Nuvation Bio - Earnings Call - Q1 2025

Executive Summary

• Q1 2025 results showed modest partner-related revenue and a larger, planned OpEx ramp ahead of potential taletrectinib launch; revenue was $3.08M and diluted EPS was $(0.16). Versus S&P consensus, revenue materially beat while EPS was a slight miss (see Estimates Context). Values retrieved from S&P Global.*
• Strategic and regulatory setup remained on track: FDA Priority Review for taletrectinib with a June 23, 2025 PDUFA, all inspections completed, and an EAP active in the U.S..
• Balance sheet strength: $461.7M in cash, cash equivalents, and marketable securities at quarter-end; plus up to $250M in non‑dilutive financing from Sagard (royalty + debt) contingent on approval, expected to fully fund U.S. launch and pipeline progress.
• Management refrained from revenue guidance and emphasized that early launch KPI focus will be “patients on therapy,” implying Street models may need to shift from revenue to patient adoption proxies post-approval.
• Near-term stock catalyst: PDUFA decision for taletrectinib on 6/23/25; call commentary stressed potential best-in-class profile (ORR 89%, median PFS 46 months, DOR 44 months in TKI‑naive) and commercial readiness (47 oncology account managers, access infrastructure).

What Went Well and What Went Wrong

What Went Well

• Regulatory momentum and publication record: Priority Review ongoing with inspections completed; pooled TRUST-I/II data published in JCO and presented at major meetings, reinforcing differentiated efficacy and CNS activity for taletrectinib.
• Commercial readiness and access: Team in place with 47 oncology account managers; plans focused on rapid identification and initiation, patient support, and market education; NCCN guideline changes highlighted as a new tailwind.
• Balance sheet and funding visibility: $461.7M quarter-end liquidity, with Sagard up to $250M non‑dilutive financing intended to fully fund U.S. launch and pipeline toward potential profitability without additional equity raises.

“Data recently published in the Journal of Clinical Oncology … further reinforce taletrectinib’s potential to deliver a differentiated profile with strong efficacy, high CNS activity, and favorable tolerability.” — David Hung, CEO

What Went Wrong

• Operating expense step‑up ahead of launch: R&D rose to $24.6M (from $12.8M YoY); SG&A grew to $35.4M (from $7.4M YoY) on AnHeart integration and pre‑commercial build, contributing to a larger net loss of $(53.2)M.
• Sequential revenue down: Q1 revenue of $3.08M declined from Q4’s $5.71M, reflecting variability in partner- and program-related activity QoQ.
• No revenue guidance: Management is not providing revenue guidance and steered investors to non‑financial KPIs post-approval, which may complicate near-term modeling and consensus alignment.

Transcript

Operator (participant)

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. At this time, all participants are in a listen-only mode. Following the formal remarks, we will open the call for questions. 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.

JR DeVita (Executive Director of Corporate Development and Investor Relations)

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 talent directives, expected FDA approval, U.S. 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 U.S. 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.

David Hung (Founder, President and CEO)

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 in 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 6-12 months when treated with chemotherapy and/or immuno-oncology agents. First-generation ROS1 tyrosine kinase inhibitors, or TKIs, entrectinib and crizotinib, changed the treatment landscape significantly, providing an overall response rate, or ORR, of approximately 70% with a median PFS 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 therapies through the emergence of resistance mutations. 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 resistance mutations. We're also seeing consistent intracranial activity with taletrectinib, including a 77% confirmed intracranial ORR in treatment-naive 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 CNS 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 one and transient, lasting about three days. We believe taletrectinib's well-tolerated CNS profile is driven by its 11-20-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% dizziness 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 event 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.

Additionally, while diarrhea is the second most common GI side effect with taletrectinib, 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 progressed on IO chemo in six 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 I 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 data sets in the ROS1 space, including a safety database of more than 400 patients. The review of our NDA 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 the 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. 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.

With our recently announced $250 million non-dilutive 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 market. Early clinical data suggest that safusidenib may offer deeper responses in both low-grade and high-grade glioma than what has 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 a 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-drug conjugate platform, represents a completely new modality in targeted cancer therapy. We look forward to providing an update for our phase I dose escalation study in difficult-to-treat solid tumors later this year. 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 I 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?

Colleen Sjogren (Chief Commercial Officer)

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 taletrectinib quickly reaches patients. Second, maximize long-term value by leveraging taletrectinib'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 U.S.

