Coherus Oncology, Inc.

Good day and thank you for standing by. Welcome to the Q4 and full year 2025 Coherus Oncology Inc. Earnings Conference Call. At this time, all participants are in a listen-only mode. After the speaker's presentation, there will be a question and answer session. To ask a question during the session, you will need to press star 1, 1 on your telephone. You will then hear an automated message advising your hand is raised. To withdraw your question, please press star 1, 1 again. Please be advised that today's conference is being recorded. I would now like to hand the conference over to your speaker today, Carrie Graham. Please go ahead.

Thank you, Heidi. Good afternoon, and welcome to Hill-Harris Oncology's fourth quarter and 2025 year-end earnings conference call. Joining me today to discuss our results are Denny Lansfair, Chief Executive Officer of Hill-Harris, Dr. Teresa Lavallee, Chief Scientific and Development Officer, Dr. Rosh Gaius, Chief Medical Officer, Samira Gorizoker, Chief Commercial Officer, and Brian McMichael, Chief Financial Officer. Before we get started, I would like to remind you that today's call includes forward-looking statements regarding O'Hara's current expectations about future events. Actual results may vary significantly, and we undertake no duty to update or revise any forward-looking statements. Please see the press release that we issued today and our annual report on Form 10-A for more information on risks and uncertainties. And now I'll turn the call over to Denny.

Thank you, Carrie, and thank you all for joining us today on our Q4 2025 call and our 2025 Annual Summary to Investors. This was a year in which we completed our strategic transformation to an innovative oncology company focused on overcoming immune resistance in cancer. This transition was initiated in September of 2023 with the acquisition of Service Oncology, a transaction through which we acquired two very promising assets, Tagnoketuk, a potentially best-in-class CCRA Treg cell depleter, and Casdozo-Ketuk, a first-in-class anti-IL-27 inhibitor. Over the subsequent 18 months or so, we have successfully divested our biosimilar franchise, putting $250 million in the balance sheet, reduced our $480 million secured in convertible debt by over 90% to $38.8 million, reduced our headcount and expenses, sharply refocusing the company. Building on our past successes, we enhanced our team as well as our board of directors to meet the new mission. We also initiated an elegantly efficient clinical development program, cross our pipeline products in combination with Lactorsi as well as partners' products, potentially enabling the initiation of a registration trial in 2027. You will hear details of our clinical strategy and progress from Dr. Raj Dias, our Chief Medical Officer. We also launched our first innovative oncology commercial product, Lactorsi, in 2024. a next-gen PD-1 inhibitor as the only available and approved product for recurrent, locally advanced, or metastatic nasopharyngeal carcinoma in the U.S., a $250 million addressable market. We have made very rapid progress on our transformation in the context of our products, our development strategies, and our dealmaking. Let me provide you then with a strategic lens through which to view the company going forward. First, to our financial strategy. Lactorsi plays a foundational role as both a revenue generator in the context of MPC and revenue multiplier in the context of combination therapy with our pipeline assets. I believe Coheris is unique as a clinical stage small biotech company because we have a commercial asset with growing sales in a rare disease space with no FDA approved competing products on the horizon, outstanding six year survival data, and we are positioned at the top of the NCCN guidelines for recurrent metastatic MPC. This gives us confidence in Lactori's continued growth. And as you will hear from my colleagues, Lactorsi more than doubled its sales in 2025 over 2024. We view Lactorsi as reliable, growing, non-dilutive revenue source and financing vehicle to support operations while we advance the promising pipeline, increasing in value along the way. That's its fundamental role. Our expected trajectory achieves peak market share sometime in 2028, corresponding to $175 million in annualized revenues, or about 70% market share of the $250 million market total. You will hear more about that from Samira Gorogakar, our Chief Commercial Officer, in just a moment. But let me make some key observations for you. First, while $175 million a year revenue may appear modest, It's very important to us, as it's more than sufficient to fund our quarter burn and overall headcount, not including development costs or other strenuous items like stock option expense. Secondly, along the way, once we achieve about 15 or 16 million a quarter in sales, the commercial effort will have paid for itself and start contributing to covering the company's overall SG&A. We believe this will happen sometime in 2026. Lastly, once we achieve approximately $30 to $35 million per quarter, our quarter burn, which does not include clinical trial expense, which are somewhat elastic and discretionary, will be paid for by such revenues. We believe this will happen sometime in 2027. We recently raised about $50 million, which included support for the commercial effort, so we can get to that $175 million run rate faster. Also, we deemed it strategically prudent to further invest in the Tegno Keto clinical program, as the Treg field is increasingly competitive with some expected data readouts by other parties this year. Given the recent raise in our financial plans, we believe we are certainly sufficiently funded through Keto Day Rayouts in 26 and on into 2027. My Chief Financial Officer, Brian McMichael, will provide more color in just a moment. Now let me turn to our product strategy. In addition to Lactorsi, we have two well-positioned product candidates, both showing promising early clinical results. Their differentiated key attributes provide risk diversification for investors. On the one hand, we see Pagmo Ketog as potentially a best-in-class in a competitive space with broad clinical therapeutic utility and very promising biology. In a moment, Dr. Lavalle will provide you some additional scientific insights on its mechanism of action and combination therapy considerations. The breadth of potential utility mandates broader early stage clinical investigation, so we have several trials underway. We intend to exploit this potential broad utility by not just pursuing proprietary combinations, but also by joining with partners. Our objective to be the Treg depleter of choice across cancer treatments and modality. On the other hand, we also believe that Caslodoketog is the first and only in class, and with impressive translational data sharply focused on barrier tissue cancers, such as liver and lung. Consistent with that data, Caslodoketog demonstrated highly durable, complete response rates in first-line hepatocellular carcinoma. A follow-on trial is underway, and Dr. Dias will describe this to you subsequently. Lastly, let me talk about the deals. Coherence has a strong track record of creating value for investors with strategic transactions, including acquisitions, divestitures, and product partnerships. We believe that this demonstrated competency is the key to unlocking latent value, opening up new markets, and creating synergies therapeutically and globally. As an example, I'll point out that the J&J collaboration is important for a number of reasons. First, it stands as the first example of our objective to be the T-reg depletor of choice broadly across companies and treatment modalities. More such relationships are in development. Secondly, it stands as validation of our high scientific competency and the quality of our asset. And lastly, it shows that we have constructed a strategy that is both executable and potentially accretive to shareholders. As you know, we have global rights to TACNO-KTUG and CASDO-SO-KTUG, and we look forward to XUS partnership opportunities as the data readouts emerge this year and next. We believe that it is reasonable to expect such partners will provide upfront payments and contribute their share to significantly offset pivotal registration trial costs as they carry the expenses for the patients in their territories. This will leave us responsible for a minority share of overall cost, which we expect to be manageable. In closing, let me summarize for you. Over the last 18 months or so, we've made substantial progress on putting together a highly executable plan comprised of integrated financial, product, and transaction strategies, positioning us to provide significant investor value accretion. Let me now turn the call over to Dr. Teresa Valle, our Chief Scientific and Development Officer, who will provide some greater insights into the use of T-regulatory cell depletion as a therapeutic approach to overcome immune resistance in cancer. Teresa?

