Thomas Shrader

Thomas Schrader asked if the OPUS-3 study format is similar to Merck's equivalent (STRIDE-6) and if the trial is complicated by the wide window of prior PCV vaccination.

Answer

Grant Pickering, CEO of Vaxcyte, confirmed that Pfizer and Merck ran similarly designed studies, though not precisely the same, noting Pfizer presented baseline immune responses while Merck did not. Jim Wassil, EVP and COO, acknowledged the heterogeneity but stated the goal is to show VAX-31 expands coverage without inducing hyporesponsiveness, which has not been observed with PCVs.

Thomas Schrader asked if the OPUS-3 study format is similar to Merck's STRIDE-6, and about the challenges of heterogeneity in the trial due to varying durations since prior PCV vaccination.

Answer

Grant Pickering, CEO of Vaxcyte, confirmed that OPUS-3 is of similar size and design to comparable studies by Pfizer and Merck, though not precisely the same. Jim Wassil, EVP and COO, added that the goal is to show VAX-31 can expand coverage without inducing hyporesponsiveness, which has been observed with polysaccharide vaccines but not typically with PCVs.

Thomas Shrader inquired about the current medical practice for boosting adults with a second PCV dose at age 65, whether it requires a formal ACIP recommendation, and the likelihood of insurance reimbursement.

Answer

CEO Grant Pickering noted that multiple adult doses have been common practice and that the ACIP has already discussed a second dose at 65, seemingly waiting for newer, broader vaccines like Vaxcyte's to become available. COO Jim Wassil added that there have not been reimbursement controls on multiple doses to date. Pickering concluded that the 'ground is fertile' for revaccination due to the high ROI and safety of the vaccines.

Thomas Schrader asked for clarification on the strategic differences between the Phil and ApolloCare specialty pharmacies for VEVYE distribution and inquired if the 'IHEZO for all' initiative involves trial programs that might impact short-term ASP.

Answer

CEO Mark Baum clarified that ApolloCare's value is its broader network of contracted insurance plans, which helps capture more commercially covered prescriptions and supports a higher overall ASP. He explained that 'IHEZO for all' is not about free drug trials but about building 'reimbursement confidence' by educating physicians on the product's pervasive insurance coverage to drive deeper utilization.

Thomas Shrader from BTIG questioned if the upcoming U.S. BLA for the COVID vaccine is for the original or an updated strain, and asked about the antigen interplay in the seasonal flu vaccine, specifically if neuraminidase antibodies could compensate for hemagglutinin response.

Answer

President and CEO Joseph Payne clarified that the initial U.S. BLA filing is to approve the vaccine platform with the original strain, with annual variant updates expected post-approval. For the flu vaccine, he stated that detailed data on the immunogenicity of the 8-valent candidate, including responses to all antigens, will be presented later in the year.

Thomas Shrader from BTIG inquired about the estimated size of the safety database required for a potential CF filing and asked if there is a method to monitor drug uptake in the liver for the OTC program independent of measuring OTC correction.

Answer

President and CEO Joseph Payne estimated that a safety database of approximately 100 patients is a reasonable expectation for the CF program, implying a Phase 3 trial of at least 50 participants. For the OTC program, he clarified that there will be no liver biopsies. Instead, the company will rely on a biomarker strategy, including glutamine levels and the functional 15N ureagenesis assay, to monitor the therapeutic effect in the liver.

Thomas Shrader questioned how preclinical data informs the delivery of CFTR mRNA in inflamed lungs and inquired about the company's interest in a seasonal flu vaccine, given the reactogenicity issues seen with competitors.

Answer

CSO and COO Dr. Pad Chivukula explained that preclinical work optimized their formulation to be stable and effective in diffusing through mucus. President and CEO Joseph Payne added that for seasonal flu, Arcturus's self-amplifying mRNA platform offers competitive advantages, including a lower dose and more durable immunogenicity, which could address the reactogenicity and duration challenges faced by other mRNA vaccines.

Thomas Shrader of BTIG asked for clarification on the INFRONT3 trial's statistical analysis plan, questioning why progranulin was added as a co-primary endpoint and whether progranulin levels consistently normalized in prior studies. He also inquired about the receptor basis for the company's ABC platform.

Answer

Chief Medical Officer Giacomo Salvadore explained the change was a specific request from an FDA statistical reviewer, noting the company has over 90% power to show a significant effect on progranulin. President & Head of R&D Sara Kenkare-Mitra confirmed the lead ABC programs use the transferrin receptor. CEO Arnon Rosenthal added that progranulin elevation has been consistently observed in all treated individuals.

