潜在能力を現実に変える、アイマブ・バイオファーマ2024年10月24日
免責事項。 このプレゼンテーションはアイマブ(以下「当社」)によって、情報提供を目的としてのみ作成されました。ここに含まれる情報の一部は、当社を含むさまざまな情報源から得られたものであり、独立して当社で検証されたものではありません。 このプレゼンテーションに含まれる情報を閲覧またはアクセスすることにより、個々の株主、役員、従業員、代理店、関連会社、顧問、または代表者によって、当社またはその関連会社の株主、従業員、代理人、関連会社、顧問、または代表者によって、真実、正確性、公正性、完全性、または合理性が示されるか、または信頼を置かれるべきであるかについて、一切の表明、保証、または承諾がないことに承諾し同意します。 このプレゼンテーションに含まれる情報または意見の真実性、正確性、公正性、完全性、または合理性について、および、このプレゼンテーションに、またはこれに含まれる、またはそれが省かれた情報または意見に対して、当社またはその役員、従業員、代理人、関連会社、顧問、または代表者は、適用可能な法律によって要求される範囲を超えて、いかなる責任も負いかねます(過失またはその他)類に由来するどの損害についても。 本プレゼンテーションに含まれる情報または内容は、ここに記載の日付を基準としてのみ、予告なく変更される場合があります。 オファーまたは勧誘なし。 このプレゼンテーションは、当社の証券またはインストゥルメントを買い、または売るための提供、またはいかなる投資活動または取引戦略に参加することを勧誘するものではありません。これまたはこれの一部が、契約または取り決めに関連して、基礎となる、または依存するものであることもできません。 本資料には勧誘あるいは売出しを意味するものではありません。本資料はいかなる州または管轄権内での証券または財務商品の購入を勧誘し、またはこれを売買するオファーを構成するものでもありません。 本資料は、特に当社の証券に関する、特に証券の投資に伴うリスクや特別な考慮事項に関連するすべての関連情報を含むものではないことを主張しない、関するすべての関連情報を含んでいません。 本資料に含まれる産業および市場データは、産業出版物やサードパーティによって実施された調査や研究、弊社が推定した市場機会に関する統計その他産業および市場データが使用されています。このプレゼンテーションで使用されるすべての市場データには、いくつかの仮定と制約が含まれており、これらのデータに過度な重みを与えないように注意する必要があります。産業出版物や第三者の研究、調査、研究は、一般にその情報が信頼できる情報源から得られたものであると述べていますが、その情報の正確性または完全性を保証するものではありません。当社の製品候補の可能な市場機会に関する見積もりには、いくつかの主要な仮定が含まれていますが、これは弊社の産業知識、産業出版物、第三者の調査、その他の調査に基づくものであり、これらはサンプルが小さいことに基づいている場合や市場機会を正確に反映していない可能性があります。私たちが内部の仮定が合理的だと考えているものの、そのような仮定が証明された独立した情報源はありません。 将来を見据えた声明。 このプレゼンテーションには将来を見据えた声明が含まれています。これらの声明は、米国プライベート証券訴訟改革法1995の「安全港」規定の下で行われました。 このプレゼンテーションの将来を見据えた声明は、「将来」、「有望」、「可能性がある」、「計画」、「可能性」、「可能性がある」、「進歩」、「ターゲット」、「設計」、「戦略」、「パイプライン」、「プロジェクト」、「および類似の用語」またはその否定を含む用語で識別できます。「の未来について、I-Mabの信念や期待について述べられたものです。このプレゼンテーションの将来を見据えた声明については、次のことを含む制限なしに、以下のことに言及しています:当社のパイプラインおよび資本戦略; uliledlimabの可能な利点、利点、約束、属性、およびターゲット使用法;会社のポートフォリオの見込み便益、進展予定および関連するマイルストーンとその時期;uliledlimab、givastomig、ragistomigに関する市場機会およびI-Mabの次のステップの見通し(拡大、差別化、または商品化の可能性);進行中および将来の試験データの影響に関する会社の期待;残存償還義務の解決の時期;共同開発パートナーとの協力の利点;特定の監査要件に引き続き遵守できることによる会社の期待;研究の時期および進行(患者登録と投与に関して);進行中の研究からのデータと情報の可用性;および会社の現金ランウェイに関する期待。 これらの将来を見据えた声明には、これらの将来を見据えた声明には、このような将来を見据えた声明において示された実際の結果が、このような将来を見据えた声明に示されたとおりに表現される可能性のある基本的なリスクと不確実性が含まれています。将来を見据えた声明には、次のリスクおよび不確実性が含まれますが、これらに限定されるものではありません。の薬剤候補の安全性と有効性を実証するI-Mabの能力; その薬剤候補の臨床結果、その薬剤候補のさらなる開発や新薬の申請/生物学ライセンス申請をサポートする可能性があるかどうかについて; 関連する規制当局によるI-Mabの薬剤候補の規制承認に関する決定の内容と時機; その薬剤候補が承認された場合の商業的成功の達成に対するI-Mabの能力; 技術と医薬品の知的財産の保護を取得し保持する能力; 薬剤開発、製造、およびその他のサービスを実施する第三者に依存するI-Mab; I-Mabの限られた運営履歴および事業の開発や商業化を完了し、事業の展開と将来のパフォーマンスに関する独立した見解を形成するための完全な資金調達を取得する能力; に関する I-Mabの最新の年次報告書20Fおよび米国証券取引委員会(SEC)とのその後の提出での、潜在的リスク、不確実性、およびその他の重要な要因に関する議論。 I-Mabは、定期報告書においても、株主に対する年次報告書においても、プレスリリースおよびその他の文書、およびその幹部、役員、または従業員が第三者に当社の当社による口頭または記述の将来を見据えた声明を行うことがあります。すべての将来を見据えた声明は、現在I-Mabが入手可能な情報に基づいています。I-Mabは、法律の定める範囲で、法的に要求される場合を除いて、いかなる将来を見据えた声明も公開的に更新または修正する義務を負いません。 免責事項
Completed divestiture of China operations Streamlined organization with US leadership team Defined clinical strategy for immunotherapeutic pipeline Executing on clinical strategy via disciplined capital approach Transition to a US-Based Biotech Primarily Complete
