Greetings, and welcome to the Nuvectis Pharma NXP900 Phase 1B Study Initiation Conference call. At this time, I'll disconnect our listen-only mode. As a reminder, this conference is being recorded. Joining me on the call today will be Ron Bentsur, Co-founder, Chairman, and Chief Executive Officer of Nuvectis Pharma. Also joining us for Q&A are Enrique Poradosu, Co-founder, Executive Vice President, Chief Scientific and Business Officer, and Shay Shemesh, Co-founder, Executive Vice President, Chief Development and Operations Officer. It's now my pleasure to turn the call over to Ron Bentsur, Chairman and CEO of Nuvectis Pharma. Ron? Thank you, Rob, and thank you, everyone, and good morning. We appreciate you joining our call today. Following our Safe Harbor statement, I will review the details of our ambitious Phase 1B program for our drug candidate NXP900. Before we begin, I'd like to remind everyone that on this call, we'll be making forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Forward-looking statements within the meaning of the federal securities laws are subject to substantial risks and uncertainties. During this call, all statements other than statements of historical fact are considered forward-looking statements and are based on our interpretations of past events, as well as current expectations, estimates, and projections about future events, including expectations for the timing and data for the NXP900 Phase 1B study. These and other risks and uncertainties are subject to market and other conditions and described more fully in the section titled Risk Factors in our Form 10-Q for the quarter ended June 30th, 2025, and our other public filings with the Securities and Exchange Commission. However, these risks are not exhaustive, and new risks and uncertainties emerge from time to time, and it is not possible for us to predict all risks and uncertainties that could have an impact on the forward-looking statements made in this call or other filings made with the SEC. Now, for the reason we're having the call today, as you know, yesterday we announced the initiation of the Phase 1B program for NXP900, our potent and selective oral small molecule SRC/YES1 kinase inhibitor. The initiation of the NXP900 Phase 1B program is a very important milestone for Nuvectis, as it is a significant step forward in our mission to develop NXP900 for the treatment of patients with serious conditions of unmet medical needs in oncology. Our excitement about the Phase 1B program stems from the fact that we believe that NXP900 is a drug candidate that just doesn't come around every day in the biotech sector. NXP900 represents a true pipeline in a pill opportunity that has the potential to address several cancers for which new treatment options are very much needed. We have high expectations for NXP900. We believe that if any of the scenarios that I'll be discussing today materialize, it'll be a transformative moment for Nuvectis and that we can potentially join the ranks of some of the esteemed precision oncology companies in our sector. As a management team that has been developing drugs for over 20 years, including several drugs that have received FDA and ex-U.S. approvals, we know how rare it is to come across an opportunity with this potential magnitude that we see with NXP900. This is truly a unique opportunity. We're embarking on this Phase 1B journey for NXP900 with a strong cash position, in fact, the strongest we have ever had, with approximately $39 million of cash pro forma as of June 30th, 2025. We believe that this provides us with over two years of cash from today, a timeframe that includes the key potential value inflection milestones that are embedded in this Phase 1B program without any near-term financial concern. Now, let's get into the background and details of the Phase 1B program. First, I'd like to express our gratitude to the patients who took part in the Phase 1A dose escalation study, the principal investigators, and clinical staff, as well as to our dedicated team at Nuvectis. Let's quickly review the progress made so far with NXP900, including the completion of the dose escalation Phase 1A study in patients with advanced solid tumors and the clinical drug-drug interaction study in healthy volunteers, both required to enable this Phase 1B program. Our Phase 1A dose escalation study evaluated escalating doses of NXP900 from 20 mg- 300 mg per day in 33 patients with various types of advanced cancers. In these patients, we observed good overall tolerability, and the dose-limiting toxicity, or DLT, level was not reached. The most common treatment emergent adverse events were fatigue, diarrhea, nausea, abdominal pain, dyspnea, and vomiting, mostly reported as grade 1-2, which is consistent with other oral anticancer agents. What particularly stands out from our Phase 1A results is the pharmacodynamic response achieved following treatment with NXP900. At clinically relevant doses, starting at 150 milligrams per day, we observed a rapid and deep inhibition of Src autophosphorylation that exceeded 90%. This level of Src inhibition is rather unprecedented, and we believe bodes well for the Phase 1B program. As you may know, NXP900 also has a unique mechanism of action where it binds to its target when it is in its closed or off conformation, enabling inhibition of both the catalytic and the scaffolding functions of the target and resulting in complete shutdown of the signaling pathway. This mechanism is different from other Src inhibitors that bind the target in its open or on conformation, thereby only inhibiting the catalytic function of the target and, in fact, paradoxically, leading to activation of the Src signaling complex. We believe that NXP900's ability to completely shut down Src signaling is an advantage that could be brought to bear in the Phase 1B