Good morning, ladies and gentlemen, and thank you for standing by. Welcome to Theratechnologies, sudocetaxel zendusortide Protocol Update and ASCO Presentation video conference call. At this time, all participants are in listen-only mode. Following the presentation, we will conduct a question and answer session with analysts. Instructions will be provided at that time for you to queue up for questions. Following the analyst Q&A session, investors wishing to submit a question may do so by clicking the Ask a Question link on the webcast platform. If anyone has any difficulties hearing the conference, please press the star key followed by zero for operator assistance at any time. I would like to also remind everyone that this conference call is being recorded today, Tuesday, June 13, 2023, at 10:00 A.M. Eastern Time. I will now turn the call over to Mr. Paul Lévesque, President and Chief Executive Officer. Lévesque, 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 issued 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. 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, will highlight the preliminary safety and efficacy data that she recently presented at ASCO 2023. Study co-investigator, Dr. Ira Winer from the Karmanos Cancer Institute, will complement the data presentation with clinical observations from a few of his 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 second, we announced that the FDA has agreed to the proposed changes in our protocol and lifted the partial clinical hold placed on the phase I trial, which we voluntarily paused in December 2022. To quickly recap, the amendments were created with the 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 its 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 along has been to bring our investigational anti-cancer 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, who are seeking ethics approval prior to resuming recruitment. We are ready to turn our full focus to restarting the study and dosing the first six 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 and the Anderson Cancer Center. She's Chair of the Department of Investigational Cancer Therapeutics, the center's phase I program, the Medical Director of the Institute for Personalized Cancer Therapy, and the Nellie B. Connally Chair in Breast Cancer. Dr. Meric is also the lead investigator of our phase I trial studying sudocetaxel zendusortide. Ira Winer is a gynecologic oncologist at the Karmanos Cancer Institute, an assistant professor and 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 you're 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 and recruiting some of those patients, and also to take the time out of their busy clinic this morning to be with us and 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 ADC, small peptide to which we attach anti-cancer drug. 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. What was uncovered recently is that this receptor is significantly overexpressed in many different solid tumors. The other advantage about this target is that, next slide, please, it is internalized within four minutes. It's a very. Oh, sorry. Can you go back to that? The rapidity of internalization makes it 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 significant increase in terms of concentration of the answer, anti-cancer drug in the cell. 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 cancer types. We started the journey about three, four 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 company working with this receptor. What we have done so far, we've worked with a third party to develop a proper immunohistochemistry staining 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 are significant expression of the receptor by the brown stain. We develop a score which goes from 0 to 300, and you can see that in the normal or healthy ovary, 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, we have tested more than 2,800 different tumor types, you can see that this receptor is expressed at a very high score in many solid tumor. In ovarian cancer, you'll understand why later we talk about ovarian cancer, there are more than 74% of those patients with ovarian cancer that are expressing this receptor at a very high level. In addition, you can see on this graph that there's also many other tumor types like TNBC, endometrial cancer, and breast cancer, HR positive breast cancer, that are expressing this receptor at a level which is about 80%-90% of the patient with the different type of cancer. Next slide, please. Now just a word about our mechanism of action and why we think that this PDC has significant advantages. First of all, what you see on the left-hand side of the slide at the top is our molecule, which is a 17 amino acid peptide with two cleavable linkers and two molecule of docetaxel. And this is a relatively simple molecule to build 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, that docetaxel or the anti-cancer drug will be released rapidly. We also have done many tests with different peptide to ensure that the peptide would attach to the receptor, but also would be released once inside the cell. This is a cartoon of the way we think it's working, but the sortilin