Thank you, Denny, and good afternoon. Today, I will focus my remarks on Tegmo-Ketog, our potent and selective cytolytic anti-CCR8 antibody, its mechanism of action, and the potential for its therapeutic use. As background, T regulatory cells, or Tregs, are an increasingly recognized important cell type for the treatment of cancer. As tumors exploit Tregs to evade the immune system, this has the consequence of promoting cancer growth and metastasis. And higher levels of Tregs are associated with poor prognosis in many different tumor types, including head and neck, lung, breast, colon, prostate, stomach cancers. The other problem with Tregs is that Tregs are not only associated with poor prognosis, but also can be upregulated with anti-cancer treatments. The reason I highlight this is, as drugs that deplete Tregs, may be able to improve patient outcomes for many different anticancer treatments. TAGMO-KETUG targets CCR8, which is preferentially expressed T-rays in tumors. We recently published the characterization of TAGMO-KETUG pharmacology and molecular cancer therapeutics. What we have shown in the clinic with TAGMO-KETUG that treatment leads to two important changes in the tumor immune makeup. First, the selective and significant depletion of CCR8 positive Tregs in tumors. And second, a massive increase in CD8 T cells. These data show that TAGMO KeyTag both removes the suppressor cell in tumors and leads to an increase in T cells that can kill the cancer cells. However, the CCR8 class of drugs has shown limited single-agent activity, which raises the question of what do these T cells need to activate them to kill the tumor? We are investigating two different approaches for T cell activation. PD-1 antibodies are one way to activate killer T cells. Over the last decade of using these drugs, we have learned the mechanism of PD-1 inhibitors is to reinvigorate T cells that have previously tried to attack the tumor but are now exhausted. We are trying to understand if the T cells observed in the tumors following TAGMO-T tug treatment our antigen-experienced exhausted T-cells, or possibly naive T-cells. Rosh will describe in more detail our TAGMO-KETA clinical studies evaluating treatment with toropalimab, our PD-1 antibody. The results of our Phase I study include a partial response in a fourth-line head and neck cancer patient who had progressed on prior PD-1 therapy. Since Tagmo-Ketad added to toropalimab rescued the prior PD-1 failed response, this exciting data demonstrated that CCR8-positive Tregs were a primary mechanism of resistance. Our ongoing expansion cohort in head and neck cancer is designed to answer if CCR8-positive Tregs are a primary PD-1 resistance mechanism in this second-line patient population. The other approach we are investigating for T cell activation following TAGMO-KETOG treatment is the direct activation of the T cell receptor complex by simulating a protein called CD3. This allows for the activation of naive T cells. Many T-cell engagers or TCEs are bispecific antibodies that bind a tumor protein on one end and CD3 on T-cells on the other end. TCEs lead to redirected T-cell killing of the tumor and have success in hematological malignancies, but limited success so far in solid tumors. Data support there are two main issues in solid tumors leading to modest TCE activity. A low density of T cells in the tumors for the molecule to bind both the tumor and the T cell in close proximity. And secondly, Treg presence and also activation leading to suppressing T cell response. We are pleased to have announced the agreement with Johnson & Johnson to study the combination of Tagmo-Ketog, a Treg depleting antibody, with Pazritamig, a prostate-specific TCE binding to KLK2 on prostate tumors. With the advancement of this combination study, Tagmo-Ketog becomes the first CCR8 antibody in prostate cancer, and the first CCR8 antibody in combination with the TCE. And coherence oncology continues to lead the science for the CCR8 class of drugs. As I indicated earlier, Tregs are known to limit cancer therapy, and Tegmo-Ketog has now shown it is a targeted therapeutic approach to deplete Tregs and change the immune balance by increasing T cells in tumors. Importantly, all immune-activating agents, immune checkpoint inhibitors like PD-1 inhibitors and TCEs, increase the number of Tregs in tumors, as do most anti-cancer treatments. For example, a recently published study showed that androgen receptor deprivation therapy increases Tregs in prostate cancer. And there is a number of scientific reports showing that radiation, chemotherapy, targeted therapies, angiogenesis inhibitors also increase Tregs and tumors. And this associates with worse outcomes for patients. We believe that there is broad potential for Tagmo Ketone to be used in combination with other therapies as a cancer treatment. And we are excited that Pazritamig-Tagmo-Ketog combination is the first with a partner company. And of course, we continue to explore novel combinations with other partners. With that, I'll turn it over to Dr. Diaz, who will further describe the clinical development. Raj?

