Olivia Brayer

Olivia Brayer inquired about the decision to keep BRINSUPRI's EU list price the same as the U.S., payer feedback on pricing, potential gross-to-net discounts in Europe versus the U.S., and the U.S. prescriber mix (academic vs. community).

Answer

Will Lewis, Chairman and CEO of Insmed, confirmed their practice of matching list prices across U.S., EU, and Japan, acknowledging that gross-to-net negotiations will impact the ultimate net price. He highlighted the broad U.S. prescriber base (academic and community) as a strength, with a focus now on increasing prescribing depth.

Olivia Brayer asked about the decision to keep Brensocatib's EU list price the same as in the U.S., payer feedback on the price point, potential gross-to-net discounts in Europe versus the U.S., and the U.S. prescriber mix (academic vs. community).

Answer

Will Lewis, Chairman and CEO, confirmed that matching U.S. list prices in Europe and Japan is company practice, as seen with ARIKAYCE. He noted that gross-to-net discussions with payers can significantly impact the net price. Regarding the U.S. prescriber mix, he highlighted the strength of broad prescribing across both centers of excellence and the community, which was a deliberate focus, but stated it's too early to discern depth of prescribing.

Olivia Brayer from Cantor Fitzgerald asked for details on the number of RYONCIL treatment kits administered, inventory dynamics, the future outlook for gross-to-net adjustments, and the specific patient population for the upcoming adult GVHD trial.

Answer

CEO Silviu Itescu clarified that the number of kits sold can be derived from the reported gross sales figures and that gross-to-net adjustments are expected to remain stable. He specified that the adult GVHD trial will not target Jakafi-refractory patients but will instead study RYONCIL as an add-on therapy to Jakafi in patients with severe disease (Grade C/D) to address the largest possible market upon entry.

Olivia Brayer of Cantor Fitzgerald asked for specifics on the FDA's request that led to the three-month PDUFA delay for narsoplimab and whether it was unexpected. She also requested more details on the potential multi-billion dollar partnership being pursued, including the asset involved.

Answer

Gregory Demopulos, Founder, Chairman, CEO & President, explained the FDA requested additional analyses, and the volume of data submitted prompted the extension. He stressed that interactions with the agency remain collaborative. Per the transcript, Nadia Dac, CCO, added that the company hopes for an earlier decision. Regarding the partnership, Mr. Demopulos confirmed substantial interest across programs but stated the company has disclosed all it can, referencing its materiality in the context of a recent financing.

Olivia Brayer from Cantor Fitzgerald inquired about the pricing strategy for narsoplimab, confidence in zaltenibart's clinical profile regarding liver toxicity, and the company's strategy for managing its cash runway and balance sheet.

Answer

Chairman and CEO Gregory Demopulos, Chief Commercial Officer Nadia Dac, and VP of Clinical J. Whitaker provided answers. On pricing, Ms. Dac noted that while not final, it will reflect the significant value of a threefold survival benefit and its use in both inpatient and outpatient settings. Regarding zaltenibart, Dr. Whitaker stated no liver safety signal has been observed and that patients with pre-existing liver disease were excluded from trials to avoid confounding data. On the balance sheet, Dr. Demopulos confirmed the company is actively pursuing a restructuring of its convertible notes and adding capital, with multiple options available including partnerships, debt, or equity.

Olivia Brayer from Cantor Fitzgerald inquired about the Phase III trial designs for the MASP-3 inhibitor, zaltenibart, seeking details on FDA/EMA feedback and patient enrichment strategies. She also asked about the company's potential strategy for the priority review voucher if awarded for pediatric C3G.

Answer

Executive Gregory Demopulos and Chief Medical Officer Andreas Grauer provided details. Demopulos described the two PNH trials (a switchover study and a study in complement inhibitor-naive patients) and noted the positive regulatory feedback. Dr. Grauer added that the designs follow established precedent and that the trials will enrich for patients with hemoglobin below 10 g/dL. Regarding the voucher, Demopulos stated it was premature to define a strategy, as it would depend on the market landscape and internal needs at the time.

Olivia Brayer of Cantor Fitzgerald inquired about the potential timeline for a Tyvaso DPI bridging study in IPF following the TETON-2 results and asked about the strategic positioning of MannKind's nintedanib DPI program, including patient enrollment criteria for its Phase 2 trial.

Answer

CEO Michael Castagna deferred to United Therapeutics on the specific Tyvaso DPI regulatory strategy but noted that positive TETON-2 results would likely accelerate FDA discussions. For nintedanib DPI, he explained the trial was redesigned for an ex-US market to accommodate a placebo-controlled design, which is difficult in the US. He positioned the drug for patients intolerant to current therapies and as a future combination treatment, with the Phase 3 trial expected to be global.

Olivia Brayer of Cantor Fitzgerald asked for details on the MNKD-201 IPF study, specifically regarding FVC as an endpoint and dose levels. She also inquired about the potential design and timing of a Tyvaso DPI bridging study for IPF.

