Kyntra Bio, Inc. · NASDAQ:KYNB
Kyntra Bio — FibroGen — Technical Presentation (June 2019)
29 slides from Kyntra Bio's technical presentation, Jun 28, 2019
Slide 1: Study 079 Phase 2 Pamrevlumab in Non-Ambulatory DMD: Preliminary Clinical Results
Study 079 – An Open-Label, Single-Arm Phase 2 Trial Evaluating Pamrevlumab, a Monoclonal Antibody to Connective Tissue Growth Factor (CTGF) in Non-Ambulatory Subjects with Duchenne Muscular Dystrophy (NCT02606136) PRELIMINARY CLINICAL RESULTS Ken Lipson, Ph.D. – Executive Director, Drug Research Bas
Slide 2: Agenda
Pamrevlumab Mechanism of Action Overall Summary of Study FG-3019-079 in Non-Ambulatory Subjects with Duchenne Muscular Dystrophy Preliminary Clinical Results: Positive data that shows improvement over previously published studies in terms of progression of DMD, as measured by Pulmonary Function Test
Slide 3: Pamrevlumab
Pamrevlumab (FG-3019), is a fully human monoclonal antibody (mAb) against CTGF, currently under development in non-ambulatory DMD patients, idiopathic pulmonary fibrosis (IPF), and locally advanced pancreatic cancer (LAPC). Pamrevlumab treatment has been shown to positively affect the course of seve
Slide 4: CTGF a Central Mediator of Tissue Remodeling and Fibrosis
Connective Tissue Growth Factor (CTGF) a Central Mediator of Tissue Remodeling and Fibrosis Adapted from Lipson et al. (2012) Fibrogenesis & Tissue Repair 5:S24 Multiple positive feedback loops with CTGF at the center contribute to the progressive nature of fibrosis Pamrevlumab is a human monoclonal
Slide 5: Current Understanding of Pamrevlumab Mechanism of Action
Current Understanding of Pamrevlumab Mechanism of Action
Slide 6: Study 079 Design (N=21)
This is an open-label, single-arm Phase 2 study in non-ambulatory subjects with Duchenne muscular dystrophy. Each subject will receive pamrevlumab (35 mg/kg every 2 weeks) for up to 156 weeks. Safety was assessed regularly by laboratory results and physical examination, and efficacy was evaluated by
Slide 7: Demographics and Baseline Characteristics
All subjects were male, non-ambulatory, with the majority being white (20 Caucasians and 1 Asian), and received 35 mg/kg IV infusions of pamrevlumab every 2 weeks. Median age at DMD diagnosis was 5.5 years (0.6, 12.2), with a median duration of being non-ambulatory prior to study enrollment of 3.4 y
Slide 8: Safety Summary
SAFETY SUMMARY
Slide 9: Safety Results - TEAEs
Pamrevlumab appears to be well tolerated in pediatric subjects with non-ambulatory DMD. Most treatment-emergent adverse events (TEAEs) were mild to moderate in severity per the Common Terminology Criteria for Adverse Events (CTCAE). There were no TEAEs that led to pamrevlumab or study discontinuatio
Slide 10: Safety Results - SAEs
Safety Results - SAEs Preferred Term All Subjects (N=21) n (%) Subjects with Any Serious TEAEs 6 (28.6) Food Poisoning 1 (4.8) Adverse Drug Reaction 1 (4.8) Pneumonia 1 (4.8) Concussion 1 (4.8) Femur Fracture 1 (4.8) Skull Fracture 1 (4.8) Metabolic Acidosis 1 (4.8) Hydronephrosis 1 (4.8) Nephrolith
Slide 11: Efficacy Summary: Pulmonary Function
EFFICACY SUMMARY PULMONARY FUNCTION
Slide 12: Pulmonary Function
Pulmonary dysfunction in DMD is progressive and restrictive in nature and is one of the most common causes of morbidity and mortality in non-ambulatory patients. In Study 079, pulmonary function was evaluated using spirometry assessments at baseline and Q12 weeks thereafter. In the preliminary analy
Slide 13: Results – Pulmonary Function (ppFVC)
Percent Predicted Forced Vital Capacity (ppFVC): Forced vital capacity assessed by spirometry is the best global assessment of all respiratory muscles, because it requires a full inspiration (reflecting function of inspiratory muscles) and a full expiration (reflecting function of expiratory muscles
Slide 14: Results – Pulmonary Function (ppFEV1)
Percent Predicted Forced Expiratory Volume at 1 Second (ppFEV1) With the exception of obstructive pulmonary disease, FEV1 very closely follows FVC with the advantage of requiring a less prolonged effort (1 second)⁷. Data from the placebo group in the DELOS study¹⁰ has shown that yearly rates of ppFE