Asset PHASE 1 PHASE 2 PHASE 3 MARKET OPPORTUNITY STATUS/POTENTIAL NEXT STEPS PARTNERSHIPS Uliledlimab CD73 mAb 1L mNSCLC: Target population of 300k+ patients2 1H 2025: First patient dosed in pembrolizumab + chemo combination for 1L mNSCLC 2H 2025: Phase 2 PFS data from ongoing TJBio study (China-only) evaluating combination with toripalimab Givastomig1 CLDN18.2 X 4-1BB Bispecific Ab 1L GC, GEJ, EAC: Target population of 100k+ patients2 Sep-2024: Phase 1 dose expansion monotherapy data presented at ESMO 2024 2H 2025: Phase 1b data in combination with nivolumab + chemo in 1L GC, GEJ, EAC Ragistomig/ABL5031 PD-L1 X 4-1BB Bispecific Ab Refractory/relapsed cancers: PD-(L)1 progression impacts most patients with metastatic disease2 May 2024: Phase 1 monotherapy data presented at ASCO 2024 Advancing a Differentiated Pipeline TJ Bio Co-developed with ABL Bio (givastomig also known as ABL111, ragistomig also known as ABL503) Global Data Epidemiology Data, Guidehouse legacy research Notes: CPI = checkpoint inhibitors; mNSCLC = metastatic non-small cell lung cancer; PD-(L)1 refers to inhibitors of PD-L1 or PD-1; Ab = antibody; GC = gastric cancers; GEJ = gastroesophageal junction; EAC = esophageal adenocarcinoma cancer; 1L = first line; ASCO 2024 = the American Society for Clinical Oncology Annual Meeting in 2024; PFS = progression free survival; ESMO 2024 = the European Society for Medical Oncology Annual Meeting in 2024
AACR 2021 Note: mNSCLC = metastatic non-small cell lung cancer; AMP = adenosine monophosphate Uliledlimab (targeting CD73) Initial development focused on 1L mNSCLC with potential to expand across multiple indications in combination with immune checkpoint inhibitors Anti-CD73 CD73 Biology Key Advantages CD73 is the rate-limiting enzyme that converts AMP into immunosuppressive adenosine Uliledlimab completely inhibits CD73 activity and the production of adenosine Blocking CD73 activity leads to complete inhibition of the adenosine pathway Uliledlimab targets CD73 non-competitively without the “hook effect” 1
CD73 is the Rate-Limiting Enzyme in the Adenosine Immunosuppression Pathway All AMP pathways converge at CD73 to generate adenosine Advantages of targeting CD73 for cancer therapy: blocking CD73 activity leads to complete inhibition of the adenosine pathway. Known potential escape pathways (ATP, cyclic AMP, and nicotinamide adenine dinucleotide through separate biochemical pathways) exist when targeting upstream CD39 or downstream adenosine receptors. NAD+ ATP CD39 CD203a ADP CD38 ADPR CD39 AMP CD203a AMP ADO A1AR A2aAR A2bAR A3AR Canonical Alternative Multiple Pathways Multiple Receptors CD73 Rate-limiting Converging Source: I-MAB information on file Notes: ATP = adenosine triphosphate; NAD+ = nicotinamide adenine dinucleotide; ADP = adenosine diphosphate; ADPR = adenosine diphosphate ribose; AMP = adenosine monophosphate; ADO = aldehyde deformylating oxygenase
