rucosopasem manganese (GC4711) / Galera Therap, Biossil - LARVOL DELTA

Galera has entered into an Asset Purchase Agreement with Toronto-based Biossil for Galera’s dismutase mimetics portfolio, including all avasopasem and rucosopasem formulations and indications. (The Manila Times) - "The agreement includes 1) an upfront payment of $3.5 million, 2) potential future regulatory milestones, commercial milestones, and contingent value rights of up to $105 million."

Commercial • Pancreatic Cancer

Pharmacological ascorbate combined with rucosopasem selectively radio-chemo-sensitizes NSCLC via generation of H2O2. (PubMed, Redox Biol) - "Most importantly, the combination of RUC + P-AscH‾ was found to sensitize both H1299T and A549 cell types to radio-chemotherapy with cisplatin (CIS) + etoposide (ETOP). Finally, in H1299T NSCLC xenografts the combination of RUC + P-AscH‾ with CIS + ETOP and 12 × 2 Gy radiation significantly inhibits tumor growth and increased median overall over survival. These results support the hypothesis that selective MnPAM dismutase mimetic + P-AscH‾ enhances the efficacy of radio-chemotherapy in NSCLC through a mechanism governed by redox active metals and H2O2 production."

Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CAT

Galera Reports First Quarter 2024 Financial Results and Recent Corporate Updates (GlobeNewswire) - "Research and development expenses were $1.5 million in the first quarter of 2024, compared to $7.3 million for the same period in 2023. The decrease was primarily attributable to a decrease in avasopasem and rucosopasem development costs. The Company has ceased all clinical trial activity and suspended the clinical development of its product candidates as it explores potential strategic alternatives."

Commercial • Gastrointestinal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor

Stereotactic body radiotherapy plus rucosopasem in locally advanced or borderline resectable pancreatic cancer: GRECO-2 phase II study design. (PubMed, Future Oncol) - "The primary end point is overall survival. Secondary end points include progression-free survival, locoregional control, time to metastasis, surgical resection rate, best overall response, in-field local response and acute and long-term toxicity."

Clinical • Journal • Metastases • P2 data • Review • Gastrointestinal Cancer • Gastrointestinal Disorder • Hepatology • Oncology • Pancreatic Cancer • Solid Tumor

GRECO-1: Phase I/II Study of SBRT and GC4711 for Centrally Located or Large NSCLC (clinicaltrials.gov) - P1/2 | N=47 | Terminated | Sponsor: Galera Therapeutics, Inc. | N=71 ➔ 47 | Trial completion date: Dec 2025 ➔ Nov 2023 | Recruiting ➔ Terminated | Trial primary completion date: Jun 2024 ➔ Nov 2023; Development GC4711 was halted after the lead study in pancreatic cancer was stopped early due to meeting the requirements of a futility analysis

Enrollment change • Trial completion date • Trial primary completion date • Trial termination • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

GRECO-2: Phase 2b Study of GC4711 in Combination With SBRT for Nonmetastatic Pancreatic Cancer (clinicaltrials.gov) - P2 | N=177 | Terminated | Sponsor: Galera Therapeutics, Inc. | Phase classification: P2b ➔ P2 | Trial completion date: Oct 2027 ➔ Nov 2023 | Recruiting ➔ Terminated | Trial primary completion date: Oct 2024 ➔ Nov 2023; Futility Analysis

Combination therapy • Metastases • Phase classification • Trial completion date • Trial primary completion date • Trial termination • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor

Galera Announces Receipt of Type A Meeting Minutes and Strategic Update (GlobeNewswire) - "Galera Therapeutics, Inc...announced that it has received official meeting minutes from the Type A meeting with the United States Food and Drug Administration (FDA) held September 28, 2023 in which the FDA reiterated the need for an additional Phase 3 trial of avasopasem manganese (avasopasem) for radiotherapy-induced SOM. The Company also decided to halt the Phase 2b GRECO-2 trial of rucosopasem manganese (rucosopasem) in patients with locally advanced pancreatic cancer (LAPC) and the Phase 1/2 GRECO-1 trial of rucosopasem in patients with non-small cell lung cancer (NCSLC), following a futility analysis of the GRECO-2 trial....In the Type A Meeting minutes, the FDA reiterated that results from an additional Phase 3 trial will be required to support resubmission of the Company’s New Drug Application (NDA) for avasopasem in radiotherapy-induced SOM."

