iTeos Therapeutics, Inc.

Relations at ITOS. Please proceed.

Thank you for joining us today. Joining me from ITOS with prepared remarks are Michelle Dittou, President and CEO, and Matthew Gall, Chief Financial Officer. Dr. Joanne Lager, Chief Medical Officer, will be available for Q&A. Before we begin, I would like to remind you all that the team will be making forward-looking statements in the prepared remarks and during the Q&A sessions. Any statements made during this call that are not statements of historical or current facts are intended to be forward-looking statements pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. We want to emphasize that such forward-looking statements reflect our current expectations and assumptions regarding timing, progress, and success of our current ongoing clinical trials, therapeutic potential thereof, expected milestones, our financial condition, including cash runway, 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 quarterly report on Form 10-Q for the quarter ended June 30, 2021, which was filed yesterday with the SEC, as well as 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?

Thank you very much, Ryan. Good morning, good afternoon, everyone. I would like to begin today's call by reflecting on the substantial progress we have made at ITOS and the recent announcement of our strategic partnership with Lexos Mclaren for our potent high affinity anti-tigit antibody EOS-448. This partnership brings value to ITOS, not only giving this program best in class resources, for clinical development now and as we look forward for both commercialization, but also validating our scientific approach and rigor. It also provides a catalyst for our talented team to continue to grow our pipeline of highly differentiated immunology therapeutics. Our team is deeply committed to developing therapies that focus on mechanisms of immunosuppression. Our approach involves targeting the pathway to reduce immunosuppression and restore the immune response against cancer, meeting the high unmet need that remains for cancer patients. In the last four years, we have put three distinct and highly differentiated programs into clinical trials And with the strategy course of significant value creation, we have shown that we can leverage our expertise in tumor genealogy and continue to build a robust pipeline going forward. Before I go into more detail on EOS-448 impediment and on our plan to further grow our pipeline, let me just take a moment to summarize our partnership with GlaxoSmithKline. We selected GSK as our partner for EOS 448 as there is a strategic focus on the TIGIT CD226 axis, and they share our belief that combination of PD-1, TIGIT, CD96, and CD112 receptor inhibitor can transform cancer care for the mini-patient who lacks effective treatment options. The deal recently closed, and as a result, we received a $625 million upfront payment. We will be eligible to receive up to an additional $1.45 billion in milestones payments should the EOS 448 program achieve certain development and commercial milestones. GSK and ITOs will share responsibility and cost with a 60-40 ratio, respectively, for the global development of EOS 448, and will jointly commercialize and equally split profits in the U.S. Outside of the U.S., GSK will receive an exclusive license for commercialization, and ICOs will receive tiered royalty payments. These attributes, both in a partner and in structure, will allow us to expand and accelerate the development of EOS 448 and meaningfully participate in the development process, commercialization, and in the value created. We could not be more happier to be working with a partner with the capabilities and portfolio of GSK, and we leverage this collaboration to generate significant value for all our stakeholders. EOS448 has the potential to achieve significant immune stimulatory effects through three mechanisms. One, docking the binding of STIGIT with LIGN, presenting an immune-mediated killing of tumor cells by T cells and NK cells. Two, engaging the S-C gamma receptor to further promote anti-tumor immune response in dendritic cells and macrophage. through the release of pro-inflammatory cytokines and chemokines, and the activation of antigen-presenting cells. And three, activating NK cells and macrophage to defeat TG-positive cells that are known to dampen the immune response, like immunosuppressive Tregs and exhausted T cells. We are highly encouraging initial sourcing human data for EOS448 and are pleased therapy in advanced solid tumor during our phase one. Data presented at ACR in April showed that out of 20 patients treated with single-agent US448, half of the patients had stable disease or better, and there was a confirmed partial response in a patient with panprolizumab-resistant melanoma. Peripheral biomarker data concern deposition of TGIT-positive Treg cells and reduction in