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spk04: Thank you, Operator. Good afternoon and good morning, and welcome to Nanobiotics Conference Calls to discuss our third quarter 2022 financial and operational results. Joining me on the call today are Laurent Levy, Co-Founder and Chief Executive Officer, and Bart Van Ryn, Chief Financial Officer. As a reminder, today's call is being webcast and will be available on our website for replay. I would like to remind you that this call will include forward-looking statements, which may include statements regarding the progress, success, and timing of our ongoing and planned clinical trials, collaborations, regulatory filing, dates of presentation, and future research and development efforts, among other things. These forward-looking statements are based on current information, assumptions, and expectations that are subject to change. They are subject to significant risks and uncertainties that could cause the company's actual results to differ materially from our current expectations. Accordingly, you are cautioned not to place undue reliance on forward-looking statements. please review the full description of risk factors that can be found in the documents we file with the AMF in France and SEC in the United States, including our most recent URD and 20F, each of which are available in the investor relations section of our website, along with the press release issued yesterday highlighting our corporate and financial results for the period. In addition, any forward-looking statements represent our views only as of today and should not be relied upon as representing our views as of any subsequent date. While we may elect to update these forward-looking statements at some point in the future, Nanobiotics undertakes no obligation to update them to reflect subsequent events or future circumstances. With that said, I'd like to turn the call over to Laurent. Laurent, please go ahead.
spk01: Thank you, Kate. I would like to welcome everyone participating to this call. As Kate mentioned, we've been releasing yesterday our third quarter operational and financial update. We like for this particular call to focus on our priority pathway, which is developing our product in head and neck cancer. As you know, we intend to build a franchise in head and neck cancer patients in order to bring this product into market with this indication and then expand it into other indication. We've been the occasion during our last call to talk about the advancement of our global phase three. And today we're gonna spend a bit more time about the 1100 trial, which is taking care of recurrent and metastatic head and neck patients and others, but this time in combination with immunotherapy. As you know, We have started, beginning of this year, our global phase three. That is a randomized phase three that will encompass 500 patients across the world. And the first patient has been injected beginning of this year. Later, our strategic partner, Leon Bio, started to enroll patients in Asia. And we also have initiated clinical sites in the United States. What we see in this trial is a ramp up, both in the site activation across the world, but also in the patient recruited. And at the next step, we expect to have our first patient enrolled in U.S., beginning of the Q4. But today, I think we should take this opportunity to really focus on our priority pathway number two, which is taking care of patients having recurrent or metastatic head and neck cancer. Here, we're talking about the study 1100 dose escalation, and we've been completing the enrollment for dose escalation and determined the recommended phase two dose. Later today, I will be presenting at CITSE an update on this clinical trial, and this is helping us to pave the way to a potential next registrational pathway. We are happy to say that at CTC not only an update on this clinical trial will be presented, but also other data on NVT-XR3, including two preclinical posters, and also a full story about NVT-XR3, how do we bring from the concept to patient this product. Before going into the details of what we have seen in this clinical trial, I just would like to remind the design of the escalation path of the phase one. So this trial will have been recruiting patients in three different cohorts. The first cohort being patients having a local relapse or recurrent metastatic head and neck cancer. The second cohort have been patients having lung med coming from any primary tumor. And the third cohort is patients having liver med coming from any primary tumor. In this trial, we'll also have patients that are either naive to anti-PD-1 or anti-PD-1 resistant. When the patient entered a trial, he will receive a one injection in a primary or secondary lesion of NBT-XR3 plus an activation by radiation therapy. And this treatment will be followed by NTPD-1 either Pembro or Nivolumab. What has been shown in this part one of the escalation is first of all, that our product is well tolerated and the treatment is feasible in combination with immune checkpoint inhibitor. We also have seen that this product in combination with radiation could and may enhance the therapeutic response to immune checkpoint inhibitors. We've been showing an objective response achieved in seven out of 21 patients and three patients out of seven having complete responses. The clinical efficacy broadly has been reported to be around 71%, 15 out of 21 patients. We've seen also that NBTXR3 in combination with RT may stimulate an immune response and potentially convert NTPD1 non-responder into responder. Of note, 67% of NTPD1 resistant patient demonstrated objective reduction in all target lesion. An interesting fact is the product in combination with artery and NTPD-1 may produce sustained response in both NTPD-1 naive patient and patient with cancer that have developed resistant to prior NTPD-1. We've seen 38% of the patient with a disease control more than six months and 24% of the patient with more than 12 months disease control. Let's go back in the detail now of what we have seen in this trial. Let's start with safety. We've been treating 28 patients that are evaluable for safety. And overall, we