foundational importance of these observations as they relate to the selective delivery of IL-two to tumor specific T cells.
Anish?
Thanks, Dan, and good afternoon, everyone. I'd like to begin by highlighting the objective of the immuno oncology sector to activate a cancer specific immune response, while avoiding the unwanted deleterious effects due to non specific immune activation. To that end, we believe that our Q100 series Immunostat platform enables the selective targeting of interleukin-two or IL-two to tumor specific T cells. As shown here and evidenced by the number of pharmaceutical and biotech companies developing IL-two centric approaches, IL-two is a well validated target for cancer immunotherapy, albeit with associated liabilities and limitations. IL-two is an approved biologic therapy for metastatic melanoma and renal cell carcinoma.
However, the lack of selectivity and safety have hindered its broad application and Wider clinical potential. Examples of associated toxicities include vascular leak syndrome and cytokine release syndrome Along with undesired effect on many immune cells, including the activation of regulatory T cells, which may counteract anti tumor immune responses. As such, a significant opportunity exists for next generation IL-two approaches to address and circumvent these challenges. Through Rational Protein Engineering, we appear to have met this challenge and have the prospects of a breakthrough solution, enabling the true potential of IL-two for selective immune activation. The next slide, Slide 6 highlights the challenges with lack of cellular specificity of IL-two or IL-two variants.
As shown here, only a minuscule fraction of the entire CD8 T cell repertoire Harvest specificity for tumor antigens. Note that the tumor specific T cells here are shaded in red, while the non tumor specific T cells are shaded yellow. The vast majority of a patient's T cells are likely greater than 99.9% are directed against other known tumor specificities. In this context, a wild type IL-two or a variant IL-two molecule like a non alpha IL-two will be inclined to indiscriminately engage the vast majority of CD8 T cells with little relevance to the minor tumor specific T cell fraction. The result of these non selective interactions is a brazen activation of the broad immune compartment with no selective bias towards the tumor specific T cells.
This lack of specificity coupled with safety considerations creates significant barriers for extracting the fullest potential of IL-two treatment. We sought to find a protein engineering solution to this challenge as shown in the next slide, Slide 7. The breakthrough here was that we exploited our Immunostat platform to specifically select for an IL-two variant in context of tumor specific T cell activation. This is very different from what others have done or we believe are doing, which is to select for an IL-two variant only in context of interactions We know from fundamental immunological principles that a key step in T cell activation is engagement of the T cell receptor or TCR to specific peptide HLA complex molecules. Hence, We use this natural biological mode of T cell engagement to design the Q100 series of immunostats, which contain tumor peptide HLA molecules, along with modified IL-two as shown in the left panel of the slide.
The modified IL-two is designed to selectively act upon tumor specific T cells whose TCR is engaged to the PHLA component of the Q100 series immunostat. If the TCR is not engaged, As would be the case with the vast majority of the non tumor specific T cells shown in yellow, then the signal from the IL-two variant on its own is relatively weak. Hence, the Q100 series is a molecular scaffold that exploits both TCR and IL-two signals to set the optimal signal amplitude for selective activation of tumor specific T cells. The ribbon structure in the right panel of the slide provides molecular details of the configuration of the IL-two based Q100 series. Each molecule is built upon an antibody Fc scaffold and consists of bivalent peptide HLA molecules, Shown in blue that engage tumor specific T cells along with 2 molecules of IL-two on either side for a total of 4 IL-two molecules.
The IL-two variant has 2 key changes. 1 abrogates binding to IL-two receptor alpha, which helps mitigate safety issues with systemic activation and minimizes the bias towards regulatory T cells. The second mutation reduces binding to the IL-two receptor beta subunit Such that the composite signal strength for T cell activation is dependent upon additional signals from the TCRs engaged to the PHLA component. This tuning of signal amplitude ensures biased activity of IL-two and TCR engaged T cells. The next slide, Slide 8 highlights the preferential activity of the Q100 series immunostats on tumor specific T cells over the majority of T cells that are not There are several advantages to our approach.
