Compass Therapeutics Jefferies 2019 Global Healthcare Conference June 7th, 2019 CONFIDENTIAL|CONFIDENTIAL| © © 2019 2019 1 Who We Are • Therapeutic focus: immuno-oncology and autoimmunity • Proprietary antibody discovery platform: First 40+ targets drugged • Broad pipeline of novel therapeutic candidates targeting multiple targets of the immune system • Growing biotech with lab/office/vivarium in Cambridge, MA Key Milestones • Developed comprehensive and deep approach to antibody discovery: novel drug candidates and building blocks for next-generation bispecific antibodies. StitchMabs™ HT screening platform. • Nominated our first clinical candidate • 2018 “Fierce 15” biotech company • Completed $132 M in series A financing: OrbiMed, F-Prime, Cowen, Borealis, Thiel, Biomatics, Alexandria, BioMed 2019 • Enroll Phase 1 Study: CTX-471 – novel CD137 agonist: https://clinicaltrials.gov/ct2/show/NCT03881488 • Begin IND enabling studies for our second candidate: first-in-class NKp30 bispecific • Nominate a third clinical candidate: two new INDs in 2020 • Series B financing; IPO ready CONFIDENTIAL| © 2019 2 Our Discovery Approach Bridges Innate & Adaptive Immunity VALIDATED ANTIBODY PANELS TO 40+ TARGETS FORM BUILDING BLOCKS FOR COMBINATION & BISPECIFIC SCREENING Innate Immunity Adaptive Immunity DC CD137 OX40 NKG2D CD94 CD40 NKG2D GITR CD226 CD2 CD226 NKp30 CD137 CD2 NKp46 TIGIT NK PD-1 Ag CD8+ CTL CD16a CD112R TIGIT shedding 2B4 CD96 CD112R CD96 PD-L1 CD155 Neutrophil CD112 CD113 CD89 Tumor MDSC PD-L1 CD47 Gal-1 SIRPa Her2 CD277 Gal-3 BCMA IL-6 CD38 CD200 CD137 CD30 TIGIT Macrophage Treg CD89 TNFR2 OX40 SIRPa GITR CONFIDENTIAL| © 2019 3 Compass Pipeline: June 2019 IND Enabling Discovery In Vitro In Vivo Phase I Phase II Studies CTX-471: Novel CD137 agonist ActivationA CTX-471 Combinations Cell Cell - T CKPT CTX-8371: PD-1 x PD-L1 Bispecific BlockadeA CTX-8573: BCMA x NKp30 Bispecific ActivationA NKp30 x TAA Platform NK Cell NK Cell CKPT BlockadeA TGFβ x TIGIT Bispecific ActivationA Receptor x TAA Bispecifics CKPT A CTX-5861: SIRPα and Combinations Macrophage Macrophage Blockade TAA: Tumor associated antigen CKPT: Checkpoint CONFIDENTIAL| © 2019 Activation CTX-471 - CD137 Agonist T-Cells Checkpoint blockade CTX-8371 - PD1 x PDL1 Bispecific CONFIDENTIAL| © 2019 5 CTX-471: Best in Class CD137 Agonist NOVEL EPITOPE WITH DIFFERENTIATED ACTIVITY SUPPORTED BY EXTENSIVE PRECLINICAL DATA CTX-471 Summary CTX-471 binds a unique, non-ligand competitive epitope in CRD3-4 of CD137 Selection ▪ Panel of 70 antibodies Urelumab, 3H3 CD137L ▪ 8 unique epitope bins ▪ Comprehensive in vitro characterization based on binding, signaling, activation, and drug-like properties CD137 ▪ 4 leads compared in vivo Molecular Profile CTX-471 ▪ Fully human, IgG4 agonist ▪ Non-ligand competitive Utomilumab ▪ Differentiated epitope in CRD3/4 ▪ Mouse/human/cyno cross-reactive CONFIDENTIAL| © 2019 6 Raising the Bar for Preclinical Efficacy - High Burden Tumor Models Small CT26 tumor: ~75 mm3 Large CT26 tumor: ~500 mm3 ➢ Typical size at which treatment begins in mouse ➢ Treating extremely large tumors of this size is efficacy