Matthew Biegler

Matthew Biegler asked if pancellularity is expected to increase beyond 12 weeks, similar to hydroxyurea, and inquired about the two patients missing 12-week assessment data, noting their absence seemed to sway the average downward.

Answer

Dr. Martin Steinberg, Professor of Medicine, Pediatrics, Pathology, and Laboratory Medicine, confirmed that pancellularity is expected to increase over time, citing hydroxyurea trial data where F cells increased from 60% at 12 weeks to over 85% later. He emphasized that pociredir's mechanism, leading to higher HbF per F cell, suggests even better protection. Iain Fraser, SVP of Early Development, stated that data for the missing patients would not be obtained due to logistical issues with sample shipping, but noted these patients had high F cell percentages at week 10, and the overall cohort showed broad F cell response.

Matthew Biegler from Oppenheimer & Co. asked if pancellularity is expected to continue increasing beyond 12 weeks, similar to observations with hydroxyurea, and sought clarification on the missing 12-week assessment data for two patients and its impact on the average F cell percentage.

Answer

Dr. Martin Steinberg (Professor of Medicine, Boston University) confirmed that pancellularity is expected to increase over time, citing hydroxyurea trial data where F cells increased from 60% at 12 weeks to over 85% over time. Iain Fraser (SVP of Early Development) explained that the missing 12-week data for two patients was due to logistics and assay variability, noting that these patients had high F cell percentages at week 10, and two other patients with lower HbF were missing at week 10, making the numerical value sensitive to missing data.

Matthew Biegler from Oppenheimer noted the baseline fetal hemoglobin (HbF) of ~7.6% was higher than anticipated for a severe patient population. He asked if this sample was representative and whether pociredir would be equally or more effective in patients with higher baseline HbF. He also questioned the reason for tightening the data release guidance from 'mid-year' to 'early Q3'.

Answer

Executive Alexander Sapir clarified that the baseline HbF was disclosed to allay investor concerns that it might be too low to show a meaningful increase. Iain Fraser, Head of Development, added that while this is a small sample, there is currently no reason to believe baseline HbF determines the response to pociredir. Regarding the timeline, Mr. Sapir stated the adjustment was due to trial execution, allowing them to report on a larger cohort of 16 patients.

Matthew Biegler of Oppenheimer & Co. Inc. requested more detail on the type of data expected from the pociredir readouts mid-year and year-end, specifically asking if it would be mature enough to show any early data on vaso-occlusive crises (VOCs).

Answer

CEO Alexander Sapir confirmed the data release will include HbF levels, other biomarkers, and comprehensive safety data. He cautioned that observing a significant reduction in VOCs is unlikely given the short 3-month study duration. Executive Iain Fraser added that while they will report any on-study VOCs descriptively, the study is not powered for that endpoint, but they will have more granular data on patients' baseline VOC frequency.

Matthew Biegler of Oppenheimer inquired about Fulcrum's high-level strategy for its platform technology, the decision-making process for keeping assets wholly-owned versus partnering, and the future therapeutic area focus.

Answer

Executive Alexander Sapir explained that the company's most advanced preclinical program in inherited aplastic anemias, which came from the Camp4 deal, will be progressed internally for the time being, retaining global rights. He noted that ex-U.S. licensing remains a future option, similar to the Sanofi deal for losmapimod, but the current focus is on internal discovery efforts. Executive Iain Fraser concurred with the summary.

Matthew Biegler asked if the FDA had requested more data on losmapimod's mechanism of action, such as DUX4 reduction biomarkers, and whether the updated timeline for REACH data was a revision or simply fine-tuning of previous guidance.

Answer

Executive Iain Fraser responded that the FDA's focus has been on functional endpoints, not biomarkers, and that the company has not received requests for more mechanism of action data. CEO Alexander Sapir clarified that the updated REACH data timeline of 'by the end of October' is simply 'fine-tuning' as the company gains more certainty with the last patient visits approaching.

Matthew Biegler of Oppenheimer & Co. Inc. asked if the company's view on the importance of cell expansion has changed for the low tumor burden MRD setting, given the discontinuation of the FCA arm which was intended to boost expansion.

Answer

CEO Dr. David Chang clarified that their thinking has not changed. The company always recognized the MRD setting was unique due to low antigen targets, which is why the trial was designed with both FC and FCA arms from the start. Unplanned data showing MRD conversion with the standard FC regimen provided confidence to proceed with that arm alone.

Matthew Biegler asked about the company's strategy for its autoimmune (I&I) program, ALLO-329, and whether Allogene would consider a partnership to preserve its cash runway.

Answer

CEO David Chang confirmed that protecting the cash runway is a top priority in the current market. He stated that the company is 'very willing to partner and derisk the autoimmune program,' especially as it is outside their core oncology expertise. He also noted the program's timeline was extended to incorporate clinical response data alongside biomarkers.

Matthew Biegler from Oppenheimer & Co. Inc. asked about the potential trade-off between efficacy and convenience, specifically how much efficacy Allogene would sacrifice to achieve a no-lymphoconditioning regimen with ALLO-329.

Answer

Dr. David Chang, President and CEO, described eliminating lymphodepletion as a 'big, big game changer' that would broaden patient access. However, he also stressed that even just lowering lymphodepletion intensity would be a 'significant win' for the program, indicating a pragmatic approach to balancing efficacy with the benefits of a simpler regimen.

