[E-Daily Reporter SHIN MIN JOON ] #PenetriumBio has stated that proceeding directly to Phase 2 clinical trials in the U.S. for “Penitrium,” a new drug candidate for intractable solid tumors, without conducting a Phase 1 trial, is a standard development procedure. PenetriumBio emphasized that there are numerous global cases where existing drugs, in addition to Penitrium, were developed into anticancer agents and immediately entered Phase 2 clinical trials.

Misunderstanding of New Drug Development Procedures... A Method Established Under FDA Regulations

In a shareholder notice on the 15th, PenetriumBio explained, “There have been repeated concerns regarding the U.S. Phase 2 clinical trial we are pursuing, claiming that ‘it is not possible to skip Phase 1.’ However, this is a misunderstanding of the new drug development process and is not factual.”

PenetriumBio clarified that since Penitrium is a drug that has already been used in humans, starting with a Phase 2 clinical trial is standard procedure. Phase 1 is generally considered the stage where a drug is administered to humans for the first time to confirm its safety.

PenetriumBio noted that a drug with the same active ingredient as Penitrium has already undergone Phase 2 and 3 clinical trials during the COVID-19 pandemic. Currently, clinical trials are underway in Vietnam to evaluate it as a treatment for dengue fever.

PenetriumBio stated, “We already have a body of safety data in humans that would typically be verified in a Phase 1 clinical trial,” adding, “Adjusting the initial stages when redeveloping a drug—whose safety has already been confirmed in humans—as a treatment for another disease (in this case, cancer) is the standard procedure under the U.S. Food and Drug Administration (FDA) regulations.”

They added, “There are numerous global cases where drugs already in use were developed into anticancer agents and immediately began with Phase 2 clinical trials.”

One example is the DART basket trial led by Professor Sandip Patel of the Moores Cancer Center at the University of California, San Diego. DART, spearheaded by Professor Patel, was a Phase 2 basket trial that applied the combination therapy of nivolumab and ipilimumab—for which clinical safety data and dosing experience had already been accumulated—to various rare solid tumors.

DART evaluated safety and efficacy in Phase 2 without repeating separate Phase 1 trials for each rare cancer. While this is similar to Penitrium’s multi-cancer basket Phase 2 strategy, it differs in that the drugs used in DART already had sufficient clinical experience in the field of oncology.

Another example is the combination trial of the antihypertensive drug losartan and the pancreatic cancer regimen Folfirinox. This combination trial was conducted as a Phase 2 study for locally advanced pancreatic cancer without a separate Phase 1 oncology trial.

This is considered a case relatively similar to Penitrium, as it entered a Phase 2 anticancer combination trial based on human safety data from existing non-oncology indications. The clinical trial applied a safety management protocol that started with a low dose of losartan and increased the dose based on tolerability.

In addition, there are combination clinical trials for pancreatic cancer involving the diabetes medication metformin, the anticancer drugs gemcitabine and erlotinib(Erlotinib) for pancreatic cancer, as well as a combination trial of the multi-receptor tyrosine kinase (RTK) inhibitor Sitravatinib with Nivolumab, are cited as other examples.

Dosage Reviewed in Collaboration with U.S. Specialized Institutions; Dosage Also Low

PenetriumBio announced that it reviewed this clinical trial plan in collaboration with U.S. specialized institutions. A PenetriumBio representative stated, “We reviewed the plan with several U.S.-based contract research organizations (CROs) and concluded that it is appropriate to begin with a Phase 2b trial,” adding, “The trial design was reviewed by a local CRO responsible for U.S. FDA approval and the U.S. clinical team led by Kim Taek-sung, President of U.S. Operations.”

PenetriumBio emphasized that the dosage is lower than what has already been used in humans. The company explained that the dosage to be used in the U.S. Phase 2 clinical trial is lower than the dosage already administered to humans in clinical trials for COVID-19 and dengue fever, and that higher doses have already been used safely in humans. Animal studies published by PenetriumScience confirmed anticancer effects even at low doses.

“Penitrium” refers to a new drug candidate for intractable solid tumors currently under development, based on a mechanism that modulates the tumor microenvironment—the environment surrounding cancer cells. Previously, in April, PenetriumBio unveiled guidelines for a U.S. Phase 2 clinical trial—which are not limited by cancer type or targeted anticancer agents—at the American Association for Cancer Research (AACR) Annual Meeting.

PenetriumBio stated, “In 1889, British surgeon Stephen Paget likened cancer to a CIAAT and the soil in which that CIAAT takes root. No matter how strong the CIAAT, it cannot take root without soil,” adding, “However, treatments to date have focused solely on eliminating the CIAAT. PenetriumBio has found a way to restore that soil to its normal state using generative artificial intelligence (AI).”

The company continued, “In particular, when the U.S. patent for Keytruda, a leading immuno-oncology drug, expires in 2028, global pharmaceutical companies will rush into the market, ushering in an era of immuno-oncology drug combinations,” adding, “Penitrium is currently preparing for this new era through a Phase 2 combination clinical trial.”