Joon Lee

Joon Lee inquired about Wave Life Sciences' internal weight loss target for the upcoming WVE-007 six-month (240mg) and three-month (400mg) data to achieve a 5% weight loss at 12 months, and the planned outcomes data to address potential payer pushbacks.

Answer

Paul Bolno, President and CEO, clarified that the 5% weight loss threshold is typically for 12 months in higher BMI patients on optimized regimens. He expects continued weight loss trajectory, building on the 0.9% decrease and substantial fat loss already observed in the low BMI Phase I study, with lean mass stabilization. The Phase IIa portion, enrolling higher BMI patients with comorbidities, will be crucial for regulatory pathways on weight loss, emphasizing body composition improvements (fat reduction, lean mass preservation) for better health outcomes and payer discussions.

Joon Lee inquired about Wave Life Sciences' internal weight loss targets for the upcoming WVE-007 6-month (240mg) and 3-month (400mg) data, aiming for confidence in achieving a 5% weight loss at 12 months, and what outcomes data are planned to minimize payer pushbacks.

Answer

President and CEO Paul B. Bolno indicated that for the current low BMI Phase 1 population, they expect to see a continued downward trajectory in weight loss, building on the 0.9% decrease with lean mass preservation and substantial fat reduction already observed. He emphasized that continued fat loss and lean mass stabilization should drive total body mass down. He highlighted that the upcoming Phase 2a portion, enrolling patients with higher BMI and comorbidities, will better align with typical obesity studies for a regulatory pathway on weight loss. Bolno stressed the importance of body composition (fat reduction, lean mass preservation) for improving health outcomes, beyond just scale weight, noting that over 5% visceral fat reduction is linked to improved cardiovascular and diabetic outcomes.

Joon Lee of Truist Securities inquired about the WVE-007 (Inhibin E) program, asking for the rationale behind expanding cohort two rather than immediately advancing to cohort three, whether the 'therapeutically relevant' dose implies semaglutide-like weight loss, and the target level for Activin E knockdown.

Answer

President & CEO Paul Bolno explained that the company is advancing to cohort three (400 mg) while simultaneously expanding cohort two (240 mg) because cohort two's dose was modeled to align with weight loss seen in preclinical DIO models. He noted that this dose is expected to show more fat loss than GLP-1s for equivalent weight reduction. Bolno added that the decision was driven by favorable safety and strong preclinical-to-clinical translation, giving them confidence to enrich the dataset at this key dose level.

Joon Lee of Truist Securities inquired about the data disclosure trigger for the INHBE obesity program, confirmation of the regulatory division (CDR vs. CBER) for the DMD and Huntington's programs, and the potential read-through from recent competitor data in Huntington's disease.

Answer

President and CEO Dr. Paul Bolno explained that the INHBE data release is tied to an internal cutoff at predefined time points, which remain undisclosed. He confirmed the programs are under the FDA's CDR division and expressed confidence in the accelerated approval pathway, citing the comprehensive nature of Wave's data. Dr. Bolno differentiated Wave's allele-selective Huntington's program from pan-silencing approaches, noting Wave's superior mutant huntingtin reduction and the strong correlation observed with caudate atrophy, which he contrasted with competitor findings.

Joon Lee of Truist Securities questioned the company's strategy for its Huntington's disease program, asking if it would pivot from an MRI-based primary endpoint if mutant huntingtin lowering were accepted as a surrogate endpoint, and inquired about the basis for the cited higher-than-historical patient prevalence.

Answer

President and CEO Paul Bolno stated that if mutant huntingtin lowering were accepted as a surrogate endpoint, Wave would be in a position to file for approval based on its existing SELECT-HD data. He explained the larger patient prevalence number reflects the opportunity to treat earlier, pre-symptomatic patients identified through genetic testing, which is a key advantage of their allele-selective approach.

Joon Lee from Truist Securities inquired about the registration trial strategy for the Inhibin E (WVE-007) obesity program to differentiate from GLP-1s, particularly concerning muscle mass loss, and also asked for an update on the status and IND timing for other DMD exon-skipping candidates.

