cemsidomide (CFT7455) / C4 Therap - LARVOL DELTA

Breakthroughs in treatment for hematological malignancies: latest updates on molecular glue, PROTACs and RNA degraders from ASH 2024. (PubMed, J Hematol Oncol) - "Currently, the main categories developed based on degraders include molecular glue (such as Cemsidomide, NX-5948), PROTACs (such as BGB-16673, AC-676, KT-333 ), and RNA degraders (such as SKY-1214). This correspondence summarizes the preclinical and clinical updates on degrader therapies presented at the ASH 2024 annual meeting."

Journal • Review • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Lymphoma • Multiple Myeloma • Non-Hodgkin’s Lymphoma • Oncology • Targeted Protein Degradation

C4 Therapeutics Reports Fourth Quarter and Full Year 2024 Financial Results and Recent Business Highlights (GlobeNewswire) - "KEY UPCOMING MILESTONES: Cemsidomide: Complete Phase 1 dose escalation and present data in MM and NHL in the second half of 2025; Open expansion cohort(s) in PTCL as part of the current Phase 1/2 trial in the second half of 2025; Enable initiation of the next phase of clinical development for MM and PTCL, with new studies expected to initiate in early 2026."

P1 data • Trial status • Multiple Myeloma • Non-Hodgkin’s Lymphoma • Peripheral T-cell Lymphoma

C4 Therapeutics Announces 2025 Milestones Across Clinical Portfolio of Degrader Medicines Pursuing Targets of High Unmet Need in Oncology (GlobeNewswire) - "Cemsidomide - Multiple Myeloma: Enable initiation of the next phase of clinical development to investigate cemsidomide in combination with dexamethasone in the late-line setting, and in combination with other MM agents for earlier lines of treatment. These new studies are expected to initiate in early 2026. Complete Phase 1 dose escalation and present data in the second half of 2025. Non-Hodgkin’s Lymphoma: Complete Phase 1 dose escalation and present data in the second half of 2025. Open expansion cohort(s) of the current Phase 1/2 trial in patients with peripheral T-cell lymphoma (PTCL) in the second half of 2025. Enable initiation of the next phase of clinical development to investigate cemsidomide monotherapy in later lines of therapy in PTCL. This new study is expected to initiate in early 2026."

New trial • P1 data • Trial status • Multiple Myeloma • Non-Hodgkin’s Lymphoma • Peripheral T-cell Lymphoma

Initial Results of a Phase 1 First-in-Human Study of Cemsidomide (CFT7455), a Novel MonoDACTM Degrader, with Dexamethasone in Patients with Relapsed/Refractory Multiple Myeloma (ASH 2024) - P1/2 | "Eligible MM pts must have received lenalidomide, pomalidomide, a proteasome inhibitor, and an anti-CD38 antibody. Dose escalation will continue until an MTD and/or the recommended phase 2 doses are identified. Updated data will be presented at the conference."

Clinical • P1 data • Anemia • Fatigue • Hematological Disorders • Hematological Malignancies • Infectious Disease • Lymphoma • Multiple Myeloma • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology • Thrombocytopenia • CRBN • IKZF1 • IKZF3

C4T has identified the…next steps in cemsidomide MM development (GlobeNewswire) - "Complete Phase 1 dose escalation trial in MM to establish go forward doses; Initiate initial combination trials; Engage regulatory authorities on registrational path."

Trial status • Multiple Myeloma

C4 Therapeutics Presents Cemsidomide Phase 1 Data at the American Society for Hematology (ASH) Annual Meeting that Demonstrated Potential to Become Best-in-Class IKZF1/3 Degrader (GlobeNewswire) - P1/2 | N=224 | NCT04756726 | Sponsor: C4 Therapeutics, Inc. | "Anti-lymphoma activity: Cemsidomide monotherapy demonstrated anti-lymphoma activity across a broad range of doses. As of the data cutoff, 21 patients were evaluable for efficacy, 16 of which had PTCL. Cemsidomide displays a differentiated pharmacokinetic profile with an approximate two-day half-life and an ability to induce rapid and potent degradation of IKZF1/3. Across all dose levels explored, cemsidomide achieved a 38 percent ORR and 19 percent CMR rate. In patients with PTCL, cemsidomide achieved a 44 percent ORR and 25 percent CMR rate."