studies generally considered futile ➢ Tumors this small are modestly sensitive to ➢ Tumors this large are highly resistant to monotherapy with α-PD-1/L1, α-OX40, α-CTLA4, monotherapy α-PD-1/L1, α-OX40, α-CTLA4, or or α-CD137 (3H3) α-CD137 (3H3) ➢ Small tumors can be eradicated by CTX-471 ➢ Large tumors can also be eradicated by CTX-471 monotherapy monotherapy CONFIDENTIAL| © 2019 7 CTX-471 Induces Regression of ~500 mm3 Tumors CTX-471 AND CTX-471-AF CLONES WERE TESTED IN CT26 THERAPEUTIC IN VIVO MODEL Control CTX-471 CTX-471-AF-1 CTX-471-AF-2 ) 3 2000 2000 2000 2000 m 0/6 4/6 6/6 4/6 m 1500 1500 ( 1500 1500 e 1000 m 1000 1000 1000 u l o 500 500 500 500 V r o 0 0 0 0 0 20 40 60 0 20 40 60 m 0 20 40 60 0 20 40 60 u Days Post-Treatment Days Post-Treatment T Days Post-Treatment Days Post-Treatment Low affinity Intermediate affinity High affinity ✓ Tumors were allowed to grow to ~500 mm3 before treatment began ✓ Therapeutic model, not a prevention model ✓ Unprecedented Monotherapy activity for an I/O Antibody CONFIDENTIAL| © 2019 8 Generation of Long Term Immunological Response POTENT AND FUNCTIONAL IMMUNOLOGICAL MEMORY – ALL CURED MICE REJECTED THE TUMOR Survival Curve: Monotherapy Treatment Survival Curve: Re-challenge P=0.0005 100 80 P=0.008 Isotype/ Naïve CTX-471 P=0.01 60 CTX-471 –AF-1 CTX-471 –AF-2 40 Percent survival Percent 20 0 0 10 20 30 40 Days Post-Re-Challenge ✓ Monotherapy treatment ✓ At > 8 x t1/2 all mice of Clone #1 and most mice of Parental survived ✓ All surviving mice re-challenged with CT-26 rejected the tumor * P values from Log-rank test compared to control CONFIDENTIAL| © 2019 9 CTX-471-AF-1 Induces Comprehensive Reprogramming Within the Tumor Microenvironment Protection/Reversion of T-cell Exhaustion Increased Infiltration of Immune Cells in the TME Control CTX-471-AF-1 Control CTX-471-AF-1 43 ± 5 % 8 ± 5 % 18 ± 1 % 62 ± 25 % 1 - PD Side scatter TIGIT CD45 Treg Reduction in the TME Tumor Associated Macrophage Reduction in the TME Control CTX-471-AF-1 Control CTX-471-AF-1 44 ± 4 % 24 ± 11 % 31 ± 9 % 7 ± 3 % F4/80 CD25 CD11b FOXP-3 CONFIDENTIAL| © 2019 10 Combinations are Synergistically Effective In Vivo CT26HuHER2 ADOPTIVE TRANSFER MODEL – T-CELL MEDIATED ACTIVITY SHOWN FOR CTX-471 Parental Clone Parental Clone Her2 + Control Her2 Mono CTX-471 Mono Her2 + 471 Cocktail CTX-471Cocktail (No T cells) + + 2000 2000 2000 2000 2000 0/8 0/8 3/8 8/8 0/8 ) 3 1500 1500 1500 1500 1500 m m ( e 1000 1000 1000 1000 1000 m u l o 500 500 500 500 500 V r o m 0 0 0 0 0 u 0 20 40 60 0 20 40 60 0 20 40 60 0 20 40 60 0 20 40 60 T Days Post-Treatment Days Post-Treatment Days Post-Treatment Days Post-Treatment Days Post-Treatment Note: Treatment initiated 6-days post tumor inoculation 100 Control 80 Trastuzumab 0% survival @ D64 60 Monotherapy 40% survival @ D64 40 Combination 100% survival @ D64 20 Percent Percent Survival Combination (No T cells) 0 0 20 40 60 80 Days post-Treatment CONFIDENTIAL| © 2019 11 CTX-471-AF causes Profound Tumor Necrosis of Very Large Tumors CONFIDENTIAL| © 2019 12 Tumor Rejection by CTX-471-AF is Associated with Increased Frequency and Penetration of