letaplimab (IBI188) / Innovent Biologics - LARVOL DELTA

Efficacy and Safety Evaluation of IBI188 in Combination With Demethylating Agents in Treatment of Patients With Acute Myeloid Leukemia (clinicaltrials.gov) - P1/2 | N=222 | Suspended | Sponsor: Innovent Biologics (Suzhou) Co. Ltd. | Trial completion date: Jun 2024 ➔ Dec 2024 | Trial primary completion date: Jun 2023 ➔ Jun 2024

Combination therapy • Trial completion date • Trial primary completion date • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • ABL1 • BCR

[VIRTUAL] First-in-human Phase I trial of IBI188, an anti-CD47 targeting monoclonal antibody, in patients with advanced solid tumors and lymphomas (SITC 2020) - P1a | "The receptor occupancy analysis at 20 mg/kg and 30 mg/kg is ongoing. Conclusions IBI188 was well tolerated at 1 mg/kg priming dose following by the maintenance dose up to 30 mg/kg."

Clinical • P1 data • Hematological Malignancies • Lymphoma • Oncology • Solid Tumor

Suppression of Extracellular Vesicle CD47 Induces Systemic Anti-DLBCL Immunity (ASH 2021) - P1b/2 | "Anti-CD47 antibody (IBI188) has shown promise in treating tumors, including Diffuse large B cell lymphoma (DLBCL)...Moreover, high levels of circulating EV CD47 would follow and correlate positively with the phagocytic activity of macrophages, and reflect the presence of a successful anti-tumor immunity elicited by the anti-CD47 therapy. Together, these findings show that EV CD47 represents an unexplored therapeutic target, which could overcome resistance to current CD47 antibody approaches."

IO biomarker • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Immune Modulation • Inflammation • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD47 • CD63 • SIRPA

A Phase 1b Study to Evaluate Safety and Efficacy of IBI188 in Combination with Azacitidine (AZA) As a First-Line Treatment in Subjects with Newly Diagnosed Higher Risk Myelodysplastic Syndrome (ASH 2022) - P1 | "IBI188 in combination with azacitidine demonstrated promising efficacy, and a manageable safety profile as a first-line treatment in subjects with newly diagnosed higher risk myelodysplastic syndrome."

Clinical • Combination therapy • P1 data • Anemia • Hematological Disorders • Hematological Malignancies • Immune Modulation • Inflammation • Myelodysplastic Syndrome • Oncology

Efficacy and Safety Evaluation of IBI188 in Combination With Demethylating Agents in Treatment of Patients With Acute Myeloid Leukemia (clinicaltrials.gov) - P1/2 | N=222 | Suspended | Sponsor: Innovent Biologics (Suzhou) Co. Ltd. | N=126 ➔ 222 | Trial completion date: May 2022 ➔ Jun 2024 | Recruiting ➔ Suspended | Trial primary completion date: Apr 2021 ➔ Jun 2023

Combination therapy • Enrollment change • Trial completion date • Trial primary completion date • Trial suspension • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • ABL1 • BCR

Safety and Efficacy of IBI188 With Azacitidine in Subjects With Newly Diagnosed Higher Risk MDS (clinicaltrials.gov) - P1 | N=120 | Suspended | Sponsor: Innovent Biologics (Suzhou) Co. Ltd. | N=12 ➔ 120 | Trial completion date: Feb 2022 ➔ Aug 2024 | Recruiting ➔ Suspended | Trial primary completion date: Dec 2021 ➔ Dec 2023

Combination therapy • Enrollment change • Trial completion date • Trial primary completion date • Trial suspension • Hematological Malignancies • Myelodysplastic Syndrome • Oncology

