Slide 1: S. epidermidis for topical treatment of EGFR inhibitor-induced dermal toxicity
NYSE: AZTR Staphylococcus epidermidis for the topical treatment of epidermal growth factor receptor (EGFR) inhibitor-induced dermal toxicity Travis Whitfill MPH MPhil PhD(c) Society of Investigative Dermatology Precision dermatology powered by synthetic biology.
Slide 2: Special Note Regarding Forward-Looking Statements
SPECIAL NOTE REGARDING 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,
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: EGFRi-induced dermal toxicity is highly prevalent with significant clinical impact
EGFRi-induced dermal toxicity is highly prevalent with significant clinical impact EGFR inhibitors cause dermal toxicity in many patients generating dysbiosis and inflammatory response; the rash is strongly linked to S. aureus colonization and elevated IL-36𝛄 • Dermatologic toxicities are the most…
Slide 5: EGFRi-induced dermal toxicity is highly prevalent with significant clinical impact
EGFRi-induced dermal toxicity is highly prevalent with significant clinical impact Grade 1 Grade 2 Grade 3 Grade 4 • Rash severity often linked to cancer drug dosing and correlates with S. aureus levels on the skin • Rash can lead to significant changes in course of therapy and QOL • Depending on ge
Slide 6: Etiology of EGFRi-driven rash: suppression of host defenses and inflammatory response
Etiology of EGFRi-driven rash: suppression of host defenses and concurrent inflammatory response 6
Slide 7: Clinical evidence of S. aureus and IL-36γ elevations in EGFRi-related skin toxicity
Clinical evidence of S. aureus and IL-36𝛄 elevations in patients experiencing EGFRi-related skin toxicity EGFR inhibition impairs the cutaneous immune defense of EGFR inhibition leads to keratinocytes allowing S. aureus colonization significant increases in IL-36𝛄 Increased IL-36𝛄 in patient…
Slide 8: ATR-04: auxotrophic S. epidermidis for EGFR inhibitor-associated rash
ATR-04: auxotrophic S. epidermidis for EGFR inhibitor-associated rash ATR-04 Summary ATR-04 Key Facts • Severity of the dermal toxicity is linked to IL-36𝛄 signaling as well as correlations to S. aureus increases Primary Mechanism: IL36𝛄 inhibition, S. aureus control • ATR-04, a drug product…
Slide 9: Proposed mechanism of action of ATR-04
Proposed mechanism of action of ATR-04 Potential decreases in IL-36𝛄 cytokine signaling Inhibits S. aureus growth and biofilm Collectively, ATR-04 addresses dermal toxicity driven by EGFR inhibition Expected to lead to decreased inflammation 9
Slide 10: Engineering of S. epidermidis to create candidate ATR-04
Engineering of S. epidermidis to create candidate ATR-04 D-alanine auxotrophy in S. epidermidis SE484: Auxotrophic S. epidermidis with deleted mupirocin resistance and putative bacteriophage genes 10
Slide 11: Confirmation of auxotrophy and growth characteristics of SE484
Confirmation of auxotrophy and growth characteristics of SE484 Confirmation of D-alanine auxotrophy and mupirocin sensitivity on agar plates SE484 does not grow without Single dose of formulated SE484 (ATR-04) SE484 does not grow in D-alanine in vitro on ex vivo pig skin dies within 24 hours human b
Slide 12: In vitro data show ATR-04 significantly reduces IL-36γ
In vitro data show ATR-04 significantly reduces IL-36𝛄 HaCaT cells Reconstructed human epidermis -75% Untreated Poly I:C Poly I:C + Poly I:C + Untreated Erlotinib Erlotinib + 107 Erlotinib + 108 inhibitor SE484 CFU ATR-04 CFU ATR-04 ü IL-36𝛄 is elevated in reconstructed human epidermis following…
Slide 13: SE484 both reduces and prevents S. aureus growth in reconstructed human epidermis
SE484 both reduces and prevents S. aureus growth in reconstructed human epidermis Prophylactic setting Treatment setting -96% -99% ü In reconstructed human epidermis models, methicillin-resistant S. aureus (MRSA) was reduced by >99% in the prophylactic setting (pretreated with SE484 then MRSA added)
Slide 14: SE484 significantly reduces S. aureus in liquid culture and on ex vivo pig skin
SE484 significantly reduces S. aureus in liquid culture and on ex vivo pig skin Liquid cultures Ex vivo pig skin -99% SA USA300 SA USA300 + SE484 + SE484 + SE484 106 CFU/cm2 107 CFU/cm2 108 CFU/cm2 0 hours 8 hours ü In liquid cultures, SE484 reduced methicillin-resistant S. aureus (MRSA) in a dose-d
Slide 15: ATR-04 significantly increases human beta defensin 2 on reconstructed human epidermis
ATR-04 significantly increases human beta defensin 2 on reconstructed human epidermis Reconstructed human epidermis after 48 hours +18x Erlotinib Erlotinib + vehicle Erlotinib + 109 CFU/g ATR-04 DP ü In reconstructed human epidermis, 109 CFU / g ATR-04 treatment led to significantly higher levels of
Slide 16: Summary
Summary ü EGFRi-associated dermal toxicity is a large, unmet need that interferes with EGFRi effectiveness and leads to discontinuations and poor quality of life in cancer patients ü ATR-04, a drug product containing SE484, an auxotrophic strain of S. epidermidis in development for EGFRi-associated
Slide 17: Acknowledgements
Acknowledgements Azitra, Inc. University of Connecticut Funding sources: David Dodds PhD Technology Incubation Program Department of Defense Trudy Grossman PhD CT Innovations Roger Leger PhD Yale University CT Biosciences New Haven Dorival Martins PhD Tara Bancroft PhD Sara Mootien PhD Leonard Milst
Slide 18: Thank You
THANK YOU Precision dermatology powered by synthetic biology.