Thank you, Teresa, and good afternoon, everyone. I'm pleased with the continued progress of our multi-regional clinical development program for both Tagmo-Ketog and Kazdoza-Ketog. Programs with both molecules address areas of clear, unmet medical need in very intentionally designed clinical studies, which are supported by strong scientific and clinical rationale. And we remain on track for initial data readouts from mid-26 onwards, as we've previously communicated. Let me now take a few minutes to highlight each program individually. Firstly, Tagma-Ketog, our highly selective CCR8 phytolytic antibody, for which we're currently running two protocols in what we've named our TregCheck program. The first protocol in a second line head and neck squamous cell population builds upon the exciting data we presented at AACR 2025 where we showed data demonstrating clear tumor remodeling with tagma monotherapy with depletion of CCR8 positive Tregs accompanied by profound increase in the CD8 positive T cells consistent with a much more cytotoxic tumor microenvironment. As you've just heard, combinations facilitate activation of these ingressed T cells. And in the same study, when toripalamab was added, we showed a partial response in a fourth-line head and neck squamous cell patient refractory to prior PD-1 therapy. Our current head and neck squamous cell approach looks at 40 patients in two doses of TAGMO in combination with tori and asks the question as to whether TAGMO is able to reverse PD-L1 resistance in the second-line population. We continue to anticipate initial data mid-year 26. Our second protocol is an umbrella protocol with four targeted tumor types in cohorts A to D, including second-line upper GI adenocarcinoma, second-line ESCC, first-line ESCC, and fourth-line plus colorectal carcinoma, respectively. The upper GI adeno cohort is a second-line cohort including gastric adeno, GEJ, and esophageal adenocarcinoma. also broadly asking the question of whether TAGMO is able to reverse PD-L1 resistance. As a reminder, this is a tumor type that has shown proof of principle of the class, with Lenovo Medicines showing data for their CCRA in combination with our PD-L1 inhibitory at ASCO24, with an encouraging overall response rate in a second-line plus gastric population. Our upper GI adeno cohort looks at two doses of TAGMO in combination with TORI in 40 subjects. And again, we continue to anticipate early data around the middle of this year. Our esophageal squamous cell cohorts take advantage of the activity of TORI irrespective of PD-L1 levels, which is perhaps most marked in this type, and which forms the basis of TORI's approval as the only EU-approved PD-1 for esophageal squamous cell irrespective of PD-L1 status. Cohort B is a second line esophageal cohort with two doses of TAGMO in combination with TORI. And cohort C looks at first line esophageal population with TAGMO in combination with both TORI and chemo with the explicit intention of developing safety data in combination with chemo, which could allow us to explore earlier treatment paradigms. We anticipate data in the second half of this year for these two cohorts. Cohort D looks at TAGMO in combination with TORI in the fourth line plus colorectal carcinoma population, an area which constitutes an increasing public health issue, particularly in younger age groups. As a reminder, the CCR8 field has shown some responses in CRC, and our approach looks at 20 patients with an initial focus on the non-liver mess population before moving on to expansion into the liver mess population. We started the CRC cohort in the second half of last year, and so we anticipate early data late this year, or perhaps even early 27. Finally, we're very excited to start the TAGMO-PASRI combination cohort, which, as you heard from Teresa, represents both the first TCE-CCR8 combination study as well as the first in CRPC, and is a very rational combination based on the mechanism of action of both agents. This combination aims to build upon the PASRI data shown at ASCO 2025, demonstrating and encouraging PSA50 in a late-line metastatic castrate-resistant prostate cancer population, supporting advancement into pivotal studies. Metastatic CRPC is considered an immunologically cold tumor and has limited treatment options once patients get to later lines of therapy. Our initial approach will be in a third-line plus population, looking at a safety cohort and additional PSA50 endpoints, which we anticipate starting in the second half of this year. Moving on now to Casdoza-Ketoc, our first-in-class antibody targeting IL-27, a context-dependent immunosuppressive cytokine, particularly relevant in tumors such as hepatocellular carcinoma and non-small cell lung cancer. Our recently named Catalyze program focuses initially in first-line HTC, and builds upon the very encouraging data presented at ASCO GI 2025, where we demonstrated that the addition of Casdozo to the current standard of care, Atizo and Bev, provided a 38% overall response rate, and perhaps more importantly, a complete response rate of 17%, both of which compare very favorably to historical benchmarks with activity irrespective of etiology and a strong durability of response with a favorable safety profile. Our current ongoing study swaps out Atizo for our PD-1 Tori and includes 72 patients in three arms, that is, two dose levels of CasDozo in combination with ToriBev versus ToriBev alone, and is designed with three aims. Firstly, to further characterize efficacy and safety, as well as address FDA's Project Optimus and address contribution of components as we move through the development pathway. This trial continues to accrue well globally, and we remain on track for initial data around mid-year 26. As a reminder, the previous study demonstrated an increase in response rate and a deepening of response with time, and so we do anticipate the same with the ongoing program. In summary, our TREC-CHECK program with TAGMO in several targeted cohorts is intended to inform us in which of these specific tumor types we may see a signal to take forward into broader programs. And our CATALYZE program with CasDozo is asking the question of whether we can improve on the current standard of care with the addition of CasDozo. The two key determinants of exact timing of data availability are, firstly, the numbers of patients accrued to study, and secondly, the numbers of scans that may be required to show activity, which will differ by program. We remain on track to show initial data mid-year 26 and beyond, and will continue to provide updates on progress. With that, I'll hand it over to Samir. Samir?

