UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549
FORM 8-K
CURRENT REPORT
Pursuant to Section 13 or 15(d)
of the Securities Exchange Act of 1934
Date of report (Date of earliest event reported): January 6, 2021
GALERA THERAPEUTICS, INC.
(Exact name of registrant as specified in its charter)
| Delaware | 001-39114 | 46-1454898 | ||
| (State or other jurisdiction of incorporation or organization) |
(Commission File Number) |
(I.R.S. Employer Identification No.) |
2 W Liberty Blvd #100
Malvern, PA 19355
(Address of principal executive offices) (Zip Code)
(610) 725-1500
(Registrant’s telephone number, include area code)
N/A
(Former Name or Former Address, if Changed Since Last Report)
Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions:
| ☐ | Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425) |
| ☐ | Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12) |
| ☐ | Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b)) |
| ☐ | Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c)) |
Securities registered pursuant to Section 12(b) of the Act:
| Title of each class |
Trading Symbol(s) |
Name of each exchange on which registered | ||
| Common Stock, $0.001 par value per share | GRTX | The Nasdaq Global Market |
Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§240.12b-2 of this chapter).
Emerging growth company ☒
If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. ☒
| Item 7.01. | Regulation FD Disclosure. |
Galera Therapeutics, Inc. (the “Company”) from time to time presents and/or distributes to the investment community at various industry and other conferences slide presentations to provide updates and summaries of its business. On January 6, 2021, the Company posted an updated corporate slide presentation in the “Investors” portion of its website at www.galeratx.com. A copy of its current corporate slide presentation is attached to this Current Report on Form 8-K as Exhibit 99.1. The Company undertakes no obligation to update, supplement or amend the materials attached hereto as Exhibit 99.1.
The information contained in Item 7.01 of this Form 8-K (including Exhibit 99.1 attached hereto) shall not be deemed “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended (the “Exchange Act”), or otherwise subject to the liabilities of that section, nor shall it be deemed incorporated by reference in any filing under the Securities Act of 1933, as amended, or the Exchange Act, except as expressly provided by specific reference in such a filing.
| Item 9.01. | Financial Statements and Exhibits. |
(d) Exhibits
The following exhibit relating to Item 7.01 shall be deemed to be furnished, and not filed:
| Exhibit |
Description | |
| 99.1 | Corporate Slide Presentation of Galera Therapeutics, Inc. dated January 6, 2021 | |
SIGNATURES
Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.
| GALERA THERAPEUTICS, INC. | ||||||
| Date: January 6, 2021 | By: | /s/ J. Mel Sorensen, M.D. | ||||
| J. Mel Sorensen, M.D. | ||||||
| President and Chief Executive Officer | ||||||
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
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. While Galera believes these third-party sources to be reliable as of the date of this presentation, it has not independently verified, and makes no representation as to the adequacy, fairness, accuracy or completeness of, any information obtained from third- party sources. While Galera believes its internal research is reliable, such research has not been verified by any independent source. This presentation contains “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. Forward-looking statements are neither historical facts nor assurances of future performance. Instead, they are based on our current beliefs, expectations and assumptions regarding the future of our business, future plans and strategies, our clinical results and other future conditions. All statements other than statements of historical facts contained in this presentation, including statements regarding future results of operations and financial position, business strategy, the safety, efficacy, regulatory and clinical progress, and therapeutic potential of current and prospective product candidates, plans and timing for the commencement of and the release of data from clinical trials, our plans to prepare for commercialization and a US launch, the anticipated direct and indirect impact of COVID-19 on Galera's business and operations, planned clinical trials and preclinical activities, potential product approvals and related commercial opportunity, current and prospective collaborations, and timing and likelihood of success, plans and objectives of management for future operations, are forward-looking statements. The words ”may,” “will,” “should,” “expect,” “plan,” “anticipate,” “could,” “intend,” “target,” “project,” “estimate,” “believe,” “predict,” “potential” or “continue” or the negative of these terms or other similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. The information in this presentation, including without limitation the forward-looking statements contained herein, represent our views as of the date of this presentation. Although we believe the expectations reflected in such forward-looking statements are reasonable, we can give no assurance that such expectations will prove to be correct. Accordingly, readers are cautioned not to place undue reliance on these forward-looking statements. Except as required by applicable law, we do not plan to publicly update or revise any forward-looking statements contained herein, whether as a result of any new information, future events, changed circumstances or otherwise. No representations or warranties (expressed or implied) are made about the accuracy of any such forward-looking statements. The forward-looking statements in this presentation involve risks and uncertainties that could cause actual results to differ materially from those reflected in such statements. Risks and uncertainties that may cause actual results to differ materially include uncertainties inherent in the drug development process and the regulatory approval process, our reliance on third parties over which we may not always have full control, and other important risks and uncertainties that are described in Galera’s Quarterly Report on Form 10-Q for the quarterly period ended September 30, 2020 filed with the U.S. Securities and Exchange Commission (SEC), Annual Report on Form 10-K for the year ended December 31, 2019 and Galera’s other filings with the SEC. New risk factors and uncertainties may emerge from time to time, and it is not possible to predict all risk factors and uncertainties. Whenever the Company uses the terms “transform radiotherapy” or “transforming radiotherapy” in this presentation, it is referring to its mission statement.