Theratechnologies Inc. (TH) Earnings Call Transcript & Summary

Good morning, ladies and gentlemen, and thank you for standing by. Welcome to Theratechnologies' sudocetaxel zendusortide protocol update and ASCO presentation video conference call. [Operator Instructions] I would like to also remind everyone that this conference call is being recorded today, Tuesday, June 13, 2023 at 10 a.m. Eastern Time. I will now turn the call over to Mr. Paul Levesque, President and Chief Executive Officer. Mr. Levesque, please go ahead.

Good morning. I want to wish everyone a very warm welcome and hope that you are as excited as we are for today's event. Before we begin, I'd like to remind everyone that our remarks today contain forward-looking statements regarding Theratechnologies current and future plans, expectations and intentions with respect to future events. You can find the FLIs posted on the screen. When we assumed that Thera's letter to shareholders in January of this year, it was with the objective to share our strategic direction and our key priorities for the year, one of those key priorities has come to a head, and on today's call, we will provide the latest update regarding the development of sudocetaxel zendusortide. So let's jump right in. I'd like to bring your attention to today's agenda on the screen. We will begin with Christian Marsolais, Theratechnologies' Senior Vice President and Chief Medical Officer. Christian will provide a brief introduction to callers on the role of sortilin, SORT1 receptors in cancer, in addition to sudocetaxel zendusortide's mechanism of action and some preclinical data. Most of our time will be spent hearing about our investigators' experience with the sudocetaxel zendusortide Phase I study and highlight the key elements of changes that led to an amended protocol. The lead investigator, Dr. Funda Meric- Bernstam from MD Anderson Cancer Center would highlight the preliminary safety and efficacy data that she recently presented at ASCO 2023. In addition, study co-investigator, Dr. Ira Winer from the Karmanos Cancer Institute will complement the data presentation with clinical observations from a few of these select patients. Following all presentations, we will go into a Q&A before we wrap up the call. As you saw from our press release published on June 2, we announced that the FDA has agreed to the proposed changes in our protocol and lifted the partial stable hold placed on the Phase I trial which we [indiscernible] in December 2022. To quickly recap, the amendments were created with a critical input from our scientific advisory committee and informed by the preliminary ASCO data. The revised protocol is designed to improve the therapeutic window of sudocetaxel zendusortide and extend it's duration of therapy. We are confident that these changes will increase our probability of success in the clinic. Both the ASCO data presentation and the FDA's agreement to our protocol update are significant milestones in the development of sudocetaxel zendusortide. Our goal, all in all, has been to bring our investigational anticancer PDC back into clinics, especially for patients who may have limited treatment options. As I'm speaking, the revised protocol is already in the hands of the study sites, we're seeking ethics approval prior to resuming recruitment. We are ready to turn our full focus to restarting the study and dosing the first 6 patients as quickly as possible. Before I hand the call over, I want to share a little more about the medical experts who have joined us today. Funda Meric- Bernstam is a medical oncologist at the University of Texas MD Anderson Cancer Center. Chief Chair of the Department of Investigational Cancer Therapeutics the center Phase I program, the Medical Director of the Institute for Personalized Cancer Therapy and now he currently Chair in breast cancer. Dr. Meric is also the lead investigator of our Phase I trial setting sudocetaxel zendusortide. Ira Winer is a gynecology, oncologists at the Karmanos Cancer Institute and assistant professor in clinical scholar at Wayne State University. Dr. Winer is a co-investigator of our Phase I trial. Without further ado, I would like to invite Christian to begin the main portion of today's call. Christian?