Answer

CEO Paul Bolno explained that the WVE-007 program aims for a differentiated label focused on 'healthy, sustainable weight loss.' He highlighted preclinical data showing fat loss with muscle mass retention, which will be a key measurement in the clinical trial starting in Q1 2025. Regarding the broader DMD pipeline, Dr. Bolno stated that other exon-skipping candidates have been synthesized and tested with encouraging results, but further guidance on their advancement is pending the 48-week data from WVE-N531 and regulatory feedback expected in Q1 2025.

Joon Lee asked about the evidence needed to convince payers to reimburse for both oxybates and orexin agonists, and whether orexin agonists might cannibalize the oxybate market, given patients' positive long-term extension results on orexin agonists alone.

Answer

Richard Pops, CEO, explained that orexin agonists primarily address wakefulness, which may suffice for many patients. However, oxybates address fragmented sleep. He believes a cohort of patients will benefit from both for daytime wakefulness and nighttime sleep consolidation. Alkermes, having agents in both categories, plans to generate data for payers to support the value of dual therapy for specific patient groups.

Joon Lee asked about the evidence needed to convince payers to reimburse for both oxybates and orexin agonists, given that patients in long-term extension studies seemed to do well on orexin agonists alone, and whether orexin agonists would cannibalize the oxybate market.

Answer

Richard Pops, CEO of Alkermes, explained that orexin agonists address wakefulness, while oxybates address fragmented sleep. He believes a cohort of patients will benefit from both. Alkermes, having agents in both categories, will generate data for payers to justify reimbursement for co-administration in specific patient groups.

Joon Lee asked if AXS-12 NDA submission is eligible for priority review, and sought confirmation from Nick Pizzie that Auvelity's gross-to-net should improve after ADA approval due to the Medicare population.

Answer

Ari Maizel (Chief Commercial Officer, Axsome Therapeutics) stated that AXS-12 is anticipated to be a standard review. Nick Pizzie (CFO, Axsome Therapeutics) confirmed that if 70%+ of ADA scripts are in the Medicare Part D channel, the gross-to-net would be more favorable than the commercial channel.

Joon Lee asked if AXS-12's NDA submission for narcolepsy would be eligible for priority review, and sought confirmation that Auvelity's gross-to-net (GTN) would improve post-ADA approval due to the Medicare population.

Answer

Ari Maizel, Chief Commercial Officer, stated that AXS-12 is anticipated to undergo a standard review. Nick Pizzie, Chief Financial Officer, confirmed that if 70% or more of ADA scripts are in the Medicare Part D channel, Auvelity's GTN would be more favorable than in the commercial channel.

Joon Lee from Truist Securities asked for additional details on the pre-NDA meeting for AXS-05 in Alzheimer's disease agitation, including any surprises or plans for further meetings. He also inquired when Axsome might be in a position to provide financial guidance for Auvelity in MDD.

Answer

Mark Jacobson, COO, offered no new color on the FDA meeting, stating the focus is now on compiling the sNDA package. Nick Pizzie, CFO, explained that it is still premature to issue sales guidance for Auvelity due to evolving payer coverage, a recent sales force expansion, and an upcoming DTC campaign. He directed investors to the previously stated peak sales potential of $1 billion to $3 billion for the MDD indication alone.

An analyst on for Joon Lee of Truist Securities asked about the statistical powering of the ADVANCE-2 study and whether the recent increase in Auvelity prescriptions was driven more by expanded insurance coverage or the earlier sales force expansion.

Answer

CEO Herriot Tabuteau stated that ADVANCE-2 is powered similarly to ADVANCE-1 at 90% to detect a comparable effect size. An executive, likely CCO Ari Maizel, noted it's difficult to compare the impact of the two drivers, but the company is pleased with demand growth post-coverage expansion, which occurred during summer seasonality.

Joon Lee asked about the upcoming PDUFA for Palynziq for adolescents with PKU, inquiring if it's a significant event for PTC Therapeutics. He also asked if the gross-to-net discount for Sephience is expected to move towards the 15%-25% range this year.

