Galera Therapeutics, Inc. · OTC:GRTX
Galera Therapeutics — Investor Presentation (November 2020)
41 slides from Galera Therapeutics's investor presentation, Nov 10, 2020
Slide 1: Transforming Radiotherapy with Dismutase Mimetics
Transforming Radiotherapy with Dismutase Mimetics November 2020 Exhibit 99.2
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 1 Delaney G, Jacob S, Featherstone C, Barton M. The role of radiotherapy in cancer treatment… Cancer. 2005;104:1129-1137 2 Begg AC, Stewart FA, Vens C. Strategies to improve radiotherapy with targeted drugs. Nat Rev Cancer. 2011;11:239-253 IMRT Intensity Modula
Slide 4: Clinical development pipeline
(1) EUSOM is a single-arm multi-center trial evaluating the safety of avasopasem in patients with HNC in Europe. (2) Phase 2a trial in patients with lung cancer building on avasopasem safety and tolerability findings from SOM trials in patients with HNC. (3) This first SBRT combination trial used GC
Slide 5: Investment Highlights
Investment Highlights Avasopasem GC4419 Reducing IMRT toxicity in patients with head & neck cancer Robust efficacy in randomized Phase 2b trial (n=223) Breakthrough therapy designation granted by FDA Single Phase 3 sufficient for registration (n450) 2nd Product GC4711 Increasing SBRT anti-cancer eff
Slide 6: Dismutase Technology
[Galera Dismutase Technology
Slide 7: Unique Technology: Dismutase Mimetics
O2 more damaging to normal cells than cancer cells Unique Technology Dismutase Mimetics Small Molecule Enzyme Mimetics Mimic human superoxide dismutase (SOD) enzymes Rapidly convert superoxide (O2) to hydrogen peroxide (H2O2) Shifts balance in normal & cancer cells from superoxide to hydrogen peroxi
Slide 8: Galera’s Dismutase Mimetics
Galera’s Dismutase Mimetics Native SOD Enzymes Native SOD Enzymes Overexpression reduces RT toxicity Large size, immunogenicity & short half-lives limit bioavailability Inactivation/inhibition by reactive oxygen species Small Molecule Mimetics Challenge: suitable small molecule dismutase mimetics Fa
Slide 9: Dismutase Mimetics Reduce Radiation Toxicities
Dismutase Mimetics Reduce Radiation Toxicities Thompson, et al., Free Radical Research, 44(5):529-540, 2010 Galera internal data Mice given GC4403 or placebo before lethal Total Body Irradiation (8.5 Gy) 100% of 40mg/kg GC4403 mice survived; 100% of control mice died Intestinal mucositis was main ca
Slide 10: Dismutase Mimetics Increase Anti-Cancer Efficacy with High Fraction-Dose RT in Preclinical Models
Dismutase Mimetics Increase Anti-Cancer Efficacy with High Fraction-Dose RT in Preclinical Models RT with Biological Equivalent Doses Days Post Treatment Days Post Treatment Days Post Treatment Days Post Treatment SBRT Stereotactic Body Radiation Therapy Courtesy of M Story (UTSW) Vehicle Increase R
Slide 11: Increasing Anti-Cancer Efficacy via H2O2
…Increasing Anti-Cancer Efficacy via H2O2 Sishc et al, AACR, 2018 Sishc, et al, AACR Pancreatic Cancer, 2019 Larger RT fraction à more O2 Dismutase Mimetics à more H2O2 • PANC-1 PDAC xenograft Genetically modified H1299CAT – with doxycycline-inducible catalase Tumor tissue H2O2 reduced when doxycycl
Slide 12: Reducing Toxicity of IMRT – Clinical Data
Reducing Toxicity of IMRT – Clinical Data (Intensity Modulated Radiotherapy)
Slide 13: GT-201: 223-Patient Randomized Phase 2b OM Trial
GT-201: 223-Patient Randomized Phase 2b OM Trial Supportive trial to the ROMAN Phase 3 for the NDA Anderson et al, JCO, 2019 Ulcers Requires a liquid diet Ulcers Unable to eat or drink Ulcers Able to eat a solid diet No ulcers Erythema and soreness 3 4 2 1 SEVERE WHO Grading Scale Randomize (1:1:1)
Slide 14: Consistent Efficacy Across All SOM Parameters
Consistent Efficacy Across All SOM Parameters And consistent dose response: 90mg > 30mg Primary endpoint was duration - defined as # days from 1st occurrence of grade 3 or 4 SOM until the 1st event of grade 2 or less (there being no subsequent grade 3 or 4 events.) *Secondary endpoints (incidence an
