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spk06: condition, our business operation, development efforts, and relationships with third parties and collaborators, and are neither predictions nor guarantees of future events or performance. Actual results could differ materially from those stated or implied by these forward-looking statements due to risks and uncertainties associated with our business, including those under the heading entitled Risk Factors in our annual report on Form 10-K. The year ended December 31, 2020. in our quarterly report on Form 10-Q for the quarter ended March 31, 2021, that will be filed with the SEC today and in subsequent reports, including our current reports on Form 8-K. The company disclaims any obligation to update or revise any forward-looking statements, except as required by law. Michel?
spk00: Thank you very much, Ryan, for the introduction, and thank you for joining us for our first quarter of 2021. For today's call, I will provide a brief recap of our corporate strategy and overview of progress within our pipeline programs, as well as the multiple opportunities and readouts for our clinical programs. And we'll turn the call over to Dr. Joe Leger, our chief medical officer, to provide the status update and review of our most recent results from our ongoing clinical trials. Finally, Our chief financial officer, Matthew Gold, will summarize our financial status, after which I'll return for closing remarks. We will be all available for the Q&A sessions. I would first like to highlight the key strengths that set ITOS apart as a cancer immunotherapy company. We are developing therapies focused on well-established mechanisms of immunosuppression. involves targeting pathway that relieves cancer-induced suppression of the immune system, and our goal is to develop therapies with the potential to fully restore the immune response against cancer. Through the first quarter of 2021, we continue to advance our differentiated clinical programs, US448, our potent high-affinity antitiget antibody, and inopadenant, a potent and highly selective A2A receptor antagonist with a robust clinical strategy to strengthen our position in the cancer immunotherapy space. We have released encouraging initial data and are pleased with the activity and safety profiles we have observed with single-agent monotherapy in both our clinical programs. We think that the monotherapy responses that we have seen with our programs are seniors of differentiations. We are looking forward to continuing the development of these drugs in combination where we see the most potential to benefit patients. We have combination studies well underway with Inopadenone, and we'll be initiating combination with EOS44AID mid-year. With our headquarters in Cambridge, Massachusetts, and our R&D center in Belgium, IT has a global presence, allowing us to attract talent worldwide and remain at the forefront of innovation in the field of immunology. Lastly, we are well capitalized with a runway well into 2023. This allows us flexibility to follow the data and competitive landscape in the design of our clinical plan with significant financial constraints. Having summarized this status, this is an exciting time for ITOS as we continue to make progress advancing our two clinical programs and our ongoing discovery efforts with the goal of improving the life of people with cancer. Our recent data presentation for our anti-digit antibody, US448, at ACR, showcased a favorable safety and tolerability profile, encouraging signs of clinical efficacy including disease stabilization and one partial response, and significant depletion of immunosuppressive T-rex and exhausted T-cells in periphery in patients with advanced cancer. While Joe will provide a more detailed review of the data and our clinical development plan later in the call, I would like to highlight that our complete data are in line with, if not better than, others in the TGX pair. We are initiating phase 1b2 combination trials in both checkpoint-naive and resistant patients. We expect that our work over the next 12 to 18 months will confirm the position of our TIGIT program within the immunology treatment landscape. We are also advancing our second clinical program, the highly selective adenosine A2 receptor antagonist in upadenone. At ASCO in June, we will report updated results from our monotherapy dose escalation study. In our view, the unique potential of inupiatin-N is based on its high potency and selectivity for the A2A receptor, the resistance to attenuation by the high adenosine concentration found in the tumor microenvironment, the favorable efficacy and safety profile as demonstrated by the Phase I data presented last year at ACR, and identification of a potential predicated biomarker based on the expression of the A2A receptor in the tumor microenvironment. We are evaluating inopanin in combination with pembrolizumab, with chemotherapy, and with EOS448 in disease-specific cohorts. In tandem with the progress of our clinical programs, we are also advancing research programs focused on targets that complement the mechanism for action of A2A receptor and TGIT programs and address additional mechanisms of immunosuppression. We are building our pipeline and expect to nominate an additional product candidate for IND enabling studies before the end of 2021. For our strategy, TGIT is an exciting new immuno-oncology target with external validation. And we have demonstrated that EOS44-AIDs potentially engage the target and the F-sigma receptor. We are exploring opportunities to accelerate and expand our development plans, potentially through a strategic partnership. Adenosine plays an important role in the suppression of the tumor microenvironment. And there have been some encouraging signals of activity with drugs that inhibit adenosine receptor and other pathway targets. Our inipadenone program was designed with properties to overcome the limitation of other drugs in this class, and we look forward to achieving a clinical proof of concept in the ongoing and planned trials in the near future. I will now pass the call over to our chief medical officer, Joe Lager, to discuss the progress in clinical development of both of inipadenone and EOS-448 in more detail. Joe, please.
