Brian Skorney

Brian Skorney asked for an update on the exclusivity of VYKAT XR, particularly regarding patents extending to 2035 and beyond, and sought guidance on Cost of Goods Sold (COGS) and gross margin, specifically if current COGS reflect previously expensed R&D inventory.

Answer

Anish Bhatnagar, Chairman and CEO, confirmed that the 2035 patent for treating hyperphagia and food-related behaviors is a step towards extending IP into the late 2030s, with additional IP filings pending. Jim Mackaness, Chief Financial Officer, stated that some zero-cost inventory is still flowing through, and COGS will gently nudge up into the mid-single digits as full-cost inventory replenishes.

Brian Skorney inquired about Soleno's current thoughts on VYKAT XR's exclusivity, particularly regarding potential patent extensions beyond 2035, and sought guidance on Cost of Goods Sold (COGS) and gross margin impact as zero-cost inventory is depleted.

Answer

Anish Bhatnagar, Chairman and CEO, confirmed that the 2035 patent, specific to methods of treating hyperphagia, is a step towards extending IP into the late 2030s, with additional IP filings underway. Jim Mackaness, CFO, stated that COGS would gently nudge up into the mid-single digits as zero-cost inventory is depleted and replenished with at-cost inventory.

Brian Skorney of Baird noted the impressive sequential decrease in operating expenditures and asked if the current OpEx level is a fair go-forward number. He also sought clarification on the cash flow from operations calculation relative to the income statement.

Answer

CFO Jim Mackaness reiterated cash OpEx guidance of $120M-$130M for 2025, potentially rising toward $140M with EU and lifecycle initiatives. He projected 2026 OpEx to be north of $150M. He explained that with a launch exceeding 'modestly successful' expectations, the company is on a path to near-term cash flow positivity.

Brian Skorney of Baird commented on the impressive sequential decrease in operating expenditures and asked if the current OpEx is a fair go-forward number. He also requested clarification on the cash flow from operations calculation.

Answer

CFO Jim Mackaness reiterated prior guidance of $120M-$130M in cash OpEx for 2025, potentially rising to $140M, and projected over $150M for 2026 depending on the European strategy. He stated that the strong launch puts the company on a path to reach cash flow positivity in the near term, exceeding their 'modestly successful' launch model.

Brian Skorney compared Vykat XR's initial start form numbers to the SKYCLARYS launch, asking why consensus models project a slower revenue ramp given the similar early traction.

Answer

Executive James MacKaness noted that Vykat XR's weight-based pricing is a key variable, particularly with a potentially younger patient mix. CCO Meredith Manning added that Soleno's sales team was more recently deployed than the SKYCLARYS team was at launch. Executive Anish Bhatnagar emphasized the broad base of 131 prescribers as a strong foundation for sustainable growth.

Brian Skorney compared Vykat XR's initial start form numbers to the SKYCLARYS launch, questioning why consensus estimates project a slower revenue ramp given the similar early traction.

Answer

CFO James MacKaness noted that Vykat XR's weight-based pricing is a key differentiating factor, especially with a potentially younger patient mix. CCO Meredith Manning pointed out that Soleno's sales force was more recently deployed than the SKYCLARYS team was at launch. CEO Anish Bhatnagar emphasized the broad base of 131 unique prescribers as a strong foundation for sustainable growth.

Brian Skorney asked about learnings from the EMBARK study applied to EXPAND, the market size of the EXPAND basket relative to PFIC and ALGS, and the anticipated dose for this population.

Answer

CEO Chris Peetz distinguished EXPAND's focus on older, post-Kasai biliary atresia patients with persistent cholestasis from EMBARK's acute infant setting. He highlighted strong compassionate use responses in this older group, estimating the EXPAND basket could represent at least 500 U.S. patients and potentially a third of LIVMARLI's $1 billion-plus peak revenue potential.

Brian Skorney asked about learnings from the EMBARK study being applied to the EXPAND study, particularly given the high proportion of biliary atresia patients, and requested context on the market size represented by the EXPAND basket relative to PFIC and ALGS, as well as the anticipated dose for this population.

Answer

CEO Chris Peetz clarified that EMBARK focused on acute post-Kasai bilirubin levels, where surgical outcomes were primary. In contrast, EXPAND enrolls older biliary atresia patients with successful Kasai procedures but persistent cholestasis and pruritus, a population where strong compassionate use responses inspired the study. He estimated at least 500 U.S. patients for the EXPAND indications, potentially contributing a third of LIVMARLI's over $1 billion peak revenue potential.

Brian Skorney asked about the in-licensed PDE4D inhibitor, MRM-3379, questioning if data from a competitor's Phase III study formed the basis for the deal, how Mirum's molecule compares, and whether Mirum would wait for the competitor's results before starting its own Phase II trial.