FDA event • Trial termination • Gastrointestinal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor

Enhanced Peroxide Fluxes and Radiosensitization in Colorectal Tumors but Not Normal Enterocytes from the Combination of Superoxide Dismutase Mimetics and Pharmacological Ascorbate. (PubMed, Int J Radiat Oncol Biol Phys) - "Co-treatment with DMs and P-AscH selectively enhanced tumor radiosensitization by increasing oxygen consumption and H0 fluxes even in tumor models which are known to be resistant to oxidative stressors (HT29). In contrast, each agent conferred a radioprotective effect in the rectum. Combination therapy with DMs and P-AscH may represent a novel, potent approach to target dysregulated redox metabolism in colorectal tumors."

Journal • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • CAT

Enhanced Peroxide Fluxes and Radiosensitization in Colorectal Tumors but Not Normal Enterocytes from the Combination of Superoxide Disumutase Mimetics and Pharmacological Ascorbate (ASTRO 2023) - "Purpose/Objective(s): Selective superoxide dismutase mimetics (DMs), including GC4419 and GC4711, are radiation (RT) modulators which induce opposite effects in tumors and normal tissues and may be ideally suited for locally advanced rectal cancer. Co-treatment with DMs and P-AscH selectively enhanced tumor radiosensitization by increasing oxygen consumption and H 2 0 2 fluxes even in tumor models which are known to be resistant to oxidative stressors (HT29). In contrast, each agent conferred a radioprotective effect in the rectum. Combination therapy with DMs and P-AscH may represent a novel, potent approach to target dysregulated redox metabolism in colorectal tumors."

Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • CAT

Galera Reports Second Quarter 2023 Financial Results and Recent Corporate Updates (GlobeNewswire) - "Enrollment is ongoing in the randomized, placebo-controlled Phase 2b GRECO-2 trial of rucosopasem in combination with SBRT in patients with LAPC. The primary endpoint of the trial is overall survival. Completion of enrollment continues to be anticipated in the first half of 2024, and topline data readout is expected by the end of 2024....Enrollment is ongoing in the randomized, placebo-controlled Phase 2 stage of the GRECO-1 trial of rucosopasem in combination with SBRT in patients with NSCLC. Completion of enrollment continues to be anticipated in the second half of 2023, and topline data readout is expected in the second half of 2024."

Enrollment status • P1/2 data • P2b data • Gastrointestinal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor

Galera Announces FDA Orphan Drug Designation Granted to Rucosopasem for Pancreatic Cancer (GlobeNewswire) - "Galera Therapeutics, Inc...announced that the U.S. Food and Drug Administration (FDA) has granted orphan drug designation to Galera’s second product candidate, rucosopasem manganese (rucosopasem), for the treatment of pancreatic cancer."

Orphan drug • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Solid Tumor

GRECO-2: A randomized, phase 2 study of stereotactic body radiation therapy (SBRT) in combination with rucosopasem (GC4711) in the treatment of locally advanced or borderline resectable nonmetastatic pancreatic cancer. (ASCO 2022) - P2b | "In a pilot phase 1/2 trial in patients with pancreatic cancer, avasopasem, a dismutase mimetic related to rucosopasem, nearly doubled median overall survival in patients receiving SBRT vs placebo plus SBRT...Materials/ GRECO-2 is a phase 2, multicenter, randomized, double-blind, placebo-controlled study (NCT04698915) to determine the effect of adding rucosopasem to SBRT on overall survival in patients with borderline resectable or locally advanced, unresectable nonmetastatic pancreatic cancer following initial chemotherapy with a FOLFIRINOX-based regimen or a gemcitabine doublet...Exploratory endpoints include PRO-CTCAE and CA19-9 normalization. This trial is now enrolling."