Thank you, Paul. Good morning, everyone. I'm very pleased to be here today this morning for this meeting following the release of our Phase I data during ASCO and the approval of our amended protocol by the FDA. I would also like to thank Dr. Meric and Dr. Winer, first of all, for being investigators in our study in improving some of those patients and also to take the time out of their busy clinic this morning to be with us and help -- their help to prepare this presentation. I will start with a brief overview, as Paul mentioned, on our platform and our PDC. Next slide, please. I think the one thing which is very important, yes, we're developing a PDC. We're developing a platform. Those are smaller molecules than A, B, C, small peptide to which we attach anti-cancer drug. But one thing which is very important about our platform is the target. And we're targeting the sortilin receptor. This is a receptor which the natural function is to internalize large molecule inside the cytosol of cells. And what was uncovered recently is that this receptor is significantly overexpressed in many different solid tumors. And the other advantage about this target is that, next slide please, is internalized with them for a minute. It's a very -- sorry, go back to -- the ability of internalization may get a significant important target because what's happening is that once the cell is exposed to the product, with the rapid internalization of this PDC, there's a significant increase in terms of concentration of the anti-cancer drug in the cell. And all of the preclinical data that we have obtained so far are showing that this is working well against many cancer. Next slide, please. As I mentioned briefly, this target is significantly overexpressed in many [indiscernible] time. We started the journey about 3, 4 years ago. At the time, there are very small number of data in terms of the expression of this receptor. We're one of the first companies working with this receptor. And what we have done so far, we've worked with a third party to develop a proper even though we still [indiscernible] test to assess the level of this receptor. As you can see on the left-hand side of this slide, in ovarian cancer, you can see there a significant expression of the receptor by the gram stain. We developed a score, which goes from 0 to 300. And you can see that in the normal or healthy over there's only a very light color. And this receptor is expressed at a very low level in most of the normal tissues. On the right-hand side, you can see that now based on all of the work that we have conducted and we have tested more than 2008 different tumor types. And you can see that this receptor is expressed at the very ice core in many solid tumor. In ovarian cancer, you'll understand why later, we talk about ovarian cancer but there are more than 74% of those patients with ovarian cancer that are expressing this receptor at a very high level. But in addition, you can see on this graph that there are also many other tumor types like TNBC endometrial cancer and breast cancer, HR positive breast cancer that are expressing this receptor at the level, which is about 80% to 90% of the patients with the different types of cancer. Next slide, please. Then now just a word about our mechanism of action and why we're playing that this [ ADC ] has significant advantages. First of all, what you see on the left-hand side of the slide, at the top, is our molecule, which has a 17 amino acid peptide with 2 [indiscernible] makers and 2 molecule of docetaxel. And this is a relatively simple molecule to dealt or to produce. The reason why we're using these cleavable linkers is because one, we want to make sure that once the drug is inside the cell those effect or the in-cancer drug will be released rapidly. We also have done many tests with different peptides to ensure that the peptide was attached to the receptor, but also will be released once inside the cell. Then this is a cartoon of the way we think it's working, but the sortilin receptor, as I mentioned before, is a SORT1 receptor, which is internalizing large molecule inside the cell. And in this case, we're mimicking the normal ligand then our PDC attached to the receptor, there's a formation of the endosome, the activation of the endophytic pathway. And after that, once it is in the endosome inside the cell, it's releases a cytotoxic and docetaxel, we have a lot of data showing that docetaxel stepwise for microtubules doing the same job as it does when it is injected as a free agent. The other advantage because of the short life of internalization as I mentioned before, we kind of significantly increase the concentration of the cytotoxic specifically inside the cancer cell. Therefore, we made up with this technology, we will be able to improve the therapeutic quintal of many anticancer compounds. Next slide, please. With all of the work that we have done over the past few years with our group of scientists on the research side, we have uncovered many additional benefits of using the sortilin receptor to enter the cancer cell. One of the first one you saw on the [indiscernible] cartoon before that we entered the cell via the endocytic pathway. One of the main negatives on resistance of taxanes is the MDR1 pump, which is kind of excluding those Cytotoxic from cancer cell. What we have shown is that by using the sortilin receptor, we are bypassing this main mechanical persistence of taxanes. We also have shown and published data that we are inducing more peptide induces apoptosis of cancer stem cells. Those cells are very resistant to many indicator treatment already on the market, but we have shown that we have very good efficacy against those interests themselves. One of the other negatives of resistance, which is recently known, is the formation of pestilogeneic mimicry, which the phenotype of the cancer cell change to form small channel to feed other cancer cells and efficiency of those small channel. We have shown that sudocetaxel zendusortide inhibit and stop the formation of those vasculogenic channel. And also because if they're a small molecule compared to larger molecule like PDC the drug penetrates the tumor microenvironment, which everybody believes that this is really where you have most of the resistance of this building up from cancer and by acting in this macro environment, we might eventually have some chance to have an impact on long-term impact on those cancer patients. The other thing that we uncovered recently and the data was published at AACR in the spring is we did some experiments in normal mice with mice tumor. And what we have shown is that sudocetaxel zendusortide significantly potentiate the infiltration of tumor infiltrating lymphocyte. This is completely new setback and it is very interesting. It says that this product is activating the innate immune system. We also have shown that there could be synergy with immunotherapy, which is very encouraging for a later part of the development of the product that would be in combination with other products. I would like now to turn to Dr. Meric that will discuss all of the data and the clinical data that we have so far. Dr. Meric?