haven't seen adverse events that are different from what we should expect from either radiation or anti-PD-1 agents in the target indications. The most prevalent adverse event observed in those escalations were mild fatigue, constipation, dyspnea, and anemia. The only one patient experienced two DLT in the cohort one at level of 22%. No DLT or other DLT has been observed in the study. Altogether, we've been able to determine a unique recommended phase II dose defined as 33% of gross tumor volume in the three cohorts. Before showing efficacy signal we've seen in this trial, I would just like to reemphasize on how we measure efficacy in this patient population. I think we should differentiate what we call all-target lesion from non-target lesion. We're going to start in this presentation to look at efficacy from the all-target lesion perspective. All-target lesions include the primary tumor, the one that will be injected and irradiated, and may also include other non-injected and non-irradiated tumor. The non-target lesions are lesions that are not present at baseline or not measurable. If we look at the overall population of evaluable patient, 21 in this trial, we've been able to see an objective reduction in all target lesion from baseline in 71% of the patient. 67% of anti-PD-1 resistant and 83% of anti-PD-1 naive patient. So all together we see a strong signal of patient having tumor size reduction versus baseline. Before going further, we would like to just highlight the changes we've been seeing and we've been highlighted in this presentation versus the last cutoff date you have seen during last ASTRO. What we see versus the last cutoff date data is that three patients have shown improvement in base percentage change from baseline in target lesion. Two naive patients had continued reduction in target lesion. and one resistant patient had previously reported PCR with subsequent follow-up visit confirming durability of the CR. In this update, we've been including five new patients available for efficacy, four anti-PD-1 resistant and one anti-PD-1 naive. One of the results we are really excited about is when you look at the NTPD-1 resistant patient, you see that 87% of them had progressive disease when entering the study, meaning a progressing in the primary lesion and potentially also in secondary lesion. Only one of those patients experienced an increase over 20% in measurable target lesion. So what does it mean? It means that when you have this patient resistant to PD-1 entering the trial with a progressive disease, to be able to either stabilize the disease or to provide a reduction in the tumor in all target lesion is a good sign that we may be able to reverse the course of the disease with this product in combination with radiation and NCPD-1. Another very interesting finding. is that we start seeing, now that the data are maturing, a long-term control in both NCPT1-naive and resistant patients. Of note, eight patients had more than six months' disease control and five patients with more than 12 months' disease control. And as we know, disease control in this population is a very good thing because that starts to be a surrogate for what we could impact for those patients in terms of survival. Now looking at the linear plot. Let's first focus on the left part of this picture. Here we see all injected target lesions, so the ones that have been injected with the product and irradiated, both for anti-PD-1 naive and anti-PD-1 resistant. What we see is a strong local control provided by the product in the tumor that has been injected. On the right part of this graph, we're looking at all target lesions, both in NCP1-naive and NCP1-resistant. And what we see is that what we see in the injected target lesion also transform into an all-target lesion response. It is interesting to see here the dynamic of the response. Not only we see some long-term delayed complete response, which could be in favor of an immune activity of the product, but also we see long duration for both local and all-target lesion control. Now let's focus on head and neck patients. Out of the 21 patients that have been treated and evaluated for efficacy, 16 had a primary head and neck cancer. And in this population, what we have seen is 43.75% of patients having a reduction in all target lesions more than 30%. This is an important data because based on this data, it is what we're going to look at to start building our next pathway to go through registration. Now, for the next set of data, we are not going to look only at the target lesion, but also at the non-target lesion, ASPERASYS 1.1. So here you will have the injected irradiate lesion, the non-injected non-irradiate lesion, and also the non-target lesion. Here, I would like to show you a case study to illustrate this point. We're talking about an anti-PD1 resistant patient. On the left, you see a PET scan image that represents two different lesions. The target lesion circled by blue and the non-target lesion circled in green. So that's the pre-treatment baseline. After treatment, at the first follow-up visit, what we could see is in target lesion, we have a partial response. That was the injected irradiated tumor. Interestingly, What we see in the non-target lesion that was outside of the field of irradiation and not injected, we see a complete response. So this case illustrates what we would like to achieve for this patient population, both having a local control and also a systemic distant control by a priming of an immune response. Now if we look at the local and systemic response, both for anti-PD-1, naive, and refractory patients, what we see overall in the 21 patients is we have a disease control of 95% and 43% of objective response. Now in naive patients, we got 100% disease control and 67% objective response. For specifically anti-PD-1 non-responder, we got to still a big number in the controlled disease of 93% and 33% of objective response. Those numbers cannot be directly compared to literature, but I think it's interesting to remember what the standard of care is providing when you treat head and neck patients naive to anti-PD-1. You usually have something around 15% to 17% of overall response