Galera Therapeutics, Inc. · OTC:GRTX
Galera Therapeutics — Investor Presentation (January 2021)
47 slides from Galera Therapeutics's investor presentation, Jan 6, 2021
Slide 1: Transforming Radiotherapy with Dismutase Mimetics
Exhibit 99.1 Transforming Radiotherapy Transforming Radiotherapy with with Dismutase Mimetics Dismutase Mimetics January 2021Exhibit 99.1 Transforming Radiotherapy Transforming Radiotherapy with with Dismutase Mimetics Dismutase Mimetics January 2021
Slide 2: Disclaimers and Forward-Looking Statements
Disclaimers and Forward-Looking Statements Certain information contained in this presentation and statements made orally during this presentation relates to or is based on studies, publications, surveys and other data obtained from third-party sources and Galera’s own internal estimates and research
Slide 3: Superoxide Dismutase Mimetics – Vision
Superoxide Dismutase Mimetics – Vision Rapid elimination of Over half of cancer patients Increase H O in tumors 2 2 Superoxide (O ) 2 receive radiotherapy IMRT SBRT 1, 2 as part of their care Intensity Modulated Stereotactic Body RT RT Potential to Reduce Toxicity Potential to Increase Efficacy Seve
Slide 4: Corporate Highlights
Corporate Highlights Phase 3 ROMAN Results with Avasopasem Reducing IMRT l Severe Oral Mucositis in Head & Neck Cancer Toxicity l Robust Phase 2b data à Breakthrough Therapy Designation Complete Survival Results from Pancreatic Cancer Pilot Increasing SBRT l 1-Year data on all patients from randomiz
Slide 5: Clinical Stage Pipeline
Clinical Stage Pipeline Phase 1 Phase 2 Phase 3 Next Anticipated Milestone 1a 1b 2a 2b ROMAN Topline Data Reducing SOM in Head & Neck Cancer avasopasem vs. placebo 2H 2021 RT Toxicity EUSOM Topline Data (1) SOM in Head & Neck Cancer avasopasem single-arm 2H 2021 IMRT AESOP Topline Data (2) Esophagit
Slide 6: Unique Technology Small Molecule Enzyme Mimetics
Unique Technology Small Molecule Enzyme Mimetics Dismutase l Mimic human superoxide dismutase (SOD) enzymes Mimetics l Rapidly convert superoxide (O ) to hydrogen peroxide (H O ) 2 2 2 Avasopasem (GC4419) O more damaging 2 GC4711 Shifts balance in normal & cancer cells to normal cells than from supe
Slide 7: Galera’s Dismutase Mimetics
Galera’s Dismutase Mimetics Native SOD Enzymes Native l Overexpression reduces RT toxicity SOD l Large size, immunogenicity & short half-lives limit bioavailability Enzymes l Inactivation/inhibition by reactive oxygen species Challenge: suitable small molecule dismutase mimetics Small l Fast catalyt
Slide 8: Reducing IMRT Toxicity (Intensity Modulated Radiotherapy)
Reducing IMRT Toxicity (Intensity Modulated Radiotherapy)Reducing IMRT Toxicity (Intensity Modulated Radiotherapy)
Slide 9: Reducing IMRT Toxicity – Large Unmet Medical Need
Reducing IMRT Toxicity – Large Unmet Medical Need Phase 1 Phase 2 Phase 3 Next Anticipated Milestone 1a 1b 2a 2b ROMAN Topline Data Reducing SOM in Head & Neck Cancer avasopasem vs. placebo 2H 2021 RT Toxicity EUSOM Topline Data (1) SOM in Head & Neck Cancer avasopasem single-arm 2H 2021 IMRT AESOP
Slide 10: Severe Oral Mucositis in HNC – Large Unmet Medical Need
SEVERE Severe Oral Mucositis in HNC – Large Unmet Medical Need Large Target Large Target Patient Patient Population Population (42K) (42K) SOM SOM Can Can Have Devastating Complications Have Devastating Complications Lack Lack of Efficacy with of Efficacy with Current Current Treatments Treatments M
Slide 11: GT-201: 223-Patient Randomized Phase 2b OM Trial
SEVERE GT-201: 223-Patient Randomized Phase 2b OM Trial Supportive trial to the ROMAN Phase 3 for the NDA Trial Design • Avasopasem (GC4419) 90mg, 30mg, or placebo WHO Grading Scale Treatment • 60 minute IV infusion, Mon-Fri. • Ending <60 mins pre-RT GC4419 90mg x 7 weeks 1 No ulcers • Patients with
