Fluorocyclopentenylcytosine

Phase 2 trial with NGC-Cap in breast cancer underway NGC-Cap Phase 1b trial demonstrated a favorable safety profile with preliminary anti-tumor activity Preclinical studies demonstrated NGC-Iri delivers more cancer-killing SN-38 molecules to tumor than either irinotecan or Onivyde® HANOVER, Md., Aug. 28, 2024 (GLOBE NEWSWIRE) -- Processa Pharmaceuticals, Inc. (Nasdaq: PCSA) (Processa or the Company), a clinical-stage pharmaceutical company focused on developing the next generation of chemotherapeutic drugs with improved efficacy and safety, provides updates on its product pipeline, upcoming milestones and business activities, and reports financial results for the three and six months ended June 30, 2024. “We made significant progress in advancing our three development programs year-to-date, with a particular focus on our lead candidate NGC-Cap,” said George Ng, Chief Executive Officer of Processa Pharmaceuticals. “Upon receiving FDA clearance of our NGC-Cap IND application, we initiated a Phase 2 clinical trial in metastatic breast cancer. We look forward to enrolling patients in this multicenter, open-label study and expect to have an initial data readout in mid-2025.” Key Program UpdatesProcessa is focused on developing next-generation chemotherapies (NGC) by improving widely used U.S. Food and Drug Administration (FDA)-approved oncology drugs to extend a patient’s survival and/or improve their quality of life. This is achieved by altering how drugs are metabolized and/or distributed in the body, including how they reach cancer cells. In addition, Processa utilizes its Regulatory Science Approach, including the principles associated with FDA’s Project Optimus Oncology initiative, in the development of its NGC drug products to achieve a more favorable benefit-risk profile. Processa’s updated corporate presentation, including its product pipeline, is available on the company’s website. PCS6422: Next-Generation Capecitabine (NGC-Cap) NGC-Cap is a combination of PCS6422 and capecitabine, which is the oral prodrug of the cancer drug 5-fluorouracil (5-FU). PCS6422 alters the metabolism of 5-FU, resulting in more 5-FU distributed to cancer cells.In July 2024, the FDA cleared the Company’s Investigational New Drug application (IND) application for a Phase 2 trial with NGC-Cap in metastatic or advanced breast cancer. Subsequently, Processa initiated the Phase 2 study (NCT06568692) , which is a global, multicenter, open-label, adaptive design trial comparing two different doses of NGC-Cap to FDA-approved monotherapy capecitabine in approximately 60 to 90 patients. As agreed to with the FDA, the breast cancer indication should lead to a more efficient development program while providing a greater likelihood of approval.The NGC-Cap Phase 1b study evaluated ascending doses of capecitabine when combined with a fixed dose of PCS6422 in patients with advanced, relapsed or refractory progressive gastrointestinal cancer. These patients had to relapse from or fail all other treatments. NGC-Cap demonstrated greater 5-FU exposure and lower fluoro-beta-alanine (FBAL) exposure with a better or similar side-effect profile compared with monotherapy capecitabine, as well as preliminary anti-tumor activity. In all evaluable patients who received one dose of PCS6422 and seven days of capecitabine, partial responses or stable disease was observed in 66.7% (8 out of 12) of patients with progression-free survival of approximately 5 to 11 months across these patients.In April 2024, Processa presented an abstract at the American Association for Cancer Research (AACR) Annual Meeting 2024, including new Phase 1b data on NGC-Cap in patients with advanced, relapsed or refractory progressive gastrointestinal cancer. NGC-Cap demonstrated 5-10 times greater 5-FU exposure than monotherapy capecitabine at a significantly lower dose, along with a favorable safety profile. As such, NGC-Cap holds potential for improved efficacy in more patients due to a higher distribution of 5-FU to cancer cells. Further, the extremely low exposure of FBAL, the primary catabolite formed from the metabolism of 5-FU, across all NGC-Cap doses resulted in fewer catabolite-related side effects, with only one patient having Grade 1 hand-foot-syndrome, an FBAL side effect that often requires dose modifications. PCS3117: Next-Generation Gemcitabine (NGC-Gem) NGC-Gem is an oral analog of gemcitabine (Gemzar®) that is converted to its active metabolite by a different enzyme system, with potential for a positive response in gemcitabine patients including those inherently resistant to or who acquire resistance to gemcitabine.Processa is evaluating the potential of NGC-Gem in patients with pancreatic and other cancers, as well as ways to identify patients who are more likely to respond to NGC-Gem than gemcitabine alone. The Company plans to meet with the FDA in late 2024 or early 2025 to