Nuvation Bio Inc (NUVB) 2025 Q1 法說會逐字稿

Good afternoon and welcome to the Nuvation Bio first-quarter 2025 financial results and business update conference call. Please be advised that today's conference call is being recorded. (Operator Instructions)

I would now like to turn the call over to JR DeVita, Executive Director of Corporate Development and Investor Relations at Nuvation Bio. Please go ahead.

Thank you, and good afternoon, everyone. Joining me on today's call are Dr. David Hung, our Founder, President, and Chief Executive Officer; Colleen Sjogren, our Chief Commercial Officer; and Philippe Sauvage, our Chief Financial Officer.

Certain statements we make during this call will be forward-looking. These include statements about taletrectinib, expected FDA approval, US commercial launch and potential benefit for patients, our commercial team's launch readiness, and our cash runway. Because such statements deal with future events that are subject to many risks and uncertainties, actual results may differ materially from those in the forward-looking statements.

For a full discussion of these risks and uncertainties, please review our annual report on Form 10-K and our quarterly reports on Form 10-Q that are filed with the US Securities and Exchange Commission. This afternoon, we released financial results for the quarter ended March 31, 2025, and provided a business update. The press release is available on the Investor section of our website at nuvationbio.com. These statements are subject to risks and uncertainties that could cause actual results to differ materially. For more information, please refer to our filings with the SEC.

Now I'll turn the call over to our Founder, President, and Chief Executive Officer, Dr. David Hung. David?

Thank you, JR, and thank you all for joining us this afternoon. I'll begin with an overview of our company and programs, near-term focus, and strategic priorities. Colleen will then share our commercial preparedness for taletrectinib, and Philippe will summarize our financial results and outlook.

We've entered a transformational period for Nuvation Bio. With the PDUFA date set for June 23 for taletrectinib, our next-generation ROS1 inhibitor for non-small cell lung cancer, or NSCLC, this quarter serves as a key inflection point as we prepare to become a commercial-stage company. We believe the potential approval of taletrectinib could be one of the most significant moments in our company's history. Over the next several weeks, our team will continue executing with discipline and focus, ensuring we are prepared to deliver a meaningful new treatment option to patients living with ROS1-positive lung cancer.

From the beginning, Nuvation Bio has been driven by a simple but powerful idea to challenge the status quo in cancer treatment, especially and particularly difficult-to-treat cancers. I always tell my employees our company mission is rooted in the premise that patients don't need more drugs. They need better drugs. Drugs that impact important metrics for patients and doctors like efficacy, safety, and convenience.

ROS1-positive lung cancer represents a well-characterized but particularly aggressive subset of non-small cell lung cancer. The median progression-free survival, or PFS, of this disease prior to the advent of targeted therapies ranged from 6 to 12 months and treated with chemotherapy and/or immuno-oncology agents.

First-generation ROS1 tyrosine kinase inhibitors, or TKIs, crizotinib and entrectinib, changed the treatment landscape significantly. providing an overall response rate, or ORR, of approximately 70% with a median GFS of about 18 months in the first-line setting. Crizotinib, however, does not cross the blood-brain barrier, and intracranial metastases in ROS1 lung cancer are common.

About 35% of patients newly diagnosed with metastatic ROS1-positive lung cancer have tumors that have already spread to their brain. And the brain is the most common site of disease progression, with about 50% of patients previously treated developing brain metastases upon progression. Second-generation repotrectinib provides an ORR of 79% and a median PFS of 36 months, a significant improvement over first-generation agents.

Unfortunately, both entrectinib and repotrectinib have CNS toxicity that has limited their use in some patients. The CNS toxicity of repotrectinib in particular is potentially due to the fact that its affinity for ROS1 is similar to its affinity for TrkB, a neurotrophic receptor in the brain that is associated with CNS side effects. We believe taletrectinib has the potential to become best in class in a space where patients, physicians, and payers are still struggling with the challenges of current ROS1 therapies.

In our clinical trials across different lines of therapy, taletrectinib has demonstrated consistent, durable responses, strong intracranial activity, and a favorable safety profile, including a low rate of discontinuation and tolerable CNS effects. In pooled data from our pivotal trials that we recently published in the Journal of Clinical Oncology, taletrectinib had a confirmed ORR of 89% in treatment-naive patients and a median PFS of 46 months. We also observed a median duration of response, or DOR, of 44 months.