Answer

CEO Dr. Matthew Klein stated that even with potential approval, Palynziq's safety, tolerability, administration challenges, and lengthy titration would likely position it as a second-line therapy behind Sephience, which offers oral convenience and a strong profile. CFO Pierre Gravier clarified that while the gross-to-net discount for Sephience is currently at the lower end, it will increase slowly and steadily over multiple quarters, not reaching the top end of the 15%-25% range this year.

Joon Lee of Truist Securities asked if a potential CBER decision on an accelerated approval path for a Huntington's gene therapy could set a regulatory precedent for CBER's review of PTC's oral drug. He also asked for clarification on whether PTC still owes royalties to Sarepta.

Answer

CEO Dr. Matthew Klein acknowledged watching the CBER review with interest, noting that positive read-throughs are possible and that regulatory agencies increasingly desire alignment between divisions like CBER and CBER on rare diseases. He expressed confidence in PTC's own data package for accelerated approval. CFO Pierre Gravier confirmed that PTC still owes a low single-digit royalty to Sarepta.

Joon Lee sought clarification on whether the decision for standard review of ulixacaltamide was influenced by the Inflation Reduction Act (IRA) to delay negotiations. He also asked about the expectation for long-term follow-up data at AAN and the company's pricing strategy for ulixacaltamide, referencing a previously telegraphed $50,000 list price.

Answer

President and CEO Marcio Souza confirmed that the IRA's dynamics and maximizing value over the drug's lifecycle, particularly for a Medicare Part D population, were key considerations for the filing strategy. He stated that more data, including long-term follow-up, would be presented at AAN to reinforce ulixacaltamide's value. While not confirming a specific list price, he emphasized a responsible launch, maximizing value, and proper drug valuation considering payer dynamics and the IRA.

Joon Lee sought clarification on the business reasons for not pursuing priority review for ulixacaltamide, specifically if it relates to avoiding negotiation under the Inflation Reduction Act. He also asked about the expectation of long-term follow-up data at AAN, given payer KOL interest in reauthorization, and whether the previously telegraphed $50,000 list price for ulixacaltamide is still accurate, requesting insight into the pricing strategy.

Answer

CEO Marcio Souza confirmed that the decision not to seek priority review for ulixacaltamide was indeed influenced by the Inflation Reduction Act and its impact on Medicare Part D, aiming to maximize long-term value. He indicated that AAN presentations would include more data reinforcing both short-term and long-term value, particularly the depth of effect on a large proportion of patients, with principal investigators presenting. He did not directly confirm the $50,000 list price but reiterated the focus on responsible launch and maximizing value.

Joon Lee of Truist Securities questioned the discontinuation rate in the RADIANT study, how discontinuations were factored into the efficacy data, and whether the placebo rate in the upcoming POWER-1 study could be expected to be lower than in previous trials for other drugs.

Answer

President & CEO Marcio Souza acknowledged the discontinuation rate was comparable to other studies but could be improved. He attributed it to a lack of background medication adjustment by some investigators, a factor they plan to address. He stated that in an open-label setting, discontinuations are more common. For POWER-1, Souza agreed that the placebo rate could be lower due to enrolling a highly refractory population and ensuring high-quality site operations and patient stability assessment.

Joon Lee asked for clarification on whether the broader GGE study for relutrigine would include LGS patients, the specifics of the ulixacaltamide interim analysis for Study 1, and if there was any anecdotal evidence of pain reduction from Vormatrigine studies.

Answer

CEO Marcio Souza confirmed that LGS patients would be included in the GGE study. He clarified the interim analysis is for Study 1 only and includes a standard futility margin, with the timing of Study 2's readout potentially influenced by the outcome. For Vormatrigine, he noted strong preclinical evidence for its use in pain and stated a full development plan would be shared early next year after a competitive assessment.

Joon Lee asked if the randomized withdrawal trial (Study 2) would maintain its year-end readout timeline if Study 1 is resized. He also asked for the success bar for the upcoming relutrigine data in DEE and about its potential for future applications beyond SCN2A and 8A.

