Allison Bratzel

Allison Bratzel from Piper Sandler Companies asked for more detail on the company's exploration of options to expand bandwidth for the ECO platform. She questioned how this affects near-term strategy, the decision between using CDMO partners versus building in-house GMP capabilities, and requested a summary of the company's IP position and competitive moat for Ecosynthesis.

Answer

CEO Stephen Dilly explained that the focus is on locking in early-phase projects and that the company is increasingly confident in its ability to handle much of the scale-up process in-house, including GLP and future GMP material. He stated that this approach strengthens their competitive position. Regarding IP, he highlighted a strong patent portfolio supplemented by crucial trade secrets and know-how, which incentivizes partners to work directly with Codexis long-term.

Allison Bratzel of Piper Sandler asked for the key assumptions underlying the guidance for achieving cash flow positivity by year-end 2026, and how potential partnerships or an investment in an internal GMP facility might affect that timeline.

Answer

CEO Stephen Dilly clarified that the cash flow positivity target is based on organic growth and does not factor in a new GMP facility, which would require separate financing based on a visible flow of orders. CFO Georgia Erbez added that spending for a potential facility would be staged, with capital costs weighted to 2026 and operating costs coming later, minimizing near-term cash burn.

Allison Bratzel asked for details on the guidance for achieving cash flow positivity by the end of 2026, including the assumed contribution from the ECO platform and how spending on a proprietary GMP facility might impact this timeline.

Answer

CFO Georgia Erbez explained that progress towards cash flow positivity will be driven by revenue growth, which is expected to ramp up in the second half of the year as new ECO and ligase contracts are executed. Regarding the GMP facility, she noted that plans are still being formulated, with more visibility expected by the summer. She indicated that the company's net loss is projected to decrease throughout the year as the revenue base expands.

Allison Bratzel of Piper Sandler Companies inquired about the regulatory process for the ASPEN breast trial design changes, investigator feedback on the new CD47 biomarker strategy, and the data threshold for the Q3 2026 interim analysis.

Answer

CEO Jason Lettmann confirmed that the trial amendment was submitted to the FDA with no holdups and that investigator feedback has been "phenomenal" due to the high unmet need post-Enhertu. CMO Alan Sandler stated that for the interim data, a response rate in the high 30s to 40% or greater would be clinically compelling compared to the standard of care's approximate 20% rate.

Allison Bratzel from Piper Sandler Companies inquired about FDA interactions beyond the CDMO issues, confidence in a broad label, and the receptiveness of U.S. payers to covering apitigramab on top of existing SMA therapies.

Answer

President of R&D Akshay Vaishnaw described the late-cycle FDA meeting as "exceptionally constructive." COO Keith Woods added that payer outreach is progressing positively, with payers impressed by the drug's durability data. He noted that a precedent for dual therapy exists, as over 20% of SMA patients already receive more than one treatment.

Allison Bratzel inquired about the progress of discussions with U.S. and ex-U.S. payers regarding coverage for apitegromab as a combination therapy, and also asked for an update on interactions with the FDA amid general concerns about the agency.

Answer

CEO David Hallal outlined a value-based pricing strategy for the rare disease space. COO Keith Woods confirmed that early payer discussions have been positive, noting that payers already cover multiple SMN therapies. President of R&D Akshay Vaishnaw assured that interactions with the FDA are collaborative and on track for the September 22 PDUFA date, stating the agency remains focused on rare diseases.

Allison Bratzel inquired about the upcoming SAPPHIRE data presentation at the MDA conference, asking what additional data points would be most meaningful. She also asked for clarity on the EMBRAZE study, specifically what level of lean mass preservation would be considered a success for advancing SRK-439 and what the company hopes to see on secondary endpoints like A1c.

Answer

Executive Jay Backstrom stated that the full SAPPHIRE data will highlight the consistency and totality of apitegromab's effect across various endpoints and age groups. Regarding EMBRAZE, he explained that a 20% to 40% reduction in lean mass loss, which translates to preserving 1-2 kilograms, would be a meaningful signal to advance SRK-439. He noted this is a snapshot at 24 weeks and the effect could deepen over a full 52-week study.

Allison Bratzel of Piper Sandler Companies asked what is gating the start of the BMN 333 dose-ranging trial and about the company's confidence in securing regulatory alignment outside the United States.

Answer

Gregory Friberg, EVP and Chief R&D Officer, confirmed that BioMarin has already achieved regulatory alignment with multiple global agencies for its Phase 2/3 plans. He stated the primary gating factor is the formal completion of the ongoing Phase 1 healthy volunteer study, which is required to finalize the dataset before initiating the patient trial in the first half of next year.