P1 data • Non-Hodgkin’s Lymphoma

C4 Therapeutics Presents Cemsidomide Phase 1 Data at the American Society for Hematology (ASH) Annual Meeting that Demonstrated Potential to Become Best-in-Class IKZF1/3 Degrader (GlobeNewswire) - P1/2 | N=224 | NCT04756726 | Sponsor: C4 Therapeutics, Inc. | "Anti-myeloma activity: Cemsidomide in combination with dexamethasone demonstrated anti-myeloma activity across a broad range of doses, highlighting a wide therapeutic range. As of the data cutoff, 42 patients were evaluable for anti-myeloma activity. Across all dose levels, cemsidomide in combination with dexamethasone achieved a 26 percent ORR and a 40 percent clinical benefit rate (CBR). At the highest dose level explored to date (75 µg QD), cemsidomide achieved a 36 percent ORR and a 45 percent CBR. At the two highest dose levels evaluated to date (62.5 µg QD and 75 µg QD), 62 percent of patients remained on therapy as of the data cutoff date."

P1 data • Multiple Myeloma

Identification of Ikaros As Novel Interaction Partner of Cyclin D1/CDK4 in MCL (ASH 2024) - "Knockdown of Ikaros and treatment with the Ikaros degrader lenalidomide and also the novel degrader CFT7455 induced apoptosis, G1-phase arrest and decreased CycD1 expression, indicating a direct effect of Ikaros on CycD1 levels. Our results indicate that Ikaros can transcriptionally regulate and stabilize CycD1, and in turn, CycD1-CDK4 may phosphorylate Ikaros and affect Ikaros transcriptional activity. This feedback loop may play an important role in the pathogenesis of MCL and could serve as a novel potential therapeutic target in MCL."

Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CCND1 • CDK4 • IKZF1 • MYC

Initial Results of a Phase 1 First-in-Human Study of Cemsidomide (CFT7455), a Novel MonoDACTM Degrader, in Patients with Non-Hodgkin's Lymphoma (ASH 2024) - P1/2 | "Dose escalation will continue until an MTD and/or the recommended phase 2 doses are identified. Updated data will be presented at the conference."

Clinical • P1 data • Adult T-Cell Leukemia-Lymphoma • Anemia • B Cell Lymphoma • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Leukemia • Lymphoma • Multiple Myeloma • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology • Peripheral T-cell Lymphoma • T Cell Non-Hodgkin Lymphoma • CRBN • IKZF1 • IKZF3

Next-Generation Novel Therapies in Multiple Myeloma (ICBMT 2024) - "A wealth of therapeutic options have been approved for the treatment of newly diagnosed (ND) and relapsed/refractory (RR) multiple myeloma (MM) over the past two decades, with proteasome inhibitors (bortezomib, carfilzomib, ixazomib), immunomodulatory drugs (IMiDs; thalidomide, lenalidomide, pomalidomide), and monoclonal antibodies (mAbs; including the CD38 mAbs daratumumab and isatuximab, as well as the SLAMF7-targeting mAb elotuzumab) currently forming the backbone of treatment approaches in each setting. Additional targeted therapies have further enhanced the armamentarium, including, previously, the histone deacetylase inhibitor panobinostat, and, more recently, the nuclear export inhibitor selinexor 1 and the peptide–drug conjugate (PDC) melflufen. 2,3 Furthermore, novel immune-based treatment options such as the antibody–drug conjugate (ADC) belantamab mafodotin, the BCMA-targeting CAR T-cell therapies idecabta-gene vicleucel (ide-cel) and ciltacabtagene autoleucel..."