spk03: Thank you, Michelle. I'd like to begin by providing a summary of the progress with our adenosine receptor antagonist in the pattern, for which we'll be presenting an update at ASCO next month. The adenosine pathway is a critical mechanism which suppresses the immune response against tumors and inhibits responses to current cancer therapies. Though there are multiple potential therapeutic targets in the adenosine pathway, The adenosine receptor A2AR is a key receptor responsible for mediating adenosine's immunosuppressive effects on immune cells. A2AR is highly expressed on effector immune cells, and potent inhibition of A2AR has the potential to block immunosuppressive signaling and restore an antitumor immune response. We selected this critical target based on our characterization of unique conditions of the tumor microenvironment. We sought to design a therapeutic that could selectively and potently inhibit A2AR, despite the high concentrations of adenosine present in the tumor microenvironment. Imifadmin is a next-generation A2AR antagonist with differentiated pharmacologic properties. Unlike prior generations of adenosine receptor antagonists, inopatinib was designed to inhibit A2AR even at high concentrations of adenosine. Inopatinib is also highly selective for A2AR and has a minimal blood-brain barrier penetration, properties which are expected to reduce off-target safety effects and improve the therapeutic index. We're currently evaluating inopatinib in several Phase 1b-2a studies, both as a monotherapy and in combination with pembrolizumab or chemotherapy. The results from the dose escalation portion of the Phase 1 study in patients with advanced stage cancer were presented at AACR last year and showed that inopatinib is well tolerated with no dose-limiting toxicities. In addition, Inopatinib demonstrated clinical benefit as monotherapy across multiple heavily pretreated advanced cancers, with durable partial responses seen in the patient with checkpoint inhibitor-resistant melanoma and in the patient with heavily pretreated castrate-resistant metastatic prostate cancer. We've also shown that when given twice daily, all of the tested doses resulted in a full inhibition of A2AR signaling at 24 hours after dosing. These results have generated much excitement for the program, and we look forward to presenting an update on our monotherapy cohort at ASCO next month, which will be focused on the tumor biomarkers evaluated in this study, and a finding that the expression of the A2A receptor in the tumor may be associated with clinical outcomes. We're currently executing a multi-arm phase 1-2A clinical trial in adult patients with advanced solid tumors where there's a strong rationale for treatment with an A2AR antagonist. We're enrolling patients in four distinct cohorts as both a single agent and in combination approaches. We have two cohorts evaluating independent in patients with castrate-resistant metastatic prostate cancer. One is monotherapy and the second cohort in combination with pembrolizumab. The third cohort is evaluating inopatinib in combination with pembrolizumab in patients with checkpoint inhibitor resistant melanoma. The fourth cohort is evaluating inopatinib in combination with chemotherapy in patients with triple negative breast cancer. We will continue to integrate a biomarker driven approach into our A2AR clinical program to choose optimal therapeutic combinations and identify the patients most likely to benefit from treatment. I'll now provide an overview of our progress with EOS-448, our high affinity potent anti-tigit antibody with a functional FC domain designed to enhance the anti-tumor response through a multifaceted immune modulatory mechanism. Yes, porphyrate has the potential to achieve significant immune-stimulatory effects through three mechanisms. One, blocking the binding of tigets with ligands, resulting in immune-mediated killing of tumor cells. Two, engaging the FC-gamma receptor-expressing effector cells that further promote anti-tumor immune responses, including through the release of pro-inflammatory cytokines and chemokines, and the activation of antigen-presenting cells. And three, depleting cells that are known to dampen the immune response, immunosuppressive Tregs and exhausted T cells. Last month at AACR, Dr. Van de Meuter presented first-in-human data from the open-label dose escalation phase one portion of the clinical trial in patients with advanced solid tumors. We