Filing
UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
Washington, DC 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)
October 2, 2019
SAVARA INC.
(Exact name of registrant as specified in its charter)
| Delaware | 001-32157 | 84-1318182 | ||
| (State or other jurisdiction of incorporation) |
(Commission File Number) |
(IRS Employer Identification No.) |
6836 Bee Cave Road
Building III, Suite 200
Austin, TX 78746
(Address of principal executive offices, including zip code)
(512) 961-1891
(Registrant’s telephone number, including 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 (see General Instruction A.2. below):
| ☐ | 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, par value $0.001 per share | SVRA | The Nasdaq Global Select Market |
Indicate by check mark whether the registrant is an emerging growth company as defined in 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. |
On October 2, 2019, Bruce Trapnell, M.D., lead Principal Investigator in the U.S. and Director, Translational Pulmonary Science Center, Scientific Director, PAP Foundation, Co-Director, Rare Lung Diseases Clinical Research Consortium, and Professor of Medicine and Pediatrics, University of Cincinnati College of Medicine, presented additional data from Savara Inc.’s IMPALA pivotal Phase 3 clinical study evaluating Molgradex, an inhaled formulation of recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF), for the treatment of autoimmune pulmonary alveolar proteinosis (aPAP) at the 2019 European Respiratory Society (ERS) International Congress in Madrid, Spain.
The presentation slides used by Dr. Trapnell are attached hereto as Exhibit 99.1.
| Item 8.01. | Other Events. |
On October 2, 2019, Savara issued a press release announcing the response from a Type C meeting with the U.S. Food and Drug Administration (FDA) regarding the Molgradex development program for aPAP. A copy of the press release is filed herewith as Exhibit 99.2.
| Item 9.01. | Financial Statements and Exhibits. |
(d) Exhibits.
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.
| Date: October 2, 2019 |
SAVARA INC. a Delaware corporation | |||||
| By: | /s/ Dave Lowrance | |||||
| Dave Lowrance | ||||||
| Chief Financial Officer | ||||||
Safety and Efficacy of Inhaled GM-CSF (Molgramostim) in Autoimmune Pulmonary Alveolar Proteinosis - The IMPALA Trial - Baseline Data and Blinded Treatment Period Results Bruce C. Trapnell, M.D. Translational Pulmonary Science Center Cincinnati Children’s Hospital Medical Center Professor of Medicine and Pediatrics Division of Pulmonary, Critical Care, and Sleep Medicine University of Cincinnati Medical Center Exhibit 99.1
Disclosures The Impala trial was sponsored by Savara Pharmaceuticals I receive grant funding from the US National Institutes of Health I have consulted for: Boehringer Ingelheim, CSL Behring, Genzyme, Gilead, Grifols, GSK, Kiniksa, Medimmune, Merck, Savara, Sanofi, Takeda
Thick layer of surfactant ‘PAP sediment’ Epithelial basement membrane Alveolar air space Endothelial basement membrane Red cell Fibroblast Normal oxygen uptake Displaced alveolar air Cellular debris Thin film of surfactant Alveolar macrophage Type II cell Interstitium Type I cell Normal Alveolus M-CSF MCP-1 Endothelial cell Polycythemia B. Trapnell GM-CSF Reduced oxygen uptake Cholesterol crystals Lymphocytes GM-CSF autoantibody Foamy alveolar macrophage GM-CSF Alveolus in PAP Background: Autoimmune Pulmonary Alveolar Proteinosis (aPAP) aPAP is characterized by: – Pulmonary surfactant accumulation – Progressive hypoxemic respiratory failure – Increased PAP biomarkers – Polycythemia (systemic response to lung disease) – Increased infection risk (uncommon) – Pulmonary fibrosis (uncommon) GM-CSF is required to regulate alveolar macrophage – Differentiation – Functions – Population size GM-CSF autoantibodies cause aPAP by blocking stimulation of alveolar macrophages, which reduces their ability to clear surfactant
