Atyr Pharma, Inc. · NASDAQ:ATYR
Atyr Pharma — European Respiratory Society International Congress 2021
14 slides from Atyr Pharma's conference presentation, Sep 7, 2021
Slide 1: Immunomodulatory protein ATYR1923 disrupts an in vitro model of sarcoid granuloma formation
Immunomodulatory protein ATYR1923 disrupts an in vitro model of sarcoid granuloma formation Dr. Suzanne Paz, aTyr Pharma, San Diego, CA Tuesday, September 7, 2021
Slide 2: Conflict of Interest Disclosure
Conflict of Interest Disclosure I have the following real or perceived conflicts of interest that relate to this presentation: Affiliation / Financial interest Commercial company Grants/research support: n/a Honoraria or consultation fees: n/a Participation in a company sponsored n/a bureau: Stock
Slide 3: Acknowledgements
Acknowledgements Collaborators from Ohio State University Dr. Elliott D. Crouser Mark W. Julian aTyr Pharma author contributors: Contact Information: Dr. David Siefker Dr. Elliott Crouser:Elliott.crouser@osumc.edu Erik Escobedo Dr. Leslie Nangle: LNangle@atyrpharma.com Clara Polizzi Dr. Suzanne Paz:
Slide 4: Aims / Learning Objectives
Aims / Learning Objectives 1. To educate the audience on ATYR1923, aTyr’s lead product candidate, that is currently in clinical development as a potential therapeutic to treat pulmonary sarcoidosis and other interstitial lung disease (ILD) 2. To demonstrate that Neuropilin-2 (NRP2), the selective bi
Slide 5: ATYR1923 Background Information
ATYR1923 Background Information A) Novel Functions of tRNA Synthetases • ATYR1923 is a clinical stage immunomodulatory protein • ATYR1923 comprises the N-terminal immunomodulatory domain of Histidyl-tRNA synthetase (HARS) fused to Human IgG1 Fc • ATYR1923 selectively binds to NRP2 (Ref #1) and exert
Slide 6: Cellular Organization of Pulmonary Sarcoidosis Granulomas
Cellular Organization of Pulmonary Sarcoidosis Granulomas A) • Granulomas contain epithelioid cells (resemble APCs such as MФ, but are not able to phagocytose), Macrophages, Multinucleated Giant Cells (MGC), Lymphocytes (B & T cells), and fibroblasts B) NRP2 mRNA expression measure by in situ hybrid
Slide 7: NRP2 is Highly Expressed in Myeloid Cells Found Within Granulomas of Sarcoidosis Patients
NRP2 is Highly Expressed in Myeloid Cells Found Within Granulomas of Sarcoidosis Patients A) B) Granuloma predominantly composed of CD14+ Monocytes FISH IF IF FISH FISH IF IF FISH RNA Protein Protein RNA RNA Protein Protein RNA FISH = fluorescent in situ hybridization; IF = immunofluorescence
Slide 8: NRP2 is Expressed in T cells From Lung Tissue of Sarcoidosis Patients
NRP2 is Expressed in T cells From Lung Tissue of Sarcoidosis Patients A) CD4+ T cells are located B) Not all CD4+ T Cells express on the outside of NRP2 granuloma and express NRP2 FISH IF IF FISH FISH IF IF FISH RNA Protein Protein RNA RNA Protein Protein RNA
Slide 9: NRP2 Expression on Myeloid and CD4+ T Cells is Upregulated Following TLR Activation
NRP2 Expression on Myeloid and CD4+ T Cells is Upregulated Following TLR Activation Myeloid Cells (CD11b+) CD4+ T Cells A) B) CD11b+ NRP2+ CD4+ T Cells NRP2 Expression NRP2 Expression 60000 TLR2 1000 800 MFI +/- SEM MFI +/- SEM TLR4 TLR8 40000 600 TLR1 TLR2 TLR3 TLR4 TLR6/2 TLR5 TLR3 TLR5 TLR3 TLR7
Slide 10: NRP2 Expressed on Murine Alveolar Macrophages and CD4+ T Cells; ATYR1923 Reduces Them
NRP2 is Expressed on Murine Alveolar MФ (AM) and CD4+ T Cell; Treatment with ATYR1923 Reduces AM & CD4+ T cells in the Lungs of Diseased Animals A) BAL (Bronchoalveolar Lavage) B) Lung tissue Alveolar Macrophages Alveolar Macrophages Alveolar Macrophages Alveolar Macrophages NRP2 Expression ✱ NRP2 E
Slide 11: ATYR1930 Prevents Granuloma Formation in a Human In Vitro Assay
ATYR1930 Prevents Granuloma Formation in a human In Vitro Granuloma Formation Assay A) C) Combined Sarcoid Patients D) Sarcoid Patient #15 n = 5 patients 800 400 600 300 B) M.tb. Antigen- * * %UNC %UNC coated beads 400 200 **** *** CD11b+ Cells 200 100 **** CD3+ Cells **** 0 0 300 nM 30 nM Uncoated
Slide 12: Conclusions
Conclusions • ATYR1923 is a potential first-in class, disease modifying therapy for patients with inflammatory lung diseases with high unmet medical needs • ATYR1923 works by selectively binding to the NRP2 receptor, which is highly expressed in granulomas from lung samples obtained from pulmonary s
Slide 13: List of References
List of References 1. Zhiwen Xu et al. ATS 2020. ATYR1923 Specifically Binds to Neuropilin-2, a Novel Therapeutic Target for the Treatment of Immune-Mediated Diseases. Poster available here: https://atyrpharma.wpengine.com/wp-content/uploads/2020/08/2020ATS_ZX-Poster_Final.pdf 2. Elisabeth Mertcshin
Slide 14: International Congress 2021 virtual
INTERNATIONAL CONGRESS 2021 vir tual
aTyr Pharma — European Respiratory Society International Congress 2021 on 6ix