Genprex(US:GNPX)2022-03-30 20:17Product Development and Clinical Trials - The company is developing REQORSA™ Immunogene Therapy for Non-Small Cell Lung Cancer (NSCLC) and Small Cell Lung Cancer (SCLC), utilizing a plasmid that expresses the tumor suppressor gene TUSC2[17]. - The company is currently enrolling two Phase 1/2 clinical trials for REQORSA, with Acclaim-1 expected to complete its Phase 1 portion by the end of 2022 and Acclaim-2 by Q1 2023[18]. - The company has expanded its pipeline to include SCLC and plans to commence a clinical trial by the end of 2022[23]. - The Acclaim-1 trial aims to enroll up to 92 patients, with the primary endpoint being progression-free survival for patients treated with REQORSA and Tagrisso[71][75]. - The Acclaim-2 trial is expected to enroll approximately 156 patients, focusing on the combination of REQORSA and Keytruda, with a primary endpoint of dose limiting toxicity[75][76]. - In the Phase 1 Monotherapy Trial, 22% of subjects achieved disease control for periods ranging from 2.6 to 10.8 months, with a median disease control period of 5.0 months[79]. - The median survival for all subjects in the Phase 1 Monotherapy Trial was 8.3 months, and the mean survival time was 13.2 months, with a range of 2 to 23+ months[79]. - In the Phase 2 portion of the trial, the disease control rate for nine evaluable patients was 78%[92]. - The response rate observed in the Phase 2 portion was 11%, with one patient achieving a complete response[92]. - The Phase 1 portion of the Phase 1/2 Combination Tarceva Trial included 18 subjects treated at various dose levels, with no dose-limiting toxicities reported[83][85]. Mechanism of Action and Efficacy - REQORSA has shown a multimodal mechanism of action, interrupting cancer cell signaling pathways, re-establishing apoptosis, and modulating the immune response[38]. - Tumor biopsy studies indicate that TUSC2 uptake in tumor cells after REQORSA treatment was 10 to 33 times higher than in normal cells[37]. - Clinical and preclinical data indicate that REQORSA combined with EGFR TKIs like Tagrisso and Keytruda may enhance anti-tumor activity, potentially benefiting a larger population of NSCLC patients[65][66][73]. - Preclinical studies have shown that TUSC2 enhances the immune response to cancer by down-regulating PD-L1 on cancer cells, thus promoting recognition by immune cells[52][66]. - The combination of REQORSA and Tarceva showed a significant improvement over the response rate of 7% and disease control rate of 58% reported for afatinib in the LUX-Lung 1 clinical trial[94]. - The combination therapy of REQORSA with Tarceva may benefit NSCLC patients with and without activating EGFR mutations[100]. - TUSC2 therapy in combination with osimertinib demonstrated synergistic antitumor efficacy in EGFR mutant osimertinib resistant NSCLC tumors, providing a rationale for the Acclaim-1 clinical trial[101]. - REQORSA shows a 10 to 33 fold differential favoring uptake by tumor cells, indicating its passive targeting property[102]. - Intratumoral administration of REQORSA resulted in significant tumor growth inhibition in A549 tumor xenografts[103]. - The combination of REQORSA and pembrolizumab inhibited tumor growth synergistically, with significant reductions in tumor burden (P<0.05 to P<0.0005)[109]. - REQORSA demonstrated synergistic antitumor activity with nivolumab, indicating its potential effectiveness with various immune checkpoint inhibitors[111]. Regulatory and Compliance Considerations - The FDA has granted two Fast Track Designations for REQORSA in the targeted patient populations of ongoing clinical trials[19]. - The FDA regulates the approval process for the company's biological product candidates, which involves substantial time and financial resources[157]. - The company must complete preclinical tests and submit an IND application to the FDA before human clinical trials can begin[159]. - The FDA requires two adequate and well-controlled Phase 3 clinical trials to demonstrate drug efficacy, with a single trial being sufficient in rare cases[166]. - The FDA's Accelerated Approval Program allows for expedited approval of product candidates for serious conditions based on surrogate endpoints, contingent on post-approval trials[186]. - Priority Review Designation aims for FDA action on marketing applications within six months, compared to ten months under standard review, facilitating faster market entry[188]. - The FDA may impose user fees on BLAs, which are adjusted annually under the Prescription Drug User Fee Act[173]. - The FDA mandates disclosure of clinical trial information, which can be used by competitors to gain insights into clinical development programs[198]. - The company must comply with various federal and state regulations, including those related to fraud and abuse, which apply once FDA marketing approval is obtained[204]. Intellectual Property and Financial Obligations - The company holds 18 issued patents and 17 pending patent applications related to TUSC2 and its therapeutic uses, supported by grants from various institutions[61]. - The company holds a worldwide, exclusive license to 18 issued patents and 17 pending patent applications related to REQORSA and its delivery system[133]. - The company is obligated to pay MD Anderson royalties of 1.5% of net sales of licensed products and 1.5% of advance payments received from third parties[144]. - The 2020 License Agreement with MD Anderson includes milestone payments aggregating up to a maximum of $6,150,000 and minimum annual royalties in a low six-figure amount[145]. - The UP License Agreement requires the company to pay milestone payments up to $3,975,000 and running royalties beginning with the first commercial sale of the licensed technology[149]. Competitive Landscape and Market Challenges - The company faces intense competition from major pharmaceutical companies and established biotechnology firms, which have greater financial resources and experience[154]. - In the U.S., there is significant uncertainty regarding the coverage and reimbursement status of new pharmaceutical products, which may be influenced by Medicare decisions[215].