Nanobiotix S.A.

Good afternoon and good morning, and welcome to the Nanobiotics Conference call to discuss updates to our NBTX R3 development plan and our first quarter. Joining me on the call today are Laurent Levy, co-founder and chief executive officer, and Bart Van Ryn, chief financial officer, who will be available during the Q&A section. 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, 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 filed with the AMF in France and SEC in the United States, which are available in the investor relations section of our website along with the press releases issued yesterday and today. 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. Before turning the call over to Laurent, allow me to highlight that we announced in a separate press release this morning our first quarter 2024 unaudited cash balance of 58.9 million euro and reaffirmed our cash runway into Q3 2025, which is inclusive of the $20 million milestone we meanwhile received. With that said, I'd like to turn the call over to Laurent. Please go ahead. Thank you, Craig.

And thank you everyone for joining us today. As Craig mentioned, we issued a press release yesterday, highlighting the company's progress in the global development of NBTXR3 and an overview of our robust pipeline and expansion strategy. For today's call, I would like to begin with updates to our NBTXR3 collaboration and discuss our pathway to long-term growth. Then, I will provide closing remarks before opening up the call for questions. Nanobiotics has been long known for the disruptive potential of NBT-XR3, a nanoparticle treatment we've been developing for patients with cancer around the world. The accomplishments we have achieved through our 20-year history stand as a testament to the hard work of our team, the potential value the industry at large sees in our technology, as well as the tremendous faith and confidence of our investors and other stakeholders, all in our vision and our plans to get there. Last summer, we entered into a collaboration with Janssen, worth potentially more than 2.5 billion plus royalties, ranging from low teens to low 20s, to expand the worldwide potential of our lead therapeutic candidate, NBT-XR3, a potential first-in-class radio enhancer with universal application across the . As part of the agreement, NBT-XR3 is being developed and potentially commercialized globally by Janssen Pharmaceutica, a Johnson & Johnson company. Our global license agreement with Janssen has brought us the possibility to deliver outcome-changing innovation for millions of patients. Today's focus with our partner is to secure the path to market for NBT-XR3 and our commitment to realize our regenerative medical and economic value remains our most important goal. We believe this agreement underscores the therapeutic and market opportunity of NBT-XR3 and importantly, further validates our platform and scientific approach. We believe that this collaboration with our partner has the potential to impact the lives of many patients. We believe this because MBT-XR3 can treat patients at a stage where the disease is local with radiation therapy, which is a treatment utilized by millions of patients. Better local control of disease at this stage, we believe, could have a fundamental impact on the overall outcome for patients. The alliance with Jensen for the co-development and global commercialization of NB-TXR3 has achieved significant progress, which we will overview today. We remain focused on the execution to secure our partnership outcomes and drive as much value in the alliance as possible for patients and nanobiotics many stakeholders. Alongside this, nanobiotics is working to explore and push forward the next generation of nanoparticle-based therapy in healthcare. I'm excited to discuss with you today our corporate strategy, which is designed to enable long-term growth for nanobiotics. Our company is developing three nanoparticle-based therapy platforms. We plan to leverage the sustainable revenue expected to come from the development and commercialization of NBT-XR3 to further advance development of our second platform, CuraDyn, and the third platform. Building on the success of NBT-XR3, we are energized to expand our leadership in nanoparticle-based therapy, and we'll discuss more on this shortly. But first, let's start with our efforts to deliver a potentially curative outcome for patients with locally advanced and metastatic cancer with NBT-XR3 as it remains our primary focus. As a reminder for those new to the story, NBT-XR3 is a biologically inert electron-dense nanoparticle designed to be a strong x-ray absorber and radiation amplifier. It is a one-time treatment designed to minimize impact on the patient's journey as it is injected directly in the tumor before the first course of radiation treatment, while it has been shown to amplify the anti-tumor activity of the radiation without increasing exposure to healthy tissue. We call this modification universal. We do so because it's based on physics and all radiation interacts with the nanoparticle and not on the specificity of the tumor type or the biology of the patient. This mode of action also lends itself to NBT-XR3's ability to be combined with many other modes of therapy, including chemotherapy regimen, targeted therapy, and importantly, immuno-oncology