Prakhar Agrawal

Prakhar Agrawal asked about the blinded acute pancreatitis (AP) event rates observed in the ongoing Phase III/4 SHTG trials, comparing them to Ionis's findings. He also inquired if the placebo event rate for AP reduction is expected to be similar to olezarsen core trials, given the comparable patient population.

Answer

James Hamilton, Chief Medical Officer and Head of R&D, declined to provide specific details on blinded AP event rates in the SHTG trials, only confirming that events are being observed. He suggested that the placebo event rate could be rationally compared to cohort two of olezarsen core trials due to similar patient populations.

Prakhar Agrawal asked about the blinded acute pancreatitis (AP) event rates observed in the ongoing SHASTA-3 and SHASTA-4 trials, comparing them to Ionis's Olezarsen core trials placebo rate, and any nuances in the patient population.

Answer

James Hamilton, Chief Medical Officer and Head of R&D, declined to provide specific details on the number or rates of AP events, only confirming that events are being observed. He noted that it is rational to consider the Olezarsen cohort two placebo rate as the population was similar, despite being different studies.

Prakhar Agrawal from Cantor Fitzgerald asked for detailed information regarding the upcoming obesity data disclosures for ARO-INHBE and ARO-ALK7, including the extent of data on the MAT side, follow-up duration for monotherapy and combo cohorts, and whether any weight loss data would be available for ARO-ALK7.

Answer

James Hamilton, Chief Medical Officer and Head of R&D for Arrowhead Pharmaceuticals, stated that ARO-INHBE, being further along, will have biomarker, MRI, and safety data from SAD and MAD cohorts, with ample post-dose follow-up. He noted that ARO-ALK7 data would be more limited, focusing on monotherapy safety and target knockdown, and that initial disclosures aim to provide an idea of progress, with more comprehensive data expected later in 2026.

Prakhar Agrawal inquired about the upcoming obesity data update for NABNE and ARC7 early next year, requesting details on the amount of data to be disclosed, particularly on the MAT side, follow-up duration for monotherapy and combo cohorts, and any expected weight loss data from ARC7.

Answer

James Hamilton, Chief Medical Officer and Head of R&D, stated that NABNE is further along, with substantial biomarker, MRI, and safety data from SAD and MAD obese healthy volunteer cohorts, plus ample post-dose follow-up for combo cohorts. He noted that ARC7 data will be more limited, focusing on monotherapy safety and target knockdown, with fuller data for both programs expected later in 2026.

Prakhar Agrawal asked about potential solutions for Sarepta's large shareholding in Arrowhead and about commercial activities to differentiate SHTG from the general lipid market for pricing purposes.

Answer

CEO Christopher Anzalone noted Sarepta's shares are still in lockup and that there has been inbound interest, mitigating concerns about a potential sale. SVP Andy Davis detailed medical education efforts for SHTG. Anzalone emphasized that plozasiran is a 'pancreatitis drug,' not a standard lipid drug, which should inform its value and pricing.

Prakhar Agrawal of Cantor Fitzgerald asked how Arrowhead's development and labeling strategy for plozasiran would be impacted if a competitor achieved statistical significance on pancreatitis events first.

Answer

An executive expressed that relying on such an endpoint was a high-risk strategy. He reiterated that Arrowhead's program is designed to meet the high standards of European payers by focusing on 'definite' pancreatitis in a purpose-built outcomes study (SHASTA-5), which he believes is a more robust approach for health authorities.

Prakhar Agrawal asked about expectations for Q4 growth and Madrigal's comfort with 2026 consensus estimates, given the gross-to-net clarity. He also inquired about the current percentage of Rezdiffra volume from Medicare and the implications of semaglutide's IRA pricing decision on that channel's long-term prospects.

Answer

Bill Sibold, Chief Executive Officer, provided the distribution: 50-55% commercial, 30-35% Medicare, and ~10% Medicaid/other. Mardi Dier, Chief Financial Officer, expects Q4 to continue steadily adding patients, with high single-digit quarter-over-quarter growth, factoring in fewer selling days and the start of commercial rebating (midpoint of 20-30% gross-to-net). For 2026, robust net sales growth is anticipated, with the full gross-to-net impact (high 30s) beginning January 1st. Bill Sibold reiterated the significant growth opportunity with less than 10% market penetration.