CD73 enzyme activity inhibition Dose-dependent CD73 inhibition without the “hook effect”2 Uliledlimab: A Differentiated CD73 Antibody Open conformation (inactive) Closed conformation (active) Oleclumab1 Intra-dimer binding mode Inter-dimer binding mode Open conformation (inactive) Closed conformation (active) Unique intra-dimer binding through a C-terminus epitope Uliledlimab inhibits CD73 by binding to the C-terminus and preventing CD73 dimerization Oleclumab inhibits CD73 by binding to the N-terminus and preventing CD73 dimerization Uliledlimab CD73 enzyme activity inhibition Uliledlimab concentration Oleclumab concentration Uliledlimab CD73 dimer Oleclumab CD73 dimer Binding site Binding site Oleclumab (MEDI9447) was internally produced based upon the published sequence AACR 2021 Source: I-MAB information on file
Partial inhibition by inter-dimer binding mode Complete inhibition by intra-dimer binding mode Uliledlimab May Completely Inhibit CD73 Function in vitro, Whereas Competitor Antibody Does Not Astra Zeneca is evaluating oleclumab in a Phase 3 study in patients with Stage III NSCLC Oleclumab (MEDI9447) was internally produced based upon the published sequence
Inhibition of CD73 Activity & Tumor Growth is Dose-Dependent for Uliledlimab Inhibition of CD73 activity and tumor growth in vivo is limited by oleclumab’s hook effect biology Inhibition of CD73 activity and tumor growth in vivo by uliledlimab is dose-dependent Dose-dependency not observed for oleclumab Source: Data on file (IMAB), based on in vivo study on a PDX mouse model of NSCLC (LU5212, Crown Bioscience) in which CD73 inhibition in tumor was evaluated using an enzyme-histochemistry assay Oleclumab (MEDI9447) was internally produced based upon the published sequence. PDX = patient derived xenograft mouse model
Safety profile of combination comparable to CPI monotherapy studies Uliledlimab + Toripalimab Data Support Patient Selection Based on CD73 Expression and Show Manageable Toxicity Notes: ORR = objective response rate; MTD = maximally tolerated dose; Q3W = every three weeks; AE = adverse events; CPI = checkpoint inhibitors; TRAEs = treatment-related adverse events; ASCO 2023 = the American Society of Clinical Oncology 2023 Annual Meeting; toripalimab (used in this study) = Approved/China and the US (Shanghai Junshi Biosciences/Coherus Biosciences) *Patient disposition based on ASCO 2023 Poster from a cohort of 70 enrolled patients with unresectable/metastatic disease, including 67 efficacy evaluable and 64 patients who received at least one post baseline tumor assessment per iRECIST. Overall study (up to n=190) enrolled 5 cohorts (3 NSCLC sub-types, 1 ovarian, 1 all comers): data in this deck are from the treatment naïve, Stage IV NSCLC patients Well tolerated up to the highest doses tested (45mg/kg Q3W), without MTD Most TRAEs/AEs were Grade 1 or 2 ORR% (n) PD-L1 All PD-L1>1% CD73High 53% (10/19) 63% (10/16) CD73Low 18% (8/45) 20% (5/25) Pembro (KN-042) PD-L1>1% NA 27% (174/637) Phase 2 ORR data from front-line NSCLC Cohort* Safety observations for uliledlimab, administered to >200 patients in combination studies with CPIs
Most Tumors Decrease in Size Notes: Response definitions per iRECIST criteria. PR = partial response; SD = stable disease; PD = progressive disease; BOR = best overall response Source: ASCO 2023 Poster Early Phase 2 Data in Treatment-Naïve NSCLC Patients
