Charles Zhu

Charles Zhu inquired about Revolution Medicines' decision to combine pipeline assets with Bristol Myers Squibb's PRMT5 inhibitor, its fit with the ongoing Tango Therapeutics collaboration, and the criteria for go/no-go decisions on later-stage clinical development with ivonesimab, considering emerging data and the broader landscape.

Answer

Mark Goldsmith, Chairman and CEO, explained that collaborating with multiple PRMT5 inhibitors is an inclusive approach, not a signal about any particular inhibitor, and allows their differentiated compounds to be considered in various contexts. Regarding ivonesimab, he stated that decisions would be data-driven, acknowledging the potential advantages of this class over first-generation PD-1 inhibitors and the company's leading position in evaluating RAS(ON) inhibitors with ivonesimab.

Charles Zhu asked about Revolution Medicines' decision to combine pipeline assets with Bristol Myers Squibb's PRMT5 inhibitor, in context with the ongoing Tango collaboration, and how the company will make go/no-go decisions for later-stage clinical development with the ivonesimab collaboration, weighing emerging data and the broader landscape.

Answer

Chairman and CEO Mark A. Goldsmith explained that assessing RAS inhibitors with multiple PRMT5 inhibitors (including Bristol Myers Squibb, Tango, and Amgen) is an inclusive approach to make their differentiated compounds available, not a specific endorsement of any one inhibitor. Regarding ivonesimab, he stated that decisions will be data-driven, noting that this class of PD-1/VEGF bispecific inhibitors could offer significant advantages over first-generation PD-1s, particularly in GI tumors where there is less precedent. He emphasized the company's position on the leading edge of evaluating RAS(ON) inhibitors with ivonesimab.

Charles Zhu inquired about the rationale for randomizing against observation in the Resolute 304 adjuvant Diraxonrasib trial, the potential to displace chemotherapy, and the requirement for at least four months of perioperative chemotherapy as an eligibility criterion.

Answer

Alan Sandler, Chief Development Officer, explained that four months of perioperative chemotherapy is the established standard of care, and the trial aims to build upon existing success. He noted that the potential to replace chemotherapy would be reassessed based on the adjuvant study results. Mark Goldsmith, Chairman and CEO, added that requiring a standardized duration of treatment helps make the patient population more uniform.

Charles Zhu inquired about the rationale for randomizing against observation in the Resolute 304 adjuvant Diraxonrasib trial, the potential to displace chemotherapy, and the eligibility requirement for at least four months of perioperative chemotherapy.

Answer

Alan Sandler, Chief Development Officer, explained that the four months of perioperative chemotherapy is standard of care, and the trial aims to build upon existing, albeit modest, success with chemotherapy. He stated that the potential to displace chemotherapy would be reassessed based on adjuvant study results. Mark Goldsmith, Chairman and CEO, added that the standardized duration of chemotherapy ensures a more uniform patient population for comparison.

Charles Zhu from LifeSci Capital, LLC asked if the TPS 70% cutoff for B7-H4 high expression is now settled and how the company will evaluate the clinical profile trade-off between the two dosing regimens (Dose A vs. Dose B) given the new mitigation strategies.

Answer

President and CEO Dr. Martin Huber responded that the upcoming expansion data will be used to finalize the B7-H4 cut point, though he anticipates the 'high' population will remain around 40-50% of patients. He explained that the key hypothesis is that Dose B, without treatment interruptions, will yield better efficacy. The upcoming data will be critical to determine if the efficacy gain justifies the higher dose; otherwise, Dose A would be the go-forward option.

Charles Zhu from LifeSci Capital asked about the clinical development strategy for Zymeworks' pipeline, questioning the competitive bar for ZW191 against other ADCs and the plan for evaluating ZW251 in liver cancer patients with more severe hepatic impairment.

Answer

CEO Kenneth Galbraith positioned ZW191 as a differentiated asset with a novel mechanism and tolerability profile, similar to zanidatumab's development path. Chief Scientific Officer Paul Moore added that ZW251's high preclinical tolerability provides flexibility to systematically study it in HCC and potentially expand into more challenging patient populations later.

Charles Zhu of LifeSci Capital asked what data Kura needs to deliver for its farnesyl transferase inhibitor, KO-2806, in the second half of 2025 to build conviction among investors, particularly in competitive areas like RCC and RAS-driven tumors.

Answer

CEO Troy Wilson stated that the key goals are to first demonstrate acceptable safety and tolerability in combination with other targeted agents, a common failure point for combos. Second, they aim to show unexpected clinical activity, such as restoring responses in patients who have failed standard therapies, which would be a strong signal of the drug's potential.

Asked about vudalimab's differentiation in NSCLC, expectations for upcoming prostate cancer data, and enrollment progress for the XmAb564 study.

Answer

The company explained vudalimab is designed for better tolerability and that comparisons are difficult but they believe it's competitive. For the prostate data, they aim to report on more patients to assess its position against a high competitive bar. For XmAb564, the timeline is driven by safety observation periods, not enrollment speed.

Charles Zhu asked about the significance of absolute tumor SDMA levels post-treatment, not just percent reduction, the impact of pre-treatment H-scores, and the meaning of cytoplasmic versus nuclear SDMA knockdown.

Answer

Michael White, Chief Scientific Officer, explained that preclinically, greater suppression of absolute SDMA values correlates with better efficacy, irrespective of the starting H-score. Matt Maurer, Head of Clinical Oncology, noted that observing cytoplasmic SDMA reduction is a positive sign of the drug reaching its target, but further conclusions on its specific meaning are premature.