Andy Hsieh

Andy Hsieh asked if there is an increased utility of CABO monotherapy in the first-line setting, driven by evolving dynamics in IO usage, particularly in the adjuvant setting.

Answer

P.J. Haley (EVP of Commercial) stated that CABO monotherapy has always had reasonable utilization in the first-line setting, referencing the CABOSUN study, and continues to play a role, particularly in the monotherapy segment of that population.

Andy Hsieh asked P.J. Haley about the potential for increased utility of cabozantinib monotherapy in the first-line setting, influenced by evolving IO usage in the adjuvant setting.

Answer

P.J. Haley (EVP of Commercial, Exelixis) stated that cabozantinib monotherapy has always had a reasonable utilization in the first-line setting, referencing the CABOSUN study, and continues to play a role, particularly in the monotherapy segment of that population.

Andy Hsieh from William Blair inquired about the percentage of CRC patients considered high-risk post-adjuvant and whether the STELLAR-303 safety profile could inform treatment duration in a potential adjuvant trial.

Answer

EVP & CMO Amy Peterson noted that high-risk patients face recurrence in months, not years. CEO Michael Morrissey added that while not providing a specific market size, the commercial opportunity in the post-adjuvant CRC and meningioma settings is estimated to be three times larger than the discontinued head and neck indication.

Andy Hsieh asked about the dose required for maintaining weight loss during the active weight loss period versus after reaching maximum weight loss, and how to extrapolate maintenance study data (where patients are still in active weight loss) to patients who have reached maximum weight loss. He also asked for interpretation of Eli Lilly's cardiovascular outcomes data in type 2 diabetes, where additional A1C and weight loss didn't translate into additional cardiovascular protection.

Answer

Brian Lian (President and CEO, Viking Therapeutics) explained that the maintenance study's goal is to understand the dose that prevents weight regain, regardless of whether patients have reached their full weight loss nadir. He believes the study will provide a signal for preventing regain from substantial weight loss. Regarding Eli Lilly's data, he noted that the full results haven't been seen, making it difficult to interpret, but he would generally expect larger weight loss and A1C reductions to translate into cardiovascular benefits.

Andy Hsieh inquired about Viking's thoughts on the dose required for maintaining weight loss during the active weight loss period versus after reaching maximum weight loss, and how to extrapolate maintenance study data where patients are still in active weight loss. He also asked for an interpretation of Eli Lilly's cardiovascular outcomes data in type 2 diabetes, where additional A1C and weight loss didn't translate into additional cardiovascular protection.

Answer

Brian Lian (President and CEO, Viking Therapeutics) explained that the maintenance study's goal is to understand the dose that prevents weight regain, regardless of whether patients have reached their full weight loss nadir. He believes a signal from substantial weight loss will be informative. Regarding Eli Lilly's data, he noted that full results haven't been seen, making it difficult to interpret, but generally expects larger weight loss and A1C reductions to translate into cardiovascular benefits.

Andy Hsieh from William Blair asked for clarification on the 26-week titration period in the 78-week Phase III trial. He also inquired if the staggered dosing scheme relative to competitor products was motivated by potential reimbursement advantages.

Answer

President & CEO Brian Lian confirmed the 26-week titration period followed by 52 weeks on the final dose. Regarding dosing, he explained that while having multiple approved dose options like 7.5mg could be attractive for maintenance and reimbursement, the primary driver for dose selection was the potential for good safety, tolerability, and efficacy based on prior data.

Andy Hsieh of William Blair & Company asked about the BYPASS study's potential to demonstrate long-term value and later inquired about the commercial and strategic implications of the company's aluminum fluoride (AlF) technology.

Answer

Regarding the BYPASS study, Group CEO Christian Behrenbruch explained its goal is to make biopsies more effective by better stratifying patients, with a follow-up period to evaluate utility. On the AlF technology, Behrenbruch described it as a way to use F-18 with kit-based workflows, combining the benefits of both isotopes. Kevin Richardson, CEO of Precision Medicine, added this allows Telix to cater to physicians who prefer F-18, expanding market reach.