I'd like to put this into context within the broader oncology treatment landscape. In my long career in oncology, I have not seen any approved agents in any solid tumor where I have observed response rates and durability like those of taletrectinib. Osimertinib, one of the most successful lung cancer drugs ever, with over $6 billion in annual sales, has an ORR of 77%, median PFS of 19 months, and median DOR of 17 months.

Enzalutamide, the most successful prostate cancer drug worldwide which Pfizer acquired from my prior company Medivation, with over $6 billion in annual sales, has an ORR of 59% and a median PFS of 20 months. Additionally, virtually all cancers eventually escape targeted therapy through the emergence of resistance mutation. Hence, drugs with extremely prolonged PFS and DOR metrics in the metastatic setting must be particularly effective at preventing the emergence of resistance.

We view taletrectinib's 46-month median PFS and 44-month median DOR as reflections of the potential for taletrectinib to delay or prevent the development of ROS1 TKI-resistant mutations. We're also seeing consistent intracranial activity with taletrectinib, including a 77% confirmed intracranial OR and treatment in IU patients with measurable brain metastases.

In the second-line setting, taletrectinib had a confirmed ORR of 56% with a median PFS of 10 months and a median DOR of 17 months. Perhaps even more importantly, in the second-line setting where brain metastases become particularly prevalent and problematic, taletrectinib demonstrated a 66% confirmed intracranial ORR. Intracranial response rate is critically important in this disease since seen as progression has the greatest impact on long-term survival.

Finally, taletrectinib has demonstrated a favorable safety profile. Most adverse events have been low grade, transient, and manageable. This includes low rates of significant neurological issues. For example, taletrectinib's rate of dizziness in our pivotal studies was 21%, and 90% of this dizziness is Grade 1 and transient, lasting about three days.

We believe taletrectinib's well-tolerated CNS profile is driven by its 11- to 20-fold selective inhibition of ROS1 over TrkB, enabling potent ROS1 inhibition while reducing dose-limiting CNS toxicity. Importantly, we believe there are subtleties to the amount of ROS1 versus TrkB inhibition that is beneficial for patients. TrkB is believed to play a role in brain metastases. Published studies suggest that high TrkB expression is linked to CNS progression in lung cancer, breast cancer, and other solid tumors. These data suggest that you do want to inhibit TrkB to some extent, just not to the extent that it compromises tolerability.

Taletrectinib is well tolerated but not entirely devoid of TrkB activity, which we believe contributes to its 21% busyness rate, more than 90% of which is Grade 1. However, we believe that taletrectinib strikes the right balance between potent ROS1 and milder TrkB inhibition, and we further believe that this balance plays a role in taletrectinib's high systemic and intracranial response rates and long durability of response.

The most common adverse events with taletrectinib is elevation of liver function tests or LFTs. Elevation of LFTs is well understood with TKIs, and oncologists are accustomed to managing these, generally by dose reduction, interruption, or, if necessary, drug discontinuation. The overall drug discontinuation rate due to treatment-emergent adverse events, or TEAEs, for taletrectinib is just 6.5%, which is low in this space.

Initially, while diarrhea is the second most common GI side effect with talent retinitis. The vast majority of this diarrhea is grade one and transient. Finally, we believe that by far the greatest threat to any ROS1 lung cancer patient is disease progression, especially in the first-line setting when particularly effective ROS1 therapies can otherwise mean years of PFS.

Recall that prior to the advent of precision oncology drugs, non-small-cell lung cancer patients generally progress in IO chemo in 6 to 12 months. As an example of how taletrectinib has affected the lives of some patients with advanced ROS1-positive lung cancer, we have recently learned that of the 15 patients dosed in a Phase 1 study of taletrectinib in the TKI-naive setting, one patient received treatment for seven years, one patient has now exceeded eight years, and two others have now exceeded the nine-year mark.

As a reminder, the FDA has granted taletrectinib breakthrough therapy designation in both the first- and second-line settings, the only ROS1 drug in development to receive such designations. Our taletrectinib new drug application, currently under priority review, is supported by one of the largest datasets in the ROS1 space, including a safety database of more than 400 patients.

The review of our MDA is progressing on time with all planned inspections now completed with favorable outcomes. Our level of engagement with the FDA is high, and our interactions have been timely and as expected. We are confident in the strength of our data package and that approval will be achieved on or before PDUFA date.