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. While Galera believes these third-party sources to be reliable as of the date of this presentation, it has not independently verified, and makes no representation as to the adequacy, fairness, accuracy or completeness of, any information obtained from third- party sources. While Galera believes its internal research is reliable, such research has not been verified by any independent source. This presentation contains “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. Forward-looking statements are neither historical facts nor assurances of future performance. Instead, they are based on our current beliefs, expectations and assumptions regarding the future of our business, future plans and strategies, our clinical results and other future conditions. All statements other than statements of historical facts contained in this presentation, including statements regarding future results of operations and financial position, business strategy, the safety, efficacy, regulatory and clinical progress, and therapeutic potential of current and prospective product candidates, plans and timing for the commencement of and the release of data from clinical trials, our plans to prepare for commercialization and a US launch, the anticipated direct and indirect impact of COVID-19 on Galera's business and operations, planned clinical trials and preclinical activities, potential product approvals and related commercial opportunity, current and prospective collaborations, and timing and likelihood of success, plans and objectives of management for future operations, are forward-looking statements. The words ”may,” “will,” “should,” “expect,” “plan,” “anticipate,” “could,” “intend,” “target,” “project,” “estimate,” “believe,” “predict,” “potential” or “continue” or the negative of these terms or other similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. The information in this presentation, including without limitation the forward-looking statements contained herein, represent our views as of the date of this presentation. Although we believe the expectations reflected in such forward-looking statements are reasonable, we can give no assurance that such expectations will prove to be correct. Accordingly, readers are cautioned not to place undue reliance on these forward-looking statements. Except as required by applicable law, we do not plan to publicly update or revise any forward-looking statements contained herein, whether as a result of any new information, future events, changed circumstances or otherwise. No representations or warranties (expressed or implied) are made about the accuracy of any such forward-looking statements. The forward-looking statements in this presentation involve risks and uncertainties that could cause actual results to differ materially from those reflected in such statements. Risks and uncertainties that may cause actual results to differ materially include uncertainties inherent in the drug development process and the regulatory approval process, our reliance on third parties over which we may not always have full control, and other important risks and uncertainties that are described in Galera’s Quarterly Report on Form 10-Q for the quarterly period ended September 30, 2020 filed with the U.S. Securities and Exchange Commission (SEC), Annual Report on Form 10-K for the year ended December 31, 2019 and Galera’s other filings with the SEC. New risk factors and uncertainties may emerge from time to time, and it is not possible to predict all risk factors and uncertainties. Whenever the Company uses the terms “transform radiotherapy” or “transforming radiotherapy” in this presentation, it is referring to its mission statement.
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 Severe Oral Mucositis Esophagitis Pancreatic Cancer Lung Cancer Locally Advanced Head & Neck Cancer NSC Lung Cancer Locally Advanced Transforming Radiotherapy (SOM in HNC) (NSCLC) (LAPC) (LANSCLC) with Dismutase Mimetics Phase 3 Phase 2 Phase 2b Phase 1b/2 ROMAN AESOP GRECO-2 GRECO-1 Normal tissue toxicity limits Radiotherapy is SoC for many local tumors but need remains for greater efficacy optimal radiotherapy treatment of tumor 1 Delaney G, Jacob S, Featherstone C, Barton M. The role of radiotherapy in cancer treatment… Cancer. 2005;104:1129-1137 3 2 Begg AC, Stewart FA, Vens C. Strategies to improve radiotherapy with targeted drugs. Nat Rev Cancer. 2011;11:239-253Superoxide 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 Severe Oral Mucositis Esophagitis Pancreatic Cancer Lung Cancer Locally Advanced Head & Neck Cancer NSC Lung Cancer Locally Advanced Transforming Radiotherapy (SOM in HNC) (NSCLC) (LAPC) (LANSCLC) with Dismutase Mimetics Phase 3 Phase 2 Phase 2b Phase 1b/2 ROMAN AESOP GRECO-2 GRECO-1 Normal tissue toxicity limits Radiotherapy is SoC for many local tumors but need remains for greater efficacy optimal radiotherapy treatment of tumor 1 Delaney G, Jacob S, Featherstone C, Barton M. The role of radiotherapy in cancer treatment… Cancer. 2005;104:1129-1137 3 2 Begg AC, Stewart FA, Vens C. Strategies to improve radiotherapy with targeted drugs. Nat Rev Cancer. 2011;11:239-253
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 randomized LAPC trial Efficacy l Promising data from this trial was presented in 2020 Large Market Opportunities with High Unmet Medical Need ~40 reps for Planning the 4,000 radiation US l Building commercial team for US launch of avasopasem Launch oncologists in U.S. l US Target Patient Population of Lead Indication is 42,000 4Corporate 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 randomized LAPC trial Efficacy l Promising data from this trial was presented in 2020 Large Market Opportunities with High Unmet Medical Need ~40 reps for Planning the 4,000 radiation US l Building commercial team for US launch of avasopasem Launch oncologists in U.S. l US Target Patient Population of Lead Indication is 42,000 4
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) Esophagitis in NSCLC Combos avasopasem single-arm 1H 2022 LAPC Pilot 1 Year Follow-up (3) Pancreatic Cancer Increasing GC4419 vs. placebo 2H 2021 RT st GRECO-1 1 Stage Data (4) Efficacy NSC Lung Cancer GC4711 vs. placebo 1H 2022 SBRT GRECO-2 Initiate Trial Pancreatic Cancer GC4711 vs. placebo 1H 2021 Combos COVID Pilot Topline Data COVID-19 Critically Ill Patients avasopasem vs. placebo 1H 2021 (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 GC4419 (avasopasem). Observations from this pilot trial have been used to guide development of GC4711 to assess anti-cancer efficacy in combination with SBRT. 5 (4) Two stage trial with first stage to assess anti-cancer efficacy of SBRT +/- GC4711 and the second stage to assess anti-cancer efficacy of SBRT and checkpoint inhibitor +/- GC4711.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) Esophagitis in NSCLC Combos avasopasem single-arm 1H 2022 LAPC Pilot 1 Year Follow-up (3) Pancreatic Cancer Increasing GC4419 vs. placebo 2H 2021 RT st GRECO-1 1 Stage Data (4) Efficacy NSC Lung Cancer GC4711 vs. placebo 1H 2022 SBRT GRECO-2 Initiate Trial Pancreatic Cancer GC4711 vs. placebo 1H 2021 Combos COVID Pilot Topline Data COVID-19 Critically Ill Patients avasopasem vs. placebo 1H 2021 (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 GC4419 (avasopasem). Observations from this pilot trial have been used to guide development of GC4711 to assess anti-cancer efficacy in combination with SBRT. 5 (4) Two stage trial with first stage to assess anti-cancer efficacy of SBRT +/- GC4711 and the second stage to assess anti-cancer efficacy of SBRT and checkpoint inhibitor +/- GC4711.