Thank you, Raj. We're happy to report that Loftrosi net revenue grew to $40.8 million for full year 2025, versus 19.1 million in 2024, representing 113% growth year over year. As we have stated previously, going forward, we expect average quarter over quarter demand growth of 10 to 15%. Similar to 2025, we will see some variability in individual quarters due to patient flow and other factors. For Q4, net revenue was $12.4 million and 11% growth over Q3. We saw strong quarter-over-quarter demand growth of 15.5% in Q4. The delta between net revenue and demand growth was driven by wholesaler inventory declines in Q4 versus Q3. Demand growth was driven by new patient starts in both new and existing accounts, and we saw an 11% increase in purchasing accounts indicating continued increase in breadth of use. While we're happy with that 2025 growth, there remains significant opportunity, especially in the community segment, where use of chemo-only and off-label IO persists. As you will recall, the NCCN guidelines for NPC were updated late in 2024, placing Loctorsi as the only preferred treatment for recurrent and metastatic NPCs. These guidelines serve as a stimulus for Lactrosy growth in 2025, and we remain focused on driving education on the guidelines and our superior overall survival versus chemotherapy alone. That brings me to the exciting and game-changing six-year long-term overall survival data that was presented at ESMO Asia in December. This new data shows that patients on Lactrosy plus chemo live for almost 65 months or over five years. In contrast, chemo-only patients live for less than three years. That is a two-and-a-half years of additional survival benefit for lactosey patients. With this data, we believe that no patient should be receiving chemo alone for NPC, a belief that is shared by a vast majority of KOLs. Our primary focus is thus on educating all target oncologists on this new survival data. We're pulling all stops to get this game-changing data in front of physicians. Our sales team has been fully trained and is focused on educating physicians as we speak. On the multi-channel side, we're taking a multi-pronged approach with several tactics, including KOL educational videos, short messages, and emails that are being delivered to target physicians. We're also making significant investments into CRM technology platform and data enhancements to raise our rare disease execution using advanced analytics. We have doubled our investment to purchase additional claims data and patient alerts data. This provides us visibility into almost 70% of all U.S. claims, which are then used to alert our sales team on real-time patient opportunities. Additionally, we have expanded our field footprint to reach more physicians. While our field team focuses on Tier 1 or high-value targets, NPC being a rare disease, patients can present at any oncology office across the country. We are thus expanding our reach by activating a remote sales team that will reach Tier 2 physicians while the field team focuses on Tier 1 targets. There's also a sizable NPC opportunity in the Veterans Affairs hospitals. The VA hospitals are typically hard to access. So we've engaged a specialized team of contract representatives, all of whom have extensive experience selling in the VA. In summary, we remain confident in meeting our goal of achieving a dominant share in the NPC market with peak share expected in 2028. With a profound survival advantage that we see in the six-year long-term data, our entire commercial organization remains committed to ensuring that no patient misses the opportunity to live longer with Loctorsi. With that, I'll now pass the call to Brian McMichael, our Chief Financial Officer.