Importantly, what stands out to us most is the potential for taletrectinib to positively impact patients' lives. These patients are typically younger, non-smoking individuals who unfortunately face an aggressive disease with limited long-term treatment options. To give them not just a new but a highly durable, efficacious, and tolerable option would be profoundly meaningful.

We believe the market is ready for new alternatives. With strong and durable efficacy and a favorable safety profile, we believe taletrectinib, if approved, is well positioned to reshape the ROS1 landscape. And our commercial team, many of whom have successfully launched leading oncology therapies at Medivation, Mirati, and other success stories, is ready to deliver.

We're entering this next chapter from a position of strength, with a deeply experienced commercial team and a focused market strategy. And with our recently announced $250 million non-diluted financing agreement with Sagard Healthcare Partners, we expect to have the flexibility and funding to launch taletrectinib and advance our broader pipeline without the need to raise additional capital to achieve profitability.

Just as importantly, we see the same kind of transformative potential across our broader pipeline. Safusidenib, our mutant IDH1 inhibitor, is being developed for diffuse IDH1 mutant glioma, a devastating brain cancer with very few treatment options, and a market opportunity that is materially larger than the ROS1-positive lung cancer measure.

Early clinical data suggests that safusidenib may offer deeper responses in both low-grade and high-grade glioma than what's been seen with other agents in this class. This includes data that has shown complete responses in high-grade glioma patients lasting years. With its high blood-brain barrier penetrance and the potential immune-based mechanism of action, we're preparing to move this program into pivotal development this year.

NUV-1511, our first clinical candidate from our drug-and-drug conjugate platform, represents a completely new modality in targeted cancer therapy. We look forward to providing an update for our Phase 1 dose escalation study in difficult-to-treat solid tumors later this year. And NUV-868, our BD2-selective BET inhibitor, demonstrated the tolerability and target selectivity we had hoped for. With nearly 1,500-fold selectivity for BD2 over BD1, it stands out as the most selective agent of its kind.

We've completed Phase 1 dose escalation and are evaluating multiple strategic options, including continued internal development or potential partnership opportunities. Each of these programs shares the same design principles, deep biological rationale, differentiated profiles, and a commitment to real patient unmet needs. We remain focused, mission driven, and confident that we have the team, strategy, and mindset to launch taletrectinib successfully and build lasting value.

With that, I'll turn it over to Chief Commercial Officer Colleen Sjogren to walk you through our commercial strategy and launch preparedness. Colleen?

Thanks, David. As we prepare for the potential approval of taletrectinib, our commercial approach is rooted in experience, a tailored strategy and a relentless focus on patients. Our launch strategy is designed to do two things upon approval. First, ensure that taletrectinibib quickly reaches patients; and second, maximize long-term value by leveraging taletrectinibib's impressive response rate, durability, and manageable safety profile.

ROS1-positive non-small-cell lung cancer is estimated to affect approximately 2% of newly diagnosed non-small-cell lung cancer patients, or approximately 3,000 new patients each year in the US. This population often skews to younger, non-smoking, otherwise healthy individuals facing rapid disease progression and a high likelihood of brain metastases. The average age of these patients is approximately 50 years old.

First-generation ROS1 TKIs like crizotinib and entrectinib generate less than $150 million in annual US net sales, a total that we believe is much smaller than the true market potential for ROS1 lung cancer. We believe these approved therapies for ROS1-positive lung cancer are underutilized, and there are important unmet needs still to be addressed.

Based on our efficacy and safety profiles, we believe taletrectinib has the potential to meet the needs of patients, differentiate from currently approved agents, and become the standard of care. We intend to grow this underdeveloped market with a strategy focused on early use and long-term persistence. If approved, taletrectinibib represents a new option for patients with a potential best-in-class clinical profile.

As David previously mentioned, we are not aware of any approved solid tumor agents that have demonstrated an 89% confirmed overall response rate, 46 months medium progression-free survival, and 44-month medium duration of response in clinical trials in the first-line setting. I can also say that I've not seen a drug with this clinical profile in my 25-plus-year career launching therapies for patients.

We know that identifying ROS1 patients remains a critical barrier. Testing rates, documentation of biomarker results, and action on those results remain inconsistent. Data show that up to 64% of non-small cell lung cancer patients potentially eligible for precision oncology treatments in the US have not yet received a targeted therapy. This is a major but addressable gap in care delivery.