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 superoxide to hydrogen peroxide cancer cells H O more toxic to 2 2 cancer cells than normal cells 6Unique 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 superoxide to hydrogen peroxide cancer cells H O more toxic to 2 2 cancer cells than normal cells 6
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 catalytic rates & high selectivity for superoxide Molecule l Firmly hold manganese in macrocyclic ring Mimetics l Stable, safe & suitable for manufacturing Dismutase Mimetics Core Structure Pentaaza Macrocycles Small Molecule Dismutase Mimetics with Attractive Drug Characteristics Speed Selectivity Stability Safety Synthesis Comparable to native SODs Interact with superoxide alone, Firmly hold Mn atom Well-tolerated Efficient & cost-effective 7 (2x10 molecules per sec) not other reactive oxygen species in macrocyclic ring preclinically and clinically manufacturing process 7Galera’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 catalytic rates & high selectivity for superoxide Molecule l Firmly hold manganese in macrocyclic ring Mimetics l Stable, safe & suitable for manufacturing Dismutase Mimetics Core Structure Pentaaza Macrocycles Small Molecule Dismutase Mimetics with Attractive Drug Characteristics Speed Selectivity Stability Safety Synthesis Comparable to native SODs Interact with superoxide alone, Firmly hold Mn atom Well-tolerated Efficient & cost-effective 7 (2x10 molecules per sec) not other reactive oxygen species in macrocyclic ring preclinically and clinically manufacturing process 7
Reducing IMRT Toxicity (Intensity Modulated Radiotherapy)Reducing IMRT Toxicity (Intensity Modulated Radiotherapy)
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 Topline Data (2) Esophagitis in NSCLC Combos avasopasem single-arm 1H 2022 US Target Patient Population Cancer Annual Target Subset Patients US Incidence Indication Market Head & Neck Severe Oral Locally 65,000 42,000 Cancer Mucositis Advanced Potential NSC Lung Central 175,000 Esophagitis 50,000 Cancer Tumors (1) EUSOM is a single-arm multi-center trial evaluating the safety of avasopasem in patients with HNC in Europe. 9 (2) Phase 2a trial in patients with lung cancer building on avasopasem safety and tolerability findings from SOM trials in patients with HNC.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 Topline Data (2) Esophagitis in NSCLC Combos avasopasem single-arm 1H 2022 US Target Patient Population Cancer Annual Target Subset Patients US Incidence Indication Market Head & Neck Severe Oral Locally 65,000 42,000 Cancer Mucositis Advanced Potential NSC Lung Central 175,000 Esophagitis 50,000 Cancer Tumors (1) EUSOM is a single-arm multi-center trial evaluating the safety of avasopasem in patients with HNC in Europe. 9 (2) Phase 2a trial in patients with lung cancer building on avasopasem safety and tolerability findings from SOM trials in patients with HNC.
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 MASCC / ISOO Guidelines for HNC OM WHO Grading Scale l Dehydration & 1 No ulcers Recommended for HNC l ~65,000 new HNC Erythema and soreness Treatment Approach Malnutrition 42,000 OM due to RT? patients in US/Year receive Often requiring PEG 2 Ulcers Basic oral care ✔ IMRT Able to eat a solid diet tube feeding l ~65% get IMRT & 3 Ulcers Anti-microbials, coating cisplatin as Requires a liquid diet l Pain agents, anesthetics, & standard-of-care ✔ Often severe pain analgesics (0.2% morphine 4 Ulcers Unable to eat or drink mouthwash) requiring opioids l ~70% of patients get Anti-inflammatories, SOM (can’t eat) ? benzydamine l Treatment interruption Each week of treatment delay l ~20-30% get Gr. 4 Low level laser & other ? decreases tumor control by >10% light therapy (can’t eat or drink) Cryotherapy for O l Increased economic burden l No approved drug 5-FU chemotherapy OM Dx à ~$32,000 in additional medical available Natural & other agents expenses in first 6 months from RT start O 10SEVERE 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 MASCC / ISOO Guidelines for HNC OM WHO Grading Scale l Dehydration & 1 No ulcers Recommended for HNC l ~65,000 new HNC Erythema and soreness Treatment Approach Malnutrition 42,000 OM due to RT? patients in US/Year receive Often requiring PEG 2 Ulcers Basic oral care ✔ IMRT Able to eat a solid diet tube feeding l ~65% get IMRT & 3 Ulcers Anti-microbials, coating cisplatin as Requires a liquid diet l Pain agents, anesthetics, & standard-of-care ✔ Often severe pain analgesics (0.2% morphine 4 Ulcers Unable to eat or drink mouthwash) requiring opioids l ~70% of patients get Anti-inflammatories, SOM (can’t eat) ? benzydamine l Treatment interruption Each week of treatment delay l ~20-30% get Gr. 4 Low level laser & other ? decreases tumor control by >10% light therapy (can’t eat or drink) Cryotherapy for O l Increased economic burden l No approved drug 5-FU chemotherapy OM Dx à ~$32,000 in additional medical available Natural & other agents expenses in first 6 months from RT start O 10