receptor, as I mentioned before, is a shuttle receptor, which is internalizing large molecule inside the cell, and in this case, we're mimicking the normal ligand, then our PDC attach to the receptor. There's a formation of the endosome, the end activation of the endocytic pathway, and after that, once it is in the endosome inside the cell, it releases cytotoxic. Docetaxel, we have a lot of data showing that docetaxel stabilize the microtubule. It's doing the same job as it does when it is injected as a free agent. The other advantage, because of the short half-life of internalization that I mentioned before, we kind of significantly increase the concentration of the cytotoxic, specifically inside the cancer cell. Therefore, we think that with this technology, we would be able to improve the therapeutic window of many anti-cancer compound. 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 human, like on the cartoon before, that we enter the cell via the endocytic pathway. One of the main mechanism of resistance of taxanes is the MDR1 pump, which is kind of excluding those cytotoxic from the cancer cell. What we have shown is that by using the Sortilin receptor, we are bypassing this main mechanism of resistance of taxane. We also have shown in published data that we are inducing, or peptide induces apoptosis of cancer stem cells. Those cells are very resistant to many anti-cancer treatment already on the market, but we have shown that we have very good efficacy against those cancer stem cells. One of the other mechanism of resistance, which is recently known, is the formation of vasculogenic mimicry, which the phenotype of the cancer cell change to form small channel to feed other cancer cells in the vicinity of those small channel. We have shown that sudocetaxel zendusortide inhibit and stop the formation of those vasculogenic mimicry channel. Also because it is a small molecule compared to larger molecule like ADC, the drug penetrates the tumor microenvironment, which everybody believes that this is really where you have most of the resistance that is building up from cancer. By acting in this microenvironment, 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. What we have shown is that sudocetaxel zendusortide significantly potentiate the infiltration of tumor-infiltrating lymphocyte. This is completely new data, and it is very interesting. It tells 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 the 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 run the Department of Investigational Cancer Therapeutics at MD Anderson, and I had the opportunity to present the phase I study results at ASCO this year. As I'll be going over some of the highlights from that presentation. Next slide. Now, this, we conducted a phase I first in human study. This was a multicenter, open label study, with an FDA Fast Track designation. 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 mg/m2, every three starting dose, and it allowed for intrapatient dose escalation until and went till MTD. Next slide. We enrolled 18 patients in the dose escalation. There was enrichment for females, naturally, because we were interested in enrolling, you know, taxane-sensitive tumor types. We enrolled, you know, majority of patients were PS 1, and this was a heavily pretreated patient population. You know, even, you know, for a phase I, I would say this is a more heavily pretreated 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 had seen taxanes with a mean of 1.8 lines of prior taxanes. You can see the cancer types that have been enrolled. Majority of the patients had ovarian cancer, also enrolled endometrial, cervical, hormone receptor-positive breast, prostate, melanoma, and lung cancer. Next slide. We had a little bit of a complicated dose escalation scheme. Again, reminder, we had a single patient dose escalation initially, and then we went up to 420 mg/m2. We explored 360, ultimately deciding to proceed with 300. You know, initially started a 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, you know, although we're using a, you know, 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 an anti-tubulin agent. When we achieved 420 mg/m2, this became, you know, quite apparent. We had two patients that had grade 3 events and two patients who had grade 2 events. You know, the severity of neuropathy was less than 300 mg/m2, though we had also seen some neuropathy at that dose level. We also saw ocular toxicity at 420, especially. We had one patient with a grade 3 event and three patients that had grade 2 events. Also had some ocular toxicity, but of lower grade at 300. Also some GI tox as well, some musculoskeletal disorders that I'll talk about a little bit more later. Ultimately, at that time, you know, it was felt that the neuropathy was potentially manageable or at least monitorable at 300. For ocular toxicities, that we could formally initiate prophylaxis to be able to minimize the ocular toxicity. Just 300 was selected to proceed for the initial dose expansion. Next slide. Just to reiterate, you know, taking together the dose escalation data, it was felt that we could initiate a basket study using 300 mg/m2, with, you know, 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 pre-existing