Our commercial and medical teams understand this gap and have the experience, relationships, and strategy to address it. We believe we will quickly identify the appropriate patients and can get taletrectinibib to them efficiently. Historically, targeted therapies with improved durability, like osimertinib and EGFR-mutated lung cancer, have not only expanded their market several fold, but also captured more than 90% market share.

With taletrectinibib's differentiated data and our efforts on rapid patient identification, we believe a similar dynamic could unfold. We've been building our commercial infrastructure with that potential in mind. We've assembled a veteran launch team, including leaders from Medivation, Mirati, and other successful precision oncology companies, each with 15- to 20-plus years of experience launching blockbuster therapies and with a track record of building market leaders.

Many have successfully introduced oral, biomarker-driven treatments in equally complex spaces. We've right-sized our commercial footprint with 47 oncology account managers, a regional marketing team, and a field access team already in place to remove barriers and drive rapid adoption at launch.

With the PDUFA date now just weeks away, our team is advancing critical pre-approval initiatives. These include finalizing our go-to-market plan focused on high-priority accounts and top ROS1 prescribers; continuing medical education to population-based decision makers and HCPs on the recent NCCN guideline update, which highlights preferred utilization of ROS1 TKIs and de-emphasizes IO chemo; designing a strategy to optimize the patient experience; ensuring timely access, provider engagement, and operational efficiency; and investing in patient support with access and affordability programs to ensure seamless access for patients.

We pair a potential best-in-class profile with a seasoned, high-performing commercial team. If approved, taletrectinib offer sustained durability, CNS penetration, and a differentiated and manageable safety profile. Our commercial team is made up of strong leaders, with proven success in targeted oncology launches. We are bringing the same focus and passion to this launch, always putting patients first.

With that, I'll turn it over now to our Chief Financial Officer, Philippe Sauvage, to walk through our Q1 results and financial outlook. Philippe?

Thanks, Colleen. I'll briefly explain our first-quarter financial results and provide an update on our cash position and readiness as we prepare for potential commercial launch. For the first quarter of 2025, we reported R&D expenses of $24.6 million, reflecting continued investment in our lead assets, taletrectinib, and in our clinical stage pipeline, including safusidenib, NUV-1511, and NUV-868.

SG&A expenses were $35.12 million, primarily driven by our pre-commercial buildup. This includes personnel-related expenses tied to commercial hiring efforts sales, market access and operations, as well as strategic investments in medical education, payer engagement, and patient support programs. Due to those investments, and as expected, our net loss of a quarter increased compared to the prior year.

We remain focused on disciplined spend as we prepare ourselves to successfully launch taletrectinib if approved. We ended the quarter with $461.7 million in cash, cash equivalents, and marketable securities. This figure does not yet include the proceeds from a recently announced financing agreement with Sagard, which provides up to $250 million in non-diluted capital.

You might remember we closed this strategic transaction in March, and it includes a $150 million royalty financing, triggered upon FDA approval of taletrectinib, and a senior secure term loan of up to $100 million, with $15 million available immediately upon approval and an additional $15 million available at all discretion from first US commercial sale until June 30, 2026.

As we stated previously, these transactions solidify our capital position and, which we expect, fund operations through profitability, including a full US launch and continued advancement of our pipeline. It also means that the investment we believe is needed to launch taletrectinib is financed upfront by the royalty component of the deal.

As a nimble biotech, we retain operational flexibility and can stay focused on execution. Our current spend is deliberate and we prioritize our launch and its future revenues in the US without further expansion of our organization. Our cash position, including the Sagard financing, is incredibly solid and strengthens our capacity to execute our strategy and offer flexibility for further strategic moves.

While we are not providing revenue guidance at this time, I want to share how we are thinking about early commercial metrics. Following approval, our primary KPI will be the number of patients on practice. In rare, genomically defined markets like ROS1-positive lung cancer, this is a more meaningful and leading indicator of adoption than net revenues, particularly early in launch.

It could be challenging to compare launch metrics like net revenue when different organizations have different distribution models. Our distribution models should limit the initial stock buildup but provide better efficiency and access over the long run. This focus on new patient styles aligns with our expectation of durable treatment duration, and we believe initial patient growth will compound over time to build a sustained revenue base.

The real metric of success is the patients we help with our differentiated therapy. In addition, we are convinced that patients today are under-diagnosed and under-treated. Internally, we will therefore be tracking metrics around time to treatment initiation, coverage approval rates, and testing-related metrics, all of which will inform our commercial effectiveness and trajectory.