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 HNC Erythema and soreness Population • Locally advanced, squamous cell • Eligible for SoC – 7 weeks IMRT + cisplatin 2 Ulcers Stratification • Tumor HPV Status: positive or negative Able to eat a solid diet Factors • Cisplatin Schedule: q3wks or weekly GC4419 30mg x 7 weeks • Primary – Reduction in median duration of SOM 3 Ulcers – WHO Grades 3 & 4 Requires a liquid diet • Secondary – Reduction in incidence and Endpoints severity of SOM at pre-specified timepoints 4 Ulcers • Exploratory – Time to SOM onset Placebo x 7 weeks Unable to eat or drink • Tumor outcomes (2 year follow-up) • Locoregional control, distant mets, PFS, OS Anderson et al, JCO, 2019 11 Randomize (1:1:1)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 HNC Erythema and soreness Population • Locally advanced, squamous cell • Eligible for SoC – 7 weeks IMRT + cisplatin 2 Ulcers Stratification • Tumor HPV Status: positive or negative Able to eat a solid diet Factors • Cisplatin Schedule: q3wks or weekly GC4419 30mg x 7 weeks • Primary – Reduction in median duration of SOM 3 Ulcers – WHO Grades 3 & 4 Requires a liquid diet • Secondary – Reduction in incidence and Endpoints severity of SOM at pre-specified timepoints 4 Ulcers • Exploratory – Time to SOM onset Placebo x 7 weeks Unable to eat or drink • Tumor outcomes (2 year follow-up) • Locoregional control, distant mets, PFS, OS Anderson et al, JCO, 2019 11 Randomize (1:1:1)
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 50% 14 p=0.009* 20% 12 40% p=0.045* 10 15% 30% 8 10% 6 20% 4 5% 10% p=0.024 2 0% 0 0% Placebo 30mg 90mg Placebo 30mg 90mg Placebo 30mg 90mg st st Primary endpoint was duration - defined as # days from 1 occurrence of grade 3 or 4 SOM until the 1 event of grade 2 or less (there being no subsequent grade 3 or 4 events.) 12 *Secondary endpoints (incidence and severity ) have nominal p values compared to placebo ITT = Intent-To-Treat population (n=223) 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 50% 14 p=0.009* 20% 12 40% p=0.045* 10 15% 30% 8 10% 6 20% 4 5% 10% p=0.024 2 0% 0 0% Placebo 30mg 90mg Placebo 30mg 90mg Placebo 30mg 90mg st st Primary endpoint was duration - defined as # days from 1 occurrence of grade 3 or 4 SOM until the 1 event of grade 2 or less (there being no subsequent grade 3 or 4 events.) 12 *Secondary endpoints (incidence and severity ) have nominal p values compared to placebo ITT = Intent-To-Treat population (n=223)
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 Follow‐up Post Radiotherapy Radiotherapy Treatment Period Follow‐up Post Radiotherapy 90 mg GC4419 Grade 3 • 34% Less Incidence SOM Grade 4 • 47% Less Grade 4 OM • 92% Shorter Duration SOM • Delayed Onset of SOM 13Efficacy 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 Follow‐up Post Radiotherapy Radiotherapy Treatment Period Follow‐up Post Radiotherapy 90 mg GC4419 Grade 3 • 34% Less Incidence SOM Grade 4 • 47% Less Grade 4 OM • 92% Shorter Duration SOM • Delayed Onset of SOM 13
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 Survival, PFS = Progression-Free Survival, LRC = LocoRegional Control, DMF = Free of Distant MetastasesTumor 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 Survival, PFS = Progression-Free Survival, LRC = LocoRegional Control, DMF = Free of Distant Metastases
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 Lymphopenia 89% 92% 88% 70 Nausea 75% 68% 82% 60 % Fatigue 69% 60% 65% 50 50 Oropharyngeal pain 64% 63% 61% 40 45 45 Constipation 53% 59% 64% 30 Radiation skin injury 47% 51% 53% 20 Vomiting 47% 52% 49% 10 1 1 1 0 Dysgeusia (taste) 49% 55% 43% Grade 2 or worse Grade 3 or worse Grade 4 or 5 Grade 5 (fatal) Dysphagia 43% 42% 47% Placebo (n=72) 30 mg GC4419 (n=73) 90 mg GC4419 (n=72) Weight decreased 35% 40% 44% Oral candidiasis 29% 45% 43% Leukopenia 39% 37% 39% Avasopasem (GC4419) was well tolerated at both doses 15 Anderson et al, J Clin Oncol 2019 Dec 1; 37(34):3256-3265Safety 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 Lymphopenia 89% 92% 88% 70 Nausea 75% 68% 82% 60 % Fatigue 69% 60% 65% 50 50 Oropharyngeal pain 64% 63% 61% 40 45 45 Constipation 53% 59% 64% 30 Radiation skin injury 47% 51% 53% 20 Vomiting 47% 52% 49% 10 1 1 1 0 Dysgeusia (taste) 49% 55% 43% Grade 2 or worse Grade 3 or worse Grade 4 or 5 Grade 5 (fatal) Dysphagia 43% 42% 47% Placebo (n=72) 30 mg GC4419 (n=73) 90 mg GC4419 (n=72) Weight decreased 35% 40% 44% Oral candidiasis 29% 45% 43% Leukopenia 39% 37% 39% Avasopasem (GC4419) was well tolerated at both doses 15 Anderson et al, J Clin Oncol 2019 Dec 1; 37(34):3256-3265
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 • Patients with Head & Neck Cancer Population • Locally advanced, squamous cell GC4419 90mg x 7 weeks • Eligible for SoC – 7 weeks IMRT + cisplatin 2 Ulcers Able to eat a solid diet Stratification • Surgery Status: post-op or definitive Factors • Cisplatin Schedule: q3wks or weekly 3 Ulcers Requires a liquid diet Placebo x 7 weeks • Primary – Reduction in incidence of SOM – WHO Grades 3 & 4 4 Ulcers Endpoints • Secondary – Reductions in severity of SOM Unable to eat or drink and number of days of SOM experienced 1 • Tumor outcomes – LRC, DM-free, PFS, OS 1 LRC = locoregional control, DM-free = free of distant mets, PFS = Progression-Free Survival, OS = Overall Survival 16 Randomize (3:2)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 • Patients with Head & Neck Cancer Population • Locally advanced, squamous cell GC4419 90mg x 7 weeks • Eligible for SoC – 7 weeks IMRT + cisplatin 2 Ulcers Able to eat a solid diet Stratification • Surgery Status: post-op or definitive Factors • Cisplatin Schedule: q3wks or weekly 3 Ulcers Requires a liquid diet Placebo x 7 weeks • Primary – Reduction in incidence of SOM – WHO Grades 3 & 4 4 Ulcers Endpoints • Secondary – Reductions in severity of SOM Unable to eat or drink and number of days of SOM experienced 1 • Tumor outcomes – LRC, DM-free, PFS, OS 1 LRC = locoregional control, DM-free = free of distant mets, PFS = Progression-Free Survival, OS = Overall Survival 16 Randomize (3:2)