Thank you, Samir, and good afternoon, everyone. I'll start with a review of the company's financial position at the end of the year and results for Q4. Then I will provide additional insights into how our balance sheet has evolved and some forward-looking color. As mentioned by Denny, over 2024 and 2025, we decreased the principal balance of our term and convertible debt by over 90%, from a high of $480 million to $38.8 million at year-end 2025. This resulted in a significant reduction of interest costs, which I will cover later. This also extended our earliest debt maturity to May 2029. Headcount decreased from about 228 at the end of 2024 to about 147 at the end of 2025. An approximate 35% reduction. Some of the most significant changes for Q4 include the reduction of legacy liabilities associated with the divested businesses. Specifically, accrued rebates, fees, and reserves, which comprise mostly legacy product liabilities, total $30 million at December 31st. This is less than half of the $67 million balance one quarter earlier. The transition of commercial contracts to accord was mostly complete at the beginning of Q4. This initiated the wind down of TSA assets and liabilities. Substantially, all of the TSA receivables were collected in Q4, bringing the balance from $241 million at the start of the quarter to less than $1 million at year end. The cash collected has been used to reduce TSA liabilities from $254 million at the start of Q4 to $65 million at year end. We expect the remainder of these legacy business liabilities to be paid down in the coming quarters in a front-weighted fashion. In addition, let me remind you that we are eligible to receive two earn-out sales milestones of $37.5 million each. The criteria to earn these milestones is based on four consecutive quarters of UDEMICA sales starting in Q3 2025. $300 million within five quarters or through Q3 2026 for the first $37.5 million milestone, and $350 million within seven quarters or through Q1 2027 for the second milestone. With two quarters of sales relative to the earn-out term behind us, we believe we are favorably positioned to earn these payments and will keep you updated. Samir covered in detail OCTORZI net revenues year-over-year growth and the additional investments in commercial infrastructure to expand sales that we are making. We expect to provide full-year 2026 revenue guidance on our earnings call in August. Let me now turn to OpEx. With Q4 falling largely in line with the trends we saw throughout 2025, specifically, FCNA expenses from continuing operations decreased to $23.6 million down from $29.6 million in Q4 last year. It's important to note that this represents the fourth consecutive quarter that these expenses were flat or down as we completed the transformation of the business. The decreases are primarily due to reduced headcount, exiting biosimilars, and spending discipline. R&D expenses from continuing operations in Q4 were $31 million as compared to $20.8 million in Q4 2024. In contrast to SG&A, R&D expenses slightly increased every quarter in 2025 as we invested in Coheris' promising pipeline. Of course, reduction of debt has resulted in significant reduction in cash paid for interest. This relates to borrowings reflected in both continuing and discontinued operations and was $9.9 million in 2025. This reflects a savings of greater than $15 million over the $25.4 million paid in 2024 and underscores the benefit from the paydowns of debt in 2024 and 2025. We had cash, cash equivalents and investments of $172.1 million at year end. As you know, we recently raised capital, including a $50 million follow-on offering last month. Use of these funds include, first, investments to support the significant upside potential of the pipeline. This includes additional indications for Tegno T-TUG as Treg depletion has emerged as a very important MOA in cancer therapy. Recent examples include our Phase IIa CRC study, as well as the anticipated start of the combination study with J&J in metastatic prostate cancer. Second, we are making additional investments in our commercial footprint and capabilities to pursue the $250 million commercial opportunity presented in Lactorsi and MPC as covered by Samir. Denny discussed how our growing Locktorzy sales will cover more and more costs in the coming years. To add some color, at the point that our commercial effort is paying for itself, we mean that Locktorzy sales will cover costs, royalties, and cash costs of the sales force. When revenues cover core burn, we're referring to these commercial efforts plus other cash costs other than those directly related to clinical trials. With that, I will hand the call back over to Denny.

Thank you, Brian. We're pleased we'll have progress in 2025, having doubled Lactorsi sales while completing the transformation from a biosimilar company to an innovative oncology company focused on overcoming immune resistance in cancer. We're particularly pleased that at the same time, we're able to reduce overall debt by over 90% since its peak in 2024 to just $38.8 million. at the end of 2025. We are now strategically well positioned with growing revenues from our fine notional PD-1 inhibitor, deal opportunities across the portfolio and geographies, and two promising pipeline candidates with multiple 2026 clinical readouts. Operator, we're ready to take the questions.