1, as mentioned, the selective activity of IL-two on TCR engaged T cells, both in CIS and trans interactions. SINCE interactions will be tumor specific T cells that engage the peptide HLA and IL-two component of the immunostat. Transinteractions refer to the IL-two variance activity On other tumor specific T cells whose TCRs may be engaged with either tumor cells or antigen presenting cells in the tumor or lymph nodes. We believe this potential could further expand the antigenic diversity of the antitumor T cell response. Furthermore, we've demonstrated expansion of NK cells, which could be an added benefit for cancer immunotherapy, while the effects on Tregs All regulatory T cells have been transient.
Matteo will discuss these findings in the clinical section of this presentation. Lastly, we have observed a generally favorable safety and tolerability profile. The lead candidate Q101 has been dosed up to 8 mgs per kg between wild type IL-two or IL-two variants and our Q100 series. For the wild type IL-two or its variants, the lack of IL-two The wild type IL-two Aldis Leukin is 37 micrograms per kilogram with a half life of about 80 to 85 minutes. Similarly, for the various nord alpha IL-two variants, the chosen clinical doses have ranged between 6 to 24 micrograms per kilogram as shown here.
In contrast, we have successfully dosed Q101, our lead clinical candidate from the Q100 series, Up to 8 milligrams per kilogram with no MTD having been identified. Hence, we believe that Q101 demonstrates a dosing range for IL-two with an adequate therapeutic window. This will be discussed further by Ken and Matteo in the following sections focused on the clinical data. Okay. With that, I'd like to hand the call over to Ken.
Ken? Thanks, Anish, and good afternoon, everyone. As shown here on Slide 10, Q101 shares the core scaffold of the Q100 series. It consists of a peptide from the E7 protein of HBV-sixteen or human papillomavirus coupled to the HLA AO2 molecules along with the IL-two variants to target cancers driven by the human papillomaviruses such as head and neck cancer and others. The molecular design of Q101 enables us to identify eligible patients based on HLA AO2 positivity And HPV-sixteen positivity for the tumor.
As always, I'd like to thank our principal investigators and the patients participating in our ongoing clinical As we've noted on previous earnings calls, we have continued to successfully screen and enroll HPV-sixteen positive head and neck cancer patients to participate in our Q101 clinical trial throughout the COVID-nineteen pandemic. Furthermore, despite the challenges of the COVID pandemic to date, we have successfully executed on our defined development plans and timelines and they have achieved our stated objectives on schedule. The next slide, Slide 11, shows our high level summary of the clinical design and dosing cohorts for our ongoing Phase 1 trial Of Q101 enrolling 3rd line and beyond patients that are HLA-two zero one positive with Recurring or metastatic head and neck squamous cell carcinoma driven by HPV-sixteen. We completed enrollment in the Part A dose escalation portion of this trial and are now enrolling into the Part B dose expansion phase of the trial at the presumed recommended Phase 2 dose of 4 mgs Representing the dose of Cohort 6 of the Part A dose escalation. Our expectation and projection is that we will complete enrollment of 20 patients by early Q1 2022.
The next Slide 12 provides a high level summary of the observations made over the course of the dose escalation part of the study. 38 patients were treated across 7 dose escalation cohorts without an MTD being identified. 1 confirmed ER in 8 patients with confirmed stable disease lasting for more than 12 weeks have been observed. Pharmacodynamic markers of therapeutic activity include the demonstration of expansion of disease relevant CDAPositive T cells And NK cell is an evidence of tumor invasion by tumor infiltrating T cells or TILs. We will be providing an I will now pass the presentation to Matteo to discuss some of our
Thanks, Ken. The next slide, Slide 13, shows some of the details about our enrolled patients to date. The vast majority of our patients, more than 90% have been treated with Q101 as third line or beyond therapy after failing both platinum based chemotherapy and a checkpoint inhibitor. Many patients also failed treatment with the epidermal growth factor inhibitor cetuximab. This is an important note.