for those patients. So here what we start seeing is a good sure guess of what the product could bring as a benefit for those patients, both for anti-PD-1 naive and anti-PD-1 refractory patients. Now if we compare this data versus what you have seen in the last cut of that, we've been improvement in certain case of disease control and the rate of objective response still continue to be important and very interesting. Now if we look per racist, that take not only into account the target lesions, but also the non-target lesions, we have an important disease control rate of 71% total, 83 in anti-PD1 naive, and 67% in non-responder. The difference between racist and non-racist are really linked to those additional non-target lesions. That will explain the difference in those data. You will see in the poster that we have also added a table, a table that presents the best overall response evaluation as per RACIS 1.1. This table has been structured in order to represent the next part of the trial that already started, which is the expansion part, that will have three different cohorts. And here it's interesting to see that both in anti-PD-1 resistant patient or anti-PD-1 naive patient, we see a good disease control rate and a good rate of response. We often note 60% of anti-PD-1 resistant head and neck patient achieve a stable disease at the best response. In a nutshell, what we see in those set of data that complete the escalation part of the trial is that we see strong signal that NBT-XR3 could be used in this patient population and bring some benefit and continue to support the hypothesis we've been establishing at the beginning of this trial. First of all, the product treatment is feasible and well tolerated in combination with immune checkpoint inhibitor in patients with advanced cancer. And BTXR3 may also enhance the therapeutic response to immune checkpoint inhibitor and may stimulate a response and potentially convert anti-PD-1 non-responder into responder. One of the important point we have been highlighting in this presentation is that the vast majority of PD-1 resistant patient enter the trial with a progressive disease. And achieving disease control or response in this patient is an important step forward to overcome or circumvent PD-1 resistance. Altogether, the first set of data of this completed escalation phase and now the ongoing expansion phase is paving the way for our next potential registration pathway that will intend to treat head and neck patient refractory to PD-1 where we think we could have and make a difference on that. As you know, we have had interacting with FDA to start defining what kind of trial we could do in this patient population, where we've been mentioning that overall response rate could be one of the surrogate for the final approval of this product in the indication. And within an interim rate out on overall response, we could be eligible for accelerated approval with a confirmation on OS. As expected, we intend to submit the protocol of this trial, Q1 2023, to continue discussion with the FDA and will inform the market in due time when we have had this information with FDA. I would like to take the occasion of this call to also welcome our Scientific Advisory Board. As you may have seen in a recent press release, we have formally formed our SAB that will bring a world renowned expert in surgery, in radiation oncology, in medical oncology, in order to help us to develop this product and to spread the use across different cancer indication. I will now turn the mic to Bart, that will make an update on the financials.
spk00: Thank you, Laurent. We continue to prioritize and execute across our initiatives to improve our financial flexibility and extend our operating runway. As indicated in our press release yesterday, cash-in-cash equivalents were €53.5 million for the first three months and the September 30, 2022, compared to €83.9 million as of December 31, 2021. In October, we were pleased to execute a final agreement with the European Investment Bank to realign approximately €30.7 million in outstanding debt obligations with the company's expected development and commercialization timelines. The cash-in-cash equivalents as of September 30th, 2022, combined with the executed debt restructuring, an existing equity line is expected to fund development programs into Q1 2024. And now I will turn the call back to Laurent. Laurent?
spk01: Thank you, Bart. I would like to conclude this first part by telling you what's in the front of us and give you some milestones that we expect to achieve in the coming months and years. Let's start with the head and neck locally advanced patient. Our phase three that I started, now we were expecting to get the fertility analysis, H2-23, and I planned the interim on PFS on H2-24. Also, the completion of the 102 study, that was the phase one-two, will present the final data mid-year next year. Now focusing on the IO pathway with the head and neck recurrent and metastatic cancer patients, we've been establishing the RP2D as you've just seen and started to look at some data and have initiated the dose expansion part of this trial. We'll take the opportunity to future medical and scientific conference to give you update on this expansion part of the trial. Now, as far as the registration pass is concerned, we are going to submit Q1 of next year, the protocol to FDA to continue the discussion we have initiated with them in order to pave our registration pass for this product in head and neck metastatic cancer patients. For other solid tumor indication, our partner MD Anderson continue to make good progress. We expect to reach the RP2D in the pancreatic cancer Phase 1 that is currently ongoing and hopefully to move into the expansion part of this trial. For the Phase 1 in esophageal cancer, we should expect next year the first results coming out at scientific conference. And a bit later, the first results of the Phase 1 in non-small cell lung cancer. So as you see, we have a rich news flow in the front of us, and we'll be happy to discuss that in future call with you. On that, this concludes the first part of the call, and now we'll open the floor for questions. Operator?