Answer

Executive Marcio Souza confirmed that if Study 1's size is increased post-interim analysis, its readout would be separated from Study 2, but any delay would be minimal due to strong patient interest. For relutrigine, Souza reiterated that a 20-30% seizure reduction would be a 'phenomenal' outcome given the severity of the patients. He also highlighted the significant unmet need and potential to expand into a broad range of pediatric DEEs where current sodium channel modulators are limited by toxicity.

Joon Lee asked if the randomized withdrawal trial (Study 2) would still read out on time if the parallel trial (Study 1) is resized after the interim analysis. He also asked for the success bar for the upcoming relutrigine data and whether its initial indications represent a larger opportunity.

Answer

CEO Marcio Souza stated that both studies are slated to read out together, but if Study 1 is resized, their readouts would be separated by a short period due to strong ongoing patient screening. For relutrigine, he noted a 20-30% seizure reduction would be 'phenomenal' given the severe patient population. He confirmed the initial indications are the 'tip of the iceberg,' suggesting a broader opportunity as a backbone therapy across many severe pediatric DEEs currently treated with toxic alternatives.

Joon Lee inquired about the primary endpoint selection for the Angelman study, specifically the rationale for choosing Bayley-4 cognition over expressive communication, and asked for an update on the percentage of patients rolling over into the long-term extension study.

Answer

Emil Kakkis, Chief Executive Officer and President, explained that Bayley cognition is a fundamental activity intertwined with communication, and while expressive communication is important, its heterogeneity and developmental complexities made it less suitable as a primary endpoint. He noted the study also uses a Multi-Domain Responder Index for a broader assessment. Eric Crombez, Chief Medical Officer, added that the phase III studies show a very high retention rate, with patients electing to continue in the long-term extension.

An analyst on behalf of Joon Lee asked if setrusumab's mechanism of action provides a greater benefit to Type 1 OI patients compared to those with Type 3 and 4, based on academic theories.

Answer

CEO Emil Kakkis firmly refuted this theory, stating that the company's clinical data from Phase II demonstrates that the drug is effective across all major OI types. He explained that while the underlying collagen defects differ, the net result of building more bone mass leads to increased bone strength and reduced fractures for all patients, regardless of their specific collagen mutation.

Joon Lee asked if the OI study going to full completion would imply a weaker drug effect and how setrusumab would compete against bisphosphonates in that scenario.

Answer

CEO Emil Kakkis asserted that going to the final analysis would not imply a weaker effect, attributing a potential delay to high statistical variation in patient fracture rates rather than drug performance. He reiterated confidence that setrusumab will be a superior treatment to bisphosphonates, referencing the consistent 67% fracture reduction seen in Phase II.

Joon Lee questioned if the evolving obesity market, including digital health platforms like Ro and Hims, alters Viking's go-to-market strategy or potential partnering considerations. He also asked about the need for outcomes data for payer reimbursement versus focusing on cash-paying patients, and if the $700 million cash balance covers oral VK2735 development.

Answer

Viking Therapeutics' President and CEO, Brian Lian, acknowledged the rapidly evolving market and the company's flexibility to adapt its commercial strategy. Chief Commercial Officer Neil Aubuchon emphasized starting from a blank slate to optimize for future market trends, considering all channel possibilities. CFO Greg Zante confirmed that the $700 million cash balance is sufficient to fund the oral Phase III trials to top-line data, along with other key catalysts.

Joon Lee asked how the growing influence of companies like Ro and Hims might alter Viking's go-to-market strategy for VK2735, including potential partnerships. He also questioned the necessity of generating outcomes data for payer reimbursement given competitor data, and whether the current $700 million cash balance is sufficient to cover the development expenses for oral VK2735.

Answer

Brian Lian, President and CEO, stated that various market access options are being considered but declined to disclose specific partnership plans. Neil Aubuchon, Chief Commercial Officer, highlighted the advantage of Viking's flexibility to adapt its commercial strategy to the rapidly evolving obesity market. Greg Zante, CFO, confirmed that the $700 million in cash is sufficient to fund the oral VK2735 Phase 3 trials through top-line data, alongside other key catalysts.