Although our R and D was originally cleared by the FDA to test Q101 as a second line agent after platinum failure In the first line, pembrolizumab was approved in the first and second line settings as our trial was being initiated. Functionally, this has de facto shifted this trial into the 3rd line setting and beyond. There is no approved therapy for recurrent HBV While presenting the increased challenge of treating highly pretreated and refractory patients, We believe that this opens a potential registration path for Q101. Several ongoing observations give us confidence that our data is Maturing in a manner that could allow us to define multiple potential registration strategies with the FDA. 1st, As shown in Slide 14, our data to date demonstrate the tolerability of Q101 in patients both as a monotherapy and in combination with Pembrolizumab, our presumed recommended Phase 2 dose of 4 mgs per kg appears to be well tolerated in the target population.
Our first cohort of patients in the combination study at Q101 dosed at 1 mg per kg did not experience a DLT, And we are now enrolling the 2nd cohort at 2 mgs per kg of Q101 in combination with pembrolizumab. All of the SAEs and AEs observed to date are consistent with those observed with IL-two administration or are typical of those observed with checkpoint inhibitors in the treatment of cancer patients. The most common AEs observed continue to be fatigue, Anemia and decreased lymphocyte counts. 2nd, our pharmacokinetic data at the recommended Phase 2 dose as shown in the next Slide, Slide 15 reveals consistent exposure without any evidence or effect of antidrug antibodies on PK and exposure in patients that have received multiple doses of Q101 as shown in the bottom panels of this slide. 3rd, our PD data, as shown in Slide 16, demonstrates a consistent increase In natural killer cells or NK cells across all subjects in Cohort 6, in contrast, we see a modest and transient increase In CD4 positive FOXP3 positive T cells, presumably regulatory T cells or Tregs that returns to baseline levels shortly after dosing.
We have also reported on evidence of increase in tumor specific T cells, an example of which will be shown later. Importantly, we have observed what appears to be a dose proportional PD effect as well as corresponding clinical benefit, including 8 patients with stable disease lasting greater than 12 weeks and a confirmed PR with the majority of these observations occurring in cohorts 5 and 6, I. E. At doses of 2 and 4 mgs per kg, respectively. The data generated in the dose escalation Part A of the trial signs of clinical activity from observations and scans from Cohorts 4, 56 that demonstrate durable stable disease.
Furthermore, the dose escalation demonstrated what appears to be a relatively broad therapeutic window with a dose range between 1 mg4 mgs TIG where PD activity as well as clinical activity and benefit have been observed, while appearing to be well tolerated. We also observed and continue to observe clinical benefit within the higher dose cohorts and have had 2 additional patients recently demonstrate confirmed stable disease on their early scans. We remain encouraged by this growing body of data and as conveyed by Ken, believe we have Registration path going forward, including as monotherapy for 3rd line and beyond. As an update from what was reported in the previous earnings calls, as shown in the Slide 17, with histo Pathology evidencing clear signs of antitumor activity and T cell infiltration. This patient has been reported by the PI as evidencing no signs of active The next slide, Slide 18, Also shown during a prior earnings call demonstrates supporting data for the mechanism of action of Q101.
We clearly observe a significant increase Tumor infiltrating lymphocytes within the tumor tissue, post treatment with Q101, demonstrating Granzyme B, a serine protease found in the granulars of NK cells and cytotoxic T cells. It is a weapon utilized by these cells to kill target cancer cells. This slide demonstrates biopsies from a patient in Cohort 5 before and after administration of 2 doses of Q101. In the post treatment picture on the right and quantified on the graph on the far right, you can see a marked increase in cytotoxic T cells secreting Granzyme B, Again, providing valuable validating data supporting the mechanism of action of Q101. Hence, The immunostats have the potential to directly engage tumor infiltrating T cells and NK cells, which may also alter the local tumor microenvironment to favor anti tumor immunity.
This mechanism of action of Q101 will be further explored in an investigator sponsored new adjuvant trial at WashU, Washington University in St. Louis, in which treatment naive patients will be given Q101 prior to surgical resection the resected tumor will be examined for evidence of tumor infiltrating lymphocytes. 4th, The clinical benefit rate as a single agent during the escalation phase of the protocol is encouraging. Slide 19 demonstrates a partial response In a patient treated at the recommended Phase 2 dose now out over 28 weeks on therapy. Increases in HPV E7 specific CD8 T cells and NK cells were observed in this patient as well.
