Jason Butler

Jason Butler asked for initial comments on the impact of the increased NUPLAZID field force and how ACADIA assesses the ROI on its full commercial investment for NUPLAZID, including non-field force components.

Answer

Catherine Owen Adams, CEO, confirmed regular ROI assessment for marketing and commercial mix. Tom Garner, Chief Commercial Officer, reported that the expanded NUPLAZID field team, fully deployed in January, has hit the ground running with a noticeable increase in activity and referral volumes, now targeting 11,000 writers (up from 7,000). Catherine added that the significant SG&A step-up in 2026 is foundational, with more incremental increases expected towards 2028.

Jason Butler asked for initial comments on the impact of the increased NUPLAZID field force and how Acadia assesses the ROI on its full commercial investment for NUPLAZID, particularly non-field force components.

Answer

Catherine Owen Adams, CEO, emphasized that Acadia regularly assesses the ROI of its marketing and commercial mix to ensure investment efficiency and effectiveness. Tom Garner, Chief Commercial Officer, reported that the expanded NUPLAZID field team, now covering 60% of the PDP market and targeting 11,000 writers, has hit the ground running with a noticeable increase in activity and referral volumes.

Jason Butler inquired about the investment strategy for NUPLAZID, asking if the company is considering more or longer-term investments in the franchise following recent DTC success and greater IP visibility.

Answer

CEO Catherine Owen Adams explained that the company is bifurcating its strategy between near-term commercial efforts and long-term brand maximization now possible through 2038. She confirmed the current DTC campaign is paying dividends and that the company was delighted to extend its agreement with Ryan Reynolds for the 'More to Parkinson's' campaign, which has been a key driver of awareness.

Jason Butler from Citizens JMP asked for details on the profile of new NUPLAZID patients, specifically whether the recent marketing campaigns and label change are attracting older patients or those earlier in their psychosis diagnosis.

Answer

Executive Brendan Teehan responded that it is still early days for the new campaigns. So far, the prescriber mix reflects previous quarters, and there has not been a substantial change in the age of patients. He noted the caregiver campaign helps families identify subtle changes in loved ones more readily.

Jason Butler asked for more details on the learnings from the prior STARS trial and the refined instructions for use in STARS-2. He also inquired about the alignment with the FDA on primary and key secondary endpoints, the confidence in repeating STARS-1 data, and the assumptions for STARS-2 enrollment timeline and patient population similarities.

Answer

Michael Shetzline, Chief Medical Officer, explained that learnings from STARS-1 primarily focused on optimizing dose administration with better kit components and instructions for use in STARS-2. He confirmed FDA alignment on using the same primary and key secondary endpoints, expressing high confidence in the STARS-2 outcome due to these refinements. Thomas McCourt, CEO, added that the study's attractive profile (high probability of success, well-tolerated, once-weekly dosing, 24-week trial) should aid enrollment.

Jason Butler from Citizens JMP Securities inquired about the specific learnings from the prior STARS trial that informed the refined instructions for use in STARS-2, the FDA's alignment on primary and key secondary endpoints, and the confidence in replicating previous data. He also asked about the feasibility of the STARS-2 enrollment timeline and the expected similarities in patient populations between STARS-1 and STARS-2.

Answer

Gregory Martini, SVP and CFO, initiated the response, followed by Michael Shetzline, Chief Medical Officer, who detailed that learnings primarily focused on optimizing dose administration with better kit components and instructions for use. Dr. Shetzline confirmed FDA alignment on maintaining the same primary and key secondary endpoints, expressing high confidence in the STARS-2 outcome due to these refinements and the successful execution of STARS-1. He also stated that the enrollment timeline is informed by STARS-1 experience, with existing STARS Extend sites aiding the process.

Jason Butler asked for details on the patient characteristics achieving enteral autonomy with apraglutide, specifically regarding stoma versus CIC patients, and whether patients who achieved autonomy in the double-blind study maintained it.

Answer

Chief Medical Officer Michael Shetzline confirmed that patients with both stoma and colon-in-continuity (CIC) are achieving enteral autonomy. He stated that the data shows a numerical benefit across all subpopulations. Shetzline also noted that patients who achieved enteral autonomy during the double-blind period have maintained it in the open-label extension study, with the total number of patients reaching autonomy now at 27.