program. We also recently completed the drug-drug interaction study in healthy volunteers supporting the combination of NXP900 with EGFR and ALK inhibitors. Since osimertinib and lorlatinib, the leading EGFR and ALK inhibitors respectively, each induce members of the cytochrome P450 family, including CYP3A, we felt that it was important to understand NXP900's drug-drug interaction, or DDI, profile upfront. Based on our recently completed DDI study, we showed that NXP900 is actually a weak inducer of CYP3A. These data were key to enabling our planned Phase 1B combination study. The Phase 1B study will evaluate the efficacy and safety of NXP900 for the first time in target patient populations as a single agent and in combination in patients suffering from advanced cancers that could highly benefit from new effective treatments. Starting with our single-agent strategy, we have previously demonstrated that certain genetic alterations in preclinical cancer models make certain tumors highly sensitive to treatment with NXP900. In particular, our data showed positive results for NXP900 in models of cancers harboring YES1 gene amplification and Hippo pathway alterations, such as mutations in FAT1 and NF2. YES1 is a very important kinase within the Src family, and FAT1 and NF2 are located downstream of it, a dependency allowing NXP900 to target the pro-cancer signaling enabled by mutated FAT1 and NF2. The well-defined biology of these models enabled us to define the patient populations that we will test in the Phase 1B study. Importantly, identification of these genetic alterations can be done using commercially and hospital-based next-generation sequencing panels that are routinely used and available across the country. We're embarking on a broad single-agent approach, and eligible patients for the single-agent study include those with the following combinations of tumor type and genetic alterations. YES1 amplified or FAT1 mutated non-small cell lung cancer, NF2 mutated mesothelioma and renal cancer, and other advanced solid tumors with any of the genetic alterations mentioned above, or other relevant Hippo pathway alterations will be included in the basket group. The specific genetic alterations were selected based on their characteristics as either direct, for example, YES1 amplification, or dependent, for example, Hippo pathway alteration, targets of NXP900, and the tumor types were selected based on the prevalence of the relevant genetic alterations and supporting scientific data. The rationale for the combination approach is also very compelling, and it is supported by data independently generated by various academic groups and other third parties, including in vitro work done by the AstraZeneca Research Group, which was published approximately three years ago, and our own sponsored studies. NXP900's potential to reverse acquired resistance to targeted therapies can address a massive clinical need, as acquired resistance at some point affects virtually all patients treated with targeted agents in non-small cell lung cancer. There's extensive scientific literature that points to activation of bypass mechanisms controlled by Src and YES1 dependent signaling as driving resistance to the EGFR inhibitor osimertinib, known by its brand name Tagrisso, or the ALK inhibitor lorlatinib, known by its brand name Lorbrena. Resensitizing the cancer to these treatments by blocking the bypass-enabling acquired resistance can change the treatment. Ladies and gentlemen, please stand by. We're experiencing technical difficulties. Our conference will resume momentarily. Thank you for standing by, everyone. Ron, please continue. Yeah, I apologize, everyone. Resensitizing the cancers to these treatments by blocking the bypass-enabled acquired resistance can change the treatment paradigm for these patients by allowing them to continue treatment with an oral regimen to which they had already previously responded to. From a business perspective, the market opportunity for NXP900 is substantial, as the potential addressable patient populations for NXP900 treatment are quite sizable. As an example, the incidence of FAT1 alterations alone in patients with lung and head and neck squamous cancers exceeds 23,000 annually, with additional considerable numbers in other tumor types. As for the combination approach, the potential addressable patient numbers are staggering by oncology standards. Earlier this year, AstraZeneca reported that more than a million patients have been treated around the world with Tagrisso since its launch in 2015. Hopefully, this provides some perspective on the size of the patient populations that we're pursuing in this Phase 1B program. In summary, our Phase 1B program is designed to evaluate NXP900 as both a single agent and in combination with existing targeted therapies to overcome acquired resistance. We believe that this dual approach maximizes our opportunities for demonstrating clinical benefit across multiple well-defined and substantial patient populations. By testing multiple hypotheses simultaneously, we could open the door to new clinical applications for NXP900. For example, if we see single-agent activity in YES1 amplified tumors or FAT1 mutations, that could open opportunities across multiple tumor types beyond lung cancer. In addition, demonstrating reversal of acquired resistance in combination studies could address one of the most significant unmet medical needs in the targeted therapy space of oncology today. Looking ahead, we believe that positive Phase 1B results could be transformative for Nuvectis Pharma. The precision oncology space has demonstrated multiple times that companies with compelling Phase 1B data in defined patient populations can generate significant interest from both the investment and pharma communities. To conclude, we remain focused on rigorous