Protalix Biotherapeutics, Inc. (de) · AMEX:PLX
Protalix Biotherapeutics, Inc. (de) — Investor Presentation (June 2024)
36 slides from Protalix Biotherapeutics, Inc. (de)'s investor presentation, Jun 26, 2024
Slide 1: for Fabry Disease
for Fabry Disease Professor Aleš Linhart, MD, DrSc., FESC General University Hospital in Prague and 1st Faculty of Medicine, Charles University Prague, Czech Republic June 26, 2024 KOL Presentation I June 2024 1
Slide 2: Disclaimer
Disclaimer • Speaker´s and consultancy honoraria • Chiesi; Sanofi; Takeda; Amicus Therapeutics • Research grant • Sanofi • Board member • Fabry Registry, FollowMe Next Registry • Clinical trials • Protalix / Chiesi, Sanofi • Imaging from files of the General University Hospital, Prague, CZ; patients
Slide 3: Prof. Aleš Linhart, MD, DrSc., FESC
Prof. Aleš Linhart, MD, DrSc., FESC Graduated in Medicine at Charles University in Prague, Czech Republic Training in cardiology and vascular medicine at General University Hospital in Prague and Broussais Hospital in Paris, France Board certified specialist in Cardiology, Vascular Medicine, Interna
Slide 4: Disclaimer
Disclaimer The data discussed in this presentation are not intended to establish noninferiority or superiority to any other marketed drug product on the basis of safety or efficacy. The FDA has indicated that the magnitude of drug effect of agalsidase beta in a study population similar to that of BA
Slide 5: Note Regarding Forward-Looking Statements
Note Regarding Forward-Looking Statements This presentation contains forward-looking statements that involve risks and uncertainties within the meaning of Section 27A of the Securities Act of 1933, as amended, or the Securities Act, and Section 21E of the Securities Exchange Act of 1934, as amended.
Slide 6: Fabry Disease
Fabry Disease KOL – Investor Presentation I June 2024
Slide 7: Lysosomal function in cells
Lysosomal function in cells 0.2 – 0.5 mm Cytosol pH ~ 7.2 pH ~ 5.0 ACID HYDROLASES Nucleases Proteases Glycosidases Lipases Phosphatases Sulphatases Phospholipases H+ H+ pump ATP ADP + Pi / Mannose receptor Alberts B, Johnson A, Lewis J, Raff M, Roberts K, Walter P. KOL – Investor Presentation I Jun
Slide 8: Lysosomal function in cells
Lysosomal function in cells 0.2 – 0.5 mm Cytosol pH ~ 7.2 pH ~ 5.0 ACID HYDROLASES Nucleases Proteases Glycosidases Lipases Phosphatases Sulphatases Phospholipases H+ H+ pump ATP ADP + Pi Electron microscopy: Charles University, Prague Alberts B, Johnson A, Lewis J, Raff M, Roberts K, Walter P. KOL
Slide 9: Lysosomal function in cells
Lysosomal function in cells 0.2 – 0.5 mm Cytosol pH ~ 7.2 pH ~ 5.0 ACID HYDROLASES Nucleases Proteases Glycosidases Lipases Phosphatases Sulphatases Phospholipases H+ H+ pump http://www.trashitman.com/ ATP ADP + Pi KOL – Investor Presentation I June 2024 9 Alberts B, Johnson A, Lewis J, Raff M, Robe
Slide 10: Timeline of Fabry disease manifestations in hemizygous male patients
Timeline of Fabry disease manifestations in hemizygous male patients Vertigo, tinnitus Stroke Stroke sequalae Swelling, Hemodialysis Proteinuria, renal failure Shortness of breath Cardiomyopathy Palpitations Angina Impact on sexual life Angiokeratomas, hypohidrosis Exercise intolerance GI symptoms D
Slide 11: Fabry disease – Genetic disease with X-linked inheritance
Fabry disease – Genetic disease with X-linked inheritance Affected female Affected male >1000 gene variants known X X X p y p q GLA gene GLA gene GLA gene q with mutation normal with mutation • Males are usually more affected than females • In females, the disease is highly variable • The type and s
Slide 12: Fabry Disease – Specific Therapies
Fabry Disease – Specific Therapies KOL – Investor Presentation I June 2024
Slide 13: Fabry disease treatment options
