lumrotatug (CM313) / Keymed Biosciences, Timberlyne Therapeutics - LARVOL DELTA

Long-term remissions in refractory ITP patients by daratumumab (ASH 2025) - "All patients were previously treated with TPO agonists and rituximab and had at least four prior ITPtherapy lines with a median disease duration of six years (range: 1-35 years)...It should be noted that the time until response can take up to 10 weeks and therefore therapyshould not be discontinued too early if an adequate increase in platelet count has not yet been reached.Another important observation is that in one relapsed case after initial response to daratumumab, wewere able to achieve a second remission with a combination therapy of daratumumab and romiplostim,which indicates that daratumumab re-exposure is a considerable option.In recent years, another CD38 antibody (CM313, Lumrotatug) has been developed for ITP, which alsoshowed an excellent response with an overall response rate of 95% in a phase 2 study for patients withrefractory/chronic ITP (Chen et al., NEJM, 2024)...Looking ahead, we are also exploring the possibility of combining daratumumab with..."

Clinical • Hematological Disorders • Hematological Malignancies • Immune Thrombocytopenic Purpura • Multiple Myeloma • Thrombocytopenic Purpura • SYK

Anti-CD38 monoclonal antibody CM313 for systemic lupus erythematosus: a randomized, double-blind, placebo-controlled phase Ib/IIa trial. (PubMed, Signal Transduct Target Ther) - P1/2 | "CM313 showed a manageable safety profile in SLE patients at 2-16 mg/kg and encouraging clinical efficacy at 8 and 16 mg/kg. The results support further investigation of CM313 for treating SLE patients (ClinicalTrials.gov ID: NCT05465707)."

Clinical • Journal • P1/2 data • Herpes Zoster • Immunology • Infectious Disease • Inflammatory Arthritis • Lupus • Nephrology • Respiratory Diseases • Systemic Lupus Erythematosus • Varicella Zoster

CM313, a Novel Anti-CD38 Antibody, As a Potential Treatment for Primary Immune Thrombocytopenia: A Phase II Trial (ASH 2023) - P2 | "The main inclusion criteria were patients (age ≥18 years) with ITP and a platelet count <30×109/L, who did not response to or relapsed after glucocorticoid therapy and at least one second-line therapy (including rituximab and/or thrombopoietin receptor agonists [TPO-RAs]). CM313, a novel anti-CD38 monoclonal antibody, has demonstrated tolerable safety and preliminary efficacy in refractory/relapsed ITP patients. Figure 1: Platelet count in 7 patients."

P2 data • Hematological Disorders • Hematological Malignancies • Immune Thrombocytopenic Purpura • Immunology • Multiple Myeloma • Oncology • Thrombocytopenia • Thrombocytopenic Purpura

Study of CM313 in Subject With IgA Nephropathy (clinicaltrials.gov) - P2 | N=106 | Not yet recruiting | Sponsor: Keymed Biosciences Co.Ltd | N=75 ➔ 106 | Trial completion date: Oct 2027 ➔ Aug 2028 | Initiation date: Mar 2025 ➔ Sep 2025 | Trial primary completion date: Apr 2026 ➔ Mar 2027

Enrollment change • Trial completion date • Trial initiation date • Trial primary completion date • Glomerulonephritis • IgA Nephropathy • Renal Disease

Pharmacokinetics, Pharmacodynamics, and Immunogenicity of CM313 in Healthy Participants: An Open-Label/Double-Blind, Randomized, Placebo-Controlled Phase 1 Trial. (PubMed, Clin Transl Sci) - P1 | "Overall, single doses of CM313 demonstrated favorable safety, tolerability, PK, and PD in healthy participants. Trial Registration: ClinicalTrials.gov (NCT06285227)."

Clinical • Journal • P1 data • PK/PD data • Immunology

Study of CM313(SC) Injection in Subjects With Platelet Transfusion Refractoriness (clinicaltrials.gov) - P1/2 | N=110 | Recruiting | Sponsor: Keymed Biosciences Co.Ltd | Not yet recruiting ➔ Recruiting | Trial completion date: Jun 2027 ➔ Nov 2027 | Trial primary completion date: Jun 2027 ➔ Nov 2027

Enrollment open • Trial completion date • Trial primary completion date

Study of CM313 (SC) Injection in Subjects With Primary Immune Thrombocytopenia (ITP) (clinicaltrials.gov) - P2 | N=62 | Active, not recruiting | Sponsor: Keymed Biosciences Co.Ltd | Not yet recruiting ➔ Active, not recruiting

