Kyntra Bio, Inc. · NASDAQ:KYNB
Kyntra Bio — Fibrogen — Investor Presentation (February 2016)
53 slides from Kyntra Bio's investor presentation, Feb 11, 2016
Slide 1: Corporate Presentation February 2016
Corporate Presentation February 2016 Exhibit 99.1
Slide 2: Forward-looking statements
This presentation, the accompanying modules, and in each case the oral commentary contain “forward-looking” statements that involve substantial risks and uncertainties. All statements other than statements of historical facts contained in this presentation, the accompanying modules, and in each case
Slide 3: Investment Highlights
IPF: idiopathic pulmonary fibrosis DMD: Duchenne Muscular Dystrophy TREAT-NMD is an EU-based network aiming to advance treatments and care for patients with neuromuscular disease; TACT, the TREAT-NMD Advisory Committee for Therapeutics, is an expert multidisciplinary body that provides the neuromusc
Slide 4: Our Platforms and Product Portfolio
HIF PLATFORM PRECLINICAL PHASE 1 PHASE 2 PHASE 3 Roxadustat (HIF-PH Inhibitor for anemia) United States / Europe China Japan Our Platforms and Product Portfolio FIBROTIC DISEASE PLATFORM PRECLINICAL PHASE 1 PHASE 2 PHASE 3 FG-3019 (Anti-CTGF Antibody) Idiopathic Pulmonary Fibrosis Pancreatic Cancer
Slide 5: Roxadustat – Recent Highlights
Roxadustat – Recent Highlights Global program on schedule to submit regulatory filings in 2016 for China and 2018 for US January 2016: DSMB chair reviewed safety data and recommended that studies continue with current protocols Target patient enrollment update (FibroGen responsible for 3 of 7 Phase
Slide 6: China Program - Recent Highlights
China Program - Recent Highlights Phase 3 clinical trials initiated First patient dosed DD-CKD Q4 2015 (N=300) First patient dosed ND-CKD Q4 2015 (N=150) Initial China regulatory submission expected in 2016 – rolling review Development expansion beyond CKD anemia AZ alignment on China CTA submission
Slide 7: FG-3019 - Recent Highlights
FG-3019 - Recent Highlights IPF – Study 067 FG-3019 vs. placebo arms >50% enrolled (target n=90) Expansion of study sites to include countries where approved IPF therapies have not fully penetrated the markets Expanding study to include patients on approved therapy Pancreatic cancer – Study 069 Pres
Slide 8: Q3 2015 Financial Highlights
Q3 2015 Financial Highlights $365.6M of cash, cash equivalents, investments, and receivables on September 30, 2015 Cap of $116.5M on FibroGen’s funding obligations for roxadustat CKD anemia development (ex-China) met in Q4 2015 Going forward, now that the cap has been met: Astellas and AstraZeneca w
Slide 9: $116.5M Cap Roxadustat Cost Share Met in Q4 2015
$116.5M Cap, 50-50 Roxadustat Development Cost Share Met In Q4 2015 Before/After Illustration – Assuming $160M total annual roxadustat development expenses (based on Q2/Q3 2015 run rates) GAAP OpEx BEFORE: AstraZeneca bills FibroGen for $40M, or 50% of its $80M in development expenses AFTER: AstraZe
Slide 10: Development Timeline
2015 2016 2017 2018 2H 1H 2H 1H 2H 1H 2H China EU / Japan IPF Pancreatic DMD Liver Development Timeline ROXADUSTAT FG-3019 Stretch Goal for Complete Enrollment in FGEN Ph3 Studies December 2015 Base Goal for Complete Enrollment in FGEN Ph3 Studies March/April 2016 26-week Data Readout from Ph3 Initi
Slide 11: Roxadustat
FIBROGEN Roxadustat
