The better the data are, the better a deal can be. Best data are if PV-10 can hit for both average and power. That is, many more PV-10 treated mPDAC patients respond and live much longer than those on Genpact. I believe Provectus has very meaningfully addressed historical PV-10 data positive and data gaps over the last several years in three very important ways. One, by collecting and collating durability of response and overall survival of patients treated with PV-10 in superficial and visceral cancer indications. Two, by trying to safely maximize PV-10’s dosing regimen, which could potentially increase the probability of success of the mPDAC trial. We believe enough PV-10 injections enough times to enough lesions for long enough can lead to durable systemic responses and long-term outcomes for patients.
A little PV-10 can go a long way, but enough PV-10 might cure you. Three, by identifying and validating that the treatment of metastatic cancers by primarily treating liver metastases is key to potential positive long-term patient outcomes, irrespective of the presence of hepatic only or both hepatic and extrahepatic disease. Increase PV-10 dosing compared to Provectus’ historical under dosing of patients led to durable systemic responses and long-term outcomes in advanced cutaneous melanoma and hepatic metastatic uveal melanoma patients. Further, PV-10 potentially improved the prognosis of patients with PV-10 treated hepatic metastases with or without extrahepatic disease. For six Stage 3 melanoma patients receiving PV-10 and checkpoint inhibitor pembrolizumab, objective response by RECIST was 83%.
50% of patients achieved a rapid, durable, complete response and were ongoing up to nearly four years. Median progression free survival had not yet been reached and median overall survival was about three years. But this figure could change because of the status of the last patient who was an ongoing complete responder at 2.5 years. For four uveal melanoma patients who received monotherapy PV-10 or PV-10 and dual checkpoint inhibitors ipilimumab and nivolumab, complete metabolic responses were ongoing after a median time of more than three years, ranging from more than two years to more than five, and median overall survival had not yet been reached. Further, comparing M1a stage patients with or without extrahepatic disease who received PV-10, ipilimumab and nivolumab to historical patients who received ipilimumab and nivolumab, Pelster, 2021, median overall survival was more than four years versus about one year.
As we prepare to start the mPDAC trial, I believe the totality of Provectus’ data speak for themselves. I believe a patient who receives enough PV-10 treatment to enough of their injectable hepatic tumor burden can potentially achieve complete metabolic response, which could potentially be prognostic of a positive long-term outcome for them. Finally, Provectus’ oncology clinical development strategy carefully considers the company’s data and cancer indications where PV-10 can beat standard of care, best display its own immunotherapeutic capabilities, potential synergy with other drugs notwithstanding, and produce the highest risk-adjusted net present value or rNPV. rNPV is a key valuation method applied by the pharma and investment communities to place an estimated value or price on a biopharma asset.
I believe Provectus possesses several attractive PV-10 data sets of different cancer types. Taking a given indication and the proposed line of treatment, the amount and quality of the company’s supporting data, the likelihood of an overall survival endpoint for drug approval, the indication standard of care, the likely number of patients required for a randomized control trial, the likely length of time to show clinical benefit, an assessment of PV-10 treatment arm’s potential effect size and an assessment of the likelihood of success. Provectus’ consequential study ranged from potentially several hundred patients in years for treatment naïve stage three cutaneous melanoma to dozens and dozens of patients in many months for treatment naïve metastatic uveal melanoma to tens of patients in months for folfirinox refractory mPDAC.
PV-10’s potential rNPV for mPDAC is significantly higher than for stage three melanoma. Third line hepatic metastatic neuroendocrine tumors rNPV was the lowest. However, this work showed that limited PV-10 dosing could still achieve durable stable metabolic disease via persist in patients. Provectus could potentially initiate two other clinical trials in 2024. One, Provectus is currently evaluating a single site randomized controlled trial for treatment naïve M1a staged hepatic metastatic uveal melanoma comparing PV-10 ipilimumab and nivolumab to ipilimumab and nivolumab, which is an institutional standard of care at MD Anderson Cancer Center, where initial clinical study was done. Provectus is considering a survival based endpoint such as an 18-month survival rate.
The company’s clinical data favorably compares with historical clinical data of a competing treatment. 50-month median overall survival of PV-10, ipilimumab and nivolumab versus ipilimumab and nivolumab 12.8 months. Tier 2 Provectus is focused on timely enrollment. Two, the company could participate in an 18 patient, currently proprietary, single site, investigator initiated study of preoperative PV-10 for penile squamous cell carcinoma or penile SCC, where standard of care is a penectomy, the partial or total surgical removal of the patient’s penis. The clinical site in question is one of two academic medical centers in the U.S. that purportedly see substantially all penile SCC patients seeking treatment. The study’s co-principal investigators, a surgical oncologist and a medical oncologist, have given us insight into potential enrollment rates.