Slide 20 shows a reduction of approximately 57% in one of the patient's target lesions. We all recognize that PRs and CRs occur infrequently in third line and beyond HBV CV positive head and neck squamous cell carcinoma patients. Importantly, we are also following patients for clinical benefit, which is defined as patients with at least stable disease on study for more than 12 weeks. In the dose escalation phase of our study, to date, we have observed a preliminary clinical benefit rate of approximately 27% in these third line and beyond patients. As noted in previous earnings calls, we also We continue to monitor progression free survival and overall survival closely and continue to observe what appears to be an enhancement of survival of patients in the Q101 dose escalation trial.
With all the caveats of a relatively small number of patients, We're intrigued and encouraged that the first nine patients on the study treated with the lowest doses of Q101 Have a median overall survival of greater than 12 months. We continue to follow patients in our latter cohorts and of course, This will be an important metric to follow in our recommended Phase 2 dose cohort as we finish accrual and monitor these patients. Our clinical trial protocol amendment for the expansion phase now cleared by the FDA since the last earnings call Allows for patients to remain on study at investigator discretion if they demonstrate radiographic progression, but are clinically stable. It furthermore adds measuring response by iResist to the exploratory endpoints and also allows the collection of data regarding follow on anticancer treatments patients may receive to gain further insights into our survival observations. I will now hand the call over to Ken to summarize our registration strategy.
Thanks, Matteo. We believe that these exciting clinical observations and the observed support of our PIs who continue to accrue patients to the study provide supporting evidence that Q101 is an active agent with promising potential For HPV positive head and neck squamous cell carcinoma patients and our emerging data opens several potential options for a registration path. First, we will be able to perform a registration study as a third line therapy for HPV positive head and neck cancer as shown in Slide 21. There may also exist an option for second line therapy in CVS Score patients less than 1 who are not eligible for pembrolizumab. 2nd, also shown in Slide 21, we will continue to perform our study in first line HPV positive head and neck cancer in combination with kenbrough as a potential registration path.
3rd, we will be initiating our neoadjuvant study at University St. Louis with the intention to demonstrate the value of Q101 treatment in patients prior to primary treatment. 4th, we plan to initiate an adjuvant study at Johns Hopkins in 2022 with a goal of demonstrating the value of Q101 with pembro in patients at high risk of recurrence. At this juncture, I turn the call back over to Anish for a brief synopsis Regarding the expansion of our drug candidate pipeline based upon the Q100 series framework. Dinesh?
Thanks, Ken. As conveyed throughout this call, the data emerging from our ongoing monotherapy trial of Q101 Support the design of the IL-two based Q100 series, which can selectively modulate tumor relevant immune cells To enhance therapeutic benefit and circumvent IL-two toxicities, a key strength of the ImmunoStat platform Is its versatility and modularity with respect to swapping different tumor derived T cell epitopes to change the indication of interest? As an example, Q101 targets HBV E7 specific T cells, while Q102, our next Clinical candidate targets Wilms Tumor 1 or WT1 specific T cells. As shown in the next slide, Slide 22, WT1 has been widely recognized as an attractive tumor antigen and is upregulated in numerous solid tumors and hematological cancers, including colorectal, pancreatic and AML amongst many others. Most of the molecular framework, including the IL-two molecules identical between Q101 and Q102 with the primary difference being the 9 to 10 amino acid T cell epitope that is tumor specific.
The next slide, Slide 23 highlights the preclinical data for Q102's ability to prime and expand WT1 specific T cells from human blood ex vivo and in vivo in transgenic mice treated with Q102. Also shown in the bottom panels And their ability to kill WT1 expressing target cells, both in vitro and in vivo. As shown in the next slide, Slide 24, It is our belief that our immunostat pipeline assets, including Q102 and Q103, which targets a mutated KRAS G12V T cell epitope, Have a significantly reduced risk profile and enhanced value potential due to the clinical observations of Q101. We have been deliberate regarding our development strategy, wherein Q101 establishes a beachhead or a foothold upon which we intend to expand our drug candidate pipeline and our market potential. We believe this strategic vision allows us to harness The maximum potential of IL-two in cancer immunotherapy.
