SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549
Pursuant to Section 13 or 15(d)
of the Securities Exchange Act of 1934
Date of report (Date of earliest event reported): November 10, 2020
GALERA THERAPEUTICS, INC.
(Exact name of registrant as specified in its charter)
(State or other jurisdiction of
incorporation or organization)
2 W. Liberty Blvd #100
Malvern, PA 19355
(Address of principal executive offices) (Zip Code)
(Registrants telephone number, include area code)
(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:
|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 2.02. Results of Operations and Financial Condition.
On November 10, 2020, Galera Therapeutics, Inc. (the Company) announced its financial results for the quarter ended September 30, 2020. The full text of the press release issued in connection with the announcement is furnished as Exhibit 99.1 to this Current Report on Form 8-K.
Item 7.01. Regulation FD Disclosure.
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 November 10, 2020, 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 99.2. The Company undertakes no obligation to update, supplement or amend the materials attached hereto as Exhibit 99.2.
The information contained in Items 2.02 and 7.01 of this Current Report on Form 8-K (including Exhibit 99.1 and 99.2 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.
The following exhibits relating to Items 2.02 and 7.01 shall be deemed to be furnished, and not filed:
|99.1||Press Release issued on November 10, 2020|
|99.2||Corporate Slide Presentation of Galera Therapeutics, Inc. dated November 10, 2020|
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: November 10, 2020||By:|
|J. Mel Sorensen, M.D.|
|President and Chief Executive Officer|
Galera Therapeutics Reports Third Quarter 2020 Financial Results and Provides Business Updates
Presented Promising Interim Data from Placebo-controlled Pilot Dismutase Mimetic SBRT Combination Trial for Pancreatic Cancer
Announced Planned Phase 2b GC4711 SBRT Combination Trial for Pancreatic Cancer (GRECO-2)
Initiated Randomized Phase 1/2 GC4711 SBRT Combination Trial for NSCLC (GRECO-1)
Remain on Track with Ongoing Phase 3 ROMAN Trial and Other Radiation-Induced Toxicity Trials of Avasopasem
MALVERN, Pennsylvania, November 10, 2020 Galera Therapeutics, Inc. (Nasdaq: GRTX), a clinical-stage biopharmaceutical company focused on developing and commercializing a pipeline of novel, proprietary therapeutics that have the potential to transform radiotherapy in cancer, today announced financial results for the third quarter ended September 30, 2020, and provided business updates.
We continue to make great strides advancing the clinical development of our small molecule superoxide dismutase mimetics ability to address radiation toxicities and augment the anti-cancer efficacy of radiation, said Mel Sorensen, M.D., President and CEO of Galera. We are delighted with the encouraging data from our placebo-controlled trial of GC4419 in combination with stereotactic body radiation therapy (SBRT) for patients with locally advanced pancreatic cancer (LAPC), which were presented during a late-breaker session at the American Society for Radiation Oncology (ASTRO) 2020 Annual Meeting. The findings are the first clinical evidence supporting our extensive preclinical science that showed synergy of our dismutase mimetics with SBRT. In this first trial with the addition of a dismutase mimetic to SBRT in patients, we observed better tumor responses, saw more patients succeed in going to surgical resection, and are particularly pleased by the initial signal in survival. With these promising early activity results in hand, coupled with the preliminary safety findings of the combination, we look forward to continuing to advance the potential of our dismutase mimetics to enhance the anti-cancer efficacy of SBRT and improve outcomes for cancer patients. We have initiated the GRECO-1 Phase 1/2 trial of GC4711 with SBRT in non-small cell lung cancer (NSCLC), and also anticipate initiating a Phase 2b trial of GC4711 with SBRT in pancreatic cancer (GRECO-2) in the first half of 2021. Our most advanced program, the ROMAN Phase 3 trial, continues to enroll well and we look forward to reporting topline results in the second half of 2021.
