Jeff Hung

Jeff Hung asked for a definition of the 41,000 bronchiectasis patients who have 'acted' on the company's website and inquired about the expected cadence of these patients seeking prescriptions post-launch.

Answer

CEO Will Lewis clarified that 'acting' means patients have visited the disease awareness website, downloaded materials, and registered for more information, providing contact details for future outreach. Regarding timing, he stated there is no direct precedent, but the high motivation observed in both patient registrations and physician surveys (90% intend to prescribe) suggests a strong initial interest at launch.

An analyst on for Jeff Hung asked for clarification on the use of the additional $150 million from Pharmakon and inquired about the design of the upcoming TPIP Phase III study in PH-ILD.

Answer

CFO Sara Bonstein clarified the $150 million will be received in Q4 and, while not earmarked for a single program, ensures the high-value brensocatib launch is fully resourced. CEO Will Lewis stated that while the final TPIP Phase III design is not yet disclosed, the Phase II study showed compelling directional data on key endpoints like time to clinical worsening, fueling enthusiasm for the program.

Lee Hung, on behalf of Jeff Hung at Morgan Stanley, asked for clarification on the use of the additional $150 million from Pharmakon and inquired about the design of the TPIP Phase III study in PH-ILD, including endpoints and the influence of Phase II results.

Answer

CFO Sara Bonstein clarified that the additional $150 million from Pharmakon is not earmarked for a specific program but ensures that the brensocatib launch is fully resourced. CEO Will Lewis stated that while the final TPIP Phase III design is not yet disclosed, the Phase II results were encouraging, showing compelling directional data on time to clinical worsening and 6-minute walk distance, which builds enthusiasm for the Phase III program.

Lee Hung, on behalf of Jeff Hung, asked if the Phase II data for setrusumab would have met the criteria for the Phase III second interim analysis and how baseline fracture rates compared.

Answer

CEO Emil Kakkis highlighted the Phase II p-value improvement from 0.04 at 6 months to 0.0014 at 14 months. He stated that the Phase II and Phase III populations are very comparable in terms of entry criteria, age, OI types, and baseline fracture requirements, making the Phase II results a reasonable model for Phase III.

Jeff Hung asked about the feedback from the FDA at the End-of-Phase-2 meetings for osavampator and NBI-568, specifically questioning if the agency had concerns about the lack of a dose response for NBI-568.

Answer

Chief Medical Officer Eiry Roberts stated that the company was very pleased with the outcomes for both meetings, receiving supportive guidance from the agency. Regarding NBI-568, she specified there was 'complete support' for advancing the 20-milligram dose into the Phase 3 program, with alignment on endpoints and the overall registration plan.

An analyst on behalf of Jeffrey Hung from Morgan Stanley asked if the NMDA NR2B program (NBI-770) is being developed as an adjunct therapy and how its competitive potential would be evaluated.

Answer

CMO Eiry Roberts confirmed the ongoing Phase II trial is studying patients with an inadequate response to current antidepressants, which could support use as either an adjunctive treatment or monotherapy. She highlighted its oral, selective mechanism as a key potential differentiator that could translate to a favorable benefit-risk profile compared to other treatments.

An analyst on behalf of Jeffrey Hung asked for more details on the Orexin program, specifically the dose reduction planned for the JZP441 Phase Ib study and whether there would be enough therapeutic leeway to expand into other narcolepsy types or IH.

Answer

EVP, Global Head of R&D Robert Iannone explained that while specific doses are not disclosed, the study will evaluate multiple doses. The goal is to characterize the dose needed in NT1 patients and determine if a sufficient safety margin exists, which will ultimately dictate the potential for a path forward in NT1 or other indications that may require higher doses.

Michael Riad, on behalf of Jeffrey Hung at Morgan Stanley, asked for more color on the planned Phase Ib study for the orexin agonist JZP441, including the dose level and potential for expansion into other indications.

Answer

EVP, Global Head of R&D, Rob Iannone, explained that while specific doses are not yet disclosed, the study will evaluate multiple doses. The primary goal is to identify a dose that provides a robust effect in narcolepsy type 1 while maintaining a sufficient safety margin. The results will determine the viability of a path forward in NT1 and other indications like IH, which may require higher doses.

Jeff Hung of Morgan Stanley asked for an update on the ACP-204 program for Alzheimer's disease psychosis, specifically whether regulators have agreed to the master protocol and a reminder of the strategy.

Answer

Executive Elizabeth Thompson stated that they have not re-engaged with regulators yet regarding the Phase III portion of the master protocol and plan to do so further into the Phase II study. She noted this may mean the European Phase III startup is slightly slower but sees no overall impact on the strategy or timeline. An advantage could be starting the European Phase III with Phase II data already in hand, which helps with investigator interest.

Speaking on behalf of Jeffrey Hung, Michael Reed asked how far into 2025 the previously expensed Pombiliti and Opfolda inventory is expected to last and when the next-generation manufacturing process might begin to impact gross margins.

Answer

Chief Financial Officer Simon Harford explained that the expensed inventory will be depleted in the 'earlier part' of 2025, resulting in a 'hybrid year' for COGS and a projected gross margin in the mid-80s. President and CEO Bradley Campbell added that the next-generation manufacturing improvements, which could lower COGS by 20-30%, are not expected to impact the P&L until the 'back half of the decade.'

An analyst on behalf of Jeffrey Hung asked about the remaining market opportunity for Galafold given the growth in diagnosed Fabry patients and the reasons for stronger uptake in naive versus switch patients.

