Azitra Inc · AMEX:AZTR
Azitra — Society of Investigative Dermatology Annual Meeting
16 slides from Azitra's conference presentation
Slide 1: Cutaneous delivery of LEKTI via an engineered strain of Staphylococcus epidermidis for Netherton syndrome
NYSE: AZTR Cutaneous delivery of LEKTI via an engineered strain of Staphylococcus epidermidis for the treatment of Netherton syndrome Travis Whitfill MPH MPhil PhD(c) Society of Investigative Dermatology Annual Meeting Precision dermatology powered by synthetic biology.
Slide 2: Forward-Looking Statements
FORWARD-LOOKING STATEMENTS This document contains forward-looking statements concerning Azitra, Inc. (“Azitra”, the “Company,” “we,” “us,” and “our”). The words “believe,” “may,” “will,” “potentially,” “estimate,” “continue,” “anticipate,” “intend,” “could,” “would,” “project,” “plan,” “expect” and
Slide 3: Personal disclosures
Personal disclosures Employment/compensation Current Shareholder • Azitra Inc. (NYSE: AZTR) (Cofounder, COO)* • Azitra Inc. (NYSE: AZTR)* • Actuate Therapeutics Inc. (Cofounder)* • Cognition Therapeutics (NASDAQ: CGTX)* • Inspired Spaces LLC (Cofounder)* • i-Lumen Scientific* • LetsImproveHealth LLC
Slide 4: Netherton Syndrome
Netherton Syndrome • Netherton syndrome (NS) is a rare, autosomal recessive disease o Estimated to occur in 1:100,000- 1:200,000 live births Clinical Presentation o Global prevalence of ~20,000 • Classic clinical triad of congenital ichthyosiform erythroderma, trichorrhexis invaginate (‘bamboo hair”
Slide 5: LEKTI is Deficient in Skin Affected by Netherton Syndrome
LEKTI is Deficient in Skin Affected by Netherton Syndrome H&E LEKTI Control NS patient Mintoff, Fischer, Mol Genet Genomic Med., 2021, 9, e1611
Slide 6: Targeting KLK5 in Netherton Syndrome via Expression of LEKTI
Targeting KLK5 in Netherton Syndrome via Expression of LEKTI KLK5 • LEKTI fragments inhibit KLK5, KLK7 and KLK14, which are involved in desquamation, PAR-2 activation, degradation of lipid hydrolases • Uncontrolled serine protease activity leads to defects in skin barrier, and release of pro- inflam
Slide 7: ATR-12: LEKTI-Secreting Staphylococcus epidermidis
ATR-12: LEKTI-Secreting Staphylococcus epidermidis Key Facts • ATR-12 is a live biotherapeutic product, comprised of an auxotrophic strain of Staphylococcus epidermidis (SE351) engineered to express domain 6 (D6) of the human LEKTI protein Primary Mechanism: o ATR-12 is formulated as a topical ointm
Slide 8: Mechanism of Action of ATR12-351 to Treat Netherton Syndrome
Mechanism of Action of ATR12-351 to Treat Netherton Syndrome 8
Slide 9: Design of ATR12-351: an auxotrophic, LEKTI-D6 secreting strain of S. epidermidis
Design of ATR12-351: an auxotrophic, LEKTI-D6 secreting strain of S. epidermidis SE27a: Plasmid expression of LEKTI-D6 SE351: Chromosomal integration of LEKTI-D6 and D- alanine auxotrophy Optimized promoters Optimized secretion peptide S. epidermidis chromosomal integration PhpaII PyxiE RBS yfhK SP
Slide 10: Confirmation of SE351 Potency and Activity
Confirmation of SE351 Potency and Activity Nanomolar IC50 of KLK5 S. epidermidis strain SE351 (LEKTI-secreting) spent broth inhibition from SE351 in vitro of human skin tape stripped extracts 4000 Trypsin-like activity 3000 NS Level (mRFU/h) 2000 7X 1000 Healthy Level 0 Healthy skin NS NS surrogate
Slide 11: ATR-12 Provides Superior LEKTI Delivery Compared to Topical LEKTI Delivery
ATR-12 Provides Superior LEKTI Delivery Compared to Topical LEKTI Delivery in ex vivo Full Thickness Human Skin LEKTI by skin layer Total LEKTI amounts ü LEKTI activity is significantly higher after 24 hours compared to vehicle and topical protein alone in all layers following ATR-12 application ü T
Slide 12: SE351 Potently Reduces IL-36g
SE351 Potently Reduces IL-36g Reconstructed epidermis induced with HaCaT cells induced with Poly I:C and treated erlotinib and treated with SE351 cells with SE351 cell-free supernatant -69% -92% 12
Slide 13: ATR12-351 Delivers High Amounts of LEKTI in Minipigs and is Safe and Well Tolerated
ATR12-351 Delivers High Amounts of LEKTI in Minipigs and is Safe and Well Tolerated LEKTI delivery by ATR12-351 over time 109 CFU/g ATR12-351 LEKTI 108 CFU/g ATR12-351 Vehicle • ATR12-351 delivers high amount LEKTI to skin of minipigs through 90 days • ATR12-351 was safe and well-tolerated in minipi
Slide 14: Summary
Summary • ATR12-351, a LEKTI-expressing strain of S. epidermidis in development for Netherton syndrome (NS) has demonstrated key proof of concept in preclinical studies: • Nanomolar IC50 values to inhibit KLK5, a key driver of NS • Delivers functional LEKTI and reduces protease activity to normal le
Slide 15: Acknowledgements
Acknowledgements Azitra, Inc. Paraza Inc. Funding sources: David Dodds PhD Peter White PhD CT Innovations Trudy Grossman PhD David Charboneau PhD CT Biosciences New Haven Alaina Kaiser PhD Majida El Bakkouri PhD National Science Foundation (NSF) #1853071 Roger Leger PhD Steven Huynh National Science
Slide 16: Thank You
THANK YOU Precision dermatology powered by synthetic biology.
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