Sudan Loganathan

Sudan Loganathan asked if upcoming catalysts, such as the CHOPIN publication, new sales regions, or increased site starts, could potentially mitigate the anticipated seasonality in the third quarter. He also inquired if the CHOPIN data could be quantified into a specific increase in new patient starts per site per month, for example, an additional 0.1 or 0.2 patients.

Answer

Gerard Michel, CEO, acknowledged that seasonality, particularly due to key personnel taking time off at high-producing sites, is likely to persist to some extent, making it difficult to fully counter. He expressed hope for upside from CHOPIN and increased site activations but emphasized a reasonably conservative approach in guidance. Michel declined to quantify the potential impact of CHOPIN on new patient starts per site per month.

Sudan Loganathan asked if potential catalysts like the CHOPIN publication, new sales regions, or additional site starts could help mitigate the anticipated seasonality in the third quarter. He also attempted to quantify the potential impact of the CHOPIN data on new patient starts per site per month, asking if it could add 0.1 or 0.2 to the current average.

Answer

Gerard Michel, CEO, explained that the seasonality primarily stems from high-producing sites losing capacity when key REMS-certified staff take time off, making it challenging to onboard new patients. He stated that while they are working to increase bench strength, it is prudent to assume the seasonality will recur. Mr. Michel acknowledged that CHOPIN or increased site activations could offer upside but preferred a reasonably conservative guidance approach. He declined to quantify the potential impact of CHOPIN on new patient starts.

Sudan Loganathan of Stephens Inc. asked about the company's ability to use upcoming CHOPEN trial data for marketing, the rationale for adjusting the year-end site activation target, and whether the revenue guidance change was driven by Hepzato or ChemoSat.

Answer

CEO Gerard Michel explained that MSLs will be able to discuss the CHOPEN data, while sales reps will be more limited. He attributed the guidance adjustment to strong performance of over two treatments per center per month offsetting slower site activations. He estimated two-thirds of the revenue guidance change was from Hepzato and one-third from ChemoSat.

Sudan Loganathan asked about the adequacy of the current sales territories for future growth, the remaining steps before initiating new Phase II trials, and the company's interest in using its cash for in-licensing opportunities.

Answer

CEO Gerard Michel stated that the current six sales territories should be sufficient to reach 40 active sites, but they are prepared to expand if needed. He also noted that while they are open to in-licensing, nothing has met their criteria for a strategic fit. Chief Medical Officer Vojo Vukovic explained the delay in starting new trials is due to the 6-12 month operational process of site activation, including protocol reviews and contracting with large academic centers.

Sudan Loganathan of Stephens asked about the company's strategic priority between maintaining cash flow positivity and investing in R&D, and also inquired about the cadence of future price increases for HEPZATO.

Answer

CEO Gerard Michel emphasized that while Delcath will be cash flow positive in 2025, the company will prioritize funding high-potential R&D opportunities over maintaining positive cash flow if conditions are right. He also clarified that future price increases are linked to the rate of inflation, per CMS rules.

Sudan Loganathan of Stephens inquired if the Q4 holiday slowdown would also affect the onboarding of new treatment sites and asked for clarity on how outstanding warrants factor into the company's cash forecast for funding future trials.

Answer

CEO Gerard Michel acknowledged that site onboarding and preceptorships would also slow during the holiday period but did not foresee a material impact on overall activation targets due to a strong pipeline of sites ready to begin. SVP of Finance Sandra Pennell clarified that the company's cash forecast does not rely on the potential $36 million from remaining warrants, as current cash, recent proceeds, and operating cash flow are expected to be sufficient to fund operations and new trials through profitability.

Sudan Loganathan asked about the specific regulatory feedback Arvinas is seeking for the PSP Phase 1b trial, any risk that this feedback could alter the Parkinson's disease (PD) development strategy, and how the trial design for both PSP and PD (endpoints, enrichment, duration, registrational credibility) is evolving.

Answer

Randy Teel (President and CEO) confirmed a typical regulatory process for the PSP Phase 1b. Noah Berkowitz (CMO) stated that regulatory feedback for PSP is viewed as an opportunity, not a risk, for PD. For PSP, they will focus on PSP-RS patients (~40% of PSP) and use the PSP rating scale for registrational studies. For PD, they are using PPMI data to identify biomarkers that predict outcomes and correlate with observed biomarker changes.

Sudan Loganathan asked about the specific regulatory feedback sought for the Phase 1B trial in PSP, any risk of this feedback altering the PD program timelines, and the planned trial design evolution for both PSP and PD, including endpoints and enrichment strategies.