therapy. NBT-XR3 is being evaluated as a therapeutic candidate with potential to easily integrate into the cancer treatment paradigm for 60% of solid tumor patients who receive radiation as part of their therapeutic regimen each year. To date, NBT-XR3 has been injected in hundreds of patients by leading physicians at several premium clinical research institutions in the United States, Europe, and Asia. To help enable the practice-changing potential of NVT-XR3 in collaboration with the interventional oncology group at Johnson & Johnson, the current NVT-XR3 development program is initially focused on the completion of NaNoWri3-12, an ongoing pivotal phase three, evaluating the for elderly patients with locally-affected head and neck cancer, as well as the launch of a randomized phase two study evaluating NVT-XR3 for patients with stage three non-small cell lung cancer for which Janssen is fully responsible. In preparation for potential regulatory submission in the event of a positive head and neck trial results, Nanobiotics and Janssen align at the Collaborations Joint Strategy Committee, or GST, to transfer the global sponsorship of the phase three pivotal head and neck cancer trial. Nanobiotics will continue to support Janssen in the execution of the Nanorad 312 during and after the sponsorship transfer is complete. This was a deliberate decision to pursue the transfer sooner rather than later, because we believe it's the best decision for the product's value and its efficient path to market. In conjunction with the sponsorship transfer, following discussion that began in late 2023, the Joint Strategy Committee aligned to modification to Nanowire 312 that include a protocol amendment removing the planned futility analysis in light of the robust positive top-line data from the expansion part of the study 102, a phase one study evaluating NBT-XR3 in a similar population, which provided satisfactory support for the nano-ray 312 trial design, which deemed the futility analysis not useful. This amendment is subject to review and approval by health authorities in all countries where nano-ray 312 is operational, as well as by the site participating in the study. To date, the amendment has been accepted by health authority in several regions, including United States, countries in Europe, and Japan. Additionally, Natobiotics and Jensen agreed to a change in the approach to the planned interim efficacy analysis, such as Jensen will realize and report on the interim data after both the requisite number of events are observed and at the end of the recruitment has occurred, which is expected in the first half of 2026. rather than immediately after the requisite number of events as originally planned. This revised approach helps to ensure that potentially positive interim analysis results do not introduce a potential bias in the remaining recruitment prior to completion of the study. As such, nanobiotics now expect the interim analysis to be reported after the last patient is recruited in H1-2026. Now, let's review other significant progress on our NBT-XR3 collaboration with Jensen in establishing development operations since executing the Global Licensing Agreement this July. We started with the formation of the Joint Strategy Committee comprised equally of executives from both companies to drive strategic decision making for the Global Development Program. We also activated joint working teams that are staffed by both companies with an initial focus on manufacturing and preparing nanoray twist wells for global regulatory submission in the event of positive trial results. In addition to establishing governance methods, key operational progress has been achieved. Highlights include, first, Jensen has begun replicating the nanobiotic manufacturing process to allow Johnson & Johnson to produce NBT XR3 in parallel with our own facility in order to increase product availability. To go on, we have started to leverage increased discretionary in-kind contribution that were allocated from Johnson to Nanobiotics that includes staff support for Nanowave 312, along with payment for manufacturing, technical assistance, and other product development support services. Third, we achieved the first operational milestone in Nano-RED 312, triggering a 20 million payment in May from Janssen to Nanobiotics. Then, the US FDA has issued a study-may-proceed letter regarding the protocol for the Janssen-led SES2 study for patients with SES3 non-small cell lung cancer. Fifth, we begin elaboration of the overall clinical development plan for NBT-XR3, including new indication beyond head and neck cancer and non-small cell lung cancer. And lastly, Jensen consolidated global development and commercialization rights via the assignment to Jensen of the licensing agreement relating to China and other Asian markets and territories from our former nanobiotics partner, Lianbio. As you have heard, we've made significant progress with Jensen advancing NBTX Part III. It is key to understand that bringing a therapeutic candidate from concept to global registration is an exciting yet daunting proposition for any development stage biotechnology company, even those working within well-known asset classes with well-established development and regulatory pathways. That is why we believe that our global licensing agreement with Jensen was and continues