Cullinan Therapeutics, Inc. · NASDAQ:CGEM
Cullinan Therapeutics — Cytokine Summit (September 2021)
12 slides from Cullinan Therapeutics's conference presentation, Sep 22, 2021
Slide 1: Mining for Tomorrow's Cures
A Cullinan Oncology Company Mining for Tomorrow’s Cures Intratumoral administration and retention of IL-2 and IL-12 bifunctional fusion proteins to drive a systemic immune response Naveen Mehta September 22, 2021
Slide 2: Amber First Principles
Amber First Principles 1 Cytokines are autocrine/paracrine in nature, not endocrine Cytokines should be administered locally rather than systemically 2 A protein injected locally will not stay local without retention A retention domain is key to enhancing local bioavailability 3 Natural responses co
Slide 3: Intratumoral Delivery of Drug Does Not Guarantee Retention in Tumor
Intratumoral Delivery of Drug Does Not Guarantee Retention in Tumor Intratumoral Drug Delivery Expectation Reality Rohner & Thomas JCR 2016 CONFIDENTIAL 3
Slide 4: IL-2 + IL-12 Is A Highly Synergistic Cytokine Combination
IL-2 + IL-12 Is A Highly Synergistic Cytokine Combination § IL-2 and IL-12 combine to potently induce orthogonal JAK and STAT signaling pathways § IL-2 upregulates the IL-12 receptor, thereby poising effector cells for enhanced Th1 signaling § The two cytokines synergize to enhance production of ant
Slide 5: IT Injection of Collagen-Anchored Cytokine Fusions Are Retained, Improving Therapeutic Index
IT Injection of Collagen-Anchored Cytokine Fusions Are Retained, Improving Therapeutic Index • The Cullinan Amber platform is based on technology from the Wittrup lab at MIT • Lumican, a collagen binding protein, and mouse serum albumin, a bulky spacer domain, were fused to cytokines to promote rete
Slide 6: The Cullinan Amber Approach: Intratumoral Delivery of Dual Cytokine Fusion
The Cullinan Amber Approach: Intratumoral Delivery of Dual Cytokine Fusion IL-12 and IL-2 act synergistically in promoting Th1 anti-tumor immunity Tumor IL-12 retention IL-2 domains Two mechanisms of retention: Ø By collagen binding Ø By bulky overall size Amber is single-chain polypeptide to aid in
Slide 7: Functionality of Cytokines in Amber
Functionality of Cytokines in Amber Amber binds to collagen with nM affinity Amber1 Tumor IL-12 retention IL-2 domains Murine surrogates used throughout presentation Both IL-2 and IL-12 remain functional in Amber, even when pre-bound to collagen-coated plates 7
Slide 8: IT Administration Reduces Systemic Exposure and Enhances Anti-Tumor Response
IT Administration Reduces Systemic Exposure and Enhances Anti-Tumor Response Levels of Amber following IT vs IV treatment Efficacy advantage of IT delivery 2h post-treatment B16F10 Tumors 8
Slide 9: Retention of IT-Administered Cytokines Is Key to Reducing Toxicity
Retention of IT-Administered Cytokines Is Key to Reducing Toxicity IT treatment with and without retention domain B16F10 Tumors n.s **** p<0.001 Amber1 Amber1 9
Slide 10: Systemic and Memory Responses as Monotherapy or in Combination with Anti-PD1 in MC38 Model
Systemic and Memory Responses as Monotherapy or in Combination with Anti-PD1 in MC38 Model Primary Tumor Results Re-challenge Study Rechallenge Amber CR’s Similar data observed in the CT26 model Treatment of Dual Flank Tumors: Monotherapy + Combination with Anti-PD1 CPI Synergy with anti-PD1 checkpo
Slide 11: Responses With Treatment of Large Established Tumors in the MC38 Model
Responses With Treatment of Large Established Tumors in the MC38 Model Large Established Tumors (500 mm3) 11
Slide 12: Cullinan Amber is a first-in-class bifunctional agent that locally co-delivers IL-2 and IL-12
Cullinan Amber is a first-in-class bifunctional agent that locally co-delivers IL-2 and IL-12 in a safe and effective manner 1 Cytokines are autocrine/paracrine in nature, not endocrine Amber is administered locally 2 A protein injected locally will not stay local without retention Amber is retained
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