Thank you. As a reminder, if you wish to ask a question, please press star 1, 1 on your telephone and wait for your name to be announced. To withdraw your question, please press star 1, 1 again. We will take our first question. And the first question comes from the line of Jay Olson from Oppenheimer. Please go ahead. Your line is open.

Oh, hey, guys. Congrats on the progress and thank you for taking the questions. We had a couple of questions on Loctorsi. Can you please provide some more color on the dynamic between new patient starts and repeat patients in 2025 and then how you anticipate that balance to shift throughout the course of 2026? And also, if you could talk about the promotional sensitivity of Loctorsi and any details in the sort of commercial infrastructure investments that you're planning to make this year, such as increased field force, and then I had a follow-up on TAGMO if I could.

Thank you. Thank you for your question, Jay. I'll let Samir address the issue on the new versus repeat patients and then move on. Go ahead, Samir.

Yeah, thank you for the question, Jay. So regarding new versus existing patients, in 2025, approximately 25% of our business came from new patients and the rest came from continuing patients. And as you mentioned, what does that look like in the future? I think that shift, that mix will shift slightly more towards new patients because we have a lot of opportunity to grow into new patients. But the existing patients will always remain a strong base of our business because over time we expect the duration of therapy to keep increasing as well. Samir, can you address Jay's question regarding the promotional sensitivity of the product? Sure. Regarding promotional sensitivity, Loctorsi is extremely promotion sensitive because our challenge is that physicians in the community, they usually see 10 to 15 different cancer types and they don't see Loctorsi. They see maybe one or two NPC patients in a given year. So they have to be continuously reminded about Loctorsi and the benefits of Loctorsi. So we have to continuously be in those doctor's offices to remind them. But I'll say this, when we do promote Loctrosy to a physician, when we present the efficacy data, almost always we get complete buy-in about using Loctrosy for their appropriation. So again, highly promotion sensitive, and we see a lot of opportunity to drive further growth. Does that answer your question, Jay?

Yeah, and I guess maybe just any details you could provide on the additional investments in commercial infrastructure. Would that include field force expansion?

Yeah, so we did do a modest Salesforce expansion about a quarter ago that we announced. We did a 15% expansion in the live Salesforce. Now we're adding about four inside sales representatives to expand our reach into Tier 2 targets. As I mentioned in my prepared remarks, we're also adding a VA-targeted contract Salesforce to focus on the Veterans Affairs business. So that's the expansion we've done in a very targeted and focused manner.

The other area of investments, Jay, is our information technology infrastructure. Because this is a rare disease, we feel that we need to make all efforts to capture as many of the patients as we can. Last year, we captured about 30-35% of the diagnosis code alerts. This year, we've expanded that to about 65-70%. We have also made investments in our display technology for the dashboards for the sales team, and then further, as Samir just alluded to, we have the inside sales force, which is also organizing and pursuing these alerts.

Great, thank you.

I would just make one closing remark. We believe all these are appropriate in the context of driving to the potential 175 million annualized sales per year. which we think is important for us to do as soon as possible.

Super helpful. Thank you for those details. And I could ask one more question on TAGMO. Can you just talk about any plans for exploring a triple combination? I know J&J just reported phase one combo data for Pazritimib and Dosataxel. How are you thinking about adding TAGMO into that for a triple combo in prostate cancer? Dr. LaValley?

Yeah, no, I think that maximizing patient benefit and CRPC is what we're looking for. So, clearly, watching the results of those studies. But I think we'll take the first step, which is the prudent step of putting the two drugs together to see what the contribution of effect is, the safety, the efficacy, and then if it's possible to move up into earlier lines through other combinations that would be of interest.

Great. Thank you so much for taking all the questions.

Thank you.

Thank you. Your next question comes from the line of Mike Nedelkovich from TD Cohen. Please go ahead. Your line is open.

Hi. Thanks for the questions. I have two. My first is on . I believe the frontline HCC trial is randomized but not blinded, so I'm curious if you're tracking responses, and if so, is what you're seeing giving you more or less confidence in Kesdozo's outlook? That's my first question, and then my second question relates to TAGNO-Ketog. You have a wealth of data coming mid this year in various tumor types, so I'm just curious how you're planning to disclose those data. Will we get press releases, kind of indication by indication, one lump release of data across a solid tumor trial? How do you plan to disclose this data? Thank you.

Thanks, Mike. I'll let Dr. Dias take those two questions for you. Brash, would you like to answer the CAS-DOZO trial and then the tag-load data questions?

