Introduction to Talphera and the NEPHRO CRRT Study

In a significant development, Talphera, Inc., a leading specialty pharmaceutical company, has announced a major breakthrough in its clinical trials for patients undergoing renal replacement therapy. Following a landmark agreement with the U.S. Food and Drug Administration (FDA), Talphera is poised to expedite the completion of its NEPHRO CRRT study, a pivotal trial aimed at evaluating the efficacy of Niyad, an innovative anticoagulant designed to address critical issues in continuous renal replacement therapy (CRRT).

Context and Significance

• Background: CRRT is a form of renal replacement therapy used in intensive care settings for patients with acute kidney injury. Current anticoagulants like heparin and citrate have limitations, including systemic effects and the need for off-label use, respectively.
• Niyad's Potential: Niyad, developed by Talphera, promises to offer a safer, more targeted anticoagulation solution for CRRT, potentially replacing or supplementing existing treatments.

FDA Agreement and Study Adjustments

Key Developments

In a strategic move, the FDA has approved a reduction in the NEPHRO CRRT study size from 166 to 70 patients, maintaining the study's primary endpoint statistical power at a robust 90%. This decision marks a crucial step in streamlining the development process and is expected to expedite study completion by the end of 2025.

Study Objectives and Endpoints

• Primary Endpoint: The study focuses on the mean post-filter activated clotting time using Niyad versus placebo over the first 24 hours.
• Key Secondary Endpoints:
• Mean post-filter activated clotting time over 72 hours.
• Filter lifespan.
• Number of filter changes over 72 hours.
• Number of transfusions over 72 hours.
• Dialysis efficacy (based on urea concentration) over the first 24 hours.

Enhanced Protocol and Enrollment Strategy

• Inclusion Criteria Changes: The FDA has also approved modifications to inclusion criteria, allowing enrollment of patients who have been on CRRT for over 48 hours and removing documentation requirements for heparin intolerance in certain institutions.
• Site Expansion: Talphera plans to expand study sites to optimize enrollment, targeting completion by year-end 2025.

Funding and Financial Strategy

Private Placement Financing

Talphera has secured a private placement financing deal worth up to $14.8 million, structured in three tranches. This financing is led by existing investors Nantahala Capital and Rosalind Advisors, along with a member of management, and is designed to align capital infusion with clinical progress milestones.

• Tranche Structure:
• First Tranche: $4.925 million with an initial closing expected on April 2, 2025.
• Second Tranche: $4.925 million contingent on enrolling at least 17 patients and a stock price of at least $0.7325 per share for five consecutive days.
• Third Tranche: $4.925 million upon enrolling at least 35 patients, with similar stock price requirements.

Financial Outlook

With $8.9 million in cash as of December 31, 2024, and the potential influx of up to $14.8 million from this financing, Talphera is well-positioned to support the study through its completion.

Regulatory Pathway and Market Impact

Regulatory Timeline

Following the completion of the NEPHRO CRRT study by the end of 2025, Talphera plans to submit a Premarket Approval (PMA) application early in 2026, with potential FDA approval anticipated in the second half of 2026.

Breakthrough Designation

The FDA's Breakthrough Designation for Niyad has facilitated expedited communication and review processes, crucial in maintaining a timely development timeline.

Market Opportunity

The successful approval of Niyad could significantly disrupt the current anticoagulant landscape in CRRT, offering a safer alternative to systemic anticoagulants like heparin, which pose bleeding risks, and citrate, which is often used off-label.

Conclusion

Talphera's accelerated timeline for the NEPHRO CRRT study, coupled with its robust financing strategy, positions the company for a significant breakthrough in the renal replacement therapy market. As it moves toward FDA approval, Talphera is poised to provide a critical solution for patients needing safer, more effective anticoagulation treatments during CRRT.