Slide 12: Anemia
Anemia 101 THE CONDITION Reduced Oxygen-Carrying Capacity of Blood ANEMIA IN CKD Dialysis & Pre-Dialysis INCREASED MORTALITY RED BLOOD CELL CREATION (ERYTHROPOIESIS) Hepcidin - Reduces Availability of Iron for RBC Production
Slide 13: Roxadustat Activates a Natural Pathway to Increase Red Blood Cell Production
LOW OXYGEN (e.g., High Altitude) or HIF-α ROXADUSTAT HIF-β HIF-α HIF-PH1 Enzymes HIF-PH Enzymes NORMAL OXYGEN ✕ Degradation HIF-α Roxadustat Stabilizes HIF-α Gene Transcription HIF-α Degrades Rapidly EPO Within or Near Physiological Range Red Blood Cell Production Hepcidin Levels Iron Transport to t
Slide 14: Roxadustat Achieves Target Hb within or near Physiologic EPO Cmax Levels
1 Cmax data for roxadustat estimated for a subset of 243 patients who achieved Hb response and were dosed at expected therapeutic doses. 2 Milledge & Cotes (1985) J Appl Physiol 59:360. 3 Goldberg et al. (1993), Clin Biochem 26:183, Maeda et al. (1992) Int J Hematol 55:111. 4 Kato et al. (1994) Ren
Slide 15: Roxadustat in Anemia of Inflammation (preclinical)
Roxadustat Increased Hb Aranesp® Increased Hb but Reduced Mean Cell Volume (Depletes Iron) IV Iron Ineffective Roxadustat Increased Hb Aranesp® or IV Iron Ineffective for Anemia of Inflammation ESAs Ineffective or Require High Doses in Presence of Inflammation in Preclinical Model Abs Hb g/dL 19.6 A
Slide 16: Roxadustat Reduces Hepcidin
Roxadustat Reduces Hepcidin Decreased Hepcidin Improves Iron Availability and Reduces ESA Resistance CKD-DD Patients Previously Treated with EPO and Randomized (Study 040a) (Conversion, ESA Hyporesponders) CKD-DD Newly Initiated Dialysis (Study 053) Mean (±SE) Hepcidin (ng/mL) n=52 n=52 Baseline Wee
Slide 17: Hb Correction Appears Independent of Inflammation (Study 053)
Hb Correction and Maintenance by Roxadustat Appear Independent of Inflammation (Study 053) As shown by CRP (marker of inflammation) Hb correction appears independent of inflammatory state Dose requirement for Hb maintenance appears independent of inflammatory state Greater reduction in hepcidin leve
Slide 18: Phase 2 Program Conducted Across Different CKD Populations
Phase 2 Program Conducted Across Different CKD Populations STUDY PATIENTS WEEKS DOSE LEVELS TIER WEIGHTS CONTROL KEY RESULTS Placebo-Controlled Pre-Dialysis 017 Dose Range Finding, NDD 116 4 4 No Placebo Reduction in Hepcidin Dose-dependent Increase in Hb 047 Pre-dialysis 91 8 2 3 Placebo Encouragin
Slide 19: Study 017: Placebo-Controlled Proof of Concept Study
Study 017: Placebo-Controlled Proof of Concept Study in Pre-Dialysis Anemic Pre-dialysis Patients not Receiving ESA Randomized to Placebo or Roxadustat, BIW or TIW 4-week Dose Ranging Study Evaluating 4 Weight-based Doses Responder = Hb rise ≥1 g/dL Mean (± SE) Δhbmax (g/dL) MEDIAN TIME TO RESPONSE
Slide 20: Study 047: Placebo-Controlled Study in Pre-dialysis
Study 047: Placebo-Controlled Study in Pre-dialysis TREATMENT N Baseline Hb MAX Change in HB P-Value vs Placebo PATIENTS WITH HB INCREASE ≥ 1 G/DL P-Value vs Placebo High Dose 31 8.9 2.4 <0.0001 93.1% <0.0001 Low Dose 30 8.8 1.6 <0.0001 88.5% <0.0001 Placebo 30 9.0 0.4 25.9% OBSERVATIONS High Dose:
Slide 21: Studies 048 and 040a: ESA Comparator Conversion Studies