were very pleased to report encouraging signs of clinical benefit with EOS-448 as a monotherapy in patients with advanced cancers. Of note, we observed a confirmed partial response with single-agent treatment with EOS-448 in one pembrolizumab refractory BRAF mutant melanoma patient. We also observed a manageable safety profile consistent with other drugs within this class and all of the tested doses were generally well tolerated. Our peripheral biomarker data demonstrated TIGIT-positive Treg depletion and a reduction in exhausted TIGIT-positive CD8 T cells, reinforcing our initial hypothesis about the FD gamma receptor engagement activity of ELS448. These robust biomarker data, coupled with the preliminary signs of efficacy as a monotherapy, indicate that ES448 is highly active with strong on-target immune responses and may potentially drive even stronger responses in combination studies. Based on these early positive results, we're pursuing a robust clinical development plan for ES448 with new combination approaches and three checkpoint-naive and checkpoint-resistant settings. We will assess the combination of ES448 with PD-1 inhibition in patients where pembrolizumab is indicated as a monotherapy, but where the addition of ES448 may improve clinical benefit to patients. We will first assess the safety of the combination of ES448 with pembrolizumab in solid tumors. And then we'll move into disease-specific trials in first-line non-small-cell lung cancer and head and neck squamous cell cancer, where we'll assess both the PD-L1 high and PD-L1 low populations. We are also planning to evaluate the combination of inopatent and EOS-448 in patients with checkpoint inhibitor-resistant melanoma and EOS-448 in combination with an image in relapsed or refractory multiple myeloma. We're planning to start these studies in mid-2021 and are continuing to evaluate our clinical development plans for ES4-4A and other solid tumors, including triple-negative breast cancer, gastric cancer, and pancreatic cancer. I now hand the call over to Matthew Gall, our Chief Financial Officer.
spk04: Thanks, Jill. I'd like to provide a brief update on our financial results for the first quarter of 2021. The company's cash and cash equivalent position was $321.4 million as of March 31, 2021, as compared to $147.7 million as of March 31, 2020. We project that based on our current clinical plan, this cash balance provides a runway well into 2023. Research and development expenses were $11.6 million for the quarter ended March 31, 2021, as compared to $5.8 million for the first quarter of 2020. This increase was primarily due to an increase in activities related to clinical trials for inupiatinib and EOS-448 and increased headcount. General and administrative expenses were $7 million for the quarter ended March 31, 2021, as compared to $2.4 million for the first quarter of 2020. The increase was due primarily to increased headcount and professional fees, and other costs associated with becoming a publicly traded company. The net loss attributable to common shareholders was $13.5 million, or a net loss of $0.39 per basic and diluted share for the quarter ended March 31st, 2021, as compared to $6.5 million, or a net loss of $25.53 per basic and diluted share for the first quarter of 2020. I'll now turn the call back over to Michelle for closing remarks.
spk00: Thank you, Matt. As outlined on this call, we are continuing to make progress, advancing our two clinical programs and our ongoing discovery efforts to move forward with our mission to improve the lives of people with cancer. With the upcoming data update for independent ASCO in June, we continue to progress our clinical execution. We are focused on our differentiated clinical development plan for both programs, And we anticipate that the next 12 to 18 months will be pivotal to establishing the position of EOS-448 in the digit space, particularly as we evaluate EOS-448 in new combination approaches in four checkpoint-naive and checkpoint-resistant settings. We believe both inupiatinant and EOS-448 have the potential to improve outcomes for cancer patients with a broad range of cancers. With our deep understanding of cancer immunology and the biology of immunosuppression, we will continue to strengthen our pipeline for the development of cancer immunotherapy. Thank you very much for your attention on today's call and your ongoing interest. I'd like to now turn the call back over to the operators for questions.