Clinical • Combination therapy • P2 data • Gastrointestinal Cancer • Gastrointestinal Disorder • Hepatology • Oncology • Pancreatic Cancer • Solid Tumor • CA 19-9

Greco-2: A randomized, phase 2 study of stereotactic body radiation therapy (SBRT) in combination with rucosopasem (GC4711) in the treatment of locally advanced or borderline resectable nonmetastatic pancreatic cancer. (ASCO-GI 2023) - P2b | "In a pilot phase 1/2 trial in patients with pancreatic cancer, avasopasem, a dismutase mimetic related to rucosopasem, nearly doubled median overall survival in patients receiving SBRT vs placebo plus SBRT... GRECO-2 is a phase 2, multicenter, randomized, double-blind, placebo-controlled study (NCT04698915) to determine the effect of adding rucosopasem to SBRT on overall survival in patients with borderline resectable or locally advanced, unresectable nonmetastatic pancreatic cancer following initial chemotherapy with a FOLFIRINOX-based regimen or a gemcitabine doublet...This trial (NCT04698915) is now enrolling. Clinical trial information: NCT04698915."

Clinical • Combination therapy • Metastases • P2 data • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Solid Tumor • CA 19-9

Galera Reports Fourth Quarter and Full Year 2022 Financial Results and Recent Corporate Updates (GlobeNewswire) - "Enrollment is ongoing in the randomized, placebo-controlled Phase 2b GRECO-2 trial of rucosopasem in combination with stereotactic body radiation therapy (SBRT) in patients with LAPC. The primary endpoint of the trial is overall survival. The Company continues to anticipate completion of enrollment in the second half of 2023....Enrollment is ongoing in the randomized, placebo-controlled Phase 2 stage of the GRECO-1 trial of rucosopasem in combination with SBRT in patients with NSCLC. The Company continues to anticipate completion of enrollment in the second half of 2023."

Enrollment status • Gastrointestinal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor

Galera Reports Third Quarter 2022 Financial Results and Recent Corporate Updates (GlobeNewswire) - "Anti-Cancer Programs: Locally Advanced Pancreatic Cancer (LAPC) - Enrollment is ongoing in the randomized, placebo-controlled Phase 2b GRECO-2 trial of rucosopasem in combination with stereotactic body radiation therapy (SBRT) in patients with LAPC....Completion of enrollment is expected in the second half of 2023."

Enrollment status • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Solid Tumor

GRECO-1: Phase 1/2 Study of Stereotactic Body Radiation Therapy (SBRT) with or without Rucosopasem (GC4711) for Early Stage, Peripheral or Centrally Located Non-Small Cell Lung Cancer (NSCLC) (ASTRO 2022) - P1/2 | "TBD"

P1/2 data • Inflammation • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pneumonia • Respiratory Diseases • Solid Tumor

[VIRTUAL] GRECO-1: Phase 1/2 Study of Stereotactic Body Radiation Therapy (SBRT) With or Without GC4711 for Early Stage, Centrally Located or Large Non-Small Cell Lung Cancer (NSCLC) (ASTRO 2021) - P1/2 | "GC4711 may improve the benefit-risk ratio of 5-fraction SBRT in early-stage NSCLC; improving tumor control while reducing the risk of lung injury."

P1/2 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pneumonia • Respiratory Diseases • Solid Tumor

[VIRTUAL] GRECO-2: A Randomized, Phase 2 Study of Stereotactic Body Radiation Therapy (SBRT) in Combination With GC4711 in the Treatment of Unresectable or Borderline Resectable Nonmetastatic Pancreatic Cancer (PC) (ASTRO 2021) - P2b | "In a pilot Phase 1/2 trial (GC4419-101), subjects with locally advanced PC were randomized to receive SBRT with a selective dismutase mimetic or placebo... GC4711 may improve the benefit-risk ratio of 5-fraction SBRT and drive survival benefit of local treatment of chemotherapy responsive PC patients."

Clinical • Combination therapy • P2 data • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Cancer • Solid Tumor • Cancer antigen 19-9

Galera to Present at 2022 American Society for Radiation Oncology (ASTRO) Annual Meeting (GlobeNewswire) - "Galera Therapeutics, Inc...announced that tumor outcomes data from its Phase 3 ROMAN trial of avasopasem for severe oral mucositis (SOM) and final data from its Phase 2 AESOP trial of avasopasem for chemoradiotherapy-induced esophagitis will be highlighted in two presentations at the upcoming 2022 American Society for Radiation Oncology (ASTRO) Annual Meeting, taking place October 23-26, 2022 in San Antonio, Texas. Additionally, poster presentations will highlight the Phase 2 EUSOM trial of avasopasem for SOM in Europe and the ongoing GRECO-1 trial of rucosopasem for non-small cell lung cancer."

