Lut Ming Cheng

Lut Ming Cheng asked if screening lags in the ALPHA3 trial were more concentrated in community-based sites and questioned the impact of international expansion on patient mix and regulatory strategy.

Answer

EVP of R&D and CMO Dr. Zachary Roberts responded that enrollment activity is encouraging across both academic and community sites. He explained that international expansion is expected to increase patient homogeneity, as R-CHOP is a more consistent global standard of care, and does not foresee any negative regulatory implications.

Lut Ming Cheng of JPMorgan Chase & Co. requested clarification on the 15% 'patient demand' growth metric for LOQTORZI and asked about the expected impact of the sales force restructure on Q2 and the remainder of the year.

Answer

Executive Vice President, Commercial, Sameer Goregaoker, clarified that 'demand' refers to end-user purchases by clinics, which directly indicates patient growth as physicians do not stock inventory. He stated the primary impact from the sales force restructure was felt in Q1 and that Q2 and Q3 are expected to be growth periods. CEO Dennis Lanfear added that more detailed projections for the year would likely be provided during the Q2 earnings call in August.

Lut Ming Cheng asked for more clarity on the timeline for the ATTR cardiomyopathy trial, specifically the base case for a first interim analysis, given that enrollment is ahead of schedule but competitor trials have seen delays.

Answer

CEO John Leonard and CMO David Lebwohl reiterated that enrollment is expected to complete by early 2027. They stated that the first interim analysis would occur after enrollment is complete, potentially in 2027. Given the drug's outstanding efficacy profile seen in Phase I, they believe it's 'certainly possible' the trial could stop early for efficacy, making an early outcome more likely than a delayed one.

Lut Ming Cheng, also known as Brian Cheng, questioned if the decision to pause ZW220 was influenced by its preclinical data or investor perception of the NaPi2b target, and asked if this shift would allow for accelerating other programs like ZW209.

Answer

Chair and CEO Kenneth Galbraith stated the decision was purely about prioritizing ZW251 due to excitement for the asset and ensuring momentum across the portfolio, including the ongoing ZW171 and ZW191 trials. He confirmed no change in guidance for ZW209 but noted the company is always looking for ways to accelerate high-impact programs.

Sean, on behalf of Lut Ming Cheng, asked about the required response bar for the PRGN-2012 confirmatory trial and whether enrollment must be completed before a potential FDA approval.

Answer

President and CEO Dr. Helen Sabzevari clarified that the confirmatory trial's design and response bar are similar to the pivotal Phase I and II trials, utilizing a single-arm, non-placebo-controlled design. She explained that under the accelerated approval pathway, the trial only needs to be initiated at the time of BLA submission and does not need to be fully enrolled or completed for the FDA to grant approval.

On behalf of Brian Cheng, Sean asked about the required response bar for the PRGN-2012 confirmatory trial and whether its enrollment must be completed prior to potential FDA approval.

Answer

President and CEO Dr. Helen Sabzevari clarified that the confirmatory trial has a similar design and endpoint as the pivotal trials, with a single arm and no placebo control. She explained that under the accelerated approval pathway, the trial only needs to be initiated at the time of BLA submission and completion is not a prerequisite for approval.

Lut Ming (Brian) Cheng asked about non-clinical items discussed with the FDA for the reni-cel BLA filing and whether the in vivo program aims for a first-in-class or best-in-class product.

Answer

CEO Gilmore O'Neill confirmed that BLA discussions involve preclinical data, particularly off-target editing, and manufacturing progress, expressing confidence in these areas. Chief Scientific Officer Linda Burkly added that the in vivo strategy could yield either first-in-class or best-in-class products, as their upregulation approach can target pathways others cannot.

Asked about non-clinical topics discussed with the FDA, other gating factors for the reni-cel BLA filing, and whether the in vivo strategy targets first-in-class or best-in-class opportunities.

Answer

The company has not provided BLA filing guidance but confirmed that progress includes preclinical data (especially off-target editing) and manufacturing, in addition to clinical data. The in vivo strategy is designed to pursue both first-in-class opportunities (by targeting genes inaccessible to knockdown strategies) and best-in-class opportunities (by aiming for a better outcome).

Asked for details on the treatment history of the responding patients and inquired about the most promising patient subset for vudalimab's future development.

Answer

The responders were heavily pre-treated with multiple lines of therapy. The most promising path is currently in post-taxane patients where the signal appears differentiated, with future potential in combination or sequence with therapies like PLUVICTO due to a non-overlapping toxicity profile.