Studies 048 and 040a: ESA Comparator Study in Stable Dialysis Patients when Switched from Epoetin α (Conversion) OBSERVATIONS – Study 048 OBSERVATIONS – Study 040a (6 wks) Hemodialysis Patients with Hb Corrected on Stable Doses of ESA Randomized to Roxadustat TIW or Continuation of EPO for 6 Weeks o
Slide 22: Study 040b: ESA Comparator Study in Stable Dialysis
Study 040b: ESA Comparator Study in Stable Dialysis Patients when Switched from Epoetin α (Conversion) Mean (±SE) Hemoglobin (g/dL) DESIGN – Stable Dialysis Conversion from ESA Hemodialysis Patients with Hb Corrected on Stable Doses of ESA Randomized to Roxadustat TIW or Continuation of EPO 19-week
Slide 23: Study 041: Dose Finding in Pre-dialysis
Study 041: Dose Finding in Pre-dialysis Different Targets, Different Correction Rates, Single Maintenance Algorithm 92% Response Rate Correction Achieved and Maintained to Ends of Treatment, Regardless of Starting and Maintenance Dose Reduction in Serum Hepcidin at Week 9 vs Baseline, p=0.0003 CKD P
Slide 24: Study 053: Roxadustat Corrects Anemia in Newly Initiated Dialysis
Study 053: Roxadustat Corrects Anemia in Newly Initiated Dialysis Patients without IV Iron Besarab, et al., J Am Soc Nephrol 23:428A and 24:91A. * p<0.05 compared to IV iron and oral iron * * Weeks on Treatment DESIGN OBSERVATIONS Incident Dialysis (Newly Initiated Dialysis) Patients with Low Hb Lev
Slide 25: Conclusions: Phase 2 Studies
Conclusions: Phase 2 Studies Evaluated Broad Range of CKD Patient Population: Stable Dialysis, Incident Dialysis and Nondialysis; ESA Hyporesponders In Dialysis and Nondialysis: Consistent, Dose-Dependent Hb Response with Roxadustat In Nondialysis: Both Tiered and Fixed Dosing Regimens Produced 90%
Slide 26: Roxadustat Safety Review
Roxadustat Safety Review No Overall Safety Signal An independent data monitoring committee reviewed data Frequency and type of AEs expected in CKD patients No Cardiovascular Signal Lowers Cholesterol Levels No Increase in Blood Pressure Reduction in Blood Pressure at End of TIW Dosing Platelet Reduc
Slide 27: Roxadustat Submissions for Marketing Approvals: US, Europe, and China
Roxadustat Submissions for Marketing Approvals: US, Europe, and China Indication Treatment of Anemia Associated with Chronic Kidney Disease (CKD) in Patients on Dialysis and Not on Dialysis Primary Efficacy Endpoints - Based on Hemoglobin (Hb) Measurements Change in Hb from Baseline, or % Hb respond
Slide 28: Roxadustat Phase 3 Program
Roxadustat Phase 3 Program STUDY NUMBER COMPARATOR RANDOM- IZATION N STUDY LOCATIONS CHINA EUROPE US STUDY SPONSOR PHASE 3 STUDIES TO SUPPORT REGULATORY APPROVAL Stable Dialysis CL-6131 Epoetin α/Darbe 376/200/174 750 EU, MEA3 36+ wks 52+wks Astellas FG-0641 Epoetin α 1:1 Up to 750 US+/-Global 36+ w
Slide 29: Roxadustat Has Potential to Address Unmet Need in Multiple Markets
Disease Dialysis Pre-Dialysis Limitations on ESA Treatment Clinician Nephrologist Where ESA Is Avail Now 36% Anemic¹ 20% Anemic¹ Endocrinologist/ Diabetologist Cardiologist/ Internist Myelodysplasia Chemotherapy Induced Anemia Oncologist IBD, Lupus, RA, etc. GI/Rheumatologist/ Internist Roxadustat H
Slide 30: Roxadustat Market Opportunity
Disease Dialysis Pre-Dialysis Roxadustat Market Opportunity Clinician Nephrologist Where ESA Is Avail Now 36% Anemic¹ 20% Anemic¹ Endocrinologist/ Diabetologist Cardiologist/ Internist Myelodysplasia Chemotherapy- Induced Anemia Oncologist IBD, Lupus, RA, etc. GI/Rheumatologist/ Internist Potential