Most Responses are Durable 18 of 21 patients with an objective response remain on treatment with a median follow-up of 10.8 months Notes: Response definitions per iRECIST criteria. PR = partial response; SD = stable disease; PD = progressive disease; iUPD = unconfirmed progressive disease Source: ASCO 2023 Poster
Rationale to Support Uliledlimab + Pembro + Chemotherapy in 1L mNSCLC Samanta D, Park Y, Ni XH, Semenza G. 2017. Chemotherapy induces enrichment of CD47+/CD73+/PDL1+ immune evasive triple-negative breast cancer cells. PNAS Vol. 115, No 6. Notes: mNSCLC = metastatic non-small cell lung cancer; IO = Immuno-oncology The addition of chemotherapy to IO monotherapy extends the benefit of IO to lower levels of PD-L1 expression Uliledlimab has a favorable toxicity profile in combination with IO agents Chemotherapy induces CD73 expression suggesting additional benefit by combining uliledlimab with pembrolizumab + chemotherapy1 Based on this rationale, I-Mab plans to dose the first patient with uliledlimab in combination with pembrolizumab + chemotherapy in newly diagnosed patients with mNSCLC in 1H 2025
Uliledlimab Development Plan: Randomized Study Design for Combination with Pembrolizumab + Chemotherapy Notes: mNSCLC = metastatic non-small cell lung cancer; R = randomized; ECOG PS = ECOG Performance Status Scale; TPS = tumor proportion score; ORR = objective response rate; PFS = progression free survival; DOR = duration of response; OS = overall survival; Q3W = dose every three weeks; IDMC = independent data monitoring committee; IND = investigational new drug; Pembro = pembrolizumab; Chemo = chemotherapy; 1L = first line IND application cleared August 2024, on track to initiate enrollment in 1H 2025 Eligibility: 1L Advanced mNSCLC ECOG PS 0/1 Stratify By: PD-L1 TPS Histology (n=96) Endpoints Primary: Safety, Efficacy (ORR) Secondary: PFS, DOR, OS IDMC Dose Escalation Lead-In (n=6) Uli Dose Level -1 + Pembro + Chemo (Q3W) SoC (n=15) Pembro + Chemo (Q3W) Uli Dose Level 1 (n=30) Uli Dose Level 1 + Pembro + Chemo (Q3W) R 2:1 IDMC R 2:1 Uli Dose Level 2 or -1 (n=30) Uli Dose Level 2 or -1 + Pembro + Chemo (Q3W) SoC (n=15) Pembro + Chemo (Q3W)
Molecular Design Key Differentiation Binding 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 Givastomig (targeting Claudin 18.2 and 4-1BB) Ongoing combination studies with nivolumab + chemotherapy across a wide range of Claudin 18.2 levels Unique bispecific Ab integrates Claudin 18.2 as a tumor engager and 4-1BB as a conditional T cell activator 4-1BB scFv CLDN18.2 Notes: scFv = single chain Fragment-variable region; TME = tumor microenvironment; Ab = antibody
Phase 1 Monotherapy Responses in Heavily Pretreated Patients Provide Support for Further Studies 5 mg/kg 8 mg/kg 12 mg/kg 15 mg/kg Numbers: CLDN18.2 % > Treatment Ongoing PD SD PR Patient Overview: 43 efficacy evaluable patients with CLDN18.2+ GC/GEJ/EAC Three median lines of prior treatment (range 1-6); dosed at 5-18 mg/kg1 Cohort is a subset of the Phase 1a (NCT04900818) Responses: Seven partial response (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 withPD-1 or PD-L1 inhibitors Conclusion: Givastomig was well tolerated and