Cheng Li

Cheng Li asked if Wave Life Sciences plans to share additional biomarker data related to inflammation or fibrosis in the upcoming INLIGHT update and if the data will be presented at a medical conference this year.

Answer

President and CEO Paul B. Bolno stated that the company has not yet guided on the presentation venue, but the update will be this quarter, with key metrics similar to previous readouts. He explained that the current Phase 1 INLIGHT study, enrolling otherwise healthy individuals with lower BMIs, presents challenges for discerning changes in inflammatory or fibrosis biomarkers. He noted that the Phase 2a portion, which will include patients with comorbidities (e.g., higher HbA1c, other lipid characteristics), will offer more opportunities to observe these additional biomarker changes.

Cheng Li asked if Wave Life Sciences plans to share additional biomarker data related to inflammation or fibrosis for the upcoming INLIGHT update, and if the data will be presented at a medical conference this year.

Answer

Paul Bolno, President and CEO, stated that the company has not yet guided on presentation venues but confirmed the update will be this quarter, with key metrics similar to previous readouts. He explained that discerning other markers like inflammation or fibrosis is challenging in the current Phase I study due to the 'otherwise healthy', low BMI population. The Phase IIa portion, which will enroll patients with comorbidities (e.g., higher HbA1c, other lipid characteristics), will offer more opportunities to observe these changes.

Cheng Li from Oppenheimer & Co. Inc. asked about the baseline characteristics of patients enrolled in cohort two of the WVE-007 study and what key metrics to watch. He also inquired if the Q4 data would provide clarity on the ultimate dosing frequency.

Answer

President & CEO Paul Bolno confirmed that patients are healthy overweight or obese individuals meeting specific BMI criteria (20-35), and full baseline characteristics will be shared with the data. Regarding dosing frequency, he explained that the data from the 75 mg and 240 mg cohorts, followed by the 400 mg cohort, will provide a good sense of the dosing kinetics using Activin E as a key biomarker to track the PK relationship over time.

Cheng Li from Oppenheimer & Co. Inc. asked for confirmation that the norovirus Phase 2b trial is contingent on securing a partnership or funding, inquired about the earliest possible start time for that study, and asked for the rationale behind the second stop-work order for the COVID-19 program.

Answer

CEO Steven Lo noted productive partnership discussions for the norovirus program since June. CFO Jeroen Grasman confirmed that progression of the norovirus study is contingent on external funding or a partnership. Mr. Lo added that funding is the primary gating factor for the trial. Regarding the COVID-19 trial, Mr. Lo stated that Vaxart has not yet received a specific rationale for the stop-work order from BARDA but remains in dialogue with them.

Inquired about the norovirus program's dependency on funding for its Phase 2b trial and other potential gating factors. Also asked for the rationale behind the second stop work order for the COVID-19 program and the prospects for resuming enrollment.

Answer

The company confirmed that the progression of the norovirus Phase 2b study is contingent on securing new funding, which is the primary gating factor. Regarding the COVID-19 trial, they have not yet received a specific rationale for the second stop work order from BARDA and are awaiting further information.

Cheng Li inquired about the key factors determining the start of patient dosing for Vaxart's 10,000-participant Phase IIb COVID-19 trial and the expected enrollment timeline. He also asked for the criteria that would define a successful outcome for the Phase I trial of the second-generation Norovirus vaccine.

Answer

CEO Steven Lo explained that following the lifting of the stop-work order, the company is proceeding with necessary next steps like patient screening before dosing can commence. Chief Medical Officer Dr. James Cummings projected an enrollment period of approximately five to six months for the COVID-19 study. Regarding the Norovirus trial, Founder and Chief Scientific Officer Dr. Sean Tucker stated that success would be demonstrated if the new vaccine constructs show a positive trend in key immunogenicity endpoints compared to the older constructs, even without statistical significance due to the study's size.

Cheng Li from Oppenheimer & Co. Inc. asked about the completion timeline for the Selectra device's DV testing, noting it seemed to extend beyond the prior H1 guidance, and also inquired about the company's thinking on a redosing strategy for INO-3107.

Answer

President and CEO Dr. Jacqueline Shea confirmed that while DV testing was a complex process with external vendors, the company remains on track for its H2 2025 BLA submission. Chief Medical Officer Dr. Michael Sumner added that Inovio plans to pursue a redosing strategy, likely annual dosing, to maintain and enhance clinical benefit, with FDA discussions to begin post-BLA submission.

On behalf of Jay Olson at Oppenheimer, Cheng Li asked for the rationale behind choosing 1,200 patients as the optimal number for the MAGNITUDE study and whether this number is considered final.

Answer

EVP & CMO David Lebwohl explained that the 1,200-patient size is optimal for demonstrating a statistically and clinically meaningful benefit in the stabilizer subpopulation. He noted this number allows for completion within the guided timeframe, accelerates event accrual for analyses, and maintains the company's cash runway. He confirmed that Intellia is not planning further adjustments to the trial size.

Cheng Li asked about the characteristics of early CABOMETYX adopters in the NET setting and whether upcoming data for the pipeline drug XL309 would include both monotherapy and combination results.

Answer

EVP of Commercial P.J. Haley noted that commercially, they do not receive detailed patient data but that qualitative feedback suggests broad utilization across NET patient types, consistent with the label. Chief Medical Officer Amy Peterson confirmed that the XL309 program is evaluating both monotherapy and combination therapies and data will be shared when a complete set is available.

Cheng Li of Oppenheimer & Co. Inc. inquired about the baseline characteristics of patients being enrolled in the REZPEG trial and asked for the geographic split of enrollment between U.S. and ex-U.S. clinical sites.

Answer

Chief Medical Officer Dr. Mary Tagliaferri explained that because the study is fully blinded, the company is not analyzing aggregated baseline data to maintain the trial's integrity. She assured that clear baseline characteristics will be provided along with the top-line data results.

Cheng Li, on for Jay Olson, asked if the follow-up time for the reni-cel adolescent cohort would be sufficient at the time of BLA filing to have both adult and adolescent patients included on the label.

Answer

Chief Medical Officer Baisong Mei expressed pleasure with the rapid enrollment of the adolescent cohort and confirmed that Editas 'certainly want to seek for a broader indication of all age cohorts' and has alignment with the FDA on the clinical trial design to support that goal.