exhausted TGIT-positive CDA T cells, whereas the other receptor T cells remain unchanged, demonstrating a multifaceted mechanism based on potent engagement of both TGIT and the S-sigma receptor by EOS44A. Based on the robust biomarker data, Preliminary signs of efficacy as monotherapy and data showing EOS448 was well-tolerated with no dose-limiting toxicities, the clinical development plan with GSK is geared towards advancing rapidly to registration-directed trials in indication and combination where we see the most potential to benefit patients. Having a partner with an approved PD-1 and a portfolio of potentially complementary programs gives us the ability to move rapidly towards approval and to work with GSK on novel regiments. We plan to start combination studies of EOS-448 with GSK recently approved anti-PD-1 drug, Janperli, or Dostarlimab, later this year, and plan to initiate trials in non-small cell-line cancer and additional indication in 2022. We are currently initiating a trial of EOS-448 in combination with Pembrolizumab and with our novel A2A receptor antagonist, Inepadinant, in patients with solid tumor. We are also moving forward with a trial to evaluate US448 as a monotherapy and in combination with a imid molecule in patients with multiple myeloma. Turning to imipadenone, adenosine suppress the immune response against tumor and inhibit responses to current cancer therapies. The adenosine receptor, A2L receptor, is a routine receptor responsible for mediating adenosine in a suppressive effect on immune cells within the tumor. Based on our understanding of the unique condition within the tumor microenvironment, we thoughtfully designed inopadenone, a drug that could selectively and potently inhibit A2A receptor, even in the high concentration of adenosine in the tumor microenvironment. Inopadinone is a next-generation A2A receptor antagonist with differentiated pharmacologic properties. Unlike prior generation of adenosine receptor antagonists, Inopadinone was designed to inhibit A2A receptor even at high concentration of adenosine. Inipazinone is highly selective for A2A receptor and has no brain penetration properties which are expected to reduce off-target safety effects and improve the therapeutic index. At ASCO in June, we reported updated results from our monotherapy dose exfoliation phase 1 to S30. In 43 patients with advanced solid tumor treated with single-agent inipazinone, We saw durable responses of stable disease greater than six months in five patients with advanced solid tumor, including the previously reported confirmed partial response in patients with checkpoint inhibitor-resistant melanoma and heavily pretreated castrate-resistant prostate cancer. Both of these responses have lasted greater than 12 months. We also newly reported a patient with non-small cell and cancer with stable disease lasting for more than 10 months. We are pleased with the best and durability of the antitumor responses we have observed today and with the tolerability of . Preliminary analysis of tumor biopsies indicated that the expression of A2A receptor in pre-treatment tumor samples is associated with clinical outcomes in patients with solid tumor treated with single-agent independent. We will continue to integrate a biomarker-driven approach into our A2L receptor clinical programs to choose optimal therapeutic combination and identify the patient most likely to benefit from treatment. We are currently evaluating in combination with pembrolizumab and with chemotherapy, and we are planning expansion in selected three tumors, including PD-1-resistant melanoma and another large indication, and we will continue to evaluate potential biomarkers. More information about our complete development plan will be shared in the near future. We will also be initiating evaluation of a triple combination of inipalinin, EOS-448, and PD-1. Turning to our discovery engine, we have a robust discovery effort ongoing, and we continue to possess research programs focused on additional targets that address pathways of immunosuppression. As we build our pipeline, we expect to nominate an additional product candidate for IND-enabling studies before the end of 2021. The team is very excited about this candidate, which targets an internally discovered mechanism of immunosuppression in the NLV pathway, and which we believe will be a 13-class agent. We believe that we have assembled significant expertise in target identification, modality selection, and that we can leverage to build upon our demonstrated of success to build a differentiated IO pipeline. With our headquarters in Cambridge, Massachusetts, and our R&D center in Belgium, IT as global presence allows us to attract talent worldwide and remain at the forefront of innovation in the field of immunology. I will now hand the call over to Mathieu Holl, our Chief Financial Officer. Thanks, Michel.