Slide 15: Safety Summary – Randomized Phase 2b Trial
Safety Summary – Rand. Phase 2b Trial Safety Profile of Both Avasopasem (GC4419) Doses Comparable to Placebo Avasopasem (GC4419) was well tolerated at both doses Most frequent AE’s are those expected with SoC cisplatin – RT regimen Most Frequent AEs (any grade) Placebo (n=72) 30 mg GC4419 (n=73) 90
Slide 16: GT-301: The ROMAN Trial – Phase 3 Confirmatory Trial
GT-301: The ROMAN Trial - Phase 3 Confirmatory Trial Enrolling Reduction in Oral Mucositis with Avasopasem Manganese (GC4419) Ulcers Requires a liquid diet Ulcers Unable to eat or drink Ulcers Able to eat a solid diet No ulcers Erythema and soreness 3 4 2 1 SEVERE WHO Grading Scale Randomize (3:2) G
Slide 17: Increasing SBRT Efficacy – Clinical Data
Increasing SBRT Efficacy – Clinical Data (Stereotactic Radiotherapy)
Slide 18: Pilot Phase 1/2 in Pancreatic Cancer: SBRT +/- GC4419
Pilot Phase 1/2 in Pancreatic Cancer: SBRT +/- GC4419 1LO-ET = Late-Onset Efficacy-Toxicity (Jin IH, Liu S, Thall PF, Yuan Y. J Am Stat Assoc 2014;109:525-36) SBRT = stereotactic body radiation therapy, LA = Locally-Advanced, BR = Borderline Resectable ORR = Overall Response Rate, LRC = Locoregional
Slide 19: Baseline Characteristics (n=42)
Baseline Characteristics (n=42) ECOG = Eastern Cooperative Oncology Group Performance Status Criteria CA 19-9 = Carbohydrate Antigen 19-9 is a tumor marker for pancreatic cancer Placebo (n=18) Avasopasem (n=24) Median age (range), yrs 68 (48–82) 72 (41–83) Male/Female 7/11 16/8 Borderline resectable
Slide 20: Safety – Grade 3+ Adverse Events
Safety – Grade 3+ Adverse Events (All Causes) AE = adverse event; GI = gastrointestinal . Placebo (n=18) Avasopasem (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 p
Slide 21: Best Response from Baseline Tumor in SBRT Field
Best Response from Baseline Tumor in SBRT Field (n=42) Waterfall plot through August 24, 2020; follow-up ongoing 1 Partial response per modified RECIST (Response Evaluation Criteria in Solid Tumors) SBRT + GC4419 NE SBRT + Placebo PR1 or better: 8 out of 24 patients on GC4419 (33%) PR1 or better: 3
Slide 22: Patients Who Underwent Resection Post SBRT
Patients Who Underwent Resection Post SBRT Surgical Decision Based on Multiple Factors (n=7) LA/BR = locally advanced or borderline resectable; pCR/pNR/pPR = pathological complete, near, or partial response; R0/R1 = resectable results: R0 = clear margins, R1 = positive microscopic margins; SBRT = st
Slide 23: SBRT + GC4419 Demonstrated Better Preliminary Outcomes Than SBRT + PBO
SBRT + GC4419 Demonstrated Better Preliminary Outcomes Than SBRT + PBO Data through August 24, 2020; follow-up ongoing Exhibited Better Local Control Exhibited Less Failures Inside & Outside RT Field Response within SBRT Field = % of patients with partial response or better per Modified RECIST; Succ
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) AVA = GC4419 or Avasopasem Note: Resected patients (n=7) censored at time of surgery for PFS (5 on GC4419 arm) Overall Survival (OS) Progression-Free Survival (PFS) Log Rank P value = 0.0643
Slide 25: Efficacy Endpoints in Patients Followed for >1 Year
Efficacy Endpoints in Patients Followed for >1 Year (n=19, ITT) HR = Hazard ratio; LRC = locoregional control; OS = overall survival, PFS = progression-free survival, TDM = time to distant metastases. Best Response Rate Medians (Weeks From SBRT) HR=0.4; P (log-rank): 0.068 HR=0.3; P (log-rank): 0.04
Slide 26: Encouraging Survival in Patients Followed for >1 Year
Encouraging Survival in Patients Followed for >1 Year Kaplan-Meier Analysis by Treatment (ITT, n=19) AVA = GC4419 or Avasopasem Log Rank P value = 0.0463, HR = 0.3 Log Rank P value = 0.078, HR = 0.4 Overall Survival (OS) Progression-Free Survival (PFS) N=19