Hi, everyone. I'm Funda Meric- Bernstam. I'm the Chair of the Department of Investigational Cancer Therapy at MD Anderson, and I had the opportunity to present the Phase I study results at ASCO this year, as all the -- going over some of the highlights from that presentation. Next slide. We couldn't have been a Phase I first-in-human study. This is a multi-center open label study with an FDA fast track dosing nation. This was a dose escalation study, where we enrolled patients with advanced solid tumors that were relapsed or refractory to standard therapy. This is an All-Comer study. We didn't do biomarker selection. We started with 30 milligrams per meter square every 3 starting dose and did allow for intrapatient dose escalation until and went to MTD. Next slide. We enrolled 18 patients in the dose escalation. There was enrichment for females naturally because we were interested in enrolling taxane sensitive tumor types. We enrolled -- the majority of patients were PSF1, and this was a heavily pretreated patient population even for Phase 1, I would say this is a more heavily patient population with a median of 6.5 lines of therapy, up to 20 prior lines of therapy in our patient population. Notably also, majority of our patients have seen taxanes with a mean of 1.8 lines on prior taxanes. If you see the cancer types that been enrolled, major of the patients had ovarian cancer, also enrolled endometrial, cervical, hormone receptor positive breast, prostate, melanoma and lung cancer. Next slide. Yes, a little bit of a complicated dose escalation scheme. So again, reminder, we had a single patient dose escalation initially, and then we went up to 420 milligrams per meter square, then we explored 360 ultimately deciding to proceed with 300 and initially started the basket with 300 as the recommended dose for the initial expansion. Next slide. The dose escalation was notable for the following adverse events we wanted to highlight. First, although we're using a taxane regimen. We didn't have significant hematological toxicities such as neutropenia or thrombocytopenia. But we did have neuropathy, which of course, could be seen with the antitubular agents. When we achieved 420 milligrams per meter squared, this became quite apparent. We had 2 patients that had grade 3 events and 2 patients who had grade 2 events. The severity of neuropathy was less at 300 milligrams per meter square, though we have also seen some neuropathy at that dose level. We also saw ocular toxicity at 420 especially. We had 1 patient with a Grade 3 event and 3 patients that had Grade 2 events. Also had some ocular toxicity of lower grade at 300. Also, some GI tox as well as some musculoskeletal discomfort. We'll talk about a little bit more later. Ultimately, at that time, it was felt that the neuropathy was -- could -- it was potentially manageable or at least monitorable at 300. And with for ocular toxicities that we could formally initiate prophylaxis to be able to minimize the ocular toxicity. So 300 was selected to proceed for the initial dose expansion. Next slide. So just to reiterate, taking together the dose escalation data, it was felt that we could initiate a basket study using 300 milligrams per meter square with focusing on tumor types with high expression of SORT1. Next slide. The plan was to select tumor types listed below. The patients were not selected based on SORT1 expression, but rather based on the data that preexisting data that these are the tumor types that have high levels of SORT1 and we're exploring the recommended dose of 300 milligrams per meter square. Next slide. We enrolled 18 patients in the dose expansion. I would have pointed out that we had ruled out a basket trial that will continue to monitor safety and efficacy and decided to stop when we reached 18 patients due to continued neuropathy signal. So I want to share with you what we have seen during the initial dose expansion. Again, this was a relatively heavily pretreated patient population, median of 5 prior lines therapy meeting at least one line of taxanes. Again, quite a few ovarian cancer patients that smattering of other 2 types endometrial breast cancer, TNBC [indiscernible] receptor positive, prostate melanoma, small cell and thyroid. Next slide. And these were treatment-related adverse events in all patients treated with 300 milligrams per meter square. So this includes both the patients we treated in the basket component as well as patients that were treating the initial expansion and where we're establishing the Phase II dose or initial recommend the Phase II dose. As I mentioned, the frequency of neutropenia and anemia was relatively low for cytotoxic strategy with only 4% of patients having Grade 3 neutropenia and 8% with anemia. The eye disorders cumulatively in all patients treated, especially keratitis was 16% with 8% of patients having Grade 3 or higher. However, the -- this majority of the higher adverse events were notable for patients that were -- had not had initial prophylaxis. We do feel that the keratitis has been under a fairly well control once we initiated routine prophylaxis. The GI tox seen included constipation, diarrhea and nausea, vomiting and then, I think, not manageable looks like. The other adverse events include musculoskeletal events, we have reported arthralgia, myalgia, pain and extremity, including some pain on infusion in the extremities. But most sort of concerning adverse event that we focused on was the peripheral neuropathy. We had all grades 20% and Grade 2 or higher 8% peripheral neuropathy. Again, although we -- our Grade 3 event rate had dropped compared to where we were at 420, we felt that for patients that we wanted to be able to give a drug that could be at a dose level we can maintain long term. We felt that this neuropathy rate was too high, making us sort of reconsider the dose of schedule where we're at. The only other sort of adverse events have now included notable fatigue, which we saw in about 36% of the patients, but none of these were high grade. Next slide. So in summary, we're looking at Part 1 and Part 2 with a focus on that, we revisited our 300 milligrams meter squared dosing cohort. And we felt that the neuropathy appears to be related to cumulative exposure of the circulated docetaxel based on PK/PD data. And the eye tox is probably not target related, but with accumulation of the PC, in the anterior chamber of the eye, similar to what we see with ADCs and indeed, our -- we are fortunate enough to have very experience ophthalmologists that are familiar with ADC eye tox. We've gotten quite a bit of guidance from them. These events have all been reversible. And ultimately, for eye tox we had initiated our care prophylaxis and to try to mitigate both eye tox and neuropathy decided to proceed with weekly administration and changes of our dosing. So all the other adverse events, neutropenia, alopecia were favorable aspects of the PDC has seen. And again, all of this data that we presented at ASCO informed the protocol changes that is being initiated. Next slide. From an efficacy standpoint, this is a heavily pretreated patient population. [ 36% ] of the patients had some signal of efficacy. This included 2 patients that had RECIST confirmed partial responses, one patient with prostate cancer, one patient with ovarian cancer and 7 patients that had overall with the clinical benefit with the 4 lines -- 4 cycles or more of treatment. Next slide. And here are some change in target lesions for precision in the breast cancer patients we've seen. You can see that we have not regression meeting the partial response metrics but some regression in patients that have had 6 prior lines of therapy. Next slide. And then radiological responses we've seen in ovarian cancer including one patient with a partial response after 7 prior lines of therapy. Next slide. So again, all of this data cumulatively has informed the amended protocol for Part III of the study. In Part III of the study, we'll be initially focusing on ovarian cancer. The dosing schedule has been changed to give treatments weekly with day 1 day, day 15 on a Q4 weeks cycle. And we will change in dose calculation. And with the plan of doing 2 dose levels that will be tested sequentially with initially starting with 1.75 milligrams per kilogram, which we feel is [ hopeful ] to 210 milligrams per meter square and then to 2.5 milligrams per kilogram which we feel is a hopeful to 300 milligrams per meter square with the ultimate expansion to 10 patients and then revisit the safety of efficacy throughout with regular meetings. And also revising eligibility criteria to limit prior failures to taxanes and have a cap on prior treatment regimens. Next slide. I'd like to introduce my colleague, Ira Winer, who will be reviewing some of the patients with clinical benefit to date.