Enrollment closed • Hematological Disorders • Immune Thrombocytopenic Purpura • Thrombocytopenia • Thrombocytopenic Purpura

2022-CM313-ITP: A Prospective, One-arm and Open Clinical Study of CM313 in the Treatment of Immune Thrombocytopenia (clinicaltrials.gov) - P2 | N=22 | Completed | Sponsor: Institute of Hematology & Blood Diseases Hospital, China | Recruiting ➔ Completed

Trial completion • Hematological Disorders • Immune Thrombocytopenic Purpura • Thrombocytopenia • Thrombocytopenic Purpura

Study of CM313 in Subject With IgA Nephropathy (clinicaltrials.gov) - P2 | N=75 | Not yet recruiting | Sponsor: Keymed Biosciences Co.Ltd

New P2 trial • Glomerulonephritis • IgA Nephropathy • Renal Disease

Study of CM313(SC) Injection in Subjects With Relapsed/Refractory Aplastic Anemia (clinicaltrials.gov) - P1/2 | N=125 | Not yet recruiting | Sponsor: Keymed Biosciences Co.Ltd

New P1/2 trial • Anemia • Aplastic Anemia • Hematological Disorders

Study of CM313(SC) Injection in Subjects With Platelet Transfusion Refractoriness (clinicaltrials.gov) - P1/2 | N=125 | Not yet recruiting | Sponsor: Keymed Biosciences Co.Ltd

New P1/2 trial

Study of CM313(SC) Injection in Systemic Lupus Erythematosus(SLE) (clinicaltrials.gov) - P2 | N=150 | Not yet recruiting | Sponsor: Keymed Biosciences Co.Ltd

New P2 trial • Immunology • Inflammatory Arthritis • Lupus • Systemic Lupus Erythematosus

CM313 Monotherapy in Patients With Relapsed/Refractory Multiple Myeloma or Marginal Zone Lymphoma: A Multicenter, Phase 1 Dose-Escalation and Dose-Expansion Trial. (PubMed, Am J Hematol) - No abstract available

Journal • Monotherapy • P1 data • Hematological Malignancies • Lymphoma • Marginal Zone Lymphoma • Multiple Myeloma • Oncology

Timberlyne Therapeutics Launches with a $180 Million Series A Financing to Advance CM313, a Potentially Best-in-Class Anti-CD38 Monoclonal Antibody, for Diseases of High Unmet Medical Needs (PRNewswire) - "Timberlyne Therapeutics...announced the close of a $180 million Series A financing to advance CM313, a potentially best-in-class monoclonal antibody targeting CD38, for diseases of high unmet medical needs....Timberlyne has obtained exclusive development and commercialization rights to CM313 worldwide outside of greater China from Keymed Biosciences, a leading drug discovery and development company. Under the terms of the licensing agreement, Keymed will receive an undisclosed upfront payment, as well as future cash milestones, royalties on any potential future net sales, and equity ownership in Timberlyne....CM313 is an IgG1 monoclonal antibody with enhanced complement-dependent cytotoxicity and has been clinically studied across numerous disease states, including immune thrombocytopenic purpura...[and] systemic lupus erythematosus...."

Financing • Immune Thrombocytopenic Purpura • Systemic Lupus Erythematosus

Timberlyne Therapeutics Launches with a $180 Million Series A Financing to Advance CM313, a Potentially Best-in-Class Anti-CD38 Monoclonal Antibody, for Diseases of High Unmet Medical Needs (PRNewswire) - "Timberlyne Therapeutics...announced the close of a $180 million Series A financing to advance CM313, a potentially best-in-class monoclonal antibody targeting CD38, for diseases of high unmet medical needs....Timberlyne has obtained exclusive development and commercialization rights to CM313 worldwide outside of greater China from Keymed Biosciences, a leading drug discovery and development company. Under the terms of the licensing agreement, Keymed will receive an undisclosed upfront payment, as well as future cash milestones, royalties on any potential future net sales, and equity ownership in Timberlyne....CM313 is an IgG1 monoclonal antibody with enhanced complement-dependent cytotoxicity and has been clinically studied across numerous disease states, including...relapsed/refractory multiple myeloma."