Slide 12: Consistent Efficacy Across All SOM Parameters
Consistent Efficacy Across All SOM Parameters And consistent dose response: 90mg > 30mg INCIDENCE DURATION SEVERITY 34% Reduction through all RT 92% Reduction in median days of SOM 47% Reduction in Incidence of Grade 4 OM 90 mg vs. Placebo 90 mg vs. Placebo 90 mg vs. Placebo 70% 20 30% 18 60% 25% 16
Slide 13: Efficacy Parameters Better on 90mg arm Compared to Placebo
Efficacy Parameters Better on 90mg arm Compared to Placebo Swimmers plot: each patient who developed at least one SOM episode is represented by a row PLACEBO Arm (45 of 74 Pts had ≥1 visit with SOM) 90MG Avasopasem (GC4419) Arm (35 of 76 Pts had ≥1 visit with SOM) Radiotherapy Treatment Period Follo
Slide 14: Tumor Outcomes Maintained - 2 year follow-up
Tumor Outcomes Maintained - 2 year follow-up 100% 90% 91% 91% 91% 90% 89% 89% 87% 86% 85% 80% 77% 77% 76% 70% 60% 50% 40% 30% 20% 10% 0% Overall Survival (OS) Progression-Free Survival (PFS) Locoregional Control (LRC) Free of Distant Mets (DMF) PBO 30 mg 90 mg Final ITT Analysis 14 OS = Overall Surv
Slide 15: Safety Summary – Randomized Phase 2b Trial
Safety Summary – Randomized Phase 2b Trial Most frequent AE’s are those expected Safety Profile of Both Avasopasem (GC4419) Doses Comparable to Placebo with SoC cisplatin – RT regimen 30 mg 90 mg 100 Most Frequent Placebo GC4419 GC4419 99 AEs (any grade) (n=72) 97 97 90 95 95 (n=73) (n=72) 94 80 Lym
Slide 16: ROMAN: Phase 3 Confirmatory Trial Enrolling
SEVERE ROMAN: Phase 3 Confirmatory Trial Enrolling Reduction in Oral Mucositis with Avasopasem Manganese (GC4419) Trial Design (n 450 pts) WHO Grading Scale • Avasopasem (GC4419) 90mg or placebo Treatment • 60 minute IV infusion, Mon-Fri • Ending <60 mins pre-RT 1 No ulcers Erythema and soreness • P
Slide 17: RT-related Mucositis Beyond Head and Neck Cancer
RT-related Mucositis Beyond Head and Neck Cancer Radiotherapy-related Esophagitis in Lung Cancer Mucositis 1 l SOM efficacy seen by radiation oncologists as supportive for esophagitis of 2 l ~50,000 lung cancer patients are treated with RT, 50% get ≥ Grade 2 esophagitis Esophagus l Effects: inabilit
Slide 18: Large Commercial Opportunities Addressing Clear Unmet Needs
Large Commercial Opportunities Addressing Clear Unmet Needs Severe Oral Mucositis & Esophagitis Severe IMRT Centers SOM Targeted Esophagitis Oral Mucositis Have Infusion Common Salesforce in Head & Neck Capabilities and Costly in U.S. Lung Cancer Cancer 1 42k Patients 77% of Centers ~$32,000 ~40 Rep
Slide 19: Increasing SBRT Efficacy (Stereotactic Radiotherapy)
Increasing SBRT Efficacy (Stereotactic Radiotherapy)Increasing SBRT Efficacy (Stereotactic Radiotherapy)
Slide 20: Increasing SBRT Efficacy – Large Unmet Medical Need
Increasing SBRT Efficacy– Large Unmet Medical Need Phase 1 Phase 2 Phase 3 Next Anticipated Milestone 1a 1b 2a 2b LAPC Pilot 1 Year Follow-up (1) Pancreatic Cancer Increasing GC4419 vs. placebo 2H 2021 RT st GRECO-1 1 Stage Data (2) Efficacy NSC Lung Cancer GC4711 vs. placebo 1H 2022 GRECO-2 Initiat
Slide 21: Unmet Medical Need with Limited Treatment Options in Pancreatic Cancer
Unmet Medical Need with Limited Treatment Options in Pancreatic Cancer Locally Advanced Pancreatic Cancer (LAPC) Increasing Number of Pancreatic Cancer Patients Diagnosed Each Year Lethal 1,2 Common l The most lethal common cancer: 5-year survival 9-13% Cancer l Over 30% present with locally advance
Slide 22: Pilot Phase 1/2 in Pancreatic Cancer: SBRT +/- GC4419
Pilot Phase 1/2 in Pancreatic Cancer: SBRT +/- GC4419 Double-blind, Placebo-controlled, Randomized Trial SBRT l Patients with Locally Advanced Pancreatic Cancer (LAPC) post ~6 mos chemo GC4419 1 l Optimal SBRT fraction selected based on 90-day safety/efficacy (LO-ET ) Pilot l Tumor outcome measures:
Slide 23: GC4419 Demonstrated Improved Local Tumor Response in SBRT Field
