Scinai Immunotherapeutics Ltd. · NASDAQ:SCNI
Scinai Immunotherapeutics — 5th DDDS Europe 2024
42 slides from Scinai Immunotherapeutics's conference presentation, Apr 16, 2024
Slide 1: Elevating dermatological drug development through inflammatory marker targeting - IL-17 in psoriasis
CLICK TO EDIT MASTER TITLE STYLE Elevating dermatological drug development through advanced inflammatory marker targeting methodology - Focus of IL - 17 in the pathophysiology of psoriasis and unmet medical need – 5th DDDS Europe, April 17, 2024 Michael P. Schön Department of Dermatology , Venereolo
Slide 2: What is Psoriasis?
CLICK TO EDIT MASTER TITLE STYLE What is Psoriasis? 1 - 4 • Systemic , chronic inflammatory disorder • Affects 2 – 3% of the fair - skinned population • Genetic and immunologic basis , can be triggered • Several comorbid diseases result in considerable impairment of quality of life • 2016: World Hea
Slide 3: Psoriasis: comorbidity and general impact on the patients' lives
CLICK TO EDIT MASTER TITLE STYLE Psoriasis: comorbidity and general impact on the patients’ lives BoD : Burden of disease ; CVD: Cardiovascular disease ; QoL : Quality of life . Adapted from WHO Global Report on Psoriasis. Available at: https://apps.who.int/iris/bitstream/handle/10665/204417/9789241
Slide 4: Microenvironment in psoriasis (I)
CLICK TO EDIT MASTER TITLE STYLE Gro a TARC RANTES MIP - 3 a TNF a IL - 10 IFN g VEGF IL - 1 IL - 6 neutrophils in epidermis , microabscesses hyperkeratosis , parakeratosis epidermal T cell recruitment altered differentiation of many cell types keratinocyte hyperproliferation , acanthosis macrophage
Slide 5: Microenvironment in psoriasis (II)
CLICK TO EDIT MASTER TITLE STYLE Schön MP. Adaptive and innate immunity in psoriasis and other inflammatory disorders. Front Immunol 10, 1764, 2019 • compartmentalization of resident and immigrating cells • innate and adaptive immune system contribute to pathogenesis • infiltration of dendritic cell
Slide 6: The current concept in brief: TNF, Th17 cells, IL-17 and IL-23
CLICK TO EDIT MASTER TITLE STYLE PMN: Polymorphonuclear leukocyte; STAT: Signal transducer and activator of transcription. 1 Adapted from Dolgin E. Nat Biotechnol. 2016;34:1218 – 1219. 2 Boehncke WH and Schön MP. Lancet. 2015;386:983 – 994. 3 Nestle F et al. N Engl J Med. 2009;361:496 – 509. 4 Lowes
Slide 7: Approved therapies and references
CLICK TO EDIT MASTER TITLE STYLE Also approved in the EU. 1 FDA. Enbrel PI. 2018. p4. 2 EMA. Enbrel SmPC. 2019. p3. 3 FDA. Remicade PI. 2018. p1. 4 EMA. Remicade SmPC. 2019. p3. 5 FDA. Humira PI. 2018. p1. 6 EMA. Humira SmPC. 2019. p89. 7 FDA. Stelara PI. 2019. p1. 8 EMA. Stelara SmPC. 2019. p19. 9
Slide 8: Current therapeutic targets in psoriasis
CLICK TO EDIT MASTER TITLE STYLE Current therapeutic targets in psoriasis Schön MP and Wilsmann - Theis D: Current developments and perspectives in psoriasis . J Dtsch Dermatol Ges 2023;21(4):363 - 73
Slide 9: Inhibition of specific mediators: IL-23 and IL-17
CLICK TO EDIT MASTER TITLE STYLE Adapted from Dolgin E. Nat Biotechnol. 2016;34:1218 – 1219. 2 Boehncke WH and Schön MP. Lancet. 2015;386:983 – 994. 3 Nestle F et al. N Engl J Med. 2009;361:496 – 509. 4 Lowes MA et al. Nature. 2007;445:866 – 873. 5 Griffiths C and Barker J. Lancet. 2007;370:263 – 27
Slide 10: Cytokine network regulates T cell differentiation
CLICK TO EDIT MASTER TITLE STYLE 1 Iwakura Y et al. J Clin Invest. 2006;116:1218 – 1222. 2 Boehncke WH and Schön MP. Lancet. 2015;368:983 – 994. Th1 Th2 Th17 Treg IL - 17 IL - 17F IL - 6 TNF - α IL - 23R IL - 4R IL - 12R IFN - γ IL - 23 IL - 12 IL - 4 TGF - β 1 IL - 6 ? TGF - β 1 FoxP3 CD25 IL - 4 I
Slide 11: There is more to IL-regulation...