Innovent Presents Phase 1b Clinical Data of IBI188 (Anti-CD47 Monoclonal Antibody) at the 2022 American Society of Hematology Annual Meeting (PRNewswire) - P1b | N=93 | "Innovent Biologics...announced that clinical data of IBI188 (anti-CD47 monoclonal antibody) as first-line treatment in newly diagnosed higher risk myelodysplastic syndrome (MDS) is presented at the 2022 American Society of Hematology (ASH) Annual Meeting, held Dec 10-13, 2022....As of the data cutoff date (Oct 20, 2022), 93 treatment-naïve newly diagnosed higher risk MDS patients received IBI188 (from 0.1 mg/kg priming dose to 30mg/kg maintenance, QW) combined with AZA. 30 patients had received treatment ≥ 6 cycles. The Objective Response Rate (ORR) was 100% (30/30), complete response rate (CRR) was 63.3% (19/30). 42 patients had received treatment ≥ 4 cycles, ORR was 97.6% (41/42), CRR was 45.2% (19/42). 49 patients had received treatment ≥ 3 cycles, ORR was 93.9% (46/49), CRR was 38.8% (19/49). The median duration of response was not reached yet."

P1 data • Hematological Malignancies • Myelodysplastic Syndrome • Oncology

Innovent Announced Clinical Data of Multiple Trials Will be Presented at the 2022 ESMO-IO and ASH Annual Meetings (PRNewswire) - "Innovent Biologics...announced that clinical data from multiple trials in relation to TYVYT® (sintilimab injection), olverembatinib (BCL-ABL TIK), IBI188 (anti-CD47 monoclonal antibody), IBI110 (anti-LAG-3 monoclonal antibody) and IBI939 (anti-TIGIT monoclonal antibody) will be presented at the upcoming international medical conferences."

Clinical data • P1 data • P2 data • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Myelodysplastic Syndrome • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Thoracic Cancer

IBI188 Combination Therapy in Solid Tumors (clinicaltrials.gov) - P1 | N=9 | Terminated | Sponsor: Innovent Biologics (Suzhou) Co. Ltd. | N=120 ➔ 9 | Trial completion date: Oct 2022 ➔ Jul 2022 | Recruiting ➔ Terminated; No signs of efficacy in solid tumors

Combination therapy • Enrollment change • Trial completion date • Trial termination • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Osteosarcoma • Sarcoma • Solid Tumor

A Phase 1 Study Evaluating the Safety, Tolerability, and Initial Efficacy of IBI188 in Advanced Malignancies (clinicaltrials.gov) - P1 | N=49 | Completed | Sponsor: Innovent Biologics (Suzhou) Co. Ltd. | Active, not recruiting ➔ Completed | Trial primary completion date: Nov 2021 ➔ Feb 2022

Trial completion • Trial primary completion date • Hematological Malignancies • Oncology • Solid Tumor

Innovent Announced 2021 Annual Results (PRNewswire) - "Seven innovative molecules achieved positive PoC data readout, plan to advance into the late stage in clinic: (i) IBI-188 (CD47): Plan to initiate Phase 3 study for 1L MDS in 2022; (ii) IBI-326 (BCMA CAR-T): Plan to submit NDA in 2022; (iii) IBI-310 (CTLA-4): Plan to submit NDA for CC in 2022."

New P3 trial • Regulatory • Cholangiocarcinoma • Gastrointestinal Cancer • Hematological Malignancies • Hepatocellular Cancer • Liver Cancer • Myelodysplastic Syndrome • Oncology • Solid Tumor

A Study Evaluating the Safety, Tolerability, and Initial Efficacy of Recombinant Human Anti-cluster Differentiation Antigen 47 (CD47) Monoclonal Antibody Injection (IBI188) in Patients With Advanced Malignant Tumors and Lymphomas (clinicaltrials.gov) - P1a; N=20; Completed; Sponsor: Innovent Biologics (Suzhou) Co. Ltd.; Active, not recruiting ➔ Completed; N=42 ➔ 20; Trial completion date: Aug 2022 ➔ Mar 2021

Clinical • Enrollment change • Trial completion • Trial completion date • Hematological Malignancies • Lymphoma • Oncology • Solid Tumor

[VIRTUAL] First-in-human Phase I trial of IBI188, an anti-CD47 targeting monoclonal antibody, in patients with advanced solid tumors and lymphomas (SITC 2020) - P1a | "The receptor occupancy analysis at 20 mg/kg and 30 mg/kg is ongoing. Conclusions IBI188 was well tolerated at 1 mg/kg priming dose following by the maintenance dose up to 30 mg/kg."