clinical execution and generating high-quality data. We know that our success will ultimately be measured by our ability to demonstrate meaningful clinical benefit for patients with advanced cancers. The initiation of the Phase 1B program for NXP900, our pipeline in a pill drug candidate, represents the culmination of years of scientific work and successful clinical execution to date. We believe that NXP900's unique mechanism of action, clinical safety profile, and robust target engagement put it in a great position to become an important player in precision oncology, and we expect to share data from the study throughout 2026. We're excited to commence the NXP900 Phase 1B program today, which will hopefully serve to showcase NXP900's robust therapeutic potential. Thank you very much for your attention, and now let's please open the call up for Q&A. Thank you. Thank you, Ron. At this time, we'll be conducting a question and answer session. If you'd like to ask a question, you may press star one from your telephone keypad. If you're using a speakerphone, please pick up your handset before pressing the keys. To withdraw your question, press star then two. Our first question comes from the line of Jonathan Aschoff with Roth Capital. Please proceed with your questions. Thank you. Good morning, Ron. I'm curious. Morning, Jonathan. What's the expected response? Thanks. What is the expected response rate for NSCLC to retreatment with the EGFRs and the ALK inhibitors you will use in combination so that we may have a sense of how much better combo with NXP900 is when we see the initial combo treatment data? You're talking about patients who have been on Tagrisso or lorlatinib, and it could be for an extended period of time because these drugs typically can provide PFSs that are measured actually in years. It could be two years, three years, which obviously is a very nice benefit. However, eventually, all patients, without exception, will become resistant to these treatments, and that's when they start progressing. When you look at a patient that falls into that category, obviously, you want to try to reverse that course, and you want to obviously try to create a response within that patient. In terms of numbers, we believe that ultimately, because this is a salvage type of a patient population, if you will, a refractory patient population, the regulatory bar will be kind of in the 15%- 20% range, but obviously, you want to be higher than that. Anything above 20% or 25%, let alone in the 30s, 40s, or higher, I think would put this combination in a very good position vis-à-vis the investment community and also, of course, the FDA. That was very helpful. Is there any minimum number of patients you are going to monotherapy prior to starting combo, or one is not dependent on the other? No, one is not dependent on the other. The single agent part of the program logistically is just easier to start. It's part of the existing Phase 1 protocol that's already in place, and obviously, for the combination studies, you need a separate protocol. We needed to finalize the Phase 1A and the drug-drug interaction study and get the final reports in and all that before we could finalize the protocol, which were the protocols for the combination studies which we're working on now. That will start hopefully very shortly. Okay, thank you. Lastly, regarding enrolling patients with specific genetic alterations or mutations, can you help us understand the size of that patient subset among the three solid tumor types that you intend to preferentially enroll, you know, lung, meso, renal? Yeah, here I'll defer to Enrique. Enrique, are you on the line? Yes, I am. Can you hear me? Enrique, if you can, please answer the question on the size of the patient populations for the YES1 gene amplification, FAT1, and so on. Yes, so in lung cancer, in particular, let's focus on squamous for a second. In squamous lung cancer, the prevalence of the FAT1 mutation is in the order of 18%, and YES1 amplification is about 5%. In renal papillary kidney cancer, NF2 is about 15%. Papillary cells are about 15% of the total renal, so we're talking about out of 15, approximately. In mesothelioma, it's about 40% NF2 mutations. All right, thank you very much, guys. That's all. Thank you, Jonathan. The next question is from the line of Christopher Liu with Lucid Capital Markets. Please receive your questions. Hey, guys, thanks for the question. Of course, Chris. Do you think that the post-EGFR and ALK setting is amenable to an accelerated approval? You mentioned kind of the ORR benchmark. What should we look to towards maybe a PFS or OS benchmark? The first question is, could it be amenable to accelerated approval? We certainly believe that could be the case. Obviously, we haven't had any formal discussion with the FDA, but acquired resistance is perhaps the biggest problem in the lung cancer space today because these patients basically, once they start progressing, there's just not much that's available for them, and their prognosis obviously becomes extremely poor at that point. The ability to reverse course, I think, is going to be incredibly important to be able to do that. On the face of it, we believe that it could qualify for accelerated approval and single-arm studies and things of that nature. With respect to PFS and what you should expect in terms of durability of response and all that, that kind of falls into the typical bucket, I believe, that the FDA looks for in these types of situations. Again, we have not had the formal discussion about any of this. This is just our supposition based on other situations that we've seen. Typically, you'd want to show six months or more of durability of response, median. That's kind of the sweet spot for what the FDA typically looks for in these types of situations. That would be my answer