Processa Pharmaceuticals: Next-Generation Capecitabine (NGC) Dosing Regimens Identified in Ongoing Phase 1B Trial with Potentially Better Safety and Efficacy Profiles Than Existing Chemotherapy – Form 8-K

Next-generation capecitabine (NGC) regimens have been identified in the ongoing Phase 1B trial with potentially better safety and efficacy profiles than existing chemotherapy

These NGC regimens are significantly more potent than FDA-approved capecitabine therapy, based on greater systemic and tumor exposure to 5-fluorouracil (5-FU), the major metabolite of capecitabine.

These NGC regimens form fewer metabolites that cause only dose-limiting side effects without tumor-killing properties.

Processa will meet with the FDA in 2023 to confirm that the Phase 2B trial design is consistent with the FDA’s Project Optimus Oncology initiative to identify optimal dosing regimens while moving away from the maximum tolerated dosing approach of the past .

In 2023, Processa plans to begin recruiting patients for the Phase 2B trial to identify treatment regimens that improve the efficacy-safety profile compared to the current treatment.

HANNOVER, MD – November 1, 2022 – Processa Pharmaceuticals, Inc. (Nasdaq: PCSA), a diversified clinical-stage company developing products to improve survival and/or quality of life for patients with an unmet medical need, announces announcing positive results from its ongoing Phase 1B trial of next-generation capecitabine (NGC). The data collected allowed Processa to estimate the timing of irreversible dihydropyrimidine dehydrogenase (DPD) inhibition and the formation of new DPD after administration of PCS6422. NGC regimens (ie, a variety of PCS6422 regimens combined with a variety of capecitabine regimens) have also been identified as safe with different systemic and tumor exposure profiles to 5-FU. These results will allow Processa to evaluate several regimens with different tumor exposures to 5-FU in the Phase 2B trial with the aim of identifying NGC regimens that offer an improved efficacy and safety profile compared to the current treatment. .

During the first 24 to 72 hours after administration of PCS6422 in the Phase 1B trial, less than 10% of 5-FU was converted to metabolites that only cause side effects (i.e. catabolites), significantly less than the 80% reported for FDA-approved capecitabine. The potency of NGC (estimated from systemic exposure to 5-FU) was approximately 50 times greater than the potency of FDA-approved capecitabine. Additionally, the half-life of 5-FU after initial administration of PCS6422 and capecitabine was found to be significantly higher at 2-6 hours compared to the typical 5-FU half-life of approximately 45 minutes. after administration of capecitabine.

Because 5-FU exposure is dependent on both the PCS6422 regimen and the capecitabine regimen, Processa identified both NGC regimens that are safe as well as regimens that cause dose-limiting toxicities, as has was observed in one patient in the phase 1B trial who had progressive disease. stage 4 cancer. This patient had grade 4 neutropenia, was admitted to hospital and subsequently died.

Dr. David Young, President and CEO of Processa, said, “We have identified NGC treatment regimens that have significantly greater potency than existing therapy and no dose-limiting side effects, unlike capecitabine therapy. In addition, we understand the effect of different NGC dosing regimens on the timing of irreversible DPD inhibition and production of new DPD by a patient, allowing us to better define the relationship between various NGC dosing regimens, 5-FU exposure, and NGC safety.”

Dr Young added: “The next step will be to demonstrate in a Phase 2B trial that these NGC regimens also have better efficacy than the existing therapy and, therefore, provide a significant improvement in the benefit-risk profile compared to the existing therapy. We plan to use a Phase 2B trial to determine which regimens offer this improved efficacy and safety profile over the current treatment using the principles of the FDA’s Oncology Project Optimus initiative to guide us in the design of the regimen. ‘trial. In 2023, Processa plans to meet with the FDA to discuss the design of our Phase 2B trial and initiate the trial.

Next Generation Capecitabine

Next-generation capecitabine (NGC) is a combination of a PCS6422 regimen and a distinct capecitabine regimen. Capecitabine is a fluoropyrimidine, like 5-fluorouracil (5-FU), the main metabolite of capecitabine, which remains the cornerstone of treatment for many types of cancers in approximately two million patients per year. Capecitabine is an oral prodrug of 5-FU and approved as first-line treatment for metastatic colorectal and breast cancer. Adverse effects of capecitabine such as the development of hand-foot syndrome from 5-FU catabolites (eg, α-fluoro-β-alanine (F-Bal)) and neutropenia from 5-FU anabolites -FU (eg, phosphate metabolites) can have serious adverse effects on a patient’s daily activities, quality of life, and may require dose interruptions, adjustments, or discontinuation of therapy, all leading to suboptimal tumor therapy.

PCS6422 is an oral, potent, selective and irreversible inhibitor of dihydropyrimidine dehydrogenase (DPD), the enzyme that rapidly metabolizes 5-FU to catabolites that can cause dose-limiting side effects. The formation of 5-FU anabolites in cancer cells and normal cells is not dependent on DPD.

By combining the PCS6422 and capecitabine regimens, altering 5-FU metabolism and hence elimination leads to an increase in capecitabine potency, as determined by systemic exposure to 5-FU per mg capecitabine administered. . As a result, less capecitabine is needed to kill cancer cells and to treat each patient. To date, Processa has found that irreversible inhibition of DPD by PCS6422 can alter 5-FU clearance, making NGC significantly more potent (more than 50 times more potent) and potentially leading to higher levels anabolites that can kill cancer replication. and normal cells causing dose-limiting side effects such as neutropenia. When administering NGC to cancer patients, the balance between anabolites and catabolites changes depending on the dosage regimens of PCS6422 and capecitabine used, making the efficacy and safety profile of NGC different from that of approved capecitabine. by the FDA and requiring further evaluation of PCS6422 and capecitabine treatment regimens to determine optimal next-generation capecitabine treatment regimens for patients.

The projected market for NGC is $500 million to $1 billion in the United States for the treatment of colorectal cancer and over $1 billion in the United States for the treatment of the many cancers for which capecitabine is used. The potential global market for NGC for colorectal cancer exceeds $1 billion.

About Processa Pharmaceuticals, Inc.

Processa’s mission is to develop products with existing clinical evidence of efficacy for patients with unmet or underserved medical conditions who need treatment options that improve survival and/or quality of life. The Company uses its regulatory science approach criteria when selecting drugs for development in order to achieve high-value milestones effectively and efficiently. Active clinical pipeline programs include: PCS6422 (metastatic colorectal cancer, breast cancer), PCS12852 (gastroparesis, functional constipation) and PCS499 (ulcerative lipoid necrobiosis). Members of the Processa development team have participated in over 30 indication approvals in nearly every division of the FDA (including drug products targeted at orphan diseases) and over 100 FDA meetings throughout throughout their career. For more information, visit our website at www.processapharma.com.

Forward-looking statements

This press release contains forward-looking statements. Statements contained in this press release that are not purely historical are forward-looking statements that involve risks and uncertainties. Actual future performance and results may differ materially from those expressed in forward-looking statements. Please refer to Processa Pharmaceuticals’ filings with the SEC, in particular the most recent reports on Forms 10-K and 10-Q, which identify material risk factors that could cause actual results to differ from those contained in forward-looking statements.

For more information:
Michael Floyd
[email protected]
(301) 651-4256

Patrick Lin
(925) 683-3218
[email protected]

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