Etzer Darout

Etzer Darout asked about the most common combination agents used with Revuforj and the average duration of therapy exiting the quarter, including any differences between NPM1 and KMT2A patients.

Answer

Michael Metzger, CEO, stated that venetoclax and azacitidine (ven/aza) are the most common combination agents, also noting use with intensive chemotherapy, expecting this to expand. He reiterated the average treatment duration for 2025 was 4-6 months, with an expectation to extend to 6-12 months in 2026, but did not differentiate between NPM1 and KMT2A for current duration.

Etzer Darout asked about the most common combination agents currently being used with Revuforj and the average duration of therapy, including how it differs between NPM1 and KMT2A patients.

Answer

Michael Metzger, Chief Executive Officer, stated that Revuforj is most often used in combination with VenAza, and also with chemotherapy, expecting this to expand over time. He confirmed the average treatment duration for Revuforj in 2025 was in the 4-6 month range, with an expectation to extend to 6-12 months in 2026. He noted that NPM1 patients will receive fewer transplants and, in turn, less maintenance compared to KMT2A patients.

Etzer Darout inquired about the near-term impact of ex-U.S. commercial launches (e.g., Canada) on gross margins, given the recent improvements.

Answer

Corleen Roche, CFO, stated that ex-U.S. launches would leverage existing in-house manufacturing operations, leading to economies of scale and potentially helping margins. Dan Kirby, Chief Commercial Officer, added that manufacturing for ex-U.S. launches would be from the Philadelphia facility, with no plans for additional global facilities, and no lower ex-U.S. price has been negotiated yet.

Etzer Darout inquired about the near-term impact of ex-U.S. commercial launches, such as in Canada, on gross margins, given the improvements seen to date.

Answer

Corleen Roche, CFO, stated that ex-U.S. launches would leverage existing in-house manufacturing, leading to economies of scale and likely helping margins. Dan Kirby, Chief Commercial Officer, added that manufacturing for ex-U.S. launches would be from the Philadelphia facility without additional global facilities, and no lower ex-U.S. price has been negotiated yet, positioning them well for negotiations.

Etzer Darout asked for additional commentary on the delay of the HORIZON Phase III trial readout for pelacarsen, inquiring about the potential drivers of the event rate dynamics.

Answer

CEO Vasant Narasimhan clarified that the delay is due to event rate modeling on the blinded data, not an interim analysis. He explained that cardiovascular outcome studies have been trending toward lower event rates over time, and it's preferable to ensure the study is adequately powered by waiting for the target number of events, which is now expected in early 2026. He remains confident in the drug's mechanism.

Etzer Darout inquired about the planned dosing strategy for the OPAL study in SMA patients under two years old, considering the learnings from the SAPPHIRE trial. He also asked for Scholar Rock's perspective on the differences between various muscle preservation approaches in obesity, such as myostatin inhibition versus amylins.

Answer

Executive Jay Backstrom stated that for the OPAL study, the company will leverage all PK/PD data from both the TOPAZ and SAPPHIRE studies to model and confirm the dose, which is expected to be based on the effective 10 mg/kg dose. Regarding obesity therapies, he emphasized that lean muscle loss is a common issue across different weight loss methods. He positioned Scholar Rock's SRK-439 as being agnostic to the primary weight loss drug, suggesting its favorable safety profile makes it suitable for broad combination strategies.

Etzer Darout inquired about the price-to-mix dynamics for DANYELZA sales in the third quarter and the key criteria for selecting the optimal antibody dose for Part B of the GD2-SADA study.

Answer

Chief Commercial Officer Sue Smith explained that a $1.5 million charge for Medicaid claims impacted the price mix, causing a 5% revenue decline despite a 5% increase in vial volume. President and CEO Michael Rossi and Chief Medical Officer Dr. Vignesh Rajah stated that the GD2-SADA protein dose of 1 mg/kg was chosen for Part B because it aligns with preclinical PK data, allowing for dosing near the nadir. They added that dosimetry in the tumor and normal tissues, along with safety, are key factors for determining the optimal dose and interval.

