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spk09: The conference will begin shortly. To raise your hand during Q&A, you can dial star 1 1. good day and thank you for standing by welcome to the nanobiotics first half 2022 corporate and financial update conference call at this time all participants are in a listen-only mode after the speaker's presentation there will be a question and answer session to ask a question during the session you will need to press star 1 1 on your telephone you will then hear an automated message advising your hand is raised If you wish to ask a question via the webcast, please use the Q&A box available on the webcast link at any time during the conference. Please be advised that today's conference is being recorded. At this point, I will turn the call over to Kate McNeill, Senior Vice President of Investor Relations of Nanobiotics.
spk07: Thank you, Operator.
spk06: Good afternoon and good morning and welcome to Manobiotics conference call to discuss our first half 2022 financial and operational results. Joining me in 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 filings, 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, your caution 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 filed with the AMF in France and SEC in the United States, including the RFS and 6K filed yesterday and our most recent URD in 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 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 via conference call and webcast today. As Kate mentioned, we issued a press release yesterday, highlighting the company's operating activity and financial results for the first half of 2022. Before we open the call for Q&A, I would like to take a moment both to review our recent progress and outline how we plan to continue our advance development of NVT XR3 and drive shareholder value in the near term and long term. Since inception, we have generated a substantial body of evidence pointing to the novel potential of NVT-XR3 to play a critical role in cancer care. Leveraging evidence of both local and distant tumor control, we have focused our development effort on the unmet need for patients with locally advanced and treatment-resistant recurrent and metastatic head and neck cancer. With this focus, we believe we can build a comprehensive head and neck franchise that could offer meaningful improvement to current standard of care, both in terms of treatment effect and quality of life, and serve as a model to replicate it across additional solid tumor indication in the future. During the first half of 2022, we made significant progress towards this goal. Year to date, The most defining moment in our clinical program has been the initiation of patient enrollment in NanoRetreatWell. Since then, with the support of our partner, LianBio, we have activated approximately 50 sites across 13 countries, including the initial site activation and first patient in LianBio's territory a few weeks ago. Having also recently initiated clinical site activation in the U.S., I'm pleased to report that Anorae 312 is now actively recruiting patients in each of the three core territories that will drive the study, Europe, U.S., and Asia. These achievements reflect the hard work of our entire nanobiotics team as well as our collaborator at LionBio and the impressive support of investigators and patients. This hard work has included nimble response in the face of multiple regional challenges. As we discussed in March, Nano 312 was initially intended to include certain sites in Russia and Ukraine. In light of the ongoing war in that region, the team set about rapidly assessing alternate strategy for achieving our patient enrollment goal and have already identified replacement sites in alternate countries. Because of this swift action, we do not currently anticipate an impact on the overall study timeline. So, we did see some shift in early enrollment curve as a result. Further, while the world continues to make significant progress in battling the pandemic, the effects of COVID-19 continue to reveal themselves in different ways across different territories, including a recent surge in cases in China, continuing shortage of clinical research staffing at the center in the US. While this process is not a simple one under the best of circumstances, I'm very proud of how our team has proven itself capable of rising to the challenges laid before them, united in a purpose for the patient we hope to serve. With each of our key territories now active in the study, we look forward not only to continuing to add new sites, but to beginning to capture data that we can use to validate and refine or underlining assumption about recruitment, enrollment, and expected event rate in our target patient population. We anticipate that it will take approximately four to six months of global recruitment to provide data-driven validation of our anticipated study timeline, including our planned fertility analysis, anticipated in MIM 23, and our planned interim efficacy analysis that is anticipated in H224. As we saw Nanowrite 312 kick off and ramp up during the first half of 2022, we were equally pleased to complete enrollment in the study 102, a dose escalation and expansion study in a similar head and neck cancer population. This study has provided incredibly valuable information regarding the activity of NBTXR3 in head and neck cancer, and indeed was a key driver in our decision to pursue registration in head and neck cancer as our first global registration pathway. Having reported median overall survival of 17.9 months in the all treated population and 23 months median survival in the available patient population as of February of this year, we made the decision to modify the protocol