I will now hand the call over to Kerry to discuss second quarter financial results, And Dan will then return for brief closing remarks. Keri?
Thanks, Anish. Turning now to Slide 25, I'd like to provide a brief update on our financial results for the 3 months ended June The company reported collaboration revenue of approximately $2,700,000 $1,100,000 for the 3 months ended June 30, 1 and 2020, respectively. The increase of $1,600,000 was primarily due to additional research and development and contract manufacturing activities In preparation of an investigational new drug filing for Q102, our second drug product candidate from the IL-two base Q100 series, which is planned for the Q1 of 2022. Research and development expenses were $8,800,000 8 and drug substance manufacturing costs as well as clinical expenses. General and administrative expenses were 4 point $3,000,000 $3,900,000 for the 3 months ended June 30, 2021 2020 respectively.
The increase was due primarily to stock based compensation and legal fees During the Q2 of 2021 as compared to the same period in 2020. We ended the quarter with approximately $73,900,000 in cash and cash equivalents and working capital of approximately $63,000,000 We believe our cash and cash equivalents as of June 30, 2021 I'll now turn the call back over to Dan for closing remarks. Dan?
Yes. Thanks, Carrie. In conclusion, The observation of clinical activity of Q101 as a monotherapy in this challenging and heavily pretreated patient population It is in fact an important step forward and supports the potential of not only our Q101 drug product candidate, But also for follow on drug product candidates as well such as Q102, Q103 from the IL-two based 100 series providing valuable proof of concept of the Immunostat platform to activate and expand cancer specific T cells and NK cells directly in the patient's body as a method to treat a myriad of cancers. We believe the data continuing to emerge
from our
ongoing Q101 trial What's the premise that our approach has in essence created the next generation solution to utilizing IL-two as a targeted and Selective immune activator for treating cancer. Furthermore, we believe the data demonstrates clear competitive advantage over other modalities and provides Q Biopharma and its shareholders with a strong foothold upon which to further demonstrate, Expand and establish this competitive positioning. We continue to execute our corporate strategy in a focused and deliberate manner with the aim of demonstrating clear competitive advantage and market positioning of the Immunostat platform and associated programs. We have successfully executed our stated corporate objectives throughout the year and believe the Q101 monotherapy trial provides The registration path forward as a single agent therapeutic and the combination trial with KEYTRUDA provides the prospects to enhance patient reach We look forward to providing trial status updates on a going forward basis. Finally, we'd like to thank our employees whose dedication to our mission through their commitment and professionalism Allows us to continue executing our corporate development strategy even through the past year with the trying times with COVID.
We'd like to thank our Board of Directors for their support and guidance and want to thank our shareholders who provide us with the essential resources to continue our important work Developing promising therapeutic candidates for patients in need. We thank our principal investigators and staff at our clinical sites We remain excited about Q101 and our rolling patients in our studies. Most importantly, we want to thank the patients themselves and their families involved in the clinical trials. Their courage and willingness to be part of a clinical study allows us the opportunity to assess potential drug activity and assess the potential for therapeutic benefit of our promising drug candidates. Thank you very much for your attention and interest.
And I'd like to now turn the call back
Thank you. Our first question comes from Marc Breidenbach with Oppenheimer. Please proceed with your question.
Hey, good afternoon, guys, and congrats on the progress. Just a few questions from me. First, with respect to The selection of your dose to take forward into the expansion cohort, I think I heard Ken mention that you saw dose dependent PD markers maxing out around the 4 mg per kg dose and that helped you pick it. I'm just wondering, does that imply there was sort of Bell shaped pharmacodynamic response and did it actually get a little bit worse at 8 mgs per kg? And if so, Any speculation as to why that might be the case?
Yes. Mark, I'm going to let Anish take that question, but I just want to clarify. We went up to 7 cohort, which was at 8 mgs per kg. We didn't actually see a plateauing on PD, etcetera. The emergence of off target activities that we felt since we had a therapeutic window emerging between 1 mg per kg and 4 mgs per kg.
