Nuvectis Pharma Inc Business Update Call

Rob: This 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?

Call today will be Ron Fincher, co founder Chairman and Chief Executive Officer of Novartis pharma.

Also joining us for Q&A and regained presario cofounder executive Vice President Chief Scientific and business Officer.

And Chase you mesh cofounder executive Vice President Chief Development and operations Officer.

It's now my pleasure to turn the call over to Ron Bernstein, Chairman and CEO of Novartis, where am I wrong.

Thank you, Rob and thank you everyone and good morning.

Ron Bentsur: Thank you, Rob, and thank you, everyone, and good morning. We appreciate you joining our call today. Following our Safe Harbor statement, we'll review the details of our ambitious phase I-B 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 I-B study.

We appreciate you joining our call today.

Following our safe Harbor statement I will review the details of our ambitious phase one B program if.

For our drug candidate <unk> 900.

Before we begin I'd like to remind everyone that this call will be.

On this call will be making forward looking statements within the meaning of the private Securities Litigation Reform Act of 1095.

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 term quotations of past events as well as current expectations estimates and projections.

About future events, including expectations for the timing and data for the.

And it's been 900 phase one B study these and other risks and uncertainties are subject to market and other conditions and described more fully in the section entitled risk factors in our Form 10-Q for the quarter ended June 32025, and our other public filings with.

Ron Bentsur: 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 30 June 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 a Phase I-B program for NXP900, our potent and selective oral small molecule SRC-YES1 kinase inhibitor.

And 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.

It's 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.

And now for the reason, we're having the call today as you know yesterday, we announced the initiation of a phase one B program for NXP 900 are potent and selective oral small molecule SAARC, yes, one kinase inhibitor.

Mission of the NXP 900 phase one B program is a very important milestone for novartis.

Ron Bentsur: The initiation of the NXP-900 phase I-B program is a very important milestone for Nuvectis as it is a significant step forward in our mission to develop NXP-900 for the treatment of patients with serious conditions of unmet medical needs in oncology. Our excitement about the phase I-B program stems from the fact that we believe that NXP-900 is a drug candidate that just doesn't come around every day in the biotech sector. NXP-900 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 NXP-900. We believe that if any of the scenarios that I'll be discussing today materializes, 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.

It is a significant step forward in our mission to develop and it's been 900.

Treatment of patients with serious conditions of unmet medical needs in oncology.

Excitement about the face amount be program stems from the fact that we believe that NXP 900 is that.

Candidate that just doesn't come around every day in the biotech sector and <unk> 900 represents a true pipeline in a pill opportunity that has the potential to address several cancers for which new treatment options are very much need it.

We have high expectations for NXP 900, we believe that if any of the scenarios that I'll be discussing today materializes. It will be a transformative moment for an effective and that we can potentially potentially joined 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 F. D E and X U S approvals, we know how rare it is to come across an opportunity with this potential magnitude that we see with NXP 900. This is truly a unique opportunity.

Ron Bentsur: As a management team that has been developing drugs for over 20 years, including several drugs that have received FDA and ex-US 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 I-B 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 30 June 2025. We believe that this provides us with over 2 years of cash from today, a time frame that includes the key potential value inflection milestones that are embedded in this phase I-B program without any near-term financial concern. Now let's get into the background and details of the phase I-B program.

We're embarking on this phase one b journey for <unk> 900, 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.

<unk> 20th 25, 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 one b program without any near term financial concern.

So now.

Let's get into the background and details of the phase one B program.

First I'd like to express our gratitude to the patients who took part in the phase one dose escalation study the principal investigators and clinical staff as well as to our dedicated team at an effective.

Ron Bentsur: First, I'd like to express our gratitude to the patients who took part in the phase I-A dose escalation study, the Principal Investigators and clinical staff, as well as to our dedicated team at Nuvectis. Now let's quickly review the progress made so far with NXP900, including the completion of the dose escalation phase I-A study in patients with advanced solid tumors and the clinical drug-drug interaction study in healthy volunteers, both required to enable this phase I-B program. Our phase I-A dose escalation study evaluated escalating doses of NXP900 from 20 to 300 milligrams 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.