Joon Lee followed up on the maintenance study, asking for specific doses for monthly subcutaneous, daily oral, and weekly oral regimens. He also questioned why the 19-week induction doses were higher than those in Phase 3, and asked about key considerations for screening multiple compounds for the amyloid receptor program.

Answer

Brian Lian (President and CEO, Viking Therapeutics) detailed the maintenance doses: monthly subcutaneous at 15 mg, 17.5 mg, 20 mg, and 22.5 mg; daily oral at 17.5 mg, 20 mg, and 27.5 mg; and weekly oral at 110 mg. He explained the higher induction doses are for range-finding the right monthly dose. For the amyloid receptor program, he noted that efficacy, toxicity, compatibility with VK2735, and formulation (small molecule, peptide, subcutaneous, oral) are all important considerations.

Joon Lee followed up on the maintenance study, asking for specific doses for monthly subcutaneous, daily oral, and weekly oral regimens. He also questioned why the 19-week induction doses were higher than those in phase three and asked about key considerations for screening multiple compounds for the amyloid receptor program.

Answer

Brian Lian (President and CEO, Viking Therapeutics) confirmed monthly subcutaneous doses of 15 mg, 17.5 mg, 20 mg, and 22.5 mg; daily oral doses of 17.5 mg, 20 mg, and 27.5 mg; and a weekly oral dose of 110 mg. He explained the higher induction doses are for range-finding the optimal monthly dose. For the amyloid receptor program, he noted efficacy, toxicology, compatibility with VK2735, and formulation (small molecule/peptide, subcutaneous/oral) are all important considerations, highlighting a promising lead compound.

Joon Lee from Truist Securities asked about the strategy for selecting an oral dose for the planned monthly subcutaneous maintenance study and whether the Phase II oral data would be available before that study begins.

Answer

President & CEO Brian Lian stated that a specific oral maintenance dose has not yet been selected, as the company is awaiting the Phase II oral data to inform that decision. He clarified that while having the oral data first would be ideal, it is not a mandatory prerequisite for initiating the maintenance study.

Joon Lee inquired about the key discussion points for the upcoming end-of-Phase-II meeting with the FDA for subcutaneous VK2735, the potential timeline for initiating Phase III trials, and clarification on whether Viking's amylin agonist is a DACRA and how it is being benchmarked.

Answer

Brian Lian, an executive at Viking, explained that the FDA meeting will focus on finalizing the Phase III protocol, including doses and trial size. He confirmed the amylin agonist is a dual amylin and calcitonin receptor agonist (DACRA) and is benchmarked against established compounds like pramlintide and cagrilintide.

Joon Lee asked for expectations regarding pricing trends in the third quarter versus the fourth quarter.

Answer

Robyn Bradbury (CFO) stated that pricing is expected to remain flattish for both the third and fourth quarters, consistent with the stable trends observed over the last few quarters.

Joon Lee of Truist Securities asked about the composition of the projected $3-5 billion hypercortisolism revenue, the strategic importance of the Teva patent litigation, and the timeline for adding a second pharmacy distributor.

Answer

CEO Joseph Belanoff clarified that the $3-5 billion revenue projection for the next 3-5 years is driven almost entirely by relacorilant, which is expected to replace Korlym. He noted the Teva patent case is not a factor in this forecast. Sean Maduck, President of Corcept Endocrinology, added that the second pharmacy will be operational in Q4 2025, with further network expansion being considered for the relacorilant launch.

Joon Lee asked for details on the corrective measures taken by the specialty pharmacy vendor and whether the current setup could handle future demand for Korlym and the potentially larger relacorilant launch. He also questioned whether the existing overall survival data for dazucorilant in ALS might be sufficient for a conditional approval.

Answer

Sean Maduck, President of Endocrinology, explained the pharmacy issue was related to staffing, which has been remedied. He noted that for relacorilant, which does not have the same restrictions as Korlym, a broader distribution network is being explored. Chief Business Officer Charles Robb responded that the company is immediately seeking guidance from US and European regulators on the next steps for the ALS program.