Hematological Malignancies • Multiple Myeloma • Oncology • Targeted Protein Degradation • CRBN • IRF4 • SLAMF7

C4 Therapeutics to Present Data from the Ongoing Phase 1/2 Trial of Cemsidomide in Multiple Myeloma and Non-Hodgkin’s Lymphoma at the American Society of Hematology (ASH) Annual Meeting (GlobeNewswire) - "C4 Therapeutics, Inc...today announced that two abstracts from the ongoing Phase 1/2 trial of cemsidomide have been accepted for presentation at the ASH Annual Meeting taking place from December 7 – 10, 2024 in San Diego, California. Non-Hodgkin’s lymphoma (NHL) data will be shared as an oral presentation and multiple myeloma (MM) data will be shared as a poster presentation."

P1/2 data • Hematological Malignancies • Multiple Myeloma • Non-Hodgkin’s Lymphoma • Oncology

C4 Therapeutics Reports Third Quarter 2024 Financial Results and Recent Business Highlights (GlobeNewswire) - "Cemsidomide: Present updated dose escalation and expansion cohort data from the 50 µg M/W/F, 37.5 µg QD, 62.5 µg QD, and 75 µg QD dose levels in approximately 40 patients from the ongoing Phase 1/2 clinical trial with dexamethasone in R/R MM at the ASH Annual Meeting in December 2024; Present dose escalation data from the 25 µg M/W/F, 50 µg M/W/F, 37.5 µg QD, 62.5 µg QD, and 100 µg QD dose levels in approximately 25 patients from the ongoing monotherapy Phase 1/2 clinical trial in R/R NHL at the ASH Annual Meeting in December 2024; Complete Phase 1 dose exploration in R/R MM and R/R NHL by year-end."

P1/2 data • Trial status • Hematological Malignancies • Multiple Myeloma • Non-Hodgkin’s Lymphoma • Oncology

Identification of Ikaros as a new interaction partner of Cyclin D1/CDK4 in MCL (DGHO 2024) - "Knockdown of Ikaros and treatment with the Ikaros degrader lenalidomide and also the novel degrader CFT7455 induced apoptosis, G1-phase arrest and decreased CycD1 expression, indicating a direct effect of Ikaros on CycD1 levels. Our results indicate that Ikaros can transcriptionally regulate and stabilize CycD1, and in turn, CycD1-CDK4 may phosphorylate Ikaros and affect Ikaros transcriptional activity. This feedback loop may play an important role in the pathogenesis of MCL and could serve as a novel potential therapeutic target in MCL."

Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CCND1 • CDK4 • IKZF1 • MYC

CFT7455-1101: Study to Assess the Safety and Tolerability of CFT7455 in Relapsed/Refractory Non-Hodgkin's Lymphoma or Multiple Myeloma (clinicaltrials.gov) - P1/2 | N=224 | Recruiting | Sponsor: C4 Therapeutics, Inc. | N=158 ➔ 224

Enrollment change • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Multiple Myeloma • Non-Hodgkin’s Lymphoma • Oncology • Peripheral T-cell Lymphoma • TNFRSF8

C4 Therapeutics Reports Second Quarter 2024 Financial Results and Recent Business Highlights (GlobeNewswire) - "KEY UPCOMING MILESTONES Cemsidomide: Present updated data from at least three dose levels from the dose escalation and expansion cohorts of the ongoing Phase 1/2 clinical trial in R/R MM in Q4 2024. Present data from at least four dose levels from the dose escalation portion of the ongoing Phase 1/2 clinical trial in R/R NHL in Q4 2024."