Now, let's quickly review the progress made so far with NXP 900, including the completion of the dose escalation phase one study in patients with advanced solid tumors and the clinical drug drug interaction study in healthy volunteers.

Both required to enable this phase one b program.

Our phase one dose escalation study evaluating escalating doses of NXP 900 from 20 to 300 milligrams per day and 33 patients with various types of advanced cancers. In these patients we observed good overall, tolerability and the dose limiting toxicity or.

L. T level was not reached the most common treatment emergent adverse events were fatigue diarrhea, nausea abdominal pain.

Ron Bentsur: 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 anti-cancer agents. What particularly stands out from our phase I-A results is the pharmacodynamic response achieved following treatment with NXP900. At clinically relevant doses, starting at 150 mg 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 I-B 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.

Dyskinesia and vomiting, mostly reported as grade one two which is consistent with other oral anti cancer agents.

What particularly stands out from our phase <unk> results is the Pharmacodynamic response achieved following treatment with NXP 900 at clinically relevant doses starting at 150 milligrams per day, we observed a rapid and deep inhibition of Sark autophosphorylation that exceeded 90%.

This level of stock inhibition is rather unprecedented and we believe bodes well for the phase <unk> program.

As you May know NXP 900 also has a unique mechanism of action, where it binds to its target when it is and it's closed or off confirmation, 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 SAARC inhibitors that bind the target and its open or on confirmation, thereby only inhibiting the catalytic function of the target and in fact, paradoxically leading to activation of the Sox signaling complex, we believes that NXP nine.

Ron Bentsur: 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 I-B 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 induced 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.

<unk> ability to completely shut down.

Sorry signaling is an advantage that could be brought to bear in the phase one b program.

We also recently completed the drug drug interaction study in healthy volunteers supporting the combination of NXP 900, with Egfr and Alk inhibitors, since Austin American and Latin to leading Egfr and Alk inhibitors, respectively, H induce members of the <unk>.

Cytochrome <unk> hundred 50 family, including sit three eight we felt that it was important to understand NXP nine hundreds drug drug interaction or DTI profile upfront based on a recently completed DDI study. We showed that NXP 900 is actually a week inducer of Sip three these data were key to enabling.

Our planned phase <unk> combination study.

Ron Bentsur: These data were key to enabling our planned phase I-B combination study. The phase I-B 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 show 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 phase one B study will evaluate the efficacy and safety of NXP 900 for the first time in target patient populations as a single agent and in combination in patients suffering from advanced.

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 NXP 900 in particular, our data show positive results, where NXP 900 and models of cancers harboring yeah.

One gene amplification in Hippo pathway alterations touches such as mutations in fact, one in F. Two yes, one is a very important kinase within the <unk> family and sat one and then it's two are located downstream of it a dependency, allowing NXP 900 to target the pro cancer signaling any.

Both by mutated sat one and then if to the.

The well defined biology of these models enabled us to define the patient populations that we will test in the phase one B study importantly.

Ron Bentsur: The well-defined biology of these models enabled us to define the patient populations that we will test in the phase I-B study. Importantly, identification of these genetic alterations can be done using commercially in-hospital-based next-generation sequencing panels that are routinely used and available across the country. We're embarking on a broad single agent approach. 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 in 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.

Identification of these genetic alterations can be done using commercially and hospital to hospital based next generation sequencing panels that are routinely used in available across the country.

We're embarking on a broad single agent approach and eligible patients for the single agent study include those the following combination.

Nations of tumor type and genetic alterations, yes, one amplified or <unk> mutated non small cell lung cancer, and that's two mutated mesothelioma and renal cancer and other advanced solid tumors with any of the genetic alterations mentioned above or other relevant hippo pathway alterations.