CLICK TO EDIT MASTER TITLE STYLE There is more to IL - 17 regulation... 1 - 3 d endritic c ell keratinocyte inflammation a nd h yperproliferation a daptive l ymphocytes ( e.g . Th17 cells ) ILC3 cells γδ T cells i nnate - like i mmun cell p opulations IL - 23 independent IL - 23 IL - 17C IL - 36 ߙ I
Slide 12: IL-17 and IL-17 receptors
CLICK TO EDIT MASTER TITLE STYLE IL - 17 and IL - 17 receptors 1 - 5 1 Lauffer F, ..., Schön MP: J Dtsch Dermatol Ges. 18(7), 675 - 681, 2020 2 Kolbinger et al. J Allergy Clin Immunol 2017;139:923 – 32 3 Reich K, et al. N Engl J Med 2021;385:142 - 52; 4 Reich K, et al. Lancet 2021;397:487 - 98; 5 Wa
Slide 13: New guidelines expanded
CLICK TO EDIT MASTER TITLE STYLE New guidelines expanded Nast A et al.: German S3 guideline treatment of psoriasis vulgaris .... J Dtsch Dermatol Ges. 19, 934 - 951, 2021 » systemic therapies are usually approved only for moderate - to - severe disease » i. e., PASI ≥ 10, BSA ≥ 10 and/ or DLQI ≥ 10
Slide 14: Why do we need more?
CLICK TO EDIT MASTER TITLE STYLE Why do we need more? » not all patients achieve complete clearance (PASI90 or PASI100) • recalcitrant lesions that do not respond adequately » some patients have psoriasis in difficult - to - treat areas • e.g. hands , feet , scalp , genitals ... » most patients are
Slide 15: Hard-to-treat lesions: scalp
CLICK TO EDIT MASTER TITLE STYLE Hard - to - treat lesions: scalp pat . #1 pat . #2 pat . #3
Slide 16: Hard-to-treat lesions: scalp
CLICK TO EDIT MASTER TITLE STYLE pat . #4 pat . #5 Hard - to - treat lesions: scalp
Slide 17: Visible areas with high burden of disease: face
CLICK TO EDIT MASTER TITLE STYLE Visible areas with high burden of disease: face pat . #6 pat . #7 pat . #8 pat . #9
Slide 18: Hard-to-treat lesions: hands
CLICK TO EDIT MASTER TITLE STYLE Hard - to - treat lesions: hands pat . #10 pat . #11
Slide 19: Sensitive areas: ano-genital region
CLICK TO EDIT MASTER TITLE STYLE Sensitive areas with high burden of disease: ano - genital region pat . #9 pat . #12
Slide 20: Special locations: navel and nipples
CLICK TO EDIT MASTER TITLE STYLE Special locations: navel and nipples image courtesy of Prof. D. Thaci, Lübeck pat . #13 pat . #14
Slide 21: Recalcitrant isolated lesions
CLICK TO EDIT MASTER TITLE STYLE Recalcitrant isolated lesions pat . #15 pat . #16 pat . #17
Slide 22: Pretreated lesions with therapy side effects: soles
CLICK TO EDIT MASTER TITLE STYLE Pretreated lesions with therapy side effects: soles pat . #18 pat . #19
Slide 23: Summary
CLICK TO EDIT MASTER TITLE STYLE Summary » psoriasis is a systemic chronic inflammatory disorder with high burden of disease » complex ( immuno ) pathogenesis with involvement of both innate and adaptive immune mechanisms , prominent role of IL - 23/IL - 17 axis » pathogenesis - oriented therapies h
Slide 24: Thank you!
CLICK TO EDIT MASTER TITLE STYLE Thank you !
Slide 25: Plaque Psoriasis: a large unmet need with mild and moderate patients
CLICK TO EDIT MASTER TITLE STYLE 25 Plaque Psoriasis: a large unmet need with the mild and moderate Psoriasis prevalence and severity SEVERE MODERATE MILD 22% of patients. 28% of patients. 50% of patients. >10% of the body Typically has a severe impact on quality of life 3 - 10% of the body Generall
Slide 26: Current plaque psoriasis treatments
CLICK TO EDIT MASTER TITLE STYLE 26 CURRENT PLAQUE PSORIASIS TREATMENTS Corticosteroid creams, vitamin E+A, vitamin D derivatives Phototherapy 1 st line systemic immunosuppressants (Methotrexate and Cyclosporine) & Immunomodulators (Otezla) 2 nd line systemic Immunomodulators (e.g., Sotyktu ) Inject
Slide 27: NanoAbs address unmet need
CLICK TO EDIT MASTER TITLE STYLE 27 NANOABs ADDRESS UNMET NEED Designed to be convenient, safe, affordable, effective biologic for mild and moderate patients Current treatment shortcomings Corticosteroids • Side effects including: Skin thinning (bruising) & Lightening of skin color • Development of
Slide 28: The need for a novel local therapeutic
CLICK TO EDIT MASTER TITLE STYLE 28 The need for a novel local therapeutic • T here ha s not been any novel local treatment in the last 25 years. • Significant patient preference for local therapies, compared to systemic drugs. • Corticosteroids are not suitable for long - term management of PsO due
Slide 29: Rationale and success factors for IL-17 NanoAb
CLICK TO EDIT MASTER TITLE STYLE 29 Rationale Success Factor IL - 17 as a molecular target in psoriasis is well understood and has been validated by existing therapies, e.g., Cosentyx, Siliq, Taltz and Bimzelx . IL - 17 is a well - established target in psoriasis IL - 17 F is highly expressed in the
Slide 30: Local ID injection of Anti-IL-17A/F VHH antibody fragment
CLICK TO EDIT MASTER TITLE STYLE 30 Local ID injection of Anti - IL - 17A/F VHH antibody fragment A novel way to using VHH antibodies - Most other entities working with VHHs (nanobodies®) aim to mimic mAbs “playbook” and hence are competing for the same patient populations and are using the same rou
Slide 31: The product
CLICK TO EDIT MASTER TITLE STYLE 31 The product An intradermal pen filled with a liquid, sustained release formulation of Scinai’s anti - IL - 17A/F nanoAb given every 3 to 6 months at the doctor’s office. • Upon a patient’s visit, a reusable pen injector will be loaded by the physician with a steri
Slide 32: Generating incentives for the customers – the three P's
CLICK TO EDIT MASTER TITLE STYLE 32 Generating incentives for the customers – the three P’s Patients: Mild to moderate plaque psoriasis patients. • Currently treated with corticosteroids and are unhappy : • Inconvenience of use (e.g. twice a day, use of ointments/creams). • Development of tolerance
Slide 33: Where is the money?