Asked about the requirements for accelerated approval for CX-2051 in fourth-line colorectal cancer (CRC), specifically the necessary overall response rate (ORR) and the relevance of ORR versus other endpoints like PFS or OS.

Answer

The company is considering an accelerated approval pathway due to the high unmet need, but acknowledges challenges. There is no precedent for accelerated approval in CRC based on ORR, and there is general regulatory uncertainty. Typically, PFS and OS are the key endpoints in this setting. The company will discuss this with the FDA at the appropriate time.

Matthew Biegler of Oppenheimer & Co. Inc. questioned what CytomX views as the regulatory bar for accelerated approval in fourth-line CRC, particularly regarding the relevance of ORR versus PFS or OS.

Answer

Sean A. McCarthy, Chairman & CEO, acknowledged the difficulty of the question, stating that while the company's data is encouraging, there is no precedent for accelerated approval in CRC based on ORR. He noted the high unmet need could support such a path and that CytomX will discuss it with the FDA at the appropriate time, while also considering the current overall regulatory uncertainty.

Matthew Biegler asked if Trodelvy's decreased demand was related to competitive pressure from recent approvals and requested a breakdown of the patient mix between triple-negative and HR-positive breast cancer.

Answer

Chief Commercial Officer Johanna Mercier stated that they have not seen an impact from new market entrants. She clarified Trodelvy's distinct positioning: it is the ADC of choice in second-line metastatic triple-negative breast cancer and in later (fourth) lines for HR-positive/HER2-negative disease, differentiating it from other ADCs used in earlier lines of therapy.

Matthew Biegler of Oppenheimer & Co. Inc. asked about the scale of the market opportunity for Trodelvy in frontline triple-negative breast cancer (TNBC), ahead of the upcoming ASCENT-03 data.

Answer

Johanna Mercier, Chief Commercial Officer, stated that the frontline TNBC market is significantly larger than later-line settings, estimating it to be 'about double' in size. She noted the market is split between PD-L1 negative and positive patients. Mercier emphasized that demonstrating an overall survival benefit in this setting would be incredibly powerful, building on Trodelvy's established standard-of-care position in second-line plus.

Matthew Biegler of Oppenheimer asked about the statistical plan for VERITAC-2, specifically if it involves hierarchical testing, and whether a hazard ratio of 0.7 would be sufficient for an all-comers label.

Answer

CMO Noah Berkowitz confirmed that VERITAC-2 has two co-primary endpoints (ESR1 mutant and ITT population) and the company can succeed on either. While not commenting on a specific hazard ratio, he noted that they expect to achieve a better hazard ratio in the ESR1 mutant population compared to the overall ITT population.

Matthew Biegler of Oppenheimer inquired about the status of Baylor's AML trial, particularly the higher-dose testing, and asked if the company planned to present side-by-side comparisons of products from the new versus old manufacturing processes.

Answer

CMO Dr. Mythili Koneru and CEO Peter Hoang clarified that Baylor is close to completing the final dose level in its Phase I trial, with some delays caused by COVID-19. Chief Development Officer Dr. Juan Vera confirmed that comparative data on the manufacturing processes is being presented at the ISCT and ASGCT meetings, highlighting the biological improvements of the new process.

Matthew Biegler of Oppenheimer inquired about the logistics for enrolling the safety lead-in patients in the Phase II AML trial, including graft sourcing, turnaround times, and the manufacturing process used. He also asked about the dosing strategy for the Phase II trial, specifically if Marker Therapeutics plans to explore the higher doses currently being tested by Baylor College of Medicine.

Answer

President and CEO Peter Hoang confirmed the company is using its new, improved manufacturing process for all patients in the Phase II trial. Chief Medical Officer Dr. Mythili Koneru detailed the patient intake and donor procurement process, noting that manufacturing for the lead-in portion will occur at Baylor before transitioning to Marker's in-house facility. Regarding dosing, Dr. Koneru stated that while Marker is starting with a flat dose, they are closely monitoring Baylor's high-dose cohorts and are interested in potentially exploring higher doses, which their new manufacturing process can support.

Matt Biegler from Oppenheimer & Co. Inc. inquired about the patient enrollment sequence for the Phase 2 AML trial, specifically asking if the first three patients using the legacy reagent must be treated before enrolling patients with the new MT-401 reagent. He also asked for details on the upcoming pancreatic cancer trial update at ASCO.

Answer

Chief Medical Officer Dr. Mythili Koneru clarified that patients from both reagent groups can be enrolled simultaneously, provided there is a two-week interval between each patient's first treatment. She confirmed that the ability to enroll patients with the new reagent depends on the manufacturer providing the certificate of analysis, not on the completion of the first cohort. President and CEO Peter Hoang noted that more details on the pancreatic cancer trial would be available after the ASCO abstracts are released.

Matt Biegler from Oppenheimer & Company asked about the potential worst-case scenario for the IND delay, the AML trial design, and the timing of new data from Baylor.

Answer

SVP of Clinical Development, Dr. Mythili Koneru, expressed confidence in initiating the Phase 2 trial in 2020, stating they have worked closely with the reagent manufacturers. She confirmed the trial design remains unchanged, targeting both adjuvant and active disease settings. Dr. Koneru also noted that updated data from the Baylor studies is expected next year and that higher-dose testing in the AML study has already commenced.