Thomas Shrader from BTIG asked if an ARIA-like MRI signal has been observed in the AL101 trial and whether seeing such a signal would help de-risk the progranulin program. He also questioned if increasing progranulin provides as broad a therapeutic effect as targeting TREM2.

Answer

Dr. Gary Romano, CMO, confirmed that while the AL101 study includes MRI surveillance, no ARIA-like signals have been observed to date, though it is still early. Dr. Arnon Rosenthal, CEO, explained that while the mechanism is different from TREM2, progranulin also has very broad effects as a lysosomal chaperone and neuronal survival factor, making it a robust therapeutic approach.

Thomas Shrader of BTIG asked for clarification on the intellectual property for NRX-100, questioning the value of the preservative-free patent upon approval and its importance relative to the pH-neutral version's IP.

Answer

Jonathan Javitt, Founder, Chairman, and CEO, explained that the patent for preservative-free ketamine is significant because drugs with toxic preservatives may be withdrawn from the market. This could grant NRX-100 extended market exclusivity via an Orange Book listing, potentially for a longer duration than initially anticipated. While the pH-neutral version is also proprietary, the preservative-free formulation's patent could provide a surprisingly long competitive advantage.

Thomas Shrader asked for clarification on the ketamine clinic acquisition landscape in Florida, specifically if deals would be 'chunky' (i.e., multi-facility), and questioned the procedural nuances at the FDA for managing a simultaneous NDA and ANDA submission for ketamine.

Answer

CEO Jonathan Javitt confirmed that clinic acquisitions are expected to be 'chunky,' generally involving more than one clinic at a time, to build out their network efficiently. He clarified that the NDA and ANDA submissions are distinct: the NDA is for the Division of Psychiatry Products to add new indications (depression, suicidality), while the ANDA is a simpler filing to offer a preservative-free generic version for existing indications, leveraging the same manufacturing data.

Thomas Shrader of BTIG asked if the commercial availability of competing Alzheimer's antibodies poses a risk to the ALTITUDE trial's dropout rate and inquired about the potential of plasma p-tau217 as a definitive treatment biomarker.

Answer

Dr. Eric Siemers, Chief Medical Officer, reported no negative impact on the trial, citing faster-than-expected enrollment and a 'quite good' discontinuation rate, partly due to the study's open-label extension. Dr. James Doherty, President and Chief Development Officer, added that while p-tau217 is critical, the field will likely use a series of markers, not a single one, to assess treatment efficacy.

Thomas Shrader posed two questions: first, how Acumen thinks about achieving efficacy with a subcutaneous antibody that may not remove plaque, and second, what the strategic advantage is of using the IADRS scale over the CDR Sum of Boxes as the primary endpoint.

Answer

Dr. Eric Siemers, Chief Medical Officer, addressed the endpoint question, noting that IADRS is viewed as having less subjectivity and variability than CDR-SB, referencing the donanemab Phase II study as an example where IADRS showed significance while CDR-SB did not. CEO Daniel O'Connell explained that the primary goal is to demonstrate a meaningful cognitive benefit by targeting soluble oligomers, with the full story on plaque effects to be revealed by the ALTITUDE-AD data.

Thomas Shrader from BTIG asked if Acumen would consider an interim analysis of the ALTITUDE-AD trial at 6 months, whether blinded ARIA data would be released during the study, and if the Phase I subcu data would be sufficient for a pivotal trial.

Answer

CEO Daniel O'Connell, President and Chief Development Officer Dr. Jim Doherty, and Chief Medical Officer Dr. Eric Siemers collectively responded. O'Connell stated there are no plans for an interim efficacy look to preserve the study's potential for registration. Dr. Doherty added this protects the study's statistical integrity. Dr. Siemers confirmed that ARIA data will not be disclosed until the trial is unblinded. Regarding the subcutaneous formulation, O'Connell reiterated that next steps will be determined after reviewing the Phase I data.

Thomas Shrader of BTIG asked whether APOE4 patients are considered inherently inflammatory and questioned if the trial is sufficiently powered to detect a statistically significant change in the CDR endpoint within six months, given its size.

Answer

CEO RJ Tesi confirmed that APOE4 is considered an 'inflammation gene,' associated with earlier disease onset and faster progression. Dr. CJ Barnum, Head of Neuroscience, addressed the trial's statistical power, stating their assumptions were conservative and have been validated by the 6-month data from the larger lecanemab and donanemab trials, which showed significance. RJ Tesi added that their trial's stringent quality control in a smaller patient population provides an unheralded advantage that could reduce data noise.