P1/2 data • P2 data • P3 data • Gastrointestinal Disorder • Head and Neck Cancer • Lung Cancer • Mucositis • Non Small Cell Lung Cancer • Oncology • Solid Tumor

GRECO-1: Phase I/II Study of SBRT and GC4711 for Centrally Located or Large NSCLC (clinicaltrials.gov) - P1/2 | N=71 | Recruiting | Sponsor: Galera Therapeutics, Inc. | Trial completion date: Jul 2023 ➔ Dec 2025 | Trial primary completion date: Nov 2022 ➔ Jun 2024

Trial completion date • Trial primary completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Galera Announces Results from Phase 1 Stage of GRECO-1 Trial of Rucosopasem with SBRT for NSCLC (GlobeNewswire) - P1/2 | N=71 | GRECO-1 (NCT04476797) | Sponsor: Galera Therapeutics, Inc. | "Enrollment is ongoing in the randomized, double-blinded, placebo-controlled Phase 2 stage of the trial, with completion of enrollment anticipated in the second half of 2023....Rucosopasem in combination with SBRT appeared well tolerated....In-field partial responses or stable disease were seen in six of the seven patients at six months follow-up, including target tumor reductions in five patients of 61%, 58%, 33%, 29% and 27% from baseline. All seven patients are alive through a minimum of nine months of follow-up...No Grade 2-4 (RTOG scale) declines in DLCO were seen in any of the seven patients receiving rucosopasem compared to a prospective trial (n=127) evaluating pulmonary function after four to five fractions of lung SBRT, in which 7-12% of patients had Grade 2-4 decline in DLCO."

Enrollment status • P1 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Galera Announces Oral Presentation at 2022 American Society of Clinical Oncology (ASCO) Annual Meeting Detailing Results from Phase 3 ROMAN Trial of Avasopasem (GlobeNewswire) - P3 | N=455 | ROMAN (NCT03689712) | Sponsor: Galera Therapeutics, Inc | P2 | N=160 | GRECO-2 (NCT04698915) | Sponsor: Galera Therapeutics | "Galera Therapeutics...today announced data from its Phase 3 ROMAN trial of avasopasem for severe oral mucositis...Results from the 455-patient Phase 3 trial demonstrated a meaningful reduction in patients’ SOM burden across multiple endpoints, with statistically significant reductions on the primary endpoint of incidence of SOM...Additionally, Galera’s Phase 2 GRECO-2 study of rucosopasem (GC4711) in combination with stereotactic body radiation therapy in pancreatic cancer will be presented at the ASCO Annual Meeting in a Trials in Progress poster session on Saturday, June 4, 2022, from 8:00 a.m. – 11:00 a.m. CDT. The primary endpoint of this trial is overall survival."

P2 data • P3 data • Gastrointestinal Cancer • Head and Neck Cancer • Mucositis • Oncology • Pancreatic Cancer

Galera Reports First Quarter 2022 Financial Results and Recent Corporate Updates (GlobeNewswire) - "A Trials in Progress abstract on GRECO-2 was accepted for presentation at the upcoming 2022 ASCO Annual Meeting; Enrollment is ongoing in the Phase 1/2 GRECO-1 trial of rucosopasem in combination with SBRT in patients with NSCLC. The Company expects to report initial data from this trial in the first half of 2022."

P1/2 data • Trial status • Gastrointestinal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor

Novel SOD mimetics GC4419 & GC4711 induce synergistic tumoricidal effects combined with radiotherapy in lung cancer models (AACR 2022) - "The radiotherapeutic effect can be vastly increased with superoxide dismutase mimetics, both within and outside the treatment field. Combination therapy requires screening of schedules regarding timing, drug dosage, and IR dose and fractionation to achieve optimal tumoricidal effects. SODm synergize with IR acting on various molecular targets that can be harnessed to overcome treatment resistance."

Preclinical • Gastrointestinal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor • CAT • TNFA • TP53BP1

Galera Reports Third Quarter 2021 Financial Results and Recent Corporate Updates (GlobeNewswire) - "Enrollment ongoing in GRECO-1 and GRECO-2 trials of rucosopasem (GC4711) in combination with SBRT in patients with NSCLC and pancreatic cancer; initial data from GRECO-1 expected in 1H 2022"

Enrollment status • P1/2 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer