Talphera (NASDAQ:TLPH) used a virtual analyst and investor event to provide a business update and to highlight what company leaders and two clinical experts described as an unmet need in anticoagulation during continuous renal replacement therapy (CRRT). The discussion focused on Talphera’s ongoing NEPHRO CRRT registrational study of Niyad (nafamostat) and the practical limitations clinicians face with the current anticoagulation approaches most commonly used in CRRT: heparin and citrate.
Trial progress and financial runway
Chief Executive Officer Vince Angotti said the NEPHRO CRRT study is “progressing nicely” and that Talphera recently reached the 50% enrollment milestone. He said that milestone, along with other conditions, triggered the closing of the third tranche of the company’s March 2025 financing, generating $4.1 million in gross proceeds.
On timing, Angotti reiterated expectations to complete enrollment later this year and to file a premarket approval application (PMA) “within about 3 months after study completion.” He emphasized the primary endpoint is measured at 24 hours, which he said should support a quick data turnaround once patients are enrolled.
During Q&A, Angotti addressed a timeline question, saying Talphera anticipates completion and PMA submission in the “second half” of 2026, noting the schedule had slipped due to delays at two sites. He said one site had paused all research studies due to internal protocol changes and only recently lifted the hold, allowing Talphera’s study to be reactivated with a training refresh. Talphera said its operating plan includes a PMA submission in the second half of 2026 and that data are being cleaned throughout the study because of the 24-hour endpoint.
CRRT basics and why anticoagulation matters
Angotti and Chief Medical Officer Dr. Shakil Aslam framed CRRT as a form of dialysis typically used in the intensive care unit (ICU), running continuously over 24 hours per day and often for 5–7 days, in contrast to intermittent hemodialysis commonly delivered over 3–4 hours in more stable patients.
Dr. Sharon McMahon (Medical University of South Carolina), a principal investigator on the trial, described ICU CRRT patients as critically ill, frequently with multiple organ failure, sometimes on mechanical ventilation, and often hemodynamically unstable on blood-pressure-supporting medications. She said the slower, continuous nature of CRRT is intended to be gentler for these patients, but the therapy depends heavily on maintaining filter function.
Both Dr. McMahon and Dr. Joao Teixeira (University of New Mexico), also a principal investigator, said filter clotting is a major operational and clinical problem in CRRT. Dr. McMahon said the risk of clotting is higher in ICU patients than in outpatient dialysis, citing inflammation in conditions such as sepsis and other factors (including liver-related issues) that can predispose circuits to clogging.
Dr. Teixeira outlined what happens when a CRRT filter clots, describing multiple consequences:
- Interrupted therapy: the patient is not receiving intended continuous kidney support, affecting management of potassium, acid-base status, and fluid removal.
- Time burden: restarting therapy can take one to three hours, depending on staff workload.
- Cost: filter sets cost “hundreds of dollars,” he said, and premature replacement adds expense.
- Potential blood loss: he said circuits may contain roughly 150 milliliters of blood (about half a unit), and if clotting occurs suddenly, nurses may be unable to return blood to the patient.
Heparin and citrate: common options with significant drawbacks
In discussing current practice, Dr. Teixeira said his institution has not implemented a single default approach, describing UNM as a “nothing first” center in part because he views both heparin and citrate as carrying significant limitations. He noted that while citrate has been recommended as first-line anticoagulation in guidelines for more than a decade, many centers have not adopted it broadly due to complexity.
Dr. McMahon said her institution typically starts citrate if a patient clots more than once in 24 hours, using ACD-A (2.2% citrate). However, she described citrate as burdensome and operationally challenging, including intensive lab monitoring (ionized calcium and post-filter calcium among others), calcium infusions, titration complexity, and issues in certain patient populations such as liver patients who may accumulate citrate. She also noted logistical challenges, including storage constraints for large CRRT fluid bags, and said her team had to make adjustments due to inventory and expiration issues, citing an audit that showed $45,000 of expired citrate-related drug product.
Heparin, in contrast, was described by both clinicians as less attractive due to systemic bleeding risk and inconsistent performance. Dr. McMahon said heparin was less effective than citrate in her experience and not regional to the circuit, increasing bleeding risk. She said MUSC does not maintain a heparin protocol for CRRT outside of research needs. Dr. Teixeira emphasized what he characterized as unpredictable dosing effects and the need for reversal in some cases.
Both clinicians also provided examples of current filter performance without anticoagulation. Dr. McMahon cited published data indicating one-third of filters fail within the first 12 hours and another third last 12–24 hours, concluding that most institutions do not reach 24 hours of filter life. Dr. Teixeira said UNM’s median filter life was around 13 hours based on his internal review, with a mean somewhat longer but still under 24 hours.
How investigators described nafamostat’s potential fit
Both physicians said their experience in the blinded Niyad trial has highlighted what they viewed as easier workflow compared with heparin or citrate, particularly for nursing staff. Dr. McMahon said nurses have been “excited” about how simple administration appears in the trial setting, while Dr. Teixeira described titration as straightforward, saying it typically stabilizes within the first hour with limited subsequent adjustments.
Asked how nafamostat might be adopted if approved, Dr. Teixeira said he would expect it to “move to the front of the line” as an anticoagulation option and that he could not foresee using heparin instead. Dr. McMahon similarly said she would move it to the frontline and replace her current protocol, adding that simpler options could be especially important for community hospitals that lack the bandwidth to implement citrate protocols.
In Q&A, the physicians also suggested that availability of a simpler anticoagulant could increase the overall use of anticoagulation in CRRT, particularly at “nothing first” centers. Dr. McMahon said she would use an option that could extend filter lifespan closer to 72 hours, which she said is a target expectation, and argued current performance is often well below 24 hours.
Enrollment challenges and regulatory questions
On trial enrollment, Dr. Teixeira said CRRT trials are inherently difficult because patients are severely ill and consent logistics can be complicated. He also said the protocol is designed conservatively, excluding many patients with higher bleeding risk—patients he said could be “ideal candidates” in real-world practice if the therapy provides regional anticoagulation with lower systemic bleeding risk.
When asked whether strict exclusion criteria could create regulatory or adoption headwinds, both clinicians said they did not expect the trial’s conservative approach to be a barrier, emphasizing that actively bleeding patients would generally not be enrolled in such studies.
Angotti also addressed market exclusivity, stating Talphera would receive six years of data exclusivity post-approval and that the company has filed domestic and international patents related to methods of use, titration schedules, and supply, which he said could extend protection into the 2040s if awarded.
About Talphera (NASDAQ:TLPH)
Talphera, Inc, a specialty pharmaceutical company, focuses on the development and commercialization of therapies for use in medically supervised settings. Its lead product candidate is Niyad, a lyophilized formulation of nafamostat, which is under an investigational device exemption as an anticoagulant for the extracorporeal circuit. It is also developing LTX-608, an anti-inflammatory and antiviral potential for the treatment of multiple conditions, including disseminated intravascular coagulation (DIC), acute respiratory distress syndrome (ARDS), and acute pancreatitis; Fedsyra, a pre-filled ephedrine syringe; and PFS-02, a pre-filled phenylephrine syringe.