<unk> will be included in the basket group the specific genetic alterations were selected based on their characteristics as either a direct for example, yes, one amplification or dependent for example, hippo pathway alteration.

Ron Bentsur: 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.

Targets of NXP, and 900, 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.

And it's been nine hundreds of 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.

His extensive scientific literature that points to activation of bypass mechanisms controlled by SAARC and yes, one dependent signaling is driving resistance to the Egfr inhibitor us American it known by its brand name to Grisso or the Alk inhibitor latinate known by its brand name <unk>.

Ron Bentsur: 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.

Re sensitizing the cancer to these treatments by blocking the bypass enabling acquired resistance can change the treatment.

Ladies and gentlemen, please standby we're experiencing technical difficulties at our conference will resume momentarily.

Operator: 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.

Thank you for standing by everyone. Ron Please continue.

I apologize everyone.

Ron Bentsur: 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 1 million patients have been treated around the world with TAGRISSO since its launch in 2015.

He sensitizing the cancers to these treatments by blocking the bypass enabled a card resistance can change the treatment paradigm for these patients by allowing them to continue treatment with an oral regimen.

For which they had already previously responded to.

From a business perspective, the market opportunity from an XP 900 is substantial is the potential addressable patient populations for NXP 900 treatment are quite sizable as an example, the incidents of fat one alterations alone in patients with lung and head and neck squamous cancers exceeds <unk>.

23000 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 to Grisso since.

Its launch in 2015, hopefully this provides some perspective on the size of the patient populations door pursuing in this phase one b program in.

Ron Bentsur: Hopefully, this provides some perspective on the size of the patient populations who are pursuing in this phase I-B program. In summary, our phase I-B 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 900. 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.

In summary, our phase one B program is designed to evaluate and it's being 900 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.

Cross multiple well defined and substantial patient populations by testing multiple hypotheses simultaneously, we could open the door to new clinical applications for 900. For example, if we see single agent activity and yes, one amplified tumors are fat one mutations that could open.

Entities 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.

So looking ahead, we believe that positive phase <unk> results could be transformative for an effective the precision oncology space has demonstrated multiple times that companies with compelling phase one data in defined patient populations can generate significant interest from both the investment and pharma community.

Ron Bentsur: Looking ahead, we believe that positive phase I-B results could be transformative for Nuvectis. The precision oncology space has demonstrated multiple times that companies with compelling phase I-B 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 I-B 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.

And 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 one b program around <unk> 900.

Our pipeline in a pill drug candidate represents the culmination of years of scientific work and successful clinical execution to date, we believe that NXP nine hundreds unique mechanism of action clinical safety profile and robust target engagement put it in a great position to become an important player.

<unk> and precision oncology and we expect to share data from this study throughout 2026, we're excited to commence the NXP 900 phase one B program today, which will hopefully serve to showcase an XP nine hundreds robust therapeutic potential.

Ron Bentsur: We're excited to commence the NXP900 phase I-B program today, which will hopefully serve to showcase NXP900's robust therapeutic potential. Thank you very much for your attention. Now let's please open the call up for Q&A. Thank you.

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 will be connect conducting a question and answer session.

Operator: Thank you, Ron. At this time, we'll be conducting a question-and-answer session. Our first question comes from the line of Jonathan Aschoff with Roth Capital. Please receive your questions.

If he would like to ask a question you May press star one from your telephone keypad infused.

If you're using a speakerphone please pick up your handset before pressing the heath.

To try your question Press Star then two.

Our first question comes from the line of Jonathan Aschoff with Roth Capital. Please proceed with your question.

Thank you good morning, Ron I'm curious with all the time that you'd respond.

Jonathan Aschoff: Thank you. Good morning, Ron. I'm curious.

Ron Bentsur: Good morning, John.

What is the expected response rate for N. S. C. L. C. Two re treatment with the Egfr and the Alex you will use in combination. So that we may have a sense of how much better combo at 900 is when we see that.