for this study to limit the required follow-up to a minimum of 12 months. Based on the date of enrollment, this decision impacts the planned follow-up for only four of the 74 patients enrolled in the study, and no position has to report a mature and robust final data set from study 102 in mid-2023, while reducing the overall expenses of this trial. The first half of 2022 has also seen significant progress in our immunotherapy programs. I'm very pleased to now be able to say that what started as exploratory study evaluating radiotherapy-activated NBT-XR3 in combination with anti-PD-1 immune checkpoint inhibitor has led to compelling evidence of activity and the identification of a sudden planned registration program for patients with local regional recurrent or recurrent metastatic head and neck cancer that are resistant to PD-1 therapy. As we reported two weeks ago, following enrollment of 29 patients across three cohort of patients with advanced metastatic disease, we have completed the dose escalation phase of the study 1100 and determined the recommended phase 2 dose to be 33% of gross tumor volume for all patient cohorts. If dose will now be further evaluated in the dose expansion path study 1100, As you will recall, in the first half of 2022, we modified the tree expansion course in the study for more robust data collection in our target population of patients with head and neck cancer resistant to prior immunotherapy. As we advance the dose expansion part of study 1100, we're looking forward to providing everyone with an updated look at data from the dose escalation phase at a medical congress in the fourth quarter. Based on previous data generated by study 1100, we initiated discussion with FDA earlier this year to better assess what a potential registration pathway for this patient population could look like. This dialogue was very informative and has put us in a strong position to develop a potential phase three protocol that we intend to submit for agency review and comment by Q1 2023. I would like now to turn the call over to Bart to briefly discuss our financial results for the period. Bart? Thank you, Laurent.
spk03: The focus execution in our clinical development programs during the first half of 2022 were matched by a similar focus on strengthening our financial position, and the success is equally apparent. This time last year, we reported that our capital resources were expected to fund operations into Q1 of 2023. Since that time, we have undertaken several initiatives intended to improve our financial flexibility and extend our operating runway. First, we implemented cost control initiatives intended to drive a double-digit reduction in 2022 SG&A expenses. And in the second quarter of this year, We expanded on these initiatives by prioritizing R&D expense, supporting our late-stage development programs, and scaling back all the clinical, preclinical, and manufacturing expense while reducing our infrastructure cost to achieve a target reduction in operating costs of approximately 12 to 15 million euro through 2023, SG&A included. These efforts collectively added nearly two quarters to our anticipated operating runway. Second, we announced our intention to restructure our existing debt obligations, and I'm pleased to report that earlier this month, we reached an agreement in principle to restructure €30.7 million in outstanding debt obligations related to the company's 2018 loan agreement with the European Investment Bank. As detailed in our prior press release and findings yesterday, this restructuring aligns the repayment schedule with our anticipated commercial timelines and defers the majority of our principal payments due in 2022 and 2023. We anticipate that this agreement will be finalized in the next several weeks and result in an additional quarter of operating runway in 2023. Finally, During the second quarter of 2022, we secured access to flexible equity financing line through . Significantly, we are not committed to issue shares now or at any time in the future, nor are we obligated to do so at any price. Through this structure, Nanobiotics has the full authority to activate or suspend access to capital through this facility at its sole discretion. It would ensure that Nanobiotics has guaranteed access to capital to extend its operating runway by approximately one quarter. These initiatives, combined with the 63 million cash and cash equivalents reported as of June 30, 2022, are expected to support our planned clinical development programs into the first quarter of 2024. As Kate mentioned, yesterday after the close of the U.S. markets, Nanobiotics reported financial results for the six months ended June 30, 2022. As both our release and associated filings with the SEC and AMF detail the financial results for the period, I will refer you to these documents for a more complete breakdown of our financial results. However, I will note that the operating cost for the period decreased from 31.1 million euro for the six months of 2021 to 27.2 million euro for the first six months of 2022. Operating costs for the period reflect an increase of approximately 1.1 million euro in R&D expense, primarily driven by costs associated with the initiation of our global phase three study, a decrease of approximately half a million euro in SG&A expense due to increased efficiencies, and a decrease of nearly 4.5 million euro in other operating income and expenses related to the pharma engine contract termination in 2021. Net loss attributable to common shareholders for the first six months and the June 30, 2022 was 26.4 million euro or euro 76 cents per share compared to a net loss of 30.4 million euro for the comparable period in 2021. And now, I will turn the call back to Laura. Laura?
