KT-413 / Kymera Therap - LARVOL DELTA

Safety, PK/PD, and Clinical Activity of KT-413 in Adult Patients with Relapsed or Refractory B-cell NHL (clinicaltrials.gov) - P1 | N=7 | Completed | Sponsor: Kymera Therapeutics, Inc. | Suspended ➔ Completed | N=80 ➔ 7

Enrollment change • Trial completion • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Indolent Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Discovery of KT-413, a Targeted Protein Degrader of IRAK4 and IMiD Substrates Targeting MYD88 Mutant Diffuse Large B-Cell Lymphoma. (PubMed, J Med Chem) - "KT-413 achieves concurrent degradation of these proteins by functioning as both a heterobifunctional degrader and a molecular glue. Based on the demonstrated activity and safety of KT-413 in preclinical studies, a phase 1 clinical trial in B-cell lymphomas, including MYD88 mutant ABC DLBCL, is currently underway."

Journal • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Targeted Protein Degradation • IKZF1 • IRAK4 • MYD88

Safety, PK/PD, and Clinical Activity of KT-413 in Adult Patients With Relapsed or Refractory B-cell NHL (clinicaltrials.gov) - P1 | N=80 | Suspended | Sponsor: Kymera Therapeutics, Inc.

Trial completion date • Trial primary completion date • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Indolent Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Safety, PK/PD, and Clinical Activity of KT-413 in Adult Patients With Relapsed or Refractory B-cell NHL (clinicaltrials.gov) - P1 | N=80 | Suspended | Sponsor: Kymera Therapeutics, Inc. | Recruiting ➔ Suspended

Trial suspension • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Indolent Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Novel agents in relapsed/refractory diffuse large B-cell lymphoma (ICML 2023) - "In recent years, numerous agents have been approved specifically for patients with DLBCL (RED) including tafasitamab, loncastuximab tesirine, polatuzumab vedotin, selinexor, rituximab, and pembrolizumab (for patients with Primary Mediastinal B-cell lymphoma)...Significant grade 3-4 toxicities were neutropenia and thrombocytopenia with 48.6% of patients requiring dose modifications, and 22.9% discontinuing treatment for toxicity.12 Ongoing and planned trials with loncastuximab include a phase III trial with rituximab, gemcitabine, and oxaliplatin (R-GemOx) (Tables 1 and 3)...Encouraging clinical activity, without unanticipated toxicities was observed when polatuzumab was combined with rituximab, ifosfamide, carboplatin, and etoposide (R-ICE) with an ORR of 89% (CR 61%).24 Combination of polatuzumab with lenalidomide and rituximab (R2) in 49 patients demonstrated an ORR of 35% (CR 29%), with median DOR, PFS, and OS of 8.1, 6.3, and 10.9 months, respectively...One notable..."

IO biomarker • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Marginal Zone Lymphoma • Mediastinal B Cell Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • BCL2 • BCL6 • CARD11 • CD79B • CDKN1A • CRBN • CTLA4 • EZH2 • IKZF1 • IRAK4 • LYN • MALT1 • MCT1 • MYC • MYD88 • NF-κβ • PD-L1 • ROR1 • SIRPA • SYK • XPO1

Kymera Therapeutics Announces Second Quarter 2023 Financial Results and Provides a Business Update (GlobeNewswire) - "Anticipated Upcoming Milestones...Kymera plans to share updates on its clinical-stage oncology programs later this year, including data evaluating anti-tumor activity in the target patient populations for KT-333 and KT-413 and initial safety and proof-of-mechanism data from the KT-253 Phase 1 clinical trial."

P1 data • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Cutaneous T-cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Leukemia • Lymphoma • Marginal Zone Lymphoma • Myelodysplastic Syndrome • Non-Hodgkin’s Lymphoma • Oncology • Peripheral T-cell Lymphoma • Solid Tumor • T Cell Non-Hodgkin Lymphoma

PHASE 1 TRIAL OF KT-413, A DEGRADER OF IRAK4 AND IMID SUBSTRATES, IN ADULT PATIENTS WITH RELAPSED OR REFRACTORY B-CELL NON-HODGKIN’S LYMPHOMAS (ICML 2023) - "Initial clinical data with KT-413 demonstrate degradation of IRAK4 and Ikaros/Aiolos in PBMC and tumor. It is anticipated that higher doses will achieve the predicted degradation profile in tumors that may confer clinical benefit in MYD88-mutant patients. Dose escalation is ongoing, and analyses from additional patients will be presented at the meeting."

