Cullinan Therapeutics, Inc. · NASDAQ:CGEM
Cullinan Therapeutics — Cullinan Oncology — Informa AET (December 2021)
18 slides from Cullinan Therapeutics's conference presentation, Dec 14, 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 December 14, 2021
Slide 2: Important Notice and Disclaimers
Important Notice and Disclaimers This presentation contains forward-looking statements of Cullinan Oncology, Inc. (“Cullinan,” “we” or “our”) within the meaning of the Private Securities Litigation Reform Act of 1995. These forward-looking statements include, but are not limited to, express or impli
Slide 3: 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 4: 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 4
Slide 5: 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 6: 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 7: Proof of Concept in Dogs: Local Administration of Retained Cytokines - Safety
Proof of Concept in Dogs: Local Administration of Retained Cytokines - Safety • Canine surrogates of LAIR-MSA-2 and 12-MSA-LAIR were tested in healthy beagles • Cytokines injected intradermally; likely overestimates toxicity due to more systemic leakage than IT Inject cLAIR-CSA-cIL2 and cIL12-CSA-cL
Slide 8: Proof of Concept in Dogs: Local Administration of Retained Cytokines - Efficacy
Proof of Concept in Dogs: Local Administration of Retained Cytokines - Efficacy • Ongoing dose escalation studies in dogs with malignant melanoma and soft tissue sarcoma • First cohort complete (n=3 per cohort); enrolling second cohort at double the dose Examples from first cohort: Example from seco
Slide 9: 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 10: Cullinan Amber is a First-In-Class Cytokine Delivery Product
Cullinan Amber is a First-In-Class Cytokine Delivery Product 1 Only Amber co-delivers IL-2 and IL-12 as a single agent No other cytokine fusion proteins are being developed for IT delivery to 2 maximize safety/efficacy Retention domains are encoded into the polypeptide chain without 3 the need for a
Slide 11: 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 11
Slide 12: 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 12
Slide 13: 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 13
Slide 14: Robust Control of Checkpoint-Refractory Tumors in Mice
Robust Control of Checkpoint- Refractory Tumors in Mice B16F10 CT26 MC38 14
Slide 15: 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 3/10 tumor free 7/10 tumor fr
Slide 16: 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) 6/10 tumor free 16
Slide 17: 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
Slide 18: Acknowledgments
Acknowledgments Cullinan Amber Team MIT Nadim Ahmed K. Dane Wittrup Patrick Baeuerle Noor Momin Jennifer Michaelson Kristan Meetze Irina Shapiro University of Illinois Kavya Rakhra Bochong Li Timothy M. Fan Jason Chang 18