Andy Hsieh from William Blair asked for any investigator feedback on the new proteinuria mitigation protocol and questioned whether the $15 million milestone payment from GSK was purely progress-based or if it could be interpreted as a sign of promising efficacy for XMT-2056.

Answer

President and CEO Dr. Martin Huber noted that investigator enthusiasm for EMILY remains high and enrollment at Dose B is continuing, with more details to come in the data release. CFO & COO Brian DeSchuytner clarified that the GSK payment was a 'development milestone' but stated that the specific criteria for achieving it are confidential.

Andy Hsieh of William Blair & Company asked for details on the technology behind Altimmune's oral pemvidutide program and its strategic positioning within the company's portfolio.

Answer

Management revealed a recent 'big breakthrough' in the oral program, highlighting that their technology is designed to avoid food restrictions and be viable from a cost-of-goods perspective. CEO Dr. Vipin Garg positioned the oral formulation as a key life cycle management strategy to enhance the commercial value proposition of pemvidutide in a growing market.

The analyst asked about the future Phase 3 trial design for FG3246, specifically the control arm, and the upcoming Q4 data update. They also inquired about the IP and market exclusivity for roxadustat, as well as details on its planned Phase 3 trial design, including the control arm and statistical assumptions.

Answer

The company stated it's too early to finalize the FG3246 Phase 3 control arm but is monitoring developments. For the Q4 update, they hope to see the RPFS hold around 10.2 months. For roxadustat, they confirmed a minimum of 7 years of exclusivity and that the Phase 3 trial will be placebo-controlled with about 200 patients in a post-ESA setting, but declined to share statistical assumptions.

Andy Hsieh of William Blair inquired about the potential Phase 3 trial design for FG3246, specifically regarding the control arm. He also asked about the key parameters for the Q4 update on the combination trial with enzalutamide. Additionally, Hsieh questioned the IP landscape for roxadustat, the design of its planned Phase 3 trial, including the control arm and statistical assumptions.

Answer

CEO Thane Wettig and Executive Director Carol Gaddum addressed the questions. For FG3246, they noted it's early for Phase 3 design but acknowledged a physician's choice control arm, potentially including docetaxel, is being considered. For the Q4 update, Wettig stated they will focus on mature RPFS data from the full 41-patient cohort. Regarding roxadustat, Wettig confirmed a minimum of seven years of exclusivity from orphan drug designation, with potential for extension. He clarified the Phase 3 trial will be placebo-controlled in post-ESA patients with a target enrollment of around 200, but declined to share statistical assumptions.

Andy Hsieh asked about the clinical development strategy for FG-3246 in light of Pluvicto's approval, potential macro disruptions affecting FDA communications for Roxadustat, and the possibility of using new capital for a colorectal cancer feasibility study.

Answer

CEO Thane Wettig explained that the FG-3246 Phase 2 trial will allow, but not require, Pluvicto-experienced patients to avoid enrollment delays. He also reported no disruptions in FDA communications, citing timely progress on the FG-3180 IND and the Roxadustat Type C meeting request. Regarding a colorectal cancer study, both Wettig and CFO David DeLucia stated that the current focus is on closing the China transaction and advancing the existing prostate cancer and MDS programs.

Andy Hsieh of William Blair & Company asked about Lantheus's strategy to increase the use of its agents in the prodromal Alzheimer's population, given the emergence of blood-based biomarkers for screening.

Answer

CEO Brian Markison positioned blood-based tests as a "market expansion opportunity" that helps identify patients and refer them to neurologists for a definitive PET scan. He emphasized that Lantheus's tracers are more sensitive and have better resolution than first-generation agents, making them crucial for early diagnosis and selecting patients for new therapies.

Andy Hsieh from William Blair asked about technical aspects of the atopic dermatitis trial protocol, specifically if patients who stop the drug can remain in the trial for follow-up to assess remittive effects, and which imputation method is being used for the primary endpoint analysis.

Answer

Executive Jonathan Zalevsky confirmed that the protocol allows for patients who discontinue treatment to remain in the study for follow-up, which is a standard practice. Regarding the analysis, he stated they are using a standard estimand approach with typical imputation methods, as recommended by FDA guidance for Phase II studies, with full details to be shared with the results.