Thomas Shrader asked for an update on the FDA's position regarding the EMACC endpoint, clarification on whether the 800 patients screened for the AD02 trial were pre-selected for inflammation, and if the patient selection criteria for the TRD program would be similar.

Answer

Dr. C.J. Barnum explained the FDA's official stance on EMACC is pending data review, but INmune Bio has followed the agency's guidance. He clarified that the 800 screened patients were not pre-selected for inflammation, and the high screen failure rate was typical for AD trials. For TRD, he noted the enrichment is similar but uses CRP and anhedonia as specific markers. CEO Dr. RJ Tesi added that a poster at the upcoming AD/PD conference would detail the patient enrollment profile.

Thomas Shrader questioned the commercialization strategy for an injectable drug in treatment-resistant depression (TRD), asking if it could leverage infrastructure like ketamine clinics. He also asked if inflammation plays a known role in psychedelics.

Answer

Head of Neuroscience Dr. CJ Barnum explained that XPro for TRD is a subcutaneous self-injection, unlike ketamine infusions, and clinicians don't anticipate adoption issues. CEO Dr. RJ Tesi added that GLP-1 drugs have normalized patient comfort with self-injections. Dr. Barnum was not prepared to answer the question about psychedelics.

Thomas Shrader from BTIG asked if the CIC vaccine is designed to have a reactogenicity profile similar to a standalone flu shot and inquired about the extent of human data for the updated COVID strain in the current BLA filing.

Answer

CEO John Jacobs responded that the CIC study is designed to show an immune response, not to meet a specific reactogenicity target, though they expect it to be reasonable. COO John Trizzino clarified that the BLA filing is for the existing vaccine based on prior Phase III data, and an updated strain would be a subsequent filing post-approval.

Thomas Shrader asked about the overlap between COPD and bronchiectasis patients, whether Ohtuvayre's performance in this subgroup is known, and if the company is affected by the Medicare Part D redesign.

Answer

Chief Commercial Officer Christopher Martin explained that Verona is not significantly affected by the Part D redesign, as approximately 80% of reimbursement is through the medical benefit (Part B or Medicare Advantage). Chief Development Officer Dr. Tara Rheault and Chief Medical Officer Dr. Kathleen Rickard added that while few patients with confirmed bronchiectasis were in the ENHANCE trials, the drug's mechanisms are applicable. They noted that while there is symptom overlap, the underlying diseases differ, and about 20% of diagnosed bronchiectasis patients may also have COPD.

Thomas Shrader from BTIG asked about the clinical overlap between COPD and bronchiectasis, whether Ohtuvayre's efficacy in these patients is known, and if the company is impacted by the Medicare Part D redesign.

Answer

Christopher Martin, Chief Commercial Officer, clarified that Ohtuvayre is primarily reimbursed under medical benefit (Part B), making the Part D redesign impact minimal. Dr. Tara Rheault, Chief Development Officer, and Dr. Kathleen Rickard, Chief Medical Officer, explained that while few patients with confirmed bronchiectasis were in the pivotal trials, the drug's mechanisms are applicable. They noted an estimated 20% of bronchiectasis patients also have a COPD diagnosis.

Thomas Shrader asked about any common themes among the 45% of Tier 1 healthcare providers who have not yet prescribed Ohtuvayre and questioned if the nebulizer delivery system poses a significant barrier to adoption.

Answer

Chief Commercial Officer Chris Martin explained that the prescribing pattern reflects typical launch dynamics of early versus late adopters, rather than a specific structural issue. He noted that market research indicates non-prescribing physicians see the drug's benefits and intend to prescribe it in the future. Regarding the delivery method, he asserted that innovation is trumping the route of administration, calling the nebulizer a 'nonissue' and noting that some patients find it a comforting way to receive their medication.

Thomas Shrader asked what physicians who are trialing Ohtuvayre with a few patients are looking for to increase adoption, and what 'power users' are saying that could refine the marketing message. He also asked for an update on the performance of the patient support and access infrastructure.

Answer

Executive David Zaccardelli and Chief Commercial Officer Chris Martin explained that physicians typically accelerate usage after positive initial patient feedback, which is encouraged by increased interaction with the sales team. Martin confirmed the support infrastructure is working well, with a significant majority of scripts being paid and over 80% of dispensed patients having a co-pay under $10.