exhibits monotherapy activity in heavily pre-treated GEC patients with a range of CLDN18.2 expression. Duration of Treatment in Gastric Cancer Patients Stomach Stomach Esophagus Stomach Stomach Esophagus Stomach Stomach Stomach Stomach Stomach Stomach Stomach Stomach Stomach Esophagus Stomach Stomach Stomach Stomach Stomach Stomach Stomach Stomach Stomach Esophagus Stomach Stomach Stomach Stomach GEJ Stomach Stomach Stomach Stomach Esophagus Stomach Stomach Stomach Esophagus Stomach Esophagus > > > > 100 100 75 90 45 85 80 100 100 100 70 80 75 95 90 20 30 1 50 95 95 100 98 90 99 95 75 15 100 90 100 30 55 7 20 50 98 25 90 55 99 95 11 0 25 50 75 100 125 150 175 200 225 250 275 300 325 350 375 400 425 450 475 500 525 550 575 600 625 650 Study Days (C1D1 to End of Treatment Date) GEJ Defined as the predicted efficacious dosing range, based on preclinical studies Source: ESMO 2024 Notes: Data cut-off as of June 1, 2024; GC = gastric cancers; GEJ = gastroesophageal junction; EAC = esophageal adenocarcinoma
Safety: Treatment Related AEs Preferred Term (all numbers are n(%)) Grade 1 Grade 2 Grade 3 Grade 4 Grade 5 All Grades Nausea 6 (14.0) 4 ( 9.3) 1 ( 2.3) - - 11 (25.6) Anemia 2 ( 4.7) 5 (11.6) 3 ( 7.0) - - 10 (23.3) White blood cell count decreased 4 ( 9.3) 3 ( 7.0) 3 ( 7.0) - - 10 (23.3) Vomiting 4 ( 9.3) 2 ( 4.7) 1 ( 2.3) - - 7 (16.3) Decreased appetite 3 ( 7.0) 2 ( 4.7) 1 ( 2.3) - - 6 (14.0) Alanine aminotransferase increased 2 ( 4.7) 2 ( 4.7) 1 ( 2.3) - - 5 (11.6) Aspartate aminotransferase increased 3 ( 7.0) - 2 ( 4.7) - - 5 (11.6) Gamma-glutamyltransferase increased 1 ( 2.3) 3 ( 7.0) 1 ( 2.3) - - 5 (11.6) Neutrophil count decreased 1 ( 2.3) 3 ( 7.0) 1 ( 2.3) - - 5 (11.6) Infusion related reaction 1 ( 2.3) 2 ( 4.7) 1 ( 2.3) - - 4 ( 9.3) Lymphocyte count decreased - - 4 ( 9.3) - - 4 ( 9.3) Fatigue 2 ( 4.7) 1 ( 2.3) - - - 3 ( 7.0) Headache 2 ( 4.7) 1 ( 2.3) - - - 3 ( 7.0) Hypoalbuminemia 2 ( 4.7) 1 ( 2.3) - - - 3 ( 7.0) Lipase increased 1 ( 2.3) 1 ( 2.3) 1 ( 2.3) - - 3 ( 7.0) Platelet count decreased 1 ( 2.3) 1 ( 2.3) - 1 ( 2.3) - 3 ( 7.0) Weight decreased 2 ( 4.7) 1 ( 2.3) - - - 3 ( 7.0) Treatment-related adverse events (TRAEs) occurring in >5% (n=43) No DLT was reported up to 15 mg/kg Q2W and 18 mg/kg Q3W, and MTD was not reached 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%) 15 subjects (34.9%) experienced at least one Grade ≥ 3 TRAE. This included one Grade 4 TRAE of platelet count decreased and no Grade 5 TRAEs Most gastrointestinal TRAEs were Grade 1 or 2 and do not appear to be dose-related Source: ESMO 2024 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 Yields Better Monotherapy Responses in Patients with Low to High CLDN18.2 Expression Compared to Phase 1/2 Zolbetuximab Studies Drug Givastomig (bi-specific) Zolbetuximab (CLDN 18.2 targeted mAb) Phase Phase 1 Phase 1 Phase 2 CLDN18.2 – Expression of the Study Group IHC ≥1+ in ≥1% cells 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 43 15 43 ORR 16% (7/43) Zero 9% (4/43) DCR (CR+PR+SD) 49% (21/43) 1 SD 23% (10/43) Source Givastomig poster #1017P ESMO 2024 U Sahin et al. European Journal of Cancer 100 (2018) 17e26 O Tureci et al. Annals of Oncology 30: 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 cancers; 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