Fabry disease treatment options Fabry Gene Mutation Type An absolute increase in α-Gal-A activity Non-Amenable Amenable ≥3.0% of wild type and a relative >50% of FD patients ~35-50% of FD patients increase ≥1.2 fold over baseline Migalastat Enzyme Replacement Enzyme Replacement Hughes et al. 2017 Ap
Slide 14: Life expectancy in untreated patients with Fabry disease: Fabry registry
Life expectancy in untreated patients with Fabry disease (FD): Fabry registry 2,848 patients with FD (1,422 males) The most common cause of death: cardiovascular diseases Life expectancy in untreated FD patients: ♂ • Males - 58 years (vs. 75 years in the general population) ♀ • Females - 75 years (v
Slide 15: Proof of concept: After ERT – Gb3 is cleared from endothelial cells
Proof of concept: After ERT – Gb3 is cleared from endothelial cells and reduced in smooth muscle cells Enzyme Replacement Therapy (ERT) = agalsidase beta – 36 months Skin biopsy Red arrows = endothelial cells Black arrows = smooth mucle cells * Pegunigalsidase alfa data – is presented in slide # 22
Slide 16: Key Issues with Classical Enzyme Replacement Therapies
Key Issues with Classical Enzyme Replacement Therapies Infusion (IV) frequency Short plasma half-life Antidrug antibodies (ADA) Every second week formation Limited coverage of the Infusion-related reactions Duration depends on dosing dosing interval and tolerability Neutralizing ADA (nAb) Instabilit
Slide 17: Innovations Addressing Several Critical Limitations
Innovations Addressing Several Critical Limitations KOL – Investor Presentation I June 2024
Slide 18: pegunigalsidase alfa (Elfabrio) – new ERT option in Fabry
pegunigalsidase alfa (Elfabrio®) – new ERT option in Fabry Elfabrio is a recombinant human α-Galactosidase-A enzyme approved in the United States and Europe for the treatment of adult patients with Fabry disease α-Galactosidase-A subunit α-Galactosidase-A subunit Plant-based production (ProCellEx®)
Slide 19: Elfabrio Clinical Development Program
® Elfabrio Clinical Development Program KOL – Investor Presentation I June 2024
Slide 20: Elfabrio Clinical Program Overview
Elfabrio® Clinical Program Overview Mechanism of action • Delivered to lysosome to reduce accumulated substrate • Prolonged drug presence in the circulation due to a long half-life • Low immunogenicity Phase 1/2 • Safety • Reduction of Gb3 and lyso-Gb3 • eGFR Endpoints • Safety • Safety • Safety • e
Slide 21: Pegunigalsidase alfa exhibits prolonged half-life in Fabry patients in Phase 1/2 Study
Pegunigalsidase alfa exhibits prolonged half-life in Fabry patients in Phase 1/2 Study n=4 n=6 n=6 • Active enzyme throughout the 2-week infusion interval • Enhanced pharmacokinetics parameters • Half-life of ~80 hours Pegunigalsidase alfa exposure-response relationship is unknown. KOL – Investor Pr
Slide 22: Phase 1/2 Study Histology: BLISS Score
Phase 1/2 Study Histology1,2 • In the overall population at 6 months there was Change in BLISS Score* with pegunigalsidase alfa 67.8% reduction in GL-3 from baseline in 9 peritubular capillaries (n=13) 8 BLISS Score, mean ± SD • Patients with classic Fabry disease (n=8) 7 exhibited a mean reduction
Slide 23: Long-term extensions of Phase 1/2 Study: Plasma Lyso-Gb3
Long-term extensions of Phase 1/2 Study Mean Lyso-Gb3 (mean +/- SE) Plasma Lyso-Gb3 (ng/mL) B, baseline; Lyso-Gb3, plasma Globotriaosylsphingosine KOL – Investor Presentation I June 2024 23 1. Hughes et al., Long-term safety and efficacy of pegunigalsidase alfa: A multicenter 6-year study in adult p
Slide 24: Long-term extensions of Phase 1/2 Study: eGFR
Long-term extensions of Phase 1/2 Study Mean eGFR (mean +/- SE) Absolute eGFR value, mL/min/1.73m2 KOL – Investor Presentation I June 2024 24 1. Hughes et al., Long-term safety and efficacy of pegunigalsidase alfa: A multicenter 6-year study in adult patients with Fabry disease. Genet Med. 2023 Dec;
Slide 25: BALANCE Study - design