I'd like to provide a brief update on our financial results for the second quarter of 2021. The company's cash and cash equivalent position was $302.9 million as of June 30, 2021, as compared to $136.9 million as of June 30, 2020. Following receipt of the upfront payment from GSK pursuant to our collaboration and license agreement earlier in August 2021, we believe that our existing cash and cash equivalents would enable us to fund our operating expenses and capital expenditure requirements into 2026. Research and development expenses were $14.2 million for the quarter ended June 30th, 2021, as compared to $6.1 million for the second quarter of 2020. This increase was primarily due to an increase in activities related to clinical trials for EOS-4048 and interpagnet and increased headcount. General and administrative expenses were $15.1 million for the quarter ended June 30th, 2021, as compared to $2.4 million for the second quarter of 2020. This increase was primarily due to increased headcount, professional fees, and other costs associated with becoming a public company, along with advisory fees incurred by the company for the collaboration and license agreement with GSK. The net loss attributable to common shareholders was $26.5 million, or a net loss of $0.75 per basic and diluted share for the quarter ended June 30, 2021. as compared to $10.3 million, or a net loss of $29.49 per basic and diluted share, for the second quarter of 2020. I'll now turn the call back over to Michel for closing remarks.

Thank you, Matt. As we move into this period of running our proof-of-concept trials in several immunology combinations, we have also begun to prepare for pivotal trials, which we plan to initiate in the next 12 to 18 months. We will be focused on execution of our clinical programs and on continuing to elucidate the mechanism of action of our drugs to inform our development programs. We expect to generate data across multiple indications in different combinations with both of our clinical stage assets, including the initiation of several clinical trials with our partners at GSK over the coming months. 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 operator for questions.

Thank you very much. If you would like to ask a question, please do so by pressing Start followed by 1 on your telephone keypads. If you change your mind, please press Start followed by 2. When preparing to ask your question, please ensure that your line is unmuted locally. Our first question today comes from Chris Raymond from Piper Sandler. Chris, please proceed.

Hey, thanks, and congrats on the progress this quarter. Just a couple. Maybe first a strategic question. I guess it's pretty remarkable you guys have funded. You're funded now about five years or so, and I'd say that kind of runway is kind of at the high end of what we've seen for an earlier stage company like you guys. Just as you think about maybe your, I guess, intertemporal maybe investment choices, can you talk about the assumptions that went into this cash runway guidance? I guess long and short of it, is there any sort of business development embedded in this? Is there any other activities? Thanks.

Hi, Chris. Michel speaking. Yes, indeed, this is something which is remarkable and that will allow to create multiple short-term goals. And the plan that we have designed with GSK incorporates us moving as quickly as possible. This includes initiating several phase 3 studies that say with GSK being 60% of development expenses, this program still only consumes about one-third of the cash balance. We believe that the data for independent will spur the advancement into the phase three studies, and we have integrated that in our cash-run way. The company has put three distinct programs into the trials over the past four years, as we said, and we have a track record of significant value creation that we think is sustainable to generate future programs. And we have, in this cash-run way, integrated several programs that will be developed in-house, And we believe we'll be able to address different mechanisms involved into moderating gene response against the tumor cells. We have also integrated a few academic partnerships that will expand our expertise in tumorology and drug discovery. And we are also integrating I would say opportunities in external innovation. I want to stress that we'll be really opportunistic and cash efficient there. We know what we are looking for, and we'll take the time to find the best opportunity to expand our pipeline within this cash runway.

Okay. And then just a follow-up, maybe more detailed. Do you have an update on the A2A biomarker for Inupiat and Ent? Just any progress there and any sort of guidance as to when we'll see additional data?

Yeah. I'm going to turn the question to Joe to give the most . Joe, please.

Thank you, Sean. Thanks, Chris. So we have reported some initial data on our biomarker at ASCO this year showing that the expression of the A2A receptor itself is associated with clinical outcomes for the patients treated with monotherapy. We are continuing to investigate those biomarkers and using that data to understand what types of cells are expressing A2A are within the tumor and are developing, I think, a more profound understanding of the mechanism of action of the drug, which is informing our indication selection and which we will be incorporating in our clinical development plan as we move forward. We anticipate reporting that data out sometime next year as we kind of put all the pieces of the story together.

Thank you.

Our next question comes from Dana Graywash from SVB Learink. Please go ahead.

Hi, good morning. Thank you for the question. I'd like to get into now that, you know, we're a little bit past the BSK deal, your guys' perspective on the broader TIDGET CD226 access. You know, there's four members now that the collaboration has together, and you mentioned CD96, and, of course, there's also PVRIG and the potential accounts. PD-1 as well. And I wonder, of all those three questions, what did you confidence to double or triple down on the CDP-26 access? Which of the various combinations are you guys most enthusiastic about? And then with CD96, I find it perhaps the most complex and controversial, with some literature suggesting you should inhibit it, and other literature suggesting you should stimulate it for anti-tumor immunity. And I believe even from the GSK approach is inhibition, and what gives you confidence that's the right approach?

Thanks, Dana. I want to mention that the primary goal of the collaboration is to move forward with the combination of Dostalimab, the PD-1 from GSK, and our digit antibody, EOS448. In some specific indication, we could look for triplet combination. That will include different options. CD96 or CD112 receptor could be appropriated in some specific indication where you are high level of one of these two partners on top of CIGIT. We are also evaluating the triple combination of PD1 plus our CIGIT antibody and our A2 receptor antagonist in epadenone. We believe there is a strong rationale there with a good clinical data. Coming to the specific question of CD96, GSK builds a strong data set showing that inhibiting CD96 will provide a silicon antitumoral effect, and that the combination of CD96 plus TGET plus PD1 in some setup could create an additional synergy that will allow to be differentiated from the double combination of PD1 plus TGET.

Got it. So no near-term plans for the PBR-IG in combination with your TGIT that was licensed surface by GSK.

Jo, do you want to comment on that question?