Joon Lee of Truist Securities asked for confirmation that the FDA shares the view of GRACE as pivotal and GRADIENT as supportive, inquired about the timing of the last FDA interaction and pre-NDA meeting, and sought to clarify if the hyperglycemia endpoint showed separation from placebo.

Answer

Chief Business Officer Gary Robb confirmed the FDA's view, citing published guidance that a single well-controlled study (GRACE) with confirmatory evidence is sufficient for approval. He expressed confidence in their position due to the extensive and consistent data across all studies. While declining to comment on specific FDA interactions, Robb stated there were no impediments to filing the NDA. Chief Development Officer William Guyer confirmed that all hyperglycemia endpoints were statistically significantly different from placebo, favoring relacorilant.

Joon Lee of Truist Securities asked about the availability of biomarker data to confirm MECP2 auto-regulation and questioned the timeline for pivotal trial enrollment and completion.

Answer

President and Head of R&D Sukumar Nagendran explained that direct measurement of the intranuclear MECP2 protein is not currently feasible, so the rapid and consistent clinical improvements seen in patients serve as the key biomarker. CEO Sean Nolan projected that pivotal trial site initiation could begin soon, with potential dosing in Q4 2025 or Q1 2026, pending the 30-day FDA review.

Joon Lee asked whether Taysha would continue to report RSBQ scores and if the new endpoints being considered for the pivotal Part B study are already being tracked in the ongoing Part A.

Answer

CEO Sean Nolan stated definitively that the company will no longer report RSBQ data, as the FDA does not consider it a viable primary or secondary endpoint. He confirmed that the key functional and milestone-based endpoints being discussed for Part B are already being collected in Part A, ensuring data continuity.

Joon Lee asked for the rationale behind the change in data disclosure strategy, from reporting early 6-week data to now waiting for a more "fulsome" dataset for the high-dose cohort.

Answer

CEO Sean Nolan candidly explained that the initial early data release was driven by the company's precarious financial position at the time. The positive result from the first patient enabled a successful financing. Now in a stronger position, the company is reverting to a more traditional and robust cohort-by-cohort reporting strategy. He defined a "fulsome" update as having data from the majority of the three patients in each high-dose cohort with over six months of follow-up.

Joon Lee of Truist Securities asked for details on the HERIZON-GEA trial, specifically the ratio of PD-1 positive patients enrolled and how it compares to previous studies.

Answer

Bruce Cozadd, Chairman and CEO, stated that he did not have that specific information available. He also noted that the definition of 'PD-1 positive' can vary depending on the assay used, but confirmed that the company is measuring the biomarker and can conduct post-hoc analyses to support regulatory filings.

An analyst from Truist Securities, on behalf of Joon Lee, asked for specifics on the potential dose reduction being explored for the JZP-441 orexin program and inquired about how much longer pending patents could extend Zepzelca's exclusivity beyond its 2029 composition of matter patent expiry.

Answer

Bruce Cozadd, Chairman and CEO, declined to provide additional details on either topic. He reiterated that the company is exploring lower doses for JZP-441 in patients and that there is no new information to share regarding the potential for longer exclusivity for Zepzelca at this time.

An analyst on behalf of Joon Lee from Truist Securities asked about the potential dose reduction being explored for JZP-441 and the potential length of patent extension for Zepzelca beyond 2029.

Answer

CEO Bruce Cozadd declined to provide additional information on either topic. He reiterated that the JZP-441 trial is exploring lower doses in patients and that the company has no further specifics to share on Zepzelca's potential patent extensions at this time.

Joon Lee asked about the drivers of Epidiolex's continued growth, questioning the split between geographic expansion and deeper penetration, the basis for confidence in a Japanese approval, and which patient segments are driving growth.

Answer

President and COO Renée Galá attributed growth to a differentiated product profile, strong commercial execution, momentum in the adult setting, and improved market access. EVP, Global Head of R&D Robert Iannone addressed Japan, stating that despite the trial not meeting its primary endpoint at an interim analysis, they believe the overall data could support registration and plan to engage with Japanese regulators.