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: inability to swallow, severe pain, ulceration, bleeding & hospitalization AESOP: Phase 2 to support Compendial Listing post-Approval for SOM Compendiall Single-arm Phase 2a trial in 60 patients w/ locally advanced lung cancers Listing l Standard IMRT to ≥ 5 cm of esophagus (30 fractions, 2Gy/day x5 for 6 weeks) l Post approval for SOM in HNC, plan to seek compendial listing in U.S. Market Research Question 1 Patients with Other Conditions Given the demonstrated ability of Product X to prevent radiation-induced toxicities in the oral mucosa, please indicate how you might use (maximum %) Product X for the following radiation associated conditions? 1 Galera Market Research (150 Radiation Oncologists) 17 2 NCI or RTOG grading scalesRT-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: inability to swallow, severe pain, ulceration, bleeding & hospitalization AESOP: Phase 2 to support Compendial Listing post-Approval for SOM Compendiall Single-arm Phase 2a trial in 60 patients w/ locally advanced lung cancers Listing l Standard IMRT to ≥ 5 cm of esophagus (30 fractions, 2Gy/day x5 for 6 weeks) l Post approval for SOM in HNC, plan to seek compendial listing in U.S. Market Research Question 1 Patients with Other Conditions Given the demonstrated ability of Product X to prevent radiation-induced toxicities in the oral mucosa, please indicate how you might use (maximum %) Product X for the following radiation associated conditions? 1 Galera Market Research (150 Radiation Oncologists) 17 2 NCI or RTOG grading scales
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 Reps 50k Patients Radiation oncologists 37% IMRT centers Patients with OM incur Focused commercial 50% IMRT Patients get ≥ 3 report severe oral currently infuse drugs ~$32,000 more in infrastructure Grade 2 esophagitis mucositis is most medical expenses burdensome side effect of Additional 40% coordinate in first 6 months ~2,500 RT sites in US SOM efficacy seen by HNC RT treatment with medical oncology to from start of RT radiation oncologists as ~60% of patients are 2 4 infuse patients treated in ~500 centers supportive for esophagitis Current approaches inadequate – while frequently used, only 1 in 5 believe they are useful 1 2 3 Primary market research with 67 IMRT centers in the US Medicare Claims Analysis by Galera in 2019 NCI or RTOG grading scales, 18 4 Galera Market Research (150 Radiation Oncologists), SOM = Severe Oral MucositisLarge 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 Reps 50k Patients Radiation oncologists 37% IMRT centers Patients with OM incur Focused commercial 50% IMRT Patients get ≥ 3 report severe oral currently infuse drugs ~$32,000 more in infrastructure Grade 2 esophagitis mucositis is most medical expenses burdensome side effect of Additional 40% coordinate in first 6 months ~2,500 RT sites in US SOM efficacy seen by HNC RT treatment with medical oncology to from start of RT radiation oncologists as ~60% of patients are 2 4 infuse patients treated in ~500 centers supportive for esophagitis Current approaches inadequate – while frequently used, only 1 in 5 believe they are useful 1 2 3 Primary market research with 67 IMRT centers in the US Medicare Claims Analysis by Galera in 2019 NCI or RTOG grading scales, 18 4 Galera Market Research (150 Radiation Oncologists), SOM = Severe Oral Mucositis
Increasing SBRT Efficacy (Stereotactic Radiotherapy)Increasing SBRT Efficacy (Stereotactic Radiotherapy)
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 Initiate Trial SBRT Pancreatic Cancer GC4711 vs. placebo 1H 2021 Combos US Target Patient Population Cancer Annual Subset Patients US Incidence Market Pancreatic Locally-Advanced 57,000 18,000 Potential Cancer LAPC NSC Lung Central Tumors or 175,000 42,000 Cancer Peripheral >3cm 1 This first SBRT combination trial used GC4419 (avasopasem). Observations from this pilot trial have been used to guide development of GC4711 to assess anti-cancer efficacy in combination with SBRT 20 2 Two stage trial with first stage to assess anti-cancer efficacy of SBRT +/- GC4711 and the second stage to assess anti-cancer efficacy of SBRT and checkpoint inhibitor +/- GC471Increasing 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 Initiate Trial SBRT Pancreatic Cancer GC4711 vs. placebo 1H 2021 Combos US Target Patient Population Cancer Annual Subset Patients US Incidence Market Pancreatic Locally-Advanced 57,000 18,000 Potential Cancer LAPC NSC Lung Central Tumors or 175,000 42,000 Cancer Peripheral >3cm 1 This first SBRT combination trial used GC4419 (avasopasem). Observations from this pilot trial have been used to guide development of GC4711 to assess anti-cancer efficacy in combination with SBRT 20 2 Two stage trial with first stage to assess anti-cancer efficacy of SBRT +/- GC4711 and the second stage to assess anti-cancer efficacy of SBRT and checkpoint inhibitor +/- GC471