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 U.S. 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, taletrectinib 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-month median progression-free survival, and 44-month median 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 U.S. 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 taletrectinib to them efficiently. Historically, targeted therapies with improved durability, like osimertinib in EGFR-mutated lung cancer, have not only expanded their market several-fold but also captured more than 90% market share. With taletrectinib'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 15-20-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 offers 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?

Philippe Sauvage (CFO)

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 asset, 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 build-out.

This includes personnel-related expenses tied to commercial hiring efforts, sales, market access, and operations, as well as strategic investments in medical education, care engagement, and patient support programs. Due to those investments, and as expected, our net loss for the 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 our recently announced financing agreement with Sagard Healthcare Partners, which provides up to $250 million in non-dilutive capital.

You might remember we closed the strategic transaction in March, and it includes a $150 million royalty financing triggered upon FDA approval of taletrectinib and a senior secured term loan of up to $100 million, with $50 million available immediately upon approval and an additional $50 million available at our discretion from first-year commercial sale until June 30, 2026. As we stated previously, this transaction solidifies our capital position and will, we expect, fund operations for profitability, including a full U.S. 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 U.S. 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 therapy. In rare, genetically 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 build-up but provide better efficiency and access over the long run.

This focus on new patient starts 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 underdiagnosed and undertreated. 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 build the right infrastructure, secure non-dilutive capital, and preserve 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.

David Hung (Founder, President and CEO)

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 (participant)

Thank you. At this time, we will begin the question-and-answer session. To ask a question, please press Star one on your telephone keypad.

To withdraw your question, please press Star two. Please hold while we compile the Q&A roster. The first question comes from Gregory Renza with RBC Capital Markets. You may proceed.

Gregory Renza (Senior Biotechnology Analyst)

Greg, 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 really helpful color on a potential launch and where you are with respect to the FDA proceedings. 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 TALI versus what else is out there. 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? 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.

David Hung (Founder, President and CEO)

Hi, Greg. Thanks for the questions. In our market research, it is 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. 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. 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. The reason for that was because of kind of a little bit of logistics in the way this cancer is found and diagnosed and then treated. Let's say you get a biopsy on a Monday. You could get your pathology back as quickly as Tuesday or Wednesday.

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. The old standard of care was to put them on IO chemo. 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 infusion after starting a systemic therapy like IO chemo, you had two choices. Choice number one was to continue that therapy, including maintenance. Choice number two was to switch to a ROS1 agent.

Because of choice number one, a lot of patients continued on their IO chemo and then were either lost to follow-up or progressed or elected not to pursue other therapy. We think that that is going to be changed now with the 2025 new guidelines, which state not only that if ROS1 infusion 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 ROS1 infusion now is a contraindication to IO use. I think that that's clearly, I think that's the right thing to do for patients.

If you look at the PFS of IO 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. 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. In relatively short order, we anticipate approval, as we said, either on or before the PDUFA date. That's only a few more weeks.

We'll be announcing at that point what the price will be.

Gregory Renza (Senior Biotechnology Analyst)

Yeah. That's really helpful. Appreciate the color. Maybe just a quick one on safusidenib. As you've talked about giving an update in the second half of 2025, certainly a lot of interest in this asset, in this area. Just would like you to 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.

David Hung (Founder, President and CEO)

Yeah. One of the important updates will be, first of all, the rationale for why we're moving forward. 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.

We believe these data will be particularly clear. We are going to show response rates, which we think will be of great interest to investors, patients, and physicians. We also think we are 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 are 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 will give you a glimpse at the PFS difference. We think that is exciting. Based on that data, we are in discussions with the FDA about a pivotal study for safusidenib.

We are contemplating both a low-grade and a high-grade study. Depending on our discussions, we'll give you more information on the design of those studies once we reach agreement with the agency.

Operator (participant)

Thank you. The next question comes from Kaveri Pohlman with Clear Street. You may proceed.

Kaveri Pohlman (Managing Director and Senior Equity Research Analyst)

Yeah. Good evening. Congrats on the progress, and thanks for the updates. Drawing 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 % of total addressable patient base do you anticipate reaching through your initial launch and marketing initiatives? I have a follow-up.

David Hung (Founder, President and CEO)

You know, Kaveri, we're in a competitive situation here, and we have a team that's very experienced.

We put together a strategy that we have a great deal of confidence in. We are not going to make a lot of comments on exactly what our strategy is for this launch. 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. That is what we are going to do. We cannot really comment on the specifics, but I think that over time, you will see the results of our efforts and our strategy, and we are confident that they will be positive.