Answer

President and CEO Randy Teel indicated that regulatory discussions for the PSP Phase 1B are typical and on track. Chief Medical Officer Noah Berkowitz explained that the FDA dialogue for PSP is an opportunity, not a risk, and that PSP and PD have different risk-benefit profiles. He noted that PSP enrollment would focus on patients with PSP-RS, and for PD, they are using existing data sources like PPMI to identify biomarkers that predict outcomes.

Sudan Loganathan asked about vepdegestrant's potential in the small first-line ESR1 mutant population and sought clarification on whether the 40% ESR1 mutation rate in second-line patients is specific to prior treatments.

Answer

CEO John Houston clarified the distinct market dynamics: the second-line setting has a high (~40%) prevalence of ESR1 mutations, representing a major opportunity. In contrast, the first-line setting is predominantly wild-type but endocrine-sensitive. He reiterated that the joint decision with Pfizer is to focus on the significant second-line opportunity and not pursue a first-line trial at this time.

Sudan Loganathan asked about the safety profile of the atirmociclib combination, specifically regarding glucose metabolism, and what makes it superior to other CDK4/6 inhibitors. He also inquired about the competitive positioning of ARV-393 against Bristol-Myers Squibb's BCL6 degrader.

Answer

Chief Medical Officer Noah Berkowitz noted that atirmociclib already has an established safety profile from another Phase III study and that hyperglycemia is not a significant concern for the vepdegestrant combination. CEO John Houston commented on the BCL6 space, stating that with little data available on the BMS compound, Arvinas is confident in its own technology and is focused on advancing its program.

Sudan Loganathan asked about ongoing trials that could challenge cabozantinib in second-line plus RCC this year and how trials like LITESPARK-033 and the Arcus combo trial with cabozantinib in the post-IO setting could help maintain RCC market share through 2026.

Answer

P.J. Haley (EVP of Commercial, Exelixis) acknowledged upcoming data at GU ASCO, emphasizing that overall survival is critical to raise the standard of care in RCC. He expressed confidence in cabozantinib's market position, team, and data, noting its ripened profile as seen in CONTACT-03.

Sudan Loganathan asked about ongoing trials that could challenge CABO in the second-line plus RCC setting this year and how trials like LITESPARK-303 and the Arcus combo trial with CABO in the post-IO setting could help retain lead share in RCC through 2026.

Answer

P.J. Haley (EVP of Commercial) acknowledged awareness of upcoming data at the GU ASCO meeting, noting that while PFS might be positive, overall survival is critical to raise the standard of care in RCC. He expressed confidence in CABO's market position, team, and data, including CONTACT-03.

Sudan Loganathan of Stephens Inc. asked if the dual endpoint design of STELLAR-303 could allow for approval in a single patient population and whether the current financial guidance includes contributions from the NET launch.

Answer

EVP & CMO Amy Peterson confirmed that a dual primary endpoint design allows a study to be positive by hitting on one endpoint. CFO Christopher Senner stated that the previous $100 million guidance increase did factor in some contribution from NET, but was primarily driven by the strong performance of the base business.

An analyst on behalf of Sudan Loganathan asked how the recent approval of CABOMETYX in NET might affect the trial design or patient recruitment for the upcoming STELLAR-311 study of zanzalitinib in the same indication.

Answer

Chief Medical Officer Amy Peterson explained that the STELLAR-311 trial is positioned in a slightly different treatment setting, evaluating zanzalitinib as a first oral therapy after progression on an SFA, versus everolimus. She stated that global thought leaders remain excited about the trial and the company is not concerned about competition from CABOMETYX for enrollment.

Sudan Loganathan asked what factors would drive the prioritization of the STELLAR-303, 304, and 305 programs for market entry, or if the company could pursue all three simultaneously.

Answer

President and CEO Michael Morrissey gave a definitive answer, stating, 'The only gauge here is a p-value.' He confirmed that if the trials are successful, Exelixis has the focus and resources to move them forward for regulatory approval with great speed, implying no forced prioritization among successful programs.

Sudan Loganathan asked about business development interests beyond the current GU and GI programs, inquiring if the company is seeking assets for novel combinations or as monotherapies.

Answer

President and CEO Michael Morrissey stated the answer is 'all of the above.' He reiterated that Exelixis is agnostic to modality and mechanism, focusing on assets that offer a high level of conviction for achieving clinical differentiation that can drive commercial success, whether as a standalone agent or in combination.

Sudan Loganathan of Stephens Inc. asked for color on the mix of new versus repeat customers, details on the Japanese market opportunity and commercialization plans, and the outlook for operating expenses in the second half of the year.