Background: Inhaled GM-CSF Therapy of aPAP 1996, Seymour: First patient treated with GM-CSF (SQ) 2000, Kavuru: 4 patients treated (SQ) 2001, Seymour: 14 patients treated (SQ) 2004, Aria: 1 patient treated (Inhaled) 2005, Tazawa: 3 patients treated (Inhaled) 2006, Wylam: 12 patients treated (Inhaled) 2005, Venkateshiah: 25 patients treated (SQ) 2010, Tazawa: 39 Patients treated (inhaled) 2014, Papiris: 6 Patients treated (inhaled) 2019, Tazawa: 64 Patients treated (inhaled) IMPALA Trial, 138 patients treated (inhaled) After Before Tazawa... 2010
Study Design of the IMPALA Trial Screening Randomized, blinded Treatment (6 m) 0 24 Placebo Open-Label Treatment (6 or 12 m) 48 or 72 Time (weeks) Intermittent GM-CSF* Intermittent GM-CSF Continuous GM-CSF Continuous – Daily administration of inhaled GM-CSF (300 µg) (n=46) Intermittent – Daily administration of GM-CSF (300 µg) every other week* (n=45) Placebo – Daily administration (n=47) Study Groups *Placebo administered on ‘off’ weeks
Study Design: Endpoints Safety: Number of adverse events (AE) and serious adverse events (SAE) Efficacy: Change from baseline at 24 weeks in the following endpoints: Disease element Variable Pathology Chest CT ground glass opacification (GGO) score Serum PAP biomarkers Physiology Alveolar-arterial difference in oxygen conc. (A-aDO2)* DLCO Health status & Function Saint Georges Respiratory Questionnaire (SGRQ) ** Six-minute walk test - Distance** Rescue therapy requirement (Whole lung lavage - WLL) Time to first WLL** Number of patients with WLL, Number of WLL Systemic response to chronic lung disease (polycythemia) Hemoglobin concentration * = Primary end point, ** = Key Secondary end point
Baseline Characteristics: Demographics Characteristic Continuous Intermittent Placebo Age, years 54.0 ± 13.3 49.2 ± 14.0 46.1 ± 14.8 Gender (Male), % 60.9 57.8 53.2 Smoking history, % Never smoker 28.3 35.6 34.0 Ex smoker 58.7 44.4 42.6 Current smoker 13.0 20.0 23.4 Geographic region, % Europe 34.8 46.7 70.2 Japan 43.5 22.2 21.3 USA 4.3 4.4 0 Other 17.4 26.7 8.5
Baseline Characteristics: Disease Severity Characteristic Continuous Intermittent Placebo A-aDO2*, mm Hg (FAS) 40.5 ± 19.6 40.9 ± 20.2 40.2 ± 14.3 DLCO, % predicted 52.1 ± 18.6 46.1 ± 14.5 49.6 ± 14.3 Disease severity score (DSS), % DSS 1 (Mild) 8.7 11.1 6.4 DSS 2 26.1 31.1 34.0 DSS 3 37.0 28.9 29.8 DSS 4 10.9 20.0 21.3 DSS 5 (Severe) 17.4 6.7 8.5 SGRQ Total score** 47.2 ± 20.4 44.4 ± 21.4 44.1 ± 21.7 6MWT-Distance**, m 412 ± 144 447 ± 117 447 ± 125 Vital capacity, % predicted 78.6 ± 32.2 74.8 ± 19.5 74.1 ± 18.6 * = Primary end point, ** = Key Secondary end point
Baseline Characteristics: Previous Therapies Characteristic Continuous Intermittent Placebo Supplemental oxygen use, % 32.6 26.7 23.4 Whole lung lavage Prior use of WLL (any), % 47.8 68.9 63.8 Total Number of WLLs 3.3 ± 2.2 3.3 ± 3.0 2.8 ± 3.0 Time since last WLL, m 25.0 ± 53.7 19.7 ± 27.4 17.7 ±20. 7 GM-CSF therapy (any), % 13.0 15.6 12.8
Safety: AE, SAE, and Respiratory AE Occurring in at least 5% of Patients No clinically significant changes in laboratory values No evidence of anti-drug antibody development Study completion: Continuous: 97.8%, Intermittent: 97.8%, Placebo: 91.5% AE (all) AE (Poss/prob related) SAE (all) Worsening of aPAP 0 20 40 60 80 100 Continuous Intermittent Placebo All Cough Dyspnea Productive cough 0 20 40 60 80 100 Respiratory AE Event rate (% patients) Event rate (% patients)
Pathology: GM-CSF Improved Chest CT GGO Score P=0.0002 P=0.1776 Continuous Intermittent Placebo *Comparison to Placebo * *
Pathology: GM-CSF Improved Serum Biomarkers * Continuous Intermittent Placebo * = P<0.05, ns = P>0.05, comparison to Placebo * * * * ns * * ns ns ns ns SP-D LDH KL-6 SP-A Cyfra21-1 CEA
Physiology: GM-CSF Trended Towards Improvement in the Primary End Point (A-aDO2) – Full Analysis Set (FAS) P=0.1688 Continuous Intermittent Placebo P=0.4444 * * *Comparison to Placebo
Correlation of PaO2 and A-aDO2 Identifies Patients Who Received Oxygen Therapy During Blood Collection as Outliers Patients that received supplemental oxygen via nasal canula during ABG specimen collection Patient A Patient B Patient C Patient D
Exclusion of Data for Patients On Oxygen Therapy During Arterial Blood Collection Significantly Influenced the Primary Endpoint (A-aDO2 – Revised) P=0.0249 Continuous Intermittent Placebo P=0.2313 *Comparison to Placebo * *
