Jin Law

Jin Law from Goldman Sachs asked about the strategic role of the Explore-CKD study in the NDA submission, the implications of lower eGFR on potassium levels as seen in publications, and whether the Explore-OSA trial data would be part of the NDA package.

Answer

Executive Jon Congleton and Chief Medical Officer Dr. David Rodman clarified that Explore-CKD is a key part of the 'totality of evidence' for the NDA, providing data on patients with eGFR down to 30 and on a lower 25mg dose. Dr. Rodman added that the study will help guide clinicians on managing higher-risk patients. Mr. Congleton stated it was too early to comment on including Explore-OSA data in the initial NDA.

Jin Law from Goldman Sachs asked for more refined guidance on the overlapping ADVANCE-HTN and Launch-HTN readout timelines, inquired about presentation plans for Launch-HTN data, and questioned patient compliance with the 24-hour ABPM device.

Answer

Executive Jon Congleton reiterated the existing guidance for the ADVANCE-HTN trial data in March and Launch-HTN data in the mid-first half of the year, stating it was too early to detail communication plans for Launch. Both Congleton and Chief Medical Officer Dr. David Rodman expressed high confidence in the ABPM data quality, citing experience from the Target-HTN trial, robust site and patient training, and an FDA-approved statistical plan to handle any missing data.

Jin Law from Goldman Sachs asked about the medication adherence rate in the Target-HTN trial and the expected improvement in the Advance-HTN trial with new tracking technology. He also sought clarification on the expected placebo-adjusted blood pressure changes with ABPM versus AOBP measurements and the statistical power for obese versus non-obese subgroups.

Answer

Dr. David Rodman, CMO, stated that accurate adherence data for Target-HTN is unavailable as it relied on unreliable pill counts, but noted Launch-HTN will analyze this. Both Dr. Rodman and Executive Jon Congleton explained that ABPM has a lower placebo effect (1-2 mmHg) than AOBP, but also a lower baseline BP, which can slightly reduce the absolute treatment effect. Mr. Congleton confirmed the overall trial power but did not disclose specific power calculations for subgroups.

Jin Law asked about the strategy for differentiating divesiran clinically from competitors like Rusfertide, beyond just dosing frequency. He also inquired about the biggest hurdles currently facing the partnering process for zerlasiran.

Answer

Steven Romano, Chief R&D Officer, responded that besides the key differentiator of infrequent dosing, they will also measure symptomatic improvement and other important outcomes, aiming for consistent hematocrit control. Craig Tooman, President and CEO, addressed the partnering question by stating there is no single hurdle; discussions are broad, focusing on business strategy and the large market opportunity, and that dialogues remain very active.

Jin Law asked about the clinical differentiation strategy for divesiran compared to competitors like Rusfertide, beyond dosing frequency. He also inquired about the biggest hurdles currently being faced in the partnering discussions for zerlasiran.

Answer

Steven Romano, Chief R&D Officer, explained that for divesiran, differentiation will focus on the significant convenience of infrequent dosing, as well as potential improvements in symptoms and the ability to consistently maintain safe hematocrit levels. Craig Tooman, President and CEO, addressed the partnering question by stating there is no single hurdle for zerlasiran, as dialogues vary by partner and often focus on business strategy and the large market opportunity.

Jin Law asked about the strategy for differentiating divesiran from competitor Rusfertide beyond just dosing frequency. He also inquired about the biggest hurdles currently facing the partnering process for zerlasiran.

Answer

Steven Romano, Chief R&D Officer, addressed the divesiran question, stating the primary goal is to be the first siRNA for PV to market. He emphasized that the infrequent dosing is a major differentiator that improves convenience and potentially long-term hematocrit control. Other points of differentiation, like symptomatic improvement, will be evaluated as more data becomes available. On zerlasiran partnering, Craig Tooman, President and CEO, noted there is no single hurdle; dialogues are active and vary by partner, often focusing on business strategy and the large market opportunity.

Asked about the clinical differentiation strategy for divesiran against competitors like Rusfertide beyond dosing frequency, and questioned the primary obstacles to securing a partnership for zerlasiran.

Answer

For divesiran, the key differentiator is the infrequent dosing and convenience, aiming to be the first siRNA for PV. They will also assess symptomatic improvement. For zerlasiran partnering, there is no single hurdle; discussions are active and revolve around business strategy and the large market opportunity.