The Phase 3 Study: Targeted Intra-Arterial Gemcitabine vs. Continuation of IV Gemcitabine plus Nab-Paclitaxel Following Induction with Sequential IV Gemcitabine plus Nab-Paclitaxel and Radiotherapy for Locally Advanced Pancreatic Cancer (TIGeR-PaC) First Interim Analysis Presented at the 2023 ESMO World Congress on Gastrointestinal Cancer

The Phase 3 Study: Targeted Intra-Arterial Gemcitabine vs. Continuation of IV Gemcitabine plus Nab-Paclitaxel Following Induction with Sequential IV Gemcitabine plus Nab-Paclitaxel and Radiotherapy for Locally Advanced Pancreatic Cancer (TIGeR-PaC)

First Interim Analysis

Dr. Michael Pishvaian1, Dr. Amer Zureikat2, Dr. Paula Novelli2, Dr. Charles Lopez3, Dr. Kenneth Meredith4, Dr. Emmanuel Zervos5, Dr. Hassan Hatoum6, Dr. Ki Chung7, Dr. Daniel J. Berg8, Dr. Antonio Ucar9, Dr. Ripal Gandhi9, Dr. Reza Nazemzadeh10, Dr. Nainesh Parikh11, Dr. Christopher Laing12, Dr. Brian Boone13, Dr. Thor Johnson14, Dr. Susan Bates15, Dr. Karyn Goodman16, Dr. Brian Kouri10, Dr. Ramtin Agah17

• Johns Hopkins University School of Medicine, NMCR Kimmel Cancer Center at Sibley Memorial Hospital, Washington, D.C., United States,2 UPMC Hillman Cancer Center, Pittsburgh, PA, United States, 3 Oregon Health & Science University, Knight Cancer Institute, Portland, Oregon, United States, 4 Sarasota Memorial Hospital, Sarasota, FL, United States, 5 East Carolina University, Greenville, North Carolina, United States, 6 University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States, 7 Prisma Health Cancer Institute in Greenville, SC, United States, 8 University of Iowa, Iowa City, Iowa, United States, 9 Miami Cancer Institute, Baptist Health South Florida, Miami, Florida, United States, 10 Atrium Health Levine Cancer Institute, Charlotte, NC, United Stated, 11 Moffitt Cancer Center, Tampa, FL, United States, 12 Sutter Medical Center, Sacramento, CA, United States, 13 West Virginia University, Morgantown, West Virginia, United States , 14 Medical University of South Carolina, Charleston, South Carolina, United States, 15 Columbia University Medical Center, New York, NY, United States, 16 Icahn School of Medicine at Mount Sinai, New York, NY, United States, 17 RenovoRx Inc. Los Altos, CA, United States

Disclosures (3 years)

Consultant/Advisory Board/Steering Committee:

• AstraZeneca, Merck, Pfizer, Novartis, Ideaya, Astellas, Trisalus, Pionyr, Seattle Genetics, Merus

Travel, accommodations, and expenses support:

• Astellas, RenovoRx

Stock/Ownership:

• Perthera, Tumor Board Tuesdays, TRICC

Research funding to my institution:

• Seattle Genetics, Tesaro, Arcus Bio, Ideaya, Repare Tx, Novartis, Pfizer, Merck, Tizonia, Takeda, RenovoRx, Biomed Valley Discoveries, Boerhinger Ingelheim, Astellas, Hutchinson Medipharma

Research funding to support CME:

• AstraZeneca, Exelixis, Caris, Incyte, Ipsen, Natera, Bayer, BMS, Eisai, Foundation Medicine, Pfizer, SeaGen, Taiho, Tempus, Merck, Novartis

Locally Advanced Pancreatic Cancer (LAPC)

• Pancreatic cancer is soon to be the second leading cause of cancer-related death in the United States
• 30% - 35% of pancreatic cancer patients present with locally advanced disease
• While 10-15% of patients with LAPC have their disease rendered surgically operable (with an R0 resection), the vast majority of patients have incurable disease
• The current standard of care therapies for patients with LAPC have led to a median overall survival of ~15 months

Rahib L, et al, Cancer Res. 2014 Jun 1;74(11):2913-2; Park W, Chawla A, O'Reilly EM, JAMA. 2021 Sep 7;326(9):851-862

Survival in Locally Advanced Pancreatic Cancer

Prospective Trials

The current standard of care therapies for patients with LAPC have led to a median overall survival of 9.3 - 19.2 months

Prospective Trials
2009	N=30	German LAPC Phase 2	RT-5FU	9.6 months
	N=32	German LAPC Phase 2	RT-Gem-cis	9.3 months
	N=31	German LAPC Phase 2	RT-Gem-cisà gem-cis	7.3 months
2011	N=69	MDACC Phase 2	Cetux-Gem-Cisà RT+cetux	19.2 months
2016	N=223	LAP 07 Phase 3	Gemcitabine	13.6 months
	N=219	LAP 07 Phase 3	Gemcitabine + erlotinib	11.9 months
2020	N=107	LAPACT Phase 2	Gemcitabine + nab-pac	18.8 months

Wilkowski R, Br J Cancer. 2009 Dec 1; 101(11): 1853-1859;Crane D, JCO. 2011 Aug 1; 29(22): 3037-3043;

Hammel P, JAMA. 2016;315(17):1844-1853; Philip PA, et al, Lancet Gastroenterol Hepatol. 2020 Mar;5(3):285-294

Chemotherapy is Not Effectively Delivered to

Primary Pancreatic Tumors

Dense fibrotic stroma | Sparse tumor cellularity | Hypovascular tumors

Liver tumors are vascularized

Pancreas tumors are hypovascular

•	Large tumor feeders - excellent targets for therapy	• Inability to identify tumor feeder vessels and penetrate
•	Large branches within tumor - easily visualize tumor	drug into the tumor