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 advanced unresectable or borderline resectable 2 First Line Treatment is Induction Chemotherapy for Over 80% of Patients Novel 3 Therapies l 60% of patients fail induction therapy within 12 months Needed 3 l 60% on FOLFIRINOX develop Grade 3-5 toxicity 4 SBRT Use is increasingly used for locoregional control (by NCCN and others) SBRT is st nd Accepted l 1 or 2 line option after 4-5 months of chemotherapy for locally advanced cancer Tx Option l For some patients with metastatic disease for palliative control of local disease 1 2 2019 SEER Data Epidemiology of Pancreatic Cancer: Global Trends, Etiology and Risk Factors, Rawla P et al. World J Oncol. 2019 Feb; 10(1): 10–27. 3 4 Suker M., Beumer B.R., Sadot E., Marthey L., Faris J.E., Mellon E.A. The Lancet Oncology. 2016;17(6):801–810. NCCN = National Comprehensive Cancer Network-2019 21Unmet 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 advanced unresectable or borderline resectable 2 First Line Treatment is Induction Chemotherapy for Over 80% of Patients Novel 3 Therapies l 60% of patients fail induction therapy within 12 months Needed 3 l 60% on FOLFIRINOX develop Grade 3-5 toxicity 4 SBRT Use is increasingly used for locoregional control (by NCCN and others) SBRT is st nd Accepted l 1 or 2 line option after 4-5 months of chemotherapy for locally advanced cancer Tx Option l For some patients with metastatic disease for palliative control of local disease 1 2 2019 SEER Data Epidemiology of Pancreatic Cancer: Global Trends, Etiology and Risk Factors, Rawla P et al. World J Oncol. 2019 Feb; 10(1): 10–27. 3 4 Suker M., Beumer B.R., Sadot E., Marthey L., Faris J.E., Mellon E.A. The Lancet Oncology. 2016;17(6):801–810. NCCN = National Comprehensive Cancer Network-2019 21
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: ORR, LRC, DM, Resectability, PFS, OS Single-center Stage Multicenter Stage Total SBRT + Placebo x 5 doses N=8 N=10 N=18 Surgical Inoperable LA or BR 2018–2019 2020 (Jan–June) Evaluation Pancreatic Cancer 90 90 90 90 90 Limited to Included R GC4419 Resection LA/unresectable borderline resectable after ~6 months SBRT If possible of induction Chemo N=24 SBRT + GC4419 x 5 doses N=11 N=13 GC4419 90mg IV over 60min >1 Year 3–6 Months Follow-Up Follow-Up 1 LO-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 22 ORR = Overall Response Rate, LRC = Locoregional Failure, DM = Distant Metastases, PFS = Progression-Free Survival, OS = Overall SurvivalPilot 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: ORR, LRC, DM, Resectability, PFS, OS Single-center Stage Multicenter Stage Total SBRT + Placebo x 5 doses N=8 N=10 N=18 Surgical Inoperable LA or BR 2018–2019 2020 (Jan–June) Evaluation Pancreatic Cancer 90 90 90 90 90 Limited to Included R GC4419 Resection LA/unresectable borderline resectable after ~6 months SBRT If possible of induction Chemo N=24 SBRT + GC4419 x 5 doses N=11 N=13 GC4419 90mg IV over 60min >1 Year 3–6 Months Follow-Up Follow-Up 1 LO-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 22 ORR = Overall Response Rate, LRC = Locoregional Failure, DM = Distant Metastases, PFS = Progression-Free Survival, OS = Overall Survival
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 better: 3 out of 18 patients on placebo (17%) -40% -50% -60% = Surgical resection (R0 = clear margins). = Surgical resection (R1 = tumor at margins). NE = not evaluable. RO R1 1 Partial response per modified RECIST (Response Evaluation Criteria in Solid Tumors) 23GC4419 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 better: 3 out of 18 patients on placebo (17%) -40% -50% -60% = Surgical resection (R0 = clear margins). = Surgical resection (R1 = tumor at margins). NE = not evaluable. RO R1 1 Partial response per modified RECIST (Response Evaluation Criteria in Solid Tumors) 23
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 PFS (5 on GC4419 arm) 24 AVA = GC4419 or AvasopasemEncouraging 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 PFS (5 on GC4419 arm) 24 AVA = GC4419 or Avasopasem
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 (log-rank): 0.051 Not Reached 13% 10% 12.7 TDM 34.7 HR=0.4; P (log-rank): 0.068 0% Avasopasem Placebo Placebo (n=8) Avasopasem (n=11) 25 HR = Hazard ratio; LRC = locoregional control; OS = overall survival, PFS = progression-free survival, TDM = time to distant metastases.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 (log-rank): 0.051 Not Reached 13% 10% 12.7 TDM 34.7 HR=0.4; P (log-rank): 0.068 0% Avasopasem Placebo Placebo (n=8) Avasopasem (n=11) 25 HR = Hazard ratio; LRC = locoregional control; OS = overall survival, PFS = progression-free survival, TDM = time to distant metastases.
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 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 Avasopasem
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 5 (28%) 7 (29%) *Only 1 patient > Gr. 3 (aspiration pneumonia, hypoxia & atrial fibrillation, resolved with supplemental O , antibiotics & beta blocker) 2 **No bleeding ulcers by 12-week endoscopy, no GI toxicity > Grade 3 AE = adverse event; GI = gastrointestinal 27 .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 5 (28%) 7 (29%) *Only 1 patient > Gr. 3 (aspiration pneumonia, hypoxia & atrial fibrillation, resolved with supplemental O , antibiotics & beta blocker) 2 **No bleeding ulcers by 12-week endoscopy, no GI toxicity > Grade 3 AE = adverse event; GI = gastrointestinal 27 .