spk06: Thank you. Dear participants, as a reminder, to ask a question over the phone, you will need to press star 11 on your telephone and wait for a name to be announced. Alternatively, you can ask a question via the webcast. In this case, please use the Q&A box available on the webcast link.
spk05: Now we're going to take our first question.
spk06: And the first question comes from the line of Mike DeFiore from Evercore. Your line is open. Please ask your question.
spk02: Hi, guys. Thanks so much for taking my question. This is Mike on with John. Congrats on the data. Just a simple question for me. Today's Study 1100 dataset was flagged as an important value driver for the company, especially with regards to extending cash runway beyond 1Q24. So my question is this. Just given today's Study 1100 results, where um the orr seems to have decreased from 50 at astro last year to 31 this year are you more or less confident in your ability to um uh do that meaning uh kind of have the study prove valuable in terms of potentially you know attracting additional capital uh or and are there any additional levels to be able to to pull to get you through uh nano ray 312 and 2024. thank you
spk01: Thank you, Mike. So a good question. I think what we see in this phase one is the first step of our development in immuno-oncology. The data we have established in the completion of the escalation give us confidence that we can find a path forward. Now we need to dig much deeper to see how we're gonna define the pivotal trial we intend to submit to FDA in Q1. But we think the signal we see for phase one is very strong. So that's something we're going to work on in order to define the right population to be treated in the phase three. Now, until we get the feedback from FDA on the design of this phase three, it will be hard to understand how much cash we will need to execute it and what will be the endpoint and timeline for that. So that's why we'll come back to the market in due time when we have more information about the next step forward. Now, as far as the financing in general is concerned, maybe I will leave Bart to answer that question.
spk00: Thank you, Laurent. Happy to follow on. Hi, Mike. Hi, John. We received a similar question via the website, so I will address these questions together. But maybe to provide a holistic perspective, we've been able to extend our runway by taking actions within our control, such as ensuring highly efficient operations in line with our company priorities. as well as defer maturity dates of our debt obligations with the EIB. And we continue to be opportunistic in BD efforts and financings when opportunities arise, and we look forward to the future with both conviction and confidence. Thank you.
spk02: Great. It's very helpful. Thanks so much.
spk06: Dear participants, as a reminder, if you wish to ask a question over the phone, please press star 11 on telephone keypad.
spk05: And now we're going to take our next question.
spk06: And the next question comes to the line of Clément Bassin from BNP Paribas. Your line is open. Please ask your question.
spk03: Good morning. Clément Bassin from Ports-en-Var. Thank you for checking my questions. This is about the next step in the IOR program. The first part will focus only on the head and neck cancer patients resistant to anti-PD-1. So could you please provide some clues about the categorization of the cohort, mostly about the control arm? Since these patients are resistant to anti-PD-1, are you going to ask them to start a treatment again with anti-PD-1, which does not work for them, just to include it in the control arm? So how will you deal with the FDA?
spk01: Thank you for the question. That's a very important question and an interesting one. You're 100% right saying that If this patient are failing PD-1, that's hard to continue treatment on PD-1 for them because we don't expect for them to get any benefit out of it. So we need to think about, in general, a control arm that would be a bit different. That could be the choice of physician of any treatment that could help the patient. So that's part of, sorry, that's just my problem. So that's part of the thinking we have in designing this phase three and also the discussion we have with FDA. Now, to be more precise, there's many options for control arm, and that's something which is under discussion, and we'll get the final feedback from FDA when we will submit that to them. All right. Okay.
spk05: Thank you very much. Thank you.
spk06: Dear participants, as a last reminder, if you wish to ask a question over the phone, please press star 11 or telephone keypad. Alternatively, you're more welcome to use the Q&A box available on the webcast. There are no further questions, and I would like to hand the call over to Kate McNeil for closing remarks.
spk01: Thank you. I'm going to take the lead on that. And I would like to thank everyone for participating to that call. Again, very happy about this new data we have generated and presented at CITSI. There are also many other data that will be presented from a pre-call perspective. And on that note, I'm going to wish you all a very good day and hope to talk with you very soon. Thank you very much.
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