spk10: Thank you, speakers. Participants, to ask a question over the phone, You may press the star key followed by the number one. Otherwise, you may press the pound key to withdraw your request. Again, that is star one to ask the question or the pound key to withdraw your request. First question is from Chris Raymond of Piper Sandler. Your line is now open.
spk07: Hey, thanks, guys. Just a couple questions on EOS 850. I guess, you know, during your AACR call, you guys noted, and I think you also talked just now on this, that you'd have data at ASCO. But I think you also framed sort of the next big update, you know, for that program would likely be a second half of that. And I guess we were thinking SITC was maybe the more appropriate venue for Can you maybe just provide some clarity, I guess, around what we should expect to see at ASCO, maybe frame that for us a little bit? And then a second question on 850. We were just looking through your corporate deck, and I think on one of your slides in the deck you note that there's additional indications under evaluation for that drug. Can you maybe... Is there something outside of melanoma, prostate, and triple negative breast that we should be thinking about there? Thanks.
spk00: Hi, Chris. Thank you for the questions. I'm going to start with the update about the data, and I will let Joe continue about additional indication under consideration. And our next update will include the monotherapy expansion with six patients in each of the following indication. melanoma, prostate, lung, and endometrial cancer, and a biopsy readout for more than 20 pair biopsies in patients treated in monotherapy. A correlation between clinical benefit and a potential biomarker would be an important discovery in IO field, and expanding data on safety PKPD is important to move forward in our combination strategy. We believe that disclosing data now will pave the next step for our independent program. What we are planning to do later in the year is to go into more detail with the data related to the biomarker and explore if there is any satisfaction that will be another one useful for shaping our clinical strategy. And I will stop here for the data disclosure that you are planning to do and turn to Joe for the additional indication that could be under consideration.
spk03: Thanks, Michel. So, Chris, as we are considering other indications for this program, there are a couple of smaller tumor indications that we are quite interested in, non-small cell lung cancer. As Michel said, we enrolled some additional patients in our monotherapy cohort, and endometrial cancer are both tumor types where we are considering doing a further expansion.
spk07: Okay, if I can ask a follow-up then also. As we're talking about other indications, I think you also in your prepared remarks on 448, I think I heard you guys talk about gastric and pancreatic cancers as possible targets. when would you guys be able to make a decision on these tumor types and, you know, what's gating, you know, in terms of gating factors, I guess, in that?
spk03: Yeah, so I did mention that we are considering gastric cancer and pancreatic cancer. You know, there we are evaluating the opportunity, potential study designs. I would say we can likely provide an update on the development programs later this year.
spk07: Thank you.
spk10: Next question is from the line of Day Graybosh of SVB Lyric. Your line is now open.
spk01: Hi, thank you for the question. This is Dana. One, a follow-up to the questions you just had now on your development plans. You know, they have evolved a bit over the years, and I wonder if you could help us understand the rationale for the current plans and what you're looking for to make decisions going forward into the next six months, and whether in pancreatic you're still considering the combination with your A2A inhibitor, inupadulant, and TIGIT, or this is more purely TIGIT.
spk00: Jo, please.
spk03: Thanks, Dana. So in terms of the rationale for our development plan, we are, and I think your question was focused on the ES448, the TIGIT program, so I'm going to focus there, and you can follow up on the 850 if you had questions there as well. So We are developing a non-small cell lung cancer that has always been an interest for us. We did have some debate over whether to pursue the first-line setting with non-small cell lung cancer or to look at an earlier adjuvant type of setting. We decided that the first-line setting provides us the opportunity to have data that we can compare more easily with our competitors and, you know, potentially improve provides a faster path forward than the adjuvant setting. So we prioritize that. Head and neck cancer, I think, has been an interesting indication for us for quite a while. We think that the biology there is quite similar to non-small cell lung cancer and anticipate that adding an anti-tiger to Pembrolizumab therapy there should be a benefit to patients. This is an indication where we feel like we have the opportunity to potentially catch up with the competitors that are ahead of us who are maybe not being as aggressive in having that cancer as they are in other tumor types. So those are the reasons why we're interested in that indication. You know, we're interested in melanoma because we think being able to show activity in a an inflamed tumor after PD-1 therapy would be quite interesting. We're encouraged by the response that we saw in the dose escalation in the patients who had acquired resistance to PD-1 after having quite long therapy on PD-1. And we've also seen a signal with intrapadmin in checkpoint inhibitor-resistant melanoma. So we are looking at that combination in that setting with the potential that that combination could benefit other patients in a post-PD-1 setting. And then we have myeloma. We've generated data to show that with a collaborator at the Fred Hutch Institute in Seattle to show that TIDGET is really a much more relevant immune target in that type of cancer than PD-1 is, and have these preclinical proof of concepts that you see activity with an anti-tissue antibody in a model of myeloma with the potential for additional benefit in combination with image. In terms of the other indications for considering, particularly around pancreatic cancer, that is something that we're continuing to think about. As you know, it is a tumor type where the historical success rate has been low. It's a challenging tumor to treat, but we do think it's quite interesting, and we are still interested in the combination with our H-way receptor antagonist. There has been some recent promising data for other targets in the adenosine pathway in pancreatic cancer. It's still very early data, but yes, we do think that combination could be interesting there. I'll stop there and see if I've answered your question or if you have any follow-up.
