I Mab : IMAB Corporate Presentation

Published: 2025-04-04 17:59:06 ET IMAB

Transforming Potential into Reality

I-Mab Biopharma

April 2025

Positioning Company for Accelerated Growth, with Focus on Precision Immuno-Oncology Therapeutics

Defined strategy for three clinically active programs

Givastomig (Claudin 18.2 x 4-1BB bispecific) leads the pipeline

Executing on clinical strategy via disciplined capital approach

Completed divestiture of China operations in 2024

I-Mab 2.0 - Lean and Focused U.S. Biotech

Legacy I-Mab

I-Mab 2.0

Taking a Step Beyond Traditional Early Drug Development

ASSET

PHASE 1

PHASE 2

PHASE 3

CLINICAL DEVELOPMENT STATUS/POTENTIAL NEXT STEPS PARTNERSHIPS

Givastomig1 CLDN18.2 X 4-1BB Bispecific Ab

1L GC, GEJ, EAC: Target population of ~137k patients2

2H 2025: Phase 1b dose escalation data presentation in combination with nivolumab + chemo

1H 2026: Phase 1b dose expansion data presentation in combination with nivolumab + chemo

Uliledlimab CD73 mAb

1L mNSCLC: Target population of 300k+ patients3

2026: Phase 2 PFS data from ongoing TJBio study (China-only) evaluating combination with toripalimab in CD73 positive patients

TJ Bio

Ragistomig1 PD-L1 X 4-1BB Bispecific Ab

Refractory/relapsed cancers: PD-(L)1 progression impacts most patients with metastatic disease

2025: Expanded dose ranging studies underway to identify appropriate tumor types for further development

1. Co-developed with ABL Bio (givastomig also known as ABL111, ragistomig also known as ABL503)

2. Kohei Shitara, et al, 2023 ASCO Annual Meeting (June 2-6), poster #4035; Markets include U.S., five E.U., and Japan based on Data Monitor Biomed Tracker

3. Global Data Epidemiology Data, Guidehouse legacy research

Notes: mNSCLC = metastatic non-small cell lung cancer; PD-(L)1 refers to inhibitors of PD-L1 or PD-1; Ab = antibody; mAb = monoclonal antibody; GC = gastric cancers; GEJ = gastroesophageal junction; EAC = esophageal adenocarcinoma cancer; 1L = first line; PFS = progression free survival;

Lead Program, Givastomig (Targeting Claudin 18.2 and 4-1BB)

A potential best-in-class CLDN18.2 therapeutic for gastric cancer

CLDN18.2

4-1BB scFv

Molecular Design

Key Differentiation

Clinical activity demonstrated across various levels of CLDN18.2 expression

Exhibits CLDN18.2 binding even on low expressing tumor cells

Higher-affinity binding to CLDN18.2 compared to reference antibody zolbetuximab

Localized T cell activation in TME to minimize 4-1BB-mediated liver toxicity and systemic immune response

First asset to be tested in US with immuno-chemotherapy standard of care in 1L gastric cancer

Notes: scFv = single chain Fragment-variable region; TME = tumor microenvironment; 1L = first line

Givastomig a Bispecific Antibody Targeting Claudin 18.2 and 4-1BB

Designed for optimal balance between anti-tumor efficacy and safety

Conditional T Cell Activation Upon Tumor Engagement

Silenced Fc: IgG1 (N297A)

In Circulation

Tumor Microenvironment

Source: Revised fromhttps://www.nature.com/articles/d43747-020-00568-5

Highly potent CLDN18.2 mAb

 Higher affinity than zolbetuximab

 Binds to tumor cells with a wide range of CLDN18.2 expression

 No ADCC or CDC

 Minimize unintended systemic immune activation driven by FcgR-mediated 4-1BB clustering

Conditional 4-1BB agonist

 Localized T cell activation in TME leading to potent tumor killing and minimal 4-1BB-mediated liver toxicity or systemic immune response

Notes: IgG1 = Immunoglobin G1; scFv = single chain Fragment-variable region; ADCC = antibody-dependent cell-mediated cytotoxicity; CDC = complement-dependent cytotoxicity; TME = tumor microenvironment

Comparison of CLDN18.2-targeted Therapeutics Mechanisms of Action

Source: Revised from Nat Rev Clin Oncol. 2024 May;21(5):354-369

Anti-CLDN18.2

Bispecific 4-1BB T Cell Activator (Givastomig)

Tumor killing by enhanced TDCC with anti-tumor

memory by activating 4-1BB costimulatory signal,

and bystander killing

Anti-4-1BB

Anti-CLDN18.2

Bispecific CD3 T Cell Engager (IBI389)

Tumor killing by TDCC and bystander killing via engagement of TCR co-receptor

Anti-CD3

High risk of CRS

Antibody-Drug Conjugate (AZD0901)

Tumor killing by cytotoxicity, bystander killing, ADCC, ADCP, and CDC

High risk of on-target GI toxicity & off-target systemic toxicity

Monoclonal Antibody (Zolbetuximab)

Tumor killing by ADCC, ADCP, and CDC

High risk of on-target GI toxicity

Notes: ADCC = antibody-dependent cell-mediated cytotoxicity; ADCP = antibody-dependent cellular phagocytosis; CDC = complement-dependent cytotoxicity; TDCC = T cell dependent cellular cytotoxicity; CRS = cytokine release syndrome; GI = gastrointestinal

Phase 1 Monotherapy Efficacy in Heavily Pretreated Patients (n=43)

