Slide 1: Powering Protein Degradation for Tomorrow's Medicines
Powering Protein Degradation for Tomorrow's Medicines Cullgen Company Overview November 2024
Slide 2: Forward-looking Statements
Forward-looking Statements This ion contains “forward-lookii ” within the meaning of the federal securities laws regarding the current plans, expectations and strategies of Cullgen Inc. and its subsidiaries (“Cullgen”), which statements a are subject to substantial risks and uncertainties and are ba
Slide 3: Overview of Cullgen and Pulmatrix Proposed Merger
Overview of Cullgen and Pulmatrix Proposed Merger Cullgen Inc. (“Cullgen”) and Pulmatrix, Inc. ("Pulmatrix") (Nasdaq: PULM) have executed a definitive merger agreement Combined company will focus efforts on developing Cullgen’s leading pipeline of protein degradation product candidates Transaction S
Slide 4: Cullgen is Founded on a Targeted Protein Degradation (TPD) Technology Platform
Cullgen is Founded on a Targeted Protein Degradation (TPD) Technology Platform to Revolutionize Drug Discovery Organization ~130 Employees aie Facilities San Diego Shanghai (HQ) (wet labs, vivarium) ~60,000 sq ft Core Technology Discovery of novel E3 ligands Targeting previously undruggable disease
Slide 5: Leadership with Academic Excellence, Industry Achievement, Public Company Experience, and Entrepreneurial Success
Leadership with Academic Excellence, Industry Achievement, Public Company Experience, and Entrepreneurial Success F Ying Luo, Ph.D. Yue Xiong, Ph.D. Thomas Eastling, Chairman and CEO cso CFO 31 years of biotech William R. Kenan 28 years experience in experience. PhD from U. Distinguished Professor,
Slide 6: Cullgen Differentiation
Cullgen Differentiation \ uSMITE platform: Discovery of multiple novel E3 ligands and development of degrader-antibody conjugate (DAC) technology Vision Combining Our Pioneering Research and Innovation to Revolutionize Drug Discovery Through Our Proprietary uSMITE™ Platform Robust therapeutic pipeli
Slide 7: Overview of Cullgen R&D Pipeline
Overview of Cullgen R&D Pipeline x E3A, E3B: Functional esse Doel nS E3 — E3G: Tumor enriched ligands Platform g Technolo: Multiple active oncoprotein gy Degrader-antibody > P legraders P conjugate (DAC) Multiple tumor-associated antigen (TAA) IIgen . a ae Target Disease Indication ——) — ———) — Degr
Slide 8: Therapeutic Pipeline
Therapeutic Pipeline «ee Target Hit PCC IND Tenseu pngication enabling) wexuGcal TRK Solid tumors 1 TRK Acute and chronic pain 2 Leukemia and GSPTL MYC+ cancers 3) Epigenetic Prostate, lung & Factor bladder cancers * Non-enzyme target > )> Utilizing proprietary Cullgen £3 ligands Partnered with 7 as
Slide 9: TRK Degrader CG001419 for Oncology
TRK Degrader CG001419 for Oncology
Slide 10: Tropomyosin Receptor Kinases (TRKs) Are Receptors for Neurotrophins Including NGF
Tropomyosin Receptor Kinases (TRKs) Are Receptors for Neurotrophins Including NGF A. TRK signaling pathways B. Activation of TRK in multiple solid tumors C. Target product profile for TRK degrader . ama “ sie Indication Solid tumors with NTRK gene alterations « Coceneided unum aes GD 6D GD Op tome p
Slide 11: CG001419 Is Active and Well Tolerated Against Oncogenic TRKA Fusion and Drug-Resistant Mutants in Preclinical Studies
CG001419 Is Active and Well Tolerated Against Oncogenic TRKA Fusion and Drug-Resistant Mutants in Preclinical Studies A. Hits discovery B. 28-day repeated oral administration of CG001419 had marginal impact on body weight ICR mouse (n=90) Beagle dogs (n=10) B12 > Vehicle ial © Vehicle 3 = 8 mg/kg, p
