CLN-617 / Cullinan Therap - LARVOL DELTA

Cullinan Therapeutics Provides Corporate Update and Reports Fourth Quarter and Full Year 2024 Financial Results (GlobeNewswire) - "CLN-049 (FLT3xCD3 T cell-engaging bispecific antibody): Enrollment continues in the ongoing Phase 1 study in patients with relapsed/refractory AML or MDS, and in the ongoing Phase 1 study in patients with measurable residual disease (MRD) in AML; CLN-617 (IL-2 and IL-12 cytokine fusion protein): Enrollment continues in the ongoing Phase 1 study in patients with advanced solid tumors."

Trial status • Acute Myelogenous Leukemia • Myelodysplastic Syndrome • Solid Tumor

Intratumoral injection and retention hold promise to improve cytokine therapies for cancer. (PubMed, Front Oncol) - "This in part reflects an inefficient biodistribution to tumors or a pleiotropic action on bystander cells and tissues. Here, we first review these issues and then argue for the intratumoral delivery of engineered cytokine fusion proteins that have been optimized for tumor retention as a potential solution to overcome these limitations and realize the potential of cytokines as highly effective therapeutics for cancer."

Journal • Oncology

CLN-617 retains IL-2 and IL-12 in injected tumors to drive robust and systemic immune-mediated antitumor activity. (PubMed, Cancer Immunol Res) - P1 | "However, the only approved human IL-2 therapy, Proleukin, is rarely used in the clinic due to systemic toxicities, and no IL-12 product has been approved to date due to severe dose-limiting toxicities. We found that IT administration of a murine surrogate of CLN-617, mCLN-617, eradicated established treated and untreated tumors in syngeneic models, significantly improved response to anti-PD1 checkpoint therapy, and generated a robust abscopal response dependent on cellular immunity and antigen cross-presentation. CLN-617 is being evaluated in a clinical trial in patients with advanced solid tumors (NCT06035744)."

Journal • Oncology • Solid Tumor • IL12A • IL2

Cullinan Oncology Provides Corporate Update and Reports Fourth Quarter and Full Year 2023 Financial Results (GlobeNewswire) - "CLN-418: Cullinan expects to provide a clinical data update from the ongoing Phase 1 dose escalation study in patients with advanced solid tumors in the second half of 2024; CLN-617: Enrollment continues in the ongoing Phase 1 study in patients with advanced solid tumors.:"

Enrollment status • P1 data • Oncology • Solid Tumor

Cullinan Oncology Announces First Patient Dosed in Phase 1 Trial Evaluating CLN-617, a Novel Fusion Protein Uniquely Harnessing Both IL-2 and IL-12 Cytokines (GlobeNewswire) - "Cullinan Oncology...announced that the first patient has been dosed with CLN-617 in a Phase 1 clinical trial. This is a first-in-human, multi-center, open label study designed to evaluate the safety, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary efficacy of CLN-617 alone and in combination with pembrolizumab, a programmed death receptor-1 (PD-1) targeted checkpoint inhibitor, in patients with advanced solid tumors."

Trial status • Melanoma • Squamous Cell Carcinoma of Head and Neck

Cullinan Oncology to Present Data Demonstrating Progress Across Its Broad Immunotherapy-Pipeline at SITC 2023 (GlobeNewswire) - "Additional presentations will highlight preclinical data for three other assets: our B7H4X4-1BB bispecific immune activator (CLN-418), our T cell-engaging, CD19-targeted bispecific antibody (CLN-978), and our collagen-binding IL-2/IL-12 fusion protein (CLN-617), as well as a Trials in Progress presentation for CLN-617.”"

Clinical data • Oncology • Solid Tumor

CLN-617 combines IL-2 and IL-12 in a single molecule to optimally balance safety and efficacy upon intratumoral injection (SITC 2023) - "Co-delivery of IL-2 and IL-12 in a single molecule optimally balanced safety and efficacy. CLN-617 is currently in Phase 1 dose escalation in patients with advanced solid tumors."

Clinical • Oncology • Solid Tumor • BATF3 • CD4 • CD8 • IFNG • IL12A • IL2 • LAIR1

A phase 1 study to assess safety, efficacy, pharmacokinetics, and pharmacodynamics of intratumoral CLN-617 (IL2/IL12 fusion protein) combined with pembrolizumab in patients with advanced solid tumors (SITC 2023) - "Secondary endpoints involve the assessment of pharmacokinetics, pharmacodynamics, and immunogenicity across the 3 parts of the trial. Patients’ enrollment is currently ongoing, and updates will be provided at the time of the presentation."

