Starton Therapeutics Inc CEO Pedro Lichtinger wants patients using cancer-fighting drug Revlimid to have better and longer lives.
Celgene created the blood cancer treatment, also known as lenalidomide, for sufferers of multiple myeloma, mantle cell lymphoma, and lymphoma to treat and boost the body’s immune system. The drug became the standard of care in multiple myeloma, the most common blood cancer in the US. Celgene was acquired by Bristol Myers Squibb.
But unfortunately for patients, the drug can produce nasty side effects, such as neutropenia, diarrhea, and kidney damage. And many patients simply can’t tolerate it at all, forcing them to turn to less-effective drugs that carry fewer side effects and the likelihood of poorer outcomes.
Another big concern with orally administered Revlimid is dosage. At high levels of concentration in the patient’s blood, unwanted side effects typically occur. When concentrations of the drug are low, it may be less effective, giving the cancer cells time to develop resistance.
For Lichtinger, who spent 16 years at Pfizer as a senior executive, patients unable to tolerate orally administered Revlimid deserve better.
Advancing STAR-LLD program
As a result of his vision, New Jersey-based Starton is developing a proprietary, continuous delivery once-weekly transdermal patch and subcutaneous wearable pump called STAR-LLD that takes lenalidomide to a higher level. The products are designed to provide 24-hour delivery of the drug at optimal dosage and avoid high and low levels of the treatment in the bloodstream while improving the drug’s efficacy.
Starton’s method of delivery could improve efficacy, decrease side effects, and enable more patients to use the drug and for longer periods of time without encountering toxicity issues. STAR-LLD uses up to 90% less of the drug when compared to approved oral formulations.
"If dose-related side effects can be reduced and people with cancer can tolerate maintenance therapy for decades to help stay in remission, these cancers, that were previously a death sentence, would become more akin to a chronic disease with a long lifespan and healthy quality of life," Lichtinger told Proactive.
Meanwhile, in September 2021, Starton achieved a milestone in STAR-LLD’s development when the company announced successful results of a preclinical toxicology study of rodents over a 28-day period, indicating excellent tolerability with no myelosuppression. The company said total white blood cell, or what is called neutrophil, and lymphocyte counts showed no significant difference via the continuous administration of lenalidomide.
“For us, this is the confirmation that the delivery of lenalidomide continuously is first, as we showed in a clinical model, more efficacious. And now we are also showing that it is safer,” Lichtinger said. “This supports our vision that we have a significantly improved product over Revlimid that will be able to go into the areas where Revlimid couldn't go.”
More specifically, Lichtinger said the company is designing STAR-LLD initially to target the 30% of MM maintenance patients who cannot tolerate nor do not receive any benefit from Revlimid.
“We believe that by proving in this subpopulation that they can actually tolerate treatment, they will get equal or better efficacy,” he added.
The most recent preclinical toxicology study builds on a preclinical proof-of-concept study for STAR-LLD in which MM tumors caused by human myeloma cells grew 25 times when left untreated and five times when treated with the equivalent of oral lenalidomide but were reduced by 80% with STAR-LLD.
Looking ahead to Phase1-2 studies of STAR--LDD
The chronic toxicology trial was the last pre-Investigational New Drug Application (IND) study as required by the US Food and Drug Administration (FDA) to move onto human studies. The next step is setting up clinical trials, which are expected to start in the first quarter of 2022 in The Netherlands where, like the rest of the EU, lenalidomide is off-patent and readily available for the trials.
Lichtinger called the Phase 1 study using the subcutaneous ambulatory pump “low risk” as it will compare oral usage versus continuous dosage by simply measuring blood levels.
The company also plans a Phase 2 trial in the 3Q of 2022 in both Europe and the US in which it expects to see partial and complete responses that are not seen with the oral. Lichtinger said he hopes that the Phase 2 study will lead to a breakthrough designation in the US and a PRIME designation in Europe.
While Starton gears up STAR-LLD for clinical trials, the company is advancing the development of its other main product, STAR-OLZ - a once weekly transdermal olanzapine for chemotherapy-induced nausea and vomiting (CINV). The drug is typically used to treat schizophrenia and bipolar disorder but is included in the treatment guidelines as an antiemetic.
STAR-OLZ successfully completed its Phase 1 human bioavailability study in December 2019. Published studies have shown that Olanzapine’s nausea control was 70% vs. 39% with the current standard of care. The company has now entered Phase 2 of the program.
To help fund its programs, Lichtinger said the company is looking at raising $70 million via a crossover initial public offering (IPO) toward the end of 2021 or in early 2022.
Looking ahead, Lichtinger said Starton is at an inflection point as it advances the development of the STAR-LLD and STAR-OLZ programs.
“We are extremely pleased with having met historically all of our milestones in advancing both programs,” he said. “The programs are entering the time when we are going to know relatively soon in the next 18 to 24 months. We will have multiple milestone achievements that will sustain and grow value for shareholders. So, from an operational point of view, this is the most exciting period of our company. The next two years will be fabulous.”
Contact the author: patrick@proactiveinvestors.com
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