CLICK TO EDIT MASTER TITLE STYLE 33 Where is the money? • Total sales of drugs in the 7MM for mild psoriasis expected to be $1.8B in 2030 • $1.3B is expected to come from prescription of biologics and $259M from TYK2 inhibitor • This is the market where the topicals and phototherapy do not help. • T
Slide 34: The Max Planck Institute & UMG bring...
CLICK TO EDIT MASTER TITLE STYLE 34 The Max Planck Institute & UMG 1 bring… • Recombinant protein drug development experience from lab to Phase 3 clinical trial • Manufacturing, quality, international regulatory experience • GMP biologics manufacturing facility • Best - in - class equipped labs • To
Slide 35: Alpaca-derived nanosized antibodies (NanoAbs)
CLICK TO EDIT MASTER TITLE STYLE 35 Alpaca - derived nanosized antibodies (NanoAbs) are also known as VHH antibodies or nanobodies 1 mAb therapeutic market size is ~ $205 billion 2 including Cosentyx for psoriasis $4.8 billion (2022) 3 NanoAbs: Human monoclonal antibody (mAb)’s biobetter 1. VHH anti
Slide 36: Anti-IL-17 NanoAb: a better neutralizer
CLICK TO EDIT MASTER TITLE STYLE 36 Anti - IL - 17 Nanoab: A better neutralizer Secukinumab* NanoAb Cytokine 0.2nM 0.56nM IL17A m M 1.00nM IL17F 2.0nM 0.25nM IL17AF Single NanoAb neutralizes IL - 17 A, F, and AF complex IL - 17 A IL - 17 F IL - 17 AF COMPLEX * Cosentyx, INN - sekukinumab (europa.eu)
Slide 37: Ex-vivo proof of concept: NanoAbs shown to block IL-17
CLICK TO EDIT MASTER TITLE STYLE 37 EX - VIVO PROOF OF CONCEPT: NANOABS SHOWN TO BLOCK IL - 17 Impact of ID injected nanoAb in comparison to current leading treatments Betamethasone and Cosentyx Designed to be local, less frequent use, safer, more convenient and more affordable *** = p<0.001 **** =
Slide 38: Preliminary PK: limited systemic exposure
CLICK TO EDIT MASTER TITLE STYLE 38 Preliminary PK: limited systemic exposure PK Study design Implications: Healthy mice were injected ID with biotinylated anti IL - 17 nanoAbs, blood samples removed periodically post administration. Limited systemic exposure will contribute to safety T1/2 in the de
Slide 39: In vivo PoC: Human xenograft skin (1/2)
CLICK TO EDIT MASTER TITLE STYLE 39 In vivo PoC: Human xenograft skin (1/2) Animal model: Normal human skin will be engrafted into SCID BEIGE mouse and disease will be induced by injection of IL - 2 activated PBMC's from psoriatic patients Study design Major outcome measures Follow up (3 weeks) Trea
Slide 40: In vivo PoC: Human xenograft skin (2/2)
CLICK TO EDIT MASTER TITLE STYLE 40 In vivo PoC: Human xenograft skin (2/2) What is being studied? The impact of local psoriasis treatments by efficacy parameters: x Clinical evaluation by medical photographs. x Macroscopic evaluation, epidermis thickness scoring & Histological analysis. x IHC analy
Slide 41: Summary
CLICK TO EDIT MASTER TITLE STYLE 41 Summary • T here is a need for a better treatment for patients with mild to moderate Psoriasis and for specific lesions that are hard to treat with current therapies. • Biological drugs are the safest and most efficient, yet – they are administered systemically an
Slide 42: Thank you
CLICK TO EDIT MASTER TITLE STYLE THANK YOU