Jonathan Aschoff: What's the expected response? Thanks. What is the expected response rate for NSCLC to retreatment with the EGFRs and the ALKs you will use in combination so that we may have a sense of how much better combo with 900 is when we see the initial combo treatment data?

Initial combo treatment data.

So.

Again, youre talking about patients, who you know has been onto grisso or latinate, but it could be for an extended period of time because you know these drugs typically can provide with PFS is that our measure it actually in years. So it could be two years three years, which obviously is a very nice benefit.

Ron Bentsur: Again, 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 2 years, 3 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, or a refractory patient population, the regulatory bar will be kind of in the 15% to 20% range.

However, eventually all patients without exception.

Will become resistant to these treatments and that's when they start progressing.

So 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. So you know in terms of numbers.

We believe that ultimately because this isn't you know a salvage type of a patient population. If you will a refractory patient population the.

The regulatory bar will be you know kind of in the 15% to 20% range.

But obviously you want to be higher than that.

Ron Bentsur: 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.

You know.

Anything above 20, or 25%, let alone you know in the thirties forties or higher.

I think would put a disc combination in a very good position vis a vis the investment community and also of course the F D. A.

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.

Jonathan Aschoff: 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 one is not dependent on the other the single agent part of the program logistically, It's just easier to start it's it's a part of the existing phase one protocol that's already in place.

Ron Bentsur: 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 I protocol that's already in place. Obviously, for the combination studies, you need a separate protocol. We needed to finalize a phase I-A 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.

And yet obviously for the for the combination studies you need a separate protocol, we needed to finalize a phase one a and banner that drug drug interaction study and get the final reports in and all of that before you know before we could finalize the protocol what's worked the protocols for the combination studies, which were working on now.

Now so Bob you know that will start up hopefully very shortly.

Okay, and thank you and lastly regarding enrolling patients with specific genetic amster all duration can you help us understand the size of that patient subset.

Jonathan Aschoff: Okay. Thank you. Lastly, regarding enrolling patients with specific genetic amplifications or alteration, can you help us understand the size of that patient subset among the 3 solid tumor types that you intend to preferentially enroll, lung, meso, renal?

Among the three solid tumor types that you intend to preferentially enroll in Oman meso.

Yeah here I'll defer to Enrique and retail you're on the line.

Ron Bentsur: Yeah. Here I'll defer to Enrique. Enrique, are you on the line?

Yes, Andrew.

Enrique Poradosu: Yes. Hi, Amber. Can you hear me?

Can you hear me good morning, the wine recapture.

Ron Bentsur: Yeah. Good morning, Amber.

Yeah. Please yeah. If you can please answer the question on that.

Ron Bentsur: Enrique, if you can please answer the question on the size of the patient populations for the YES1 gene amplification, FAT1, and so on.

The size of the patient populations.

For the the yes, one gene amplification sat one and so on.

Yes fine.

In lung cancer.

Enrique Poradosu: Yes. 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%, so papillary cells is about 15% of the total renals, so we're talking about 15 out of 15 approximately. In mesothelioma, it's about 40% NF2 mutation.

In particular, the let's focus for non squamous for a second and squamous lung cancer.

The prevalence of desktop one mutation is in the order of 18%.

S dollar communications about the 5%.

In phenol popularly kidney hunker.

And there still is about 15% of popular popular. He tells me the rotation of our scientific without reading also are thinking about 15 out of 15 approximately.

And then he needs of any I'll make about 40%.

The limitation.

I. Thank you very much guys that's all.

Jonathan Aschoff: All right. Thank you very much, guys. That's all.

Thank you Jonathan.

Ron Bentsur: Thank you, Jonathan.

The next question comes from the line of Christopher Lu with looser capital market. Please proceed.

Operator: The next question is from the line of Christopher Lu with Lucid Capital Markets. Please receive your questions.

Your question.

Hey, guys. Thanks for the question.

Christopher Lu: Hey, guys. Thanks for the question.

Two for me.