Slide 12: Clinical Development of CG001419 for Cancer
Clinical Development of CG001419 for Cancer Phase 1a Dose Escalation Phase 1b Dose Expansion Phase 2 Basket Trial Group 1: NTRK fusion w/o prior TRK- TKI u a 34+3 800 ma ee Dose #1, n=6~12 Group 2: 2: NTRK fusion failed prior | Dose #2, n=6~12 | 5A pee } Group 3: NFRK point mutations | } Group 3: NF
Slide 13: Summary of CG001419 for Cancer
Summary of CG001419 for Cancer > Positioning « First-in-Class, selective, clinically active oral TRK degrader for the treatment of adult cancer patients with N7RK gene abnormalities ¢ Potential use in cancer patients with N7TRK gene fusion who acquire resistance to prior TRK kinase inhibitors via NT
Slide 14: TRK Degrader CG001419 for Pain
TRK Degrader CG001419 for Pain
Slide 15: Opioid Crisis Created an Urgent Unmet Medical Need and Significant Market for Pain Management
Opioid Crisis Created an Urgent Unmet Medical Need and Significant Market for Pain Management A. Three waves of opioid overdose deaths in the US B. Short-term opioid use leads to long-term dependence x 81,806 people died from drug overdoes in 2022 _// “”°P = ‘> >10 million people misused opioid each
Slide 16: The Role for the NGF-TRKA Pathway in Nociception and Analgesia Has Been Validated in Humans
The Role for the NGF-TRKA Pathway in Nociception and Analgesia Has Been Validated in Humans A. Injection of NGF into human muscle B. TRKA mutation in humans causes congenital C. Anti-NGF reduces the pain and causes long-lasting hyperalgesia insensitivity to pain and anhidrosis (CIPA) improves the fu
Slide 17: Clinical Development of CG001419 for Acute Post-Operative Pain
Clinical Development of CG001419 for Acute Post-Operative Pain Phase 1a Dose Escalation, IND Enabling Phase 2 Proof-of Concept Trials* Part A: Single Ascending Dose Dosing on Day 1 ‘Cohort E (200 mg) (1) Post-bunionectomy - Randomized placebo controlled c Part B: Multiple Ascending Dose <p> Dosing o
Slide 18: CG001419: A Potential First in Class Non-Opioid Medicine for Treatment of Pain
CG001419: A Potential First in Class Non-Opioid Medicine for Treatment of Pain oo LR BIO eullgen Risk of developing dependency, GI GI TES REGEN eels Preclinical Studies Moderate Moderate TBD v Preclinical Studies Neuron scars Nav1.8 inhibitor Nav1.8 inhibitor TRK degrader a hyperpolarization CoPe Ma
Slide 19: Summary of CG001419 for Pain
Summary of CG001419 for Pain > Rationale + The opioid crisis created an urgent unmet medical need and significant market for non-addictive analgesics. Short-term opioid use leads to long-term dependence. Additionally, no non-NSAID, non-opiate analgesics have been approved in the last 25 years for ac
Slide 20: GSPT1 Degrader CG009301 for Oncology
GSPT1 Degrader CG009301 for Oncology
Slide 21: Estimation of Therapeutic Window and Targeted Product Profile for CG009301
Estimation of Therapeutic Window and Targeted Product Profile for CG009301 le of targe’ —_— —_— GTP Peptide Hydrolysis, Release > GSPT1 (also known as eRF3) is a small GTPase and a translation termination factor that, in partnership with eRF1, promotes the release of nascent peptides when a ribosome
Slide 22: CG009301 Induces Rapid Tumor Regression in Leukemia and Solid Tumor Models
CG009301 Induces Rapid Tumor Regression in Leukemia and Solid Tumor Models A. CG009301 strongly degrades GSPT1 B. CG009301 inhibits multiple cancer types in vitro and in xenograft tumor models Famed 69301 Cell line MOLM-16 (IC;o = 0.3 nM) MOLM-16 (AML) Cone.nm_| 0 [007] 02] 06 [19] 56 [16.7] 50 = 10