data, that these are the tumor types that have high levels of SORT1 and, you know, exploring the recommended dose of 300 mg/m2. Next slide. We enrolled 18 patients in the dose expansion. I want to point out that we had rolled out a basket trial that will continue to monitor safety, and efficacy, and decided to stop when we reached 18 patients due to the continued neuropathy signal. I want to share with you know, what we had seen during the initial dose expansion. Again, this was a relatively heavily pretreated patient population, median of five prior lines of therapy. you know, median of at least one line of taxanes. again, you know, quite a few ovarian cancer patients, but, you know, a smattering of other tumor types, endometrial, breast cancer, TNBC and hormone receptor-positive, prostate, melanoma, small cell, and thyroid. Next slide. These were our treatment-related adverse events in all patients treated with 300 mg/m2. This includes both the patients we treated in the basket component, as well as patients that were treated in the initial expansion, where we were establishing the, you know, recommended phase II dose or initial recommended phase II dose. As I mentioned, the frequency of neutropenia and anemia was relatively low for a cytotoxic strategy, with only, you know, 4% of the patients having grade 3 or higher neutropenia and 8% with anemia. The eye disorders cumulatively in all patients treated, you know, especially keratitis, was 16%, with 8% of patients having grade 3 or higher. However, the, you know, this majority of the higher adverse events were notable for patients that had not had initial prophylaxis. We do feel that the keratitis has been under fairly well control once we initiated routine prophylaxis. The GI tox seen, you know, included constipation, diarrhea, nausea, and vomiting. None of these are, you know, I think, not manageable. Next slide. The other adverse events include musculoskeletal events. You know, we had reports of arthralgia, myalgia, pain in extremity, including some, you know, pain on infusion in the extremities. You know, most sort of concerning adverse events that we focused on was the peripheral neuropathy. We had all grades, 20% and grade 3 or higher, 8% peripheral neuropathy. Again, you know, although our grade 3 event rate had dropped compared to when we were at 420, we felt that for patients that we wanted to be able to give a drug that could be, you know, at a dose level, we can maintain long- term, we felt that the, this neuropathy rate was too high, making us sort of reconsider the dose and schedule where we were at. Only other sort of adverse events of note included, you know, notable was fatigue, which we saw in about 36% of patients, but none of these were high grade. Next slide. In summary, you know, we, looking at part one and part two, you know, with a focus on that, you know, we revisited our 300 mg/m2 dosing cohort. You know, we felt that the neuropathy, it appears to be, you know, related to cumulative exposure of the circulating docetaxel based on PK/PD data. The eye tox is probably not target related, but, you know, relates to accumulation of the PDC in the anterior chamber of the eye, similar to what we see with ADCs. Indeed, our, you know, we were fortunate enough to have very experienced ophthalmologists that are familiar with ADC eye tox, and, you know, we've gotten quite a bit of guidance from them. You know, these events have all been reversible, and ultimately, for eye tox, we had initiated ocular prophylaxis. To try to mitigate both eye tox and neuropathy, decided to proceed with weekly administration, and, you know, changes our dosing. All the other adverse events, you know, the neutropenia, you know, no alopecia were, you know, favorable aspects of the PDC as seen. Again, you know, all of this data that we presented at ASCO informed the protocol changes that is being initiated. Next slide. From an efficacy standpoint, you know, this is a heavily pretreated patient population. You know, 36% of the patients had some signal of efficacy. This included two patients that had RECIST-confirmed partial responses, one patient with prostate cancer and one patient with ovarian cancer, and seven patients that had, you know, overall with the clinical benefit, with the four lines, four cycles or more of treatment. Next slide. Here's some, you know, change in target lesions, progression in the breast cancer patients we've seen. You can see that we have, you know, not regression meeting the partial response metrics, but some regression patients that have had six prior lines of therapy. Next slide. Radiological responses we've seen in ovarian cancer, including one patient with a, you know, partial response after seven prior lines of therapy. Next slide. Again, you know, all this data cumulatively has informed the amended protocol for part three of the study. In part three of the study, we'll be initially focusing on ovarian cancer. The dosing schedule has been changed to give treatments weekly, with day one to day 15 on a Q 4-week cycle. You know, change in dose calculation and with a plan of doing two dose levels that will be tested sequentially. With initially starting with 1.75 mg/kg, which we feel is equivalent to 210 mg/m2, and then to 2.5 mg/kg, which we feel is equivalent to 300 mg/m2, with the ultimate expansion to 10 patients. Then, you know, revisit the safety and efficacy throughout with regular readings. Also revising eligibility criteria to limit prior failures to taxanes and, you know, have a cap on prior treatment regimens. Next slide. I'd like to introduce my colleague, Ira Winer, who'll 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 a developmental therapeutics lead, in our network at Wayne State University and Karmanos Cancer Institute. I'll present a few examples of patients that have achieved clinical benefit in the initial stages of this trial. Next slide, please. 