Joon Lee from Truist Securities inquired about the drivers behind Epidiolex's sustained growth, the company's confidence in securing approval in Japan, and the specific patient segments contributing to its success.

Answer

President and COO Renée Galá attributed the 18% year-over-year growth to Epidiolex's differentiated profile, especially data on non-seizure benefits, along with strong commercial execution and momentum in the adult setting. EVP, Global Head of R&D, Rob Iannone, addressed the Japan situation, stating that despite the trial's interim analysis not meeting its primary endpoint, they believe the overall data could support registration and plan to engage with Japanese regulators.

An analyst on behalf of Joon Lee asked about the expected gross-to-net change for FIRDAPSE in 2025 and what proportion of FIRDAPSE patients are currently on the higher 100-milligram dose.

Answer

Executive Michael Kalb addressed the gross-to-net question, stating the 2024 impact from the Inflation Reduction Act (IRA) was minimal (<1%), but is expected to increase to a 3% to 3.5% impact in 2025 and continue rising. CCO Jeffrey Del Carmen responded on dosing, noting the average daily dose has increased by about 2 milligrams since the label expansion and that approximately 20% of patients are currently at or around the 100-milligram dose.

Joon Lee inquired about Catalyst's strategy for securing commercialization partners for FIRDAPSE in new regions like China, and also asked for the drivers behind the gross-to-net adjustment for FYCOMPA and its expected future trend.

Answer

COO & CSO Steven Miller confirmed the company is actively evaluating new territories for FIRDAPSE expansion. CEO Rich Daly added that opportunities in China are being explored. Regarding FYCOMPA, Executive Michael Kalb explained that the gross-to-net is higher due to new fee structures with distributors and government agencies post-TSA with Eisai, and this level is expected to be the new baseline. Daly reiterated that underlying prescription demand for FYCOMPA remains solid.

Joon Lee pointed to a wide range in reimbursement rates and asked about the underlying drivers and the company's improvement efforts. He also asked if a potential European partnership would include a clawback clause similar to the Nuance deal.

Answer

Regarding a European partnership, Executive David Zaccardelli stated that the deal structure would depend on the partner's capabilities and that the company would prioritize the best outcome for shareholders. On reimbursement, Chief Commercial Officer Chris Martin clarified that the issue is not access but patient out-of-pocket costs. He noted that about 80% of claims fall under medical benefit, and for patients with supplemental insurance or who have met their deductible, co-pays are typically low. He also highlighted the availability of patient assistance programs.

Joon Lee asked about reimbursement rates, prescription abandonment rates, and the potential inclusion of Ohtuvayre in upcoming COPD treatment guidelines like GOLD. He also followed up on whether the 50% usage rate in triple-therapy patients has shifted since the launch began.

Answer

Chief Commercial Officer Chris Martin reported that over 80% of prescriptions are processed through medical benefit with minimal hurdles, and most patients have a co-pay under $10. He confirmed the GOLD guidelines committee is meeting soon, which presents an opportunity for Ohtuvayre's inclusion. He also noted that while use on top of triple therapy is at 50%, the other 50% is encouragingly spread across other patient types, consistent with market research.

Jane, on behalf of Joon Lee, asked for more details on the non-CF bronchiectasis program, including ensifentrine's competitive differentiation and any preclinical data supporting its use in this indication.

Answer

An unnamed executive explained that ensifentrine's potential in non-CF bronchiectasis stems from its dual mechanism targeting neutrophilic inflammation and improving mucociliary function, which could reduce exacerbations and make patients feel better. While there is no specific bronchiectasis animal model data, they cited the wealth of data from COPD on reducing cough and sputum, which involves similar pathophysiology.

Joon Lee asked about the proportion of patients receiving ZURZUVAE as a first-line therapy and the challenges preventing its use in patients who are prescribed other treatments.