So that is another combination that we're interested in, Dana. The PBR-IG or TB112 receptor antibody at GSK has not yet entered into clinical trials. it will be a later step, but it is another combination that we're interested in.

Thank you very much.

Our next question comes from from HC Wainwright. Your line is now open.

Thank you. This is from HC Wainwright. Good morning, Michelle. I apologize if this question has been asked. I've been jumping between calls. On the Inupiaq land, you know, in your press release, you state that, you know, you're going to be looking at several indications and also will be using different biomarkers to select patients. Could you highlight, you know, a couple of indications that you would be going after and also what sort of biomarkers are you looking to work with?

Good morning, Arca. Well, we've been very excited by the data we published at ASCO two months ago about the relationship between the expression of the receptor identified by immunohistochemistry and the antipyretic effect in patients. And we are currently expanding this biomarker validation in order to select a specific patient with different indications. Joe, can you give more detail on what you are planning to do for this biomarker strategy, please?

Yes, hello, RK. So as Michelle said, A2AR seems correlated with clinical outcome. That's the data that we presented at ASCO. We are exploring, using this data to really explore the mechanism of action of the drug. We think that this, we're getting from our translational data from our clinical trials new insight into how the drug is working to restore anti-tumor immunity. And we are evaluating, based on that data, a number of indications. We are planning to proceed, as we've previously discussed, with a cohort in post-PD-1 melanoma. And we are evaluating other solid tumors based on the data that's coming in. So we anticipate giving an update on the clinical development plan later this year.

Thank you both. And then, you know, with the... You know, it's a good war chest for cash now, thanks to GSK collaboration. Michelle, if you had the chance to bring in molecules or if you're looking for additional molecules to be brought into the pipeline, what sort of molecules would you be looking at? You know, would you be looking to add more to the A3AR franchise or to other tumor microenvironment molecules?

Yes, indeed. Then with the five plus years of cash runway, we have integrated our investment into the digital development plan, our eight-way investment program also, and expanding the pipeline. And as I said before, with our expertise in thermal energy, we have shown that we have been able to select the right targets the best possible modality, and that we have also an expertise in terminology to select or to identify relevant patient population. We have a preclinical program, which is a new target And we are going to nominate a clinical candidate before the end of the year for this program, and we will give more information about the specificities of the program and why we are excited to discover this first-in-class program. We are also considering other, I would say, axes in order to promote the anti-inflammatory response of the immune system. So far, we have worked with independent on a mechanism which is targeting T cells, but also additional immune cells. And we will publish more data, as you mentioned, in the near future. We are targeting T cells, NK cells, dendritic cells, and macrophage. And we believe there are other mechanisms that could be used either in standalone or in combination with standard healthcare or our pipeline to continue to boost the immune response against cancer cells in different tumor types. Then if we look for external innovation, it will be with mechanisms targeting additional types of immune cells which are not covered by our current program at the clinical stage or in the preclinical pipeline.

Thank you. Thank you very much, and good luck with everything. Thanks. You're welcome.

Our next question today comes from Anupam Rama from JP Morgan. Please proceed.

Hey, guys. Thanks for taking the question, and congrats on all the progress. Maybe just a quick one on 448 for me. Strategically, What's the rationale and value of studying in combination with PEMBRO if the dostarilumab combination, I think, Joe, you said was supposed to start later this year or maybe early next year? Thanks so much.

Hi, Andy Pan. While we agreed that our work on the combination with dostarilumab could help to inform our next steps, and what was getting started in order to generate data as quickly as possible on the safety of the combination and evaluate the efficacy in adult neck cancer in BL1 high and low population. In parallel, we are also working to accelerate the evaluation of the combination of EOS448 with Dr. Riva. which will be evaluated in platform trials in non-small cell lung cancer to be initiated by GSK, and we have additional indication that will be added to the clinical development plan. Joe, do you want to add something?

No, I'll just emphasize what you said, Michelle, that, you know, the intent of moving forward with this study is really to continue to accelerate the program and to generate data in this time as we're getting started with the distal and that combination.

Thanks for taking that question.

As a reminder for everyone, if you would like to ask any further questions, please do so by pressing Start followed by 1 on your telephone keypad now. We currently have no further questions registered, so I will now hand back to Michelle for any closing comments.

Well, I would like to thank everyone for taking time to review our progress. As we said, we are focused on the execution, both at the clinical stage and preclinical pipeline, and we'll continue to move forward with our clinical strategy to deliver strong data for our clinical assets and to build our pipeline. Have a nice day. Bye.

Thank you, everyone, for joining us today. This now concludes today's conference call. And you may now disconnect your lines. Please have a lovely rest of your day.