GC4419 Demonstrated Improved Local Tumor Response in SBRT Field Waterfall plot of best response through August 24, 2020; follow-up ongoing (ITT, n=42) SBRT + GC4419 SBRT + Placebo 40% 30% 20% 10% NE R0 R0 R0 R1 0% R0 R0 R0 -10% -20% -30% 1 1 PR or better: 8 out of 24 patients on GC4419 (33%) PR or b
Slide 24: Encouraging Survival in All Patients
Encouraging Survival in All Patients (data as of Aug 24, 2020) Kaplan-Meier Analysis by Treatment (ITT, n=42) Overall Survival (OS) Progression-Free Survival (PFS) N=42 Log Rank P value = 0.0643, HR = 0.4 Log Rank P value = 0.29, HR = 0.6 Note: Resected patients (n=7) censored at time of surgery for
Slide 25: Favorable Efficacy Across Multiple Anti-Cancer Measures
Favorable Efficacy Across Multiple Anti-Cancer Measures in Patients Followed for >1 Year (ITT, n=19) Best Response Rate Medians (Weeks From SBRT) 60% 0 1020 3040 5060 54% 50% 40.4 OS HR=0.3; 1 P (log-rank): 0.046 Not Reached 40% 12.7 PFS 30% 29.3 HR=0.4; P (log-rank): 0.078 15.0 20% LRC HR=0.1; 1 P
Slide 26: Encouraging Survival Maintained in Patients Followed for >1 Year
Encouraging Survival Maintained in Patients Followed for >1 Year Kaplan-Meier Analysis by Treatment (ITT, n=19) Overall Survival (OS) Progression-Free Survival (PFS) N=19 Log Rank P value = 0.0463, HR = 0.3 Log Rank P value = 0.078, HR = 0.4 26 AVA = GC4419 or AvasopasemEncouraging Survival Maintain
Slide 27: Safety – Grade 3+ Adverse Events (All Causes)
Safety – Grade 3+ Adverse Events (All Causes) Placebo Avasopasem (n=18) (n=24) Acute Adverse Events (up to 90 days post SBRT) * Patients with acute Grade 3+ AEs 4 (22%) 6 (25%) ** Grade 3 acute GI toxicity 2 (11%) 2 (8%) Late Adverse Events (91 days–1 year post SBRT) Patients with late Grade 3+ AEs
Slide 28: GRECO-1: Ongoing Phase 1b/2 Trial in Locally Advanced NSCLC
GRECO-1: Ongoing Phase 1b/2 Trial in Locally Advanced NSCLC Double-blind, Placebo-controlled, Randomized Trial after Short Phase 1 SBRT st GC4711l NSCLC Locally Advanced – Previously untreated (1 line) Combo l Objectives: Safety (reducing Pneumonitis), ORR, LRC, DM, PFS, OS Trial l Stage 1 to access
Slide 29: GRECO-2: Initiating Randomized Phase 2b Trial in LAPC
GRECO-2: Initiating Randomized Phase 2b Trial in LAPC 5-Year Survival is ~10% 8% th 1/6 get attempted Not surgical resection 10% Known Annual new cases 1 460,000 Globally rd 2 1/3 get 57,000 in US Local chemotherapy upfront 9-13% 5-year Survival then some considered for SBRT Metastatic GRECO-2 Half
Slide 30: Corporate Highlights
Corporate Highlights Phase 3 ROMAN Results with Avasopasem Reducing IMRT l Severe Oral Mucositis in Head & Neck Cancer Toxicity l Robust Phase 2b data à Breakthrough Therapy Designation Complete Survival Results from Pancreatic Cancer Pilot Increasing SBRT l 1-Year data on all patients from randomiz
Slide 31: Appendix
APPENDIXAPPENDIX
Slide 32: Back-up Preclinical Slides
Back-up Preclinical SlidesBack-up Preclinical Slides
Slide 33: Dismutase Mimetics Reduce Radiation Toxicities
Dismutase Mimetics Reduce Radiation Toxicities Mice given GC4403 or placebo before lethal Total Body Irradiation (8.5 Gy) Lethal dose of Total Body Irradiation (8.5 Gy) to mice Reduce l 100% of 40mg/kg GC4403 mice survived; 100% of control mice died Radiation l 100% death on control, 100% survival w
Slide 34: Dismutase Mimetics Increase Anti-Cancer Efficacy with High Fraction-Dose RT
Dismutase Mimetics Increase Anti-Cancer Efficacy with High Fraction-Dose RT in Preclinical Models Focal irradiation of human tumor xenografts (H1299 NSCLC) in mice Increase l RT anti-cancer synergy of GC4419 increases with bigger RT fractions Radiotherapy l Bigger fraction à More Oà More H O Efficac
Slide 35: Increasing Anti-Cancer Efficacy via H2O2