CD8+ T Cells Day 7 Day 10 Day 14 Control AF - 471 - CTX Anti-CD8 IHC CONFIDENTIAL| © 2019 13 CTX-471 Clinical Development Plan • Vision: a broad T-Cell and NK-cell activator that has efficacy after PD-1/PD-L1 blockade in the immune-sensitive tumors (‘hot tumors’) and activity in selected cold tumors – Widely expressed on T cells and NK cells – Activation via CTX-471 leads to efficacy across a broad set of syngeneic tumors in mice – Demonstrable activity in cold tumors such as colorectal cancer, pancreatic cancer, etc. • Phase 1 will test the activity of CTX-471 in the relapsed patient population after PD-1 axis blockade – Immunological architecture is required for response: patients can not be refractory to PD-1 blockade – Once efficacy has been established in the 2L, 3L, we will proceed to front line therapy • Tumor types: all approved PD-1 and PD-L1 indications – Immunologically responsive based on at least 3 months of stable disease PD-1 Refractory – High unmet medical need due to limited response to CKPT blockers Cold tumors – Second line NSCLC is a major commercial opportunity CTX-471 • Execution Immune competent ~50% of PD-1 population – IND open as of 3/2019 – 6-8 Centers in the US: Dana Farber, MGH, Wash. U., Mary Crowley CC, Mt. Sinai, ITOR, Hackensack – Currently screening patients CONFIDENTIAL| © 2019 14 Activation CTX-8573 – BCMA x NKp30 Bispecific NK-Cells NKp30 Engager Platform Checkpoint blockade TIGIT x TGFβ Bispecific CONFIDENTIAL| © 2019 15 Empirical Identification and Optimization of NK Bispecific Antibodies COMPASS SCREENING WORKFLOW FOR MULTISPECIFIC CONSTRUCTS Panel of BCMA-NKR StitchMabs™ and bispecifics Comprehensive antibody discovery expressed and purified at 24 well scale BCMA Combinatorial library IgG1 NK-R Primary Screen Primary NK cells IgG1 Fc Secondary screen – Effect of CD16a engagement CONFIDENTIAL| © 2019 16 Next Generation NK Cell Bispecific Platform Targeting NKp30 Receptor NK-Cell • First in class bispecific antibody targeting NKp30 activating receptor expressed by NK cells NKp30 • Overcomes CD16a deficiency • CD16a Lowers the threshold of NK cell activation and induces NK cell- mediated killing of tumor cells expressing high, medium and low levels of TAAs with >100 fold increased potency compared to mAb • Induces NK cell proliferation and cytokine release in the presence of target cells TAA • Wide therapeutic window with no activity in the absence of target antigen • Leverages Compass common light chain and StitchMabs™ technologies Tumor cell CONFIDENTIAL| © 2019 17 NKp30 Bispecific Platform Significantly Enhances ADCC Potency of α-BCMA mAb SUPERIOR TUMOR CELL KILLING ACTIVITY MAINTAINED IN THE ABSENCE OF CD16A Target cell killing by primary NK cells Target cell killing by CD16- KHYG-1 cell line Aglycosylated Fc – no CD16a t a r g e t s : R P M I - 8 2 2 6 BCMA IgG1 Fc – CD16a Engagement 1 0 0 4 0 C T X 4 4 1 9 4 0 s i 8 0 B C M A - I g G 1 ( m A b ) s s i 3 0 y s 3 0 s i l y s l H e r 2 - I g G 1 y 6 0 c l B C M A - N K p 3 0 i c i f c f i i 2 0 i 2 0 f i c B C M A m A b c c e e 4 0 e IgG1 p p p s H e r 2 m A b s 1 0 s 1 0 % % 2 0 % 0 0 0 0 .