Answer

Executive Michael Castagna explained they are finalizing the protocol but are looking at a couple of doses and aiming to see a delta from placebo, though the study isn't powered for a specific statistical endpoint. Regarding the Tyvaso bridging study, he noted it's premature to comment but expects it to be a BREEZE-like study, deferring to partner United Therapeutics for official comments.

Olivia Brayer of Cantor Fitzgerald inquired about the future trajectory of MannKind's margins considering new investments, the gross-to-net discounting for TYVASO DPI, and the potential timeline for a TYVASO DPI bridging study for IPF.

Answer

Executive Christopher Prentiss stated that margins are approaching a steady state due to increased manufacturing utilization. Executive Michael Castagna confirmed that Q4's TYVASO DPI gross-to-net levels are the new norm and that a bridging study for IPF would be discussed with partners in Q2, with timing dependent on the TETON trial readouts.

Olivia Brayer from Cantor Fitzgerald asked for details on MNKD-201's profile, its differentiation from other inhaled nintedanib competitors, and whether pharmacokinetic (PK) data was compared to the oral formulation.

Answer

Executive Michael Castagna highlighted MannKind's speed to clinic and dry powder formulation as key differentiators for MNKD-201. He noted the trial aims to reduce patient reliance on anti-diarrhea medication compared to OFEV. Castagna confirmed plasma PK was measured to compare with animal models, with a full analysis pending for an FDA submission, but did not commit to a public disclosure timeline.

Olivia Brayer of Cantor Fitzgerald asked for an update on the citizen petition filed with the FDA and inquired what specific factors are influencing the timing of the updated long-term financial guidance.

Answer

President and CEO Alexander Hardy stated that they do not expect to hear from the FDA on the citizen petition until the competitor's PDUFA date of November 30. EVP and CFO Brian Mueller added that there is no single event gating the guidance update; rather, they are conducting a comprehensive review considering market trends, the Inozyme acquisition, and ongoing IP litigation.

Olivia Brayer from Cantor Fitzgerald asked for an update on the citizen petition filed with the FDA and inquired about the specific factors causing the delay in updating the company's long-term financial guidance.

Answer

President and CEO Alexander Hardy stated that the FDA considers the citizen petition during the competing drug's review, so no update is expected until that drug's PDUFA date of November 30. EVP and CFO Brian Mueller added that there is no single event holding up the long-term guidance update; rather, they are refreshing their view based on multiple factors, including market trends, the recent Inozyme acquisition, and the ongoing VOXZOGO IP litigation.

Olivia Brayer of Cantor Fitzgerald sought clarification on the timing of data from VOXZOGO's other short stature indication studies, asking if any could arrive before 2027. She also asked for commentary on BioMarin's future earnings power.

Answer

Greg Friberg (Chief R&D Officer) clarified that while the commitment is to have data to initiate Phase 3 studies in 2027, it's possible data could be presented publicly before then, but he did not commit to an earlier timeline. Brian Mueller (CFO) pointed to the company's long-term guidance, including a 40%+ non-GAAP operating margin target, as indicative of significant earnings power beyond the current year's strong growth.

Olivia Brayer asked about the expected growth level for the enzyme business over the next few years and the potential for margin expansion in that franchise, considering factors like weight-based dosing for aging patients.

Answer

CFO Brian Mueller affirmed the high single-digit CAGR target for the enzyme business through 2027, with PALYNZIQ as a key driver. He noted that while specific business unit margins are not disclosed, the franchise is 'substantially profitable' with margins well above the consolidated company average. He also confirmed that weight-based dosing contributes to the durability and growth of the franchise.

Olivia Brayer of Cantor Fitzgerald inquired about the market uptake of a competitor's product, Yutrepia, its impact on Tyvaso DPI, and the reasons for a sequential decline in ex-U.S. nebulized Tyvaso revenue.

Answer

Michael Benkowitz, President & COO, responded that the competitive launch is proceeding as expected. He acknowledged physician curiosity about new products but expressed confidence in Tyvaso DPI's long-term growth, citing its strong product profile, extensive patient support, and a deep prescriber base of nearly 3,000 physicians.

Olivia Brayer asked about the treatment effect being targeted in the study's powering assumptions, whether the FDA has a specific threshold for 6-minute walk improvement for approval, and if the data readout timeline was affected by any changes to the protocol or safety follow-up period.

Answer

CEO Faheem Hasnain confirmed the study was powered for a 30-meter treatment effect with a standard deviation of 70, yielding over 90% power. He also stated the data readout timeline includes the safety follow-up and has not been changed by any protocol amendments. EVP, Regulatory Affairs, Caryn Peterson, added that the FDA had reviewed and agreed to the protocol's design and powering assumptions.

Olivia Brayer sought details on the upcoming AUR200 Phase I single ascending dose (SAD) trial data, asking about the number of patients and dose levels studied. She also inquired about the target dosing schedule needed to be competitive and the planned level of detail for the data disclosure.