Third Quarter 2020 and Recent Corporate Highlights
In October, presented interim efficacy and safety data from the randomized, double-blind, multicenter, placebo-controlled pilot Phase 1/2 clinical trial of avasopasem manganese (GC4419) in combination with SBRT in patients with LAPC at ASTRO. In the analysis of the intent-to-treat population, multiple endpoints to date show a positive trend in favor of improved anti-
cancer efficacy with avasopasem compared to placebo. While many of the patients are early in their follow-up post treatment, addition of the dismutase mimetic to SBRT appears to improve overall survival (OS) versus placebo (HR=0.4, 95% CI: 0.12-1.11; median OS not yet reached for avasopasem vs. 38.7 weeks for placebo; p=0.06). Best overall response within the SBRT field was partial response, according to modified RECIST criteria, or better in 33% of avasopasem patients versus 17% of placebo patients. Five patients in the avasopasem arm and two in the placebo arm were surgically resected. Among the resected avasopasem patients, all five achieved clear margins (R0), compared to only one of the two in the placebo arm. Progression-free survival hazard ratio as of the cut-off date also appears to favor the avasopasem arm (HR=0.6, 95% CI: 0.23-1.56; p=0.29). Toxicity was comparable across both treatment arms, with no significant differences in overall or Grade 3 GI toxicity post-SBRT. The data presented included all patients followed for a minimum of three months and 19 for more than one year, with data through August 24, 2020. The Company plans to provide an update on this trial with at least one year of follow-up on all patients in the second half of 2021.
In October, announced that the first patient had been dosed in the Phase 1/2 GRECO-1 trial of GC4711 in combination with SBRT in patients with central or large peripheral NSCLC tumors. GC4711 is Galeras second highly selective small molecule superoxide dismutase mimetic candidate and is being developed specifically for use in combination with SBRT. Following a safety run-in cohort, up to 66 NSCLC patients with locally advanced disease will receive GC4711 with SBRT or placebo with SBRT over five consecutive weekdays in a first stage of the randomized, double-blind, placebo-controlled Phase 2 portion of the GRECO-1 trial. A second stage is planned to add a checkpoint inhibitor to the SBRT combination. The GRECO-1 trial is supported in part by a recently awarded Small Business Innovation Research grant (4R44CA206795-02) from the National Cancer Institute of the National Institutes of Health. The Company anticipates reporting topline data from the first stage of this trial in the first half of 2022.
In October, hosted a virtual Key Opinion Leader (KOL) event featuring Sarah Hoffe, M.D., Section Head of GI Radiation Oncology and Senior Member at Moffitt Cancer Center. Dr. Hoffe provided an overview of the management of patients with localized pancreatic cancer, including the current clinical treatment paradigm and the use of SBRT.
In September, announced the first patient had been dosed in a pilot Phase 2 clinical trial of avasopasem to evaluate its ability to improve 28-day mortality in hospitalized patients who are critically ill with COVID-19. The Company anticipates reporting topline data from this trial in the first half of 2021.
Continued enrollment in multiple clinical trials of avasopasem for radiation-induced toxicities, including the Phase 3 ROMAN trial to assess its ability to reduce the incidence and severity of severe oral mucositis induced by radiotherapy in patients with locally advanced head and neck cancer (HNC), the Phase 2a EUSOM multi-center trial in Europe assessing the safety of avasopasem in patients with HNC undergoing standard-of-care radiotherapy, as well as the AESOP Phase 2a trial to assess its ability to reduce the incidence of esophagitis induced by radiotherapy in patients with lung cancer. The Company remains on track to announce topline data from the ROMAN trial in the second half of 2021.
Third Quarter 2020 Financial Highlights
Research and development expenses were $12.1 million in the third quarter of 2020, compared to $11.0 million for the same period in 2019. The increase was primarily attributable to avasopasem development costs due to increased expenses in the Phase 3 ROMAN trial, additional clinical trials including the Phase 2a trial for the treatment of esophagitis in patients with lung cancer and the Phase 2a multi-center trial in Europe assessing the safety of avasopasem in patients with HNC. In addition, employee-related costs also increased due to increased headcount and share-based compensation expense. The increases were partially offset by decreased avasopasem preclinical spend and decreased GC4711 development expenses.
General and administrative expenses were $3.9 million in the third quarter of 2020, compared to $1.8 million for the same period in 2019. The increase was primarily the result of employee-related costs from increased headcount and share-based compensation expense, and increased insurance, professional fees and other operating costs as a result of becoming a public company.