Thank you for allowing me to join you all today. Again, I'm a Gynecologic/Oncologist by trade as well as Theratechnologies lead in our network at Wayne State University in Karmanos Cancers Team. So I'll present a few examples of patients that have achieved clinical benefit in the initial stages of this trial. Next slide please. So the first patient is one of my patients with endometrial cancer who was initially treated many years ago and then ultimately recurred and unfortunately then progressed on repeat platinum as well as immunotherapy. Once she started progressing, she unfortunately then progressed subsequently on 2 investigational regimens and clinical trials rapidly and then was enrolled on the current trial in mid -- basically mid-2022 about 1 year ago. She did receive 2 cycles of trial drug and then developed significant neuropathy, which of note was a little different in terms of mechanism. This was more of an autoimmune response. Ultimately. It was not related to the drug itself. And this is something that could occur with any chemotherapeutic agent. But she was discontinued from treatment about a year ago and has had no progression of disease since the initiation of her treatment with only 2 cycles of therapy, and it's now been over 12 months. The only treatment that she did receive was radiation to a vaginal tumor secondary to bleeding, but not actually progression of disease. She's actually doing much better with treatment for her neuropathy. And will be seeing here in the next month to confirm whether or not she has continued stable disease. Next slide, please. Second patient is a patient that had triple negative or has triple-negative breast cancer. She had progressed on 4 prior regimens with rapid progression on a prior antibody-drug conjugate right before entering into the current study. She was started in late 2022 on the current therapy. And she was initiated during the basket trial in the 300 milligrams per meter squared, but ultimately reduced to 200 milligrams per meter square, which is the protocol moving forward. And this was secondary to a recurrence of her baseline neutropenia, she had significant neutropenia baseline from prior regimens. And so the dose reduction, she's actually done quite well, and she's remained at the current dose for greater than 7 cycles and has had stable disease since that time. In fact, she's due to repeat imaging at the end of June. But currently, when we last saw her in clinic, she noted that the symptoms from her cancer, which had been uncontrolled prior to our entry into the trial, have been significantly controlled on the current therapy, and she's requiring less pain medications and her overall performance status has improved as well. Next slide, please. Again, the last patient that I wanted to highlight is a patient, again, with endometrial cancer, who had been on 2 prior platinum therapies, and unfortunately progressed as well as hormonal therapy, which is standard of care in some instances for endometrial cancer. She was 1 of the patients that was intrapatient escalated from the very early part of the trial from 60 milligrams per meter square to 360 milligrams per meter square every 3 weeks. And this is over 11 cycles of treatment. Her only relatively minimal side effects for mild blurred vision as well as Grade 1 neuropathy, which was very light. This is at the highest dose. And while she achieved only stable disease. This was for a very prolonged period for greater than 4 months. Ultimately, she decided to withdraw consent for further treatment, not because of side effects from the therapy, but rather she had been on treatment for a significant amount of time and wanted to spend more time with quality of care and with her family. So her side effects ultimately did recover from the treatment. Last contact with the patient was approximately April of this year, and she continued to have stable disease and been doing well. So next slide, please. So overall, these are 3 examples of patients that did have significant benefit from the current therapy. And again, this is in the context of the current protocol. With the changes in the upcoming protocol, we hope to see even increased benefit from the drug therapy with significantly reduced side effects. And again, the most important aspect is we want to see clinical benefit for our patients while minimizing the side effects and improving quality of life. And that's what I have.