Slide 31: China Opportunity
China Opportunity Unique Positioning as a Domestic Chinese Company CFDA Green Pass Status AZ, Our Commercial Partner, 2nd Largest Multinational Pharmaceutical Company by Sales in China 1st Phase 3 Results with Roxadustat – Potential 1st Launch Country Potential Entry into #2 Pharma Market in the Wor
Slide 32: China Phase 3 Program
China Phase 3 Program Completion of Enrollment (Dialysis Study): Projected Q2 2016 Completion of Enrollment (Non-Dialysis Study): Projected Q3 2016 Primary Efficacy Safety Subjects Arm Endpoint Assessment 200 Roxadustat 26 weeks 100 ESA 52 weeks 100 Roxadustat 8 weeks 50 Placebo Total 2 Studies: 300
Slide 33: Corneal Implants – FG-5200 (China)
URGENT, SEVERE UNMET MEDICAL NEED Approximately 4 to 5 Million Patients with Corneal Blindness in China 100,000 New Cases per Year, Approx. 3,000 Corneal Implant Surgeries Cadaver Transplants Very Limited by Cultural Restriction PLATFORM TO FOCUS ON CHINA FIRST FG-5200 Targets Patients Treatable wit
Slide 34: Roxadustat Global Partnerships
Roxadustat Global Partnerships $ Millions JAPAN, EU, ETC. U.S., CHINA, ROW Cash Received to Date* Equity Investment in FibroGen $81 $20 $101 Upfront, Non-Contingent $360 $402 $360 + $340 Development & Reg. Milestones $543 $571 $118 Commercial Milestones $15 $653 $0 POTENTIAL TOTAL $918 M $1,626 M $6
Slide 35: FG-3019 Monoclonal Antibody to CTGF
FG-3019 Monoclonal Antibody to Connective Tissue Growth Factor (CTGF)
Slide 36: Central Role of CTGF in Fibrosis
Central Role of Connective Tissue Growth Factor (CTGF) in Fibrosis FIBROGEN: SCIENTIFIC LEADERSHIP IN FIBROSIS FibroGen’s founding focus on the pathophysiology of fibrosis and diseases associated with persistent and excessive scarring FG-3019 is an internally discovered antibody to CTGF CELLULAR RES
Slide 37: FG-3019 Improved Fibrosis in Mouse Model and in Human Disease
FG-3019 Improved Fibrosis in Mouse Model and in Human Disease Improved / Stable Fibrosis Correlates with Improved Lung Function Improved/ Stable Fibrosis Worse Fibrosis Reversal of Lung Fibrosis by High Resolution CT at Week 48 Improved/Stable 38% Subject NORMAL Hounsfield Units Increasing Fibrosis
Slide 38: Dose-Dependent Survival in Advanced Pancreatic Cancer
Relationship of 1-Year Survival to Dose Percent 1 Year Survival Rate Dose-Related Increase in Survival Day-15 Minimum FG-3019 Plasma Level ≥ 150 µg/mL 2x Median Survival (9.4 vs. 4.8 Months) (p=0.025) 3x One-Year Survival (37% v 11%) (p=0.01) Phase 2 Dose-Dependent Survival in Advanced Pancreatic Ca
Slide 39: Phase 2 Trials in Pancreatic Cancer, DMD and IPF
Phase 2 Trials in Pancreatic Cancer, DMD and IPF Main goal: convert to operable state N=42 Randomization 2:1 up to 6 months of FG-3019, gemcitabine, nab-paclitaxel Gemcitabine and nab-paclitaxel Endpoint: complete tumor removal Currently enrolling LOCALLY ADVANCED INOPERABLE PANCREATIC CANCER Open-l
Slide 40: Localized Pancreatic Cancer
Localized Pancreatic Cancer 47,000 new cases of pancreatic cancer per year in U.S. 1 50% of patients with pancreatic cancer have no detectable metastases at presentation 23,500 classified as clinically localized (50%)1 8,225 with pancreatic cancer that precludes resection1 15,275 with tumors that ar
Slide 41: Preliminary Data from Open-Label Resection Study