Answer

CEO Christopher Peetz acknowledged that the competitor's Phase II proof-of-concept data was a factor but stated Mirum's study start is independent due to their molecule's differentiated profile. Chief Medical Officer Joanne M. Quan emphasized that MRM-3379 is highly selective and has a significantly higher brain-to-plasma ratio, which she described as a key potential advantage for treating a CNS condition like Fragile X.

Brian Skorney asked about the initial launch metrics for Modeyso, how they contextualize the greater than $500 million U.S. peak sales guidance, whether the ACTION study is necessary to achieve this guidance, and if a positive ACTION study readout would alter the peak sales projection.

Answer

Sam Pearce, Chief Commercial Officer, expressed delight with Modeyso's early launch ($48 million in 4.5 months), driven by high unmet need and anticipation. She confirmed that the $500 million peak sales opportunity assumes a positive ACTION study readout, which would enable earlier use post-radiotherapy. She also noted ongoing efforts to understand real-world treatment duration, epidemiology, and increasing testing rates.

Brian Skorney inquired about the initial launch metrics for Modeyso (dordaviprone), asking how they contextualize the greater than $500 million U.S. peak sales guidance, whether the ACTION study is critical for achieving this guidance, and if a positive ACTION readout would alter the peak sales projection.

Answer

Sam Pearce, Chief Commercial Officer, expressed satisfaction with Modeyso's early launch, generating $48 million in 4.5 months, driven by high unmet need and awareness. She confirmed that the >$500 million peak sales opportunity assumes a positive ACTION study, which would enable earlier use in the first-line setting. She also noted the need for further understanding of real-world treatment duration, epidemiology, and testing rates to refine the opportunity.

Brian Skorney asked for preliminary thoughts on whether the review division has indicated an advisory committee for either relutrigine or ulixacaltamide.

Answer

President and CEO Marcio Souza stated there has been no indication whatsoever regarding an advisory committee at this point, and such an indication would not typically be expected before day 60 or day 74 interactions with the agency.

Brian Skorney asked for preliminary thoughts on whether the review division has indicated an advisory committee for either relutrigine or ulixacaltamide, noting that outcomes are becoming rarer and relutrigine's mechanism seems straightforward.

Answer

CEO Marcio Souza stated there has been no indication whatsoever regarding an advisory committee at this point, as such indications typically wouldn't be expected before Day 60 and Day 74 interactions with the agency.

Brian Skorney from Baird requested a breakdown of the safety profile by background medication to identify drivers of AEs like dizziness and somnolence, and also asked for confirmation that the data presented was exclusively from focal onset seizure patients.

Answer

President & CEO Marcio Souza confirmed the data was entirely from focal onset seizure patients, with generalized epilepsy data to come later. He explained that a direct safety breakdown by background ASM is difficult because patients were on multiple drugs. However, he noted that analysis of blood levels showed a significant portion of patients were at toxic concentrations of their background ASMs, which likely contributed to side effects and reinforces the strategy of proactively reducing background doses.

Brian Skorney asked about the commercial opportunity for BIIB080 (anti-tau ASO), considering the challenges faced by Leqembi's IV administration, and what specific clinical data would be necessary to achieve a higher level of commercial success compared to Leqembi.

Answer

Christopher A. Viehbacher, President and CEO of Biogen, highlighted the neurology community's strong interest in tau as a critical target for Alzheimer's, noting BIIB080's proven ability to reduce tau. He emphasized the importance of observing data on cognitive impact and the safety profile, anticipating no ARIA-like events. He described BIIB080 as breakthrough science with potential for combination therapies alongside anti-amyloid treatments or expansion into other tauopathies. He cautioned that even with positive Phase 2 data, a multi-year Phase 3 program would be required before product launch.

Brian Skorney from Baird asked for details on the XEN1101 pain program, including the molecule's pharmacokinetic profile for dosing, the potential for an IV formulation, and the planned clinical model for the initial proof-of-concept study.

Answer

President and CEO Ian Mortimer explained that human PK data is needed to confirm dosing frequency but that an IV formulation is a future possibility. For the proof-of-concept study, he indicated that the company is evaluating postoperative pain models, such as bunionectomy and abdominoplasty, with more details to be shared at an upcoming R&D webinar.

Brian Skorney requested details about the fMRI primary endpoint in the investigator-sponsored MDD study, including the original expectations, the rationale for its selection, and how it compares to neuroimaging endpoints for other approved MDD drugs.