We believe we are well positioned, both financially and operationally, to deliver on the near- and long-term potential of taletrectinib. We built the right infrastructure, secured non-dilutive capital, and preserved flexibility to grow responsibly. If approved, we are confident in our ability to execute a disciplined, high-impact launch while advancing the rest of our pipeline in parallel.

With that, I'll hand it back to David.

Thanks, Philippe. As we look ahead to the June 23 PDUFA date for taletrectinib, we do so with a strong conviction in the strength of our data and the readiness of our team. This milestone has the potential to transform our company and validate our strategy of building best-in-class therapies around well-understood mechanisms.

Taletrectinib leads a broader portfolio of oncology programs designed to tackle some of the most difficult challenges in cancer treatment. As I said earlier, Nuvation Bio's mission is rooted in the premise that the world is in need of better drugs, not more drugs. We're aiming to deliver on this mission with patients in mind.

With that, I'll hand it back to the operator to open the line for questions.

(Operator Instructions) Gregory Renza, RBC Capital Markets.

Great. Good afternoon, David and team, and congrats on the progress. Thanks for the update, and thanks for taking my question. David, you and the team have provided a really helpful color on a potential launch and where you are with respect to the FDA proceedings. And certainly, as you prepare for that launch, I just wanted to ask a little bit on maybe some of those tailwinds that you've been alluding to.

There are several when it comes to the NCCN guidelines, when it comes to the potential differentiation of tale versus what else is out there. And then, quite frankly, just that potential longer-term duration that you're alluding to. Number one, can you just talk about how you sort of prioritize those as you think about going before patients and providers and physicians? And then number two, maybe just thinking about that value proposition, how are you thinking about maybe pricing for value to sort of harness that longer-term potential? Thanks so much.

Hi, Greg. Thanks for the question. So in our market research, it's pretty clear that the most meaningful metric to patients and for prescribing physicians is the duration of response. Progression-free survival and DOR are really at the top of the list of many considerations. We think that our 46-month PFS and 44-month DOR in the first-line setting is robust. We think it compares very favorably historically with all oncology agents, and we think that we should be well-positioned with that.

On top of that, as Colleen mentioned, we think that our tolerability profile is differentiated, and we think that it also positions the drug well. So we feel that we're in a good position to launch that. The question about NCCN guidelines is a tailwind. I think that's something that we didn't really expect. As you know, until the end of 2024, many ROS1 patients were not receiving ROS1 agents. And the reason for that was because of a little bit of logistics in the way this cancer is found and diagnosed and then treated.

So let's say you get a biopsy on a Monday, you could get your pathology back as quickly as Tuesday or Wednesday. But if it takes two to three weeks for your NGS test to come back, because these patients are particularly young, 50-year-old on average, they've got families, they've got careers, they're really nervous, and they want to be on something. And the old standard of care was to put them on IL chemo, and you might think that two to three weeks later when their ROS1 test comes back positive, they might switch.

The issue has been that if you look at historical NCCN guidelines, the old guidelines said that if you were found to subsequently have a ROS1 fusion after starting a systemic therapy like IL chemo, you had two choices. Choice number one was to continue that therapy, including maintenance; and choice number two was to switch to a ROS1 agent.

Because of choice number one, a lot of patients continued on their IL chemo, and then were either lost to follow up or progressed or elected not to pursue other therapy. And we think that that is going to be changed now with the 2025 new guidelines which state not only that if ROS1 fusion is found after systemic therapy is started, the recommendation now is singular. It is to stop that therapy and to start a ROS1 therapy.

Another additional benefit, I think, to us of the new NCCN guidelines is that, for the first time, the identification of a ROS infusion now is a contraindication to [IOUs]. So I think that's -- clearly, I think that's the right thing to do for patients. If you look at the PFS of IL chemo, which we said is six to 12 months. And if you're talking about a potential PFS of up to 46 months as a median, we think that that is the right thing to do for patients.

So we think that's an important tailwind for us. We did not anticipate that. We feel lucky that that change was instituted, but we think it is the right thing to do for patients. With regard to your third question about pricing, we're not really at liberty to discuss it at this point. We certainly have some ideas about where that will be. Looking at our data, We've tested multiple scenarios, and in relatively short order, we anticipate approval, as we said, either on or before the PDUFA date, so that's only a few more weeks. So we'll be announcing at that point what the price will be.