Preliminary Data from Open-Label Resection Study ITT Still On Treatment Completed 6-month course of therapy Re-scored as eligible for resection R0 (no residual disease) R1 (microscopic residual disease) SOC alone (gemcitabine + nab-paclitaxel) 6 2 2 (2 others discontinued due to disease progression)
Slide 42: Preliminary LAPC Data
Preliminary LAPC Data Need to see more patient data, but trends are encouraging Subjects who failed resection scoring and were deemed inoperable were randomized to two treatment arms: chemotherapy vs. chemotherapy + FG-3019 In the FG-3019 + chemotherapy treatment arm, the tumors in 3 of the first 4
Slide 43: Changes in Tumor Marker CA19.9
Changes in Tumor Marker CA19.9* Chemo + FG-3019 Chemo Percent Change in CA19.9 *Preliminary Data
Slide 44: Change in Tumor Size (RECIST criteria)
Change in Tumor Size (RECIST criteria)* Percent Change in Tumor Size Chemo + FG-3019 Chemo *Preliminary Data Baseline Week 8 Week 16 Week 24
Slide 45: Duchenne Muscular Dystrophy (DMD) and CTGF Blockade
Duchenne Muscular Dystrophy (DMD) and CTGF Blockade DMD – rare hereditary disease: ~1 in 3,500 boys in the US No FDA/EU approved treatment to date Progressive muscle weakness and respiratory failure (age 5-18) DMD leads to muscle fibrosis and loss of muscle function: muscles replaced by fibrotic tis
Slide 46: FG-3019 Decreased Fibrosis and Increased Muscle Strength in mdx Mice
FG-3019 Decreased Fibrosis and Increased Muscle Strength in mdx Mice FG-3019 significantly reduced collagen content/fibrosis in muscle (mdx mouse) FG-3019 fibronectin content/fibrosis in muscle (mdx mouse)
Slide 47: Decreased CTGF Increased Skeletal Muscle Function in mdx Mice
Decreased CTGF Increased Skeletal Muscle Function in mdx Mice CTGF hemi-zygous or FG-3019-treated mdx mice exhibited increased isometric force WT- wild type, normal mice; mdx - disease model
Slide 48: FG-3019 Increased Muscle Endurance in mdx Mice
FG-3019 Increased Muscle Endurance in mdx Mice 5-min treadmill exercise tolerance test: mdx mice treated with FG-3019 stopped fewer times to rest than untreated mice (mdx-control) and were more similar to normal mice Morales, Hum Mol Genet-Suppl Data (2013)
Slide 49: HIF Research
FIBROGEN HIF Research
Slide 50: Targeting Tumor Metastasis
Targeting Tumor Metastasis Metastasis, the process by which cancer spreads to nearby lymph nodes or distant organs, is a defining feature of cancer. Metastasis occurs in tumors of all types but especially in melanoma, lung, breast, ovarian, prostate, and pancreatic cancers. Metastases are the major
Slide 51: FG-6888 Reduced Tumor Burden in Experimental Metastasis Model
FG-6888 Significantly Reduced Tumor Burden in An Experimental Metastasis Model The “tail vein” experimental metastasis model is used to evaluate the ability of tumor cells to arrest, extravasate, and grow in various organs following intravascular injection. Uses MDA-MB-231-luc human breast tumor cel
Slide 52: FG-6888 Reduced Tumor Burden: Dose Response Study
FG-6888 Significantly Reduced Tumor Burden in Tail-Vein Model: Dose Response Study Female BALB/c nude mice (n=14/group) inoculated with 1 million cells by tail vein injection on Day -3 Oral daily dosing of 20-80mg/kg FG-6888 (or vehicle) starting on Day 0 (3 days after tumor cell injection) and cont
Slide 53: FibroGen
FIBROGEN February 2016