Sure. Hi, Mike. Thanks for the question. So in response to your first question on CAS-DOZO, so obviously these are ongoing trials. These are open labels, but obviously because they're ongoing trials, we will report them when they are mature. What I will remind you is that for the previous ATISO, BEV, CASDOZO study, you know, I outlined the top line results in my prepared remarks. We did see a maturation of data with time in terms of an increase in response rate and a deepening of the response. So again, CASDOZO ongoing study, so no further comments at this stage on that. In terms of the TAGMO question, Your question is essentially, how will we be reporting them? So, you know, again, as I said in my prepared remarks, there are really two determinants of data availability, the numbers of patients and then the numbers of scans. These will differ by the different tumor types and the different programs. And what that essentially means is that it's not easy to predict the exact timing, right? So fundamentally, there are two scenarios. Either the timing aligns to the submission deadlines for Congress or it doesn't. If it's a former, we will release it at a Congress. If it doesn't, we will essentially release by corporate disclosure. I'll just remind you that we have, we do have like a track record of releasing data as it becomes available. I'll refer you to, you know, the AACR data last year. So that would be our kind of high-level plan.

Great. Thank you so much. Thanks, Deng.

Thank you. Your next question comes from the line of Colleen Clissy from Baird. Please go ahead. Your line is open.

Hi. Good afternoon. Congrats on all the progress. Thanks for taking our questions. Maybe a follow-up on the Casdozo Frontline HTC study to start. Understanding those data will continue to mature over time, but can you give us a sense of, you know, what you think that maturation timeline is and how many of those patients that you'll report in this initial readout will be in that, you know, mature window? And is there a bar at this kind of early readout that you'd be hoping to set?

Yeah, so let me unpack that a little bit. So your first question, in terms of, you know, in terms of what we will be expecting, you know, what we'd want to do is really, you know, have an overall response rate over what we saw, you know, previously in terms of the current standard of care. I'll remind you that was around 30% for the Atizobev alone combination. The maturation time period for our previous study was somewhere between 6 to 12 months, right? So there were several different data cuts, and over those three data cuts, over that kind of, you know, six, nine, 12-month period, there was an increase in response rate and a deepening of the response. So that's really, again, what we would expect. In terms of the numbers of patients and what data we will be likely to report, that's a bit of a tough one to comment on exactly, primarily because of what I said in my prepared remarks, right? There are two determinants. It's how patients are accrued, but also the number of scans that were reported out. So we will continue to report that out as we know. What I will say is that I think we'll have enough patients with enough scans to give an indication of early activity around mid-year timeframe, as we've communicated previously.

Great. That's helpful. Thank you. And then if you could just kind of walk us through what you're viewing as some of the important updates on the competitive front for CCR8 this year and how that might impact your development strategy going forward.

Oh, thanks for the question, Colleen. We'll let Dr. LaVallee address that. Trista, any comments on the competitive dynamic in the CCR8 space?

Yeah. I mean, I think we expect to see the bookends of more data disclosures would be the positive and seeing updates from the programs, particularly from some of the big players that have upwards close to 1,000 patients on their study. So we would anticipate, I mean, what I'll note for BMS is that they and the last two JP Morgans have had CCR8 on their launch map by the end of the decade. a data disclosure soon would be there. And then we may see other programs being parked because of molecule issues.

Colleen, one additional point that I could... Colleen, just one additional point I wanted to also mention in terms of data availability. Obviously, you know, I've said this before and I'll repeat it, we are not just looking at ORR alone. You know, durability is important, safety is important, and, you know, overall clinical benefit rate is important. So it's really that kind of totality of data that we'll be looking at as we move through the program. Thank you, Colleen.

And then last one, if I can, just congrats again on the recent J&J deal. Just thinking about what for the next BD deals, what you might find most attractive for TAGMO. Would you stay within T-cell gators or what would be most appealing to you there? Thank you.

Well, as we mentioned in our prepared remarks, one of the very interesting things that's so promising about Tangent Keto is the potentially broad application of the mechanisms of action across modalities, whether it be ADCs, T-cell engagers, radiation. And as Dr. O'Valley indicated in her prepared remarks, a lot of cancer therapies result in greater T-reg generation. So we think it's very broad, and we think we'll focus on doing additional arrangements with other parties and, you know, see what we can get done so far this year.

Great. Thanks for taking the questions.

Thank you, Colleen.

Thank you. We will take our next question. And the question comes from the line of Brian Chang from J.P. Morgan. Please go ahead. Your line is open.

Hey, guys. Thanks for asking our questions this afternoon. Just for TACMO, how should we think about the strategy to develop your prostate cancer combo here with PAS3 in terms of a priority, given your hands is currently in multiple indications today?

Yeah, I think all the studies are executable. So, I mean, I think really getting the data across the tumor types that have a strong scientific rationale for a high degree of target expression with different immune contexts is our priority. I mean, given the prevalence and the need in CRPC, I mean, those studies should enroll relatively quickly. So, it could be a very exciting indication to look at. But it's equally important to all the other ones. We're really looking for the data to learn As Rasha and I have talked about in the past, our program is very intentional to learn the best context for how to use TAGMO, TTAG, and now not just with Torapalimab, but also with the T-cell linkager.

And if you think about the bar for, you know, MCRPC here, what would you want to see in this third line plus setting in terms of PSA50 endpoints?

Yeah, I mean, a couple of points I'll say.