That's really helpful. Appreciate the color. And then just maybe a sneak -- a quick one in on safusidenib. As you've talked about giving an update in the second half of '25, certainly a lot of interest in this asset, in this area. Just would like you to just elaborate, what should we be looking for when it comes to the study design and the details that you'll be disclosing for that update? Thanks, and congrats again, guys.

Yes, so one of the important updates will be, first of all, the rationale for why we're moving forward. And so we're going to be announcing later this year the second safusidenib study, which is an important study because this is a study of only low-grade glioma and only one dose of safusidenib, so we believe these data will be particularly clear. And we're going to show response rates which we think will be of great interest to investors, patients, and physicians. And we also think we're going to show for the first time progression-free survival.

You might recall that vorasidenib's approval based on the indigo study showed a low-grade response rate of 11% and an improvement in PFS from 11 to 27 months, so a 16-month improvement in PFS. We're going to show later this year for the first time not only a second study with an ORR, which we think really speaks to the differentiation of safusidenib over vorasidenib, but for the first time, we'll give you a glimpse at the PFS difference, and we think that's exciting.

So based on that data, we are in discussions with FDA about a pivotal study for safusidenib, and we are contemplating both a low-grade and a high-grade study. But depending on our discussions, we'll give you more information on the design of those studies once we reach agreement with the agencies.

[Kaveri Paulman], Clear Street.

Yes, good evening. Congrats on the progress and thanks for the updates. Going from your commercialization efforts, what is your targeted account strategy for ROS1 patients? What quantity and types of community centers will you prioritize, your top targets, like you mentioned on the call, considering the concentration of patient populations? And what percentage of total addressable patient base do you anticipate reaching through your initial launch and marketing initiatives? And I have a follow up.

You know, Kaveri, we're in a competitive situation here, and we have a team that's very experienced. We've put together a strategy that we have a great deal of confidence in. But we're going to not make a lot of comments on exactly what our strategy is for this launch.

But that said, we think that in any case, no matter how we look at it, this is a show-me story from the Street, and we intend to show the Street what we can do, and that's what we're going to do. So we can't really comment on the specifics, but I think that over time you'll see the results of our efforts and our strategy, and we're confident that they'll be positive.

Got it. That's fair. And I would really appreciate additional color on the comments you made about the CNS disease. You mentioned that the early gen, first-gen drugs don't really cross the blood-brain barrier effectively. And the CNS disease occurs at higher rates in late-line patients. Do you expect taletrectinibib with CNS activity to be mostly used in late-line patients where it's more needed? And how much data is there to support that taletrectinibib can prevent the CNS disease? Thanks for taking my question.

Well, first of all, yes, sure. Thanks, Kaveri. Well, so first of all, no, our intention is to primarily push taletrectinib with the first-line settings where our PFS is 46 months and DOR is 44 months. And we think that the best way to not have to deal with a [brain mat] is to use a good drug upfront and not have it develop. We think that our high CNS penetrance, our strong activity, our strong intracranial response rates in both the first- and second-line setting, we think, position us well to be an upfront agent.

Now our second-line data are also very strong. As you know, our response rate is 56%. Our intracranial response rate is 66%. So we have robust data in the second-line setting, but the market is really a first-line market, and that's where we really intend to see our drug use. We think that the trend in oncology now has been for some time now that if you have a bad disease, you want to treat it as hard as you can right upfront, and we think that's the right position for taletrectinib to be in.

We do think that the CNS profile of some drugs -- we know that crizotinib doesn't cross the blood-brain barrier. And clearly, that's not a -- that probably doesn't position it well for preventing CNS meds. But if you look at progression or the development of CNS meds, some of that is subsumed within a progression-free survival.

When you have a long TFS, by definition, you're not progressing either systemically or intracranially. And while we cannot speak specifically to whether or not that is due to a drug treating those nascent tumors or preventing them, we can't really speak that specifically. The fact that the DLR and PFS are as long as they are by definition must mean that the cancer is having a more difficult time finding resistance pathways through which they can grow. And so we think that our data are strong and suggest that our drug should be used early and upfront. And that's what we intend to push it hardest.

I appreciate the color.

Soumit Roy, Jones Research.

Afternoon, everyone, and congratulations on the progress. During your market research with the physicians, anything -- trying to understand how much physician education is needed in terms of features of taletrectinib that needs to stand out, how -- or how the adverse events will be managed, if you can provide any color on that.