spk01: Thank you, Bob. To close out this call, I would like to reiterate how excited we are about our continued clinical and operational progress so far this year. This discipline execution of our priority pathways and careful management of our resources have enabled us to continue to invest in our pipeline, drive value across our business, and ultimately, advance our goal of delivering significant innovation and improved outcomes for patients with head and neck cancer. Looking ahead, Lanovoid 312 remains a key operational priority, and we look forward to critical advancement in this study over the coming months. Additionally, as Study 1100 continues to offer validation of our IO combination strategy, we look forward to each step that moves us closer to our second stage 3 registrational program. With dose escalation complete, we will now set out to add a dataset supporting our second targeted indication through the dose expansion phase of CD1100 and leveraging our existing data to support development of the phase 3 protocol submission to FDA by Q1 of next year. We look forward to keeping you updated on our programs through the years. This concludes our prepared remarks. We will now open the call to questions.
spk07: Operators, We will now take the first question.
spk09: The next question comes from the line of Mike DeFiore from Evercore. Please go ahead. Your line is open.
spk00: Hi, guys. This is actually John Miller with Mike. I was going to ask about your efforts to extend cash runway. It seems like you've made a great deal of progress extending cash runway potentially out into 2024, but still not to potential data readouts for NanoRay 312. So I guess in the interim, as we're seeing more results from study 1100, what additional levers are you going to have to pull to further extend that cash runway and get coverage for the pivotal trial?
spk07: Hi, John. This is Bart.
spk03: Thank you for your question. As you can tell, we're sensitive to the financing demands of the pipeline and the product that we have. We have undertaken numerous internal and external initiatives that have begun to reflect in the H1 2022 financials. We'll see more of that in the second half of this year. We're very diligent in every opportunity to drive additional efficiency and we're optimistic and we'll explore all options, including all the ways that biotechs would consider including BD. More specifically, we have a conference ahead of us with CITSE where we will do an update that I think will be of interest. In addition, we'll look forward to bringing to the market results on the pancreatic study that is ongoing, as well as esophageal early in 2023.
spk00: Great. That makes great sense. Can we focus then on what we could potentially see at CITC? That'll be the dose escalation, I assume, for most of the patients in that cohort. Can you confirm how many additional patients we'll have there versus prior times you shared that data?
spk01: Hey, John. Mike. Good morning, so that's Florent speaking. So for the CITC conference, what we do expect to present is the result of the escalation part of the phase one we have completed. In total, there have been 28 patients injected and evaluable for safety and feasibility, and there will be 10 patient evaluables for efficacy that will be presented. And also now we've started the recruitment in the expansion phase, but it's too early to show the expansion phase as we speak.
spk00: Awesome, awesome. That makes sense. I guess one final one from me. What is your pathway towards developing further indications? I know you've already mentioned pancreatic and esophageal, and obviously you have an ongoing pathway. collaboration with MD Anderson, but given your bandwidth limitations, I'm wondering what the opportunity is to start expansion cohorts or start additional early cohorts in indications beyond head and neck.
spk01: So, good question. Right now, the company is really focused in this head and neck franchise, both with the phase three that is ongoing across the world and the other one we're preparing in combination with IO in refractory patients. Now, as you may have noticed, the collaboration with MD on the CERN is including already five ongoing trials and there's still remaining space in this collaboration to go further. not only for phase one, but for also potential phase two or randomized trial. So here there is an opportunity at low cost to move forward into this program. But I think as we continue to grow and bring new data to the market, we may have new opportunity raising to develop further indication. But right now, all the cash and the company is really focused in this head and neck franchise.
spk00: Great. Thanks so much for the call, Laurent.
spk01: You're welcome.
spk09: Thank you. As a reminder, if you wish to ask a question, please press star 1 1 on your telephone. We will now take the next question. And the first next question comes from the line of cooling Bristol from UBS. Please go ahead. Your line is open.
spk02: Hi, this is Elliot Bosco. I'm for Colin, UBS. Could you, I just want to confirm some timelines here. So, it sounds like MBTX R3 might be on the market in 2025 following the completion or the interim analysis of NanoRay 312. Could you just give your thoughts on that? When might we expect a readout of the expansion phase of study 1100? Thank you.