spk01: That was very helpful. And maybe a follow-up that's on a different topic around your biomarkers, your biomarker for inopaduant. Maybe you can remind us, as context, I know some competitors have developed adenosine signatures. And can you remind us what's in that signature? And if you're seeing something different and it sounds like you are, why you could be seeing something different than others have seen? And thank you very much.
spk03: Yeah. Yeah, thanks. That's a good question. So in terms of biomarkers, in our studies, both our studies, but focusing in on the in the patent or EOS 850 A2A program, we are doing immunohistochemistry for immune cells, as well as various targets within the identity pathway, so the A2A receptor. and enzymes that produce adenosine. And we are also doing nanostring RNA profiling to evaluate potentially gene signatures. So in terms of what we are seeing, you know, as indicated by the title of our ASCO abstract, we think that there's a potential correlation between the expression or cells expressing the A2A receptor in the tumor and the clinical outcomes of patients. The A2A receptor IHC assay was quite difficult to develop. It is a challenging target to generate an antibody for being a G protein coupled receptor. And it took our team quite a bit of effort to be able to develop that assay and then transfer it to the CRO that's doing the testing for it. So as far as we know, others haven't looked at the expression of A2AR within the tumor as a potential correlate with patient outcomes. So that may be why we're seeing something unique here. It may also be because we have a very selective A2A receptor antagonist, whereas a number of the other adenosine receptor antagonists that are under development are less selective, target other receptors of adenosine. In terms of the gene signatures, the adenosine gene signature that people have reported on, we do have those gene signatures. in that signature in our monitoring profiling, and we will be looking at that. Mainly, that's looking at, you know, if you put adenosine in the system, what genes come up. And they are mainly genes that are related to myeloid cells that are in that signature that's been reported in the literature. It is a way, I guess, of looking for tumors that have a higher concentration of adenosine. As some may know, adenosine is quite difficult to measure because it has a very short half-life. So it's challenging to just go in and do a biopsy and identify whether a tumor has a high adenosine concentration or not. So this is a surrogate way of doing that. And we will be looking at that as well with our gene signature.
spk01: Very helpful. Thank you very much. You're welcome.
spk10: Next question is from the line of Anupam Rama of JP Morgan. Your line is now open.
spk09: Hey, guys. Thanks so much for taking the question, and congrats on all the progress. I was also actually flipping through the corporate deck, and on the A2A program and 850 here, saw a comment in the deck about a new formulation entering phase one. Any color here or tidbits you can provide? Thanks so much.
spk00: Joe, please, can you update Anupam about the status of our new, the phase one of the new formulation?
spk03: I'd be happy to. So Anupam, the formulation that we initially brought into clinic was a free base, yes, a free base formulation. We now have a salt formulation. that we think could improve some of the properties of the drug in terms of dissolution at high pH. So we are moving forward with the clinical trial of that new salt formulation and are anticipating that will start in the coming months, coming to both months.
spk09: Thanks for taking our question.
spk03: Thank you.
spk10: Next question is from the line of Arthur Fell of HC Wainwright. Your line is now open.