Jason Butler questioned the key drivers of LINZESS demand growth through its LOE, beyond promotions, and asked about the commercial readiness activities for apraglutide planned during its regulatory review.

Answer

CEO Thomas McCourt identified LINZESS demand drivers as overall market growth, increased patient care-seeking, broader physician adoption, the pediatric indication, and the future potential for an OTC switch. For apraglutide, he detailed ongoing market preparation, including disease awareness programs and the creation of a critical patient services hub to support the launch.

Jason Butler questioned the remaining gating items for the apraglutide BLA submission and asked about the feedback management is receiving from potential prescribers on the clinical data.

Answer

Chief Medical Officer Michael Shetzline stated that remaining work includes finalizing the commercial supply chain and supporting CMC documentation for the enhanced vial kit. He added that feedback from KOLs is excellent, praising the once-weekly dosing and tolerability. CEO Thomas McCourt and CBO Andrew Davis added that market preparation is leveraging new ICD-10 codes to identify patients and guide the go-to-market strategy.

Jason Butler asked about the pre-commercial activities being undertaken to build brand awareness for apraglutide and questioned the contribution of the pediatric market to LINZESS's growth.

Answer

CEO Thomas McCourt detailed the pre-launch strategy for apraglutide, which includes a disease education program targeting the GI community and patients to raise awareness and help identify eligible patients. CFO Sravan Emany addressed the pediatric launch, stating that while still early, they are encouraged by strong new-to-brand prescription growth, noting that a large portion of the 18% NBRx growth is from the 72-microgram dose approved for pediatric use.

Jason Butler asked for color on the types of centers signing up for the MYQORZO REMS program, specifically if they are current CMI prescribers, new CMI prescribers, or non-CMI prescribers.

Answer

Andrew Callos, EVP and CCO, and Robert Blum, President and CEO, stated that while the majority are current CMI prescribers, they are also seeing a higher-than-expected number of new CMI prescribers and non-CMI prescribers completing REMS certification.

Jason Butler asked for color on the types of centers signing up for the MYQORZO REMS program, specifically if non-current CMI prescribers or first-time CMI prescribers are enrolling, or if the majority are existing CMI prescribers.

Answer

EVP and Chief Commercial Officer Andrew Callos confirmed that while the majority of REMS-certified prescribers are current CMI users, they are also seeing a higher-than-expected number of non-CMI and first-time CMI prescribers. President and CEO Robert Blum added that initial efforts are focused on high-volume prescribers.

Jason Butler of JMP Group LLC asked about the similarities and differences in commercial readiness preparations for the European launch versus the U.S. launch.

Answer

President and CEO Robert Blum and EVP & CCO Andrew Callos explained the EU launch is a country-by-country process gated by reimbursement negotiations, unlike the single U.S. launch. Germany is the initial focus. They also noted the EU manages risk via labeling rather than a formal REMS program, and spending is gated by reimbursement milestones.

Jason Butler of Citizens JMP asked about the data disclosure plan for the first two cohorts of the AMBER study for CK-586 and whether these initial doses should be considered effective.

Answer

Fady Malik, EVP of R&D, emphasized that AMBER is a Phase II dose-finding study. Stuart Kupfer, SVP and CMO, clarified that results will be disclosed from the totality of the data, not by individual cohorts. He described the study as a careful, systematic dose-titration effort to identify the optimal benefit-risk profile, starting with lower doses.

Jason Butler of JMP Securities asked about the recent safety update submitted to the FDA, inquiring how much data came from after the FOREST-HCM protocol was amended to reduce echo monitoring frequency and if the safety profile remained consistent.

Answer

EVP of R&D Fady Malik explained that while the protocol amendment was implemented last year, not much data has yet accumulated with the 6-month monitoring schedule. He emphasized that the thousands of 3-month monitoring echoes showed very little impact on dosing or safety. He confirmed the overall safety profile of aficamten remains strong and consistent as more data is gathered, with no other protocol amendments currently planned for FOREST.

Jason Butler from Citizens JMP inquired about the new neuromuscular candidate, CK-089, and how it differs from the company's previous fast skeletal muscle troponin activators (FSTAs).