Answer

CEO Jeff Hackman explained that while new account acquisition is critical, the customer mix is beginning to even out with a higher percentage of repeat customers compared to the initial AYA launch. Regarding Japan, he described the market as roughly one-third the size of the U.S. and Europe, noting a partner would be required for regulatory submission and that discussions are ongoing. CFO Robert Andrade projected that cash operating expenses would decrease in the second half of 2025, expecting full-year cash OpEx to be consistent with 2024's figure of approximately $33 million.

Inquired about the new prescriber tiering strategy, including provider awareness and incentives. Also asked about the national coverage of Tier 1 accounts, competition from compounding pharmacies, and the revenue target for achieving cash flow breakeven.

Answer

The prescriber tiering is an internal tool for focus; providers are not notified of their tier and there are no related financial incentives. The commercial team covers Tier 1 accounts across the entire U.S. The company is actively re-engaging with institutions that previously used compounding and is seeing some progress. The quarterly revenue target for cash flow breakeven is approximately $8.5 million to $9 million.

An analyst on behalf of Sudan Loganathan asked about PEDMARK's competitive landscape in the U.S., pricing and prescription trends, and the future outlook for SG&A expenses. He also inquired if potential label expansions would necessitate new clinical trials.

Answer

Executive Robert Andrade explained that while one-time 2024 expenses like CEO severance won't recur, aggregate 2025 cash operating expenses are expected to be similar to 2024's ~$33 million due to increased marketing spend and headcount. CEO Jeffery Hackman added that PEDMARK's WAC is $11,000 per vial with variable patient usage and favorable reimbursement. He acknowledged compounded STS as a competitor, primarily in pediatrics, but highlighted PEDMARK's adoption in major academic centers. Regarding label expansion, he confirmed openness to discussions with institutions and said updates would be provided as they develop.

Sudan Loganathan of Stephens Inc. requested a reminder of the median prior surgeries for patients in the INO-3107 trial and asked about potential enrollment headwinds for the confirmatory trial if a competitor's product is approved.

Answer

Chief Medical Officer Dr. Michael Sumner clarified that the median number of prior surgeries was four (mean of 4.1). He also expressed confidence in meeting enrollment targets for the confirmatory trial, citing broad site distribution across the U.S. and potential lags in competitor insurance coverage. CEO Dr. Jacqueline Shea added that the trial's modest size of 100 patients across 20 sites makes it achievable.

Sudan Loganathan of Stephens asked if a competitor's potential approval could jeopardize priority review for INO-3107 and whether the BLA data package was now considered final for submission.

Answer

CCO Michael Sumner expressed confidence in receiving accelerated approval, arguing INO-3107's unique mechanism offers a distinct advantage for certain patient populations. Sumner confirmed the clinical data package is 'pencils down' and ready. CEO Jacqueline Shea emphasized the package was significantly strengthened with new immunology and 2-3 year durability data, creating a compelling case for the FDA.

Sudan Loganathan questioned why INOVIO is waiting to start the rolling BLA submission with completed modules, asked if the device breakage was originally found during DV testing, and inquired about any health economics research conducted for INO-3107's pricing.

Answer

CEO Dr. Jacqueline Shea explained the FDA prefers all modules within a 3-4 month window, so they want to ensure progress on device testing before starting the clock. CMO Dr. Michael Sumner confirmed the issue was found during DV testing and expressed confidence in the fix. CCO Steve Egge stated that payer research has been conducted, indicating that a rare disease price point, analogous to products like OGSIVEO at ~$360k/year, is considered acceptable.

Sudan Loganathan questioned INOVIO on the competitive landscape, specifically asking how INO-3107 differs from Precigen's PRGN-2012. He also asked if the company would consider changing the manufacturer for the device's plastic component.

Answer

CEO Dr. Jacqueline Shea and CMO Dr. Mike Sumner differentiated INO-3107 as a DNA medicine versus Precigen's adenoviral vector. They emphasized a key difference in trial design: INOVIO counted every surgery from day zero, whereas the competitor's trial included proactive surgeries during the treatment window. Dr. Shea stated that INOVIO is working with its existing manufacturer to implement the identified resolution and is not currently planning a change.

Sudan Loganathan of Stephens Inc. asked about commercial strategy, including plans for sales force growth to address a larger market, potential marketing collaboration with Roche for the glufetamab combination, and the timeline for MSLs to discuss LOTUS trial data. He also inquired about the potential impact of Roche's SKYGLOW study on the second-line DLBCL landscape.

Answer

CEO Ameet Mallik responded that the current commercial and MSL footprint is sufficient, covering 90% of the DLBCL market, with minor resource additions planned for launch. He clarified there is no planned commercial collaboration with Roche for the LOTUS-7 combination; MSLs will reactively answer questions, but the sales team will not promote it off-label. Regarding SKYGLOW, Mallik stated it is hard to speculate but acknowledged it is intended as Roche's confirmatory study, pending FDA agreement.