discuss potential trial designs, including implementation of the Project Optimus initiative. PCS11T: Next-Generation Irinotecan (NGC-Iri) NGC-Iri is an analog of SN38, the active metabolite of irinotecan, that is expected to have an improved safety-efficacy profile in every type of cancer where irinotecan is used.As announced earlier this month, two studies in a human melanoma xenograft mouse model measured SN-38 in tumors, plasma and other tissues following administration of NGC-Iri, irinotecan and Onivyde®, the liposomal formulation of irinotecan. One study compared NGC-Iri with irinotecan, and the other compared irinotecan with Onivyde®. The results found that mice administered NGC-Iri had greater accumulation of SN-38 in the tumor compared with other tissues and that less SN-38 accumulated in non-cancer tissues, which could lead to improved efficacy with a more favorable adverse event profile compared with irinotecan and Onivyde®.In April 2024, Processa presented a second abstract at AACR titled “Application of phase 1 and pre-clinical data to assist in determining the optimal dosage regimen for cancer drugs using the principles of Project Optimus.” This abstract describes the FDA Project Optimus Initiative and draft optimal dosage regimen (ODR) guidance, which requires an ODR justified by a dose-ranging efficacy and safety study, as opposed to a maximum tolerated dose approach. Processa provided NGC-Iri preclinical study examples to demonstrate how the shape of the exposure-response relationships for safety and efficacy can be determined from these pre-clinical studies. By better understanding the exposure-response relationship earlier in the development process, defining the recommended dose range and optimal dosage regimen becomes easier in an efficacy-safety study, in a pivotal study, and for FDA approval.The Company is currently evaluating the manufacturing process and potential sites for NGC-Iri. In addition, Processa is defining the potential paths to approval, which include defining the target patient population and the type of cancer, with the expectation to conduct IND-enabling toxicology studies in 2025. Second Quarter Financial Results Research and development expenses for the second quarter of 2024 were $1.7 million, unchanged from the second quarter of 2023. General and administrative expenses for the second quarter of 2024 were $1.4 million, compared with $1.0 million for the second quarter of 2023, primarily due to an increase in professional fees. The net loss for the second quarter of 2024 was $3.0 million, or $1.01 per share, compared with the net loss for the second quarter of 2023 of $2.6 million, or $1.94 per share. All per-share figures reflect a 1-for-20 reverse stock split that was effective as of January 22, 2024. Cash and cash equivalents were $5.6 million as of June 30, 2024. About Processa Pharmaceuticals, Inc. Processa is a clinical-stage pharmaceutical company focused on developing the Next Generation Chemotherapy (NGC) drugs with improved safety and efficacy. Processa’s NGC drugs are modifications of existing FDA-approved oncology therapies resulting in an alteration of the metabolism and/or distribution of these drugs while maintaining the existing mechanisms of killing the cancer cells. By combining its novel oncology pipeline with proven cancer-killing active molecules and its Regulatory Science Approach, Processa’s strategy is to develop more effective therapy options with improved tolerability for cancer patients through an efficient regulatory path. For more information, visit our website at www.processapharma.com. Forward-Looking Statements This release contains forward-looking statements. The statements in this press release that are not purely historical are forward-looking statements which involve risks and uncertainties. Actual future performance outcomes and results may differ materially from those expressed in forward-looking statements. Please refer to the documents filed by Processa Pharmaceuticals with the SEC, specifically the most recent reports on Forms 10-K and 10-Q, which identify important risk factors which could cause actual results to differ from those contained in the forward-looking statements. Company Contact:Patrick Lin(925) 683-3218plin@processapharma.com Investor Relations Contact:Yvonne BriggsLHA Investor Relations(310) 691-7100ybriggs@lhai.com [Financial Tables to follow]PROCESSA PHARMACEUTICALS, INC. CONDENSED CONSOLIDATED BALANCE SHEETS(in thousands, except share information) (unaudited) June 30, 2024 December 31, 2023 ASSETS Current Assets Cash and cash equivalents $5,571 $4,706 Prepaid expenses and other 1,907 926 Total Current Assets 7,478 5,632 Property and Equipment, net 2 3 Other Assets Lease right-of-use assets, net of accumulated amortization 115 146 Security deposit 6 6 Total Other Assets 121 152 Total Assets $7,601 $5,787 LIABILITIES AND STOCKHOLDERS’ EQUITY Current