Sure. So I think physician education is always needed. No matter how you look at any field in oncology and no matter how you look at any drug launch, it's always harder to convert physicians to become prescribers than you would think. And so we are not going to underestimate the importance of physician education, and that's a huge focus of our efforts. And in fact, our medical affairs people, or even out in the field, talking about the ROS1 landscape to increase awareness in general about ROS1 agents.

It is a rare tumor. People don't always see it a lot, so we're well aware of the importance of that. But I think that it's pretty clear, though, that the way oncologists look at diseases is, what's treatable? And what's really interesting about the lung cancer space is if you look at EGFR, ALK, RET, and ROS1, with the new precision oncology agents that are out there, these have suddenly become one of the most treatable cancers out there.

Lung cancer used to be perceived as a death sentence. With these specific mutation-driven lung cancers and the agents that have been targeted against those mutations, these cancers have become eminently treatable. And that's a really important point for physicians and patients to realize. And we think that our data demonstrate how treatable ROS1 lung cancer is with taletrectinib.

89% response rate, 46-month PFS, 44-month DLR, those are numbers that indicate that this is a highly treatable type of cancer and that we believe that knowing that will incentivize doctors to prescribe it and patients to seek it. And that's our strategy. With regard to safety, we think our safety profile speaks for itself. Our drug discontinuation rate is low.

In terms of -- you mentioned management. Our most common adverse event is elevation of LFTs, liver function tests, and fortunately oncologists have been using TKIs for decades. And the management of LFTs with TKIs is well known by oncologists and we believe that we probably don't need a lot of training in that area because it's been done with so many other agents.

So we think this is going to be a pretty easy drug to prescribe and a pretty easy drug for patients to take. But the most important thing of all, independent of any safety issue, we've always said that the greatest safety issue facing any patient is disease progression. And to address that, you want a drug that has a high response rate and a long durability of response, and we think taletrectinib offers that. So that's the platform upon which we are educating physicians and patients.

That's really helpful. Question on how are you internally modeling the adoption rate? Should we look at it as a rare disease drug type where the decision-making events are a little bit infrequent than other tumor types? So it's a steady ramp, or should we think of it as initial bolus of physicians would be quickly adopting it, and then it will -- the growth rate will slow, will meter out?

Well, I've been through enough drug launches to know that nothing is as quick as you want in the early stages. So I would say that we've always said that physician adoption is always slower than you'd like. It takes education. But we think that the good drugs always declare themselves, and I think it's going to be apparent that taletrectinib offers potential benefits to patients and physicians that we think will be very attractive to them.

So I'm not going to say that we think this is going to be necessarily a rapid launch. It's hard to predict that. It's hard to convince patients and doctors, or doctors especially, to switch a therapy, but we do think that our profile is compelling enough that we are confident in the prospects of our commercial launch, but I can't say that it's going to be all up front.

Sure, and I appreciate your candid answer. Congratulations again, and good luck with the approval.

Thanks, Soumit.

(Operator Instructions) Michael Yee, Jefferies.

Hey, guys, great. Thanks, and congrats on all the progress. Looking forward to an exciting year. Two questions, maybe just on assuming approval. Can you tell us a little bit about the Expanded Access Program, whether or not there could be at least an initial bolus from people who could swap over, whether you think that there's quick formulary access, maybe just some of the things in the first six months that I know Wall Street will be hyper-focused on to suggest that, yes, we think we're going to get a bunch of patients on, whether that's expanded access or even a bolus of swappers.

And then number two is on IDH1. We're really excited about the potential for that drug. I know that you were in dialogue with trying to get an agreement to present some more data, as well as sort of meet with the FDA. And that's all sort of, in the minds of Wall Street, a bit confusing these days. So maybe just talk a little about what we should expect there in terms of the next step and how confident you are about the next data set. Thank you.

Sure. So with regard to EAP, while we can -- whether we publicize that we have an EAP, clearly because we're in the pre-approval period. We cannot really push that. I would not expect a large bolus from EAP, but we think that this launch will go well, and we are confident in it. But I wouldn't say that it's going to come from -- I wouldn't expect a large bolus from the EAP.

With regard to safusidenib, I would say that we really like the data we've seen. We've stated that our intention is to go into a pivotal study. We wouldn't have made that decision if it weren't for a very sound rationale. We think the data are compelling. We think they're differentiated. We believe the right thing to do is try to bring this drug to patients as quickly as possible. So we're trying to explore with the agency what the fastest pathway is.

