Nanobiotix S.A. (NASDAQ:NBTX) Q3 2022 Earnings Call Transcript November 10, 2022 8:00 AM ET
Company Participants
Kate Mcneil – Senior Vice President, Investor Relations
Laurent Levy – Co-Founder & Chief Executive Officer
Bart Van Rhijn – Chief Financial Officer
Conference Call Participants
Mike DiFiore – Evercore
Clément Bassat – BNP Paribas
Kate Mcneil
Thank you, operator. Good afternoon and good morning, and welcome to Nanobiotix Conference Call to discuss our Third Quarter 2022 Financial and Operational results.
Joining me in the call today, are Laurent Levy, co-Founder and Chief Executive Officer, and Bart Van Rhijn, 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, data 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. This 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 our most recent URD and 20-F, each of which are available in the Investor Relations section of our website, along with a 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, Nanobiotix 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 around the Laurent. Laurent, please go ahead.
Laurent Levy
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.
I would 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 indications.
Within the occasion during our last call to talk about the advancement of our global Phase 3, and today, we’re going to spend a bit more time about the 1,100 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 3 that is a randomized Phase 3 that will encompass 500 patients across the world. And the first patient that’s been injected beginning of this year later, our Strategic partner, LianBio 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 a first patient enrolled in US 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 1,100 dose escalation, and we’ve been completing the enrollment for those escalation and determine the recommended Phase 2 dose.
Later today, I will be presented at SITC, an update on this clinical trial. And this is helping us to pave the way to our potential next registrational pathway. We are happy to say that at SITC not only an update on this clinical trial will be presented but also other data on NBTXR3, including two preclinical poster, and also a full story about NBTXR3, how do we bring from the concept to patients these products.
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 part of the Phase 1. So this trial will – I have been recruiting patients in three different cohort, the first cohort being patient having a local relapse or recurrent metastatic head and neck cancer. The second cohort have been patient having lung met coming from any primary tumor. And the third cohort is patient having liver met coming from any primary tumor.
In this trial, we allowed to have patients that are either naive anti-PD-1 or anti-PD-1 resistance. When the patient entered the trial, he will receive a one injection in the primary or secondary lesion of NBTXR3 plus an activation by radiation therapy, and this treatment will be followed by anti-PD-1 either pembro or nivolumab.
What have 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 have been reported to be around 71% to 15 out of 21 patients. We’ve seen also that NBTXR3 in combination with RT may stimulate an immune response and potentially combat anti-PD-1 non-responder into responder. Of note, 67% of anti-PD-1 resistant patients demonstrated objective reduction in all target lesion.
An interesting fact is, the product in combination with RT and anti-PD-1 may produce sustained response in both anti-PD-1 naive patients and patients with cancer that have developed resistant to prior anti-PD-1. We’ve seen 38% of the patients with disease control more than six months and 24% of the patients with more than 12 months is 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 1 at a level of 22%. No DLT on other DLTs have been observed in the study. Altogether, we’ve been able to determine a unique recommended Phase 2 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 all target lesions from non-target lesion. We’re going to start in this presentation to look at efficacy from the all target lesion perspective.
All target lesion 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 lesions from baseline in 71% of the patient. 67% of anti-PD-1 resistant and 83% of anti-PD-1 naive patients. Altogether, we see a strong signal of patients having tumor size reduction versus baseline.
Before going further, we would like to just highlight the changes which been seeing and which we have been highlighted in this presentation versus the last cut off date you have seen during actual. What we see versus the last cut of date data is that three patients have shown improvement in best percentage change from baseline in target lesion. Two naive patients had continued reduction in target lesion and one resistant patient that previously reported PCR, with subsequent follow-up basic confirming durability of PCR.
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 anti-PD-1 resistant patients, 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 of 20% in miserable target vision. 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 anti-PD-1.
Another very interesting finding is that we start seeing now that the data are maturing a long-term control in both anti-PD-1 naive and resistant patients. Of note, eight patients had more than six months disease control and five patients with more than 12-month disease control. And as we know, this is controlling this population. It’s 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 upload[ph] . 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 anti-PD-1 naive and anti PD-1 resistant. And what we see is that what we see in the injected target lesion also transform into a all target lesion response. It is interesting to see here the dynamic of the response. Not only we see some long-term delay 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 evaluable for efficacy, 16 had a primary head and neck cancer. And in this population, what we have seen is 43.5% of patients having a reduction in all target lesion 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 to 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 as per RECIST 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 your case study to illustrate this point. We’re talking about an anti-PD-1 resistant patient. On the left, you see a PET scan image that represent two different lesions, the target lesion circle by blue and the non-target lesion circled in green. So that’s the pretreatment 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 control disease of 93% and 33% of objective response. This number cannot be directly compared to literature, but I think it’s interesting to remember what the standard of care is providing when you treat 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 surrogate 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 care update would be improvement in certain cases of disease control and the rate of objective response still continue to be important and very interesting.