Slide 23: Clinical Development of CG009301 in Patients with Recurrent or Refractory Hematologic Malignancies
Clinical Development of CG009301 in Patients with Recurrent or Refractory Hematologic Malignancies 10 mg QD, n=3~6 8.25 mg QD, n=3~6 6.50 mg QD, n=3~6 BOIN 5.00 mg QD, Design a Seomy ER Dose #1, n=9~18 (1) R/R AML or (2) HR-MDS or 2.50 mg QD, (3) R/R ALL im n=306 Dose #2, n=9~18 1.60 mg QD, “n=306 I
Slide 24: Summary of CG009301 for Cancer
Summary of CG009301 for Cancer > Survival of AML patients has not significantly improved over the past three decades. The AML market size is growing in line with the aging population. > CG009301 is a clinically active and selective GSPT1 degrader that demonstrates strong anti- tumor activity in pre-
Slide 25: uSMITE™ Platform
uSMITE™ Platform
Slide 26: Discovery of Novel E3 Ligands Represents Significant Opportunities for Targeted Protein Degraders
Discovery of Novel E3 Ligands Represents Significant Opportunities for Targeted Protein Degraders @ Yo E3 ligases in human cell ia Ub Ub rw a — — Eee ; i vege 1 E3 ligand used in orally active TPD Targeted protein degradation (TPD) allows: Dale et al (2021) Nat Rev Cancer PMID 34131295, > Higher eff
Slide 27: Discovery of Functional Ligands for E3 Ligase B (E3B)
Discovery of Functional Ligands for E3 Ligase B (E3B) A. Two Scaffolds of Cullgen E3B Ligands Discovered and Confirmed by X-ray Co-Crystal Structure CG-DF-555 (from Scaffold 1) HTRF ICSO: 46 nM CG-DF-231 (from Scaffold 2) HTRF IC50: 4.7 uM SPR (Kd): 19uM DSF (100uM): +5.5 °C Solubility: 147 uM + Sol
Slide 28: Discovery of Ligands for E3 Ligase G (E3G)
Discovery of Ligands for E3 Ligase G (E3G) A. E3G expression is enriched in many tumor types Median expression Log2 (TPM+1) ~~ eo i E3G MDM2 6 2 Median expression Log2 (TPM+1) ne) Normal Tumor Normal Tumor TCGA tumor types CG016383 BRCA, CESC, CHOL, COAD, ESCA, GBM, : Reece nM HNSC, KICH, KIRC, KIRP
Slide 29: Degrader-Antibody Conjugates (DACs) Combine the Advantages of ADCs and TPD
Degrader-Antibody Conjugates (DACs) Combine the Advantages of ADCs and TPD and Represent the Next-Generation of ADCs TPD ADC DAC (Targeted protein degradation) (Antibody drug conjugate) (Degrader antibody conjugate) al E3 ligase + —_—_ Intravenous Oral or IV Intravenous Indiscriminate Tumor target s
Slide 30: Cullgen Has Discovered Clinically Active Degraders Targeting Multiple Different Proteins Suitable as Payloads for DACs
Cullgen Has Discovered Clinically Active Degraders Targeting Multiple Different Proteins Suitable as Payloads for DACs TRK <1 23} Epigenetic target IC50: 0.02 - 0.17 nM Signaling pathway target DC50: 0.02 - 0.4 nM cG11498 Mour-4 GSPT1 <1 0.4 “g. BRVI 1505 ((Caq=0.12 nM = -® 0618701 DC50=0.4nM = -® 6
Slide 31: DACs Combine the Advantages of TPD and ADCs
DACs Combine the Advantages of TPD and ADCs A. DAC inhibits prostate tumor cell growth in vitro Antigen positive cells Antigen negative cells 7c" —® Naked antibody (IC50: > 1uM) > Linker-degrader (IC50: 24.25 nM) —l Degrader (IC50: 0.08nM) -¥ DAC (IC50: 0.08 nM) ° 408 1 10 108 1s 10? TO Compounds (M
Slide 32: Cullgen Has Developed Strong Platforms for Targeted Protein Degradation
Cullgen Has Developed Strong Platforms for Targeted Protein Degradation Vv Vv Vv > Cullgen has developed a robust pipeline of therapeutic degraders, six of which have been announced. This includes two that are currently in human clinical trials, several that target non-enzyme proteins, and several w
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