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 two investigational regimens in clinical trials rapidly and then was enrolled on the current trial in basically mid 2022, about one year ago. She did receive two cycles of trial drug, 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. She was discontinued from treatment about a year ago and has had no progression of disease since the initiation of her treatment, with only two cycles of therapy. 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. We'll be seeing her 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 Breast Cancer or has Triple-Negative Breast Cancer. She had progressed on four 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 on the 300 mg/m2, but ultimately reduced to 200 mg/m2, which is the protocol moving forward. This was secondary to a recurrence of her baseline neutropenia. She had significant neutropenia baseline from her prior regimens. The dose reduction, she's actually done quite well, and she's remained at the current dose for greater than seven cycles, and has had stable disease since that time. In fact, she's due to repeat image at the end of June. Currently, when we last saw her in clinic, she noted that the symptoms from her cancer, which had been uncontrolled prior to her 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 two prior platinum therapies and unfortunately progressed as well as hormonal therapy, which is standard of care in some instances for endometrial cancer. She was one of the patients that was intrapatient escalated from the very early part of the trial, from 60 mg/m2 to 360 mg/m2 every three weeks. This was over 11 cycles of treatment. Her only relatively minimal side effects were mild blurred vision as well as grade 1 neuropathy, which is very light. This is at the highest dose. While she achieved only stable disease, this was for a very prolonged period, for greater than four months. Ultimately, she decided to withdraw her 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. Her side effects ultimately did recover from the treatment. Last contact with the patient was approximately April of this year, and she had continued to have stable disease and been doing well. Next slide, please. Overall, these are three examples of patients that did have significant benefit from the current therapy. 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. Again, the most important aspect is we want to see clinical benefit for our patients while minimizing side effects and improving quality of life. That's what I have today. 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 analyst, and after that, we'll open the questions to other people. Let me start with one more. Hmm? Okay, Sorry, I'm sorry. We will now begin the question and answer session. To ask a question, you may press star, then one on your touch-tone phone. If you're using a speakerphone, please pick up your handset before pressing the keys. To withdraw your question, please press star then two. At this time, we will pause momentarily to assemble our roster. Our first question comes from Louise Chen with Cantor. Please go ahead. Hi, congratulations on all the progress with sudocetaxel. I wanted to ask you two questions here. First of all, where do you think this drug would fit into the treatment paradigm? If it's approved, is it a monotherapy, combination therapy? You know, can you comment on the combinability of the drug? Which solid tumors do you think present the best opportunity or best commercial opportunity for the drug and why? Thank you. Thank you, Louise. Yes, we do believe that there, 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 today, and the clinical benefit on the three 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 chance of combination. The first one will be the 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 innate immune system, and synergy with immunotherapy. 