Answer

COO Chris Benecchi reported that over 70% of patients treated by targeted healthcare providers receive ZURZUVAE as a first-line medication. He explained that patients who do not receive it first-line typically have a prior history on other antidepressants. CEO Barry Greene added that the primary challenge to broader first-line use is overcoming historical prescribing habits, rather than issues of access or cost.

An analyst on for Joon Lee asked for quantification of the ZURZUVAE prescriber base growth from Q1 to Q2 and how it is expected to grow following the sales force expansion.

Answer

CEO Barry Greene confirmed the prescriber base is growing quarter-over-quarter and that the sales force expansion is designed to accelerate this trend. CBO Chris Benecchi emphasized the large untapped market, noting that the 2,000 Q2 prescriptions are just scratching the surface of the 500,000 annual PPD cases, indicating substantial room for growth.

Joon Lee asked whether the plan to start a multiple ascending dose (MAD) study for VY7523 in 2025 implies positive findings from the single ascending dose (SAD) study, and what metrics beyond safety are being tracked in the SAD study.

Answer

Dr. Toby Ferguson, Chief Medical Officer, clarified that the SAD study is being conducted in healthy volunteers, not patients. Therefore, the key data points being collected are pharmacokinetics (PK), initial immunogenicity, and safety to determine appropriate exposures and doses for the subsequent MAD study. The decision to proceed is not based on efficacy signals.

Joon Lee of Truist Securities asked about the expected expression levels of Voyager's vectorized antibodies compared to other methods, plans for preclinical data, and the cadence of any interim data releases for VY-TAU01 before the planned 2026 PET imaging data.

Answer

Executives Alfred Sandrock and Todd Carter explained that while vectorized antibody expression is different from IV dosing (lacking a Cmax but providing constitutive expression), they have experience optimizing payloads and promoters to achieve sufficient levels, and are exploring regulatable expression. For VY-TAU01, CMO Dr. Toby Ferguson reiterated that the key data readout will be from the Multiple Ascending Dose (MAD) trial in 2026, with the current Single Ascending Dose (SAD) trial informing that next step.

A representative for Joon Lee asked for details on Intellia's future plans for its gene writing technology, particularly whether it would be used for in vivo or ex vivo programs.

Answer

CEO John Leonard explained that gene writing is a key part of their platform, and the choice of tool depends on the specific therapeutic problem. He noted its suitability for certain conditions and mentioned that its first application is expected to be an adjunct to their alpha-1 program, addressing both lung and liver disease.

Asked about the timing and potential outcomes of the upcoming Type C meeting with the FDA for the IV ganaxolone program, and for specific discontinuation rates due to somnolence in the Phase II and Phase III TSC trials.

Answer

The company plans to submit the Type C meeting request by the end of August to discuss the IV program, with a meeting expected in Q4. The goal is to align with the FDA on more objective endpoints for a future trial, as the original endpoint was flawed. In the Phase III TSC trial, only 2 patients discontinued due to somnolence, contributing to an overall discontinuation rate below 7%, a significant improvement from the 26% rate in Phase II which was driven by tolerability issues.

Inquired about the potential for clinical differentiation for EDIT-301 following the recent competitor AdCom, whether this would be evident at the upcoming ASH conference, and asked for comments on specific markers like platelet engraftment and hemolysis.

Answer

The company sees its key differentiator in the consistent and robust correction of anemia to normal physiological levels, which is by design. They confirmed they will present data from 17 patients at ASH with longer follow-up, and noted they have seen successful engraftment timelines and are happy with their hemolytic markers.

Joon Lee from Truist Securities inquired about the potential design of the pivotal trial for ADVM-022 in wet AMD, asking about the comparator arm, whether it would include steroid prophylaxis, and other key design elements.

Answer

Chief Medical Officer Aaron Osborne outlined a strategy to conduct a study comparing both the high and low doses of ADVM-022 against the standard of care, aflibercept, administered every other month. This trial would help select a single dose for a Phase 3 study. The primary endpoint would likely be non-inferior visual acuity at around nine months, and the study would also help resolve questions regarding the need for neutralizing antibody screening.