Savara (NASDAQ:SVRA) executives provided an update on the company’s regulatory timeline, manufacturing changes, clinical evidence, and commercial preparations for MOLBREEVI during a presentation at Guggenheim’s Emerging Outlook Biotech Summit.
Company focus and near-term regulatory timeline
Chair and CEO Matt Pauls described Savara as a “single asset, rare disease company” focused on orphan rare pulmonary diseases. The company’s late-stage program, MOLBREEVI, is intended for autoimmune pulmonary alveolar proteinosis (aPAP), which management characterized as a rare lung disease with no approved pharmacological treatment option.
Outside the U.S., Pauls said the company has guided to filing marketing authorization applications (MAAs) in Europe and the U.K. by the end of the first quarter and stated that process remains on track.
Manufacturing change following refusal to file
Pauls addressed the company’s prior regulatory setback. He said Savara received an unexpected refusal to file (RTF) in May of last year due to “in-process manufacturing data” the agency wanted before accepting the filing. Management believed the issue could have been resolved during the review, but the FDA required the additional information prior to filing acceptance.
Following a Type A meeting with the FDA, Savara aligned with the agency on moving to an alternate drug substance manufacturer and on an analytical comparability protocol. Pauls said the company completed a tech transfer to Fujifilm—an effort that had already been underway for about 18 months—and resubmitted the BLA in December with Fujifilm as the primary drug substance manufacturer.
On the topic of potential pre-approval inspections (PAIs), Pauls said it is difficult to speculate on the FDA’s process after an application is accepted, noting that the timing and requirements can vary by program and division. He characterized the company as “very confident” in the resubmitted BLA.
Clinical package and endpoint rationale
Pauls and EVP of Global Medical Affairs Brian Robinson, MD, discussed the clinical evidence supporting MOLBREEVI, including the choice of DLco as the primary endpoint in the company’s IMPALA-2 study.
Pauls described DLco as a surrogate endpoint and emphasized that, as a first mover in an orphan rare disease, Savara also viewed it as important to show clinical benefit in key secondary endpoints. He highlighted robust results in the St. George’s Respiratory Questionnaire (SGRQ) measures and exercise tolerance testing using exercise treadmill tests. Pauls also noted that DLco reached statistical significance at 24 weeks (the primary endpoint) and remained statistically significant at 48 weeks as a key secondary endpoint, which he said supported durability of effect.
Robinson outlined several reasons DLco was used and considered clinically meaningful in aPAP, including:
- It is well studied and used clinically to help diagnose autoimmune PAP, monitor treatment, and assess disease progression.
- It reflects the impact of surfactant burden on gas transfer, as it measures the diffusing capacity of the lungs for carbon monoxide.
- It is described as more responsive than other pulmonary function tests in aPAP patients treated with GM-CSF.
- It is easy to perform and reproducible, with Savara standardizing equipment and training across trial sites.
On secondary endpoints, management referenced the concept of minimal clinically important difference (MCID) for SGRQ established in other pulmonary diseases. Robinson said SGRQ has not been validated specifically in autoimmune PAP but has been validated in conditions including COPD and lymphangioleiomyomatosis (LAM). He cited a four-point reduction as the MCID in COPD and said Savara observed that level of change in its SGRQ total and activity scores.
Commercial preparation: patient identification, awareness, and launch execution
Chief Commercial Officer Braden Parker discussed Savara’s view of the U.S. market and its patient-finding efforts. He said the company’s claims database analysis identified approximately 5,500 diagnosed prevalent aPAP patients in the U.S. Parker described “line of sight” as the company’s process of profiling accounts associated with claims, confirming that patients are actively managed at those locations, and identifying who is currently managing them. Parker said Savara has reached a goal of having line of sight to 1,000 patients—about 20% of the market—through a small field effort, which he said increased confidence that the market is “real and underappreciated.”
Parker added that the market is concentrated, stating that the top 500 accounts represent about two-thirds of the market. He cautioned that launches are labor intensive and that there will be time lags between approval, physician visits, prescribing, and the reimbursement and fulfillment steps within the U.S. healthcare system. Pauls noted that Savara recently announced PANTHERx as its single specialty pharmacy partner and characterized it as an experienced rare disease pharmacy that has supported multiple launches.
On disease awareness and diagnosis, Parker said Savara has been running physician disease awareness efforts for a couple of years and added patient-level disease awareness campaigns in the last year. He highlighted the aPAP ClearPath testing program, which transitioned from a blood draw to a dry blood spot test (four drops of blood on a card), with results returned within seven days including a yes/no result and titer level.
Pauls said the company has identified newly diagnosed (“de novo”) autoimmune PAP patients through testing efforts and described a pilot in an interstitial lung disease (ILD) clinic at the University of Florida, which suggested there are undiagnosed patients in ILD settings due to nonspecific symptoms. He said Savara is scaling the ILD clinic pilot to additional sites.
Pauls also compared the company’s patient estimates to published epidemiology ranges, stating the literature spans from about six or seven per million diagnosed prevalence to the mid-20s. He said the company’s approximate 5,500 U.S. estimate equates to about 15–16 per million—“right in the middle of the fairway”—and suggested the ceiling could be higher as testing expands.
Pricing, ex-U.S. strategy, and capital position
On pricing, Parker said Savara previously identified a corridor of $300,000 to $500,000 per patient per year and has since narrowed that to $400,000 to $500,000. He said payer feedback suggested limited budget-impact concerns within that range and anticipated coverage with typical prior authorization criteria.
For Europe and the U.K., Pauls said Savara plans to commercialize on its own in EU4 and the U.K., citing a well-articulated market with reference centers and a patient opportunity similar to the U.S. He also said the company believes it is important to maintain full control over MOLBREEVI given policy-related uncertainty.
On Japan, Pauls said the company is still in a “wait and see” posture and that Asia-Pacific could involve a different go-to-market approach than Europe and the U.K.
Pauls reviewed Savara’s capital position, stating the company reported $264 million pro forma on the balance sheet. He also noted a royalty agreement with RTW that includes a $75 million payment based on FDA approval, and said Savara restructured its debt facility with Hercules to allow a unilateral option to draw up to $75 million upon FDA approval—providing at least $75 million and potentially up to $150 million in incremental non-dilutive capital if fully utilized.
Looking ahead, management said it expects an FDA filing decision in the coming weeks and reiterated that, assuming priority review, the key catalyst would be an August PDUFA timeline. Pauls said a decision on whether to host a commercial day is “still to be determined.”
About Savara (NASDAQ:SVRA)
Savara Inc (NASDAQ:SVRA) is a clinical-stage biopharmaceutical company focused on developing and commercializing therapies for rare respiratory diseases. The company specializes in in-licensing, advancing and potentially bringing to market novel treatments that address severe pulmonary conditions with high unmet medical need.
The company’s lead candidate, Molgradex (recombinant human granulocyte-macrophage colony-stimulating factor, or GM-CSF), is under regulatory review for the treatment of autoimmune pulmonary alveolar proteinosis (PAP), a rare lung disease characterized by the accumulation of surfactant.