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, like toxicity, which was one that we had at higher dose. By lowering the dose, there will be less, and with the preventative measures, it is manageable, similar for the neurotoxicity. There will be also the possibility to combine the drug with other agent. Dr. Meric, do you have anything to add to this answer? Yeah, I know. Thanks for that. I agree. I think the fact that we're seeing you know, minimal neutropenia and anemia makes it an opportunity to be able to combine with other cytotoxic agents. You know, clearly, there's room for exploring novel targeted therapy option, combination options, but IO definitely is one of the early things to look at, based on the, you know, preclinical data already generated by Thera. Great, thank you. In terms of your second part, or your second question, the tumor type. At the moment, based on the data that we have so far, we made the decision to focus on ovarian cancer because this is where we have seen better signs of efficacy. As I mentioned earlier in the presentation, there is a number of solid tumors significantly expressing that receptor. Of course, like TNBC was also shown as an example where we had good signs or preliminary signs of efficacy in a heavily pretreated patient population. We do believe that we will be able to expand in many different tumor type. Maybe Dr. Winer, if you have anything to add to this answer? 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 one 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, you know, the amended protocols has gone into clinics, and we show efficacy as well as tolerability. Thank you. Our next question comes from Andre Uddin with Research Capital. Please go ahead. Thank you. 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 guess in it, but if you actually look at the data, the patients were quite sick, yet responses were seen. If you look at the swimmer plot 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. Go ahead, Dr. Winer. Again, I think the reason that ovarian cancer was chosen as the first tumor type to move forward with was the fact 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. 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, that's what ovarian cancer will be, and then the decision will be made regarding others that were previously included in the basket trial. Thank you, Doctor. Dr. Meric, do you have anything to add for other potential tumor types? Yeah, I know. I agree. I mean, I think we, as investigators, focused on traditionally taxane-sensitive tumor types, and the overlap of that with SORT1 expression. Of course, we don't know if higher concentrations of delivery of the payload will expand, you know, sensitivity to other tumor types as well. You know, I think there's definitely opportunities not just in gynecological cancers, but, you know, tumors like breast cancer, where we don't have a tubulin, you know, payload ADC yet, sort of in clinical use. You know, definitely, systematically reviewing indications as for option is worthwhile. Okay, that's great. Maybe Dr. Meric can answer this other one. In terms of the safety, if one looks at the safety profile of TH1902, it does appear to be better than docetaxel if one 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'd be great. Yeah, thanks. You know, whenever we have, you know, strategies that are direct delivery, I tox is something we look at, and this has definitely been something that over the last several years, the field of oncology has learned how to deal with. I think, yeah, with the dose mitigation and prophylaxis we've put in place, the I toxicity is manageable. The neuropathy is really gonna be the key determinant, I think, on the drug development plan. You know, we definitely had more neuropathy than we were hoping in the basket trial to date. You know, we're hoping that the new dosing schedule will be able to help control that. Thank you. You know, our goal isn't to give treatment for a few months. We want a treatment plan that will allow our patients to stay on study for a long period of time. Andre, just to add, we did a lot of pharmacokinetics and pharmacodynamic analysis, like looking at the drug level versus the adverse event, and that's one of the reason why we changed the dosing administration. Instead of giving the drug in surface area, we'll give it by body weight. What we have uncovered is in patient that have a lower weight because the drug was given in body surface area, they were kind of overdosed, and we had some patient that had 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 three-dosing Taxol. 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 take it and we hope that this will be manageable in the next step. Okay, that's great. Thanks for sharing, Dr. Meric. If you'd like to ask a question, please press star then one. Our next question comes from Bill Maughan with Canaccord Genuity. Please go ahead. Hey, good morning. 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? I guess, how onerous would that be to test for that before enrolling somebody? Yeah, thank you for the question. In the study at the moment, we did not, and we had some exchange with the FDA, and the FDA didn't want us to look for patient with, SORT1 expression. They wanted to see more or less all comers. What we have done, we, in our inclusion criteria, we selected patients that were high expresser, like ovarian cancer, it's 74%, and, other cancer are in the range of 80% or more. 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. There are a number of drugs that are already approved on the market where they have diagnostic tests. I don't think it will be much different than for some of those products. The other part of your question was the SORT1 receptor expression in the cancer enrolled. Yes, we did the biopsy at baseline. We'll continue to do so in the next phase of the study to ensure that we know what are the level of the SORT1 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 SORT1. We need a lot more patients than that before we can do correlation between the expression of the receptor and the efficacy of the drug. Okay, just thinking through the neuropathy, is that is there, 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, the neuropathy? 