Galera reported a net loss of $(17.1) million, or $(0.69) per share, for the third quarter of 2020, compared to a net loss of $(13.4) million, or $(51.43) per share, for the same period in 2019.
As of September 30, 2020, Galera had cash, cash equivalents and short-term investments of $89.2 million. Galera expects that its existing cash, cash equivalents and short-term investments, together with the expected payments from Blackstone in the amount of $57.5 million upon the achievement of certain clinical enrollment milestones in the ROMAN trial and the anti-cancer program in combination with SBRT under the amended royalty agreement, will enable Galera to fund its operating expenses and capital expenditure requirements into the second half of 2022.
About Galera Therapeutics
Galera Therapeutics, Inc. is a clinical-stage biopharmaceutical company focused on developing and commercializing a pipeline of novel, proprietary therapeutics that have the potential to transform radiotherapy in cancer. Galeras lead product candidate is avasopasem manganese (GC4419), a highly selective small molecule superoxide dismutase (SOD) mimetic initially being developed for the reduction of radiation-induced severe oral mucositis (SOM). Avasopasem is being studied in the Phase 3 ROMAN trial to assess its ability to reduce the incidence and severity of SOM induced by radiotherapy in patients with locally advanced head and neck cancer (HNC), its lead indication. It is also being studied in the EUSOM Phase 2a multi-center trial in Europe assessing the safety of avasopasem in patients with HNC undergoing standard-of-care radiotherapy, the AESOP Phase 2a trial to assess its ability to reduce the incidence of esophagitis induced by radiotherapy in patients with lung cancer, and a Phase 2 trial in hospitalized patients who are critically ill with COVID-19. A pilot Phase 1/2 trial of avasopasem in combination with stereotactic body radiation therapy (SBRT) in patients with locally advanced pancreatic cancer has completed enrollment and reported interim results, with follow-up ongoing. The FDA granted Fast Track and Breakthrough Therapy designations to avasopasem for the reduction of SOM induced by radiotherapy. Galeras second dismutase mimetic product candidate, GC4711, is being developed specifically to augment the anti-cancer efficacy of SBRT, and is currently being studied in the GRECO-1 Phase 1/2 clinical trial in combination with SBRT in patients with non-small cell lung cancer. Galera is headquartered in Malvern, PA. For more information, please visit www.galeratx.com.
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. All statements contained in this press release that do not relate to matters of historical fact should be considered forward-looking statements, including without limitation statements regarding expectations surrounding our growth and the continued advancement of our product pipeline, the potential, safety, efficacy, and regulatory and clinical development of Galeras product candidates, plans and timing for the commencement of and the release of data from Galeras clinical trials, expected payments from Blackstone, and the sufficiency of Galeras cash, cash equivalents and short-term investments. These forward-looking statements are based on managements current expectations. These statements are neither promises nor guarantees, but involve known and unknown risks, uncertainties and other important factors that may cause Galeras actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements, including, but not limited to, the following: Galeras limited operating history; anticipating continued losses for the foreseeable future; needing substantial funding and the ability to raise capital; Galeras dependence on avasopasem manganese (GC4419); uncertainties inherent in the conduct of clinical trials; difficulties or delays enrolling patients in clinical trials; the FDAs acceptance of data from clinical trials outside the United States; undesirable side effects from Galeras product candidates; risks relating to the regulatory approval process; failure to capitalize on more profitable product candidates or indications; ability to receive Breakthrough Therapy Designation or Fast Track Designation for product candidates; failure to obtain regulatory approval of product candidates in the United States or other jurisdictions; ongoing regulatory obligations and continued regulatory review; risks related to commercialization; risks related to competition; ability to retain key employees and manage growth; risks related to intellectual property; inability to maintain collaborations or the failure of these collaborations; Galeras reliance on third parties; the possibility of system failures or security breaches; liability related to the privacy of health information obtained from clinical trials and product liability lawsuits; unfavorable pricing regulations, third-party reimbursement practices or healthcare reform initiatives; environmental, health and safety laws and regulations; the impact of the COVID-19 pandemic on Galeras business and operations, including preclinical studies and clinical trials, and general economic conditions; risks related to ownership of Galeras common stock; and significant costs as a result of operating as a public company. These and other important factors discussed under the caption Risk Factors in Galeras 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 Galeras other filings with the SEC could cause actual results to differ materially from those indicated by the forward-looking statements made in this press release. Any forward-looking statements speak only as of the date of this press release and are based on information available to Galera as of the date of this release, and Galera assumes no obligation to, and does not intend to, update any forward-looking statements, whether as a result of new information, future events or otherwise.