5 mg/kg

8 mg/kg

12 mg/kg

15 mg/kg

> Treatment Ongoing

Numbers: CLDN18.2 %

PD SD

18 mg/kg x = Death

Source: Data on file (IMAB)

1. Defined as the predicted efficacious dosing range, based on preclinical studies

Notes: Data cut-off as of July 30, 2024; GC = gastric cancer; GEJ = gastroesophageal junction; EAC = esophageal adenocarcinoma

Conclusion:

 Givastomig was well tolerated and exhibits monotherapy activity in heavily pre-treated GC patients with a range of CLDN18.2 expression

Patient Overview:

 43 efficacy evaluable patients with CLDN18.2+ GC/GEJ/EAC

 A median of three prior lines of systemic therapy (range 1-6); doses between 5-18 mg/kg1

 Cohort is a subset of Phase 1a (NCT04900818)

Responses:

 Seven partial responses (PR) observed with an objective response rate (ORR) of 16.3% (7/43)

 Stable disease (SD) was reported in 14 patients, implying a disease control rate (DCR) of 48.8% (21/43)

 CLDN18.2 expression in responders ranged from 11% to 100%. Additionally, five responders had received prior treatment with PD-1 or PD-L1 inhibitors

Safety: Treatment Related AEs

Treatment-related adverse events (TRAEs) occurring in >5% (n=43)

Preferred Term (all numbers are n(%))

Nausea

Anemia

White blood cell count decreased Vomiting

Decreased appetite

Alanine aminotransferase increased Aspartate aminotransferase increased Gamma-glutamyl transferase increased Neutrophil count decreased

Infusion related reaction Lymphocyte count decreased Fatigue

Headache Hypoalbuminemia Lipase increased Platelet count decreased Weight decreased

Source:ESMO 2024

Grade 1

Grade 2

Grade 3

Grade 4

Grade 5

All Grades

6 (14.0)

2 ( 4.7)

5 (11.6)

4 ( 9.3)

3 ( 7.0)

1 ( 2.3)

- - - - - - - - - - - - - - - 1 ( 2.3)

- - - - - - - - - - - - - - - - -

10 (23.3)

11 (25.6)

 No DLT was reported up to 15 mg/kg Q2W and 18 mg/kg Q3W, and MTD was not reached

4 ( 9.3)

3 ( 7.0)

10 (23.3)

4 ( 9.3)

2 ( 4.7)

1 ( 2.3)

7 (16.3)

1 ( 2.3)

3 ( 7.0)

2 ( 4.7)

3 ( 7.0)

2 ( 4.7)

1 ( 2.3)

2 ( 4.7)

1 ( 2.3)

6 (14.0)

5 (11.6)

 Most commonly reported TRAEs (>20% of subjects): Grade 1, 2 or 3 nausea (25.6%), anemia (23.3%), white blood cell count decreased (23.3%)

1 ( 2.3)

3 ( 7.0)

1 ( 2.3)

5 (11.6)

1 ( 2.3)

2 ( 4.7)

1 ( 2.3)

4 ( 9.3)

2 ( 4.7)

1 ( 2.3)

4 ( 9.3)

- - -

4 ( 9.3)

3 ( 7.0)

 15 subjects (34.9%) experienced at least one Grade ≥ 3 TRAE with no Grade 5 TRAEs

2 ( 4.7)

1 ( 2.3)

3 ( 7.0)

2 ( 4.7)

1 ( 2.3)

3 ( 7.0)

1 ( 2.3)

2 ( 4.7)

1 ( 2.3)

- -

3 ( 7.0)

 Most gastrointestinal TRAEs were Grade 1 or 2 and do not appear to be dose-related

Notes: Data cut-off as of June 1, 2024; DLT = dose-limiting toxicity; MTD = maximum tolerated dose; AE = adverse event; TRAE = treatment emergent adverse event; Q2W = every two weeks; Q3W = every three weeks

Givastomig Efficacy Across Broader Claudin 18.2 Expression

Drug

Givastomig (bispecific)

Zolbetuximab (CLDN18.2 targeted mAb)

Phase

Phase 1

Phase 2

CLDN18.2 - Expression (Study Group)

IHC ≥1+ in ≥1% cells

IHC ≥ 2+ in ≥ 50% cells

Diagnosis

Previously treated GC/GEJ/EAC

Previously treated GC/GEJ

Previously treated GC/GEJ/EAC

Efficacy Evaluable (n)

ORR (%)

16% (7/43)

Zero

9% (4/43)

DCR (CR+PR+SD, %)

49% (21/43)

1 SD

23% (10/43)

Source

Givastomig poster #1017P ESMO2024

U Sahin et al. European Journal ofCancer 100 (2018) 17e26

O Tureci et al. Annals of Oncology30: 1487-1495, 2019

Notes: mAb = monoclonal antibody; ORR = objective response rate; DCR = disease control rate; CR = complete response; PR = partial response; SD = stable disease; GC = gastric cancer; GEJ = gastroesophageal junction; EAC = esophageal cancer; IHC = immunohistochemistry. Note that the comparisons in the table above are not based on data from head-to-head trials and are not direct comparisons. Differences in trial designs, patient groups, trial endpoints, study sizes and other factors may impact the comparisons

Disclaimer

I-Mab published this content on April 04, 2025, and is solely responsible for the information contained herein. Distributed via , unedited and unaltered, on April 04, 2025 at 21:58 UTC.