Thank you very much, Dr. Winer and thank you very much, Dr. Meric. We will now open the session for the questions. We will start with the questions from the analysts. And after that, we will open the questions through other people.

[Operator Instructions] The first question comes from Louise Chen with Cantor.

Congratulations on all the progress with sudocetaxel. I wanted to ask you 2 questions here. So first of all, where do you think this drug would fit into the treatment paradigm? If it is approved? Is it a monotherapy, combination theory -- combination therapy, can you comment on the combinability of the drug? And then which solid tumors do you think present the best opportunity or best commercial opportunity for the drug and why?

Thank you, Louise. Yes, we do believe that the like as a single agent, first, this is the objective with the changes that we have made in the protocol and the results that we presented to be in the clinical benefit on the 3 patients presented by Dr. Winer that there's room as a single agent for the next stage of development. After that, of course, we think that there will be significant of combination. The first 1 will be immunotherapy based on the data that we have presented at ASCO. We have demonstrated that there is significant infiltration of tumor-infiltrating lymphocytes, activation of the immune system and synergy with immunotherapy. But in addition of immunotherapy, if we reach the objective with the second phase showing better efficacy and better safety profile, as you can see on the data that we presented today. The adverse events are manageable, eye toxicity which was one that we had a higher dose by lowering the dose that will be less. And with the preventive measures is manageable similar for the neurotoxicity, then there will be also the possibility to combine the drug with other agents. Dr. Meric, do you have anything to add to this answer?

Yes. Thanks, Chris. I agree. I think the fact that we're seeing minimal neutropenia and anemia makes it an opportunity to be able to combine with other cytotoxic agents. Clearly, there's room for exploring novel targeted therapy combination options, but I definitely with the early things to look at based on the data already generated by Thera.

Then in terms of your second part was your second question, the tumor type. At the moment, basically data that we have so far, we made the decision to focus on ovarian cancer because this is where we have seen sign of efficacy. But as I mentioned earlier in the presentation, there is a number of solid tumors significantly expressing that receptor. And of course, like TNBC was also shown as an example, where we have good signs or preliminary signs of efficacy and then heavily pretreated patient population, we do believe that we will be able to expand in many different tumor types. And maybe Dr. Winer, if you have anything to add to this answer?

No, I agree. I think the fact that this is a widely expressed receptor makes this potential for expanding into multiple tumor types, of course, proof of principle and 1 tumor type is the way to go first. And then it can be expanded. The other thing of note is, again, these were in later lines of therapy. So there was a question regarding positioning. And so this offers opportunity both for later as well as earlier lines as we move forward once the protocol has been -- the amended protocol has gone into clinic and we show efficacy as well as tolerability.

Our next question comes from Andre Uddin with Research Capital.

So my first question is actually for Dr. Winer. I realize this is early data, but it is promising, and I know it's a bit of a guesstimate. But if you actually look at the data, the patients were quite sick yet responses were seen. So if you look at the swimmer plots and all the data that you reviewed, which indication do you think would have the highest probability of success in the new protocol -- dosing protocol?