Potential Differentiations of Givastomig from Other Claudin 18.2 Targeted Competitors Givastomig (bi-specific) Zolbetuximab (mAb)1 CMG901 (ADC)2 Mechanism of Action CLDN18.2 dependent T cell activation in tumor 4-1BB agonism to increase T cell expansion in tumor and reinvigorate exhausted T cells Bi-specific antibody designed to have conditional 4-1BB activation Direct killing of CLDN18.2 tumor cells by ADCC may also release the tumor antigen CLDN18.2 targeted chemotherapy and direct killing by ADCC Lysis of tumor cells by toxin can release the tumor antigen to mediate immune response Efficacy ~20% monotherapy ORR in previously treated CLDN18.2 + GC/GEJ/EAC ~10% monotherapy ORR in previously treated CLDN18.2 + GC/GEJ/EAC1 33% monotherapy ORR in previously treated CLDN18.2 + GC/GEJ Safety <5% Grade 3 neutropenia <5% Grade 3 vomiting 22% Grade 3 vomiting1 20% Grade 3+ Neutropenia 10% Grade 3 vomiting3 Claudin 18.2 Targetable Expression Extending to low levels of expression due to high affinity binding to CLDN18.2 Limited to targeting higher CLDN-expressing tumors Likely limited to targeting high CLDN-expressing tumors 1. Annals of Oncology, 2. CMG901 is a CLDN18.2 ADC being developed globally by AstraZeneca 3. ASCO Plenary Series 2023 Notes: ORR = objective response rate, GC/GEJ/EAC = gastric cancer, gastroesophageal junction, EAC = esophageal adenocarcinoma, CLDN = claudin, ADCC = antibody dependent cellular cytotoxicity
Givastomig Development Plan: Phase 1b Study Design for Combination with Nivolumab + Chemotherapy Eligibility: 1L unresectable or metastatic GC/GEJ/EAC HER2 negative CLDN 18.2 ≥1+ on ≥1% of tumor cells Endpoints: Primary: Safety Secondary: ORR, PK/PD, BoR, DoR, PFS, OS Notes: GC/GEJ/EAC = gastric cancer, gastroesophageal junction, EAC = esophageal adenocarcinoma, CLDN = claudin, ADCC = antibody dependent cellular cytotoxicity, FOLFOX6: standard of care chemotherapy regimen for GEJ, nivo = nivolumab, Q2W = every two weeks, Giva = givastomig, MAD/MTD = multiple ascending dose or maximum tolerated dose, ORR = objective response rate, PK = pharmacokinetic, PD = pharmacodynamic, BoR = best overall response, DoR = duration of response, PFS = progression free survival, OS = overall survival Dose Escalation Lead-In (n=5) Giva dose level 1 + nivo + mFOLFOX6 Q2W Dose Escalation (n=15) Dose Expansion (n=6-8) Dose Expansion Selected Giva dose (or MAD/MTD) + nivo + mFOLFOX6 Q2W Dose Escalation (n=6) Giva dose level 2 + nivo + mFOLFOX6 Q2W Dose Escalation (n=4) Giva dose level 3 + nivo + mFOLFOX6 Q2W