P1/2 data • Hematological Malignancies • Lymphoma • Multiple Myeloma • Non-Hodgkin’s Lymphoma • Oncology

C4 Therapeutics Reports Second Quarter 2024 Financial Results and Recent Business Highlights (GlobeNewswire) - "KEY UPCOMING MILESTONES: (i) Cemsidomide: Present updated data from at least three dose levels from the dose escalation and expansion cohorts of the ongoing Phase 1/2 clinical trial in R/R MM in Q4 2024; Present data from at least four dose levels from the dose escalation portion of the ongoing Phase 1/2 clinical trial in R/R NHL in Q4 2024; Complete Phase 1 dose exploration in R/R MM and R/R NHL by year-end 2024; (ii) CFT1946: Present data from at least five dose levels from the ongoing Phase 1 monotherapy dose escalation trial in BRAF V600X solid tumors as a mini oral presentation on Saturday, September 14, 2024 from 2:45 – 2:50 CEST at the ESMO Congress 2024 in Barcelona, Spain."

P1 data • P1/2 data • Trial status • Multiple Myeloma • Non-Hodgkin’s Lymphoma • Solid Tumor

Study to Assess the Safety and Tolerability of CFT7455 in Relapsed/Refractory Non-Hodgkin's Lymphoma or Multiple Myeloma (clinicaltrials.gov) - P1/2 | N=158 | Recruiting | Sponsor: C4 Therapeutics, Inc. | Trial completion date: Dec 2024 ➔ Dec 2025 | Trial primary completion date: Sep 2024 ➔ Sep 2025

Trial completion date • Trial primary completion date • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Multiple Myeloma • Non-Hodgkin’s Lymphoma • Oncology • Peripheral T-cell Lymphoma • TNFRSF8

C4 Therapeutics Reports Fourth Quarter and Full Year 2023 Financial Results and Recent Business Highlights (GlobeNewswire) - "FOURTH QUARTER 2023 AND RECENT ACHIEVEMENTS - CFT7455:...Advanced the Phase 1/2 Clinical Trials. The dose escalation portion of the Phase 1/2 trials evaluating CFT7455 in combination with dexamethasone for R/R MM and as a monotherapy for R/R NHL continues to progress. As of February 2024, two dose levels are open for enrollment in the Phase 1/2 trial for R/R MM and one dose level open for enrollment in the Phase 1/2 trial for R/R NHL."

Trial status • Multiple Myeloma • Non-Hodgkin’s Lymphoma

C4 Therapeutics Announces 2024 Priorities and Extended Cash Runway to Advance Portfolio of Targeted Protein Degradation Medicines (GlobeNewswire) - "The company announced the following key milestones for 2024: CFT7455: (i) Present updated data from the ongoing Phase 1 dose escalation trial in relapsed/refractory multiple myeloma (R/R MM) in 2H 2024; (ii) Present data from the ongoing Phase 1 dose escalation trial in relapsed/refractory non-Hodgkin’s lymphomas (R/R NHL) in 2H 2024; (iii) Complete Phase 1 dose exploration in R/R MM and NHL by year-end 2024."

P1 data • Trial status • Multiple Myeloma • Non-Hodgkin’s Lymphoma

C4 Therapeutics Announces Positive Data from CFT7455 Phase 1 Trial in Relapsed/Refractory Multiple Myeloma (GlobeNewswire) - P1/2 | N=158 | NCT04756726 | Sponsor: C4 Therapeutics, Inc. | "CFT7455 in Combination with Dexamethasone for R/R MM Patients: As of the November 28, 2023 data cutoff date, nine patients had received CFT7455 in combination with dexamethasone across two initial dose escalation cohorts (50 µg MWF for 14 days on/14 days off; or 37.5 µg daily for 14 days on/14 days off)....All three patients evaluable for efficacy at 37.5 μg daily achieved SD or better according to IMWG criteria. These assessments include: (i) One patient achieved a Stringent Complete Response (sCR), after initially achieving a Very Good Partial Response (VGPR). This patient was refractory to BCMA therapies; (ii) One patient achieved a PR. This patient was refractory to BCMA therapies; (iii) One patient achieved SD."