So again, I think the reason that ovarian cancer was chosen as the first tumor type to move forward with, was the fact of, again, of the receptor positivity and the high levels of receptor positivity as well as the complete response or at least in some of the RECIST lesions. So again, I think there are multiple potential tumor types that could benefit. But again, as with many protocols, you want to show proof of principle first. And so that's what ovarian cancer will be and then the decision will be made regarding others that were previously included in the basket trial.

Dr. Meric, do you have anything to add for other potential tumor types?

No. I agree. I mean I think we, as investigators focused on traditionally taxane sensitive tumor types and the overlap of that was SORT1 expression. Of course, we don't know higher concentrations of delivery at the payload will expand sensitivity to other tumor types as well. But I think there's definitely opportunities not just in gynecologic cancers, but tumors like breast cancer, where we don't have a tubulin payload ADC in clinical use. And definitely systematically reviewing indications as for opportunities is worthwhile.

Okay. That's great. And maybe Dr. Meric can you answer this other one. In terms of the safety, if 1 looks at the safety profile of 1902, it does appear to be better than docetaxel 1 looks at the prescribing info. Just in terms of clarity, I wanted to get an idea of if -- was the eye toxicity all transient and also was the neuropathy transient as well. If you could just clarify that for me, that would be great.

Yes. Thanks. Whenever we have strategies that are direct delivery, eye tox is something we look at, and this has definitely been something that over the last several years, the field that oncology has learned how to deal with. I think yes, with the dose mitigation and prophylaxis, we've put in place the eye toxicity is manageable. The neuropathy is really going to be the key determinant, I think, on the drug development plan. We definitely had more neuropathy than we were hoping in the basket trial to date. And we're hoping that the new dosing schedule will be able to help control that.

Okay. Thanks.

Our goal isn't to give treatment for a few months on what we want to treat them to all our patients to stand for long period of time.

And Andre just to add, the -- we did a lot of pharmacokinetics and pharmacodynamics analysis, like looking at the drug level versus the adverse event. And that's one of the reasons why we changed the dose administration instead of giving the drug in surface area, will be by body weight. And what we have uncovered is a patient that has a lower weight because the drug was given in body surface areas. They were kind of overdosed, and we had some patients that have neuropathy. The other thing is, based on those analysis, we do believe that the neuropathy seems to be linked to the area under the curve of 3 dose effect on then by giving the drug on a weekly basis with slightly lower doses, we think that this will be manageable. When you look at the data, there's a big difference from 420 to 300, and we've taken that this will be manageable in the next step.

[Operator Instructions] Our next question comes from Bill [ Mahon ] with Canaccord Genuity.

So you mentioned that there was no biomarker inclusion criteria. Did you look at SORT1 expression post hoc? And do you plan on introducing SORT1 positivity as an inclusion criteria going forward? And I guess, how onerous would that be to test for that before enrolling somebody?

Yes. Thank you for the question. In the study at the moment, we did that, and we had some exchange with the FDA models to look for patients with SORT1 expression, they wanted to see more or less All-Comers. But what we have done, we -- in our [ inclusion ] criteria, we selected patients that were high expressor like ovarian cancer 74%, and other cancer are in the range of 8% or more. And we do not believe that we need to do a diagnostic test before treating those patients. Eventually, if we go in other tumor type, we might need to have a diagnostic test, and we're working on this. In terms of the cost, I don't know, but there are a number of drugs that are already approved in the market, where we have diagnostic test, and I don't think it will be much different than for some of those products. The earlier part of your question was the sortilin receptor expression in the cancer enrolled. Yes, we did a [ TNBC ] baseline and we'll continue to do so in the next phase of the study to ensure that we know what are the level of assortment receptor, before we treat the patient eventually when we will have enough patients at the moment, we know that most of those patients have high level of sortilin, but we need a lot more patients than that before we can do a correlation between the expression of the receptor and the efficacy of the drug.

Okay. And then just thinking through the neuropathy. Is that -- is the neuropathy going to be -- is it a result of SORT1 targeting? Or is there potential to maybe improve specificity for sortilin targeting and thereby reduce neuro?

Well, with the additional PK/PD analysis that we have done, at this stage, it looks like it is linked with the low level of docetaxel in the area under the curve of docetaxel. This is the association that we were able to make. We do not believe that it is linked with the sortilin receptor activity or [indiscernible] action per se. And we'll see with the next stage in terms of the type of adverse event that we'll see on the neuropathy side, but we do believe that they will be more manageable. Dr. Meric, if you have anything to add on this question?

Yes. This is a challenging question, of course. It's not a surprise when we have a tubulin agent with neuropathy I don't know that we 100% excluded that there isn't target-related component to this.