Clinical • P1 data • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Lymphoplasmacytic Lymphoma • Marginal Zone Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Waldenstrom Macroglobulinemia • IKZF1 • IRAK4 • IRF4 • MYD88 • NF-κβ

Kymera Therapeutics Announces Updated Clinical Data from the Phase 1 Trials of STAT3 Degrader KT-333 and IRAKIMiD Degrader KT-413 (GlobeNewswire) - P1 | N=80 | NCT05233033 | Sponsor: Kymera Therapeutics, Inc. | "Kymera Therapeutics...announced new data demonstrating that its oncology programs...KT-413...in the online abstract book of the International Conference on Malignant Lymphoma (ICML)....As of the abstract cut-off date of February 3, 2023, 3 patients had been treated in the first 3 dose levels of the trial, including transformed activated B-cell-like (ABC)-diffuse large B-cell lymphoma (DLBCL), follicular lymphoma and marginal zone lymphoma, all of which were MYD88 wild-type: Plasma PK results were in line with the modeled predictions. Dose-dependent, sustained target knockdown in PBMC was observed, with up to 57% reduction in IRAK4 and 96-100% reduction in Ikaros and Aiolos by DL3. Degradation was also demonstrated in serial tumor biopsies obtained in DL1....Accrual into the study is ongoing, and analyses from additional patients will be shared in an update from Kymera in conjunction with the KT-333 ICML update."

P1 data • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Marginal Zone Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Kymera Therapeutics’ STAT3 Degrader KT-333 and IRAKIMiD Degrader KT-413 Demonstrate Desired Target Knockdown and Safety with Continued Dose Escalation in Ongoing Phase I Clinical Trials (GlobeNewswire) - P1 | N=80 | NCT05233033 | Sponsor: Kymera Therapeutics, Inc. | "Five patients were treated across DL1-4 and received a mean of 2.2 doses. These included patients with transformed activated B-cell-like (ABC)-diffuse large B-cell lymphoma (DLBCL), follicular lymphoma, marginal zone lymphoma, and plasmablastic lymphoma, all of whom were MYD88 wild-type except for one who had a MYD88 gain-of-function mutation. Data reported across the 4 DLs through the cut-off date show: Plasma exposure increased with dose, reaching levels close to those predicted to be efficacious. KT-413 achieved dose-dependent degradation of up to 70% IRAK4 and 96-100% Ikaros and Aiolos in PBMC after a single dose. Degradation profiles at DL3-4 were consistent with knockdown levels associated with profound antitumor activity in preclinical models of MYD88 mutant lymphomas. No DLTs or drug-related neutropenia were observed in the study."

P1 data • PK/PD data • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Kymera Therapeutics Announces First Quarter 2023 Financial Results and Provides a Business Update (GlobeNewswire) - "Anticipated Upcoming Milestones: Kymera will present preclinical data highlighting KT-253’s pharmacological profile at the European Hematology Association (EHA) Congress in June and plans to share initial safety and proof-of-mechanism data from the Phase 1 clinical trial later in 2023; The Company will provide clinical trial updates focused on PK/PD and safety on its KT-333 and KT-413 programs at the International Conference on Malignant Lymphoma (ICML) in June. Kymera, as previously announced, intends to present data evaluating anti-tumor activity in the target patient populations for KT-333 and KT-413 later this year."

P1 data • Preclinical • Trial status • Hematological Malignancies • Lymphoma • Oncology

Phase 1 Study of KT-413, a Targeted Protein Degrader of IRAK4 and IMiD Substrates, in Adult Patients with Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma (ASH 2022) - P1 | "Furthermore, based on new genetic classifications, co-mutations in MYD88 and CD79 (C5 and MCD subgroups) are associated with an inferior survival after standard R-CHOP. Enrollment in the Phase 1a portion of the KT413-DL-101 study is ongoing. NCT05233033."

Clinical • IO biomarker • P1 data • Bone Marrow Transplantation • CNS Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Targeted Protein Degradation • Transplantation • IKZF1 • IL1R1 • IRAK4 • IRF4 • MYD88

Kymera Therapeutics Announces Fourth Quarter and Full Year 2022 Financial Results and Provides a Business Update (GlobeNewswire) - "In January, the Company outlined its strategic objectives for 2023...Demonstrate clinical anti-tumor activity in target patient populations for KT-333 and KT-413; Initiate KT-253 Phase 1 trial in solid and hematological tumors and demonstrate clinical proof-of-mechanism in patients....Kymera plans to commence the KT-253 Phase 1a dose escalation study in early 2023, with IV doses of KT-253 administered every 3 weeks to patients with solid tumors and hematological malignancies, including AML."