So do you think that the post Egfr and Alex setting is amenable to an accelerated approval.

Ron Bentsur: Good morning, Chris.

Christopher Lu: Just two from me. Do you think that the post-EGFR and ALK setting is amenable to an accelerator approval? You mentioned kind of the ORR benchmark. What should we look to towards maybe a PFS or OS benchmark?

And also you mentioned kind of the over our benchmark what should we look to tow words, maybe a PFS or OS My Department.

Yeah.

So.

The first question is you know could it be amenable to <unk>.

Ron Bentsur: The first question is, could it be amenable to accelerated approval? We certainly believe that 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. Again, 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.

Accelerated approval.

You know, we we certainly believes that that could be the case, obviously, we haven't had any formal discussions with the F. D. A.

But acquired resistance is you know, perhaps you know the biggest problem.

In the lung cancer space today.

Because you know these patients basically once they start progressing there.

There's just not much that's available for them.

And their prognosis, obviously becomes extremely poor at that point.

So again the ability to reverse course, and I think there's going to be incredibly important.

To be able to do that.

So on the face of it we believe that it could qualify for accelerated approval.

You know single arm studies and things of that nature.

And with respect to PFS and what you could you know what.

Ron Bentsur: 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 6 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.

You should expect in terms of durability of responses and all that.

So you know that kind of falls into the typical.

Bucket I believe that the FDA looks for in these types of situations and again, we have not had the formal discussion about any of this is just a this is just ourselves a supposition based on other situations that we've seen.

But typically you would want to show.

Now six months or more of durability of response median that's kind of the sweet spot for what the FDA typically looks for these types of situations. So.

That that would be my answer to that to that question.

Great. Thanks, maybe one more if I may do you have any.

Christopher Lu: Great. Thanks. Maybe one more, if I may. Do you have any, I guess, internal estimates for what the market opportunity might look like in dollars for this post-ALK, post-EGFR setting?

I guess internal estimates for what the market opportunity might look like in dollars for this post our proposed egfr setting.

Yeah. So V. We're talking about billions of dollars here in terms of market potential. This is truly a blockbuster potential opportunity and its down.

Ron Bentsur: Yeah. We're talking about 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, it can extend TAGRISSO use for patients and extend their tenure on TAGRISSO. We can all do the math on that. To keep a patient longer on TAGRISSO is very, very important for AstraZeneca or whoever the EGFR player is. Of course, our drug comes into joins that picture as well.

So when you think about take rates. So as an example, so tourists who is going to probably generate around $7 billion. This year something like that.

But keep in mind that roughly.

A third of the patients progress every year.

So basically if you take the patients that progress.

And and you start treating them with a combination and you're able to change the course.

That alone is a massive sliver ah that basically it can extend to Chris so use for patients and extend their tenure onto Grisso I and we can you know we can all do the math on that.

To keep a patient longer onto Grisso is is a very very important you know for for Astrazeneca whoever the Egfr player is and of course, our drug that comes into joins that picture as well.

We're talking about very substantial numbers and on the alk side.

Ron Bentsur: 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, EGFR is about 4% or some 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 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.

We're talking about a subset that is roughly half of the egfr patient population in terms of size. So if egfr is at roughly 10% of the patients in a in lung Egfr is about 4% or something or alk is about 4%.

And there I think a good example would be a company like new failing for example, some new Zealand.

Right now has a data in the third line alk. So after patients have gone through elective may have been long winded.

They go on.

No valence drug.

And they generated.

Between the 30 and a 40% response rate obviously, they want to move upstream in and dialed they started up.

For a first line study and so on and so forth, but 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.

And and you know their market cap is $5 $5 billion or something like that and the expectation. There ultimately is that they will take there'll be able to capture a you know either a third or you know or maybe even a little bit more of the alk market, which is currently about two and a half to 3 billion expected to grow obviously the forest.