Etzer Darout inquired about the anticipated number of patients for the randomized portion of the frontline BCC study and whether the SADA Part A study could yield enough data on GD2 expression to inform expansions into specific tumor types.

Answer

Chief Medical Officer Dr. Vignesh Rajah stated that the design for the randomized BCC study is still under evaluation, so patient numbers cannot be confirmed yet. President and CEO Michael Rossi added that while the SADA study collects data on various tumor expressions, Part A likely won't provide enough information to focus on or eliminate a specific tumor type for Part B.

Etzer Darout questioned whether potential Phase Ib studies for CX-904 would focus on monotherapy or explore combinations with standard of care, particularly in head and neck or non-small cell lung cancer.

Answer

CEO Sean McCarthy responded that the company is currently focused on monotherapy for CX-904, which aligns with the goals of their partner, Amgen. He added that while combination strategies are under consideration, there are no defined plans for a combination component in a potential Phase Ib study at this time.

Etzer Darout from BMO Capital Markets asked if MacroGenics is observing any notable differences in the safety and efficacy profiles between its two B7-H3 ADCs, vobra duo and MGC026, based on available data.

Answer

Dr. Scott Koenig, President and CEO, responded that he expects distinct safety profiles due to their different mechanisms (DNA-alkylating agent vs. Topo 1 inhibitor). However, he noted that with MGC026 still in mid-dose escalation, it is too early to provide a direct side-by-side comparison of the two assets.

Requested an update on the combination study of vobra duo with lorigerlimab, asking about the program's status and its viability given the safety profile of vobra duo.

Answer

The executive confirmed the combination program is on track. The dose-finding portion is in its final evaluation phase, and they plan to initiate enrollment in expansion cohorts for prostate cancer and another tumor type in the second half of 2024.

Etzer Darout of BMO Capital Markets requested more details on the combination study of vobra duo with lorigerlimab, asking about its progress and viability given vobra duo's safety profile.

Answer

Dr. Scott Koenig, President and CEO, confirmed the combination program is on track. He stated they are in the final stages of evaluating the dose-finding cohorts to determine the optimal doses and expect to begin enrolling expansion cohorts in prostate cancer and another tumor type in the second half of 2024.

Etzer Darout from BMO Capital Markets inquired about expectations for the fulvestrant control arm in the VERITAC-2 trial and whether there are any potential read-throughs from upcoming data from Eli Lilly's EMBER-3 trial.

Answer

CEO John Houston stated the trial is designed to show superiority over fulvestrant. CMO Noah Berkowitz elaborated, expecting the fulvestrant arm's PFS to be in the 3-4 month range. He noted that for Lilly's data, they will need to analyze the prior CDK4/6 exposure of the patient population to make a valid comparison.

Lukas Shumway, on behalf of Etzer Darout, asked about the zanzalintinib colorectal cancer trial, specifically how patients without liver metastases are identified and if a companion diagnostic would be required.

Answer

Chief Medical Officer Amy Peterson explained that identifying liver metastases is a standard part of care for advanced colorectal cancer patients, done via routine imaging scans. She clarified that it is a straightforward clinical assessment and does not require a companion diagnostic.

Etzer Darout of BMO Capital Markets requested details on planned Phase III trial designs. He asked about the target patient population and control arm for Tivdak in head and neck cancer, and the expected initial indication and line of therapy for ProfoundBio's Rina-S, which has a potential 2027 launch.

Answer

Chief Development Officer Judith Klimovsky explained that for Tivdak, Genmab is finalizing the Phase III design with health authorities, based on data in second and third-line head and neck cancer patients who have progressed after standard therapies. Chief Medical Officer Tahamtan Ahmadi, citing the pending acquisition, carefully noted that ProfoundBio has publicly stated plans for a Phase III trial for Rina-S and a study to evaluate folate receptor expression.

Inquired about the safety profile of vudalimab, specifically the case of autoimmune hepatitis, and the rationale for pausing the XmAb564 program.

Answer

The hepatitis event was an isolated case in a complex patient; existing monitoring protocols are in place. The XmAb564 pause was a strategic decision to focus resources on T-cell engagers, not a data-driven one.