Now if we look per RECIST 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-PD-1 naive and 67% in non-responders. The difference between RECIST and non-RECIST are really linked to those additional non-target lesion that will explain the difference in those data.
You will see in the poster that we have also had a table, a table that presents the best overall response evaluation as per RECIST 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 we 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, which of note, 60% of anti-PD-1 resistant head and neck patients achieved a stable disease as a 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 a strong signal that NBTXR3 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. NBTXR3 may also enhance the therapeutic response to immune checkpoint inhibitor and may stimulate a response and potentially convert anti-PD-1 non-responder into responders.
One of the important points we have been highlighting in this presentation is that the vast majority of PD-1 resistant patients, entered 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 this is ongoing expansion phase is paving the way for our next potential registration pathway that will intend to treat head and neck patients 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 raid out on overall response, we could be eligible for accelerated approval with the 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 The Scientific Advisory Board. As you may have seen in our recent press release, we have formally formed or 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 indications.
I will now turn the mic to Bart that will make an update on the financials.
Bart Van Rhijn
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 and cash equivalents were €53.5 million for the first three months ended September 30th, 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 time lines.
The cash and cash equivalents as of September 30th, 2022, combined with the executed debt restructuring and existing equity line is expected to fund development programs into Q1 2024.
And now I will turn the call back to Laurent, Laurent?
Laurent Levy
Thank you, Bart. I have to conclude the first part by tell 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 station. Our Phase 3 that has started. Now, we were expecting to get the futility analysis H2, 2023 and as planned the interim on PFS on H2 2024.
Also, the completion of the 102 Study that was the Phase 1/2, will present the final data midyear 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 path 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 path 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 are scientific complaints. 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 calls with you.
On that, this concludes the first part of the call, and now we will open the floor for questions. Operator?
Question-and-Answer Session
Operator
Thank you. [Operator Instructions] Now we’re going to take our first question. And the first question comes from the line of Mike DiFiore from Evercore. Your line is open. Please ask your question.
Mike DiFiore
Hi, guys. Thanks so much for taking my questions. This is Mike on with John. Congrats on the data. Just a simple question for me. Today’s study 1100 data set was flagged as an important value driver for the company, especially with regards to extending cash runway beyond 1Q 2024. So my question is this. Just given today’s study 1100 results, where 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 do that, meaning kind of have the study prove valuable in terms of potentially attracting additional capital, or — and are there any additional levels to be able to pull to get you through NANORAY-312 in 2024? Thank you.
Laurent Levy
Thank you, Mike. So good question. I think what we see in this Phase 1 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 going to define pivotal trial, we intend to submit to FDA in Q1. But we think the signal we see for Phase 1 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 3.
Now until we get the feedback from the FDA on the design of this Phase 3 would be hard to understand how much cash we will need to execute it, and what would be the endpoint and time line 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.
Bart Van Rhijn
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 deferred 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.
Mike DiFiore
Great. Very helpful. Thanks so much.
Operator
[Operator Instructions] And now we’re going to take our next question. And the next question comes from the line of Clément Bassat from BNP Paribas. Your line is open. Please ask you question.
Clément Bassat
Good morning. Clément Bassat from Portzamparc. Thank you for taking my questions. This is about the next step in the IO programs. The first one will focus only on the head and neck cancer patient resistant to Anti-PD-1. So could you please provide some colors about the categorization of the core, mostly about the control arm since these patients are resistant on Anti-PD-1. Are you going to happy then to start treatment again with Anti-PD-1s, which do not work for them, just to be included in the control arm. So how will you deal it with the FDA?
Laurent Levy
Thank you for the question. That’s a very important question and an interesting one. You’re 100% right, saying that if these patients 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, 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, just mic problem — so that’s part of the thinking we have in designing this Phase 3 and also the discussion we have had with FDA. Now to be more precise, there’s many options for a 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.
Clément Bassat
All right. Okay. Thank you very much.
Operator
Thank you. [Operator Instructions] There are no further questions. And I would like to hand the call over to Kate Mcneil for closing remarks.
Kate Mcneil
Thank you. I’m going to take the lead on that. And I would like to thanks everyone for participating to do that call. Again, very happy about this new data we have generated and presented at SITC. There are also many other data that will be presented from a clinical 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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