Summary: 

The National Cancer Institute (NCI) seeks research co-development partners and/or licensees for a delivery system to improve transplant outcomes through inhibition of the JAK/STAT pathway. 

Description of Technology: 

Value Proposition

•    Novel Therapy:  Hydro(LNp), is a new therapeutic application to improve outcomes for organ transplant recipients
•    Broad Scope: Potential to adapt for applications beyond transplantation, such as cancer, autoimmunity, and regenerative medicine
•    Convenient Delivery: Hydro(LNp) is a two-phase delivery system to increase effectiveness in regulating transplant rejection
 
Unmet Need

Transplantation becomes the only therapeutic option after end-stage organ diseases and other devastating tissue loss. However, transplanted patients need to receive high doses of multi-drug immunosuppressive therapy for the rest of their life to prevent rejection. This current standard of care often entails dangerous side effects –including nephrotoxicity, cardiovascular disease, diabetes, and higher predisposition to infections and cancer. Therefore, there is an unmet need to identify a safer and effective treatment plan for transplant recipients.
 
Technology Description

Researchers from the National Cancer Institute (NCI), Johns Hopkins University (JHU) and Johns Hopkins Applied Physics Laboratory (JH-APL) have identified that concomitant inhibition of the JAK/STAT pathway (via small molecule inhibitors) and of a key costimulatory pathway (via the biologic CTLA4-Ig) improves the control of the immune response to a transplant. As a combination therapy, they create “Enhanced Costimulation Blockade,” generating positive results without many rejection episodes or side effects. The multidisciplinary team of researchers engineered a dual component delivery system called Hydro(LNp), which delivers JAK inhibitors (JAKi) in a dual form: (1) microcrystalline drug deposits in the hydrogel and (2) lipid nanoparticles encapsulated drug. This product can be injected near the transplant site. The microcrystalline drug is released locally, while the lipid nanoparticle (LNp) carry it to the specific distal sites where the immune response against the transplant is initiated. The net result is a localized synergy with CTLA4-Ig effectively preventing graft rejection. 

This technology could positively impact transplantation-control of immune response to prevent transplant rejection. An autoimmunity-based therapeutic that inhibits JAK signaling could bring therapeutic benefit to autoimmune diseases such as rheumatoid arthritis, psoriasis, systemic lupus erythematosus and inflammatory bowel disease. Cancers with a dysregulated JAK/STAT pathway could also be treated with this technology.

This technology is co-owned by JHU and The National Institutes of Health (NIH), and was co-developed by NCI, JHU and JH-APL. The summary of the technology was provided by Johns Hopkins Technology Ventures (JHTV) and Dr. Giorgio Raimondi. The technology is cross-listed on JHTV’s website Tech Publisher. The  Hydro(LNp) is as a modification of an earlier NCI-JHU co-owned technology (NCI  E-123-2018 which is cross-listed as Case ID:15347 on Tech Publisher. A publication describing the technology is Majumder, et al. Multiphase assembly of small molecule microcrystalline peptide hydrogel allows immunomodulatory combination therapy for long-term heart transplant survival. (PMID: 32812339)

Since Hydro(LNp) is an NCI Intramural Research Program developed technology, it is eligible for special funding through NCI’s Small Business Innovation Research Technology Transfer (SBIR-TT) program. In addition to funding, SBIR-TT awardees may work closely with the NCI inventor to further develop the technology. Additional information and links to apply to the SBIR-TT program can be found here. 

Potential Commercial Applications:

•    Prevent transplant rejection
•    Autoimmunity diseases such as rheumatoid arthritis, psoriasis, systemic lupus erythematosus and inflammatory bowel disease
•    Cancer therapeutic 

Competitive Advantages:

•    Drug delivery method that extends the half-life of tofacitinib
•    Provide continuous, rate-controlled, localized and targeted release of tofacitinib
•    Treat autoimmunity or prevent transplant rejection when combined with CTLA4-Ig, an immunosuppressive agent, for Enhanced Costimulation Blockade