Unique Design to Enable Potential Wide Use Plus Favorable Initial Safety Profile Encouraging Responses in Previously Treated Patients, Including Those with Low CLDN18.2 Expression Levels Dose Expansion Data and New Nivolumab + Chemotherapy Combo Study Ongoing Unique Bispecific Design Properties and Monotherapy Data in Gastric Cancers May Position Givastomig as Best-in-Class Claudin 18.2 bispecific Objective responses seen in patients with gastric and esophageal cancer who had received multiple lines of prior treatment, including PD-(L)1, and exhibited low levels of CLDN18.2 expression Response rate and tolerability supports combination in 1L SoC regimens New dose expansion in combination with nivolumab + chemotherapy cohort study began in 1Q 2024 in treatment naïve patients with gastric cancers Updated monotherapy dose expansion data in CLDN18.2+ patients with gastric cancers whose disease has progressed after previous treatment was presented at ESMO 2024 Bispecific design results in CLDN18.2 conditional 4-1BB and T cell activation, potentially limiting toxicity and inducing long-lasting immune memory response Phase 1 dose escalation reached highest planned dose without encountering DLT or liver toxicity signals Notes: Gastric cancers = gastric, gastroesophageal junction and esophageal cancer; ESMO 2024 = the European Society for Medical Oncology Annual Meeting in 2024; SoC = standard of care; DLT = dose limiting toxicity, 1L = first line
Molecular Design Target Drug Profile Molecule binds to PD-L1 to inhibit PD-1/PD-L1 interaction Targeting PD-L1+ tumor cells Blocking PD-L1/PD-1 immune inhibitory signaling PD-L1-dependent 4-1BB activation at the tumor site Potent tumor-directed 4-1BB activation to enhance anti-tumor immunity Enhances anti-tumor immunity and re-invigorates exhausted T cells1 Localized 4-1BB activation in TME to mitigate liver toxicity and systemic immune response Ragistomig (ABL503/TJ-L14B, targeting PD-L1 and 4-1BB) A novel bispecific integrates PD-L1 as a tumor engager and 4-1BB as a conditional T cell activator 4-1BB scFv PD-L1 IgG Phase 1 efficacy data presented at ASCO 20242 JITC 2021 ASCO 2024 Notes: scFv = single chain Fragment-variable region; TME = tumor microenvironment; ASCO 2024 = the American Society for Clinical Oncology Annual Meeting in 2024
Phase 1 Data Support Further Development as a Monotherapy and in Combination with Other Agents Overview: 44 efficacy evaluable patients (53 enrolled) with advanced or relapsed/refractory solid tumors (NCT04762641) 64.2% (34/53) of patients enrolled had at least three prior lines of systemic anti-cancer treatment Efficacy Results at 3 and 5 mg/kg Q2W: Objective Response Rate (ORR) of 26.9% (7/26), Clinical Benefit Ratio (CBR) of 69.2% (18/26) One CR, six PRs, eleven SDs 71.4% of responders had received prior anti-PD-(L)-1 inhibitors The CR was observed in a heavily pretreated ovarian cancer patient dosed at 3 mg/kg (seven lines of prior therapy) Conclusion: Compelling clinical data in checkpoint inhibitor relapsed/refractory and IO naïve patients Treatment Duration (Days) CR start PR start On-going PD start 0.7 mg 2 mg/kg 2 mg 3 mg/kg 7 mg 5 mg/kg 0.3 mg/kg 7 mg/kg 1 mg/kg 10 mg/kg Source: ASCO 2024 Notes: Data cut-off as of April 19, 2024. CR = complete response; PR = partial response; PD = progressive disease; SD = stable disease; IO = Immuno-oncology, Q2W = every two weeks