Prakhar Agrawal asked about expectations for Q4 growth and comfort around 2026 consensus estimates, the percentage of Rezdiffra volume currently from Medicare, and the implications of semaglutide IRA pricing decisions on the long-term prospects for that channel.

Answer

CFO Mardi Dier expects Q4 to continue steadily adding patients, but with a high Q3 base, fewer selling days, and commercial rebating starting (midpoint of 20-30% gross-to-net), anticipates high single-digit Q-o-Q growth. For 2026, she expects robust net sales growth driven by steadily adding patients, despite the full gross-to-net impact (high 30s) starting in January. CEO Bill Sibold provided the distribution: 50-55% commercial, 30-35% Medicare, 10% Medicaid/other. He reiterated the focus on patient additions and the large untapped market.

Prakhar Agrawal asked for the long-term gross-to-net outlook for 2026 and beyond, and questioned the company's business development capacity given ongoing launch investments.

Answer

CEO William Sibold and CFO Mardi Dier both stated it was too early to comment on 2026 gross-to-net specifics but reiterated a disciplined, long-term strategy. Regarding business development, Dier confirmed they are not pursuing a 'bet the company' strategy and that their strong cash position supports current launch plans, though a future deal could alter the cash flow outlook.

Prakhar Agrawal of Cantor Fitzgerald asked for an update on adoption trends among gastroenterologists versus hepatologists, referencing earlier commentary that GIs might be slower to adopt.

Answer

CEO William Sibold clarified that gastroenterologists are the vast majority of their target prescribers and have been the driving force of the launch's success. He explained that any initial slowness was mechanical, related to 'wiring' their practices for a new disease, but their adoption has been extremely strong and is critical to the product's performance.

Prakhar Agrawal requested commentary on the month-over-month trend of patient additions in Q3 to better understand the revenue figures and asked if similar sequential growth in new patients is expected for Q4.

Answer

CEO William Sibold stated that patient and prescriber additions were steady and consistent throughout the quarter, with the strong quarterly results reflecting a cumulative effect. He declined to provide monthly breakdowns. CFO Mardi Dier referred back to earlier remarks indicating Q4 growth is expected to track with successful specialty launches.

Prakhar Agrawal followed up on the dermatomyositis trial, asking about the typical steroid dose used for a flare-up and whether it's protocol-defined. He also asked about Roivant's business development strategy regarding assets from China, including views on quality, competition, and valuation.

Answer

CEO Matt Gline reiterated that the trial protocol focuses on consistently defining 'rescue therapy' for worsening patients, rather than specifying a steroid dose for 'flares.' Regarding business development, Gline confirmed Roivant is an 'agnostic hunter' that actively looks in China, noting the high quality and rapid development of drug candidates from the region, particularly for mechanisms where creative clinical development can add significant value.

Prakhar Agrawal of Cantor Fitzgerald sought details on how the dermatomyositis (DM) trial mitigates placebo response, asking about the consistency and subjectivity of the steroid tapering protocols and any other incorporated risk-mitigation steps.

Answer

CEO & Director Matt Gline confirmed that the steroid taper is mandatory and follows a clear, consistently applied protocol. He mentioned that other risk-mitigation strategies are in place, such as managing discontinuations and measurement time points. He emphasized that strong site relationships and "boots on the ground" work help ensure protocol adherence, and deferred more detailed discussion to the upcoming investor event.

Prakhar Agrawal of Cantor Fitzgerald asked for qualitative commentary on the eGFR curves in the FSGS trial, the FDA's expectations for eGFR data, and the gross-to-net trends seen in Q2 with expectations for the rest of the year.

Answer

CMO Dr. Jula Inrig explained that the focus for FSGS is on proteinuria, not eGFR, per the Parasol findings, and the eGFR curves are consistent with expectations (acute decline then stabilization). CFO Chris Cline addressed gross-to-net, noting relief in Q2 and that they remain squarely in line with the full-year guidance of the low 20% range.

Prakhar Agrawal from Cantor Fitzgerald asked about the overlap between the FSGS patient population and top FILSPARI prescribers, launch expectations, and payer feedback on a potential higher price for the FSGS indication.

Answer

CEO Eric Dube and CCO Peter Heerma responded. Dube stated that while broad access is key, a higher price for FSGS is likely given the double dose and is justified by the high unmet need. Heerma added that a rapid uptake is expected due to significant prescriber overlap, strong brand awareness, established payer access, and the recognized urgency to treat FSGS.