Answer

Robert I. Blum, President and CEO, and Fady Malik, EVP of R&D, explained that CK-089 is a third-generation molecule from a different chemical scaffold. It is more potent, has better pharmaceutical properties, and is being developed for a specific muscular dystrophy, not ALS, applying key learnings from prior programs.

Jason Butler inquired about the amount of data Prothena believes is necessary to secure a partnership for its CYTOPE platform, or alternatively, what data would be required to de-risk initial clinical development if Prothena chose to advance a CYTOPE program internally.

Answer

Gene Kinney, President and CEO, highlighted the TDP-43 CYTOPE program's robust CNS activity and specific intracellular targeting with systemic administration in aggressive ALS mouse models, addressing both toxic gain-of-function and loss-of-function. Brandon Smith, COO, emphasized the CYTOPE technology's broad, therapeutic area-agnostic applications, ongoing research collaborations, and the process of potential partners validating the technology with their own targets before formal partnerships.

Jason Butler (Citizens JMP) asked for a broader perspective on the amount and type of data Prothena would deem necessary to secure a partnership for its CYTOPE platform, or alternatively, what data would be required to de-risk internal clinical advancement of a CYTOPE program, such as TDP-43 CYTOPE.

Answer

Gene Kinney, President and CEO, highlighted the compelling in vivo data for TDP-43 CYTOPE, demonstrating systemic administration leading to robust CNS activity and removal of intracellular aggregates in an aggressive ALS mouse model. He emphasized the technology's ability to specifically target abnormal TDP-43 while preserving normal function, correcting both toxic gain-of-function and loss-of-function pathologies. Brandon Smith, COO, noted the broad, therapeutic area-agnostic applications of CYTOPE, leading to active research collaborations and partner interest since its public introduction in November 2025.

Jason Butler of Citizens JMP inquired about the PRX012 data expected by year-end and the key information needed from that data to inform the design of a late-stage clinical program.

Answer

President and CEO Gene G. Kinney emphasized two key areas: assessing the risk-benefit profile (amyloid reduction vs. ARIA) and confirming the reduced treatment burden of a once-monthly, at-home subcutaneous injection. Executive Mark Johnson detailed that initial data from ~225 patients in the ASCENT-2 trial will be shared mid-year, with potential follow-up data later in the year, all aimed at defining the optimal dose for a registration-enabling trial.

Jason Butler of Citizens JMP asked about the PRX012 data expected by year-end and what specific information the company is looking for to inform the design of a late-stage development program.

Answer

President and CEO Gene G. Kinney emphasized two key factors: the risk-benefit profile (ARIA vs. amyloid reduction) and reducing treatment burden via a once-monthly, at-home subcutaneous injection. Executive Mark Johnson added that initial data from ~225 non-homozygous APOE4 patients will be shared mid-year, with data from homozygous carriers and long-term extensions to follow. The primary goal is to define the optimal dose for a registration-enabling trial.

Jason Butler asked about the PRX012 data expected by the end of the year and what specific information the company is looking for to inform the design of a late-stage development program.

Answer

CEO Gene G. Kinney highlighted the importance of both risk-benefit (ARIA vs. amyloid reduction) and reduced treatment burden via a once-monthly, at-home subcutaneous injection. Executive Mark Johnson detailed that initial data from ~225 participants in the ASCENT-2 'A' cohorts will be shared mid-year, with later updates from 'B' cohorts and the ASCENT-3 extension study. The goal is to find the optimal dose regimen by evaluating safety, PK, and PD.

Jason Butler inquired about the regulatory pathways for Halozyme's ADC strategy, differentiating between improving approved therapies and developing unapproved molecules. He also asked for context on current treatment paradigms for approved ADCs and how subcutaneous delivery with ENHANZE could impact patient time in IV centers.

Answer

Helen Torley, President and CEO, and Chris Wahl, Chief Scientific Officer, addressed the questions. Chris Wahl explained that for converting IV to subQ ADCs, a traditional PK non-inferiority approach is expected. For unapproved products seeking additional efficacy/safety benefits, appropriate phase trials beyond PK non-inferiority would be needed. He noted that many ADCs are used in combo therapy, where subQ could reduce infusion center time. As more drugs go subQ, a significant reduction in infusion center visits is anticipated, especially as ADCs move to first-line therapy.

