The Potential of Superoxide Dismutase Mimetics in Radiotherapy for Cancer

Superoxide, a highly reactive molecule, is produced by every cell as a part of normal metabolism, but left uncontrolled, is highly toxic, leading to cell damage or cell death. As a defense, the body produces superoxide dismutase enzymes that convert superoxide into hydrogen peroxide. Hydrogen peroxide is much less toxic than superoxide to normal tissue, but more toxic to cancer cells. Radiotherapy cancer treatment generates a large burst of toxic superoxides in irradiated tissues, overwhelming the natural enzymes, leading to normal cell damage and cell death.

Galera’s novel small molecules mimic the body’s natural dismutase enzymes with fast catalytic rates and high selectivity for superoxides, aiming to protect healthy cells from radiation and increase the anti-cancer efficacy of radiotherapy.

Radiotherapy-Induced Toxicity

0:00

00:00 / 00:00

Protecting healthy tissue from toxic bursts of superoxides in patients with cancer

Standard-of-care radiotherapy for head and neck cancer generates bursts of toxic superoxides, which can damage healthy tissues in the mouth and throat. Patients may experience this tissue damage as pain, redness, and/or sores, a condition called oral mucositis. In its worst grades, known as severe oral mucositis (SOM), patients are unable to eat solid food and/or drink liquids because of the extremely painful mouth sores. SOM’s impact can be debilitating to patients receiving radiation therapy and may impact their ability to receive their full course of radiotherapy.

Galera’s radioprotective dismutase mimetic, avasopasem manganese, was developed to reduce SOM and other radiotherapy-induced toxicities by rapidly and selectivity converting toxic superoxides generated by radiation therapy to hydrogen peroxide, which is less damaging to healthy tissue.

There are currently no drugs approved by the U.S. Food and Drug Administration to reduce radiotherapy-induced SOM in patients with head and neck cancer.

Increase Radiotherapy Anti-Cancer Efficacy

Harnessing the power of hydrogen peroxide to damage cancer cells

Galera’s next-generation selective dismutase mimetic, rucosopasem manganese (rucosopasem), is a radiosensitizer in development to increase the anti-cancer efficacy of stereotactic body radiation therapy (SBRT), a type of high fraction dose radiotherapy, in patients with lung cancer and pancreatic cancer. Rucosopasem converts the large bursts of superoxide generated by SBRT into bursts of hydrogen peroxide, a compound harmful to cancer cells.

Rucosopasem is in the clinical development phase with the goal of augmenting the anti-cancer efficacy of SBRT in patients with lung cancer and pancreatic cancer.

GRECO-1

Phase 1/2 Study of Rucosopasem in Combination with SBRT for NSCLC

GRECO-1 is a Phase 1/2, randomized, placebo-controlled study of rucosopasem in combination with stereotactic body radiation therapy (SBRT) in patients with early-stage, peripheral or centrally located non-small cell lung cancer (NSCLC).

GRECO-2

A Phase 2b Study of Rucosopasem in Combination with SBRT for Pancreatic Cancer

GRECO-2 is a Phase 2b randomized, double-blind, placebo-controlled study of rucosopasem in combination with stereotactic body radiation therapy (SBRT) in patients with nonmetastatic pancreatic cancer.