spk01: Thank you for the question. I think as far as the time to market is concerned, it's not something we did communicate because that will involve multiple steps for that. What we think is that if the interim readout on the primary endpoint PFS is positive and according to previous discussion we have had with the FDA, we may be eligible for an accelerated approval. So if we assume that H224 will be the readout for this interim, then we need to have the usual time for getting the data submission and getting approval through FDA. So that's a possibility, but now let's move forward in the trial, get the results and see where they are to move forward into the next steps. So that's for the head and neck phase three trial ongoing. Now about your question on the 1100, as I just did mention, we started recruitment in the expansion phase that will include three cohorts. A little different from the three cohorts from the escalation phase because here we want to look at the patient based on their need. For example, cohort number one being head and neck patient refractory to PD-1 that could have either liver met or lung met or local relapse in the head and neck area. And this quote is particularly important because it will pave the way to our pathway to registration with the same population. So now that will be an open-level trial, so we will be able to give along the way some update, but we did not define yet when will be the first one. But I think as soon as we get a good number of patients in one of the calls or all calls, then we will give that update.
spk02: Thank you. That's all from me.
spk09: Thank you. We will now take the next question. One moment, please. And the next question comes from the line of Suzanne Van Portuisen from Kempen. Please go ahead. Your line is open.
spk08: Hi. Good afternoon, guys. This is Suzanne from Kempen. Can you perhaps elaborate a bit more on what benchmark we should keep in mind for the study 1100 data that we will be getting at CITI? I believe we saw somewhat higher response rate in treatment in the previous preliminary data set, although these were small number of patients. So I'm wondering, should we be expecting different response rates between patients that had prior immune checkpoints inhibition or those who are treatment-naive? And then I have a follow-up after that as well.
spk01: Thank you, Suzanne, and thanks for the question. So here in the phase one escalation part, there is a mixed population of patients. So it's not direct when you want to make a comparison with what's happening in those patients. Nevertheless, I think looking at what has been published in the IO world and especially in the head and neck population could be a good basis to think about it. And we could have two different paths for that. The first one is For example, Keynote 048, which gives a reference in head and neck patient early line getting PD-1, where we see an overall response at the end, a true responder around 15%. So that could be a good baseline to look at for naive patients, meaning that there's around 85% of those patients that will not respond, being either primary or secondary refractory patients. Now, looking at literature, when you look post failure of PD-1 in this population, as an example, we see a fairly low response of the patient, regardless of the treatment they will get. Would it be chemo or other type of treatment? But I think we should assume something around 5 to 7%, maybe, but depending on the series. So let's say those could be some of the baseline for responders. And from a more broader perspective, I think when you look at naive patients as refractory, you see patients that have different baseline, not only being refractory, but also in time for the disease progression. And obviously we could think that we could have a greater effect for naive versus refractory. But for that, we need to wait and see the data we have generated that, as we speak, we are extracting at the moment to be ready for sequencing.
spk07: Thank you. We will now take the next question.
spk09: And the next question comes from Arthur He from HCW. Please go ahead. Your line is open.
spk04: Hi, everyone. This is Arthur He. I had two questions. One is regarding the MBTXR3 immunotherapy combination trial. for the plan to submit to the FDA regarding the registration pathway. Could you give us more color on that part? And I assume that's to focus on the PD-1 resistant patient population.
spk01: So where we are at the moment, having Being complete the escalation part, we have our recommended phase two dose, so we're able to complete and finalize our proposal to FTA for the protocol that we expect to submit for discussion beginning of next year, let's say Q1. That's what our plan is. And I'm sorry, I'm not sure I got the second part of your question.
spk04: The second part is, The patient population for the potential regenerational part is for the PD1-resistant patient population or also including PD1-naive?
spk01: Okay. So at this stage, what we want to achieve is to show a big delta in patients that are refractory to PD1. That could include both primary or secondary resistant to PD-1. And this was in the head and neck metastatic setting or local regional resistant setting. When you look at the cohort number one of our 1100 trial expansion phase, you should have a similar population.
spk04: Gotcha. Thanks for that. And my second one is I'm just curious, sir, regarding your collaboration with MD Edison for the pancreatic cancer patient. For those data, by the end of this year, which value we could expect it from? And, yeah, so that's it.
spk01: So what we expect to get by the end of the year is to get the RP2D from the phase one part and assuming the data are positive to be able to move in the expansion part of this trial. Just maybe as a reminder, the escalation part was on three inoperable patients, post pancreatic cancer patients. And if we think that there is enough sign here and a good safety and feasibility, then we will move into the borderline operable setting. So that's the information we should get by the end of this year. Then MD Anderson, based on that, will decide when they present those data in a medical congress. But at this stage, we don't have yet the date for that presentation.