Jason Butler asked about the regulatory pathways for ENHANZE-enabled antibody-drug conjugates (ADCs), differentiating between approved and unapproved molecules, and sought context on current treatment paradigms for approved ADCs to understand the potential for reduced IV center visits.

Answer

Helen Torley, President and CEO, and Chris Wahl, Chief Scientific Officer of Halozyme Therapeutics, addressed the questions. Chris Wahl explained that for converting IV to subQ ADCs, a traditional PK non-inferiority approach is expected. For unapproved products seeking additional efficacy and safety benefits, appropriate phase trials beyond PK non-inferiority would be required. He noted that while many ADCs are used in combo therapy, reducing infusion center time, the increasing use of ADCs in first-line therapy and combination with subQ products (often ENHANZE-enabled) suggests a significant reduction in infusion center visits over time.

Jason Butler from Citizens JMP questioned the potential for updating long-term guidance, given the strong sequential royalty growth expected in 2025. He also asked for details on the Ocrevus launch patient mix and the level of partner interest in the high-volume auto-injector.

Answer

CFO Nicole LaBrosse clarified that while current year guidance is updated quarterly, long-term guidance is updated annually at the start of the year. President and CEO Dr. Helen Torley reported that for Ocrevus, Roche has indicated about 50% of new subcutaneous patients are new to the brand, with the other 50% switching from IV. Dr. Torley also confirmed strong partner interest in the high-volume auto-injector, with multiple discussions underway.

Jason Butler asked if the development work for the large volume auto-injector is broadly leverageable across partners and inquired about the remaining amount on the $250 million accelerated share repurchase (ASR) program.

Answer

President and CEO Dr. Helen Torley confirmed the auto-injector component work is designed to be suitable for multiple partners. CFO Nicole LaBrosse explained that while the ASR is ongoing, approximately 80% of the shares were delivered and retired in December 2024, with final settlement occurring by the end of Q1 2025.

Jason Butler from Citizens JMP inquired about the progress of Argenx's VYVGART Hytrulo prefilled syringe with the FDA and how Halozyme's experience with other collaborators has informed this specific regulatory process.

Answer

President and CEO Dr. Helen Torley confirmed the PDUFA action date is expected in April 2025. She clarified that while Halozyme advises on the ENHANZE formulation, Argenx is leading the development and regulatory work for the device itself, and she could not share further details on the process.

Jason Butler asked about PolyPid's preparations for D-PLEX100 approval in 2026, focusing on building awareness and engaging with payers. He also sought clarification on the strategic approach for the GLP-1 program, including partnership timing, data generation, and market differentiation.

Answer

CEO Dikla Czaczkes Akselbrad and COO Ori Warshavsky detailed commercial readiness efforts, including new branding, website, packaging, commercial name development, market research, pricing strategies, KOL network expansion, conferences, publications, and health economic analyses. Mr. Warshavsky noted that on-the-ground market preparation would largely depend on the commercial partner. For the GLP-1 program, Ms. Akselbrad explained the strategy to leverage Kynatrix for 60-day sustained release, aiming for early-stage partnership after generating robust preclinical efficacy and PK data, building on D-PLEX100's validated approach.

Jason Butler asked about PolyPid's readiness for potential D-PLEX100 approval, focusing on efforts to build awareness and prepare with payers. He also inquired about the strategic approach for the GLP-1 program, including when to generate data internally versus seeking a partner, and its long-term positioning and differentiation.

Answer

CEO Dikla Czaczkes Akselbrad detailed ongoing commercial preparation, including new branding, website, packaging, and market research on pricing and awareness. She mentioned building a KOL network and increasing abstracts/articles. COO Ori Warshavsky added that data dissemination through conferences and publications is key, with health economic work commencing. He noted that on-the-ground market preparation would largely depend on an experienced commercial partner. For the GLP-1 program, Ms. Akselbrad explained that it leverages the Kynatrix technology for approximately 60 days of sustained release, targeting improved patient compliance. The vision is to partner at a relatively early stage after generating robust preclinical efficacy and PK data, expected around mid-year, building on D-PLEX100's validation of the technology.