Galera Therapeutics, Inc.
Consolidated Statements of Operations
(unaudited, in thousands except share and per share data)
|Three Months Ended
|Nine Months Ended
Research and development
General and administrative
Loss from operations
Other income (expense), net
Accretion of redeemable convertible preferred stock to redemption value
Net loss attributable to common stockholders
Net loss per share of common stock, basic and diluted
Weighed average common shares outstanding, basic and diluted
Galera Therapeutics, Inc.
Selected Consolidated Balance Sheet Data
(unaudited, in thousands)
Cash, cash equivalents, and short-term investments
Total current liabilities
Total stockholders equity
Galera Therapeutics, Inc.
Transforming Radiotherapy with Dismutase Mimetics November 2020 Exhibit 99.2
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 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 Modulated RT Potential to Reduce Toxicity Severe Oral Mucositis Head & Neck Cancer (SOM in HNC) Esophagitis NSC Lung Cancer (NSCLC) Normal tissue toxicity limits optimal radiotherapy treatment of tumor Phase 3 ROMAN Phase 2 Trial Potential to Increase Efficacy Pancreatic Cancer Locally Advanced (LAPC) Lung Cancer Locally Advanced (LANSCLC) Radiotherapy is SoC for many local tumors but need remains for greater efficacy Phase 1b/2a SBRT Combo Phase 1b/2a SBRT Combo SBRT Stereotactic Body RT Rapid elimination of Superoxide (O2) Increase H2O2 in tumors Over half of cancer patients receive radiotherapy as part of their care1, 2 Transforming Radiotherapy with Dismutase Mimetics
(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. (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. Phase 1 Phase 2 Phase 3 1a1b 2a2b SOM in Head & Neck Cancer Esophagitis in NSCLC (2) SOM in Head & Neck Cancer (1) ROMAN avasopasem vs. placebo AESOP avasopasem single-arm EUSOM avasopasem single-arm Pancreatic Cancer (3) NSC Lung Cancer (4) LAPC Pilot GC4419 vs. placebo GRECO-1 GC4711 vs. placebo Pancreatic Cancer GRECO-2 GC4711 vs. placebo Topline Data 2H 2021 Topline Data 1H 2022 Topline Data 2H 2021 1 Year Follow-up 2H 2021 Initiate Trial 1H 2021 1st Stage Data 1H 2022 Topline Data 1H 2021 COVID-19 Critically Ill Patients COVID Pilot avasopasem vs. placebo Reducing RT Toxicity IMRT Combos Increasing RT Efficacy SBRT Combos Next Anticipated Milestone Clinical Stage Pipeline
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 efficacy in patients Improved local control and overall survival in pilot LAPC trial (n=42) Preparing to initiate randomized Phase 2b trial in pancreatic cancer Randomized Phase 1/2 trial ongoing in NSCLC Planning US Launch Galera is building a commercial team for the US Launch 65,000 head & neck cancer patients diagnosed annually in the US 4,000 radiation oncologists in ~2,500 radiotherapy sites in US Galera’s quantitative market research reached ~5% of US Rad Oncs ~40 reps for the 4,000 radiation oncologists in U.S.