Manageable Safety Profile MTD established with 7 mg/kg every two-week dosing Most common TRAEs were increased ALT and increased AST None of the transaminase elevations were accompanied by clinically significant, treatment-related bilirubin increases Grade ≥ 3 ALT or AST increases occurred in 24.5% (13/53) of patients and improved with corticosteroids or ragistomig treatment interruption No cytokine release syndrome occurred, and one infusion-related reaction occurred at 5 mg/kg (Grade 2) ABL503 monotherapy Demography All patients (N = 53) All grades, n(%) Grade ≥ 3, n(%) Any TRAE 40 (75.5) 22 (41.5) TRAE occurring in ≥ 10% of patients Alanine aminotransferase increased 17 (32.1) 12 (22.6) Aspartate aminotransferase increased 16 (30.2) 11 (20.8) Pyrexia 8 (15.1) 1 (1.9) Nausea 7 (13.2) - Rash 7 (13.2) 2 (3.8) Fatigue 6 (11.3) 1 (1.9) Platelet count decreased 6 (11.3) 1 (1.9) Source: ASCO 2024 poster, Table 2 Notes: Data cut-off as of April 19, 2024. MTD = maximally tolerated dose; TRAE = treatment-related adverse events; ALT = alanine aminotransferase; AST = aspartate aminotransferase
Ragistomig Results Compared to Acasunlimab Phase 1 Ragistomig (ABL503) Acasunlimab (GEN1046) Phase Phase 1 (NCT04762641) Phase 1 (NCT03917381) Treatment Monotherapy 0.7 mg – 10 mg/kg, Q2W Monotherapy 25 – 1,200 mg, Q3W Diagnosis Advanced or refractory solid tumors Advanced or refractory solid tumors Efficacy Evaluable 26 (sum of 3 mg/kg and 5 mg/kg) 61 (25 – 1,200 mg) 30 (80 – 200 mg) ORR 26.9% (7/26) 6.6% (4/61) 13.3% (4/30, 80 – 200 mg) DCR (CR+PR+SD) 69.2% (18/26) 65.6% (40/61) Safety Grade 3 AST / ALT: 24.5% (13/53) Grade 3 AST / ALT: 10% Source Ragistomig poster ASCO 2024 Cancer Discovery 2022 Notes: ASCO 2024 = American Society for Clinical Oncology Annual Meeting; ORR = objective response rate; DCR = disease control rate; CR complete response; PR = partial response; SD = stable disease; AST = aspartate aminotransferase; ALT = alanine aminotransferase. Q2W = every two weeks. 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
Cash, cash equivalents and short-term investments as of June 30, 2024 were $207.5M Expected cash runway into 2027 supporting multiple potential inflection points Issued and outstanding ordinary shares of 187.3M representing the equivalent of 81.4M ADSs1 Financial Information and Upcoming Milestones Timing Program Milestone Sep-2024 givastomig Updated Phase 1 dose expansion data at ESMO 2024 Monotherapy (CLDN18.2+ patients with GC, GEJ, EAC) data 1H 2025 uliledlimab First patient dosed in Phase 2 Randomized study in combination with pembrolizumab + chemo 2H 2025 uliledlimab Phase 2 PFS data from uliledlimab + toripalimab Randomized study (TJ Bio China-only data) 2H 2025 givastomig Phase 1b in combination with nivolumab + chemo Safety and ORR data in 1L GC, GEJ, EAC Selected Financial Information Recent and Anticipated Upcoming Milestones Assuming the conversion of all ordinary shares into ADSs Notes: CPI = checkpoint inhibitor; CLDN = Claudin; GC = gastric cancers; GEJ = gastroesophageal junction; EAC = esophageal adenocarcinoma; ESMO 2024 = the European Society for Medical Oncology Annual Meeting in 2024; PFS = progression free survival; ORR = objective response rate
Stay connected I-Mab Biopharma IR Contact Tyler Ehler Sr. Director, Investor Relations IR@imabbio.com