# A Once-Weekly Oral Tacrolimus-Prednisone Fixed-Dose Combination Therapy for Post-Transplant Maintenance Immunosuppressive Therapy

> **NIH NIH R44** · LYNDRA THERAPEUTICS, INC. · 2020 · $1,000,000

## Abstract

Solid organ transplantation is a highly successful form of intervention following irreversible organ failure, with
approximately 35,000 transplants performed annually in the US. Adequate suppression of the immune system
is required for graft survival, and once- or twice-daily immunosuppressive therapy with the calcineurin inhibitor
tacrolimus is central to allograft rejection prevention. Immunosuppression with tacrolimus presents significant
pharmaceutical challenges, including highly variable pharmacokinetics and a narrow therapeutic index, where
once- or twice-daily administration results in peaks in blood concentration which contribute to toxicity and troughs
which can lead to graft rejection. In addition, while adherence to immunosuppressive therapy is critical to graft
survival, non-adherence rates among transplant recipients are high, averaging about 23% across all solid organ
transplant types, with highest rates (36%) observed for kidney transplants. Non-adherence is most problematic
during adolescence and young adulthood, which is also the time of maximal immune system activity and
biological risk for organ rejection.
Lyndra has developed a novel oral drug delivery technology that provides extended therapeutic drug levels with
infrequent dosing. The technology is based on a gastric residence dosage form that delivers drug continuously
to the stomach and then exits the body through the lower GI tract. Lyndra dosage forms have been manufactured
under cGMP and are currently in multiple clinical trials. Studies in large animals demonstrate continuous drug
release and gastric retention for one week or more. Human clinical data from multiple studies show an excellent
safety profile and sustained drug delivery.
The proposed research is a collaboration between Lyndra and the NYU Langone Transplant Institute. Our goal
is to develop a once-weekly oral tacrolimus-prednisone fixed-dose combination for maintenance therapy in
kidney transplant recipients previously stabilized on daily therapy. Once-weekly tacrolimus-prednisone may
benefit patients by (1) providing a safer, more effective therapy by maintaining trough tacrolimus concentrations
within the therapeutic range with reduced peak-trough variation, (2) reducing total dose and side effects, and (3)
substantially improving adherence to long-term maintenance immunosuppressive therapy. Lyndra has
established technical feasibility of this concept by demonstrating tacrolimus and prednisone encapsulation,
stability and controlled release under simulated gastric conditions.
The objective of this Direct-to-Phase II SBIR proposal is to develop and manufacture a tacrolimus-prednisone
dosage form for a Phase 1 clinical trial and to lay the clinical and regulatory groundwork for development of the
product. The proposed work includes IND-enabling pharmaceutical development and GMP manufacturing of
clinical supplies along with regulatory and clinical planning activities that culminate in the submission of an ...

## Key facts

- **NIH application ID:** 9908525
- **Project number:** 1R44AI149979-01
- **Recipient organization:** LYNDRA THERAPEUTICS, INC.
- **Principal Investigator:** Stephen ZALE
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $1,000,000
- **Award type:** 1
- **Project period:** 2020-03-02 → 2022-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9908525

## Citation

> US National Institutes of Health, RePORTER application 9908525, A Once-Weekly Oral Tacrolimus-Prednisone Fixed-Dose Combination Therapy for Post-Transplant Maintenance Immunosuppressive Therapy (1R44AI149979-01). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/9908525. Licensed CC0.

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