J-Pharma
Unlocking the Curative Powers of Solute Carrier Transporters

In the new world of healthcare and medicine, novel drug formulations and innovative technologies continue to spring from the drawing board. Despite these advances, certain life threatening cancers and autoimmune diseases still hold a slim chance of curability. Notably, incurable biliary tract cancers (BTC), and pancreatic cancers have very low survival rates. Currently available treatments like chemotherapy and radiation have poor outcomes, low response rates, and short progression-free survival rates. These high unmet needs in the pharmaceutical industry heighten the need for an advanced, state-of-the-art treatment option.

The Yokohama-based J-Pharma fulfilled this compelling need with the development of a targeted therapeutic compound for solute carrier (SLC) transporters. Since 2005, the clinical-stage bio-venture company has been conducting an array of unique drug development with ground-breaking expertise in SLC transporters.

SLCs—metabolic gatekeepers of cells—play a vital role in mediating the transportation of essential amino acids while also being a novel class of tumor suppressors. The clinical studies in SLC, nevertheless, remained unclear until recent years, owing to their complex molecular structures and diverse functionalities. However, with the help of cryo-electron microscopy (cryo-EM), the molecular architecture and the transport mechanism of one such L-type neutral amino acid transporter (LAT1/SLC7A5) were revealed in 2019.

While LAT1 is highly expressed in cancer and immune cells, it enhances in expression when the tumor grows rapidly. This leads to increased uptake of amino acids and explosive tumor-cell proliferation.

“Taking LAT1 as the novel drug target, we are striving to achieve our pipe dream of treating highly complex disorders in liaison with cutting edge academic institutions,” says Max Yoshitake, President and CEO of J-Pharma.Currently, J-Pharma is undertaking the clinical development of two small compounds, selectively targeting LAT1: JPH203 for the treatment of BTC and OKY-034 for pancreatic cancers and multiple sclerosis (MS). These potent LAT1 inhibitors instantly thwart the supply of essential amino acids to tumor cells.

With a unique mode of action, JPH203 causes an intracellular decrease of amino acids that slows down protein synthesis and regulates key signaling pathways, leading to decreased tumor cell proliferation. It also brings extracellular changes in the tumor microenvironment (TME). Ultimately, JPH203 enhances CD8+ cells infiltration into tumors causing BTC tumor cell death. Likewise, OKY-034 exhibits enhanced cell differentiation in animal models of MS against demyelination, an inflammation in the brain caused by myelin damage. By the same token, J-Pharma scientists are collaborating with the National Institutes of Health (NIH) and Georgetown University in developing MS clinical studies. In a couple of years, the company is aspiring to launch a remyelination-centered therapy that reduces the disability progression of MS, for which a subsidiary is to be set up in D.C. this year.

Expecting topline results in the coming months, J-Pharma is on target to launching JPH203 for BTC in the U.S. by 2026. The LAT1 inhibitor is currently in the pivotal Phase 2 of multi-center, randomized, placebo controlled, double-blind clinical studies. Moreover, OKY-034 for refractory pancreatic cancers is undergoing Phase 1/2a clinical study. The clinical study report (CSR) will be available in the second quarter of 2022. J-Pharma envisions testing their critical milestones for other oncologic and immunological diseases. The company also plans to validate other SLC transporters as therapeutic targets for multiple high-impact diseases. “We are on a mission to unlock the potential of various SLC transporters, driven by our ambitious goal of treating the incurable diseases in a blue ocean market,” states Yoshitake.