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VILTEPSO Increases Dystrophin, a Key Protein for Supporting Muscle Health1

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VILTEPSO Increases Dystrophin, a Key Protein for Supporting Muscle Health1 For the treatment of DMD in patients amenable to exon 53 skipping VILTEPSO increases dystrophin, a key protein for supporting muscle health1 The first and only exon 53-skipping therapy to demonstrate an increase in dystrophin in children as young as 4 years1 • Patients taking VILTEPSO showed a mean increase in dystrophin expression from 0.6% at baseline to 5.9% of normal after 20 to 24 weeks of treatment1 Indication VILTEPSO is indicated for the treatment of Duchenne muscular dystrophy (DMD) in patients who have a confirmed mutation of the DMD gene that is amenable to exon 53 skipping. This indication is approved under accelerated approval based on an increase in dystrophin production in skeletal muscle observed in patients treated with VILTEPSO. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial. Important Safety Information Warnings and Precautions: In clinical studies, no patients experienced kidney toxicity during treatment with VILTEPSO. However, kidney toxicity from drugs like VILTEPSO may be possible. Serum cystatin C, urine dipstick, and urine protein-to-creatinine ratio should be measured before starting and during treatment with VILTEPSO. Consider measuring GFR before starting VILTEPSO. Please see Important Safety Information throughout. For more information about VILTEPSO, see accompanying full Prescribing Information. Lack of dystrophin (dystrophinopathy) VILTEPSO is the first and only causes a progressive loss of muscle strength exon 53-skipping therapy to and motor function2,3 demonstrate an increase in dystrophin in children as young as 4 years1 Duchenne muscular dystrophy (DMD) HEALTHY COMPLETE 3,5 is caused by mutations in the DYSTROPHIN GENE DYSTROPHIN VILTEPSO is designed to bind to and induce dystrophin gene, which leads to a skipping of exon 53 of the lack of dystrophin production.4 EXONS 1-79 dystrophin pre-mRNA, resulting in the production of a shortened dystrophin protein that contains essential functional portions1 Patients with DMD experience MUTATED INCOMPLETE An estimated 10% of patients with DMD DYSTROPHIN GENE DYSTROPHIN progressive muscle weakness, with would be amenable to exon 53 skipping9* symptom onset as early as 2 years.6 EXONS 1-51 EXON EXONS 53-79 52 VILTEPSO was discovered through an innovative triple-screening approach designed to identify antisense oligonucleotides with the highest possible exon-skipping efficiency10 EARLY DIAGNOSIS is instrumental to inform the management of progressive muscle weakness and function decline in patients with DMD.7, 8 *Common dystrophin gene mutations eligible for exon 53 skipping include deletions in exons 45-52, 47-52, 48-52, 49-52, 50-52, and 52.9 mRNA=messenger RNA. Please see additional Important Safety Important Safety Information Information throughout. For more Adverse Reactions: The most common adverse reactions include upper respiratory tract information about VILTEPSO, see infection, injection site reaction, cough, and pyrexia. accompanying full Prescribing Information. 2 3 The safety and efficacy of VILTEPSO have been studied in an ongoing clinical trial program1,5,11,12 Study endpoints Description Day 1 Week 5 Week 24 Primary: Safety, tolerability, A 2-period, North American dose-finding MUSCLE BIOPSY MUSCLE BIOPSY (week 25) dystrophin protein study with ambulant males aged 4 to <10 Period 1 Period 2 Extension production (Western blot) years with a confirmed mutation of the (168 weeks) 80 MG/KG/WK 40 mg/kg 40 mg/kg; n=6 IS THE APPROVED DMD gene amenable to exon 53 skipping (Phase II) 40 mg/kg; n=8 40 mg/kg; n=8 Secondary: Other dystrophin n=8 RECOMMENDED who were receiving a stable dose of Placebo; n=2 DOSE FOR measures (RT-PCR, MS, IFS), 1,5,11 N=16 VILTEPSO motor function tests (6MWT, corticosteroids for ≥3 months (N=16) 80 mg/kg; n=5 80 mg/kg TTCLIMB, TTRW, TTSTAND), 24 weeks, followed by a 168-week Study 1 n=8 80 mg/kg; n=8 80 mg/kg; n=8 Placebo; n=3 NSAA, QMT extension study Primary: Dystrophin measures A multicenter, parallel-group, open-label, Week 12 Week 24 (Western blot, IFS, RT-PCR) dose-finding study conducted in Japan in n=4 80 MG/KG/WK 40 mg/kg ambulant and nonambulant* males aged IS THE APPROVED Secondary: Safety, n=8 n=4 5 to <18 years with a confirmed mutation (Phase I/II) RECOMMENDED pharmacokinetics, motor N=16 MUSCLE BIOPSY of the DMD gene amenable to exon 53 (week 25) DOSE FOR function tests (6MWT, TTRW, 80 mg/kg n=4 VILTEPSO skipping (N=16)1,5 n=8 TTSTAND, Timed Up & Go test), n=4 muscle strength, serum CK levels 24 weeks Study 2 Primary: TTSTAND A global, multicenter, randomized, double- blind, placebo-controlled study in ambulant 48 weeks Secondary: TTRW, TTCLIMB, males aged 4 to <8 years with a confirmed Placebo 6MWT, NSAA, muscle strength (Phase III) mutation of the DMD gene