spk04: Got you. So as of now, this trial is fully sponsored by MDMZone. Correct. Got you. Thanks for taking my question.
spk01: You're welcome.
spk09: Thank you. We will now take a written question. It will be read by Kate McNeil. Please go ahead.
spk05: Yeah. Hi, Bart and Laurent. I have a question that's come in from .
spk06: Unfortunately, he's having a little bit of difficulty with his connection, so he asked that I share. His questions are on two fronts. The first relates to Study 312, and he is asking about some information about the progression of enrollment in 312, as well as what is the biggest location expected in the study, the U.S., Europe, or Asia. His second questions relate to the anticipated Phase 3 in 312. Immune Oncology, asking if we could please provide more information about the endpoints for the planned study, asking if we will watch the PFS like we do in 312 or the response rate. Also, will we have a control arm or do we plan to have a control arm in that study as we do in 312?
spk01: Thank you, Kate. Let's start with the 312, which is our ongoing phase 3 recruiting. To give you an overall view on where we are and the progress we've made, as you know, we've started injecting patients at the beginning of this year in Europe, and we've been pleased to also be able to treat the first patients in Asia a few weeks ago. and now US have activated sites that are recruiting. So we see a very good progress in the number of open sites. We mentioned 50 in our press release, and as we speak, we even have more than 50 sites now. So we're happy about that. Now I think, too, To get a good view on how fast we're going to recruit patients in this trial and to refine the readout timeline for interim or futility, we will need, I guess, around four to six months full site recruiting to get a good view and especially of the number of patients that could be recruited per month per site. So we're progressing. We're happy about the progress and in months we will be able to give a bit more visibility on patients and time to read out, refine based on the actual life recruitment. So that's for the 312 part. On the IO front, what we expect, but of course, this is subject to a final approval by FDA, nevertheless, based on the previous discussion we have had with them, is that we may go for endpoint linked to overall response rate as one of the key endpoints along with, at the end, overall survival, which is one of the key I think during our last call, we also mentioned that during the last interaction we have had with FDA on that matter, they told us that we could have the possibility to design a trial where a readout on overall response rate could be used for an accelerated approval. So that's along those lines that we are designing the trial. And to your question about a control arm, yes, this trial will need a control arm. knowing that in the head and neck metastatic refractory setting, as an example, it's hard to find another standard of care. So here we're looking at what could be done as a control arm especially because we have seen in many clinical trials, no later than ESMO, there was another one, that when you just use radiation alone with a checkpoint inhibitor, anti-PD-1, you do not provide benefit for patients. So I think it will be more along a more open control arm than just radiation plus PD-1.
spk09: Thank you. We will now take the next question. One moment, please. And it's a follow-up question from Suzanne from Kempen. Please go ahead. Your line is open.
spk08: Hi, thank you. Sorry, I got disconnected for a bit, so maybe you have touched upon it already, then I apologize. But I had a follow-up regarding the Study 1100's upcoming data. There's a portion of patients that you are resensitizing to checkpoint therapy, And I was wondering if there is data available on what is seen with pure anti-PD-1 retreatment. How would patients do on that? Thank you.
spk01: Well, it's hard. Thank you for the question, Suzanne. And that's a very key question. And it's hard to find data, post-failure of patients that are continuing treatment under PD-1 alone. What we see and that was part of the answer I've mentioned here is when you have patients refractory or non-refractory that you treat with radiation plus PD-1, the add-on of that does not bring a lot of value. Altogether, patients that are refractory to PD-1 could get chemo Some of them will get a continuation of PD-1 and some of them some other experimental treatment, but there's no predefined treatment for those patients. So it's coming more to a palliative thing than any standard of care.
spk08: Got it. Thank you very much.
spk01: You're welcome.
spk09: Thank you. There are no more questions at this time. I would like to hand back over to Laurent Levy for final remarks.
spk01: Thank you. This was a good call. Happy to have answered to your question and interacted with you. And we hope to see you soon during the different conferences or different calls or investor conference that we are planning to attend. On that note, I'm going to wish you an excellent day and a very good week. Thank you very much.
spk09: That does conclude our conference. Thank you for participating.
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