ORGAN TRANSPLANT

The immunosuppressive drugs required post-transplantation cause serious toxicities that impact organ and patient health. Limerick has developed an adjunctive therapy for CNIs to improve their safety profile and potentially establish a new standard of care.

UNMET MEDICAL NEEDS

There are ~350,000 patients living with transplanted organs worldwide and an additional 50,000 new transplants annually. Following transplant, organ rejection is the main concern. To prevent rejection, patients require chronic therapy with immunosuppressants; the mainstays are the calcineurin inhibitors, tacrolimus and cyclosporine, with 85% of U.S. transplant patients taking tacrolimus.

CNIs are potent and highly efficacious immunosuppressants. However, their efficacy is mitigated by serious dose-limiting toxicities such as nephrotoxicity and new-onset diabetes after transplant (NODAT). CNI-induced nephrotoxicity is the most common side effect and increases over time; by 10 years post-transplant, 100% of CNI-treated patients show significant kidney damage, including kidney transplants. NODAT is also common, affecting up to 50% CNI-treated patients. New products that can improve the safety profile of CNIs are needed to preserve the health of transplant patients and their grafts, which offer the potential to reduce healthcare costs, improve outcomes, and alleviate the pressure of constrained organ supply.

LIMERICK SOLUTION

Limerick’s compounds have been optimized specifically to improve the safety profile of CNIs, and restore metabolic control. Limerick compounds have been studied in over 120 human subjects to date, with the following observations:

Appears safe and well tolerated in healthy volunteers.
Reduces the nephrotoxic effects of tacrolimus.
Improves glycemic control and reduces the diabetogenic effects of tacrolimus.

Preclinical Studies Demonstrating the Effect of Limerick Compounds in Transplantation

When administered to rats at clinically relevant doses, tacrolimus produced hyperglycemia and nephrotoxicity within 30 days. LIM co-administered with tacrolimus, in a treatment model, attenuated tacrolimus-induced hyperglycemia and nephrotoxicity including reduction of glomerular filtration rate (not shown) and tissue vacuolation (shown below), a key contributor to kidney remodeling and damage.

Immunohistochemistry results from male Sprague Dawley rat kidneys after 30 day exposure to tacrolimus IP injections. Significant vacuolation is noted in the left panel (Vehicle). Animals co-administered LIM demonstrated improvement in vacuolation (right panel).

COMMERCIAL OPPORTUNITY

CNIs are used in virtually all solid organ transplant patients. Worldwide sales of CNIs are currently ~$3 billion. Several pipeline programs are targeting the CNI market with novel immunosuppressants intended to avert the CNI-associated side effects. However, these programs tend to have somewhat diminished efficacy and have been associated with serious opportunistic infections in clinical studies. Due to their unsurpassed efficacy, clinicians expect CNIs to remain the standard of care for immunosuppression for transplant patients.

Limerick’s compounds have been optimized specifically to improve the safety profile of CNIs and are intended for use as adjunctive therapy in any CNI-treated patient. Limerick has designed it program to address the key issues facing physicians and patients in this important area, and has the potential to fundamentally establish a new standard of care in a marketplace with blockbuster revenues.