We were better served to go with the Cohort 6 dose, which was just much better tolerated. So I think that was the key metric. It wasn't that we saw the PD plateauing, but I'll turn it to Anish to elaborate.
Yes, I think that's right, Mark. Where we saw the PD Signals clearly emerges around the Cohort 4 dose, which have been subsequently continued to build on through 56 And have not we've not seen a bell curve. We certainly when you look at, for example, broad changes in NKs, which is a broad IL-two sensitive population that tends to be very consistent at these high doses and that we thought was very favorable for the choice of the RP2D. Similarly, as Matteo sort of mentioned in contrast, when you see the other end of our very IL-two sensitive broad population visavis the regulatory T cells, Tregs, We saw the transient uptick, but then returned back to baseline and we it just sort of made sense to us that there seemed to be a really great window to be in.
Okay. That's helpful. And can you just remind us on the study, if the patients were receiving Prophylactic oral or IV fluids to prevent hypertension associated with vascular leak. Just asking because we've seen this approach used Another IL-two variant trials.
Yes, I'll turn it to Ken to answer that.
Very simply, they were not. There was no Three medications, no prophylactic medications used.
Okay, good, good. And final question for me, just with respect to the other 2 100 series immunostats.
Do you see any risk that
If there are higher baseline prevalence of, let's say, WT1 specific T cells, Could that potentially translate to a narrower therapeutic window based on the different antigen specificity? And is there any preclinical evidence to suggest that you can safely dose different Q100 immunostats targeting different tumors without seeing dramatic safety differences?
Yes. We don't anticipate that, Mark, and that's much of that is actually based upon some good preclinical data, including In for example, with Q102 that targets WT1, we see the induction and expansion in HLA AO2 trans Genic mice as we showed in that slide and we'll continue to expand upon this as we release data towards for the rest of the year. That expansion is significantly higher when you compare it to, for example, what we could achieve with the E7 specific. I We could do C7 specific, but in this case, for whatever reason, the precursor frequencies and the baselines tend to favor WT1. And with no sort of observations, if any growth sort of safety or tolerability issue.
So we think again coming back to how the IL-two was selected That it is quite relevant to the TCR engaged population. And in this case, when you've got ranges where that population is skewed towards a higher abundance, again, that tends to be can be quite safely, at least with the early evidence we have. So, there's although we'll keep an eye out on that, Mark, the data so far supports that we should be able to move in with a great degree of confidence.
Perfect. Thank you so much for clarifying and thanks for taking the questions.
Thank you, Mark. Thank you. Our next question comes from Stephen Willey with Stifel. Please proceed with your question.
Yes, good afternoon. Thanks for taking the questions. Maybe just one on the Date that you guys had mentioned was planned for SITC. Should we expect to also get some preliminary dose
Yes. Thanks, Steve.
Ken, you want to take that?
Yes. Thanks for the question. I think we'll have some data About that as well as certainly later in the year, we've Finished Cohort 1, we're dosing Cohort 2. So we're and we're following those patients. So we expect news, yes.
Okay. And then maybe if you could just expand a little bit on the organizational strategy that you're, I guess, now speaking to. And I guess, when you think about the path Forward for monotherapy, how do you, I guess, juxtapose That approach, I. E, single arm response rate based endpoint versus Something whereby you're looking at a comparator arm of maybe best supportive care or Physicians Choice of Palliative Chemo and in addition to generating that response rate data, maybe having a back Stop. That is event driven data in the form of either PFS or OS, which seems to be encouraging at this point.
And How do you think about the execution of something like that relative to just kind of the traditional monotherapy response rate based approach?
Well, fantastic question and really perceptive. And we're Clearly, going to have to go to the FDA to get a sign off on any trial we do. As you know, there is Certainly no approved third line therapy. So it would be our preference to Certainly do a single arm study based on clinical benefit rate as well as overall survival And just power it with enough patients, for example, just continuing on the expansion phase study And just power it that way. If the FDA requires us to do A comparator arm, I think it's going to be difficult because You'd be asking to randomize to sort of best supportive care or best palliative care, Which is never very exciting for patients.