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 peroxide Avasopasem (GC4419) GC4711 H2O2 more toxic to cancer cells than normal cells
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 Fast catalytic rates & high selectivity for superoxide Firmly hold manganese in macrocyclic ring Stable, safe & suitable for manufacturing Dismutase Mimetics Core Structure Pentaaza Macrocycles Small Molecule Dismutase Mimetics with Attractive Drug Characteristics Comparable to native SODs (2x107 molecules per sec) Interact with superoxide alone, not other reactive oxygen species Firmly hold Mn atom in macrocyclic ring Well-tolerated preclinically and clinically Efficient & cost-effective manufacturing process Speed Selectivity Stability Safety Synthesis
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 cause of death Reduce Radiation Mucositis Lethal dose of Total Body Irradiation (8.5 Gy) to mice 100% death on control, 100% survival with 40mg/kg Main cause of death was intestinal mucositis
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 Radiotherapy Efficacy Focal irradiation of human tumor xenografts (H1299 NSCLC) in mice RT anti-cancer synergy of GC4419 increases with bigger RT fractions Bigger fraction à More O2 à More H2O2 Also demonstrated with human pancreatic cancer xenografts
…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 doxycycline added, losing the synergy
Reducing Toxicity of IMRT – Clinical Data (Intensity Modulated Radiotherapy)
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) GC4419 90mg x 7 weeks GC4419 30mg x 7 weeks Placebo x 7 weeks Treatment Avasopasem (GC4419) 90mg, 30mg, or placebo 60 minute IV infusion, Mon-Fri. Ending <60 mins pre-RT Population Patients with HNC Locally-advanced, squamous cell Eligible for SoC – 7 weeks IMRT + cisplatin Stratification Factors Tumor HPV Status: positive or negative Cisplatin Schedule: q3wks or weekly Endpoints Primary – Reduction in median duration of SOM – WHO Grades 3 & 4 Secondary – Reduction in incidence and severity of SOM at pre-specified timepoints Exploratory – Time to SOM onset Tumor outcomes (2 year follow-up) Locoregional control, distant mets, PFS, OS Trial Design
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 and severity ) have nominal p values compared to placebo ITT = Intent-To-Treat population (n=223) DURATION 92% Reduction in median days of SOM 90 mg vs. Placebo p=0.024 INCIDENCE 34% Reduction through all RT 90 mg vs. Placebo p=0.009* SEVERITY 47% Reduction in Incidence of Grade 4 OM 90 mg vs. Placebo p=0.045*
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 mg GC4419 (n=72) Lymphopenia 89% 92% 88% Nausea 75% 68% 82% Fatigue 69% 60% 65% Oropharyngeal pain 64% 63% 61% Constipation 53% 59% 64% Radiation skin injury 47% 51% 53% Vomiting 47% 52% 49% Dysgeusia (taste) 49% 55% 43% Dysphagia 43% 42% 47% Weight decreased 35% 40% 44% Oral candidiasis 29% 45% 43% Leukopenia 39% 37% 39% % Anderson et al, JCO, 2019
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) GC4419 90mg x 7 weeks Placebo x 7 weeks Treatment Avasopasem (GC4419) 90mg or placebo 60 minute IV infusion, Mon-Fri Ending <60 mins pre-RT Population Patients with Head & Neck Cancer Locally-advanced, squamous cell Eligible for SoC – 7 weeks IMRT + cisplatin Stratification Factors Surgery Status: post-op or definitive Cisplatin Schedule: q3wks or weekly Endpoints Primary – Reduction in incidence of SOM – WHO Grades 3 & 4 Secondary – Reductions in severity of SOM and number of days of SOM experienced Tumor outcomes1 – LRC, DM-free, PFS, OS Trial Design (n450 pts) 1 LRC = locoregional control, DM-free = free of distant mets, PFS = Progression-Free Survival, OS = Overall Survival
Increasing SBRT Efficacy – Clinical Data (Stereotactic Radiotherapy)
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 Failure, DM = Distant Metastases, PFS = Progression-Free Survival, OS = Overall Survival R Inoperable LA or BR Pancreatic Cancer after ~6 months of induction Chemo SBRT + GC4419 x 5 doses SBRT + Placebo x 5 doses GC4419 90mg IV over 60min Surgical Evaluation Resection If possible N=11 N=8 2018–2019 Limited to LA/unresectable >1 Year Follow-Up SBRT GC4419 Pilot Double-blind, Placebo-controlled, Randomized Trial Patients with Locally Advanced Pancreatic Cancer (LAPC) post ~6 mos chemo Optimal SBRT fraction selected based on 90-day safety/efficacy (LO-ET 1) Tumor outcome measures: ORR, LRC, DM, Resectability, PFS, OS 90 90 90 90 90 GC4419 SBRT Single-center Stage N=24 N=18 N=13 N=10 2020 (Jan–June) Included borderline resectable 3–6 Months Follow-Up Multicenter Stage Total
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/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
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 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 O2, antibiotics & beta blocker) **No bleeding ulcers by 12-week endoscopy, no GI toxicity > Grade 3
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 out of 18 patients on placebo (17%) R0 R0 R0 R0 R0 R0 R1 RO R1 = Surgical resection (R0 = clear margins). = Surgical resection (R1 = tumor at margins). NE = not evaluable.