Clinical • P1 data • Hematological Malignancies • Lymphoma • Oncology • Solid Tumor

A Phase 1 Study Evaluating the Safety, Tolerability, and Initial Efficacy of Recombinant Human Anti-cluster Differentiation Antigen 47 (CD47) Monoclonal Antibody Injection (IBI188) in Patients With Advanced Malignancies (clinicaltrials.gov) - P1; N=49; Active, not recruiting; Sponsor: Innovent Biologics (Suzhou) Co. Ltd.; Recruiting ➔ Active, not recruiting; N=92 ➔ 49; Trial primary completion date: Jul 2020 ➔ Nov 2021

Clinical • Enrollment change • Enrollment closed • Trial primary completion date • Hematological Malignancies • Oncology • Solid Tumor

IBI188 Combination Therapy in Solid Tumors (clinicaltrials.gov) - P1; N=120; Recruiting; Sponsor: Innovent Biologics (Suzhou) Co. Ltd.; Not yet recruiting ➔ Recruiting

Clinical • Combination therapy • Enrollment open • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Osteosarcoma • Sarcoma • Solid Tumor

Ascentage Pharma and Innovent Biologics Reach Multifaceted Strategic Agreement Totaling US$245 Million Including Commercialization of Olverembatinib (HQP1351) in China, Joint Clinical Development of Lisaftoclax (APG-2575) and Equity Investment (PRNewswire) - "According to the agreement, Innovent and Ascentage Pharma will be jointly responsible for the subsequent R&D of HQP1351 in China. Upon being granted a New Drug Application (NDA) approval, the two companies will jointly commercialize HQP1351 in China and equally split the profit generated by the joint commercialization...The two companies agree to jointly explore the development of APG-2575 with the anti-CD20 monoclonal antibody HALPRYZA® (rituximab biosimilar injection) and the anti-CD47 monoclonal antibody letaplimab (IBI188) in certain indications."

Clinical • Commercial • Licensing / partnership • Oncology

Combined strategies for effective cancer immunotherapy with a novel anti-CD47 monoclonal antibody. (PubMed, Cancer Immunol Immunother) - "CD47 expression was evaluated following azacytidine (AZA) treatment, a standard-of-care for patients with multiple myeloma; enhanced anti-tumor efficacy was observed in the combination group in AML xenograft models. Notably, IBI188 treatment increased vascular endothelial growth factor-A (VEGF-A) levels in a solid tumor model, and combined treatment with an anti-VEGF-A antibody and IBI188 resulted in an enhanced anti-tumor effect. These data indicate that IBI188 is a therapeutic anti-CD47 antibody with anti-tumor potency, which can be enhanced when used in combination with standard-of-care drugs for cancer treatment."

IO biomarker • Journal • Acute Myelogenous Leukemia • Hematological Malignancies • Immunology • Inflammation • Multiple Myeloma • Oncology • Solid Tumor

IBI188 Combination Therapy in Solid Tumors (clinicaltrials.gov) - P1; N=120; Not yet recruiting; Sponsor: Innovent Biologics (Suzhou) Co. Ltd.

Clinical • Combination therapy • New P1 trial • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Osteosarcoma • Sarcoma • Solid Tumor

Innovent Announced Financial Results for Full Year Ended December 31, 2020 and Corporate Progress (PRNewswire) - “The Company plans to enter phase III or pivotal clinical trial this year for 1L MDS for IBI-188…The Company plans to obtain proof-of-concept (PoC) data for IBI-322 in 2021…The Company has completed phase 1b enrollment for IBI-110 and will obtain PoC data in 2021. The potential first-in-class PD- L1/LAG-3 bispecific antibody has also received IND approval recently, and the Company will start Phase 1 study in 2021…In TIGIT area: the TIGIT monoclonal antibody IBI-939 has entered Phase 1b study, with plan to obtain PoC data in 2021. The Company also submitted the IND application for its PD-1/TIGIT bispecific antibody IBI-321 recently, and plans to start clinical study in 2021.”