Prakhar Agrawal asked for perspective on how long the accelerated approval pathway in IgAN might remain open now that multiple drugs have full approval, and what competitors would need to demonstrate for such an approval.

Answer

SVP of R&D, Dr. Bill Rote, responded that while it is an FDA decision, an agency official has publicly stated the pathway will not remain open indefinitely. With three approved therapies now available, Dr. Rote believes the unmet need has been significantly addressed, raising the bar for future accelerated approvals. He does not expect many more drugs to successfully use that pathway for IgAN.

Prakhar Agrawal of Cantor Fitzgerald asked for commentary on Ibsrela's performance trends for the rest of the year, given historical strength in the second half. He also sought comment on consensus estimates for Xphozah and expectations for sequential growth.

Answer

CEO Mike Raab acknowledged historical trends but emphasized the current $10 million guidance increase for Ibsrela was a significant and thoughtful step. He declined to provide specific guidance for Xphozah but highlighted the strong $25 million Q2 performance and month-over-month demand growth since March as a positive trajectory.

An analyst on behalf of Prakhar Agrawal of Cantor Fitzgerald asked about the strategy for expanding XPHOZAH uptake in non-Medicare channels and the expected timing for this to materialize.

Answer

CEO Michael Raab outlined the strategy, which involves a closed distribution system via ArdelyxAssist. This system removes the burden from physicians to differentiate between insurance types. The program adjudicates prescriptions, transitioning Medicare patients who qualify to the patient assistance program for free drug, while processing non-Medicare prescriptions through their respective payers.

Prakhar Agrawal asked for details on the subcutaneous BRIUMVI program, including the potential for quarterly dosing, expected injection volume, and the timing of Phase 1 data release. He also requested a breakdown of the 16% sequential revenue growth between volume and price, and an update on gross-to-net trends.

Answer

CEO Michael Weiss confirmed that preliminary bioavailability data supports both every-other-month and quarterly dosing for subcutaneous BRIUMVI, with an injection volume likely near 2ml. Chief Commercial Officer Adam Waldman added that the sequential revenue growth was driven mostly by volume. He reiterated the full-year gross-to-net guidance of 70-75%, noting Q2 was closer to 70% due to increased sales in the hospital segment, which has higher mandated discounts.

Prakhar Agrawal asked about the start date for the subcutaneous Briumvi pivotal trial, the criteria for further investment in myasthenia gravis, and the percentage of Briumvi patients switching from Ocrevus.

Answer

CEO Michael Weiss confirmed the subcutaneous trial remains on track to start this year and that the decision to invest in myasthenia gravis depends on an aggregate of market factors, not a single data point. CCO Adam Waldman added that while there is a 'healthy amount' of switches from Ocrevus, the trend has remained consistent since launch without a notable inflection.

Prakhar Agrawal inquired about the key drivers for the strong 2025 revenue guidance and asked for TG Therapeutics' perspective on the market role of a competitor's potential high-dose product.

Answer

Chief Commercialization Officer Adam Waldman attributed the growth to broad customer adoption in both academic and private clinic settings, driven by strong 5-year data, real-world evidence, and an expanded field team. Regarding the competitor's high-dose product, both Waldman and CEO Michael Weiss stated it was too early to comment without seeing the full data profile, including infusion time and safety.

Prakhar Agrawal from Cantor Fitzgerald asked about the on-the-ground impact of the subcutaneous OCREVUS launch and questioned the company's broader capital allocation priorities, including plans for the share buyback program.

Answer

Chief Commercialization Officer Adam Waldman reported seeing no impact from the subcutaneous OCREVUS launch to date, highlighting that October was a record enrollment month. CEO Michael Weiss confirmed the share buyback will continue but emphasized that capital will also be allocated to growing BRIUMVI's commercial efforts, funding clinical programs, advancing azer-cel, and pursuing business development.

Prakhar Agrawal from Cantor Fitzgerald questioned the top doses being tested in the ZUPREME-2 trial for type 2 diabetes patients and sought commentary on why the weight loss benefit for amylins in diabetes appeared muted with CagriSema.