Physiology: GM-CSF Improved DLCO P=0.0074 Continuous Intermittent Placebo P=0.3097 *Comparison to Placebo * *
Health Status: GM-CSF Improved SGRQ Total Score P=0.0103 Continuous Intermittent Placebo P=0.0173 + MCID is 4 Points in COPD patients *Comparison to Placebo * *
The Improvement in SGRQ was Robust as Shown by Responder Analysis ß Favors Placebo | Favors GM-CSF à Odds Ratio 8 points 6 points 4 points Threshold value used as ‘cut off’ for a positive response Placebo versus GM-CSF (Continuous)
A Pattern of Improvement was Seen Across all SGRQ Domains Continuous Intermittent Placebo Activity Impact Symptoms P=0.0107 P=0.0223 P=0.4884
Function: GM-CSF Trended Towards Improved 6MWT-Distance P=0.3159 Continuous Intermittent Placebo P=0.7809 *Comparison to Placebo * *
Rescue Therapy: GM-CSF Trended Towards a Reduction in WLL WLL Therapy Requirement Group # patients # treatments Rate Ratio vs Placebo Continuous (n=46) 4 9 0.284 Intermediate (n=45) 4 7 0.367 Placebo (n=47) 6 17 - ß Favors Placebo | Favors GM-CSF à Hazards Ratio Placebo versus GM-CSF Time to WLL: Intermittent Time to WLL: Continuous
Systemic Response: GM-CSF Trended Towards Reduced Hemoglobin Levels P=0.0506 Continuous Intermittent Placebo P=0.5886 *Comparison to Placebo * *
Totality of Outcome Data Favors Continuous GM-CSF over Placebo Disease element Endpoint Units Treatment effect P-value Pathology Chest CT – GGO Score -2.4 0.0002 Serum LDH, KL-6, SP-D, CEA, Cyfra 21‑1 IU/L pg/ml All favor GM-CSF <0.05 Physiology A-aDO2* – FAS mm Hg -4.6 0.1688 A-aDO2* – Revised mm Hg -6.5 0.0249 DLCO % predicted 7.9 0.0074 Health status & Function SGRQ** total score -7.6 0.0103 6MWT-Distance** m 20.6 0.3159 Rescue therapy Time to WLL** WLL frequency Hazard ratio Rate ratio 0.59 0.28 0.4204 0.1918 Systemic response Hemoglobin (g/dL) -0.5 0.0506 * = Primary end point, ** = Key Secondary end point
Conclusions Baseline clinical features of aPAP A large, global cohort of adult aPAP patients was identified and carefully characterized Study groups were well-balanced for demographics and disease severity Clinical trial observations The Placebo group experienced an unexpected degree of improvement in A-aDO2 Inhaled recombinant human GM-CSF therapy (molgramostim) of aPAP is: Safe and well-tolerated Effective as shown by changes in lung pathology, physiology, health status, function, and the systemic response to chronic lung disease More effective when administered continuously than on alternating weeks
Acknowledgments We are grateful to and thank: Our PAP patients whose collaboration made the IMPALA trial possible IMPALA Investigators - PAP care providers and staff – at 30 centers in 18 countries including: Australia Troy S (Sydney); Denmark Bendstrup E (Arhus); France Jouneau S (Rennes); Israel Kremer M (Tikva); Italy Campo I (Pavia); Germany Bonella F (Essen), Kreuter M (Heidelberg), Behr J (Gauting), Bohnet S (Lübeck); Greece Papiris S (Athens); Japan Inoue Y (Osaka), Yamaguchi E, (Aichi), Nakata K (Niigata), Baba T (Yokohama), Kobayashi M (Sendai); Portugal A Morais (Porto) Ferreira L (Lisboa); Russia Ilkovich M (St. Petersburg); Slovakia Slivka R, Hagy V; South Korea Pyo Chung P, Woo Song J, Mi Choi S (Seoul); Spain Molina M (Barcelona); Switzerland Lazor R (Lausanne); The Netherlands Veltkamp M (Nieuwegein); Turkey Cetinkaya E (Istanbul); United Kingdom Morgan C (London); United States Wang T (Los Angeles), Ataya A (Gainesville), Trapnell B (Cincinnati) IMPALA Protocol Committee: Denmark Bendstrup E; Germany Costabel U, Bonella F; Italy Campo I; Japan Inoue Y; France Jouneau S; UK Morgan C; Greece Papiris S; USA Trapnell B Waterer G (Perth, Australia) who provided clinical and analytical expertise Savara Pharmaceuticals who sponsored the IMPALA trial
Exhibit 99.2
SAVARA ANNOUNCES FDA RESPONSE FROM TYPE C MEETING
ON MOLGRADEX FOR APAP DEVELOPMENT PROGRAM
AUSTIN, TX – Oct. 2, 2019 – Savara Inc. (Nasdaq: SVRA), an orphan lung disease company, today announced the response from a Type C meeting with the U.S. Food and Drug Administration (FDA) regarding the Molgradex development program for autoimmune pulmonary alveolar proteinosis (aPAP). Molgradex is an inhaled formulation of recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF).