Jason Butler asked for details on DefenCath's LDO utilization, specifically patient numbers and types, given faster-than-expected ordering. He also sought clarification on the upcoming real-world data, including patient count, endpoints, and its relevance to Phase 3 results.

Answer

CEO Joe Todisco confirmed faster-than-expected LDO utilization, believing patient numbers are significantly higher than the initial 6,000 target, though exact figures are unavailable. EVP and COO Liz Hurlburt added that the real-world evidence study includes approximately 2,000 patients (double Phase 3), with endpoints focusing on reduction in CRBSI, hospitalizations, mistreatment sessions, TPA, and antibiotic utilization, compared to historical rates, with results expected in 6-7 weeks.

Jason Butler from Citizens asked for details on DefenCath's utilization by the Large Dialysis Organization (LDO), specifically regarding the number and type of patients. He also sought clarification on the upcoming real-world evidence data, including patient count, endpoints, and its relevance compared to Phase III results.

Answer

CEO Joe Todisco stated that LDO utilization was faster than expected, with patient numbers significantly higher than the initial 6,000 target, though exact figures were not disclosed. EVP and COO Liz Hurlburt added that the year-one real-world evidence study involves approximately 2,000 patients, double the Phase III Locket study, and will report on reductions in CRBSI, hospitalizations, mistreatment sessions, TPA, and antibiotic utilization compared to historical rates.

Jason Butler asked for details on the implementation process with the contracted Large Dialysis Organization (LDO), the basis for confidence in a midyear start, whether the expected usage volume has changed, and the status of signing other LDOs or smaller providers.

Answer

Executive Joseph Todisco confirmed CorMedix is providing significant support to the contracted LDO and remains hopeful for a midyear implementation start. He noted the potential usage volume could change and that the company is working to accelerate the rollout. Regarding new customers, Todisco mentioned progress with another LDO has been slow, but they are now working through JV partners and are actively building inroads with smaller customers.

Jason Butler of Citizens JMP inquired about the drivers of DefenCath utilization, asking if it's initiated by individual physicians or institutional protocols. He also questioned how the actual reimbursement mix between Medicare fee-for-service and Medicare Advantage compares to initial expectations, and asked for the outlook on operating expenses for Q4.

Answer

CEO Joseph Todisco explained that DefenCath adoption is almost entirely driven by top-down institutional protocols, which takes longer to set up but leads to a faster patient conversion ramp. He noted that claims data lags, but the initial trend shows facilities starting with fee-for-service patients before expanding to other payers. Regarding expenses, CFO Matt David and CEO Joseph Todisco confirmed they expect Q4 operating expenses to be in the 15% to 17% range, with significant R&D upticks not expected until 2025.

Jason Butler inquired about the Q3 sales run rate beyond the $5.2 million reported quarter-to-date, asking if initial orders would be worked through before reordering. He also asked for the number of outpatient centers showing pull-through and the key assumptions to reach breakeven EBITDA by year-end 2024.

Answer

CEO Joseph Todisco stated that consistent, repeat orders from several hundred clinics suggest strong patient pull-through with minimal trade stocking in the $5.2 million figure. He affirmed that reaching breakeven EBITDA by the end of 2024 is achievable, assuming the current sales trajectory from small and mid-sized operators continues and new, larger accounts are onboarded, which would cover the guided quarterly OpEx of $15 million to $18 million.

Jason Butler of JMP Group LLC asked about the average time from a Myclifa enrollment form to a patient receiving reimbursed drug, the retention rate for non-EAP patients, and the level of investment in Olpruva that is distinct from Myclifa.

Answer

Chief Commercial Officer Joshua Schafer stated that the time from enrollment to paid drug is decreasing dramatically, sometimes to as little as 72 hours, though it varies by payer. President and CEO Neil McFarlane noted it's too early for formal persistency data on new patients but confirmed high retention among converted EAP patients. Regarding Olpruva, McFarlane emphasized the significant commercial synergies with Myclifa, stating the infrastructure is highly overlapped and the incremental investment is very limited.