Liabilities Current maturities of lease liabilities $93 $84 Accounts payable 953 312 Due to licensor - 189 Due to related parties - - Accrued expenses 505 146 Total Current Liabilities 1,551 731 Non-current Liabilities Non-current lease liabilities 26 67 Total Liabilities 1,577 798 Commitments and Contingencies - - Stockholders’ Equity Common stock, par value $0.0001, 100,000,000 shares authorized: 2,873,883 issued and 2,868,883 outstanding at June 30, 2024; and 1,291,000 issued and 1,286,000 outstanding at December 31, 2023 1 - Additional paid-in capital 87,429 80,658 Treasury stock at cost — 5,000 shares at June 30, 2024 and December 31, 2023 (300) (300)Accumulated deficit (81,106) (75,369)Total Stockholders’ Equity 6,024 4,989 Total Liabilities and Stockholders’ Equity $7,601 $5,787 PROCESSA PHARMACEUTICALS, INC. CONDENSED CONSOLIDATED STATEMENTS OF OPERATIONS(in thousands, except per share data)(unaudited) Three Months Ended June 30, Six Months Ended June 30, 2024 2023 2024 2023 Operating Expenses Research and development expenses $1,730 $1,688 $3,270 $3,343 General and administrative expenses 1,352 1,026 2,622 3,477 Operating Loss (3,082) (2,714) (5,892) (6,820) Other Income (Expense), net 72 102 155 185 Net Operating Loss Before Income Tax Benefit (3,010) (2,612) (5,737) (6,635)Income Tax Benefit - - - - Net Loss $(3,010) $(2,612) $(5,737) $(6,635) Net Loss per Common Share - Basic and Diluted $(1.01) $(1.94) $(2.11) $(5.34) Weighted Average Common Shares Used to Compute Net Loss Applicable to Common Shares - Basic and Diluted 2,983,283 1,346,808 2,724,903 1,243,475 # # #

Eight of 12 evaluable patients (66.7%) had progression-free survival (PFS) ranging from 5 to 11 months At the highest NGC-Cap dose, all three evaluable patients had PFS with two partial responses (PR) and one stable disease (SD) For all NGC-Cap doses, 5-Fluorouracil (5-FU) exposure was greater and fluoro-beta-alanine (FBAL) exposure was lower with a better or similar side-effect profile than monotherapy capecitabine HANOVER, MD., June 11, 2024 (GLOBE NEWSWIRE) -- Processa Pharmaceuticals, Inc. (Nasdaq: PCSA) (Processa or the Company), a clinical-stage pharmaceutical company focused on developing the next generation of chemotherapeutic drugs with improved efficacy and safety, today announced positive efficacy results from the preliminary evaluation of its recently completed Phase 1b clinical trial which defined the Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose Range (RP2DR) for Next Generation Capecitabine (NGC-Cap) administered to patients with Stage III or IV gastrointestinal tract (GI) cancer. “We are encouraged by the preliminary efficacy analysis from our NGC-Cap Phase 1b dose-escalating safety/tolerability trial demonstrating some anti-tumor activity in patients with advanced GI cancer who have progressive cancer after relapsing or not responding to prior therapy. The favorable response is likely due to NGC-Cap’s ability to distribute more 5-FU to cancer cells than monotherapy capecitabine. The promising Phase 1b safety and tolerability profile plus these early efficacy signals provide validation for further development of NGC-Cap,” stated David Young, PharmD, Ph.D., President of Research and Development at Processa. “From this Phase 1b trial, we have been able to define the MTD and the RP2DR to use in our Phase 2 Optimal Dosage Regimen trial in breast cancer in the third quarter of 2024.” Dr. Young added, “Given the need for more effective chemotherapy treatment with improved tolerability across multiple types of cancer, we believe that NGC-Cap has the potential to provide a safer, more efficacious option to treat the different cancers for which capecitabine and 5-FU are presently used.” The NGC-Cap Phase 1b trial is evaluating ascending doses of capecitabine when administered after a single dose of PCS6422 in Stage III or IV patients with advanced, relapsed or refractory progressive GI cancer. All patients relapsed from or failed all other treatments, including prior treatment with capecitabine or 5-FU. For all doses of capecitabine in the Phase 1b NGC-Cap trial, exposure to 5-FU was greater and exposure to FBAL was lower with a better or similar side effect profile compared with monotherapy capecitabine. In addition, preliminary analysis of the efficacy data demonstrated early evidence of anti-tumor activity of capecitabine combined with PCS6422, which was assessed using RECIST 1.1 evaluations (Response Evaluation Criteria in Solid Tumors) by scans every eight weeks. Key Efficacy Findings from Preliminary Analysis of NGC-Cap Phase 1b Clinical Trial (NCT04861987) In all evaluable patients receiving one dose of PCS6422 and seven days of capecitabine, PR or SD was observed in 66.7% (8 out of 12) of evaluable patients, including two with PR and six with SD. The length of PFS was approximately 5 to 11 months across these patients.At the MTD of 225 mg of