to that question. Great, thanks. Maybe one more, if I may. Do you have any internal estimates for what the market opportunity might look like in dollars for this post-ALK, post-EGFR setting? Yeah, so, we're talking about, you know, billions of dollars here in terms of market potential. This is truly a blockbuster potential opportunity, hands down. When you think about, take Tagrisso as an example. Tagrisso is going to probably generate around $7 billion this year, something like that. Keep in mind that roughly a third of the patients progress every year. Basically, if you take the patients that progress and you start treating them with a combination and you're able to change their course, that alone is a massive sliver that basically, you know, it can extend Tagrisso use for patients and extend their tenure on Tagrisso. We can, you know, we can all do the math on that. To keep a patient longer on Tagrisso is very, very important, you know, for AstraZeneca or whoever the EGFR player is. Of course, you know, our drug, you know, comes into, joins that picture as well. We're talking about very substantial numbers. On the ALK side, we're talking about a subset that is roughly half of the EGFR patient population in terms of size. If EGFR is roughly 10% of the patients in lung, ALK is about 4%. There, I think a good example would be a company like Nuvalent, for example. Nuvalent right now has data in third-line ALK. After patients have gone through alectinib and lorlatinib, they go on Nuvalent's drug and they generated something between a 30% and a 40% response rate. Obviously, they want to move upstream and they started a first-line study and so on and so forth. The actual data that they have so far is in the third-line setting with about a 35%-ish response rate, as far as I know. Their market cap is $5.5 billion or something like that. The expectation there ultimately is that they will take, they will be able to capture, you know, either a third or, you know, or maybe even a little bit more of the ALK market, which is currently about $2.5 billion- $3 billion, expected to grow obviously to $4 billion, $5 billion, $6 billion in a few years. The numbers that get thrown around, particularly in lung, and I didn't even talk about YES1 overexpression and FAT1 for non-small cell lung cancer alone, which represent another big sliver within the patient population. When you look at the dollars and the patient numbers in non-small cell lung cancer, the numbers are pretty substantial. We're talking about tens and tens of thousands of patients, which would be candidates for our drug. Thanks, Ron. Appreciate it. Thank you. The next question is from the line of El Jen with Libra. Please proceed with your question. Good morning, and thanks for taking the question. Good morning. Congrats on the kickoff, the trials. Just a few here. The first one is in terms of the monotherapy for 1B study. What will be the study patient size as well as how many centers you anticipate to engage? I have a follow-up. Yeah, so, in terms of the patients, each one of the groups that we described, so YES1 amplification, FAT1 mutation, and so on, each one of these groups ultimately will end up being about 25 patients. You start off with 12 and you look for a signal, then you expand based on that. We plan to have four groups, so potentially a total of 100 patients there. In terms of the number of sites, right now we're starting the study with roughly 15 sites. That number will grow, but we believe that in terms of critical mass to start the study with, I think we're in very good shape. Of course, very importantly, these are all sites that have these panels that are required readily available because we want to be able to screen patients immediately and not have to go through implementation of panels at sites and go through that logistical step, which we don't believe is necessary. Obviously, it's a prerequisite for sites to have these panels already in place. Many do. The overwhelming majority of sites in the country already have that. I think from that perspective, we're in good shape. I think we can start the study off with very good cadence. All these sites are in the United States, is that right? All U.S. Okay. The second question is that you mentioned a little bit in terms of in the combo setting that could be a little bit savage nature of the study. Yeah. If so, would that be possible that you need an overall survival of either primary or secondary endpoint? Yeah. What would you feel the, again, the bar for that is? Yeah, so, obviously, I can't speak on behalf of what the FDA may say or think in this particular case. We do believe that based on a lot of other studies that take place in the lung space and the types of endpoints that people are pursuing with their drug candidates, we believe that a single-arm response rate type of a study showing obviously adequate durability and, of course, tolerability and things of that nature should be enough. For me to say that conclusively would be irresponsible at this point and premature. We do believe that these types of patient populations and the trial and, again, the salvage setting that these patients qualify or fall into, I think, would be amenable to these types of clinical trials. That's basically going to be our approach. Of course, until we have a discussion with the FDA, we won't know for sure. Okay, great. Very helpful. Maybe squeezing one more. You mentioned about the combo study will start after the monotherapy. Just curious in terms of the timeline and the needed data, needed the sort of status as well as the protocol setup. Would that be something in 2026, or do you think that could be started liberally? Thanks for the question. We believe that the combo studies will start this year. Like you said, logistically, it's a little bit more complicated to start