Jason Butler from Citizens JMP Securities asked for visibility into the source of new MIPLYFFA patients (undiagnosed vs. diagnosed but untreated), the expected cadence for onboarding them, and how inventory levels ended Q1 2025 compared to year-end 2024.

Answer

Chief Commercial Officer Joshua Schafer confirmed that new patients are coming from both the diagnosed and undiagnosed cohorts as a direct result of the company's awareness initiatives. Chief Financial Officer R. Clifton addressed inventory, stating that the company manages levels using a target days on hand and successfully maintained that target at the end of Q1, consistent with the end of Q4 2024.

Jason Butler asked for more quantitative details on the Q4 MIPLYFFA sales, specifically regarding specialty pharmacy inventory levels and the proportion of patients receiving refills. He also questioned how to model future net patient additions, asking if they would be steady or more volatile after the initial EAP conversion.

Answer

CFO R. Clifton explained that the $10.1 million in Q4 MIPLYFFA revenue included initial patient dispenses, refills for some early enrollees, and the establishment of target inventory levels at the specialty pharmacy. CCO Joshua Schafer noted the rapid EAP conversion and stated that future growth will focus on diagnosed but untreated patients and new diagnoses, implying a different cadence than the initial bolus.

Jason Butler inquired about the remaining logistical steps for shipping MIPLYFFA to patients with reimbursement approval, the manufacturing readiness, and the anticipated timeline for securing reimbursement for new patients not previously in the Expanded Access Program (EAP).

Answer

President and CEO Neil McFarlane confirmed that Zevra is on track with its 8-to-12-week post-approval timeline for getting MIPLYFFA into the channel, with no significant hurdles remaining besides logistics. Chief Commercial Officer Joshua Schafer added that the reimbursement process for patients new to the drug is identical to that for former EAP patients, with no additional steps or hurdles anticipated.

Jason Butler of JMP Group LLC asked about any substantial FDA information requests beyond the 120-day safety update and for an update on commercial preparations to increase Anafilm awareness.

Answer

CEO Daniel Barber confirmed there have been no major data requests from the FDA, only standard interactions. Chief Commercial Officer Sherry Korczynski detailed awareness efforts, including medical conferences and CME events, noting positive feedback from HCPs who believe Anafilm will improve patient carry rates and lower barriers to use.

Jason Butler of Citizens JMP inquired about the current level of healthcare provider awareness of Anaphylm, how Aquestive is measuring its growth, and how market seasonality and payer access timelines are expected to shape the launch's adoption curve.

Answer

Executive Sherry Korczynski explained that awareness is growing significantly through medical team engagement at numerous conferences, with progress tracked against a baseline ATU trial from December 2024. For the launch curve, she noted the market's seasonality peaks during the back-to-school period. While acknowledging payer timelines can take months, she expressed confidence in achieving majority market access by the crucial August-September period, suggesting the adoption curve might be similar to neffy's.

Jason Butler questioned the commercial investment strategy for Libervant following the adverse court decision and asked about the additional awareness activities planned for Anaphylm this year.

Answer

CEO Daniel Barber stated the immediate focus for Libervant is ensuring continued access for current patients (ages 2-5) while they contest the court ruling. For Anaphylm, Executive Sherry Korczynski outlined a comprehensive awareness strategy, including a significant presence at medical conferences, CME programs, publications, and building relationships with patient advocacy groups.

Jason Butler of JMP Securities inquired about the aspects of the Anaphylm product label that might still be under discussion with the FDA and how recent data could support a differentiated label. He also asked about the expected revenue trends for legacy products, like Suboxone, heading into 2025.

Answer

Chief Medical Officer Carl Kraus stated that while the primary goal of the FDA meeting is to align on the program's completeness, the company sees opportunities to use data from studies like OASIS to differentiate the label. CEO Daniel Barber agreed, noting the potential for a unique label. CFO Ernie Toth commented on legacy revenues, explaining that while Suboxone remains an important cash generator, the company anticipates some market dislocation going forward.

Jason Butler asked about the commercial preparation activities Syros is undertaking for the potential launch of tamibarotene in MDS, particularly in the months following a positive data release.

Answer

Conley Chee, Chief Executive Officer, detailed that the team has been preparing for launch for the past year. Post-data, they plan to accelerate market awareness, educate on RARA biology, build out the field force and infrastructure, and ensure manufacturing and diagnostic tests are ready for launch.