capecitabine dosed twice daily after a single dose of PCS6422, all three evaluable patients (100%) had PFS with the time to progression being approximately 5 to 7 months.At the second highest dose of 150 mg capecitabine dosed twice daily after a single dose of PCS6422, 66.7% (2 out of 3) of evaluable patients had SD with the time to progression of approximately 3 to 7 months.These two dosage regimens will be further evaluated in the Phase 2 trial in breast cancer patients to determine the optimal dosage regimen for the pivotal trial.By comparison, in the capecitabine product label, 301 metastatic colorectal cancer patients treated with monotherapy capecitabine had an overall response rate of approximately 21% and the time to progression of approximately 4.5 months. About Capecitabine Administered with PCS6422 (NGC-Cap) NGC-Cap combines the administration of PCS6422, the Company’s irreversible dihydropyrimidine dehydrogenase (DPD) enzyme inhibitor, with low doses of capecitabine. Capecitabine is the oral form of 5-FU, and along with 5-FU is among the most widely used chemotherapy drugs, particularly for the treatment of solid tumors. When metabolized (after oral ingestion) it becomes 5-FU in the body, which, in turn, metabolizes to molecules called anabolites that actively kill duplicating cells, such as cancer cells, and to molecules called catabolites that only cause side effects. The presence of the DPD enzyme plays an integral role in the undesirable conversion of 5-FU to catabolites. PCS6422 irreversibly inhibits DPD. PCS6422 is neither toxic nor active as a single agent in animals at comparable dose levels. However, when administered in combination with capecitabine or 5-FU, PCS6422 decreases the metabolism of 5-FU to the catabolites that only cause side effects, allowing more of the 5-FU to reach the cancer cells. About Processa Pharmaceuticals, Inc. Processa is a clinical-stage pharmaceutical company focused on developing the Next Generation Chemotherapy (NGC) drugs to improve the safety and efficacy of cancer treatment. By combining its novel oncology pipeline with proven cancer-killing active molecules and the Processa Regulatory Science Approach, as well as experience in defining Optimal Dosage Regimens for FDA approvals, Processa not only will provide better therapy options to cancer patients but will also increase the probability of FDA approval for its NGC drugs following an efficient path to approval. Processa’s NGC drugs are modifications of existing FDA-approved oncology drugs resulting in an alteration of the metabolism and/or distribution of these drugs while maintaining the existing mechanisms of killing the cancer cells. The Company’s approach to drug development is based on more than 30 years of expertise to efficiently design and conduct clinical trials that demonstrate a positive benefit/risk relationship. The Processa team has a track record of obtaining over 30 indication approvals across almost every division of the FDA. Using its proven Regulatory Science Approach, the Processa Team has experience defining the Optimal Dosage Regimen using the principles of the FDA’s Project Optimus Oncology initiative. The advantages of Processa’s NGCs are expected to include fewer patients experiencing side effects that lead to dose discontinuation, more significant cancer response and a greater number of patients – in excess of 200,000 for each NGC drug – who will benefit from each NGC drug. Processa is currently 1) starting to initiate sites for the Phase 2 study that will identify the optimal dosage regimen for Next Generation Capecitabine (PCS6422 and capecitabine to treat breast, metastatic colorectal, gastrointestinal, pancreatic and other cancers), 2) defining the design of the Next Generation Gemcitabine (PCS3117 to treat pancreatic, biliary, lung, ovarian, breast and other cancers) Phase 2 optimal dosage regimen study to discuss with FDA, and 3) defining the formulation and toxicology program for Next Generation Irinotecan (PCS11T to treat lung, colorectal, gastrointestinal, pancreatic and other cancers). For more information, visit our website at www.processapharma.com. Forward-Looking Statements This release contains forward-looking statements. The statements in this press release that are not purely historical are forward-looking statements which involve risks and uncertainties. Actual future performance outcomes and results may differ materially from those expressed in forward-looking statements. Please refer to the documents filed by Processa Pharmaceuticals with the SEC, specifically the most recent reports on Forms 10-K and 10-Q, which identify important risk factors which could cause actual results to differ from those contained in the forward-looking statements. Company Contact:Patrick Lin(925) 683-3218plin@processapharma.com Investor Relations Contact:Yvonne BriggsLHA Investor Relations(310) 691-7100ybriggs@lhai.com # # #