Ron Bentsur: Their market cap is $5.5 billion or something like that. The expectation there ultimately is that they'll be able to capture either a third or maybe even a little bit more of the ALK market, which is currently about $2.5 to 3 billion, expected to grow, obviously, to $4, $5, $6 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 slivers 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.

Five six in a few years, so the numbers that get thrown around particularly in lung and I didn't even talk about yes, one over expression in fact, one in it for non small cell lung cancer alone witches, which represent another big slivers within the other patient population so.

When you look at the dollars and the patient numbers and 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 for our drug.

Thanks, Ron appreciate it.

Christopher Lu: Thanks, Ron. Appreciate it.

Thank you.

The next question is from the line of E. L. Jen with Laidlaw. Please proceed with your question.

Ron Bentsur: Thank you.

Operator: Next question is from the line of ELGen with Leerink. Please receive your questions.

Good morning, and thanks for taking the question and congrats on the kickoff the trials just said it.

[Analyst] (Leerink): Good morning. Thanks for taking the question.

Ron Bentsur: Morning.

[Analyst] (Leerink): Congrats on the kickoff trials. Just a few here. The first one is in terms of the monotherapy for phase I-B study, what would be the study's patient size as well as how many centers you anticipate to engage? I have a follow-up.

A few here the first one is in terms of the monotherapy one.

One piece 31 will be this study's patient side as well as the how many centers are you all anticipate too.

To engage and have a follow up.

Yeah. So in terms of the patient so each one of the groups that we described so yes, one annapolis up amplification sat one.

Ron Bentsur: Yeah. In terms of the patients, so 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, and then you expand based on that. We plan to have 4 groups, so potentially a total of 100 patients there. In terms of the number of sites, so right now, we're starting the study with roughly 15 sites. That number will grow. We believe that in terms of critical mass to start the study with, I think we're in very good shape.

Mutation and so on each.

Each one of these groups are ultimately wound up being about 25 patients you start off with.

12, and you look for a signal and then you expand based on that.

So we plan to have four groups so.

Potentially a total of 100 patients there.

And in terms of the number of sites.

So you know right now we're starting the study with roughly 15 sites that number will grow but.

But we believe that in terms of the critical mass to start the study, which I think we're very good shape.

And 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. It at sites.

Ron Bentsur: 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. Of course, 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.

And you know go through that logistical step, which we don't believe it's necessary.

So obviously, that's a prerequisite for sites to have these panels already in place and of course, many do them. The overwhelming majority of our sites in the country already have that.

So I think from that perspective, we're in good shape. So I think we can start the study off.

You know and with with very good cadence.

And so all these are the in the United States is that right.

[Analyst] (Leerink): All these sites are in the United States. Is that right?

O U S.

Okay. The second question is that you mentioned a little bit in terms of in the combo sets, adding that could be a little bit Savage.

Ron Bentsur: All US.

[Analyst] (Leerink): Okay. The second question is that you mentioned a little bit in terms of in the combo setting, that could be a little bit safety nature of the study.

The nature of that this did this study yes.

If so would that be possible that you would need a overall survival.

Ron Bentsur: Yeah.

[Analyst] (Leerink): If so, would that be possible that you need overall survival either primary or secondary endpoint? What would you feel the again, the bar for that is?

Yes in a primary ethic of EM and what would you feel the again the bar for that is.

Yeah. So you know obviously I can't speak on behalf of what the FDA May may say you're think.

Ron Bentsur: Yeah. 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. Of course, 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.

In this particular case, but we do believe that.

<unk>.

Based on our <unk>.

A lot of other studies that take place in the lung space.

And are the types of endpoints that people are pursuing are about you know what 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 are should be enough.

But of course for me to say that conclusively it would be irresponsible at this point in premature.

But we do believe that that these types of patient populations in the trial.

And the again the salvage setting that these patients qualify or fall into.

I think it would be amenable to these types of clinical trials.

And that's basically going to be our our approach but of course until we have a.

Ron Bentsur: Of course, until we have discussion with the FDA, we won't know for sure.