In the written response received by Savara on October 1, the FDA indicated that the data provided in the briefing package do not provide sufficient evidence of efficacy and safety and did not recommend that the Company submit a Biologics License Application (BLA). The Company is working to determine the next steps for the Molgradex development program.
“While we are disappointed in the FDA’s response, considering the IMPALA study results presented today at the ERS annual conference, we remain committed to the Molgradex development program and believe that it will provide aPAP patients with a meaningful treatment option,” said Rob Neville, Chief Executive Officer, Savara. “Our priority is to further assess the content of the FDA’s feedback and determine the best development path forward.”
As noted above, additional data from the IMPALA study were presented today at the 2019 European Respiratory Society (ERS) International Congress in Madrid, Spain. The data were presented in an oral session by Bruce Trapnell, M.D., lead Principal Investigator in the U.S. and Director, Translational Pulmonary Science Center, Scientific Director, PAP Foundation, Co-Director, Rare Lung Diseases Clinical Research Consortium, and Professor of Medicine and Pediatrics, University of Cincinnati College of Medicine. Slides from the presentation were attached to Savara’s Form 8-K dated October 2, 2019 and will be posted to the Investor Relations section of the Company’s website.
About Savara
Savara is an orphan lung disease company. Savara’s pipeline comprises Molgradex, an inhaled granulocyte-macrophage colony-stimulating factor (GM-CSF) in Phase 3 development for autoimmune pulmonary alveolar proteinosis (aPAP), in Phase 2a development for nontuberculous mycobacterial (NTM) lung infection in both non-cystic fibrosis (CF) and CF-affected individuals with chronic NTM lung infection; and AeroVanc, a Phase 3-stage inhaled vancomycin for treatment of persistent methicillin-resistant Staphylococcus aureus (MRSA) lung infection in CF. Savara’s strategy involves expanding its pipeline of potentially best-in-class products through indication expansion, strategic development partnerships and product acquisitions, with the goal of becoming a leading company in its field. Savara’s management team has significant experience in orphan drug development and pulmonary medicine, identifying unmet needs, developing and acquiring new product candidates, and effectively advancing them to approvals and commercialization. More information can be found at www.savarapharma.com. (Twitter: @SavaraPharma, LinkedIn: www.linkedin.com/company/savara-pharmaceuticals/)
Forward Looking Statements
Savara cautions you that statements in this press release that are not a description of historical fact are forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Forward-looking statements may be identified by the use of words referencing future events or circumstances such as “expect,” “intend,” “plan,” “anticipate,” “believe,” and “will,” among others. Such statements include, but are not limited to, statements regarding working to determine the next steps for the Molgradex development program, that we remain committed to the Molgradex development program and believe that it will provide aPAP patients with a meaningful treatment option, that our priority is to further assess the content of the FDA’s feedback and determine the best regulatory path forward, and Savara’s strategy. Savara may not actually achieve any of the matters referred to in such forward-looking statements, and you should not place undue reliance on these forward-looking statements. These forward-looking statements are based upon Savara’s current expectations and involve assumptions that may never materialize or may prove to be incorrect. Actual results and the timing of events could differ materially from those anticipated in such forward-looking statements as a result of various risks and uncertainties, which include, without limitation, the outcome of our assessment of the feedback from our Type C meeting with the FDA regarding our IMPALA data and path forward, risks and uncertainties associated with the outcome of our ongoing and planned clinical trials for our product candidates, the ability to project future cash utilization and reserves needed for contingent future liabilities and business operations, the availability of sufficient resources for Savara’s operations and to conduct or continue planned clinical development programs, the ability to obtain the necessary patient enrollment for our product candidates in a timely manner, the ability to successfully identify product acquisition candidates, the ability to successfully develop our product candidates, the risks associated with the process of developing, obtaining regulatory approval for and commercializing drug candidates such as Molgradex and AeroVanc that are safe and effective for use as human therapeutics, and the timing and ability of Savara to raise additional equity capital as needed to fund continued operations. All forward-looking statements are expressly qualified in their entirety by these cautionary statements. For a detailed description of our risks and uncertainties, you are encouraged to review our documents filed with the SEC including our recent filings on Form 8-K, Form 10-K and Form 10-Q. You are cautioned not to place undue reliance on forward-looking statements, which speak only as of the date on which they were made. Savara undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made, except as may be required by law.
Contacts:
Savara Inc. IR & PR
Anne Erickson (anne.erickson@savarapharma.com)
(512) 851-1366
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