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 = stereotactic body radiation therapy Treatment SBRT Arm Initial Tumor Staging LA or BR Margins Post Resection R0/R1 Histopath Analysis Post Resection Avasopasem (n=5) LA R0 pCR BR R0 pPR BR R0 pPR BR R0 pPR LA R0 pPR Placebo (n=2) BR R0 pPR LA R1 pNR No significant perioperative complications after SBRT for all 7 patients
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; 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
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, HR = 0.4 Log Rank P value = 0.29, HR = 0.6 N=42
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): 0.046 HR=0.4; P (log-rank): 0.078 HR=0.1; P (log-rank): 0.051 Not Reached Not Reached
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
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) Progression-Free Survival (PFS) 0.4 (0.15-1.14) 0.6 (0.23-1.56) Loco-Regional Control (LRC) 0.1 (0.01-1.37) 0.2 (0.02-2.22) Time to Distant Mets (TDM) 0.4 (0.11-1.13) 0.4 (0.13-1.29)
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 Placebo-controlled Randomized trial Annual new cases 460,000 Globally1 57,000 in US2 9-13% 5-year Survival 5-Year Survival is ~10% 1/6th get attempted surgical resection 1/3rd get chemotherapy upfront then some considered for SBRT Half at diagnosis are beyond locoregional control and receive chemotherapy, with some getting RT as palliation to primary
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-controlled, Randomized Trial after Short Phase 1 NSCLC Locally Advanced – Previously untreated (1st line) Objectives: Safety (reducing Pneumonitis), ORR, LRC, DM, PFS, OS Stage 1 to access SBRT +/- GC4711; Stage 2 SBRT + Checkpoint Inhibitor +/- GC4711 1st–line NSCLC Centrally located or Large Tumors ECOG PS 0-3 Phase 1 (n=5 pts) R SBRT + GC4711 x 5 SBRT + Placebo x 5 Randomized Phase 2 (n66 pts) SBRT + GC4711 x 5 30 Day Safety SRC Review 100 100 100 100 100 GC4711 SBRT 100 100 100 100 100 GC4711 SBRT GC4711 100 mg IV in 15min SBRT 10-12 Gy* x 5 1st Stage: GC4711 100 mg IV in 15min SBRT 10-12 Gy* x 5
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 Oncologists), Rad Oncs = Radiation Oncologists, SOM = Severe Oral Mucositis Patients with OM incur ~$32,000 more in medical expenses in first 6 months from start of RT Current approaches inadequate – while frequently used, only 1 in 5 believe they are useful SOM common and costly ~$32,000 ~65k new cases/year in US 2/3rd get IMRT & cisplatin as standard-of-care à 70% get SOM 20-30% get Grade 4 No approved drug Rad Oncs report severe oral mucositis is most burdensome side effect of HNC RT treatment Severe Oral Mucositis Head & Neck Cancer 42k HNC Pts Galera’s quantitative market research to date includes ~5% of US radiation oncologists Supports significant, rapid uptake2 220 Rad Oncs in market research 5% of Rad Oncs Targeted salesforce In U.S. Focused commercial infrastructure ~2,500 RT sites in US ~60% of patients are treated in ~500 centers1 ~40 reps for the 4,000 radiation oncologists in U.S. ~40 Reps ~50k NSCLC patients treated with IMRT, 50% get ≥ Grade 2 esophagitis3 à inability to swallow, severe pain, ulceration, bleeding & hospitalization SOM efficacy seen by radiation oncologists as supportive for esophagitis4 Esophagitis in Lung Cancer 50k NSCLC Pts
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. 5NCCN = National Comprehensive Cancer Network-2019 Unmet Medical Need with Limited Treatment Options Pancreatic Cancer Lethal Common Cancer Increasing Number of Pancreatic Cancer Patients Diagnosed Each Year Annually, 57,000 newly diagnosed in US1 and 460,000 globally2 It is the most lethal common cancer: 5-year survival 9-13%1,2 Over 30% present with locally advanced unresectable or borderline resectable (18,000 in US)2 Novel Therapies Needed First Line Treatment is Induction Chemotherapy for Over 80% of Patients2 FOLFIRINOX or Gemcitabine/Abraxane most commonly used3 60% of patients fail induction therapy within 12 months4 60% on FOLFIRINOX develop Grade 3-5 toxicity4 SBRT is Accepted Tx Option SBRT Use is increasingly used for locoregional control (by NCCN and others)5 1st or 2nd line option after 4-5 months of chemotherapy for locally advanced cancer For loco-regional recurrence after surgical resection For some patients with metastatic disease for palliative control of local disease
