RENOVO RX RENOVO RX Delivering therapy where it matters Delivering therapy where it matters Trans-Arterial Chemotherapy for Treatment of Locally Advanced Pancreatic Cancer: Treatment Factors Impacting Survival H. Charles Li – RenovoRx Alex S. Tsobanoudis, Jiali Li, Alexander Rosemurgy, J. Augusto Bastidas, Emmanuel Zervos, Steven Goldin, Peter Muscarella II, Charles Nutting, Barish Edil, Reza Malek, Ramtin Agah 1
RENOVO RX Delivering therapy where it matters Disclosures • This study was funded by RenovoRx (Los Altos, CA) 2
RENOVO RX Delivering therapy where it matters LAPC Background and Current Treatments • By the end of 2020, pancreatic cancer is expected to be 2 nd most deadly cancer • While surgical resection is the best course, due to location of pancreas, tumors in the pancreas are hard to detect until locally advanced and unresectable • Current standard treatment for locally advanced unresectable pancreatic cancer is systemic chemo • Pancreatic tumors are avascular and surrounded by dense matrix, hence systemic chemo not efficacious • Median OS is generally 12 to 15 months 3
RENOVO RX Delivering therapy where it matters LAPC Background and Current Treatments • Trans-Arterial Micro Perfusion (TAMP) is a new technique being used to deliver gemcitabine locally to pancreatic adenocarcinoma in patients that are not candidates for curative resection • The technique involves occluding the vessel adjacent to the tumor, using a dual balloon catheter, then infusing the drug between the balloons to create a pressure gradient resulting in diffusion of the drug across the arterial wall into the surrounding tissue – including the tumor 4
RENOVO RX RENOVO RX Delivering therapy where it matters Delivering therapy where it matters Confidential Do Not Distribute RenovoRx is developing therapies for localized treatment of solid cancer tumors to Increase Survival & Improve Quality of Life RX The RenovoCath TM System Trans-Arterial Micro-Perfusion (TAMP) isolates the anatomy and micro-perfuses targeted tissue with (Intra-Arterial gemcitabine) Targeted localized therapy where Standard of Care systemic chemotherapy can’t reach 5
RENOVO RX RENOVO RX Delivering therapy where it matters Delivering therapy where it matters Confidential Do Not Distribute Mechanism: pressure Gemcitabine mediated Trans-Arterial distribution Micro-Perfusion (TAMP) At ~45mmHg - At ~45mmHg - tissue pressure is tissue pressure is Distal overcome, forcing overcome, forcing 70 1% balloon chemotherapy out chemotherapy out 60 Remaining in of vessel of vessel Pressure (mmHG) arterial wall 50 Catheter in artery 40 Start infusion 30 Proxim 20 al First balloon up balloon Second 10 balloon up 99% 0 Permeating through arterial wall into tissue 6
RENOVO RX Delivering therapy where it matters Methods • Eight US sites enrolled 43 patients receiving over 190 total IA treatments using RenovoCath, as part of a Phase I/II safety and follow-up registry studies. Nineteen patients were treatment naïve, 11 patients had prior chemotherapy, and 12 had prior chemoradiation, with 1 patient having had prior whipple procedure. • Treatment involved isolating portion of artery abutting pancreatic tumor and infusing gemcitabine over 20 minutes. • Most received full dose (1000mg/m 2 ) and was well tolerated • Treatment arteries included SMA, celiac, common hepatic, and splenic, or a combination 7
RENOVO RX Delivering therapy where it matters Methods • We analyzed these data in 43 patients in 2 studies that received up to 190 TAMP treatments • The following variables showed correlation for improved survival in multivariate analysis: • Prior treatment (radiation, chemotherapy, or treatment naïve) • Location of treatment • Number of treatments 8
RENOVO RX Delivering therapy where it matters Results – Prior Treatment Prior Treatment on Median OS 30 25 20 p < 0.01 Months 15 10 5 0 Radiation (n=12) Chemo Only (n=11) Tx Naïve (n=19) 9
RENOVO RX Delivering therapy where it matters Results – Treatment Location Treatment Location on Median OS 35 30 25 20 p < 0.01 Months 15 10 5 0 SMA (n=13) Non-SMA (n=17) Mixed (SMA+Others) (n=13) 10
RENOVO RX Delivering therapy where it matters Results – Number of Treatments Number of Treatments on Survival (from 1st Tx) 12 10 8 p < 0.05 Months 6 4 2 0 1-5 Tx (n=27) 6 or more Tx (n=16) 11
RENOVO RX Delivering therapy where it matters Summary/Conclusion • Intra-arterial gemcitabine/TAMP is safe and efficacious • Increased number of treatment shows greater survival benefits • Patients had varying number of treatments, ranging from 1 to 14 • Patients receiving radiotherapy prior to direct, intra-arterial gemcitabine infusion were shown to have better survival than patients receiving prior systemic chemo or no prior treatments. • Radiation damages and eliminates microvasculature around the tumor, allowing targeted, local chemotherapy to more directly reach the tumor, as opposed to washing out in the vasculature. 12
RENOVO RX RENOVO RX Delivering therapy where it matters Delivering therapy where it matters Confidential Do Not Distribute Mechanism : Trans-Arterial Radiation reduces venous Micro-Perfusion (TAMP) outflow by decreasing the combined with radiation microvasculature Native vasculature and IA chemo Irradiated vasculature Distal RenovoCath™ lead to Micro-vascular washout and IA chemo lead to Diffusion balloon Microvascular washout Proximal RenovoCath TM balloon 13
RENOVO RX Delivering therapy where it matters Summary/Conclusion • Using the RenovoCath via the SMA showed increased benefit compared to treatment in other arteries. • Despite avascular tumor, the SMA is the largest and closest artery supplying the pancreas. SMA is surrounded by pancreatic tissue = better tissue penetration 14
RENOVO RX Delivering therapy where it matters Summary/Conclusion • Current Phase III trial on-going to compare intra-arterial gemcitabine (TAMP) vs. SOC gemcitabine and nab-paclitaxel (systemic IV) 15
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