Slide 15: Results – Pulmonary Function (ppPEFR)
Percent Predicted Peak Expiratory Flow Rate (ppPEFR) The 1-year change for ppPEFR was −5.8% ± 0.6%/year (mean ± SE) based on prospective data in DMD patients (68% of patients were being treated with steroids, 42% were non-ambulatory), collected in the Neuromuscular Clinic at CHOP from 2005–2010⁸. In
Slide 16: Efficacy Summary: Cardiac Function
EFFICACY SUMMARY CARDIAC FUNCTION
Slide 17: Cardiac Function
Cardiac Function Patients with DMD have progressive cardiac muscle dysfunction, which is considered to be one of the leading causes of mortality. Cardiac magnetic resonance imaging (cMRI) was used at baseline and Week 52 to assess the left ventricular ejection fraction percentage (LVEF%) and cardiac
Slide 18: Results – Left Ventricular Ejection Fraction (LVEF)
Left Ventricular Ejection Fraction (LVEF) Based on data tracking the natural disease history, a decrease in LVEF -0.82% per year of age has been observed (McDonald et al. 2018¹⁴ - N=305). Study 079 Baseline LVEF: For All Subjects (ITT), the mean LVEF percentage at baseline (N=19) was 56.74% and the
Slide 19: Results – Cardiac Fibrosis by MLGE
Cardiac Fibrosis Score Assessed by Mass of Late Gadolinium Enhancement (MLGE) Mass of Late Gadolinium Enhancement (MLGE) is a strong marker for the progression of left ventricular systolic dysfunction in DMD patients. Additionally, myocardial fibrosis burden correlates strongly with LVEF¹⁵. In Study
Slide 20: Efficacy Summary: Muscle Function
EFFICACY SUMMARY MUSCLE FUNCTION
Slide 21: Muscle Function: Upper Arm Function
Upper Arm Function Preserving upper limb strength is very important in non-ambulatory DMD patients, because it provides functional independence. In Study 079, biceps brachii MRI was assessed at baseline and at Week 52. Additionally, functional assessments including the performance of upper limb (PUL
Slide 22: Results – Performance of the Upper Limb
Performance of the Upper Limb (PUL) PUL assessment was specifically developed for patients with DMD to assess the function of the upper limb in young ambulant males to older and weaker non-ambulant adults. Baseline mean PUL score: In Study 079, the mean score at baseline (N=21) was 24.4 and the medi
Slide 23: Results – Upper Arm Muscle Fibrosis and Fat by MRI
Upper Arm (biceps brachii) MRI Fat and Fibrosis (T2 Mapping) In recent years, several longitudinal studies have reported the potential value of MRI as a biomarker to assess disease progression and treatment effect in DMD. T2-mapping can help determine the level of inflammation, edema and fat infiltr
Slide 24: Results – Upper Arm Function Grip by HHM
HHM - Grip Strength Hand held myometry has shown very good reliability and feasibility in non-ambulatory DMD patients¹⁸. Baseline Grip Score In Study 079, at baseline (N=21), the mean grip strength score was 45.86 newton (median 37.00) for the dominant hand and 41.97 (median 37.00) for the non-domin
Slide 25: Cautions
Small number of patients (N=21) Single-arm, open-label study All comparisons are with historical published data, therefore, they should be interpreted with caution as there are, among other things, differences in subject numbers, baseline characteristics, inclusion/exclusion criteria, treatment prot
Slide 26: Conclusion
Preliminary clinical results from Study 079, showed that one year of pamrevlumab treatment in non-ambulatory DMD subjects was well tolerated. The most common TEAEs occurred in >25% of subjects in descending order were: headache, nasopharyngitis, vomiting and cough. Most of the patients, who experien
Slide 27: Thank You
THANK YOU
Slide 28: References
¹ Andrews J and Wahl R. (2018) Duchenne and Becker muscular dystrophy in adolescents: current perspectives. Adolesc Health Med Ther. 9:53-63. ² Henricson EK, Abresch RT, Cnaan A, et al. (2013) The cooperative international neuromuscular research group Duchenne natural history study: glucocorticoid t
Slide 29: Questions?
Questions?