So once we have some clarity on that, we'll be happy to share that. And then you'll of course have timelines and budgets and all the things that you guys need to figure out. We do think that that drug is really interesting and compelling, and we think that the data are impressive. So we're really looking forward to sharing that sometime this year, hopefully in a larger than smaller or -- I can't tell when that will be.

Got it. Thank you very much.

Thanks, Mike.

Yaron Werber, TD Cowen.

Great. Thanks so much for doing the call. We appreciate it. So a couple of questions for David, and then maybe a couple of financial questions. Maybe, David, just remind us, how many patients in the trust studies were in the US? So at least we can start thinking about those converting over.

And then secondly, on the launch metrics, the time-to-treatment initiation or testing rates, the covered reimbursement rates, how would you show sort of those as a barometer for kind of future demand? And then maybe just two financial questions. The $3 million, the $3.1 million in revenues, what was those from? And then just want to double check, your [339,840] is the share count that we should use? Thank you.

We haven't broken out specifically the US versus Asian patients. But we believe that the full data are well-balanced. We mentioned that the TRUST-I study is 100% Chinese, but the TRUST-II study is 90% non-Chinese and includes US, Canada, Western Europe. So we believe that the package is far more robust and necessary to get approval.

We have been in discussions with the agency for some time now, and we've always been pretty consistent that we're confident in approval. So I can't give you specific numbers there, but I think that the bottom line is we feel that we have a well-balanced population across multiple demographics that we think should get this drug approved in pretty much all jurisdictions. Phillippe?

Yes, for the revenue, I mean, we do have product revenue. For the revenue, especially, we share. Of course, the product we ship to our partners, for which we charge and forecast, and they give us some product revenues. And the big chunk of it is also just R&D charging, again, to our partner, and even to [ECU] and Innovent. And that's the two of these signs, actually, which are the premium for the product.

So maybe just a quick follow p on safusidenib. In terms of that Phase 2 data from Daiichi in the low-grade setting, we noticed -- I don't think there was an abstract at ASCO. Is there any sense -- which medical meeting -- is that going to come at a medical meeting? Is that going to come as a publication? Maybe help us understand.

So we're still in discussions with Daiichi on getting their full approval to release that data. So depending on when they agree to that, we'll try to put it out at the nearest meeting to that. But until -- because they haven't given us their full approval yet, it's hard for me to predict which meeting it's going to be. We'd love it to be at a bigger meeting. It's not going to be at ASCO, unfortunately; but hopefully, it could be at another big meeting in the second half of the year. We would love to put it out as soon as possible.

And Yaron, I'm sorry, I forgot to answer your question about the number of shares. You will find that in our 10-Q today, it's 340.

Yes, I assume we could use the Series A plus Series B together, right? 339,840? That would be the diluted share count?

Yes, more or less, that's [340,262]. So yes, safe.

Okay, great. Thank you.

Thanks, Yaron.

Silvan Türkcan, Citizens.

Thank you. Good afternoon and thanks for taking my questions and congrats on the progress. I just wanted to know if there's any learnings from your launch by a partner in China that you have to date and that will be appropriate for your launch here in the US. And then with respect to expanding the market, obviously, osimertinib was great, expanding the market. Since you mentioned you have Mirati sales force, KRAS was less good. Obviously, you have the benefit of an outsized duration here. It's just how exactly, what are your various steps to expand the market in ROS1? Thanks.

Yes, I think to your question, obviously, China and the US are very different markets, so we don't consider that one market will be transferable at less than to the other. What is clear when we talk about [Innovent] as we did recently in our discussion together in our steering committee, is that there is a lot of excitement in the community in China about the drug and what it brings to the patients.

These being said, the drug is not yet on the NLDL, so the dynamic of the market here is not of a reimbursed product, which obviously makes it not very comparable to what's going to happen in the US. But it's exciting to learn that doctors in China are very interested by the product.

And thank you for your question on expanding the market. We think about this all the time, and I'll say three points that we're very confident on. Number one, that we have a different drug. Number two, we have a different team, and we absolutely have a different strategy. You mentioned our team. And when we look at this team and their experience, this is not a team who hasn't been here before. Their track record of success is repeated success in equally complex markets. I spoke to that previously. So we are absolutely confident in this team and our ability to execute on the strategy that we've put together.

Thank you for taking my question.

Thank you. There are currently no other questions queued at this time. I'll turn it back over for closing remarks.

Thank you all for joining us today. We look forward to updating you with more progress. Thanks so much.