Andy Hsieh of William Blair & Company asked about the logistical process with the FDA for the recent protocol amendment and sought clarification on whether any new preclinical data was disclosed during the call.

Answer

Dr. Puneet Arora clarified that the protocol amendment process with the FDA does not typically involve meetings; Skye submitted the amendment, responded to minor clarification requests, and expects to proceed. CEO Punit Dhillon confirmed that no new data was released on the call, but that updates to recently shared data sets will be presented at upcoming scientific conferences like ECO and ADA.

An associate for Andy Hsieh asked if a recent patient death in a competitor's gene therapy trial has influenced Insmed's development strategy for its own gene therapy programs.

Answer

CEO William Lewis differentiated Insmed's approach, highlighting its use of an intrathecal delivery method that requires lower doses and bypasses the liver, a key site of immune reactions. He stressed that their strategy, which includes taking extra time on development and focusing on CMC, is designed to enhance safety in light of concerns across the field.

Asked about the target number of clinical trial sites, the strategy for dose selection for the pivotal study under Project Optimus, FDA requirements for advancing, and any other potential data catalysts before Q3 2025.

Answer

The company has 24 active sites and aims for 35, with the process being dynamic. They plan to select a single dose for the registrational trial based on efficacy and safety data from CRDF-004, as per FDA guidance. While there are other ongoing investigator-initiated trials, the company is not providing specific timelines for those readouts and remains laser-focused on the CRDF-004 trial.

Asked about dose-response between the 20mg and 30mg doses, the impact of liver metastases on patient response, plans for managing neutropenia in the CRDF-004 study, and requested an update on the small cell lung cancer program.

Answer

The company stated that both the 20mg and 30mg doses appear similarly active, allowing them to combine the arms for efficacy analysis. They noted that responses in prior trials were independent of liver metastases, with bev-naive status being the key factor. Standard neutropenia management protocols are in place. The small cell lung cancer trial has slowed due to the principal investigator moving to a new institution.

Andy Hsieh of William Blair asked for details on the quality control and data integrity measures for the DUBLIN-3 trial and sought clarification on why P-values were presented as a range in the top-line results. He also asked for perspective on interpreting the PFS data in the context of the positive OS result and inquired about subsequent therapies used by patients in the trial.

Answer

CEO Lan Huang affirmed the trial's high quality, citing the use of top-tier CROs like ICON and Covance and an independent statistical company. She explained that P-values were given as a range in the top-line release to save the specific data for the major ESMO medical conference. She noted that the statistically significant improvements in PFS and ORR demonstrate a clear drug effect, and that subsequent therapies were balanced between the two study arms.

Andy Hsieh of William Blair questioned the regulatory sentiment from the FDA regarding plinabulin's benefits, particularly in light of the NCCN's aggressive guideline updates for CIN management during the pandemic. He also asked for guidance on the anticipated SG&A expense ramp leading up to and following the PDUFA date.

Answer

Dr. Lan Huang, CEO, noted that while the FDA is independent, the granting of Breakthrough Therapy and Priority Review designations signals the agency's recognition of the unmet need. COO Richard Daly added that the updated NCCN guidelines have doubled the addressable market and are expected to remain. Daly also outlined a three-fold prelaunch strategy, with sales team hiring contingent on approval. CFO Elizabeth Czerepak assured that the company is sufficiently funded for the next year while evaluating non-dilutive financing options.

Andy Hsieh of William Blair inquired about the payer breakdown for the CIN indication between commercial and Medicare/Medicaid, and how the company plans to leverage cost-related endpoints in reimbursement discussions. He also sought clarification on the potential launch timing, noting the CFO's guidance for 2022 versus a possible earlier approval.

Answer

Richard Daly, COO, detailed that historically, about 50% of G-CSF use is covered by Medicare/Medicaid, ensuring coverage from day one. He emphasized the strategy of focusing on the 'neutropenia vulnerability gap' to demonstrate value and cost reduction to payers and providers, particularly in the community oncology setting. He reiterated that launch timing depends on the approval date, suggesting a launch just before the holidays would be ineffective and that a 2022 launch is a more probable and strategic opportunity.