Steve Seedhouse

Steve Seedhouse asked about the expected confirmatory trial requirements for WVE-006's accelerated approval pathway in AATD, including post-marketing requirements for full approval and clarity on lung and liver labeling.

Answer

Paul Bolno, President and CEO, stated that these details are part of the ongoing conversation with the agency to align on efficient pathways. He highlighted two development pathways (respiratory and liver) and noted that the dramatic decreases in Z-AAT protein open opportunities for liver indications. The goal is to establish the right pathway for both lung and liver labeling in AATD patients.

Steve Seedhouse asked about the anticipated confirmatory trial requirements for WVE-006 in AATD, assuming alignment on an accelerated approval pathway, and sought clarity on post-marketing requirements for eventual full approval.

Answer

President and CEO Paul B. Bolno stated that aligning on efficient confirmatory trial pathways is a key part of their ongoing discussions with the agency. He noted that WVE-006's dramatic decreases in ZAAT protein open opportunities for liver indications in addition to respiratory. The goal is to establish an accelerated approval pathway for AATD patients, ultimately aligning with the agency on labeling for both lung and liver manifestations of the disease.

Steve Seedhouse from Cantor Fitzgerald asked for elaboration on the confidence that the 200 mg multi-dose of WVE-006 would yield higher liver exposure than the 400 mg single dose. He also inquired if blinded weight loss data played a role in the WVE-007 cohort expansion decision.

Answer

President & CEO Paul Bolno explained that confidence in higher liver exposure for WVE-006 comes from preclinical models showing good translation and drug retention with repeat dosing. He highlighted that Wave's chemistry is designed for high intracellular stability, allowing the drug to accumulate. For WVE-007, he clarified the expansion decision was based on robust biomarker (Activin E) data and safety, not on an analysis of blinded weight loss data, as the initial cohort was too small for that.

Steve Seedhouse asked about early signs of patient persistence and discontinuation rates in the Phase 3 VANQUISH Obesity Program, and details regarding the 19-week induction phase and doses contemplated for the maintenance study. He also inquired about changes to tablets or the availability of an auto-injector for the maintenance study.

Answer

Brian Lian (President and CEO, Viking Therapeutics) stated that enrollment in VANQUISH studies is ahead of schedule with no notable persistence issues yet. For the maintenance study, he explained that patients are titrated up to 17.5 mg, 20 mg, 22.5 mg, or 15 mg over 19 weeks, which is an accelerated titration compared to Phase 3. He clarified that the maintenance study uses vial and syringe, not an auto-injector, and mentioned tablet doses of 17.5 mg, 27.5 mg (daily), and 110 mg (weekly).

Steve Seedhouse inquired about early signs of patient persistence and discontinuation rates in the phase three Vanquish studies, and requested more details on the 19-week induction phase and doses contemplated for the maintenance study. He also asked about changes to tablets or auto-injector availability for the maintenance study.

Answer

Brian Lian (President and CEO, Viking Therapeutics) stated that enrollment for Vanquish studies is ahead of schedule with no notable persistence issues yet. He detailed the maintenance study's titration to 17.5 mg, 20 mg, 22.5 mg, and 15 mg over 19 weeks, noting an accelerated titration schedule. He clarified that the maintenance study uses vial and syringe, not an auto-injector, and specified daily oral doses of 17.5 mg, 27.5 mg, and a weekly oral dose of 110 mg.

Steve Seedhouse of Cantor Fitzgerald asked if Viking would need another FDA meeting to move the oral VK2735 program into Phase III and what efficacy and tolerability hurdles the company would need to see to proceed. He also requested guidance on R&D expense trends.

Answer

President & CEO Brian Lian confirmed that since the oral program is under a different IND, an end-of-Phase-II meeting with the FDA would likely be required to advance to Phase III. He stated it was hard to handicap the efficacy/tolerability hurdles before seeing the data. CFO Greg Zante guided for R&D expenses to increase by approximately 25% to 33% in Q3 and Q4 compared to Q2.

Steve Seedhouse asked about the drivers of VEVYE's Q2 new prescription growth, specifically the impact from Clarity C switchers, and questioned the assertive guidance for the Specialty Branded and Triassence segment, which implies a significant second-half revenue ramp.

Answer

CEO Mark Baum quantified that Clarity C contributed about 7,000 units and noted the company has been cautious about VEVYE marketing to ensure adequate supply, a constraint they are working to resolve. Regarding guidance, he acknowledged that while some specialty products have underperformed, the ramp is achievable, driven primarily by Triassence's expansion into the large post-surgical ocular inflammation market, which is expected to gain traction in Q4.

Steve Seedhouse from Cantor Fitzgerald questioned the early market impact of new HAE drug approvals on Orlodeyo demand and requested additional details regarding the PDUFA date delay for the pediatric formulation.

Answer

President & CCO Charlie Gayer responded that Q2 saw the highest number of new patient prescriptions ever, indicating physicians are not delaying treatment for new market entrants. Chief R&D Officer Dr. Helen Thackray clarified that the pediatric PDUFA date was moved to December 12 after the FDA classified the submission of final reports as a major amendment requiring more review time, a possibility the company had anticipated.

Steve Seedhouse of Raymond James asked about potential dorsal root ganglion (DRG) toxicity, inquiring if it was observed in preclinical work or if the FDA had raised concerns. He also asked about the preclinical safety margin for the AT132 pivotal dose.

Answer

CEO Matt Patterson confirmed that the company has never observed DRG toxicity in its preclinical or clinical work and has not received any related inquiries from the FDA. He stated that for the MTM program, GLP toxicology studies in nonhuman primates tested doses up to 8x10^14 vg/kg, providing a significant safety margin over the 3x10^14 vg/kg pivotal dose.

Steve Seedhouse of Raymond James inquired about the FDA's receptivity to the final AT132 pivotal study design and asked if the company is considering Spinal Muscular Atrophy (SMA) as a potential future indication.

Answer

Chairman and CEO Matt Patterson conveyed strong confidence in the AT132 study plan, noting it was based on a series of productive interactions with the FDA. Regarding SMA, he stated that while the company is always looking for opportunities, its current focus remains on executing its existing pipeline of MTM, Pompe, Duchenne, and myotonic dystrophy programs.