Discussion with the FDA, we won't know for sure.

Okay, great very helpful and maybe it's squeak in one more you mentioned about a combo study will start.

[Analyst] (Leerink): Okay. Great. Very helpful. Maybe squeezing one more. You mentioned about a combo study will start after the monotherapy. Just curious in terms of the timeline and the needed data needed sort of status as well as protocol setup. Would that be something in 2026, or you think that could be started a little bit early? Thanks for the question.

After the mono therapy, just curious in terms of the timeline and the needed data.

Needed the initial data as well as the.

Portola set up would that be something in 2020. Thanks, All you think that could be thought of liberty and thanks for the question.

No. We believe yeah, we believe that the combo studies that will start this year.

Ron Bentsur: No. Yeah. We believe that the combo studies will start this year. Like you said, logistically, it's a little bit more complicated to start those. When you need to write a new protocol, it obviously takes more time, and you need to wait for the basically include the final data from the phase I-A 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.

But like you said logistically, it's a it's a little bit more complicated to start those others more.

When you need to write a new protocol you obviously it takes more time and you need to wait for the.

You need to basically include the final data from the phase one day and the drug drug interaction studies and so on we needed to wait before we could.

Finalize the protocol and show it to the Pea eyes and circulated around and go to the IRB is which we plan to do next.

It just takes a little bit longer.

But we believe that both of these studies will be up and running this year.

Okay, great. Thanks, and congrats I'll kick off the thing, though we are anticipated.

[Analyst] (Leerink): Okay. Great. Thanks. Congrats on kickoff the things we all anticipate.

Thank you. Thank you very much.

Ron Bentsur: Thank you. Thank you very much.

Thank you. Our final question is from the line of Joe Pat Guinness with H C. Wainwright. Please proceed with your question.

Operator: Thank you. Our final question is from the line of Joseph Pantginis with H.C. Wainwright & Co. Please receive your questions.

Hey, guys. Good morning, Thanks for taking the questions.

Joseph Pantginis: Hey, guys. Good morning. Thanks for taking the questions.

Two questions Hey, Ron two questions. If you don't mind. So first on the conduct of the study so a lot of discussions about the market size and what have you and I think youre going after a good number of patients here to get signals potentially so far.

Ron Bentsur: Hey, Joe.

Joseph Pantginis: Two questions. Hey, Ron. Two questions, if you don't mind. First, on the conduct of this study. 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. First, what are the triggers with regard to 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?

First are the what are the triggers.

With regard to number of responses in order to expand and with regard to the expansion is are the two studies, but basically monotherapy and combination independent of each other or do you need the response rates from the monotherapy to expand into the combos.

Yes. So the on the second question is easier for me to answer the answer is they're independent of each other so you don't you do not need to see.

Ron Bentsur: 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 the going up from, let's say, 12 to 25, what would trigger that?

Something in one before you can start the other so are there going to be completely independent.

For the statistical question I will refer to Enrique who.

It's much better and statistics and I am so Enrico if you can answer that question.

Regarding the.

You know.

Gone up from lets say 12 to 25, what would trigger that.

Yeah.

Enrique Poradosu: Yeah. The statistical design is essentially based on the Simon's two-stage design. A response in a particular combination of mutation and an histological setting will trigger the expansion of that particular mutation and histology into a larger group of patients.

The statistical design, especially based on.

Simon two stage design.

So our response.

Particular combination of up mutation and a histologic all setting will trigger the expansion of that particular mutation.

Mutation in histology and to a larger group of patients.

So I guess you know if it were 12 patients like is there like what is the particular number do you need to see to responses three responses or you're not disclosing sort of the actual trigger yet.

Joseph Pantginis: I guess if it were 12 patients, what is the particular number? Do you need to see two responses, three responses, or are you not disclosing sort of the actual trigger yet?

Okay.

No it will not be present et cetera, but it's essentially a you know a responder and a combination of a mutation in histology subtype and of course, we are.