Thomas Shrader asked for any early read on the types of patients receiving the first Ohtuvayre prescriptions, specifically if they are patients failing triple therapy or being treated earlier. He also inquired about the development pathway for a fixed-dose combination in a handheld device.

Answer

Chief Commercial Officer Chris Martin explained it's too early for a detailed patient profile analysis but confirmed the initial prescribers are from their top-tier target list of physicians. These doctors report a high unmet need for patients with persistent symptoms. An unnamed executive clarified that developing a fixed-dose combination typically requires working through the monotherapy's development in that specific formulation first.

Thomas Shrader from BTIG inquired whether patient dropout rates in the trials are tracking as expected given the study's complexity and if the company is increasing the number of patients to be enrolled.

Answer

An unnamed executive responded that the patient attrition rate is currently running slightly below their plan, indicating better-than-expected retention. He also confirmed that the company is not making any adjustments to the trial's sample size.

Thomas Shrader from BTIG asked if the FDA has previously seen the open-label extension data and whether Minerva anticipates needing to present a new trial design at the upcoming Type C meeting.

Answer

CEO Remy Luthringer clarified that the FDA has not seen the detailed open-label extension data, only high-level information from press releases. Regarding a new trial, Luthringer stated that the immediate focus of the Type C meeting is to discuss the monotherapy approach based on the existing data. He believes their two well-controlled studies align with the FDA's 2019 guidance for unmet medical needs, and any decisions about further studies will depend on the outcome of this meeting.

Thomas Shrader inquired about the design of the Phase IIb trial, specifically regarding the stratification of younger versus older infant groups, how results would be reported, and the potential for the trial to be considered pivotal. He also asked about the rationale and timing for conducting the nonhuman primate Lung Deposition Study.

Answer

Chief Development Officer Dr. Steven Simonson explained that the Phase IIb trial protocol allows for flexibility in adjusting the proportion of babies in each age group, informed by ongoing studies. He clarified it will be analyzed as a single trial, not two separate ones. Dr. Simonson stated the Phase IIb is a crucial supportive piece for the planned Phase III program. Regarding the primate study, he noted it provides key data on lung deposition for the development package and future device work. CEO Craig Fraser added that overall trial timelines remain unchanged despite the added flexibility.

Thomas Shrader inquired about the rationale behind the different dosing and re-dosing rules for the AEROSURF Phase IIa and IIb trials, the possibility of the Phase IIb trial serving as a pivotal study, and the company's cash burn outlook for the year.

Answer

Chief Development Officer Dr. Steve Simonson explained that the IIa dosing strategy was designed to build a broad foundational database, while the IIb doses were selected based on that data to optimize for efficacy, safety, and efficiency. He clarified that repeat dosing is triggered by clinical need. Dr. Simonson also stated it was premature to consider the IIb trial as pivotal. Executive John Tattory addressed the financials, projecting a temporary increase in quarterly cash burn during the first half of the year as both trials run concurrently, followed by a decrease as the IIa trial concludes mid-year.

Thomas Shrader inquired about the projected rapid enrollment for the second Phase IIa study, the suitability of younger babies as the target market for AEROSURF, the patient demographics for the Phase IIb trial, and the specific differences in dosing protocols across the various studies.

Answer

Chief Development Officer Steven Simonson explained that while younger babies are fewer in number, a higher percentage meet the trial's inclusion criteria, which could accelerate enrollment. He confirmed this younger group is a key target due to greater surfactant deficiency. Simonson clarified the Phase IIb trial will enroll babies from 26 to 32 weeks gestational age. CEO John Cooper added that the Phase IIb trial will begin with the 29-32 week group before enrolling the younger 26-28 week cohort. Simonson also detailed that both ongoing Phase IIa studies allow for repeat dosing and the Phase IIb trial will test two dose levels against a control group.

Thomas Shrader of Stifel questioned the strategic rationale for unlinking SURFAXIN and AEROSURF in partnership discussions, after years of them being presented as a combined strategy. He also asked about the company's history with late-stage SURFAXIN negotiations, the reason for the large control group in the AEROSURF trial, and whether the collaboration with Battelle aims to increase the dosing rate.

Answer

CEO John Cooper explained that the company believes it can create more value by advancing AEROSURF further before partnering it, and that the current focus is on finding a partner for SURFAXIN and its lyophilized version. Chief Development Officer Steven Simonson clarified that the large control group is necessary to create a robust reference for safety and tolerability in this novel patient population. He also confirmed that optimizing the delivery device with Battelle is a key focus.