So, you know, as I said in my prepared remarks, we'll be looking at safety as well as PSA 50, so both will be important. I won't comment too much on expectations at this stage, but what I will say is if you look at the current treatment environment for PSA 50, you know, it really goes, it drops dramatically after the the second line, right? So first line, you know, can go up to about, it's around 70% or up to 70% in terms of PSA 50. When you get to second line, it's in the 45% range. And then when you get to third line, it's, you know, around the 20% or less stage. So those are really kind of the current benchmarks. Further than that, I won't comment until we, you know, start opening up the study, which we anticipate to be in the second half of this year.

Brian, I think you can look forward to having a little more comment on the study on the August call, which will report Q2, given the fact that we anticipate initiating it in the second half of the year.

Great. Well, thank you so much for your time.

Thanks. Thanks, Brian.

Thank you. Once again, if you wish to ask a question, please press star 1, 1 on your telephone. Your next question comes from the line of Douglas Sal from HC Wainwright. Please go ahead. Your line is open.

Hi, good afternoon. Thanks for taking the questions. Danny, I think it was, you know, you said that around $35 million, you know, the revenue level, you know, you sort of basically become sort of cash flow break even, excluding R&D. I guess And then you made a comment sort of that R&D was discretionary or sort of you had a – or not discretionary, but you sort of had sort of ability to make choices where you're spending the money and how much. And I guess maybe if you could just help us with a framework in terms of what you think is an appropriate level of R&D spend and how do you find that balance between sort of the revenues that you're bringing in versus maybe needing some additional outside capital to fund the R&D program, just given the fact that the aperture of opportunities for the company seems to have been expanding quite nicely. Thank you.

Thanks, Doug. Let me try to frame our view and provide you a lens through which to view the budgetary considerations. You know, firstly, as I indicated, with the commercial team, you know, The commercial spend includes, you know, the commercial team itself. All the commercial spends, you know, the computer systems, the IT spends, you know, whatever the sales force needs. You know, also royalties, you know, there's a, for example, there's a 20% royalty to Junshi. You know, there's clogs. You know, I characterize all that as sort of the spend to get the sales. And that is probably, you know, 15, 16-ish, you know, million a quarter. Regarding the other spends, you know, the 30 to 35 million, that includes carrying also those same commercial spends, you know, with the increased costs because of, you know, increased sales. But also, you know, the internal SG&A, the rest of the headcount in the company and so on. In fact, everything except what I would characterize as additional development or clinical trial costs. So those we view in a separate bucket, and I would put those in bucket number three. And so when we initiated the development of the assets post the biosimilar spin-out, we had $250 million, and we were moving forward, and we identified a series of trials that we wanted to do. What we had done since then, of course, we did expand that a bit. We feel that it's very strategically worthwhile to pursue the engagement with J&J, with Prostate. We also think that CRC is an area of unmet medical need. But for the time being, we feel we're clearly funded for the clinical trials that we've done. Tagnol and Ketog, as Dr. Lavalle recited to you, has very broad potential applicability. But on the other hand, I think that we've shown ourselves to be very judicious and thoughtful with our spends, and we'll continue to do so. We want to understand the mechanism of action. We want to understand really where it works and why it works and place our bets there. But I think that overall, we've positioned the company well for the future. As you've noticed a long time, we took a pretty sharp high on our finances. And lastly, I think that our track record with La Corse over the past couple of years, particularly the doubling of revenues, you know, 25 over 24, you know, it gives us a fair degree of confidence that we'll be able to march it up to, 175 million as annualized sales in 2028. And as I pointed out, you know, signposts along the way are some 15 or 16 million where the commercial team pays for itself and then on to, you know, 30 plus where we carry the rest of the company. And that's the fundamental role of live tourism, really, is to pay for all those things for us so we can develop the drugs. And that's the lens through which we view it.

Okay, Danny, that's really helpful. And then just maybe a follow-up for Sameer. Just what is the current duration of therapy for patients on lock towards you right now? And, I mean, I think you sort of indicated that you expected to see an increase in the number of new patients start. I'm just curious, how much of an opportunity is there for you to see an improvement on the persistence equation?

Yeah. Thanks for the question. So just to remind you, there's two types of indications we have. We've got a frontline indication in a locally advanced recurrent setting and the frontline metastatic. And then we also have the second-line metastatic and third-line metastatic indications. The duration of therapy in the second-line indication should be much shorter than the frontline indication. So that's kind of the basic assumption from the clinical trials. That being said, we look at the duration of therapy every three months, looking at claims data. The duration of therapy continues to grow every time you look at it. I'm still not ready to give you a number on the average duration of therapy because we simply don't have enough patients and cohorts to look at an average number. But what I can say is the duration continues to increase and we still have room to grow from where we are today to where the clinical trial duration was. So to answer the other implied question you had, The contribution from the existing patients and the contribution from new patients will continue to both grow as it goes through the next couple of years.

Okay, great. Thank you. Thank you, Doug.

Thank you. This concludes today's conference call. Thank you for participating. You may now disconnect.