Intezyne Technologies Granted Orphan Drug Designation For IT-139 In Pancreatic Cancer


 

program overview

IT-139 is a novel Cancer Resistance Pathway (CRP) inhibitor that reduces drug resistance in tumors to other anti-cancer agents by inhibiting stress induction of GRP78.

  • Synergistic with numerous anti-cancer agents in preclinical models

  • Completed Phase 1 monotherapy trial

    • IT-139 was well-tolerated, with manageable side effects
  • Received Orphan Drug Designation (ODD) in Pancreatic Cancer

    • EMA Orphan application in process
 

Next Steps

  • cGMP manufacturing (to be completed in 2Q18)
  • Phase 1b/2 combination trials (3Q18)
    • Pancreatic cancer (Gemzar® [+Abraxane®] +/- IT-139)
    • Gastric cancer (Camptosar® +/- IT-139)
    • Other combination trials, as funding allows:
      • BRAF-mutated cancers (Taflinar® + Mekanist® +/- IT-139)
 

ABOUT GRP78 as a critical resistance pathway

 
 
 

IT-139 inhibits stress induction of GRP78, one of the most important cancer resistance pathways

 

Phase 1 clinical trial

Dose Escalation Study of IT-139 to Treat Advanced Solid Tumors

(NCT01415297)

 
Phase 1 open-label dose-escalation study to evaluate the safety and tolerability of IT-139 in patients with advanced solid tumors refractory to treatment

Study Design


Primary – Safety, tolerability and maximum tolerated dose (MTD)
Secondary – To estimate the pharmacokinetic (PK) parameters, report any responses in patients with advanced tumors, and explore pharmacodynamic endpoints which may be of use in further development

Endpoints


Scottsdale Healthcare Research Institute, Scottsdale, AZ
Sarah Cannon Cancer Center, Nashville, TN

Trial Sites


Daniel Von Hoff, MD; CSO for HonorHealth's Clinical Research Institute
Howard Burris, MD; CMO, Sarah Cannon

Lead Investigators


41

No. of Participants


Intravenous

Administration


Safe and generally well-tolerated; RP2D of 625 mg/m²
Stable disease, partial response, and/or tumor size reduction in a clinically meaningful proportion of patients

Results


 

About Pancreatic Cancer

3.2% of cancer (54,000), 7.2% (48,000) of cancer deaths

  • 5-year survival rate of only 8.2%
  • Significant unmet therapeutic need
 

IT-139 Development Rationale

  • High-risk, high-reward strategy supported by compelling data
  • IT-139 awarded ODD in Pancreatic Cancer (June 2017)
    • Provides numerous benefits including opportunity for market exclusivity and better coordination with FDA
  • Decreasing GRP78 levels improved outcomes in transgenic models
  • Statistically significant improvement in survival in preclinical pancreatic cancer models in combination with Gemzar® (gemcitabine)
 

Phase 1b/2 clinical development strategy in Pancreatic cancer

 
Phase 1b/2 open-label study to evaluate the safety, tolerability, and efficacy of adding IT-139 to Gemzar® (gemcitabine) [and Abraxane® (nab-paclitaxel)] in high-risk patients with stabilized pancreatic cancer

Study Design


20

Participants


Primary - Safety, tolerability, maximum tolerated dose (MTD), and improved survival outcomes (PFS, OS)
Secondary - To estimate the pharmacokinetic (PK) parameters of IT-139 in combination with Gemzar® [and Abraxane®], report any responses in patients, and explore pharmacodynamic endpoints (GRP78 biomarker)

Endpoints


Keck School of Medicine of USC, Los Angeles, CA

Trial Sites


Anthony El-Khoueiry, MD; Associate Professor of Clinical Medicine and Norris Cancer Center Ciso Chair

Lead Investigator


 

Median survival in this high-risk patient population is approximately 5 months; we believe we can increase this to 8+ months

 

IT-139 in Pancreatic Cancer

 

About gastric Cancer

1.7% of cancer (28,000), 1.8% (11,000) of cancer deaths

  • 5-year survival rate of only 3.1% in advanced gastric cancer
  • Significant unmet therapeutic need
  • Orphan market in U.S., but 5th most common cancer worldwide
    • Extremely high incidence in Pacific Rim (China, Japan, and Korea)
 

IT-139 Development Rationale

  • Moderate-risk, high-reward strategy supported by compelling data
  • Limited competition, both in the U.S. and worldwide
  • Opportunity for Orphan Drug Designation
    • Provides numerous benefits including opportunity for market exclusivity and better coordination with FDA
    • Orphan applications with FDA and EMA
  • High GRP78 levels correlate with poor prognosis in gastric and esophageal cancers (Oncotargets and Therapy, 2017)
 

Phase 1b/2 clinical development strategy in gastric cancer

 
Phase 1b/2 open-label study to evaluate the safety, tolerability, and efficacy of adding IT-139 to Camptosar® (irinotecan) in 3rd line patients with advanced gastric cancer

Study Design


20

Participants


Primary - Safety, tolerability, maximum tolerated dose (MTD), and improved survival outcomes (PFS, OS)
Secondary - To estimate the pharmacokinetic (PK) parameters of IT-139 in combination with Camptosar®, report any responses in patients, and explore pharmacodynamic endpoints (GRP78 biomarker)

Endpoints


HonorHealth, Scottsdale, AZ (tentative)

Trial Sites


Daniel Von Hoff, M.D.; CSO for HonorHealth's Clinical Research Institute

Consultant


 

Median survival in this patient population is approximately 7 months; we believe we can increase this to 10+ months

 

IT-139 in Gastric Cancer

 

GRP78: A critical Resistance Pathway

 

IT-139 impact on grp78 stress induction