We are showing no further questions from analysts. I'd now like to turn the call back over to Philippe Dubuc for questions from the chat.

Thank you. So we have a few questions from Justin Walsh, an analyst with JonesTrading. So I'll read them for you at this time. For the KOLs, recognizing that it's still early, can you comment on what details of the data you find most encouraging. What are the biggest remaining questions in your mind?

Maybe Dr. Meric, if you want to start. And after that, we'll go to Dr. Winer.

Yes. Thanks, I think this is of course, completely novel strategy. It's the expression pattern data generated by Thera that this is expressed across so many different tumor types at relatively high intensity. And that sort of high scores across tumor types, I think is really encouraging for the potential of this treatment strategy. There's obviously a lot of developments in the ADC, PDC space, but there's definitely a need for tubulin agents that are accessible for across tumor types. So that's I think the novelty of the strategy is great. To answer an earlier question, of course, more data is needed to look at how much expression is sufficient. But for disease like ovarian cancer where there's high expression in so many of the patients. I think the strategy of looking -- taking All-Comer of that tumor type. And then that are determining whether there's a certain amount of intensity or a certain amount of percentage expression that's required to be able to decide if there's any value-add is another tumor types to select is worthwhile.

Dr. Winer, do you have anything to add or...

Yes. No, I agree with Dr. Meric. I also think it's really important is that the fundamental mechanism by which this PDC is acting is across both conventional mechanisms as well as alternative mechanisms to even affect the immune environment in the microenvironment. And I think this is a novel component of this agent that will allow it both to overcome resistance to conventional agents, hopefully, in patients that have been heavily pretreated as long as the risks don't outweigh the benefits and also, ultimately, the ability to combine this with other agents in that sphere.

And the second question from Justin Walsh is as we see the increasing use, particularly in ovarian cancer. Is there a concern about overlapping adverse event profiles, such as eye toxicity, limiting the potential utility of sudocetaxel zendusortide?

I'll start with this one with the -- some of the most recent results with some of the PDC were in the kind of some group of patients. If we think about [indiscernible], those are in patients that are expressing [ novel ] receptor. Therefore, there is still a high need to for other drugs in ovarian cancer. Dr. Meric, do you have anything to add?

Yes. So I think when we're talking about eye tox, we're predominantly thinking about the most recent approval for mirvetuximab, where there is some eye toxin that is [ anti-tubulin ]. We don't know whether there'll be cross resistance in the payloads, of course, only a fraction of patients, a small portion of the patients with ovarian cancer still have fully receptor target expression. So that's an area of continued drug development. And we'll need to monitor, I think, now that more of our patients will have been exposed to that, whether that will be something to consider. But we will be doing pretreatment assessment. So we'll be only enrolling patients that don't have preexisting eye tox before study -- entire study.

So another question from Justin Walsh. Now that we're focused more on ovarian cancer. Can you comment on the current treatment landscape and what benchmarks we should look for to evaluate future efficacy and safety results.

Maybe we'll go back to Dr. Winer to answer the question.

Sure. So now that we are focusing more on ovarian cancer, again, just to kind of also put it in context, even though there are multiple ADCs in this sphere right now, not all patients have, as Dr. Meric said, have each of the specific receptors. And so there's definitely space. This specific trial, again, as I commented before, is allowing for heavily pretreated patients, which most of the other ADCs do not allow in most of their upfront trials. Many of the ADCs that are approved for ovarian cancer are currently in development are allowing 1 or 2 prior, maybe up to 3. So this is a very interesting place to position the current PDC. And in terms of what we're looking for, for outcomes, I think that's number 1 is toxicity. So we have to see that. But in terms of efficacy, I think, again, it's not only the partial responses, et cetera, but it's also clinical benefit rate. And I think that we're looking somewhere, hopefully, in the PFS or progression-free survival of somewhere in the 3 to 6 months in a moment, heavily pretreated patients. But if we can succeed with more, especially in stable disease, then you have a winner. And again, there's definitely a signal there currently, and we'll know more when we move forward with the current trial.

Thank you. Thank you, Dr. Meric. I know that you have to leave probably shortly in you can see a few more minutes. We'll go to the next question.

Final question from Justin Walsh is any comments on physicians and scientists that you'd like to highlight from ASCO? How well was this received?

Dr. Meric, well at ASCO and you have any questions and you address any questions, I think that we can probably address this question.

Yes. No, I think the poster was -- presented this in a poster fashion, which is a really interactive format that I enjoy so much. And we had a lot of visitors and a lot of people who are very interested in the data. So it was well received.