P1 data • Multiple Myeloma

C4 Therapeutics Announces Positive Data from CFT7455 Phase 1 Trial in Relapsed/Refractory Multiple Myeloma (GlobeNewswire) - P1/2 | N=158 | NCT04756726 | Sponsor: C4 Therapeutics, Inc. | "CFT7455 as a Monotherapy for R/R MM Patients: Monotherapy dose escalation is complete. As of the November 28, 2023 data cutoff date, 22 patients had received CFT7455 as a monotherapy.....Four patients received the maximum dose administered of 75 µg daily. Three patients were refractory to BCMA therapies. Responses were measured in accordance with the International Myeloma Working Group (IMWG) criteria for multiple myeloma. All four patients achieved Stable Disease (SD) or better and one patient achieved a Partial Response (PR)....T-cell activation was observed at well tolerated monotherapy doses, supporting the potential use of CFT7455 in combination with bi-specific T-cell engagers and monoclonal antibody therapies."

P1 data • Multiple Myeloma

C4 Therapeutics Announces Positive Data from CFT7455 Phase 1 Trial in Relapsed/Refractory Multiple Myeloma (GlobeNewswire) - "C4T expects to present the following data on CFT7455 in 2024: (i) Complete Phase 1 dose escalation data from the ongoing Phase 1/2 clinical trial in R/R MM; (ii) Complete Phase 1 dose escalation data from the ongoing Phase 1/2 clinical trial in NHL."

P1 data • Multiple Myeloma • Non-Hodgkin’s Lymphoma

C4 Therapeutics to Host Webcast to Present New Dose Escalation Data from CFT7455 Phase 1 Study in Relapsed/Refractory Multiple Myeloma (GlobeNewswire) - "C4 Therapeutics, Inc...announced that it will host a webcast on Tuesday, December 12, 2023 at 4:30 PM ET to present new Phase 1 dose escalation data for relapsed refractory multiple myeloma from the ongoing Phase 1/2 clinical trial of CFT7455, a MonoDAC™ degrader of IKZF1/3, for the potential treatment of relapsed/refractory multiple myeloma and relapsed/refractory non-Hodgkin’s lymphoma."

P1 data • Hematological Malignancies • Multiple Myeloma • Oncology

C4 Therapeutics Reports Third Quarter 2023 Financial Results and Recent Business Highlights (GlobeNewswire) - "Clinical Trial Application (CTA) Accepted for Review by China National Medical Products Administration (NMPA). Betta Pharmaceuticals announced that their CTA submission for CFT8919 has been accepted for review by China NMPA....CFT7455: Present data from the Phase 1 dose escalation portion of the ongoing Phase 1/2 clinical trial focusing on CFT7455 as a monotherapy in R/R MM on December 12 at 4:30 PM ET at a virtual company-sponsored event."

New trial • P1 data • Hematological Malignancies • Multiple Myeloma • Oncology

C4 Therapeutics Announces Upcoming Data Presentations for CFT8634, an Orally Bioavailable BiDAC Degrader in Development for Synovial Sarcoma and SMARCB1-Null Tumors, and CFT7455, an Orally Bioavailable MonoDAC Degrader in Development for Multiple Myeloma and Non-Hodgkin’s Lymphoma (GlobeNewswire) - "C4 Therapeutics, Inc...announced plans to share data from the Phase 1 dose escalation portions of the ongoing Phase 1/2 trials of CFT7455 and CFT8634. The CFT8634 Phase 1 dose escalation data has been accepted as a poster presentation at the Connective Tissue Oncology Society (CTOS) Annual Meeting taking place from November 1 – 4, 2023 in Dublin, Ireland."

P1 data • Hematological Malignancies • Lymphoma • Multiple Myeloma • Non-Hodgkin’s Lymphoma • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • Synovial Sarcoma