Answer

CEO Bradley Campbell and CDO Dr. Jeff Castelli explained the diagnosed Fabry market has grown significantly to over 18,000 patients, with many more still undiagnosed. They cited improved diagnostics and screening as key tailwinds. Newly found patients are often late-onset with amenable mutations, making Galafold a first-line standard of care. CBO Sebastien Martel added that Galafold's 19% growth outpaced the overall Fabry market's growth of over 12% in Q2.

Jeff Hung asked if the French real-world data showed a correlation between treatment benefit and time since surgical resection for hypothalamic obesity (HO) patients. He also inquired about the strategic goals of the Axovia partnership for Bardet-Biedl syndrome (BBS) and its potential to improve access to the U.K. patient registry.

Answer

Chairman, CEO and President David Meeker stated that time since resection does not appear to impact efficacy, as patients treated over a decade after injury showed benefits consistent with those in the Phase II trial. Regarding Axovia, he and EVP, Head of International Yann Mazabraud explained the partnership supports research into BBS eye findings and epidemiology, noting they already support the U.K. BBS registry.

Asked about the expected demand for the lumateperone LAI formulation and for details on upcoming data presentations from the Phase III MDD studies.

Answer

It is too early to predict demand for the LAI formulation, but they do not expect it to have a huge impact on the oral franchise, citing low LAI penetration in the market. They confirmed they will be presenting more detailed data from the MDD studies (501, 502, and 503) at the upcoming ACNP conference, including secondary endpoints and post-hoc analyses.

Inquired about the baseline INVOKE-2 data, specifically if the mean amyloid PET levels differed between MCI and mild dementia patients, and asked about expectations for amyloid reduction.

Answer

The company does not have the amyloid PET data broken down by MCI versus mild dementia subgroups. Regarding amyloid reduction, they would not be surprised to see it given the ARIA-like signal, but emphasized that AL002's mechanism is broader than just amyloid clearance, so reaching a specific centiloid threshold is not considered a necessary condition for success.

Michael Riad, on behalf of Jeffrey Hung at Morgan Stanley, questioned the baseline INVOKE-2 data, asking if the mean amyloid PET centiloid levels differed between MCI and mild dementia patients and what the expectation is for centiloid reduction.

Answer

Dr. Gary Romano, Chief Medical Officer, responded that he did not have the centiloid data broken down by disease severity. He explained that while some amyloid reduction might be expected given the ARIA-like signal, AL002's broad microglial restoration mechanism means that reaching a specific centiloid threshold, like the 24-centiloid level relevant for anti-amyloid antibodies, is not considered a necessary condition for success.

Asked about the expected ramp-up of patient collections across the 49 activated QTCs in the first half of the year and inquired about the patient start numbers required to achieve the gross profit milestone for the third tranche of the Hercules term loan.

Answer

The company did not provide specific guidance on a per-QTC basis but noted excitement and early enrollments across multiple centers. They declined to comment on the specific number of patient starts needed to reach the gross profit milestone for the third loan tranche, only reiterating the start-based milestones for the second tranche.

Asked about the predictive power of ctDNA on overall survival in cutaneous melanoma versus uveal melanoma, how much treatment time is needed to gain confidence in this marker, and if its predictive power increases in earlier lines of therapy.

Answer

David Berman stated that the ctDNA-survival link is well-validated in uveal melanoma. For cutaneous melanoma, confidence is still emerging. In the current trial, they will look at ctDNA directionally alongside survival data, hoping to establish a similar association. They will need to see both endpoints to make decisions.

Jeffrey Hung from Morgan Stanley asked if the AACR data suggested certain RAS mutations would be harder to treat and whether the broad activity seen in 3D tumor assays would translate to even broader activity in in vivo models and humans.

Answer

President and CEO Benjamin Zeskind asserted that activity is independent of the specific RAS mutation, with resistance being linked to mutations in parallel pathways. Chief Scientific Officer Brett Hall confirmed this, adding that their 3D assay results correlate well with in vivo animal model outcomes, where deeper 3D responses predict better tumor inhibition. Zeskind highlighted the proprietary nature of their 3D assay and informatics platform as a key differentiator.

Jeff Hung of Morgan Stanley questioned the current refill rate for Phexxi, how this rate is factored into the 2022 net product sales guidance, and the demographic profile of women who are refilling their prescriptions compared to initial launch expectations.

Answer

CEO Saundra Pelletier reported a 37% refill rate in December, which was ahead of expectations for an on-demand product. She highlighted that the primary user base is women under 35, a younger demographic than perhaps initially anticipated, which represents a long-term growth opportunity. CFO Jay File added that the 2022 guidance assumes continued growth in refills driven by improved access and a post-COVID environment, rather than being based on a specific, fixed rate.

Melina Santoro, on behalf of Jeff Hung from Morgan Stanley, requested more detail on the Q3 disconnect between prescription growth and net sales, asking when it might resolve. She also asked for an update on prescription refill rates.

Answer

CFO Jay File attributed the disconnect to the mix of patients utilizing copay assistance programs, a situation he expects to continue through Q4 2021. He stated that planned adjustments to the copay program starting in Q1 2022 will improve the gross-to-net ratio. An unidentified company representative added that while the refill rate percentage has declined due to a surge in new patients, the absolute volume of refills is growing.

Jeff Hung from Morgan Stanley inquired about the nature of the ex-U.S. partnership process, asking if it was competitive. He also sought an update on payer conversations regarding preventive treatment coverage for 2022.

Answer

CEO Dr. Vlad Coric confirmed that the partnership process was competitive and involved multiple parties, though he could not disclose further details due to confidentiality. CCO Bj Jones reported that payer discussions for 2022 are progressing "extremely well," expressing confidence in maintaining strong acute therapy coverage and securing favorable preventive coverage.