Sudan Loganathan from Stephens inquired about the necessity and potential benefits of engaging with the FDA for the LOTIS-7 compendia listing strategy. He also asked if the discontinuation of the ADCT-602 program would free up capital for preclinical exatecan-based ADCs and about plans for out-licensing these assets.

Answer

CEO Ameet Mallik and CMO Mohamed Zaki clarified that while FDA meetings are not required for a compendia strategy, they are crucial for a potential regulatory approval pathway and are planned for H2 2025. CFO Pepe Carmona explained that discontinuing the partnered ADCT-602 program has minimal cost implications and does not free up significant capital, adding that the company continues to advance its preclinical assets toward a partnerable stage.

Sudan Loganathan of Stephens asked for examples of bispecifics that gained market share via compendia listing and inquired about the anticipated time to reach peak sales penetration for ZYNLONTA's potential new indications.

Answer

CEO Ameet Mallik cited the recent NCCN guideline additions for glofitamab, epcoritamab, and mosunetuzumab combinations, which were based on data from approximately 100 patients. While not providing a specific timeline for ZYNLONTA, he noted that industry analogs in oncology often achieve peak sales penetration within the first two years of launch or label expansion due to rapid physician adoption of effective new therapies.

Sudan Loganathan asked how a potential FDA approval for PTC Therapeutics' Translarna might affect Agamry's market position and growth. He also inquired about the company's current stance on near-term strategic initiatives, such as M&A, to offset the Fycompa loss of exclusivity.

Answer

EVP & CCO Jeff Del Carmen asserted that Translarna would not impact Agamry's role, as steroids are the foundational treatment for DMD. President & CEO Richard Daly addressed strategy, stating that the company is actively evaluating numerous M&A opportunities in a favorable buying environment, while also pursuing organic growth through Agamry's lifecycle management and Firdapse's expansion into oncology.

Asked about the breakdown of operating expense spend between commercial and R&D programs, and whether profitability or free cash flow is expected this year.

Answer

The company is disciplined in its capital allocation, investing in both AYVAKIT commercialization and priority pipeline programs like elenestinib and BLU-808. They expect modest increases in both R&D and SG&A spend to drive near- and long-term growth and did not commit to profitability this year.

Asked about the company's business development appetite for external assets versus focusing on the internal pipeline, and about potential enrollment challenges for the elenestinib HARBOR study given AYVAKIT's availability.

Answer

Business development is a strategic lever, but the primary focus is on the internal mast cell disorder franchise, with the company's prolific discovery engine setting a high bar for external deals. For the HARBOR study, the company does not anticipate major enrollment challenges, as the trial is designed to differentiate elenestinib and will enroll internationally to support recruitment.

Sudan Loganathan of Stephens Inc. inquired about the expected allocation of R&D spending between the KT-621 and KT-295 programs and how the expense profile might change based on trial progress.

Answer

CFO Bruce Jacobs noted that cash burn will increase, with a steeper trajectory in 2026 as clinical activity intensifies, but the current cash runway extends into mid-2027. CEO Nello Mainolfi added that spending on the STAT6 program (KT-621) will be 'dramatically superior' to the TYK2 program (KT-295) over the next few years.

Sudan Loganathan asked if IRF5 degradation could trigger feedback mechanisms activating other pathways and potentially cause relapse. He also questioned if the required STAT6 degradation level differs by indication and between blood and skin.

Answer

President and CEO Nello Mainolfi responded to both questions. On IRF5, he stated that no rebound or resistance mechanisms have been observed in long-term preclinical studies. On STAT6, he explained the initial goal is over 90% degradation in both blood and skin to maximize success, and that upcoming Phase 2b dose-ranging studies are designed to determine the precise degradation levels needed for clinical benefit in different diseases.

Sudan Loganathan, on behalf of Andrew Fein from H.C. Wainwright, asked for details on the confirmatory Phase 3 study design, including the expected efficacy and tolerability bar from the FDA and potential patient numbers. He also questioned if enrollment delays would alter the operating expense guidance for fiscal year 2021.

Answer

President and CEO Dan Gold indicated it was premature to provide specifics on the Phase 3 study design as discussions with the FDA are ongoing, but noted the primary endpoint would likely be Progression-Free Survival (PFS) and that tolerability remains a key focus. Regarding financials, he stated that the one-quarter enrollment delay for the TIDAL study is not expected to have a significant impact on operating expenses, particularly as development costs are now shared 50/50 with Kyowa Kirin.