Rapamycin Holdings Plans Tests of Old Immune Drug in Prostate Cancer

Xconomy Texas — 

San Antonio — Executives at Rapamycin Holdings believe a decades-old drug used to prevent organ transplant rejection could find a new use as a treatment for prostate cancer, and hope to  begin a clinical trial as soon as this summer.

San Antonio-based Rapamycin Holdings has developed a new formulation of the drug, also called rapamycin, which was initially developed as an immunosuppressant. CEO and President Dan Hargrove says the drug can have a more nuanced effect on the body, broadening the potential therapeutic applications of the compound

“Rapamyacin can modulate the body’s immune system. At high doses you can actually suppress the body’s immune system,” Hargrove told Xconomy in a phone interview. “What we believe, and what our preclinical studies show, is that at low doses it rejuvenates the body’s immune system. What we want is the optimal dose to rejuvenate the body’s immune system.”

Rapamycin was discovered 44 years ago and is now best known as the Pfizer (NYSE: PFE) product sirolimus (Rapamune), which is used for organ transplants. That drug, now off-patent, has since gained an additional FDA approval in a rare lung disease, also by Pfizer. There are other derivatives (or analogues) of rapamycin that are structurally similar but not the same. Rapamycin Holdings’ version, eRapa, was developed with a coating that allows the drug to pass through the stomach before being released, Rapamycin chief science officer Dana Vaughn told Xconomy in 2016.

The American Cancer Society estimates that more than 164,000 new cases of prostate cancer will be diagnosed this year. Approximately 29,430 patients will die from the disease. The standard of care for early prostate cancer cases is watching to see if the cancer progresses—known as active surveillance, he says. Surgery or radiation therapy can have unpleasant consequences, such as incontinence and sexual dysfunction, Hargrove says.

Rapamycin is seeking approval for eRapa through a 505(b)(2) application, which allows drug developers to include in its submission data from earlier clinical trials conducted by other companies. A company can “rely on the safety and effectiveness of the previously approved product,” something the FDA allows in order to “encourage innovation without creating duplicate work,” according to the FDA guidelines. This regulatory pathway is different than the one for new molecules that must rely on data from new studies.

By pursuing the 505(b)(2) pathway, Rapamycin hopes the existing data will permit the biotech to run smaller clinical trials with fewer subjects, potentially making the process faster and less costly, Hargrove says. In the next few months, Rapamycin plans to start a Phase 1b clinical trial to study the safety and optimal dosage of the drug, and expects the trial of 12 to 24 patients to last between 9 months to one year, However, this pathway hasn’t always turned out to be faster, as more companies have begun seeking approval through it, according to one study.

The FDA reviewed 56 applications for 505(b)(2) approval in 2014, the most since data on the subject started being recorded in 2002, according to the Regulator Affairs Professional Society, citing Thomson Reuters data. Meanwhile, the mean approval time for 505(b)(2) applications actually took five months longer than that of new molecular entities between 2009 to 2015, the society said, citing a study by the Tufts Center for the Study of Drug Development. Tufts said the alternative approval pathway accounted for 63 percent of total IND applications during that period.

The success and speed of the approval always depends on the drug in question, Hargrove says, as well as prior uses of the active pharmaceutical ingredient and how long previously approved versions have been on the market. Because rapamyacin has been approved for multiple diseases, and has been sold for more than two decades, Hargrove says he is comfortable that the existing safety data and new data they will gather will be sufficient.

“Because we know the toxicity profile from all the prior use of the drug, we have great confidence that a lot of the prior data and studies around rapamyacin can be incorporated into our drug development process and therefore actually expedite the development of our drug,” he says.

The company’s drug aims to be a buzzkill for overactive cells, such as cancer cells, which have been ramped up to divide and multiply at a faster rate than normal cells, Vaughn told Xconomy. The drug is meant to inhibit a signaling molecule that tells the cancer to multiply, limiting progression.

George Peoples, Rapamycin’s chief medical officer, is planning the trial with Cancer Insight, a San Antonio-based clinical research organization that Peoples and Hargrove run together. The trial will be conducted at University of Texas Health Science Center at San Antonio and the university’s Mays Cancer Center, and it will be led by Michael Liss, a urologist at the university. The new formulation of the drug was originally developed at UT Health, and further progressed by the Southwest Research Institute, Hargrove says.

Rapamycin has raised $3.5 million in convertible notes so far. Hargrove had previously expected to raise more in a Series B funding round, but canceled it and says he may seek a Series B round of funding next year to finance further trials, depending on the results of this clinical study. Hargrove said he decided to raise a smaller amount of convertible notes after discussing with the FDA the possibility of going through the 505(b)(2) process.

Though Hargrove is hopeful the company will can move through clinical trials more quickly, he says the FDA could require a longer testing period under certain circumstances, such as if it takes a long time to see changes in the prostate cancer, which is a slow developing disease.

“We want to get the data from our first human clinical subjects to put the last bits of the puzzle together to make a better decision going forward on our next steps,” he says.

Notably, Rapamycin already sells its formulation to academic research institutions in the U.S. and elsewhere, which use it as part of investigations into a variety age-related conditions and diseases in animals, Hargrove said last year. The company brings in about $250,000 in annual revenue from that, which he said he expects will grow.

Based on preclinical research, the drug could also target non-muscle invasive bladder cancer and one or more orphan diseases, though Hargrove didn’t specify which.