Answer

CEO Adam Steensberg confirmed that ZUPREME-2 will use similar top doses as ZUPREME-1. He argued the CagriSema data was strong, likely doubling the weight loss over semaglutide alone, and suggested its amylin component was not dosed to its full potential. Chief Medical Officer David Kendall added that the ZUPREME-2 monotherapy trial is expected to confirm comparable weight loss in patients with and without diabetes.

Prakhar Agrawal of Cantor Fitzgerald questioned the company's conviction in petrelintide's dose response, given the similar weight loss curves for the 4.8 mg and 9 mg doses. He also asked about key factors in a partnership structure, particularly the importance of a U.S. co-commercialization deal, and the company's expectations for the cagrilintide monotherapy arm data.

Answer

President and CEO Adam Steensberg emphasized that a U.S. co-commercialization structure is 'extremely important' for any partnership. Regarding competitor data, he noted that while the cagrilintide mono-arm will be informative, petrelintide's higher dosing potential makes their own Phase IIb trial critical. Chief Medical Officer David Kendall explained their confidence in a dose response is based on preclinical data and factors in the Phase Ib trial, such as the limited number of female participants, which the larger Phase IIb is designed to clarify.

Prakhar Agrawal sought more clarity on the petrelintide dose-response, given similar weight loss at 4.8mg and 9mg doses. He also asked about key factors in a partnership structure and the implications of upcoming CagriSema data, especially the cagrilintide mono-arm.

Answer

CEO Adam Steensberg and CMO David Kendall replied. Dr. Kendall attributed confidence in a dose response to individual patient data and the potential for greater separation with longer duration in Phase IIb. Mr. Steensberg emphasized that a key partnership term is a shared vision for petrelintide as a foundational therapy with co-commercialization rights. He noted the cagrilintide mono-arm data will be insightful but stressed petrelintide's potential for much higher dosing.

Prakhar Agrawal inquired about the upcoming ASCO data presentation, specifically whether efficacy data for the third patient would be included. He also sought clarification on the full-year patient dosing target for Phase 1 and questioned the company's cash runway relative to the timing of the Q3 interim data release.

Answer

CEO Kevin Boyle confirmed that translational data for the first three patients will be presented at ASCO but could not disclose further details on efficacy due to the embargo. He clarified that the full-year guidance of 12-15 patients remains unchanged, as the 9-12 patient target for 2023 is in addition to the three patients treated in 2022. VP of Finance Mike Wong addressed the financial question, stating the cash runway extends into Q4 2023, positioning the company for the next data readout, and that they remain opportunistic regarding all financing options.

Prakhar Agrawal of Cantor Fitzgerald inquired about patient dosing since Q4, seeking confirmation on the FDA's approval of IND enhancements and details on the implementation and rationale for multiplex TCR therapy.

Answer

CEO Kevin Boyle confirmed that while they will not report on a patient-by-patient basis, enrollment progress is strong and there are no outstanding questions from the FDA regarding the IND amendment. VP of R&D Drew Deniger added that multiplexing is a feasible near-term opportunity, with about one in five patients matching multiple TCRs, and the scientific rationale is that attacking more targets increases the chances of durable remission.

Prakhar Agrawal asked about the six-month interval between dosing patients, potential bottlenecks, the dose level for the third patient, the reason for progression in patient one despite T-cell persistence, and the company's cash runway and financing strategy.

Answer

CEO Kevin Boyle Senior attributed the patient dosing timeline to momentum building after the CICON conference and stated enrollment is expected to accelerate. He confirmed the cash runway extends into Q2 2023 and that multiple financing options are available, including an ATM and a shelf registration. VP of Research and Development, Drew Deniger, added that for patient one, the tumor target remained intact and T-cells were persistent, with further analysis ongoing.

Prakhar Agrawal of Cantor Fitzgerald inquired about the status of the second patient in the TCR-T trial, the expected data for the Q3 update, and the key differences between Alaunos's therapeutic approach and those detailed in recent NEJM and Cancer Immunology Research publications.

Answer

CEO Kevin Boyle explained that while he could not provide specifics on patient dosing or the upcoming data due to conference restrictions, an update would be provided at a scientific meeting in Q3. He confirmed the safety review for dose escalation occurs after a 28-day window. VP of Research and Development, Drew Deniger, highlighted that unlike the retroviral vectors and high-dose IL-2 used in the published studies, Alaunos utilizes its proprietary non-viral Sleeping Beauty system and does not require high-dose IL-2, which they believe offers significant advantages.