BALANCE Study - design pegunigalsidase alfa pegunigalsidase alfa agalsidase beta agalsidase beta Wallace EL, Goker-Alpan O, Wilcox WR, Holida M, Bernat J, Longo N, Linhart A, Hughes DA, Hopkin RJ, Tøndel C, Langeveld M, Giraldo P, Pisani A, Germain DP, Mehta A, Deegan PB, Molnar MJ, Ortiz D, Jovanov
Slide 26: BALANCE Study - Key Results
BALANCE Study - Key Results pegunigalsidase alfa agalsidase beta pegunigalsidase alfa agalsidase beta Wallace EL, Goker-Alpan O, Wilcox WR, Holida M, Bernat J, Longo N, Linhart A, Hughes DA, Hopkin RJ, Tøndel C, Langeveld M, Giraldo P, Pisani A, Germain DP, Mehta A, Deegan PB, Molnar MJ, Ortiz D, Jo
Slide 27: BALANCE Study - Key Results: Plasma Lyso-Gb3 Over Time
BALANCE Study - Key Results Plasma Lyso-Gb3 Over Time (Females) Plasma Lyso-Gb3 Over Time (Males) pegunigalsidase pegunigalsidase alfa agalsidase beta alfa agalsidase beta Lyso-Gb3 (nM) Lyso-Gb3 (nM) Increase in lyso-Gb3 more prominent in patients with high UPCR and ADA positive Patients with baseli
Slide 28: Impact of Baseline Proteinuria on Renal Outcomes in BALANCE
The Impact of Baseline Proteinuria on Renal Outcomes in the BALANCE Study of pegunigalsidase alfa vs. agalsidase beta in Fabry Disease Post-hoc analysis Difference in Annualized eGFR Slope for pegunigalsidase alfa vs agalsidase beta in Overall Patient Population pegunigalsidase alfa agalsidase beta
Slide 29: BALANCE Study - rates of Adverse Events and Infusion-Related Reactions
BALANCE Study - rates of Adverse Events and Infusion-Related Reactions pegunigalsidase alfa agalsidase beta ADA negative ADA positive ADA negative ADA positive (n=34) (n=18) (n=17) (n=8) Number of related TEAEs (rate*) 13 (20.08) 29 (87.18) 28 (83.64) 48 (295.80) Total number of IRRs (rate†) 5 (0.3)
Slide 30: pegunigalsidase alfa Immunogenicity
pegunigalsidase alfa Immunogenicity KOL – Investor Presentation I June 2024
Slide 31: Assessment of immunogenicity from the pegunigalsidase alfa clinical program
Assessment of immunogenicity from the pegunigalsidase alfa clinical program Integrated analysis of de novo and pre-existing anti-drug antibodies Number of Patients Receiving pegunigalsidase alfa Patient Subgroups by ADA Status E2W in Clinical Trials included in this Pooled Analysis Number of patient
Slide 32: Immunogenicity assessment - Antibody characteristics
Assessment of immunogenicity from the pegunigalsidase alfa clinical program - Antibody characteristics 27/108 (25%) of FD recruited to pegunigalsidase alfa studies were ADA+ and the rest 81 (75%) patients were ADA- (n=36 ADA+) (n=8 ADA+) • 17/81 (21%) patients who were ADA– at baseline developed de
Slide 33: Lower affinity of anti-drug antibodies to pegunigalsidase alfa
Lower affinity of anti-drug antibodies to pegunigalsidase alfa • Analysis of the cross-reactivity of ADAs against agalsidase alfa and agalsidase beta from 49 patients with Fabry disease against the novel PEGylated enzyme pegunigalsidase alfa (PRX-102). • Affinities of ADAs of individual patients aga
Slide 34: Conclusions
Conclusions KOL – Investor Presentation I June 2024
Slide 35: Main conclusions from the overall clinical program of Elfabrio
Main conclusions from the overall clinical program of Elfabrio® Elfabrio is now approved in the EU and US, based on clinical program included >140 patients who received at least 1 infusion of pegunigalsidase alfa; some patients have been treated with pegunigalsidase alfa for >7.5 years Pharmacokinet
Slide 36: Indication and Important Safety Information
Indication and Important Safety Information Indication: Elfabrio® (pegunigalsidase alfa-iwxj) is a prescription infusion medicine used to treat adults with confirmed Fabry disease. WARNING: HYPERSENSITIVITY REACTIONS INCLUDING ANAPHYLAXIS Patients treated with ELFABRIO® have experienced hypersensiti
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