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 2019* SBRT commonly used for smaller peripheral tumors Lung toxicity limits use in larger (>3cm) or centrally-located tumors GC4711 GC4711 – SBRT Clinical Candidate Same mechanism of action as avasopasem (GC4419), with IV & oral forms Novel chemical entity with IP through 2036 Completed 14-day Phase 1 in healthy volunteers: 15-minute infusion 14,600 Peripheral Tumor > 3cm 175,000 NSCLC (US*) 102,000 Stage I, II, III 55,100 Node-negative 2,500,000 NSCLC (World*)
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 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 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.
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; Cuzzocrea, et al, Crit Care Med, 2004; Ndengele, et al, Shock, 2005 GC4419 For COVID-19 Double-blind, Placebo-controlled, Randomized Trial Superoxide plays a central role in pathophysiology of acute respiratory distress syndrome (ARDS) Causes endothelial cell damage, increased microvascular permeability, peroxynitrite (ONOO-) Galera’s dismutase mimetics inhibited these effects in animal ARDS models Randomize (1:1) Avasopasem 90mg x 7 days BID + SSC PBO + Standard Supportive Care (SSC) Active Regimen Avasopasem 90mg 3 hr IV infusion BID x 7d Patients COVID-19 test + critical phase respiratory failure Stratification Age < 60 or > 60 years Sites Multi-center Primary 28-day mortality (overall survival) Secondary Safety of avasopasem in COVID patients Ventilator weaning Vent-free days in hospital ICU-free days Catecholamine support, BP <65mmHg SOFA scores
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 Treatment Approach Recommended for HNC OM due to RT? Basic oral care ✔ Anti-microbials, coating agents, anesthetics, & analgesics (0.2% morphine mouthwash) ✔ Anti-inflammatories, benzydamine ? Low level laser & other light therapy ? Cryotherapy for 5-FU chemotherapy O Natural & other agents O Current Treatments 42,000 receive IMRT WHO Grading Scale 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 Dehydration & Malnutrition Often requiring PEG tube feeding Pain Often severe pain requiring opioids Treatment interruption Each week of treatment delay decreases tumor control by >10% Increased economic burden OM Dx à ~$32,000 in additional medical expenses in first 6 months from RT start MASCC / ISOO Guidelines for HNC OM
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 visit with SOM) 90MG Avasopasem (GC4419) Arm (35 of 76 Pts had ≥1 visit with SOM)
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
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 indicate how you might use (maximum %) Product X for the following radiation associated conditions? Mucositis of Esophagus Radiotherapy-related Esophagitis in Lung Cancer SOM efficacy seen by radiation oncologists as supportive for esophagitis1 ~50,000 lung cancer patients are treated with RT, 50% get ≥ Grade 2 esophagitis2 Effects: inability to swallow, severe pain, ulceration, bleeding & hospitalization Compendial Listing Phase 2 to support Compendial Listing post-Approval for SOM Single-arm Phase 2a trial in 60 patients w/ locally-advanced lung cancers Standard IMRT to ≥ 5 cm of esophagus (30 fractions, 2Gy/day x5 for 6 weeks) Post approval for SOM in HNC, plan to seek compendial listing in U.S.