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 that mechanism of action per se. We'll see with the next stage, in terms of the type of adverse events that we'll see on the neuropathy side, but we do believe that it will be more manageable. Dr. Meric, do you have anything to add on this question? No, this is a challenging question of course. You know, it's not a surprise when we have a tubulin agent with neuropathy. You know, I don't know that we 100% excluded that there isn't a target-related component to this. Thank you. 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. We have a few questions from Justin Walsh, an analyst with JonesTrading. I'll read them for you, Christian. For the KOLs, recognizing that it's still early, can you comment on what detail 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. Yeah, thanks. You know, I think, you know, this is of course, completely novel strategy. You know, it's the expression pattern data generated by Thera that, you know, this is expressed across so many different tumor types at relatively high intensity and, you know, with sort of high H-scores across tumor types, I think is really encouraging for the potential of this treatment strategy. You know, there's obviously a lot of development in the ADC PDC space, but there's definitely need for tubulin agents that are accessible for across tumor types. Thus, I think the novelty of the strategy is great. To, or answer your earlier question, you know, of course, that more data is needed to look at, you know, how much expression is sufficient, but for diseases like ovarian cancer, where there's high expression in so many of the patients, I think this strategy of looking, taking all comer of that tumor type and then better determining whether there's a certain amount of intensity or a certain amount of percentage expression that's required to be able to better decide if there's any value added in other tumor types to select, is worthwhile. Dr. Winer, do you have anything to add on? Yeah, no, I agree with Dr. Meric. I also think it's really important is that the, you know, 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 and the tumor microenvironment. 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 in that sphere. The second question from Justin Walsh is: As ADCs see increasing use, particularly in ovarian cancer, is there a concern about overlapping adverse event profiles such as I 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 ADC were in a kind of a subgroup of patients. We think about NRN2, those are in patients are expressing their receptor. Therefore, there's still a high need to other, for other drugs in ovarian cancer. Dr. Meric, do you have anything to add? I think, you know, when we're talking about I tox, we're predominantly thinking about, you know, the most recent approval for mirvetuximab, where there is some I tox, and that's the anti-tubulin agent. We don't know whether there'll be cross-resistance in the payloads. Of course, only, you know, a fraction of the patients with, you know, a small portion of the patients with ovarian cancer still have enough folate receptor target expression. That's an area of continued drug development. We'll need to monitor, I think, now that, you know, more of our patients will have been exposed to that, whether that will be something to consider. We will be doing pretreatment, you know, assessments. We'll be able to get, you know, we'll be only enrolling patients that don't have pre-existing I tox before the study, you know, entire study. 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, Dr. Winer, if you want to pick up the question. Sure. You know, 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 the 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 one or two priors, maybe up to three. This is a very interesting place to, you know, to position the current PDC. In terms of what we're looking for, for outcomes, I think that's, you know, number one is toxicity, so we have to see that. In terms of efficacy, I think, again, it's not only, you know, the partial responses, et cetera, but it's also clinical benefit rate. I think that, you know, we're looking somewhere, hopefully in the PFS or progression-free survival, somewhere in the three to six months minimum in heavily pretreated patients. If, if we can succeed with more, especially in stable disease, then you have a winner. 