And I think the FDA is, as you know, Struggling with what to do with single arm studies right now, but there's also a general consensus that if patients don't deserve to I'll be randomized to care that is not going to extend their life. So I think we have a really good chance I'm doing a single arm study and we're going to go to the FDA with that idea.
Okay. And so when you speak to, I guess, powering a single arm study for something like survival, is Would that be compared against a natural history arm? I'm just trying to understand what you would be powering against in the confines of it being A single arm?
Well, so again, a really good question. And I think if you look at The data from the survival data from single agent pembro second line Or any of the Check Point's second line in head and neck cancer, I think we'll be able to use those as a competitor, as a traditional comparator. And I believe that If we say that we're going to increase that survival by a significant percent that we will That will be compelling to the FDA.
This is Matteo. If I can also just add that A component of the regulatory strategy that's gaining further traction may be to present To FDA, if there's pushback on just a single arm expansion, the use of real world data or a synthetic control arm or at least a fractional synthetic So there are opportunities in this setting where it's really close to unfeasible to do a good randomized trial where FDA will work with a sponsor to come up with a powering of a sample size To a synthetic control arm, that's acceptable.
Okay. Thanks for taking the questions.
Thanks, Steve. Thanks, Steve.
Thank you. Our next question comes from Tom Schrader with BTIG. Please proceed with
your question. Good afternoon. Congratulations. I had one question on this interesting OS Study or OS signal you're seeing in early patients. And if you want to if you're saving this for SITC, just tell me.
But is there any structure to that? Because in some of the earliest cohorts, patients got very little drug. So is there any correlation with this effect with patients that actually got Significant amounts of treatment?
So thanks for the question. And what I can say That it's too early for us to talk about the later cohorts. We just don't have enough depth yet to know. So I think that is as good as the answer as I can give you. We were able to look at the first nine patients even who got a whiff of drug And we were able to sort of look very preliminarily at a median overall survival.
We just don't have enough data on the later cohorts
Okay. And then a question on Slide 19, where you have this very long response, Where the patient has, I don't know, 3 months of stable disease. How literally can we take that line? How noisy is that? Is this really a patient that at 4.5 months the tumor starts to dissolve further?
And maybe for Anish, is
So Firstly, I'll let Ken and Matteo answer to the clinical question, Tom, because these are all hard metrics. Ken and Matteo, if you want to just comment on the tumor measurements on Slide 19?
Yes. So, thanks. Those are resist criteria. Those are measured At the site, so we have nothing to do with those measurements. And what we've seen is that with the latest measurements The tumor shrank even more than it did previously.
This is a Patients that were following 2 lesions in and we're seeing a response in both lesions. And certainly, Anish can talk about the biology of that, but Again, with immunotherapy as it has time to work, you have a balance of necrosis, fibrosis, As well as killing of tumor cells going on. So I'm very encouraged and this is one of the reasons why We really wanted to keep patients on study who were having some clinical benefit to give them time to have potentially these Kinds of results come in. So I feel really justified in putting that amendment in To allow our investigators to keep patients on even though their tumors You know, are equivocal, but if they are clinically benefiting. Matteo, do you want to add anything before Anish talks?
No, I think that covers it quite well. With regards to the mechanism, I think we're learning more and more that different immunotherapies have a kinetics to monocost their treatment effect That's a bit more prolonged or unique. And again, we could hypothesize that there's amplifying loops So increases in T cells that are E7 specific that occur as the tissue as the tumor is being killed and as antigen goes into the Antigen presenting compartments and then restimulates, and T cells. But again, it's just very reassuring to
So Tom, just mechanistically, there's several access we believe could be operational, which is why I sort of try to highlight. As you see in this patient in the first scan, which is 6 weeks after 2 doses, you see about a 45% to 48% reduction in that range, Which is now reaching 60 close to 60%. Patient is being dosed every 3 weeks. We see a nice uptick of E7 specific T cells, but One of the reasons we highlighted NKs is as you have the chronicity of the immune system and the response set and Other elements could be operational, including T cells, including NK cells, including the fact that the IL-two is active in trans, This is one of the reasons, Tom, because of this kind of observation and the histology that Matteo showed you with the Granzyme B positivity pre and post biopsy Well, the neoadjuvant study becomes really, really exciting for us, where we will have tumor tissue from every patient pre and post Blood pre and post to be able to make these kinds of heart assessments, including Till infiltrates, including their specificities, the diversity in the phenotype. So we think There are multi nodal operational elements of the ImmunoStat platform that must be appreciated and we've got to look at this with a wide sort of set of eyes here.