Kaveri Pohlman (Managing Director and Senior Equity Research Analyst)

Got it. That is fair. I would really appreciate additional color on the comments you made about the CNS disease. You mentioned that the early-gen, first-gen drugs do not really cross the blood-brain barrier effectively. The CNS disease occurs at higher rates in late-line patients.

Do you expect taletrectinib 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 taletrectinib can prevent the CNS disease? Thanks for taking my question.

David Hung (Founder, President and CEO)

First of all, yeah, sure. Thanks, Gregory. First of all, no, our intention is to primarily push taletrectinib in the first-line setting where our PFS is 46 months and DOR is 44 months. We think that the best way to not have to deal with a brain met 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, position us well to be an upfront agent. Our second-line data are also very strong.

As you know, our response rate is 56%. Our intracranial response rate is 66%. We have robust data in the second-line setting, but the market is really a first-line market. That is where we really intend to see our drug used. 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 up front. We think that is the right position for taletrectinib to be in. We do think that the CNS profile of some drugs, we know that crizotinib does not cross the blood-brain barrier. Clearly, that is probably not—does not position it well for preventing CNS met. If you look at progression or the development of CNS mets, some of that is subsumed within a progression-free survival.

When you have a long PFS, by definition, you're not progressing either systemically or intracranially. 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 to that specifically. The fact that the DOR 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. We think that our data are strong and suggest that our drug should be used early and upfront. That's what we intend to push it hardest.

Kaveri Pohlman (Managing Director and Senior Equity Research Analyst)

Appreciate the color.

Operator (participant)

Thank you. The next question comes from Soumit Roy with Jones Research. You may proceed.

Soumit Roy (Biotech Research Analyst)

Afternoon, everyone. And congratulations, David and the team, on the progress.

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

David Hung (Founder, President and CEO)

Sure. 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. We are not going to underestimate the importance of physician education. That's a huge focus of our efforts. In fact, our medical affairs people are even out in the field talking about the ROS1 landscape, increased awareness in general about ROS1 agents. It is a rare tumor. People do not always see it a lot.

We're well aware of the importance of that. I think that it's pretty clear, though, that the way oncologists look at diseases is what's treatable. 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. That's a really important point for physicians and patients to realize. We think that our data demonstrate how treatable ROS1 cancer is with taletrectinib. 89% response rate, 46-month PFS, 44-month DOR.

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. That is 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. Fortunately, oncologists have been using TKIs for decades. The management of LFTs with TKIs is well known by oncologists. We believe that we probably do not need a lot of training in that area because it has been done with so many other agents. We think this is going to be a pretty easy drug to prescribe and a pretty easy drug for patients to take.

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. To address that, you want a drug that has a high response rate and a long durability of response. We think taletrectinib offers that. That is the platform upon which we are educating physicians and patients.

Soumit Roy (Biotech Research Analyst)

That's really helpful. One 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? It is a steady ramp, or should we think of it as an initial bulk of physicians who would be quickly adopting it, and then the growth rate will meter out?

David Hung (Founder, President and CEO)

I've been through enough drug launches to know that nothing is as quick as you want in the early stages. I would say that we've always said that physician adoption is always slower than you'd like. It takes education. We think that the good drugs always declare themselves. 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. 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. We do think that our profile is compelling enough that we are confident in the prospects of our commercial launch. I can't say that it's going to be all upfront.

Soumit Roy (Biotech Research Analyst)

Fair enough.

I appreciate your candidacy. Congratulations again and good luck with the approval.

David Hung (Founder, President and CEO)

Thanks, Soumit.

Operator (participant)

Thank you. As a quick reminder, if you'd like to ask a question, please press star one. The following comes from Michael Yee with Jefferies. You may proceed.

Michael Yee (Managing Director)

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, yeah, we think we're going to get a bunch of patients on, whether that's expanded access or even a bolus of swappers.

Number two is on IDH1. We're really excited about the potential for that drug. I know that you are in dialogue with trying to get an agreement to present some more data as well as sort of meet with the FDA. That is all sort of in the minds of Wall Street, a bit confusing these days. 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.

David Hung (Founder, President and CEO)

Sure. With regard to EAP, while we can—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.

I would not say that it is going to come from—I would not expect a large bolus from the EAP. With regard to safusidenib, I would say that we really like the data we have seen. We have stated that our intention is to go into a pivotal study. We would not have made that decision if it were not for a very sound rationale. We think the data are compelling. We think they are differentiated. We believe the right thing to do is to try to bring this drug to patients as quickly as possible. We are trying to explore with the agency what the fastest pathway is. Once we have some clarity on that, we will be happy to share that. You will, of course, have timelines and budgets and all the things that you need to figure out. We do think that that drug is really interesting and compelling.