And I think that most of the question. Many questions in on the receptor because what we have presented so far is usually in basic science meeting when we talk about the mechanics of action, but people who are very curious about the receptor. And when you talk about fact that there is a receptor have internalized rapidly for internalization of [indiscernible]. It's really something that capture their attention, and they are very curious about this new receptor.

Okay. There are a few questions on the selection of ovarian cancer as opposed to triple-negative breast cancer. Is there a specific reason why we went with ovarian and not TNBC.

Well, it was mainly based on the results so far, we had a bit more ovarian cancer patients, of which one had the complete response unhistoric reason. This was a partial response overall. Then we do believe that it's something that's the reason why we're focusing there. But like if we see signs of efficacy and that second step, we'll probably be able to move rapidly to TNBC and other cancer types. Dr. Meric, any additional...

Yes. I mean I think breast cancer is definitely an opportunity both for TNBC and hormone receptor positive disease. There is an unmet need still for targeted delivery systems. So especially if we can demonstrate that there's enhanced immunogenicity and IO combination potential that we make it specialty appealing.

Another question, how are you correlating the fact that TH-1902 is actually working as intended, if you're not preceding for sortilin?

Well, for this question more or less because the patients that have been selected at the moment were selected based on the fact that they were high tumor types for high expresser of the sortilin receptor. And that was confirmed more or less by the biopsy that we have done at baseline. We assessed the sortilin level, this was pretty high above for all patient enroll in that setting.

I mean, I just want to remind everybody that most of ADCs recently that have been approved have been approved in disease-specific fashion using diseases that we know have high expression. [indiscernible] for bladder cancer, type II bladder cancer, breast cancer. So this model, I think, has eliminated the need for selecting with biomarker assessment and allowing for a retrospective assessment of, is there a differential sensitivity. So -- but I agree that if we look across tumor types and into tumors that are less people expressing SORT1, we will eventually need a strategy to do patient selection. So this will allow us and determine how much is enough.

Can you explain how changing both dosage and timing can make this drug more effective? Any comparable studies you've seen where this works.

Dr. Meric, I think that we have some experience with also other growth and highlights.

No, I'll start off by admitting changing 2 things at the same time. Of course, it makes them a little bit more complex. But I think we've seen at least other antitubulin strategies where neuropathy had issues using a lower dose, more frequent schedule, get -- allow them to get the clinic. So at least in part, inspired with this decision. A lot of discussion with a lot of expert drug developers going into this decision.

Dr. Winer, anything to add?

No, I agree. We've used this in GYN malignancies and various types to get drugs to patients in the past, and it has mitigated the side effects, but actually improved outcomes because also of other off-target effects that you see when you do a dose dense as we call it.

And maybe I will add that the 2 doses that we are using, the dose that we're starting at 1.75 milligrams, I know that's for people that have been following us. You used to see dose of 200 milligrams per meter square, 300-kilogram. The dose of 1.75 milligram per kilogram is in the range of the 200-milligram per square meter. It is divided in 3 weeks, and it's like 3 weeks in a row with one rest. But every week based on our mechanism of action, we know based on the data, that there is a higher concentration, specifically in fiber cancer cells. And we do believe that on a weekly basis, the concentration, hopefully, of the psychotoxic cancer cell could be similar to a full dose of docetaxel. And that's the reason why we decided to move with this strategy and to have a cytotoxic fight against a cell on a weekly basis, it's probably better than to give it only in a few dose.

We're coming up on the hour. So a question on Page #2. Was the [indiscernible] suspended or the dosing change before starting to docetaxel and in sortilin in late 2022.

That patient no, the priority was -- she was off. She had come off of treatment at that point. So I apologize, all I need to head off because I've got interviews for fellowship. So I want to thank you all, and I'm going to head out.

Thank you very much for joining, Dr. Winer.

So Paul, we're coming up on the hour, so a few last words.

Sure. Based on the data presented to you today and the important slides shared from the leading experts. All patients in the next part of our Phase I trial will be treated at doses within the therapeutic window. We are, therefore, very confident that we could observe additional efficacy signals. I would like to pay a special thank you to today's guests Dr. Meric and Dr. Winer who took the time out of their very busy clinic surgery and research schedules to join us and provide their insights into the next part of the sudocetaxel zendusortide trial. Thanks to their extraordinary expertise and that of other external advisers as well as the dedication and focus of our team, our first in human oncology study is back on track for advanced cancer patients. Please stay tuned for our upcoming second quarter earnings call. Thank you again for joining the session today. Have a great day.

The conference has now concluded. Thank you for attending today's presentation. You may now disconnect.