New P1 trial • New P3 trial • P1 data • Myelodysplastic Syndrome • Oncology • Solid Tumor

Safety and Efficacy of IBI188 With Azacitidine in Newly Diagnosed Higher Risk MDS (clinicaltrials.gov) - P1; N=12; Recruiting; Sponsor: Innovent Biologics (Suzhou) Co. Ltd.; Not yet recruiting ➔ Recruiting

Clinical • Combination therapy • Enrollment open • Hematological Malignancies • Myelodysplastic Syndrome • Oncology

A Study Evaluating the Safety and Efficacy of IBI188 in Combination With AZA in Subjects With Newly Diagnosed MDS (clinicaltrials.gov) - P1b; N=32; Suspended; Sponsor: Innovent Biologics (Suzhou) Co. Ltd.; Recruiting ➔ Suspended

Clinical • Combination therapy • Trial suspension • Hematological Malignancies • Myelodysplastic Syndrome • Oncology

Efficacy and Safety Evaluation of IBI188 in Combination With Azacitidine in Treatment of Patients With Acute Myeloid Leukemia (clinicaltrials.gov) - P1/2; N=126; Recruiting; Sponsor: Innovent Biologics (Suzhou) Co. Ltd.; Not yet recruiting ➔ Recruiting

Clinical • Combination therapy • Enrollment open • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

Innovent Releases Phase 1a Results of CD47 Monoclonal Antibody (Letaplimab) in Monotherapy for Advanced Malignancies at SITC 2020 (PRNewswire) - P1, N=42; NCT03763149; Sponsor: Innovent Biologics (Suzhou) Co. Ltd.; "A total of 20 subjects were enrolled in this study. As of June 18, 2020, letaplimab completed all the preset doses (maximum dose was 30mg/kg QW) without dose-limiting toxicity and was well tolerated in general. Most of the treatment-related adverse events were grade 1-2, with no drug-related adverse reactions leading to permanent discontinuation and treatment-related deaths...Meanwhile, anti-tumor activity was observed in the monotherapy of letaplimab in this study, with multiple patients obtained stable disease for long period...Innovent will conduct clinical studies of letaplimab combined with TYVYT®(Sintilimab injection) in the treatment of multiple solid tumors."

New trial • P1 data • Oncology • Solid Tumor

A Study Evaluating the Safety and Efficacy of IBI188 in Combination With AZA in Subjects With Newly Diagnosed MDS (clinicaltrials.gov) - P1b; N=32; Recruiting; Sponsor: Innovent Biologics (Suzhou) Co. Ltd.; Not yet recruiting ➔ Recruiting

Clinical • Combination therapy • Enrollment open • Hematological Malignancies • Myelodysplastic Syndrome • Oncology

Innovent Announces Financial Results for Six Months Ended June 30, 2020 and Corporate Progress (PRNewswire) - "Post-Reporting Period (Expected) Milestones - IBI-188: (i) In China, initiate a pivotal Phase 1b/2 trial in recurrent or refractory acute myeloid leukemia ('r/r AML') with first patient of the Phase 1b study enrolled; (ii) In China, initiate the China arm of a global pivotal Phase 1b/3 trial in MDS ('myelodysplastic syndrome') with first patient of the Phase 1b study enrolled; (iii) In the U.S., initiate the Phase 1b trial in MDS with plan for a registration development thereafter; (iv) Present the safety results of the phase 1a study to evaluate IBI-188 in advanced malignant tumors and lymphomas in the U.S. at the annual meeting of SITC."

P1 data • Trial initiation date • Acute Myelogenous Leukemia • Hematological Malignancies • Lymphoma • Myelodysplastic Syndrome • Oncology • Solid Tumor