Financing • Multiple Myeloma

A Randomized, Double-blind, Placebo-controlled, and Multi-center Clinical Study of CM313 in the Treatment of Immune Thrombocytopenia (clinicaltrials.gov) - P2 | N=45 | Active, not recruiting | Sponsor: Institute of Hematology & Blood Diseases Hospital, China | Recruiting ➔ Active, not recruiting | Trial completion date: Jan 2026 ➔ Dec 2024 | Trial primary completion date: Jan 2026 ➔ Nov 2024

Enrollment closed • Trial completion date • Trial primary completion date • Hematological Disorders • Immune Thrombocytopenic Purpura • Thrombocytopenia • Thrombocytopenic Purpura

Study of CM313 (SC) Injection in Subjects With Primary Immune Thrombocytopenia (ITP) (clinicaltrials.gov) - P2 | N=60 | Not yet recruiting | Sponsor: Keymed Biosciences Co.Ltd | Phase classification: P1/2 ➔ P2 | N=36 ➔ 60

Enrollment change • Phase classification • Hematological Disorders • Immune Thrombocytopenic Purpura • Thrombocytopenia • Thrombocytopenic Purpura

A Randomized Study on Pemphigus Treatment With Humanized CD38 Antibody CM313. (clinicaltrials.gov) - P1/2 | N=100 | Not yet recruiting | Sponsor: Chao Ji

New P1/2 trial • Dermatology • Immunology • Pemphigus Vulgaris

Study of CM313 in Healthy Subjects (clinicaltrials.gov) - P1 | N=51 | Recruiting | Sponsor: Keymed Biosciences Co.Ltd | Not yet recruiting ➔ Recruiting

Enrollment open

Study of CM313 (SC) Injection in Patients With Primary Immune Thrombocytopenia (ITP) (clinicaltrials.gov) - P1/2 | N=36 | Not yet recruiting | Sponsor: Keymed Biosciences Co.Ltd

New P1/2 trial • Hematological Disorders • Immune Thrombocytopenic Purpura • Thrombocytopenia • Thrombocytopenic Purpura

Keymed Biosciences Announces Safety and Efficacy Results of CM313 for Primary Immune Thrombocytopenia Published in NEJM (PRNewswire) - P2 | N=20 | 2022-CM313-ITP (NCT05694767) | "Keymed Biosciences Inc. (HKEX: 02162) today announced that Lei Zhang/Renchi Yang's team from the Institute of Hematology, Chinese Academy of Medical Sciences has recently published a research paper entitled 'A Novel Anti-CD38 Monoclonal Antibody for Treating Immune Thrombocytopenia' in the New England Journal of Medicine...Results showed that 95.5% of patients (21/22) achieved a platelet count of ≥50 × 109/L during the 8-week treatment period, with a median cumulative response duration of 23 weeks (interquartile range, 17 to 24)...Throughout the entire study, overall response (complete or partial response) was observed in 21 patients, with 20 patients achieving complete response...Safety analyses showed that CM313 was well-tolerated."

P2 data • Hematological Disorders • Thrombocytopenia

Preclinical characterization of a novel investigational monoclonal antibody CM313 with potent CD38-positive cell killing activity. (PubMed, Front Immunol) - "In vivo, CM313 dose-dependently inhibited xenograft tumor growth, both as a monotherapy and in combination with dexamethasone or lenalidomide. Furthermore, CM313 was well tolerated with no drug-related clinical signs or off-target risks, as evidenced by 4-week repeat-dose toxicology studies in cynomolgus monkeys and B-hCD38 mice, with the later study showing no observed adverse effect level (NOAEL) of 300mg/kg once weekly. CM313 is a novel investigational humanized mAb with a distinct CDR sequence, showing comparable killing effects with daratumumab and stronger CDC activity than isatuximab, which supports its clinical development."

Journal • Preclinical • Hematological Disorders • Hematological Malignancies • Immunology • Inflammatory Arthritis • Lupus • Multiple Myeloma • Oncology • Systemic Lupus Erythematosus • Thrombocytopenia • Thrombocytopenic Purpura

Study of CM313 in Healthy Subjects (clinicaltrials.gov) - P1 | N=51 | Not yet recruiting | Sponsor: Keymed Biosciences Co.Ltd

New P1 trial

A Randomized, Double-blind, Placebo-controlled, and Multi-center Clinical Study of CM313 in the Treatment of Immune Thrombocytopenia (clinicaltrials.gov) - P2 | N=45 | Recruiting | Sponsor: Institute of Hematology & Blood Diseases Hospital, China

New P2 trial • Hematological Disorders • Thrombocytopenia • Thrombocytopenic Purpura

A Study of CM313 in Subjects With Relapsed or Refractory Multiple Myeloma (clinicaltrials.gov) - P1/2 | N=120 | Not yet recruiting | Sponsor: Keymed Biosciences Co.Ltd

New P1/2 trial • Hematological Malignancies • Multiple Myeloma • Oncology