those. There's more, when you need to write a new protocol, it obviously takes more time, and you need to wait for the, you need to basically include the final data from the Phase 1A and the drug-drug interaction studies and so on. We needed to wait before we could finalize the protocol and show it to the PIs and circulate it around and go to the IRBs, which we plan to do next. It just takes a little bit longer. We believe that both of these studies will be up and running this year. Okay, great. Thanks. Congrats on kickoff, the things that we all anticipate. Thank you. Thank you very much. Thank you. Our final question is from the line of Joe Pantginis with H.C. Wainwright. Please receive your question. Hey, guys, good morning. Thanks for taking the questions. Hi. Two questions. Hey, Ron. Two questions, if you don't mind. First, on the conduct of this study. There are a lot of discussions about the market size and what have you. I think you're going after a good number of patients here to get signals potentially. What are the triggers with regard to the number of responses in order to expand? With regard to the expansion, are the two studies, basically monotherapy and combination, independent of each other, or do you need the response rates from the monotherapy to expand into the combos? Yeah, the second question is easy for me to answer. The answer is they're independent of each other. You do not need to see something in one before you can start the other. They're going to be completely independent. For the statistical question, I will refer to Enrique, who is much better in statistics than I am. Enrique, if you can answer that question regarding going up from, let's say, 12 patients- 25 patients, what would trigger that? Yeah, the statistical design is essentially based on Simon two-stage design. A response in a particular combination of mutations in a histological setting will trigger the expansion of that particular mutation and histology into a larger group of patients. If it were 12 patients, is there, what is the particular number? Do you need to see two responses, three responses, or are you not disclosing the actual trigger yet? No, we are not disclosing the exact trigger, but it's essentially a responder in a combination of a mutation and histology subset. Of course, we are recruiting patients in sufficient numbers so we can have meaningful mutations in each histology group. Got it. Thanks for that. My second question is about the broader profile of 900. I'll ask the question somewhat vaguely, but I'm hoping you can give a good reminder to us. You have a lot of independent Nuvectis data that has compared 900 from a Src standpoint with many others, including pharma studies. I'm just hoping you can sort of review that for those on the call because it seems like you really have a differentiated asset. Sure. We believe that the ability of NXP900 to inhibit the target, which is Src, and obviously, we saw that in the Phase 1A, is actually far superior to what we've seen with the other Src inhibitors, the sunitinib, saracatinib. The assays themselves were not identical, but they were close cousins of one another. I think they are, to some extent, very much comparable. You see a dramatic difference in terms of NXP900's ability to inhibit Src versus the other drugs. It's very consistent, and it happens quickly, and you see it at trough levels and so on. We know that the inhibition profile is very robust. In fact, pretty much saturated. Once you get to 150 and you start hitting 90%, 93%, 94%, it's very hard to get much higher than that. We're very pleased by the inhibition profile that we're seeing. There's definitely very strong target engagement. In terms of the kind of anecdotal information that's out there to support what we're doing and the different patient populations that we're trying to pursue, one interesting example would be a saracatinib study in non-small cell lung cancer that was done a few years ago by AstraZeneca. What they showed there, about 25 patients were in that program, were enrolled, and they had two partial responses confirmed. They had one stable disease with 29% tumor shrinkage, 1% away from being a responder as well. This was in an unenriched patient population. They did not enrich for YES1 amplification or FAT1 or anything like that. This was kind of an all-comers non-small cell lung cancer study. We know that saracatinib is not believed to be a very potent inhibitor of Sr. Again, the numbers that you see for saracatinib are just not nearly as compelling as what you see with NXP900. If you take those two kind of anecdotal data points and you try to connect the dots, you've got a study here that's showing some activity. Obviously, it wasn't enough to move forward. It was a little bit less than a 10% response rate, but in an unenriched patient population. You still see activity with a Src inhibitor that is not believed to be very potent. We believe that that's actually a case study that provides very strong justification for what we want to do in lung using the single-agent approach because we will be enriching the patient population in the study. We'll be looking for YES1 amplification and the FAT1 mutation only. We believe we've got a much more potent Src inhibitor than saracatinib. If you kind of evaluate all that from a top level, we really like our chances. Thanks a lot. Thank you. Thank you. I'll now turn the call over to Mr. Bentsur for his closing remarks. Thank you, Rob. Thank you all for joining the call. Really appreciate it. We also appreciate your continued support of Nuvectis. We look forward to updating you on the progress as we advance NXP900 through the Phase 1B study. Have a good day, and thank you so much. Ladies and gentlemen, this concludes today's presentation. Thank you once again for your participation. You may now disconnect.