New P1 trial • P1 data • Cutaneous T-cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Peripheral T-cell Lymphoma • Solid Tumor

Kymera Therapeutics Shares Key 2023 Goals to Support its Evolution into a Fully Integrated Degrader Medicines Company (GlobeNewswire) - "Key objectives include....Demonstrate KT-413 clinical anti-tumor activity in target patient populations; Demonstrate KT-333 clinical anti-tumor activity in target patient populations; Initiate KT-253 Phase 1 trial in solid and hematological tumors and demonstrate KT-253 clinical proof-of-mechanism in patients."

New P1 trial • P1 data • Cutaneous T-cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Non-Hodgkin’s Lymphoma • Oncology • Peripheral T-cell Lymphoma • Solid Tumor

Precision Targeting of MYD88 Mutant DLBCL Using the Novel Combination of Irakimids and BCL2 Inhibition (ASH 2022) - "Background: Based on new genetic classifications, co-mutations in MYD88 and CD79B (C5 and MCD subgroups) are associated with an inferior survival after standard R-CHOP. Preclinical studies highlight the potential of IRAKIMiDs as a therapeutic approach for the treatment of MYD88MT DLBCL. KTX-582 demonstrates preferential activity in MYD88MT ABC-DLBCL. Single agent venetoclax demonstrated varying potency in ABC-DLBCL cell lines, irrespective of MYD88 mutational status."

IO biomarker • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Oncology • BCL2 • CD79B • IKZF1 • IRAK4 • MYD88

Kymera Announces Positive Results from Phase 1 Clinical Trial Evaluating KT-474 in Patients with HS and AD and Sanofi’s Decision to Advance KT-474 into Phase 2 Clinical Trials (GlobeNewswire) - P1 | N=80 | NCT05233033 | Sponsor: Kymera Therapeutics, Inc. | "The Phase 1 clinical trial of KT-413 is designed to evaluate the safety, tolerability, PK/PD and clinical activity of KT-413 administered as an IV infusion once every 3 weeks to adult patients with relapsed and/or refractory B-cell non-Hodgkin's lymphomas....Plasma PK and PD also translated as expected in humans with DL1 and DL2 showing dose-dependent degradation of IRAK4, Ikaros and Aiolos in PBMC, with up to 95/100% knockdown of Ikaros/Aiolos and 40% knockdown of IRAK4 in DL2. Serial tumor biopsies at Cycle 3/Day 4 in the patient treated at DL1 showed comparable knockdown of Ikaros/Aiolos and IRAK4 as in plasma. There were no DLTs or treatment-related SAEs and no neutropenia observed in DL1 and DL2 patient cohorts. Phase 1a dose escalation is ongoing and DL3 (0.51 mg/kg) is currently enrolling....Kymera plans to share additional IRAKIMiD clinical data in 2023."

P1 data • PK/PD data • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Preclinical Data from Kymera Therapeutics’ Collaborations Demonstrate Therapeutic Potential of STAT3 Degraders in CTCL and IRAKIMiD Combination with BCL-2 Inhibitor in MYD88-Mutant DLBCL at the American Society of Hematology Annual Meeting (GlobeNewswire) - "Activity of STAT3 degrader in preclinical model of cutaneous T-cell lymphoma (CTCL) validates selective STAT3 degradation as a potential therapeutic strategy for STAT3-driven T cell malignancies; Preclinical study highlights the potential of IRAKIMiDs combined with BCL-2 inhibitor as a therapeutic approach for the treatment of MYD88-mutant diffuse large B-cell lymphoma (DLBCL)."

Preclinical • Cutaneous T-cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • T Cell Non-Hodgkin Lymphoma

Phase 1 study of KT-413, a targeted protein degrader, in adult patients with relapsed or refractory B-cell non-Hodgkin lymphoma. (ASCO 2022) - P1 | "In Phase 1b, up to 40 R/R DLBCL patients will be enrolled into one of two cohorts (n = 20): MYD88MT or MYD88WT to further characterize tolerability, PK, PD and evaluate the clinical activity of KT-413. KT413-DL-101 began enrollment in February 2022."