Answer

Chief Medical Officer Dr. Chris Kenney explained that the fMRI endpoint was chosen by the academic investigators to mechanistically explore the drug's effect on the brain's reward circuit, following up on a prior study. He acknowledged the fMRI endpoint was negative but stressed that Xenon's focus was on the clinical scales (MADRS and SHAPS), which showed consistent and positive signals, reinforcing the drug's potential antidepressant effects.

Brian Skorney from Baird asked about the strategic plan for Xenon's Nav1.7 pain program, including the initial target indication for proof-of-concept and whether they would consider using a recently approved competitor as an active control in trials.

Answer

President and CEO Ian Mortimer stated that while early proof-of-concept studies would likely be in traditional acute pain models like bunionectomy, he believes the program has broad potential in both acute and chronic pain. He confirmed that trial design elements, including the potential use of an active comparator, are currently under consideration, with more details to be shared at a future R&D-focused event.

An analyst on behalf of Brian Skorney of Robert W. Baird & Co. asked about the anticipated distribution model for paltusotine and whether its sales data would be captured by services like IQVIA.

Answer

Chief Commercial Officer Isabel Kalofonos stated that paltusotine will use a closed distribution system. She confirmed that the company does not plan to make the data available and that it will be blocked from services like IQVIA to allow Crinetics to track the launch and uptake across different segments internally.

Brian Skorney asked how the inclusion/exclusion criteria for the CAH study compare to the CATALYST study and whether the pediatric Phase II/III plan includes a formal dose-finding component.

Answer

Dr. R. Struthers, CEO, clarified that their trial is designed to enroll a broader patient population than the crinecerfont study. He confirmed the pediatric plan involves ensuring correct doses for different age groups, not just a change in nomenclature. A key differentiator he noted is that their study includes glucocorticoid reduction, which the other trial did not.

An analyst on behalf of Brian Skorney asked about the treatment landscape for hyperparathyroidism, the potential benefits of a PTH antagonist, and the size of the addressable patient population.

Answer

Chief Endocrinologist Dr. Alan Krasner explained that surgery is the main treatment, but many patients do not receive it, and the current medical option only addresses hypercalcemia, not bone or kidney damage. He stated a PTH antagonist could treat all aspects of the disease. CEO R. Struthers added that it could transform the treatment paradigm for non-surgical candidates and that an R&D Day is planned to provide more detail.

Brian Skorney requested more detail on the diabetic retinopathy Phase 2b/3 trial design, including the cadence of readouts, whether the control arm would be sham or active, and the overall trial structure.

Answer

President & CEO Curran Simpson explained the trial is designed for efficiency, with an interim readout from the Phase 2b portion that allows it to roll into a Phase 3 portion and trigger the start of a second pivotal study. CMO Dr. Steve Pakola confirmed the trials will be double-masked with a sham injection control, a plan aligned with the FDA. He noted an active comparator is not feasible as repeated injections are not the standard of care for this patient population.

Brian Skorney from Baird asked for REGENXBIO's perspective on continuity at the FDA's CBER division following recent leadership changes, given the company's frequent interactions. He also requested color on the screening process for the RGX-202 pivotal trial, particularly regarding patient age distribution and the influence of Elevidys's availability.

Answer

CEO Curran Simpson stated that from their viewpoint, it is 'business as usual' with the FDA, with no significant changes in response times or team stability. Chief Medical Officer Dr. Steve Pakola responded that trial screening shows a broad distribution across ages. He emphasized that RGX-202's key differentiators, especially its strong safety profile with no SAEs or LFT elevations and high microdystrophin expression in older boys, are compelling factors for families across the entire age spectrum.

Brian Skorney of Baird requested more detail on the Crinesity Q2 revenue figure, asking about inventory dynamics and the number of billed prescriptions to better understand the net price per TRx.

Answer

CFO Matt Abernethy clarified that there was a $5 million inventory build in the channel during the quarter, reflecting the product's growth trajectory. He noted that the gross-to-net calculation is currently driven primarily by co-pay assistance and distribution fees, as they have not yet entered into significant payer contracting for the product.

Brian Skorney asked if Neurocrine would consider pursuing an adjunctive therapy setting for its M4 agonist NBI-'568, given a competitor's recent failure in that indication, and what a potential trial design might look like.

Answer

CEO Kyle Gano responded that their competitor's drug appears to be used primarily as a monotherapy, and he emphasized the difficulty of running adjunctive treatment trials. He stated Neurocrine's current strategy is to focus on the large standalone opportunity for its muscarinic agents in acute psychosis and other indications like bipolar mania.

Speaking for Brian Skorney, Charlie Moore asked about the Friedreich's ataxia gene therapy collaboration with Voyager, its potential differentiation from other clinical-stage therapies, and its timeline for entering human trials.

