Slide 1: Briquilimab, an Anti-CD117 (c-Kit) Antibody, Prevents Cockroach Allergen-Induced Allergic Asthma in Mice
Briquilimab, an Anti-CD117 (c-Kit) Antibody, Prevents Cockroach Allergen-Induced Allergic Asthma in Mice Expressing Chimeric Human and Mouse CD117 Mang Yu, Andrew Wells, Sambidhan Kattel, Revati Nerkar, Karl Meneses, Hye-Sook Kwon, and Wendy W. Pang Jasper Therapeutics, Inc., Redwood City, CA Briqui
Slide 2: Briquilimab inhibits c-Kit leading to mast cell apoptosis
Briquilimab (humanized anti-human c-Kit mAb) inhibits c-Kit leading to mast cell (MC) apoptosis Briquilimab is an investigational product and not approved for any indication
Slide 3: Mast Cells play a critical role in allergic inflammation and tissue remodeling in asthma
Mast Cells (MC) play a critical role in allergic inflammation and tissue remodeling in asthma MC Lung Distribution ➢ Airway epithelium ➢ Submucosal glands Non-asthmatic person ➢ Airway smooth muscle ➢ Alveolar epithelium Smooth muscle MCs MC Pathological Mediators ➢ Proteases Submucosal MCs ➢ Proteo
Slide 4: Chimeric human/mouse CD117 (h/mCD117) mice
Chimeric human/mouse CD117 h/mCD117 (h/mCD117) mice Wildtype Homozygous Marrow Marrow B6 mice with h/mCD117 knock-in, replacing endogenous wildtype CD117 SCF CD117 (c-Kit) Briquilimab is an investigational product and not approved for any indication
Slide 5: PK characterization of briquilimab in chimeric h/mCD117 mice
PK characterization of briquilimab in chimeric h/mCD117 mice • Chimeric h/mCD117 mice received single dose of intravenous briquilimab Briquilimab serum conc. • Pharmacokinetic clearance of briquilimab 300000 is dose-dependent 5 mg/kg • Pharmacokinetic clearance of Briquilimab (ng/mL) 10 mg/kg briqui
Slide 6: Study design: preclinical prophylactic vs. therapeutic models of asthma in h/mCD117 mice
Study design: preclinical prophylactic vs. therapeutic models of asthma in h/mCD117 mice Prophylactic Model: Cockroach allergen (CRA) Briquilimab Tx CRA i.n. challenge i.n. sensitization (10 mcg/0.03 mL) (60 mg/kg, i.p.) (10 mcg/0.03 mL) Naïve h/mCD117 ➢ NECROPSY Day (D) 1 D2 D3 D15 D18 D21 D22 mice
Slide 7: Prophylactic briquilimab treatment inhibits development of airway inflammation in h/mCD117 mice
Prophylactic briquilimab (Briq) treatment inhibits the development of airway inflammation in h/mCD117 mice following cockroach allergen sensitization and challenge Briquilimab is an investigational product and not approved for any indication
Slide 8: Preventive briquilimab decreased mast cells in lung and back skin
Nineteen days after one-time briquilimab (Briq) preventive treatment, cockroach allergen-sensitized and challenged h/mCD117 mice exhibited significantly decreased numbers of mast cells in the lung and back skin Lung Mast Cells 6060 Lung MCs Mast cells/mm2 4040 2020 00 PBS Asthma Asthma+Briq PBS Asth
Slide 9: Therapeutic briquilimab prevented recurrence of asthma exacerbation in established asthma models
One-time therapeutic briquilimab (Briq) treatment prevented recurrence of asthma exacerbation following allergen exposure in established asthma models elicited in h/mCD117 mice BALF and Airway PMN Pulmonary Resistance Airway PMNs (per mm2) 25 25 600 600 BALF PMNs (x104) 6 20 20 400 400 Asthma+Briq 1
Slide 10: Therapeutic briquilimab decreased mast cells in lung and back skin after allergen exposure
Three days after one-time therapeutic briquilimab (Briq) treatment, established asthma models in h/mCD117 mice exhibited significant decreases in the numbers of mast cells in the lung and back skin following allergen exposure Lung Mast Cells Lung MCs Mast cells/mm2 60 60 40 40 20 20 00 PBS Asthma As
Slide 11: Conclusions & Takeaways
Conclusions & Takeaways • Mast cells play a key role in asthma pathophysiology. • Briquilimab can deplete mast cells in both inflamed (lung) and non-inflamed tissue (back skin) in an allergen-induced asthma model elicited in h/mCD117 mice. • Briquilimab exhibits potential prophylactic and therapeuti
Slide 12: Acknowledgements
Acknowledgements Jasper Therapeutics Stanford Univeristy Edwin Tucker Judy Shizuru Daniel Adelman Stephen Galli Patricia Carlos Ryan Taylor Anne Le Ameer Alameddin Kavitha Arulprakasam Minyoung Youn Song Lee Hind Bouzid Meet us at Jasper’s booth #444. Copies of the abstract are available on request