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 SBRT +/- GC4711; Stage 2 SBRT + Checkpoint Inhibitor +/- GC4711 st 1 Stage: Randomized Phase 2 (n 66 pts) Phase 1 (n=5 pts) SBRT + Placebo x 5 1st–line NSCLC 30 Day 100 100 100 100 100 100 100 100 100 100 Safety Centrally located GC4711 GC4711 R SRC or Large Tumors SBRT SBRT Review ECOG PS 0-3 SBRT + GC4711 x 5 SBRT + GC4711 x 5 GC4711 100 mg IV in 15min GC4711 100 mg IV in 15min SBRT 10-12 Gy* x 5 SBRT 10-12 Gy* x 5 *SBRT dose is 10-12 Gy x 5, determined by SBRT Planning. 28 GRECO = Galera Radiotherapy Efficacy Cancer Optimization, NSCLC = Non-Small Cell Lung Cancer; ECOG PS = Eastern Cooperative Group Performance StatusGRECO-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 SBRT +/- GC4711; Stage 2 SBRT + Checkpoint Inhibitor +/- GC4711 st 1 Stage: Randomized Phase 2 (n 66 pts) Phase 1 (n=5 pts) SBRT + Placebo x 5 1st–line NSCLC 30 Day 100 100 100 100 100 100 100 100 100 100 Safety Centrally located GC4711 GC4711 R SRC or Large Tumors SBRT SBRT Review ECOG PS 0-3 SBRT + GC4711 x 5 SBRT + GC4711 x 5 GC4711 100 mg IV in 15min GC4711 100 mg IV in 15min SBRT 10-12 Gy* x 5 SBRT 10-12 Gy* x 5 *SBRT dose is 10-12 Gy x 5, determined by SBRT Planning. 28 GRECO = Galera Radiotherapy Efficacy Cancer Optimization, NSCLC = Non-Small Cell Lung Cancer; ECOG PS = Eastern Cooperative Group Performance Status
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 at diagnosis are Double-Blind 52% Regional beyond locoregional Placebo-controlled control and receive Randomized chemotherapy, with Phase 2b trial (SBRT +/- GC4711) some getting RT as 29% palliation to primary 1 2 2019 SEER Data Epidemiology of Pancreatic Cancer: Global Trends, Etiology and Risk Factors, Rawla P et al. World J Oncol. 2019 Feb; 10(1): 10–27 29 GRECO = Galera Radiotherapy Efficacy Cancer OptimizationGRECO-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 at diagnosis are Double-Blind 52% Regional beyond locoregional Placebo-controlled control and receive Randomized chemotherapy, with Phase 2b trial (SBRT +/- GC4711) some getting RT as 29% palliation to primary 1 2 2019 SEER Data Epidemiology of Pancreatic Cancer: Global Trends, Etiology and Risk Factors, Rawla P et al. World J Oncol. 2019 Feb; 10(1): 10–27 29 GRECO = Galera Radiotherapy Efficacy Cancer Optimization
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 randomized LAPC trial Efficacy l Promising data from this trial was presented in 2020 Large Market Opportunities with High Unmet Medical Need ~40 reps for Planning the 4,000 radiation US l Building commercial team for US launch of avasopasem Launch oncologists in U.S. l US Target Patient Population of Lead Indication is 42,000 30Corporate 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 randomized LAPC trial Efficacy l Promising data from this trial was presented in 2020 Large Market Opportunities with High Unmet Medical Need ~40 reps for Planning the 4,000 radiation US l Building commercial team for US launch of avasopasem Launch oncologists in U.S. l US Target Patient Population of Lead Indication is 42,000 30
APPENDIXAPPENDIX
Back-up Preclinical SlidesBack-up Preclinical Slides
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 with 40mg/kg l Intestinal mucositis was main cause of death Mucositis l Main cause of death was intestinal mucositis Thompson, et al., Free Radical Research, 44(5):529-540, 2010 33 Galera internal dataDismutase 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 with 40mg/kg l Intestinal mucositis was main cause of death Mucositis l Main cause of death was intestinal mucositis Thompson, et al., Free Radical Research, 44(5):529-540, 2010 33 Galera internal data
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 Efficacy 2 2 2 l Also demonstrated with human pancreatic cancer xenografts RT with Biological Equivalent Doses Vehicle Days Post Treatment Days Post Treatment Days Post Treatment Days Post Treatment SBRT 34 Courtesy of M Story (UTSW) Stereotactic Body Radiation TherapyDismutase 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 Efficacy 2 2 2 l Also demonstrated with human pancreatic cancer xenografts RT with Biological Equivalent Doses Vehicle Days Post Treatment Days Post Treatment Days Post Treatment Days Post Treatment SBRT 34 Courtesy of M Story (UTSW) Stereotactic Body Radiation Therapy
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 Sishc, et al, AACR Pancreatic Cancer, 2019Increasing 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 Sishc, et al, AACR Pancreatic Cancer, 2019
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 in unirradiated secondary tumors 2000 1500 1000 500 0 010 20 30 40 Days 36 Courtesy of M Story (UTSW) 3 Mean Tumor Vol. (mm )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 in unirradiated secondary tumors 2000 1500 1000 500 0 010 20 30 40 Days 36 Courtesy of M Story (UTSW) 3 Mean Tumor Vol. (mm )
Back-up Pilot Phase 1/2 LAPC Trial DataBack-up Pilot Phase 1/2 LAPC Trial Data
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) CA19-9 at randomization, median (range) 26.25 (0.5–2186) 28.5 (0.3–70) Smokers/Nonsmokers 3/15 2/22 ECOG = Eastern Cooperative Oncology Group Performance Status Criteria 38 CA 19-9 = Carbohydrate Antigen 19-9 is a tumor marker for pancreatic cancerBaseline 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) CA19-9 at randomization, median (range) 26.25 (0.5–2186) 28.5 (0.3–70) Smokers/Nonsmokers 3/15 2/22 ECOG = Eastern Cooperative Oncology Group Performance Status Criteria 38 CA 19-9 = Carbohydrate Antigen 19-9 is a tumor marker for pancreatic cancer
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 Failure outside SBRT Field Placebo (n=18) Avasopasem (n=24) Data through August 24, 2020; follow-up ongoing 39 Response within SBRT Field = % of patients with partial response or better per Modified RECIST; Successful Surgery = % of patients with R0 margins post resection Failure within SBRT Field = % of patients with locoregional failure; Failure outside SBRT Field = % of patients with distant metastasesSBRT + 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 Failure outside SBRT Field Placebo (n=18) Avasopasem (n=24) Data through August 24, 2020; follow-up ongoing 39 Response within SBRT Field = % of patients with partial response or better per Modified RECIST; Successful Surgery = % of patients with R0 margins post resection Failure within SBRT Field = % of patients with locoregional failure; Failure outside SBRT Field = % of patients with distant metastases
