Spero Therapeutics Q4 2024: Navigating Contradictions in Trial Unblinding, Regulatory Paths, and Drug Development

These are the key contradictions discussed in Spero Therapeutics' latest 2024Q4 earnings call, specifically including: Trial Unblinding and Alpha Spend for the Interim Analysis, Trial Management and Unblinding, Regulatory Path Forward for SPR206, 720 Program's Path Forward and Enrollment, and Drug Penetration Studies:



Tebipenem HBr Phase 3 Trial and Strategic Partnership:
- Spero Therapeutics announced that a prespecified interim analysis in the Phase 3 PIVOT-PO clinical trial for tebipenem HBr is expected to be completed in Q2 2025.
- The company is co-developing tebipenem HBr with GSK, with the potential for Spero to qualify for about $400 million in contingent milestones, including $25 million upon GSK submitting an NDA.
- The goal is to offer patients and prescribers a convenient oral treatment option for complicated cUTI, potentially reducing length of hospitalization.

SPR720 Phase IIa Trial and Interim Analysis:
- An interim analysis of the Phase IIa proof-of-concept trial for SPR720 as an oral treatment for NTM-PD was completed in October 2024.
- The trial did not meet its primary endpoint, with evidence of antimicrobial activity but insufficient separation from placebo, and potential dose-limiting safety signals.
- The company will analyze the full data set from all 25 patients and determine next steps for the program, which may include a reformulation strategy.

Discontinued Development of SPR206:
- Spero Therapeutics discontinued the development of SPR206, an IV-administered next-gen polymyxin antibiotic, following a thorough review and reprioritization.
- The decision was made based on a strategic refocusing of resources towards priority programs, such as tebipenem HBr, which is in a Phase 3 trial.

Financial Performance and Cash Position:
- Total revenue for the year ended December 31, 2024, was $48 million, compared to $103.8 million for the prior year, with a decrease primarily due to a decrease in collaboration revenue from agreements with GSK and Pfizer.
- As of December 31, 2024, Spero had cash and cash equivalents of $52.9 million, with an estimated cash runway into Q2 2026 based on existing cash and earned milestone payments from GSK.
- The decrease in revenue and increased R&D expenses were primarily due to increased clinical trial activity related to the Phase 3 PIVOT-PO trial for tebipenem HBr.