Tsan-Yu Hsieh

Tsan-Yu Hsieh asked for Mersana's perspective on recent data suggesting a longer-term resistance phenotype to topo-1 ADCs. He also inquired about the clinical status of three specific TNBC patients who were noted as ongoing in the January data update.

Answer

An executive, likely CEO Dr. Martin Huber, declined to comment on the resistance phenotype data as he had not personally seen the presentation. Regarding the status of the three ongoing patients from the January update, he deferred the question to the upcoming ASCO presentation, stating he did not want to front-run the data disclosure.

Tsan-Yu Hsieh requested a deeper analysis of the evolving competitive landscape for B7-H4 ADCs, following recent discontinuations by competitors.

Answer

COO & CFO Brian DeSchuytner responded that Mersana views the landscape favorably. He positioned Emi-Le as the most advanced auristatin B7-H4 ADC and the only one with positive data in the post-topo-1 breast cancer setting. He noted that competitors focusing on other tumors helps validate the B7-H4 target and that Emi-Le's safety profile may allow for combination therapies that are challenging for others.

Tsan-Yu Hsieh sought clarification on the STELLAR-303 statistical plan, asking about the difference between dual and co-primary endpoints and the alpha split. He also asked about the strategy for expanding the company's ADC toolkit.

Answer

Chief Medical Officer Amy Peterson clarified that a dual primary endpoint allows the study to be positive if either endpoint is met, unlike co-primary, and that the alpha split is not necessarily equal. Chief Scientific Officer Dana Aftab commented on the ADC strategy, highlighting the exciting preclinical data for XB628 and teasing more details on their discovery pipeline at a future R&D Day.

Tsan-Yu Hsieh asked about the potential impact of a new PET imaging agent on the RCC market and questioned the assumptions for the $1 billion small molecule NET market, suggesting zanzalintinib could achieve longer treatment durations.

Answer

EVP of Commercial P.J. Haley stated the RCC market is relatively stable. For NET, he agreed that earlier use of zanzalintinib could lead to longer durations but stressed the immediate opportunity for CABOMETYX to rapidly penetrate the ~$1 billion market as the only branded oral therapy with comprehensive patient support.

Tsan-Yu Hsieh of William Blair asked about the company's strategy for designing clinical studies to address the weight maintenance opportunity for petrelintide, and whether this would be explored in Phase II or Phase III.

Answer

CEO Adam Steensberg emphasized that the maintenance phase is a key differentiator, as petrelintide's satiety mechanism is better tolerated long-term than the appetite suppression of GLP-1s. Chief Medical Officer David Kendall added that future studies will be 'clinically practical,' potentially assessing switches from incretins to amylins and leveraging amylin's leptin sensitization to maintain higher quality weight loss.

Tsan-Yu Hsieh asked about the long-term view on the Alzheimer's diagnostic market, particularly the threat from serum-based biomarkers, and requested more detail on the growth drivers for the 2030 PYLARIFY revenue outlook.

Answer

CEO Brian Markison positioned serum biomarkers as a complementary screening tool, arguing they cannot replace the quantification and geographical detail of PET imaging. President Paul Blanchfield added that payers would likely require a PET scan to confirm diagnosis before approving expensive therapies. Regarding PYLARIFY, Blanchfield highlighted radioligand therapies (RLT) as a key driver, with associated scans expected to grow significantly by 2030.

Tsan-Yu Hsieh asked about the strategy for building a data set to highlight the competitive differentiation of Alzheimer's agents MK-6240 and NAV-4694 ahead of regulatory submissions.

Answer

CEO Brian Markison highlighted recent data from a federally funded trial demonstrating a significant advantage for MK-6240 over other tau tracers. He noted its recognition as an extraordinary asset for detecting early tau tangles is evidenced by its use in over 100 clinical trials and partnerships with major pharma companies. He added that NAV-4694 is also showing promise in detecting early beta-amyloid.

Tsan-Yu Hsieh requested details on the assumptions behind the $1.5 billion to $2.5 billion Total Addressable Market (TAM) for Alzheimer's diagnostics, specifically regarding the number of scans per patient and the strategy for payer dialogue to ensure coverage for longitudinal monitoring.

Answer

President Paul Blanchfield explained the TAM is grounded in consensus forecasts for therapeutic uptake, such as 500,000 patients on therapy by the end of the decade. He positioned PET imaging as a valuable 'insurance policy' for payers, ensuring the right patients receive expensive therapies, which creates a strong value proposition for diagnosis, staging, and monitoring, ultimately justifying the cost of the scan.

Tsan-Yu Hsieh, also known as Andy Hsieh, asked about the design of a potential maintenance study, the commercial viability of a direct-to-consumer model for Viking, and how learnings from VK2735 could be applied to the amylin program.

Answer

Brian Lian, President and CEO, indicated a maintenance study would explore transitions to less frequent or oral dosing without waiting for a weight plateau. He acknowledged that direct-to-consumer channels are now a proven, viable option, providing future commercial optionality. Regarding the amylin program, he noted that while it is a different molecule, they believe it is also amenable to an oral formulation and has a PK profile supporting weekly dosing.