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 R1 pNR • No significant perioperative complications after SBRT for all 7 patients LA/BR = locally advanced or borderline resectable; pCR/pNR/pPR = pathological complete, near, or partial response; 40 R0/R1 = resectable results: R0 = clear margins, R1 = positive microscopic margins; SBRT = stereotactic body radiation therapy 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 R1 pNR • No significant perioperative complications after SBRT for all 7 patients LA/BR = locally advanced or borderline resectable; pCR/pNR/pPR = pathological complete, near, or partial response; 40 R0/R1 = resectable results: R0 = clear margins, R1 = positive microscopic margins; SBRT = stereotactic body radiation therapy
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) Progression-Free Survival (PFS) 0.4 0.6 (0.15-1.14) (0.23-1.56) Loco-Regional Control (LRC) 0.1 0.2 (0.01-1.37) (0.02-2.22) Time to Distant Mets (TDM) 0.4 0.4 (0.11-1.13) (0.13-1.29) 41Hazard 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) Progression-Free Survival (PFS) 0.4 0.6 (0.15-1.14) (0.23-1.56) Loco-Regional Control (LRC) 0.1 0.2 (0.01-1.37) (0.02-2.22) Time to Distant Mets (TDM) 0.4 0.4 (0.11-1.13) (0.13-1.29) 41
COVID-19 TrialCOVID-19 Trial
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 illustrates 3 escalating phases of COVID-19 disease progression, with associated signs, symptoms, and potential phase-specific therapies. ARDS, acute respiratory distress syndrome; CRP, C-reactive protein; JAK, janus kinase; LDH, lactate dehydrogenase; NT-proBNP, N- terminal pro B-type natriuretic peptide; SIRS, systemic inflammatory response syndrome; GM-CSF, Granulocyte Macrophage Colony Stimulating Factor. COVID-19 illness in native and immunosuppressed states: A clinical–therapeutic staging proposal 43 Hasan K. Siddiqi, MD, MSCR, Mandeep R. Mehra, MD, MSc Published:March 20, 2020 DOI:https://doi.org/10.1016/j.healun.2020.03.012Superoxide 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 illustrates 3 escalating phases of COVID-19 disease progression, with associated signs, symptoms, and potential phase-specific therapies. ARDS, acute respiratory distress syndrome; CRP, C-reactive protein; JAK, janus kinase; LDH, lactate dehydrogenase; NT-proBNP, N- terminal pro B-type natriuretic peptide; SIRS, systemic inflammatory response syndrome; GM-CSF, Granulocyte Macrophage Colony Stimulating Factor. COVID-19 illness in native and immunosuppressed states: A clinical–therapeutic staging proposal 43 Hasan K. Siddiqi, MD, MSCR, Mandeep R. Mehra, MD, MSc Published:March 20, 2020 DOI:https://doi.org/10.1016/j.healun.2020.03.012
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 Causes endothelial cell damage, increased microvascular permeability, peroxynitrite (ONOO-) COVID-19 l Galera’s dismutase mimetics inhibited these effects in animal ARDS models Active Avasopasem 90mg Regimen 3 hr IV infusion BID x 7d Primary • 28-day mortality (overall survival) Avasopasem 90mg x 7 days BID + SSC COVID-19 test + Secondary Patients critical phase • Safety of avasopasem in COVID patients respiratory failure • Ventilator weaning • Vent-free days in hospital • ICU-free days Stratification Age < 60 or > 60 years • Catecholamine support, BP <65mmHg PBO + Standard Supportive Care (SSC) • SOFA scores Sites Multi-center SSC = Standard Supportive Care, SOFA = Sequential Organ Failure Assessment 44 Salvemini, et al, Br J Pharmacology, 2001; Macarthur, et al, Crit Care Med, 2003; Cuzzocrea, et al, Crit Care Med, 2004; Ndengele, et al, Shock, 2005 Randomize (1:1)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 Causes endothelial cell damage, increased microvascular permeability, peroxynitrite (ONOO-) COVID-19 l Galera’s dismutase mimetics inhibited these effects in animal ARDS models Active Avasopasem 90mg Regimen 3 hr IV infusion BID x 7d Primary • 28-day mortality (overall survival) Avasopasem 90mg x 7 days BID + SSC COVID-19 test + Secondary Patients critical phase • Safety of avasopasem in COVID patients respiratory failure • Ventilator weaning • Vent-free days in hospital • ICU-free days Stratification Age < 60 or > 60 years • Catecholamine support, BP <65mmHg PBO + Standard Supportive Care (SSC) • SOFA scores Sites Multi-center SSC = Standard Supportive Care, SOFA = Sequential Organ Failure Assessment 44 Salvemini, et al, Br J Pharmacology, 2001; Macarthur, et al, Crit Care Med, 2003; Cuzzocrea, et al, Crit Care Med, 2004; Ndengele, et al, Shock, 2005 Randomize (1:1)
Backup Commercial SlidesBackup Commercial Slides
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
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 toxicity limits use in larger (>3cm) or centrally-located tumors NSCLC (US*) 102,000 GC4711 – SBRT Clinical Candidate Stage I, II, III l Same mechanism of action as avasopasem (GC4419), with IV & oral forms GC4711 l Novel chemical entity with IP through 2036 55,100 Node-negative l Completed 14-day Phase 1 in healthy volunteers: 15-minute infusion 14,600 12,120 15,430 Peripheral Central Central Tumor > 3cm Tumor ≤ 3cm Tumor > 3cm *Globocan & US SEER Data 47 Decision Resources Group (DRG) Primary Market Research, Oct 2020SBRT 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 toxicity limits use in larger (>3cm) or centrally-located tumors NSCLC (US*) 102,000 GC4711 – SBRT Clinical Candidate Stage I, II, III l Same mechanism of action as avasopasem (GC4419), with IV & oral forms GC4711 l Novel chemical entity with IP through 2036 55,100 Node-negative l Completed 14-day Phase 1 in healthy volunteers: 15-minute infusion 14,600 12,120 15,430 Peripheral Central Central Tumor > 3cm Tumor ≤ 3cm Tumor > 3cm *Globocan & US SEER Data 47 Decision Resources Group (DRG) Primary Market Research, Oct 2020