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. Winer. I know that you have to leave probably shortly, but if you can stay with us a few more minutes, we'll go to the next question. I have a final question from Justin Walsh. Is there any comment from physicians and scientists that you'd like to highlight from ASCO? How well was this received? Dr. Meric, you were with us at ASCO, and you had many questions, and you addressed many questions. I think that you can probably address this question. No, I think the poster was presented as in a poster fashion, which is a really interactive format that I enjoy so much, and, you know, we had a lot of visitors, and a lot of people were very interested in the data, so it was well received. I think that most of the questions, many questions came on the receptor because what we have presented so far is usually in basic science meeting when we talk about the mechanism of action. People were very curious about the receptor, and when we talk about the fact that there's a receptor that internalize rapidly, half-life of internalization of four minutes, it's really something that captured their attention, and they're very curious about the distal receptor and how it can work. Okay, there are a few questions on the selection of ovarian cancer as opposed to Triple-Negative Breast Cancer. Mm-hmm. Is there a specific reason why we went with ovarian and not, TNBC? It was mainly based on the results observed so far. We had a bit more ovarian cancer patient, of which one had a complete response on target lesion. It was a partial response overall. We do believe that it's something that's the reason why we're focusing there. I think, like, if we see signs of efficacy in that second step, we'll probably be able to move rapidly to TNBC and other cancer types. Dr. Meric, any additional comments? Yeah, 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, you know, a targeted delivery system. Especially if we can demonstrate that there's enhanced immunogenicity and IO combination potential that, you know, would make it especially appealing. Another question, how are you correlating the fact that TH1902 is actually working as intended if you're not prescreening for Sortilin? Well, this, for this question, more or less, it's because the patients that have been selected at the moment, were selected based on the fact that they were high tumor type that were high expresser of the Sortilin receptor. That was confirmed, more or less, by the biopsy that we had done at baseline. We assessed the Sortilin level. It is what's fairly high, above 100 for most patients enrolled in that study. 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. You know, Nectin-4 for, you know, bladder cancer or Trop-2 for bladder cancer, breast cancer. This model, I think, has eliminated the need for selecting with biomarker assessment and allowing for retrospective assessment of, you know, is there a differential sensitivity? I agree that if we're gonna look across tumor types and into tumors that are less frequently expressed in Sortilin-1, we will eventually need a strategy to do patient selection. This will allow us to determine, you know, 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 you have some experience with also other drugs and highlights on them. No, I'll start off by admitting, changing two things at the same time, of course, it makes it a little bit more complex. I think, you know, we've seen at least, you know, other anti-tubulin strategies where neuropathy had issues using a lower dose, more frequent schedule, you know, allow them to get to clinic. At least in part, that, you know, inspired this decision. A lot of discussion with a lot of, you know, expert drug developers, you know, went into this decision. Dr. Winer, anything to add? No, I agree. We've used this in gynecologic malignancies and various types to get drugs to patients in the past, and it has mitigated the side effects, but actually improved outcomes because of also other off-target effects that you see when you do a dose-dense, as we call it. ... Maybe I'll add that the two doses that we are using, the doses we're starting at 175 mg. I know that for people that have been following us, you used to see dose of 200 mg/ m², 300 mg. The dose of 1.75 mg/ kg is in the range of the 200 mg/ m². It is divided in three weeks, like, it will be three weeks in a row with one week rest. Every week, based on our mechanism of action, we know based on the animal data, that there's a higher concentration specifically inside the cancer cells. We do believe that on a weekly basis, the concentration, hopefully of the cytotoxic inside the cancer cell could be similar to a full dose of docetaxel. That's the reason why we decided to move with this strategy and to have a cytotoxic inside the cancer cell on a weekly basis is probably better than to give it only every few weeks. Any other questions, though? We're coming up on the hour, a quick question, on patient number two, was Trodelvy suspended or the dosing changed before starting sudocetaxel zendusortide in late 2022? All right. Oh, that patient? No, the prior ADC was she was off. She had come off of treatment at that point. Okay. I apologize. I all I need to head off because I've got interviews for fellowship. I want to thank you all, and I'm gonna head out. Thank you very much, Dr. Winer. Paul, we're coming up on the hour, a few last words. Sure. Based on the data presented to you today and the important insights shared from 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 advisors, 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 is now concluded. Thank you for attending today's presentation. You may now disconnect.