to be the right move for the patient, for healthcare professionals, and for all the supporters of NBT-XR3's potential. We are confident that the leadership of the Joint Strategy Committee will optimize the probability of success for Manure 312. Importantly, our global licensing agreement with Jensen also includes plans to further evolve the NVT-XR free development pipeline. These plans include an established framework for potential complementary co-development of relevant indications in the near, medium, and long term. The Joint Strategy Committee will recommend the next indication beyond the immediate operation priorities in head and neck and non-small cell lung cancer. Our current pipeline beyond stage 3 lung and locally advanced head and neck cancer has already shown the expensive potential of NBT-XR3 and continues to progress. In our IO combination program, NBT-XR3 in combination with NTPD1 therapies for patients with recurrent or metastatic head and neck cancer that is naive or resistant to anti-PD1 treatment with and without metastasis is being explored in two cores in study 1100, an ongoing nanobiotics-led phase one clinical trial that has completed dose escalation and is in ongoing dose expansion. We expect to present initial data from the head and neck cancer trial expansion core at ASCO this June. The third quarter of this study, including patients with metastasis for multiple primary cancer, will be presented later in 2025. Expansion opportunity in additional cancer setting in the medium to long term are being investigated in several trials that are part of our ongoing collaboration with MD Anderson Cancer Center in Texas. This includes phase one studies that have completed dose escalation and are in ongoing dose expansion in locally advanced pancreatic cancer and inoperable recurrent lung cancer and in an ongoing phase one study in dose escalation evaluating NVTA surgery in combination with chemotherapy in patients with locally advanced esophageal cancer. We expect multiple readouts from this study in the next 12 months. Additionally, several nanobiotics-led phase 1 studies have been completed with primary endpoints met in patients with hepatocellular carcinoma with and without liver metastasis and in rectal cancer. Our main focus and priority for NBT-XR3 program is validating the safety and efficacy of radiotherapy activated in NBT-XR3 and moving to global registration in locally abandoned head and neck cancer. account for the majority of operational and financial resource allocation. Nanobiotics expect to lead a new Phase II randomized study in a new indication in due time once nanoratritual sponsorship transfer has been completed, additional funding has been secured, and approval has been confirmed by the Joint Strategy Committee. Now let's turn to the promising future of nanobiotics beyond NB-CXR3. As the NBT-XR3 program moves toward the ultimate goal of reaching millions of patients with cancer around the world, through the execution of our study, both ongoing and planned, we are working to expand the impact of nanoparticle-based therapy in healthcare through continued early-stage development of our nanoparticle expertise, which includes two additional platforms, Curadine and O3T. Like NBT-XR3, this platform has been years in the making, and we are excited to share some of our progress with you today. Curadime has produced a nanoprimer, has its first product candidate, which is designed with specific physical chemical properties to allow its nanoparticles to transiently occupy liver cells responsible for therapeutic clearance. This allows a subsequently delivered therapeutic to bypass the liver's clearance mechanism. This is intended to increase bioavailability and subsequent accumulation of therapeutic in targeted tissue, thus allowing the medicine to do its work. This has the potential to see increases in the efficacy or decreases in the toxicity or reduction in the needed dose of subsequently administered medicine. The OQT platform is based on the principle that nanoparticle materials can interact with and influence neuronal network via their electrical properties. The goal is to potentially enable modulation of malfunctioning neuronal network toward a normal state. In particular, the reduction of neuronal hyperacceptability associated with neuropathic pain has been observed in both in vitro and mouse model with several nanoparticle candidates. We expect to provide the next update and plan an operation progress for curadine platform in the second half of 2024. As you heard today, we've made significant strategic and operational progress in our NBT-XR3 global alliance with Jensen. This includes the intended sponsorship transfer of the Pivotal Nanowire 312 trial, modification of the Nanowire 312 to optimize the regulatory pathway, and continued ongoing exploration of expansion opportunities for NBT-XR3 in other indications. These achievements validate the potential of our nanoparticle platform and strongly position us to expand our nanobiotics corporate strategy. We plan to allocate some of the expected proceeds from NBTXR3 to further develop our Curada NanoQT nanoparticle platform to foster and enhance long-term growth potential and value of nanobiotics. We look forward to providing you updates along the way. I will now ask the operator to begin the Q&A session. Operator?