Clinical • IO biomarker • P1 data • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Targeted Protein Degradation • IKZF1 • IL1R1 • IRAK4 • IRF4 • MYD88

Kymera Therapeutics to Hold Investor Webcast on December 14 to Share Clinical Data from KT-474 Phase I Patient Cohort and Oncology Pipeline (GlobeNewswire) - "Oncology Clinical Update: Kymera is currently in the dose escalation stage for the ongoing Phase 1 trials of its STAT3 (KT-333) and IRAKIMiD (KT-413) degraders and expects to file an IND for its MDM2 Degrader (KT-253) before year end."

IND • Trial status • Cutaneous T-cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Peripheral T-cell Lymphoma • T Cell Non-Hodgkin Lymphoma

Discovery and characterization of potent degraders of IRAK4 and IMiD substrates for oncology indications (ACS-Fall 2022) - "These efforts culminated in the identification of KT-413, a heterobifunctional degrader currently being evaluated in Phase I clinical trials. A detailed description of the preclinical pharmacokinetic/pharmacodynamic/efficacy relationships associated with KT-413 will also be described."

Oncology • Targeted Protein Degradation • IKZF1 • IRAK4

Kymera Therapeutics Announces Second Quarter 2022 Financial Results and Provides a Business Update (GlobeNewswire) - "Patient enrollment and dosing are ongoing in a Phase 1 clinical trial of KT-333 evaluating the safety, tolerability, PK/PD and clinical activity of KT-333 in adult patients with relapsed and/or refractory lymphomas and solid tumors...Present KT-333 clinical patient data, including initial safety and proof-of-mechanism (4Q22); Patient enrollment and dosing are ongoing in a Phase 1 clinical trial of KT-413 evaluating the safety, tolerability, PK/PD and antitumor activity of KT-413 in patients with relapsed and/or refractory B-cell non-Hodgkin's lymphomas...Present KT-413 clinical patient data, including initial safety and proof-of-mechanism (4Q22); Kymera is completing IND enabling studies for KT-253 and expects to file an IND in 2H22...Present preclinical translational data to inform long-term clinical strategy (2H22)"

IND • P1 data • Preclinical • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor

Kymera Therapeutics Doses First Patients in Phase 1 Oncology Trials of STAT3 and IRAKIMiD Degraders KT-333 and KT-413 (PRNewswire) - "Kymera Therapeutics, Inc...has recently dosed the first patients in separate Phase 1 clinical trials evaluating the STAT3 degrader KT-333 and the IRAKIMiD degrader KT-413. The KT-333 trial includes patients with relapsed/refractory liquid and solid tumors, including T cell lymphomas and leukemia, and the KT-413 study is enrolling patients with relapsed/refractory B cell lymphomas, including MYD88-mutant diffuse large B cell lymphoma (DLBCL)....'The initiation of dosing in these studies represents important progress for Kymera toward understanding the pharmacology and safety of these first-in-class investigational medicines, and we look forward to sharing initial dose escalation clinical data later this year'."

P1 data • Trial status • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor

Safety, PK/PD, and Clinical Activity of KT-413 in Adult Patients With Relapsed or Refractory B-cell NHL (clinicaltrials.gov) - P1 | N=80 | Recruiting | Sponsor: Kymera Therapeutics, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Indolent Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Safety, PK/PD, and Clinical Activity of KT-413 in Adult Patients With Relapsed or Refractory B-cell NHL (clinicaltrials.gov) - P1 | N=80 | Not yet recruiting | Sponsor: Kymera Therapeutics, Inc.

New P1 trial • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Indolent Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Kymera Therapeutics Announces FDA Clearance of Investigational New Drug Application (IND) for IRAKIMiD Degrader, KT-413 (GlobeNewswire) - "Kymera Therapeutics...announced the clearance of its Investigational New Drug (IND) application from the U.S. Food and Drug Administration (FDA) for its IRAKIMiD degrader, KT-413....'We look forward to initiating our KT-413 Phase 1 study in patients with relapsed/refractory B cell lymphomas, including MYD88 mutant DLBCL'..."

IND • New P1 trial • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Kymera Therapeutics to Host Virtual R&D Day on December 16, 2021 (GlobeNewswire) - "The event will provide a comprehensive update on Kymera’s lead programs and discovery pipeline and platform, including....Updates on IRAKIMiD (KT-413) and STAT3 (KT-333) programs"

Clinical data • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Oncology • Solid Tumor