Increasing Anti-Cancer Efficacy via H O 2 2 • Tumor tissue H O reduced when doxycycline Larger RT fraction à more O 2 2 2 Dismutase Mimetics à more H O added, losing the synergy 2 2 CAT Genetically modified H1299 – with doxycycline-inducible catalase PANC-1 PDAC xenograft Sishc et al, AACR, 2018 35
Slide 36: Dismutase Mimetics Also Enhance Immuno-Radiotherapy in Preclinical Models
Dismutase Mimetics Also Enhance Immuno-Radiotherapy in Preclinical Models SBRT + Checkpoint Inhibitor therapy of syngeneic tumors (LLC) in mice Increase IO + SBRT l GC4419 enhances tumor response to SBRT + anti-PD-L1, PD-1 or CTLA-4 Efficacy l Also appeared to reduce metastasis & increase response i
Slide 37: Back-up Pilot Phase 1/2 LAPC Trial Data
Back-up Pilot Phase 1/2 LAPC Trial DataBack-up Pilot Phase 1/2 LAPC Trial Data
Slide 38: Baseline Characteristics (n=42)
Baseline Characteristics (n=42) Placebo Avasopasem (n=18) (n=24) Median age (range), yrs 68 (48–82) 72 (41–83) Male/Female 7/11 16/8 Borderline resectable/Locally advanced 2/16 7/17 ECOG Performance status 0/1/2 9/9/0 12/11/1 Prior chemo, duration median (range), wks 21.9 (12.0–36.3) 17.9 (9.1–67.1)
Slide 39: SBRT + GC4419 Demonstrated Better Preliminary Outcomes Than SBRT + PBO
SBRT + GC4419 Demonstrated Better Preliminary Outcomes Than SBRT + PBO Exhibited Better Local Control Exhibited Less Failures Inside & Outside RT Field 44% 45% 40% 35% 33% 30% 25% 25% 21% 20% 17% 17% 15% 10% 8% 6% 5% 0% Response within SBRT Field Successful Surgery (R0) Failure within SBRT Field Fai
Slide 40: Patients Who Underwent Resection Post SBRT
Patients Who Underwent Resection Post SBRT Surgical Decision Based on Multiple Factors (n=7) Treatment Initial Tumor Staging Margins Post Resection Histopath Analysis SBRT Arm LA or BR R0/R1 Post Resection LA R0 pCR BR R0 pPR Avasopasem BR R0 pPR (n=5) BR R0 pPR LA R0 pPR BR R0 pPR Placebo (n=2) LA
Slide 41: Hazard Ratios on all Efficacy endpoints appear to favor GC4419 arm
Hazard Ratios on all Efficacy endpoints appear to favor GC4419 arm Comparison of Mature (n=19) and All Patients (n=42) – as of August 24, 2020 Comparison of Hazard Ratios Initial Stage Pts All Patients (95% Confidence Intervals) (n=19) (n=42) Overall Survival (OS) 0.3 0.4 (0.09-1.05) (0.12-1.11) Pro
Slide 42: COVID-19 Trial
COVID-19 TrialCOVID-19 Trial
Slide 43: Superoxide plays important role in Late Stages of COVID-19 Infection
Superoxide plays important role in Late Stages of COVID-19 Infection Building Cytokine Storm ARDS à Shock Superoxide plays an important role in the hyperinflammatory stage and in hypotensive sepsis/shock Classification of COVID-19 disease states and potential therapeutic targets. The figure illustra
Slide 44: Phase 2 Pilot Trial of Avasopasem in Patients with COVID-19
Phase 2 Pilot Trial of Avasopasem in Patients with COVID-19 Randomized Placebo-Controlled Trial in Patients with Critical Illness (n=50) Double-blind, Placebo-controlled, Randomized Trial GC4419 l Superoxide plays a central role in pathophysiology of acute respiratory distress syndrome (ARDS) For Ø
Slide 45: Backup Commercial Slides
Backup Commercial SlidesBackup Commercial Slides
Slide 46: 77% of the IMRT Centers Have the Ability to Infuse Today
77% of the IMRT Centers Have the Ability to Infuse Today Primary market research with 67 IMRT centers in the US 4677% of the IMRT Centers Have the Ability to Infuse Today Primary market research with 67 IMRT centers in the US 46
Slide 47: SBRT Commonly Used for Central and Peripheral NSCLC Tumors
SBRT Commonly Used for Central and Peripheral NSCLC Tumors Potential Opportunity for SBRT + GC4711 Non-Small Cell Lung Cancer (NSCLC) 2,500,000 NSCLC (World*) l Leading cause of cancer death in US – 142,670 deaths in 2019* NSCLC l SBRT commonly used for smaller peripheral tumors 175,000 l Lung toxic
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