Thank you. To ask a question, please press star 1 1 on your telephone and wait for your name to be announced. To answer your question, please press star 1 1 again. Please stand by while we compile the Q&A roster. We will now take the first question. Coming from the line of Jonathan Chan from Learing Partners, please go ahead.

Hi, guys. Thanks for taking the questions. First question, can you discuss how you're thinking about strategies to extend the company's cash runway? And then second question, can you provide any color on the alignment process with J&J on a global development plan? for NBTXR3 and when we might hear more on the potential medium to long term opportunities. Thank you.

Thanks Jonathan. So maybe let's answer the question number two before going to question number one. So maybe before, let's give some context in this shift in sponsorship. I think when we, if we put ourselves one year ago, The focus of the company was about getting the 312 to the interim rate out as fast as possible. And that was the context in which we've been operating. Then, last July, we've been signing this deal. And the whole idea of this deal being to, with our new partner, making sure that we can reach the largest number of patients possible and to grow the pie and to grow the market, if I may say so. So we've been shifting from having all focus on getting this interim readout as fast as possible to a focus which is enlarging the number of indications like having the lung cancer which is again a bigger market than head and neck but also to go in a more secure or direct way. So that's why along and around all this discussion we have had on what's the best timing to transfer the sponsorship, we ended up in this decision. So there have been some internal discussion, of course, at our partner level, then there have been an agreement at the GSC, and then an endorsement by our board. So that have been the process to get to this decision. And I think that there's a big question about why now versus later. So first of all, in order for J&J to be able to register the product, to start pre-market activity, and to launch the product effectively, they need to be sponsored of this trial. So there was a choice to do it either now or after the interim readout. Given the work and the heavy lifting that represents such a transfer for a global trial with 500 patients, It will take months and months to get there effectively. So we thought the best thing to do is to do it now, take the burden now, and don't have this burden post-intern readout. Then after the intern readout, assuming the data are positive, we can be fully focused on, and GenJ could be fully focused on, registering the product and starting all market activities. So that's the context in which we operate, and we've been, of course, doing this press release. Now, as you mentioned, this is opening a question about the current cash runaway and financing, but maybe I'll let Bart answer that question.

Thank you, Laurent. Thank you, Jonathan, for the question. Yeah, just to recap, we believe that it's an important step forward in de-risking of the assets, positioning it for success, and really optimizing its potential. for the benefit of patients and HCPs. As we indicated in the press release, the cash runway is unchanged, and yes, it implies that we need to finance through the updated timeline that we communicated. That said, we have much data to deliver. between now and mid of 2025 for the milestones that we shared in the PR. And based on prior study results, we look forward with conviction to sharing those updates. And as any other biotech, we have multiple options, and we're very confident that we will work through this And as you may appreciate, we cannot message on either the timing or the compositional sizing of the milestones.

Understood. Thanks for taking my questions. Thank you.

Thank you. We will now take the next question. From the line of Lucy Codrington from Jefferies, please go ahead. Hi there.

Thanks for taking my questions. So just again, sorry, the transfer of the sponsorship, just in terms of what does the timing look like for that whole process? It sounds like you do expect it to be done before the interim readout from first half 26. But I guess once that sponsorship is transferred, J&J then take over financing of that trial and therefore that alone could help extend your cash runway were it to happen sooner rather than later. Secondly, just your level of confidence in completing recruitment by first half 26 and therefore the potential timing of that interim and is there a minimum time after the the completion of recruitment, at which point that interim would need to take place. And then just in terms of the funding for the new indications that you might take into phase two, I guess that's on top of your commitment to funding 312, or if If J&J were to take over 312, that might free up some funds. Thank you.

So first of all, the expected timing for the transfer of the 312. So we're early in the process as the intent has just been agreed in the past few days. So it will take time, that's for sure, but the intention of course is to complete that way before the interim results. That's the whole intention of making this transfer now. Now in terms of Obviously this will add some investment on the partner side. Now we were just establishing what's the joint plan, not only to transfer the trial, but to continue to run the trial up to the end. Knowing that there will be no interruption of the trial during the transfer, that's the whole game we're trying to achieve here. So for the financing part and how much this will cost to Nano, how much it will cost to our partner, we can't talk for our partner, but on our side, we think for now it's neutral. We may look at it in the future to be a bit positive, but we can't say more right now because we're, as I said, early in the process. So now to your second question about H126 to get the end of recruitment. I think that's a good estimate that we could qualify as a biotech as conservative estimate, but we think given the experience of recruitment we have had so far, plus what we expect to improve the recruitment with the involvement of our partner, we should be able to reach this target. That's within the realm of possibility. So now, you asked a question about how the interim will play versus the last patient in and timing for that. So we expect to get the 283 event before, of course, at the end of recruitment. And there's plenty of work that could be done prior to trigger the interim per se. So talking theoretically here, because we again can talk for our partner, the idea would be to be ready to just push the button and to have almost concomitant last patient in and the interim readout for the trial. So, your third question, if I recall correctly, was about new indication and how we select and move forward in that direction. And what about the finance? First of all, I think that overall in our plan, including the transfer of the 312, there's still a lot of work to be done here. So we don't expect to have opening bandwidth from the team within the period of the transfer because we'll be heavily working on that versus what we're doing today already. But the new indication, I think we have a large pipeline today showing all the possibilities, or at least a big part of the possibilities of NVT XR3. And based on that and some other consideration, we will define what could be a new indication for nanobiotics. And the goal here being when we start freeing up some bandwidth of the team when the transfer is complete, then we could start thinking about adding a new trial. And this will of course depend on potential additional funding and at a later stage when the milestone payment coming from also the contract we have with GMJ. So we'll keep you updated on that, obviously. And over time, we can start building all the next opportunities we have for NBTXR3, but also, as we mentioned, in the PR beyond NBTXR3.