We think that the data are impressive. We are really looking forward to sharing that sometime this year, hopefully in a larger than smaller form. I cannot tell when that will be.

Michael Yee (Managing Director)

Got it. Thank you very much.

David Hung (Founder, President and CEO)

Thanks, Mike.

Operator (participant)

Thank you. The next question comes from Yaron Werber with TD Cowen. You may proceed.

Yaron Werber (Managing Director and Senior Biotechnology Analyst)

Great. Thanks so much for doing the call. We appreciate it. 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 U.S. so at least we can start thinking about those converting over? Secondly, on the launch metrics, the time to treatment initiation or testing rates, the COVID reimbursement rates, how would you show those as a barometer for kind of future demand?

Maybe just two financial questions. The $3 million, the $3.1 million in revenues, what was those from? I just want to double-check your 339,840 is the share count that we should use. Thank you.

David Hung (Founder, President and CEO)

We have not broken out specifically the U.S. 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-2 study is 90% non-Chinese and includes U.S., Canada, Western Europe. We believe that the package is far more robust than necessary to get approval. We have been in discussions with the agency for some time now, and we have always been pretty consistent that we are confident in approval.

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. Philippe?

Philippe Sauvage (CFO)

Yeah. For the revenue, I mean, you do have product revenue for the revenue, especially for the product we ship to our partners, for which we charge them for costs and they give us some product revenues. A big chunk of it is also just R&D charging against our partner, Nippon Kayaku and Innovent. The two of these lines are clearly what drives the $3 million for the product.

Yaron Werber (Managing Director and Senior Biotechnology Analyst)

Maybe just a quick follow-up on safusidenib. In terms of that phase II data from the HE in the low-grade setting, we noticed I don't think there's 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.

David Hung (Founder, President and CEO)

We are still in discussions with the HE on getting their full approval to release that data. Depending on when they agree to that, we will try to put it out at the nearest meeting to that. Because they have not given us their full approval yet, it is hard for me to predict which meeting it is going to be. Clearly, we would love it to be at a bigger meeting. It is not going to be at ASCO, unfortunately. 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.

Philippe Sauvage (CFO)

Yeron, I am sorry, I forgot to answer your question about the number of shares.

David Hung (Founder, President and CEO)

You will find that in our phase II today, it's 340.

Yaron Werber (Managing Director and Senior Biotechnology Analyst)

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

Philippe Sauvage (CFO)

Yeah. Yeah. More or less. That's 340 to 62. So yeah, it's the same.

Yaron Werber (Managing Director and Senior Biotechnology Analyst)

Okay. Great. Thank you.

David Hung (Founder, President and CEO)

Thanks, Yaron.

Operator (participant)

Thank you. The next question comes from Silvan Türkcan with Citizens. You may proceed.

Silvan Türkcan (Senior Research Analyst)

Hey, thanks. Good afternoon. And thanks for taking my questions and congrats on the progress. I just want to know if there's any learnings from your launch by your partner in China that you have to date and that would be appropriate for your launch here in the U.S. And then with respect to expanding the market, obviously, osimertinib was great at expanding the market. Since you mentioned you have a Mirati Salesforce, KRAS was less good.

Obviously, you have the benefit of an outsized duration here. It's just how exactly what are your variational steps to expand the market in ROS1? Thanks.

Philippe Sauvage (CFO)

Yeah. I think to your question, obviously, China and the U.S. are very different markets. We don't consider that one market will be transferable as lessons with the other. What is clear when we talk to our partner 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. This being said, the drug is not yet on the NRDL. The dynamic of the market here is not a reimbursed product, which obviously makes it not very comparable to what's going to happen in the U.S.

David Hung (Founder, President and CEO)

Exciting to learn that doctors in China are very interested by the product.

Colleen Sjogren (Chief Commercial Officer)

Thank you for your question on expanding the market. We think about this all the time. 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. 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. We are absolutely confident in this team and our ability to execute on the strategy that we've put together.

Silvan Türkcan (Senior Research Analyst)

All right. Thank you for taking my questions.

Operator (participant)

Thank you. There are currently no other questions queued at this time.

I'll turn it back over for closing remarks.

David Hung (Founder, President and CEO)

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

Operator (participant)

This concludes today's conference call. Thank you for your participation. You may now disconnect your line.