Slide 27: Hazard Ratios on all Efficacy Endpoints 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 (95% Confidence Intervals) Initial Stage Pts (n=19) All Patients (n=42) Overall Survival (OS) 0.3 (0.09-1.05) 0.4 (0.12-1.11) Pro
Slide 28: Pancreatic Cancer Population in US
Pancreatic Cancer Population in US 1 2019 SEER Data 2Epidemiology of Pancreatic Cancer: Global Trends, Etiology and Risk Factors, Rawla P et al. World J Oncol. 2019 Feb; 10(1): 10–27 GRECO = Galera Radiotherapy Efficacy Cancer Optimization Metastatic Regional Local Not Known GRECO-2 Double-Blind Pla
Slide 29: GRECO-1 for Lung Cancer SBRT +/- GC4711
GRECO-1 for Lung Cancer SBRT +/- GC4711 *SBRT dose is 10-12 Gy x 5, determined by SBRT Planning. GRECO = Galera Radiotherapy Efficacy Cancer Optimization, NSCLC = Non-Small Cell Lung Cancer; ECOG PS = Eastern Cooperative Group Performance Status SBRT GC4711 Combo Trial Double-blind, Placebo-controll
Slide 30: Commercial Considerations
[Galera Commercial Considerations
Slide 31: Large Commercial Opportunity Addressing Clear Unmet Need
Large Commercial Opportunity Addressing Clear Unmet Need Severe Oral Mucositis & Esophagitis 1 Medicare Claims Analysis by Galera in 2019 2Hypothetical Product X for SOM with a similar profile to avasopasem Phase 2b results 3NCI or RTOG grading scales, 4Galera Market Research (150 Radiation Oncologi
Slide 32: Unmet Medical Need with Limited Treatment Options: Pancreatic Cancer
1 2019 SEER Data 2Epidemiology of Pancreatic Cancer: Global Trends, Etiology and Risk Factors, Rawla P et al. World J Oncol. 2019 Feb; 10(1): 10–27. 3Acta Oncologica, 2015; 54: 979–985 4Suker M., Beumer B.R., Sadot E., Marthey L., Faris J.E., Mellon E.A. The Lancet Oncology. 2016;17(6):801–810. 5NCC
Slide 33: GRECO-1 Trial: GC4711 + SBRT Combination in NSC Lung Cancer
GRECO-1 Trial: GC4711 + SBRT Combination in NSC Lung Cancer Globocan & US SEER Data* Decision Resources Group (DRG) Primary Market Research, Oct 2020 12,120 Central Tumor ≤ 3cm 15,430 Central Tumor > 3cm NSCLC Non-Small Cell Lung Cancer (NSCLC) Leading cause of cancer death in US – 142,670 deaths in
Slide 34: COVID-19 Trial
[Galera COVID-19 Trial
Slide 35: Superoxide Plays Important Role in Late Stages of COVID-19 Infection
Superoxide plays important role in Late Stages of COVID-19 Infection ARDS à Shock Building Cytokine Storm Superoxide plays an important role in the hyperinflammatory stage and in hypotensive sepsis/shock COVID-19 illness in native and immunosuppressed states: A clinical–therapeutic staging proposal
Slide 36: 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) SSC = Standard Supportive Care, SOFA = Sequential Organ Failure Assessment Salvemini, et al, Br J Pharmacology, 2001; Macarthur, et al, Crit Care Med, 2003; Cuzzoc
Slide 37: Appendix
[Galera Appendix
Slide 38: Oral Mucositis in HNC – Large Unmet Medical Need
Oral Mucositis in HNC – Large Unmet Medical Need SOM and Head & Neck Cancer Can Have Devastating Complications ~65,000 new HNC patients in US/Year ~65% get IMRT & cisplatin as standard-of-care ~70% of patients get SOM (can’t eat) ~20-30% get Grade 4 (can’t eat or drink) No approved drug available Tr
Slide 39: 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 Grade 4 Grade 3 90 mg GC4419 34% Less Incidence SOM 47% Less Grade 4 OM 92% Shorter Duration SOM Delayed Onset of SOM PLACEBO Arm (45 of 74 Pts had ≥1
Slide 40: Tumor Outcomes Maintained – 2-year Follow-up
Tumor Outcomes Maintained - 2 year follow-up Final ITT Analysis OS = Overall Survival, PFS = Progression-Free Survival, LRC = LocoRegional Control, DMF = Free of Distant Metastases
Slide 41: RT-related Mucositis Beyond Head and Neck Cancer
RT-related Mucositis Beyond Head and Neck Cancer 1Galera Market Research (150 Radiation Oncologists) 2 NCI or RTOG grading scales Market Research Question Patients with Other Conditions1 Given the demonstrated ability of Product X to prevent radiation-induced toxicities in the oral mucosa, please in
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