Thank you. Thank you. We will now take the next question. coming from the line of Suzanne Van Fortuizen from Van Lanscott Kempen. Please go ahead.

Hello, this is Chiara Monteroni. I'm on behalf of Suzanne. Thanks a lot for taking my question. I have two questions, if possible. The first one will be, can you provide some color on how imminent will be the phase 2 lung cancer? And if it's not imminent, which are the gatekeeping items here? And the second question is more about the new programs, the new platform, CuraDiamond OQT. Which kind of updates should we expect in H224? How concrete is that? Are you already working on some product candidates? Thank you.

Thank you. So about lung cancer, which is the randomized phase two trial that GNJ is going to run, We've been publishing recently a good update explaining that FDA got the green light or get the green light about the protocol design and obviously that's going to trigger a number of activities and work around that by our partner. So we can't say more at that stage, but as time always comes in what we do, then you can imagine that everyone is working heavily to get that done and started as soon as possible. I think we'll be able to give some update over time in agreement with our partner about the development of this clinical trial. Now for the question on Curadime, the expected update we want to give in H2 is about how we're going to build the strategy and the business model around this new platform. which could give not only one product, but multiple products, and in any case, multiple applications in different therapeutic areas. So, as I think I have mentioned in the past few calls, that's a technology that offers many, many opportunities, and some of the key things and key questions we would like to answer and discuss with you in H2 is how we're going to build sustainable business model with all different possibilities we have with this type of technology both on internal development and of course external collaboration and business development activities. Now to your question, do we have already a lead in this technology? Yes, we have multiple products that could be used to continue to develop this platform, but obviously we will give you much more on this in Edge 2.

Okay, thank you very much.

Thank you.

Thank you. We will now take the next question. from the line of Swayampakula Ramakant from HCW. Please go ahead.

Thank you. This is OK from HCW. Good afternoon, Lauren. Just on the long term, thinking about Q2 Diamond or Q3, so you have certainly generated a lot of validation on your NB-TXL3 program. you know, how much of that validation can be transferred into these two new nanoparticle platforms? The reason for that question is, can you point to NPTXR3 if a partner comes in and wants to talk about either Curadimer or Acuity? Is that enough or you need to generate data Only with that sort of data would the partner actually sit at the table.

Thank you, Arke. That's a good question. Maybe just before I answer this question, I just want to reiterate that on NBTX R3, we still have a lot of work to do. And there is a lot of untapped value for this first product within the collaboration we have. And the primary focus of this collaboration and the company being to make that work. And also to get the value of this product and collaboration recognized in the value of the company. Now we're starting building the future as we've been discussing that. And in terms of curadime of opportunity, There is a broader validation that our product is bringing in the introduction of nanophysics-based model faction into the healthcare. Now, as all products are different and have different therapeutic applications, of course, we need to generate a number of data to get to a potential partnership and so on. The main difference being that for both platform OQT and Curadime, we are talking here about a wide range technology platform where we can not only work with products and co-develop or license products, but we could also start licensing part of the technology to partners for them to develop their own product. So again, there's multiple opportunities here from very short term to medium and long term and that's what we intend to be able to explain to you in the second part of this year.

So should we expect some sort of a preclinical data from both CuraDem and OQD, if not in the second half, but over the next, say, 12 months? You know, trying to do this parallel track? I'm just trying to understand how you would be developing all three programs, albeit at different levels of development, of course.

Yes, without giving you any precise date for second half, yes, we'll be able to show all this. Perfect.

Thank you. Thank you very much. Thank you, Ok.

Thank you. There are no further questions. I will now turn the call over to Dr. Levy for his closing remarks.

Thank you. And maybe before I make some closing remarks, I just want to remind the audience that we have been publishing that we will present at ASCO all data on the immuno-oncology program with our lead product NBT-XR3 and we think this data and this specific application of NBT-XR3 is very important in regards to opening new doors and also potential new indication for for nanobiotics. So I hope to see you at that call when we will disclose and explain and discuss the data. And on that note, I'm going to thank you and wish you a very good day and rest of the week. And let's stay tuned for the next piece of news that will come in the coming few days. Thank you very much. Have a great day.