Tsan-Yu Hsieh (Andy Hsieh) asked about the pharmacokinetic data presented at ObesityWeek, specifically regarding the accumulation multiple that supports a longer dosing interval and the minimum plasma level needed to prevent weight regain.

Answer

CEO Brian Lian explained that the plasma levels achieved with the 2.5mg dose, which resulted in 9% weight loss, serve as a benchmark for preventing significant weight regain. He highlighted that the drug's continued accumulation at 13 weeks suggests long-term efficacy may be understated by current data and clarified that the poster's decay graph showed data out to 19 weeks.

Tsan-Yu Hsieh (Andy Hsieh) asked for investigator feedback on the CBeyond study, whether the 52-week extension includes additional DEXA scans for body composition, and if removing the interim analysis preserves statistical power.

Answer

Executive Puneet Arora confirmed significant investigator enthusiasm for obesity trials, which contributed to rapid enrollment. He stated that DEXA scans will continue during the extension phase to provide longitudinal data on body composition. He also affirmed that removing the interim analysis eliminates any concerns about its potential impact and preserves the full statistical power for the final analysis.

Tsan-Yu (Andy) Hsieh from William Blair asked about the estimated number of cirrhotic patients in the Phase III trials, whether this number is flexible, and how the company's multi-scale modeling data would compare to Epclusa.

Answer

Dr. Janet Hammond, Chief Development Officer, explained that they are targeting approximately 10% cirrhotic patients but have flexibility in the final number. Dr. Jean-Pierre Sommadossi, CEO and Founder, addressed the modeling question by directing the analyst to existing publications that evaluate other direct-acting antivirals using a similar approach.

Tsan-Yu Hsieh of William Blair asked about the primary goal of the Phase III trial, questioning if Atea is aiming for superiority or non-inferiority. He also inquired about the company's commercial strategy regarding volume-based contracts as a potential cost-efficient path to market.

Answer

Chief Medical Officer Dr. Arantxa Horga stated the trial will be powered for non-inferiority but is designed to allow for a superiority test. CEO Dr. Jean-Pierre Sommadossi added details on the non-inferiority margin. On the commercial question, Chief Commercial Officer John Vavricka noted that government payers like Medicare and Medicaid are significant, and the market has been stable. He highlighted that the prescriber base is highly concentrated, allowing for an efficient commercial approach.

Tsan-Yu Hsieh from William Blair inquired about the company's perspective on the velocity of tumor size reduction as a potential de-risking factor for endpoints like PFS and OS. He also asked if the patient numbers from Pfizer's BREAKWATER trial could serve as a framework for Cardiff's upcoming FDA discussions on an accelerated approval pathway.

Answer

Executive Mark Erlander acknowledged that historical data in first-line CRC shows a correlation between earlier, deeper tumor responses and improved PFS and OS. Regarding the BREAKWATER trial, he stated that while Cardiff is looking at Pfizer's trial size (110 patients per arm) as a reference, the key takeaway is that fewer patients were needed for both accelerated and full approval, a point they will discuss with the FDA to finalize their own trial design.

Tsan-Yu Hsieh of William Blair & Company asked for an update on the number of activated clinical trial sites for CRDF-004, questioned if both study doses could potentially advance to a pivotal trial, and inquired about other potential data catalysts before the company's cash runway ends in Q3 2025.

Answer

Executive Mark Erlander reported that 24 clinical sites are currently active, with a goal of activating 35, noting the process is dynamic. He confirmed the plan is to select a single dose for the registrational trial, not two, based on FDA's Project Optimus guidance which evaluates both efficacy and safety. Regarding other catalysts, Erlander stated that while there are ongoing investigator-initiated trials, the company is not prepared to provide specific timelines for data readouts from them, as the laser focus remains on the CRDF-004 trial.

Tsan-Yu Hsieh of William Blair & Company inquired about the scope of the top-line data release expected in the first half of 2025 for the investigator-sponsored Phase 2 study of FG-3246. He also asked about the logistical patient experience for the FG-3180 PET imaging agent, specifically the time between infusion and imaging.

Answer

CEO Thane Wettig clarified that the H1 2025 data for the combination study will include results from both the dose escalation and expansion cohorts, totaling approximately 36 patients, with rPFS data maturing over time. Regarding the PET agent, he explained that imaging would occur days after infusion, not minutes, with the exact timing being determined in ongoing studies.

Tsan-Yu Hsieh of William Blair & Company asked about the SITC poster for NKTR-255, inquiring about other cell populations analyzed besides NK cells and the consistency of the historical control arm's lymphocyte count compared to other studies.

Answer

Chief Medical Officer Dr. Mary Tagliaferri detailed the MD Anderson historical control data, highlighting the poor outcomes for patients with radiation-induced lymphopenia and the statistically significant improvement with NKTR-255. Chief R&D Officer Dr. Jonathan Zalevsky added that the study is also assessing T cell populations and overall lymphocyte recovery, not just NK cells.