Jason Butler inquired about new CCO Phil Tennant's perspective on the RRP opportunity and his priorities, and also asked for an update on the strategic plan for the UltraCAR-T programs, including data and partnership interest.

Answer

Chief Commercial Officer Phil Tennant stated he was attracted by the high unmet need in RRP, consistent with his background in rare oncology. His priorities include building a precise commercial and medical affairs footprint to support the launch. President and CEO Dr. Helen Sabzevari added that while the company remains excited about the UltraCAR-T platform, pausing two trials was a strategic move to focus resources on PRGN-2012. She announced that Phase Ib enrollment for PRGN-3006 in AML is complete, and they are preparing for FDA discussions on next steps.

Jason Butler inquired about new CCO Phil Tennant's motivation for joining and his priorities for the PRGN-2012 launch. He also asked for an update on the UltraCAR-T programs, including potential data releases for PRGN-3006 and partnership interest.

Answer

Chief Commercial Officer Phil Tennant cited the high unmet need in RRP and his experience in rare diseases as key attractions, stating his priority is to build an appropriately sized, integrated commercial and medical affairs team. President and CEO Dr. Helen Sabzevari added that while the UltraCAR-T platform remains valuable, some trials were paused to prioritize PRGN-2012. She confirmed Phase Ib enrollment for PRGN-3006 is complete and they are preparing for FDA discussions, with data updates to be communicated in the future.

Jason Butler inquired about new CCO Phil Tennant's perspective on the RRP opportunity and his priorities, and also asked for an update on the UltraCAR-T programs, including potential data releases and partnership interest.

Answer

Chief Commercial Officer Phil Tennant highlighted the high unmet need in RRP as a key attraction and stated his priority is to build an appropriately sized, integrated commercial and medical affairs team. President and CEO Dr. Helen Sabzevari added that while pausing two UltraCAR-T trials to focus resources on PRGN-2012, the company has completed enrollment for the PRGN-3006 Phase Ib trial in AML and is preparing for FDA discussions on the regulatory strategy.

Jason Butler asked about the expected time course for cognitive improvements in the ACT-AD study relative to the rapid effects seen on P300. He also inquired about the mechanistic rationale for the SHAPE trial in Parkinson's disease dementia (PDD) and dementia with Lewy bodies (DLB) and whether ACT-AD results could influence the SHAPE trial's design.

Answer

Chief Medical Officer Hans Moebius explained that the 26-week trial duration is designed to assess effects beyond any initial placebo response, with multiple assessments tracking both P300 and ADAS-Cog11. He clarified that the rationale for SHAPE is based on the broad neurotrophic effects of the HGF/MET system, which could benefit neuronal populations in PDD/DLB, and confirmed that the ACT-AD results would not alter the SHAPE trial's design.

Jason Butler of JMP Securities questioned whether the FDA has accepted the bioequivalence data, if a pre-NDA meeting would still be necessary after the Type C meeting, and how much the discussion topics would overlap between the two meeting types.

Answer

CEO Remy Luthringer responded that the FDA has not yet reviewed the detailed bioequivalence data but expects no issues as it was a pivotal study that met its key parameters. He explained that the Type C meeting will focus on the critical clinical topic of monotherapy, which was a planned part of the pre-NDA discussion. The main difference is that a pre-NDA meeting would also cover non-clinical modules like CMC. Luthringer affirmed that Minerva is still targeting an NDA submission in the first half of 2022, pending the meeting's outcome.

Jason Butler of JMP Securities inquired about the specific efficacy measures for the Fragile X Rocket study, preclinical data supporting earlier treatment in Angelman syndrome, and other notable data presentations planned for the upcoming AAN conference.

Answer

Executive Amit Rakhit, with a follow-up from Executive Matthew During, detailed that the Fragile X study will use scales like ABC-C and ADAMS, with endpoints chosen to reflect preclinical data. During also referenced public literature on mouse models supporting the benefit of earlier intervention in Angelman syndrome. Rakhit highlighted that new baseline data from both the STARS and OV935 adult studies would be presented as posters at the AAN meeting.