Allison Bratzel of Piper Sandler asked for clarification on what is gating the start of the BMN-333 dose-ranging trial and about the company's confidence in achieving regulatory alignment outside the United States.

Answer

Gregory Friberg, EVP and Chief R&D Officer, stated that the primary gating factor is the formal completion of the current Phase 1 healthy volunteer study, which is required for regulatory submissions to begin the next phase. He expressed excitement to share that BioMarin has already achieved regulatory alignment with multiple global agencies for the Phase 2/3 plans, and the study initiation is on track for the first half of next year.

Allison Bratzel inquired about the progress of the confirmatory IGNYTE-3 trial, including enrollment and timelines, and asked about the company's confidence in securing a broad label for RP1.

Answer

CEO Sushil Patel explained that the IGNYTE-3 trial is a large, 400-patient global study expected to take a couple of years to fully enroll. He noted that enrollment efforts are currently focused on U.S. sites ahead of the PDUFA date, with plans to expand to ex-U.S. sites afterward. Regarding the label, Mr. Patel expressed high confidence in a broad indication, as the IGNYTE trial enrolled a real-world population and showed consistent benefit across all patient subgroups, which he expects the final label to reflect.

Allison Bratzel questioned what is driving Vafseo demand—its clinical profile or the economic incentives from TDAPA—and asked for details on reimbursement trends, particularly with Medicare Advantage plans.

Answer

CEO John Butler and CCO Nicholas Grund asserted that demand is fundamentally driven by physicians' belief in Vafseo's clinical value, with the TDAPA economics acting as an 'enabler' for access. They pointed to strong refill rates as evidence of perceived clinical benefit. On reimbursement, they reported an encouraging 80/20 split between Medicare fee-for-service and other plans, including Medicare Advantage, which is better than they had initially planned for.

Allison Bratzel of Piper Sandler inquired about the initial Q1 Vafseo revenue, asking if it included inventory stocking. She also asked about the typical dose frequency being observed and the timeline for protocol adoption and uptake at large dialysis organizations (LDOs).

Answer

CEO John Butler confirmed that the Q1 revenue guidance includes some initial inventory channel fill, which is expected to be in the 2-4 week range. He stated that dosing is almost all once-daily (QD) at this early stage. Regarding LDOs, Butler explained that while contracts are in place, operationalizing protocols is taking time. He noted that one LDO is allowing prescriptions on a medical exception basis and expects more significant movement from larger providers in the second half of the year.

Allison Bratzel inquired about the expected update on Vafseo's label expansion into the non-dialysis patient population and the potential outcomes from FDA interactions. She also asked for a characterization of physician feedback from the recent ASN Kidney Week conference.

Answer

CEO John Butler stated that Akebia plans to engage the FDA this year to define a clinical path for a non-dialysis indication, aiming for clarity on study requirements. Regarding ASN feedback, Butler described overwhelming optimism from nephrologists and patient groups. Chief Commercial Officer Nick Grund added that physician questions have become more granular and practical, indicating a readiness to prescribe Vafseo and a recognized need for an alternative to existing ESA therapies.

An analyst on behalf of Allison Bratzel from Piper Sandler requested an update on the Kidney PATIENT Act and the company's strategy for acquiring or in-licensing external assets.

Answer

CEO Michael Raab characterized the Kidney PATIENT Act as a "free call option," confirming their $750 million XPHOZAH peak sales forecast does not depend on it. He also affirmed that a dedicated team is actively pursuing business development opportunities in renal, GI, and adjacent areas to build the company, with news to be shared when available.

Allison Bratzel of BofA Securities inquired about the competitive landscape for AbCellera's ABCL575 program, particularly in light of recent data from competitors, and sought the company's view on the advantages of its OX40 ligand-targeted approach in atopic dermatitis.

Answer

President and CEO Dr. Carl Hansen explained that recent competitor data reinforces their view that non-depleting OX40 ligand antibodies are the leading approach. He differentiated ABCL575 as a non-depleting antibody engineered for a best-in-class profile, contrasting it with depleting antibodies like rocatinlimab. Dr. Hansen expressed strong confidence in the program's potential in atopic dermatitis and other indications, noting plans to present preclinical data next year.

Allison Bratzel requested clarification on several points: the total number of patients dosed in the IGNITE DMD study, the cadence for future data updates from these patients, and a breakdown of the important clinical milestones expected to be covered by the company's cash runway through Q2 2024.

Answer

CEO Ilan Ganot confirmed that a total of nine patients were dosed in IGNITE DMD before enrollment was concluded. He assured that the company will continue to provide clinical and biomarker data updates throughout the year, emphasizing the durability seen so far. He also stated the cash runway extends through Q2 2024 and will support significant clinical milestones for both the SGT-001 and SGT-003 programs.