spk08: Hey, good afternoon, everyone, and thanks for taking my question. I had two questions regarding the adenosine and TechNet program. So first, it seems like the AstraZeneca and RQs are more focused on a triplet combo for the CRPC. And could you guys give us more color on your confidence on your molecule for a duplet or even monotherapy in that indication?
spk00: Thanks for the question indeed. Well, we believe that doing monotherapy will help us to get a better understanding of the mechanism of adenosine receptor antagonist prostate cancer, and that could also help us to identify a specific subpopulation that would be more adapted to such treatment. And this is, I would say, the main rationale for going in monotherapy, and we are currently at the end of the stage one of this monotherapy expansion. For the combination, the combination with pembrolizumab is additional added value. It would allow to explore, I would say, treatment which is chemo-free, which is also a significant expectation from the patient with prostate cancer, and could help us to differentiate our program compared to competitors. Jo, do you want to add something for this strategy in prostate cancer?
spk03: I think you summarized it well, Michel.
spk08: Thank you. Thanks for that. And my second question is regarding the pipeline. So what can we expect from the pipeline targeting the adenosine pathway? I believe you guys are planning to announce the additional candidate in later this year.
spk00: Yes, indeed. Based on the characterization of inupiaq demand, our research team has identified a new target, which has never been described explain your role in the adenosine pathway for cancer immunosuppression. And we've been very excited with this new target that is both of interest to go forward with other standard of care and could be also used in combination with inopadenine and A2A. We continue to make progress on the identification of the clinical candidate and we are planning to report the this clinical candidate before the end of the year and move forward in INV-enabling studies thereafter. On top of this adenzine pathway program, we are also planning to add additional programs in our pipeline. As I said, that will be complementary to TGTAN A2A receptor programs and will allow to address additional mechanisms of immunosuppression.
spk08: Thank you for taking my question.
spk00: Welcome.
spk10: As a reminder, participants, again, it's star one to ask a question over the phone or the pound key to withdraw your request. Our next question is from the line of David Nierengarten of Wedbush Securities. Your line is now open.
spk05: Thanks for taking the question. A bit of a follow-up to Dana's. When you think about your assay or thinking about assaying tumors for A2A receptor expression, I guess the question is, you know, thinking about the competition between One, how proprietary or can you protect your assay to use with 850? And then two, are we going to see or have you seen a situation where maybe it's not 100%, but 70% or something, a majority of tumors express the receptor in your hands, and so a competitor could potentially just say, I'll focus on that tumor, you know, seeing your results and go after that. I'm just curious, you know, how you see if your assay, if your, you know, research here provides you a competitive edge on the development. Thanks.
spk00: Hi, David. Thanks for the question. As mentioned by Chris in former questions, timing to disclose our data was also related to the protection of our our patents or any patent application. And we've been able to the best extent to protect this new, I would say biomarker related to a receptor antagonist. As Joe mentioned, it has been a significant challenge to develop an assay that will be robust to be used with clinical samples. And we are very confident that we'll be able to use this assay at large scale. We are still working on additional data because this assay also gives us, I would say, insight into a making fraction that has never been described so far for adenosine receptor antagonists, and this is the reason why we will disclose additional data later in the year or early next year. In terms of the application and the the percentage of positive patients, I would like to turn to Joe and get additional comments to explain why we believe that it will be a competitive advantage for ITOs.
spk03: Thanks, Michel. So we are continuing to generate data on the use of this assay. We are looking at the number of cells within the tumor expressing the HLA receptor. So that's a continuous variable. So we're continuing to work on, you know, what is the cutoff and what would be considered high and what would be considered low. And we're using the information that we have to interrogate the expression in different tumor types. Because this has been such a challenging assay to develop, there's not a lot of data out there available to say what the expression is of this H2A receptor by IHC in different tumor types. So our lab has been working on that, and we have some internal data there. But I think it is a competitive advantage because we've at least had a head start on doing these assays and understanding expression in different tumor types.
spk05: Okay, thank you.
spk10: I'm showing no further questions in the queue at this time. Ladies and gentlemen, thank you for participating in today's conference. This does conclude your program, and you may now disconnect. Everyone, have a great day.
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