Answer

CEO Kyle Gano expressed excitement for the program, highlighting its key differentiator: an IV-administered gene therapy using advanced capsids designed to deliver frataxin to both the cardiovascular system and the CNS, addressing cornerstone symptoms of the disease. He confirmed the program is on track to advance from preclinical to clinical development later in the year.

Brian Skorney asked if formal meetings with CBER are part of the label update process and inquired if a biopsy was performed on the deceased patient and if any information on latent virus reactivation was available.

Answer

President and CEO Douglas Ingram stated that the autopsy results are not yet available but are expected in the next month. Head of R&D Dr. Louise Rodino-Klapac explained the label update is a process of finalizing language with the FDA, which has already confirmed general agreement, rather than awaiting a decision, and the agency would simply ask questions if needed.

Brian Skorney from Baird asked for a rank ordering of the potential rate-limiting steps for ELEVIDYS revenue recognition, such as insurance authorization or center capacity, given that demand is not the issue.

Answer

CEO Douglas Ingram and Chief Customer Officer Dallan Murray explained that it's not a single bottleneck but a complex, multi-step cadence that takes about four months per patient. Murray summarized the key factor as 'time,' as the process involves robust demand, ample site capacity, and positive reimbursement trends, but requires coordination of ~25 people per institution for each dose. Ingram emphasized that their team's expertise in managing this detailed process gives them confidence in their guidance.

Brian Skorney of Baird asked about the timeline for initial data from the antibody-clearing studies for ELEVIDYS, the clinical development strategy for these patients, and whether the Hansa collaboration includes next-generation imlifidase.

Answer

CEO Doug Ingram clarified the studies are for naive patients with pre-existing antibodies, not redosing. Head of R&D Dr. Louise Rodino-Klapac projected initial safety and expression data in early 2025, which will inform any future redosing strategy. Ingram added that Sarepta has a right of first negotiation for Hansa's next-generation therapies.

Brian Skorney questioned why PMO cannibalization isn't a straightforward calculation based on patient prevalence, and asked if patients are being treated with both ELEVIDYS and PMOs concurrently.

Answer

CCO Dallan Murray and CEO Douglas Ingram explained the calculation is not simple due to confounders, primarily the significant and robust PMO sales that occur outside the U.S. Murray stated that they have not seen concurrent commercial use of both therapies to date, though they are aware of some patient interest in that possibility, similar to what has been seen in the SMA space.

Brian Skorney of Baird asked about the upcoming Part 3 data for AB-101 in HBV patients, specifically questioning if any HBV-specific biomarkers are expected to show movement after a 28-day treatment period.

Answer

An executive, likely Dr. Karen Sims, explained that while a robust set of biomarkers is being collected, there are no clear expectations for significant changes in HBV-specific markers after a short 28-day treatment, as AB-101 is an immune modulator, not a direct-acting antiviral. Chief Scientific Officer Dr. Mike Sofia added that the primary strategic goal is to establish AB-101's monotherapy profile before advancing it into combination therapy with imdusiran.

On behalf of Brian Skorney, Charlie asked if the 25mg dose of AB-101 is considered a cap, whether emerging data from the nivolumab combination is influencing the durvalumab trial design, and for the company's perspective on ALPK1 agonism as a therapeutic target.

Answer

Chief Medical Officer Dr. Karen Sims clarified that 25mg is not necessarily a dose cap for AB-101, as the trial design allows for flexibility. She stated she could not comment on unreleased nivolumab data but affirmed the company takes a holistic view of all its trials. Chief Scientific Officer Dr. Michael Sofia responded that the company is aware of a recent abstract on ALPK1 agonism and will evaluate the target more fully after its presentation at EASL.

Inquired about the rationale for the PD-L1 antibody study designs, the company's perspective on targeting PD-1 versus PD-L1, and the specific reasons for choosing nivolumab and durvalumab for different trials.

Answer

The company explained that targeting PD-L1 with a small molecule fits their liver-centric strategy. Nivolumab was chosen for the 202 trial based on collaborator Barinthus's prior positive data. Durvalumab was chosen for the 203 study to specifically inform the future proprietary combination of imdusiran and AB-101 by exploring optimal timing and administration.

The analyst asked about the powering assumptions for the RAISE trial, specifically whether the targeted 30% treatment delta is informed by any blinded data. He also requested details on the statistical analysis for the secondary endpoint, time-to-status cessation.

Answer

The company has not looked at blinded data. Their confidence in a low placebo rate (and thus being well-powered) comes from the trial's design, which enrolled a highly refractory population that had failed an average of 3.5 drugs. The secondary endpoint, time-to-status cessation, is a continuous variable and considered statistically very robust. They expect a large separation, as ganaxolone-treated patients in Phase 2 stopped seizing in a median of 5 minutes, while placebo patients would likely not stop for hours until receiving another treatment.