A unique formulation of sodium thiosulfate (STS)

Development

  • We believe PEDMARK is the only agent that is specifically in development for the prevention of ototoxicity from cisplatin in pediatric patients
  • PEDMARK is a small molecule, unique formulation of STS

Drug Delivery

  • PEDMARK STS is administered 6 hours post completion of cisplatin infusion in an intravenous (IV) bolus dose over 15 minutes

Toxicology

  • STS is generally recognized as safe (GRAS) in the United States with respect to active ingredient STS but not established in current proposed use

Intended mechanism of action

  • Anticancer activity of cisplatin occurs during the first 2 hours after administration when the free (unbound) cisplatin distributes into the cancer cells1
  • Cisplatin is readily cleared from most organs but is longer term retained in the cochlea2
  • Cisplatin-induced ototoxicity is caused by irreversible damage to hair cells in the cochlea3
  • Cochlea is very sensitive to oxidative stress, which has been shown to be involved in ototoxicity4
  • STS inhibits oxidative stress5
  • Administering STS 6 hours after completion of cisplatin infusion ensures that levels of unbound cisplatin are minimal5

Two randomized studies have been completed

Proof of Concept Study | COG ACCL0431

  • 131 patients with heterogenous solid tumors
  • Achieved primary efficacy endpoint – ASCO 2014
  • Final results published in Lancet Oncology, December 2016

Pivotal Study | SIOPEL 6

  • 109 patients with standard risk hepatoblastoma (SR-HB)
  • Achieved primary endpoint – SIOP 2017
  • Showed no evidence of tumor protection
  • Final results published in New England Journal of Medicine, June 2018

US regulatory milestones achieved

  • Granted Fast Track and Breakthrough Therapy Designation by the FDA
  • Completed NDA to FDA and MAA to EMA – PEDMARK (US) is proposed to be indicated for the prevention of ototoxicity induced by cisplatin chemotherapy in patients 1 month to <18 years of age with localized, non-metastatic solid tumors
  • Priority review granted upon acceptance by FDA
  • FDA issued CRL August 2020 – Pre-approval inspection identified deficiencies with the facility of the drug product manufacturer. No clinical or safety issues identified. Resubmission pending
  • Potential for 7.5 YEARS US market exclusivity with Pediatric Orphan Drug Designation
  • Patent protection in the US until 2038 for the for the unique anhydrous form of the active ingredient in Fennec’s PEDMARK product, as well as related methods of synthesis

EU regulatory milestones achieved

  • EMA validation received for MAA
  • Positive opinion on PIP received by PDCO at EMA
  • Potential for 10 YEARS EU market exclusivity with Pediatric-use Marketing Authorization (PUMA), if granted

PEDMARK has the potential to be the first and only therapy indicated in this area of significant high unmet medical need

Collaboration with Oregon Health and Science University (OHSU)

  • Fennec Pharma licensed 1 US and 9 foreign patents from OHSU for STS. The STS methods of use patents expire in Europe and Japan in 2021 and are currently pending in the US
  • Patent Protection was recently granted in the US until 2038 for method of use for children <5 years of age

References: 1. Cisplatin Injection [prescribing information ]. WG Critical Care, LLC., Paramus, NJ; February 2019. 2. Breglio AM, Rusheen AE, Shide ED, Fernandez KA, Spielbauer KK, McLachlin KM, et al. Cisplatin is retained in the cochlea indefinitely following chemotherapy. Nat Commun. 2017;8(1):1654. 3. Landier W. Ototoxicity and cancer therapy. Cancer. 2016;122(11):1647-1658. 4. Langer T, am Zehnhoff-Dinnesen A, Radtka S, Meitert J, Zolk O. Understanding platinum-induced ototoxicity. Trends Pharmacol Sci. 2013;34(8):458-469. 5. Data on file, Fennec Pharmaceuticals 2020.

PEDMARK™ is a registered trademark of Fennec Pharmaceuticals Inc.