amenable to n=37 N=74 exon 53 skipping who were receiving a stable (recruiting) 12 80 mg/kg n=37 dose of corticosteroids for ≥3 months (N=74) n=37 48 weeks RACER53 As part of the accelerated approval of VILTEPSO, NS Pharma is *Defined as patients with a 6MWT distance of <75 meters. CK=creatine kinase; IFS=immunofluorescence staining; MS=mass spectrometry; NSAA=North Star Ambulatory Assessment; conducting a CONFIRMATORY STUDY, begun in October 2019, QMT=Quantitative Muscle Testing; RT-PCR=reverse transcriptase-polymerase chain reaction; 6MWT=6-Minute Walk Test; to further evaluate the functional benefit of treatment. TTCLIMB=Time to Climb 4 Stairs; TTRW=Time to Run/Walk 10 Meters; TTSTAND=Time to Stand from Supine. Important Safety Information Warnings and Precautions: In clinical studies, no patients experienced kidney toxicity Please see additional Important Safety during treatment with VILTEPSO. However, kidney toxicity from drugs like VILTEPSO may be Information throughout. For more possible. Serum cystatin C, urine dipstick, and urine protein-to-creatinine ratio should be information about VILTEPSO, see measured before starting and during treatment with VILTEPSO. Consider measuring GFR accompanying full Prescribing Information. before starting VILTEPSO. 4 5 VILTEPSO provided significant improvements 100% of patients showed an increase in dystrophin expression9 in dystrophin levels with VILTEPSO1 In Study 1 the efficacy of 20-24 weeks of VILTEPSO was evaluated in ambulant males aged 4 to <10 years.9 Study 1: Mean increase in dystrophin expression to nearly 6% of normal Study 1: Dystrophin levels at 25 weeks vs baseline5 with VILTEPSO (80 mg/kg/wk) vs 0.6% at baseline1,9 16.0% 14.42% 14.0% % 7.0% % 88 of patients (7/8) showed 5.9 increased dystrophin levels at Baseline 6.0% 12.0% ~3% of normal or higher 10.40% Week 25 5.0% 10.0% 4.0% % 8.0% 7.40 3.0% 6.0% 2.0% % 3.97% 4.07% Mean normal dystrophin (%) 1.0% 0.6 P=0.01 4.0% % 3.06% normalized to myosin 2.97 0.0% heavy chain* 2.0% 1.14% Baseline Treated 20-24 weeks (n=8) (n=8) 0.0% 0.46% 0.46% 0.43% 0.40% 0.09% 2.61% 0.09% 0.51% Dystrophin expression (% of normal) normalized to myosin heavy chain Patient Patient Patient Patient Patient Patient Patient Patient A B C D E F G H *P-value for change from baseline at week 25 was statistically significant.9 Exon 53 skipping was observed, on average, in 43.9% of dystrophin mRNA molecules in DYSTROPHIN WHERE IT MATTERS: Immunofluorescence staining patients treated with VILTEPSO (80 mg/kg/wk), as measured by RT-PCR5 showed VILTEPSO-induced increases in dystrophin levels were correctly localized to the muscle cell membrane.5,9 Please see additional Important Safety Important Safety Information Information throughout. For more Adverse Reactions: The most common adverse reactions include upper respiratory tract information about VILTEPSO, see infection, injection site reaction, cough, and pyrexia. accompanying full Prescribing Information. 6 7 Safety profile evaluated in two 24-week VILTEPSO offers a choice of clinical studies1,5 treatment location—at home Adverse reactions reported in ≥10% of DMD patients treated with or at a treatment center VILTEPSO 80 mg/kg once weekly (pooled Studies 1 and 2)1,5 Adverse reaction VILTEPSO (80 mg/kg once weekly) VILTEPSO is given as an 80-mg/kg weekly 1 (N=16); n (%) intravenous infusion Upper respiratory tract infection* 10 (63%) Injection site reaction† 4 (25%) Cough 3 (19%) The appropriate dose of VILTEPSO is calculated based upon patient weight, at a recommended Pyrexia 3 (19%) weekly dose of 80 mg/kg1 Contusion 2 (13%) Arthralgia 2 (13%) VILTEPSO is infused for 60 minutes by (13%) Diarrhea 2 a healthcare professional at home or at a treatment center1 Vomiting 2 (13%) Abdominal pain 2 (13%) Ejection fraction decreased 2 (13%) Urticaria 2 (13%) *Upper respiratory tract infection includes the following terms: upper respiratory tract infection, nasopharyngitis, sinusitis, and rhinorrhea. †Injection site reaction includes the following terms: injection site bruising, injection site erythema, injection site reaction, and injection site swelling. For more information about VILTEPSO, see accompanying full Prescribing Information. 8 9 Comprehensive care Indication and Important Safety Information coordination and Indication VILTEPSO is indicated for the treatment of Duchenne muscular dystrophy (DMD) in support from NS Pharma patients who have a confirmed mutation of the DMD gene that is amenable to exon 53 skipping. This indication is approved under accelerated approval based on an increase in dystrophin production in skeletal muscle observed in patients treated with VILTEPSO. At NS Support we are dedicated to being a committed partner to the families coping Continued approval for this indication may be contingent upon verification and with DMD. We stand ready to provide optimal access support and resources—every step description of clinical benefit in a confirmatory trial.
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