One, start an FDA cleared lead clinical development program for hepatic metastatic pancreatic cancer. Two, continue to raise capital at valuations that respect the fundamental value of Provectus and try to pursue corporate development that can potentially unlock the true value of the company’s platform. Three, increase Provectus investor communications and engagement and expand the company’s visibility and outreach to the investment community. Dominic will now discuss Provectus’ clinical development programs in cancer and the company’s work in other disease areas.
Dominic Rodrigues: Thank you, Ed. Provectus’ lead oncology indication is FOLFIRINOX refractory pancreatic ductal adenocarcinoma or PDAC, metastatic to the liver or mPDAC. At less than 10% PDAC has the worst five-year survival rate, overall survival rate of all common cancers. Liver or hepatic metastases, which are common, are associated with increased mortality. Intratumorally administered PV-10 will be combined with systemically administered chemotherapies gemcitabine and nab-paclitaxel or GemPac. GemPac is the standard of care in second line when first line systemic chemotherapy regimen FOLFIRINOX fails patients. Survival data in metastatic pancreatic cancer for GemPac as second line to FOLFIRINOX are available from several clinical trials such as Portal 2015, Zhang 2015, NIDA 2019, HA 2021, King 2022, Zipet 2022 and Huffman 2023.
The fraction of patients with metastatic disease and the fraction of metastatic patients with liver metastases varies. Of these studies, where at least 80% of patients had metastatic disease, the weighted average median overall survival and progression-free survival were 6.8 months and 3.9 months, respectively. In King 2022, one in two year overall survival were 23% and 8%, respectively. To Tabernero 2015 analysis of Von Hoff, 2013 of first line GemPac showed that the presence of liver metastases was strongly prognostic of an increased risk of death, 25% shorter median overall survival and 17% shorter progression free survival. Provectus previously treated an 83-year-old mPDAC patient who received first line, single agent, PV-10, one injection to one of two liver metastases.
The patient received no other treatment, declined systemic chemotherapy, and survived for 29 months before succumbing to disease progression. Conroy 2011 shows 11.1 months as the median overall survival for first-line FOLFIRINOX and an overall survival rate at 30 months of 2%. The company plans to run an 18-patient, currently proprietary, single site, dose escalation Phase 1 trial that Provectus believes should align with FDA initiative Project Optimus and its dose optimization principles. Three proposed six-patient dose levels would be tried by varying PV-10’s tumor fill factor, which essentially represents the amount of rose bengal sodium given to a patient’s injectable tumor burden. Fill factor is the ratio of the volume of PV-10 injected into a lesion to the lesion’s estimated volume.
The high dose of these three doses, half the lesion volume, or 0.5 milliliters PV-10 per cubic centimeter of lesion volume, 50% of the lesion has been the typical fill factor for treating patients with liver metastases and Provectus’ clinical trials. In contrast, traditional dosing of systemic therapies is based on the amount of drug given to the patient, a ratio of the amount of drug to the patient’s weight, to assess efficacy potential while monitoring safety and tolerability. Further, while dosing of competing intratumoral biologic drugs, oncolytic virus and logic and drug product candidates such as oncolytic viruses and viral vector gene therapies embraces the fill factor concept. Their mechanisms of action center around viral replication inside and outside of the four walls of the injected lesion.
Whereas PV-10 is well established mechanism of action targets cancer cells within the injected lesion’s four walls before rose bengal sodium is quickly discharged by the body. PV-10 is well documented mechanism of immune action suggests the immune system is doing the work outside of the four walls. We believe Provectus can scientifically and empirically connect mechanism to dosing for the FDA. We believe Provectus’ clinical work in support of historical biomedical literature already define rose bengal sodiums and thus PV-10 safety profile. While it is necessary to establish a dose response under Project Optimus’ framework, we think it is critical to safely maximize PV-10’s dosing to maximize the patient’s response and their long-term outcome.
Thus, Provectus’ goal for the mPDAC study are threefold. One, safely inject enough PV-10 into enough liver metastases, enough times for long enough. Two, show whether PV-10 plus Genpact [ph] can exceed standard of care Genpact historical second line benefit. And three, show whether PV-10 can put patients on a trajectory towards curative outcomes. Proposed endpoints are safety and tolerability, progression free survival by resist for primary efficacy, overall survival, immune correlative markers – and immune correlative markers. Provectus plans to measure objective response by resist and objective metabolic response by persist via positron emission tomography, computed tomography or PET-CT scan. Persist may be more suitable for assessing tumor response and patient disease status after anticancer treatment than RECIST.
However, RECIST is the customary yardstick for measuring response and oncology clinical trials. The first PET-CT scan would be at 24 weeks or about six months after initial PV-10 treatment. If most patients are having their first PET-CT scan, the mPDAC study is potentially in good shape. Overall survival would very likely be the primary endpoint of the potential next clinical trial step. The company’s immune correlative work is designed to confirm or refute PV-10’s established innate immune signaling – system signaling, the release of damaged associated molecular pattern molecules, and explore the potential implication of myeloid derived suppressor cells based on preclinical research at Moffitt Cancer Center and/or macrophages favored by the study’s principal investigator.
Based on estimates from the investigator, enrollment time could be 12 months to 18 months or less. Provectus plans to do multiple interim assessments, such as for each dose level cohort and a preliminary assessment of full study results. The company plans to seek FDA clearance for the mPDAC program and its initial trial via a Type C meeting request. Provectus would clearly communicate its authentic desire to partner with the FDA for PV-10’s drug development. Pharma company search and evaluation teams want randomized control trial data of PV-10 versus standard of care in a cancer indication of interest for possible co-development, licensure or M&A. Pharma companies do not directly tell us what study to run, but based on Provectus’ data sets and external feedback, we are confident that data from a successful, comprehensive, well designed, data rich, efficient mPDAC study under FDA clearance compared to established, well characterized, historical standard of care Genpact data is a potential catalyst for company recognition in the pharma and investment communities.