Enrique Poradosu: 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 the meaningful mutations in each histology group.

We are recruiting patients that are in sufficient numbers. So we can have been meaningful mutation in the jaw histology group.

Got it thanks for that and then my second question is about the broader profile of 900 and I'll ask the question somewhat vaguely, but I'm, hoping you can give a good reminder to us so.

Joseph Pantginis: 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 of 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.

You have a lot of independent of new vectors of data that has compared 900 from Src standpoint, with many others, including you know a pharma study. So I'm just hoping you can you know sort of review that for those on the call because it seems like you really have an orange Yates asset.

Sure. So we believe that.

Ron Bentsur: Sure. We believe that the ability of NXP900 to inhibit the target, which is SRC, and obviously, we saw that in the phase I-A, is actually far superior to what we've seen with the other SRC inhibitors, the dasatinib, 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. 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.

The ability of NXP 900 to inhibit the target, which is socgen and obviously, we saw that in the phase one a.

Is actually.

Far superior.

Two what we've seen with the other <unk> inhibitors, the sadness suite nips our cabinets.

The assays themselves were not identical.

But there were close cousins of one another so I think they are to some extent not very much comparable.

And you see a dramatic difference in terms of NXP nine hundreds ability to.

To inhibit two inhibits arc versus the other drugs.

And it's very consistent and it happens quickly.

And you see a trough levels.

And so on so so we know that the inhibition profile is.

Very robust in fact, I'm pretty much saturated so.

Once you once you get to a 150 and you start getting 90 90, 394%, it's very hard to get much higher than that.

So we're very pleased by the inhibition profile that we're seeing so there's definitely a very strong target engagement.

Ron Bentsur: 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 2 partial responses confirmed. They had 1 stable disease with 29% tumor shrinkage, so 1 percentage point 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.

And in terms of the you know kind of anecdotal information that's out there to support.

What we're doing.

And the the different patient populations that were trying to pursue.

So one interesting example would be.

Ah sorry Cat <unk> study in non small cell lung cancer that was done a few years ago.

Astrazeneca and what they showed there about 25 patients where we're in that program that were enrolled.

And they had a two partial responses confirmed they had one stable disease with a 29% tumor shrinkage. So one percentage point away from being a responder as well.

And this was in an enriched patient population they did not enrich for yes, one amplification or fat one or anything like that this was kind of an all comers non small cell lung cancer study and we know that's our cat nib.

Ron Bentsur: We know that saracatinib is not believed to be a very potent inhibitor of SRC. 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.

Not believed to be a very potent inhibitor of sark.

Again, the numbers that you see for sort of cat nib or are just not nearly as compelling as like what you see with NXP 900. So if you take those two kind of anecdotal data points and you try to connect the dots you have got a study here that showing some activity obviously wasn't enough to move forward. It was a.

A little bit a little bit less than a 10% response rate.

But in an unearned rich patient population.

But you still see activity.

With a sock inhibitor that isn't I believe to be very potent so.

We believe that that's actually a case study that.

It provides very strong justification for what we wanted 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 the S. One amplification in the fat one mutation only.

Ron Bentsur: 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. Again, if you kind of evaluate all that from a top level, we really like our chances.

And we believe we've got a much more potent SAARC inhibitor than sorry cat nib.

So.

Again, if you are.

Kind of evaluate all that from a top level.

We really like our chances.

Thanks, a lot.

Thank you.

Joseph Pantginis: Thanks a lot.

Thank you.

Ron Bentsur: Thank you.

I'll turn the call over to Mr. Vincent for his closing remarks.

Operator: 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.

Ron Bentsur: 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 I-B study. Have a good day, and thank you so much.

Really appreciate it and we also appreciate your continued support of unaffected.

And we look forward to updating you on the progress as we advance NXP 900.

Through the phase one B 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.

Operator: Ladies and gentlemen, this concludes today's presentation. Thank you once again for your participation. You may now disconnect.