Answer

President and CEO Peter Greenleaf declined to provide specific details ahead of the data release, reiterating that the SAD trial results would be reported by the end of June. He stated that the company first needs to see the ongoing trial's data and discuss disclosure strategy with the board before providing further guidance on the program's next steps or competitive positioning.

Olivia Brayer inquired about the long-term growth outlook for LUPKYNIS beyond 2025 and whether a low-double-digit growth rate is a reasonable expectation. She also asked if the Q2 AUR200 update would include the MAD study dose and potential dosing frequency.

Answer

President and CEO Peter Greenleaf declined to provide long-term guidance but suggested historical trends are the best indicator for future performance. Regarding AUR200, he stated the company would wait to see the SAD data before committing to specific disclosures for the MAD study, but acknowledged the natural next step is to provide clarity on the MAD study design.

Olivia Brayer asked about the clinical development strategy for AUR200, specifically regarding potential dose levels to balance efficacy and safety, given the history of the drug class. She also questioned if the subcutaneous administration implies development of an at-home product.

Answer

President and CEO Peter Greenleaf stated that questions regarding AUR200's optimal dosing, safety profile, and administration regimen are precisely what the ongoing single-ascending and multi-ascending dose studies are designed to determine. He indicated that the company will report on these findings once the data from these human studies becomes available.

Olivia Brayer followed up on the gross-to-net trend, asking where it might ultimately stabilize. She also questioned if the company could maintain its operating cash flow positivity and commented on its potential earnings power into 2026.

Answer

CFO Mark Hahn clarified that while gross-to-net is stabilizing with potentially minor further improvement, the company was not technically cash flow positive from operations due to an accounts receivable build. However, he confirmed that the revenue run rate now exceeds cash expenses, a pace he believes is sustainable as sales grow. He reiterated that with a lean commercial spend, the business has strong long-term profitability potential.

Olivia Brayer of Cantor Fitzgerald inquired about the potential stabilization point for the gross-to-net discount and whether the company can sustain its positive operating cash flow run rate, considering its future earnings power.

Answer

Mark Hahn, Chief Financial Officer, indicated that the gross-to-net percentage is nearing stabilization with potentially minor room for improvement. He clarified that while the company was not technically cash flow positive from operations due to an accounts receivable build, its revenue run rate now exceeds cash expenses. He expressed confidence in maintaining this pace and achieving long-term profitability, supported by a lean commercial spend.

Olivia Brayer inquired about the potential for quantity limits or other utilization management controls on JOURNAVX and asked for a timeline on how quickly P&T committees might grant formulary coverage.

Answer

COO Stuart Arbuckle reiterated that the goal is to minimize utilization management controls like step-edits through payer negotiations. He noted that while P&T committee reviews can take up to 12-18 months, Vertex is working to significantly accelerate this process for JOURNAVX and believes many institutions will move more quickly than usual.

Olivia Brayer from Cantor Fitzgerald asked for clarification on the internal bar for advancing VX-548 in lumbosacral radiculopathy (LSR), questioning if an early separation from placebo would be sufficient to proceed if the treatment effect curves converge by the 12-week endpoint.

Answer

CEO Dr. Reshma Kewalramani reiterated that the primary goal of the Phase II study is to determine the magnitude of the treatment effect in both the suzetrigine and placebo arms to appropriately size a Phase III trial. While all data details will be considered, the magnitude of effect is the key determinant for moving forward.

Olivia Brayer of Cantor Fitzgerald asked for details on the data submitted to the FDA for the less restrictive Camzyos REMS and sought clarification on the specifics of the European label update regarding monitoring frequency.

Answer

CMO Samit Hirawat confirmed the FDA submission included both clinical trial and real-world evidence but declined to share specific asks ahead of the agency's decision. CCO Adam Lenkowsky clarified the European label update: for patients in the maintenance phase (post-week 12), echo monitoring was reduced from every quarter to once every six months.

Olivia Brayer asked about expectations for the adjunctive schizophrenia data for Cobenfi, potential for off-label use, and whether the milvexian data timeline should now be considered later in 2027.

Answer

Head of Global Drug Development Samit Hirawat confirmed the adjunctive ARISE study will read out in 2025 and that the 2027 milvexian timeline remains an estimate as it is event-driven. Chief Commercialization Officer Adam Lenkowsky added that while adjunctive use is common in the market, the commercial team is focused on driving on-label monotherapy use for Cobenfi.

Olivia Brayer asked about the anticipated level of investment for the MariTide Phase III program and sought clarification on whether Amgen has already seen the Phase II data internally.

Answer

CEO Robert Bradway described the planned Phase III program as a large, global trial. EVP of R&D James Bradner confirmed planning is on track. CFO Peter Griffith emphasized Amgen's history of manufacturing leadership and noted that recent increases in CapEx and R&D spending reflect investment in key innovations like MariTide. The executives did not confirm if they had seen the data.