Okay. Thanks for tackling a tough question.
No, no, no. Very pertinent. Thank you, Tom.
Thank you. Our next question comes from Brian Skorney with Baird. Please proceed with your question.
Hey, good afternoon, everyone. Thanks for taking my questions. I guess, I just had some questions sort of on how you guys think about patient selection. I mean, starting with 101, Based on the early data that you have so far, is there any sort of biomarker that kind of defines a subgroup that has some level of Predictive response, and if not, is there any subgroup that you kind of think in the registrational pathway looks particularly attractive targeting that you think it'd be generally a more challenging subgroup because of that maybe has a lower hit hurdle, but you would still expect 101 to work well. And then likewise, when you think about the Q102 program, obviously, there's a broad range of HemOnc indications applicable here, but we'll be doing any baseline screening
So I think at this point, we don't have a biomarker to choose. What I think the power This is that I'm not sure we need one. I think that the mechanism of action is such That in delivering attenuated IL-two stimulation right to the appropriate T cells Abrogates the need to worry about subgroups of patients. And in fact, we really don't want to parse out Then if we don't need to. And at this point, I don't see a need to do that.
We, of course, as the Trial matures and we're looking at data. For example, we'll be following patients for circulating tumor HPV Data, DNA, that may give us a marker of Who might benefit and as well as how folks are responding and clearing that. And we've got some other biomarkers we're looking at So, but my hope is that we don't need 1.
And for 102, Ken, do you want to just comment on the WT1 expression?
So yes, sorry. So Again, for WT1, we'll be doing again HLA-two zero one patients. And then we are working right now with the FDA in our IND filing to choose a very specific Assay where patients will have some level of WT1 expression, different Studies that have used WT1 as vaccines, etcetera, have used different criteria For enrollment, what I can say right now is that we intend to have a very Liberal enrollment policy as far as WT1 expression on the tumor tissue goes.
Great. Thank you. That's helpful.
Yes.
Thank you. Our next question comes from Shiqiu Shu with Berenberg, please proceed with your question.
I'd like to ask about the registration path you guys laid out earlier on the slides, particularly for The PD L1 negative patients, just wondering what are you thinking in terms of getting the trial running in terms And also, as far as I know, physicians usually use chemo to treat these type of patients. I wonder, have you considered maybe combining your drug with chemo to run a frontline trial? Thanks very much.
Yes. Well, thank you for those questions. So in the 3rd line setting, the patients will have received A platinum combination therapy, often with or without cetuximab as 1st line therapy or second line therapy, many of those patients in the adjuvant setting or neoadjuvant setting will have also seen A platinum or 5 FU based regimen. As you know, pembro with chemo is quite effective In first line patients, and so what we're expecting is that in the third line setting And the 2nd line patient with CPS scores less than 1, patients will have already seen chemotherapy. And again, there is no approved chemotherapy for second and third line patients Beyond the platinum combination therapy platinum or platinum combination therapies.
So we're not in the short term expecting to certainly in second and third line Combine Q101 with chemotherapy at this point. What where we will floor with the FDA is and we don't know what they'll say about this yet. But again, Patients who don't have a CPS score greater than 1 are not eligible for pembro. It simply doesn't work. We do believe, however, given the mechanism of action of Q101 that our drug will be just As effective in those patients, and so we would like to include them as part of A third line study, and we will present that idea to the FDA, and we think that There's a good possibility they will allow that given all of the data I just heard all the things I just said.
So that's our strategy right now.
Got it. Thanks very much.
Thanks, Pete. Thank you.
Thank you. There are no further questions at this time. I would like to turn the floor back over to management for any closing comments.
All right. Thank you. Thanks again for your attention on today's call. And as always, we look forward to providing further updates
This concludes today's conference.