Clinical • Metastases • P1 data • PK/PD data • Head and Neck Cancer • Melanoma • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • IL12A • IL2

CLN-617 Alone and in Combination With Pembrolizumab in Patients With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=86 | Recruiting | Sponsor: Cullinan Oncology, LLC | Not yet recruiting ➔ Recruiting

Combination therapy • Enrollment open • Metastases • Head and Neck Cancer • Melanoma • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck

CLN-617 Alone and in Combination With Pembrolizumab in Patients With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=86 | Not yet recruiting | Sponsor: Cullinan Oncology, LLC

Combination therapy • Metastases • New P1 trial • Head and Neck Cancer • Melanoma • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck

Cullinan Oncology Provides Corporate Update and Reports Second Quarter 2023 Financial Results (GlobeNewswire) - "CLN-619: Cullinan intends to present initial data from the combination dose escalation arm of the study at a medical meeting in the future; CLN-418: Enrollment continued in the ongoing Phase 1 dose escalation study in patients with advanced solid tumors. Initial clinical data are expected in 2024; CLN-617: Cullinan received FDA clearance of its IND application for CLN-617 in March and anticipates initiating a Phase 1 clinical study in the second half of 2023."

P1 data • Trial initiation date • Oncology • Solid Tumor

Cullinan Oncology Announces U.S. FDA Clearance of Investigational New Drug Application for CLN-617, a Novel Fusion Protein Harnessing IL-2 and IL-12 Cytokines (GlobeNewswire) - "Cullinan Oncology, Inc...announced the U.S. Food and Drug Administration (FDA) has cleared its Investigational New Drug (IND) application for CLN-617, a fusion protein comprised of two potent and synergistic antitumor cytokines, IL-2 and IL-12, with a collagen binding domain designed for retention in the tumor microenvironment (TME) following intratumoral injection. Cullinan Oncology will initially evaluate CLN-617 in a Phase 1 trial in patients with advanced solid tumors....The first-in-human clinical study is a Phase 1, open-label, dose-escalation and dose-expansion study designed to evaluate the safety and efficacy of CLN-617 alone and in combination with pembrolizumab in patients with advanced solid tumors."

IND • Oncology • Solid Tumor

"$CGEM Cullinan Oncology Announces U.S. FDA Clearance of Investigational New Drug Application for CLN-617, a Novel Fusion Protein Harnessing IL-2 and IL-12 Cytokines https://t.co/xEQlXr5qbT" (@stock_titan)

FDA event • IND • Oncology • IL12A • IL2

Cullinan Oncology to Present New Preclinical Data for CLN-619 and CLN-617 at the 2023 American Association for Cancer Research Annual Meeting (GlobeNewswire) - "Cullinan Oncology...announced that posters of preclinical data highlighting the therapeutic potential of two assets, CLN-619 and CLN-617, will be presented at the 2023 American Association for Cancer Research (AACR) Annual Meeting taking place in Orlando, Florida, April 14-17, 2023."

Preclinical • Oncology

Cullinan Oncology Provides Corporate Update and Reports Fourth Quarter and Full Year 2022 Financial Results (GlobeNewswire) - "CLN-418....Enrollment is ongoing in a Phase 1 dose escalation study at U.S. and Australian sites in patients with advanced solid tumors with initial clinical data expected in 2024....Consistent with prior guidance, Cullinan received FDA clearance of its Investigational New Drug (IND) application for CLN-978 in January and anticipates initiating a Phase 1 clinical study by the end of 2023....Consistent with prior guidance, Cullinan recently filed the IND application for CLN-617 in February 2023 and intends to initiate a Phase 1 clinical study by the end of 2023, pending IND clearance."

IND • New P1 trial • P1 data • Oncology • Solid Tumor

CLN-617 is an intratumorally injected and locally retained fusion of IL-2 and IL-12 that drives systemic anti-tumor activity (SITC 2022) - "Although aldesleukin (recombinant IL-2 for high-dose infusion) has been approved for the treatment of melanoma and renal cell carcinoma, adoption has been hindered by frequent grade 3 and 4 severe adverse events. E) In a dual flank MC38 tumor model, one tumor was treated with mCLN-617 IT with or without systemic anti-PD1 administered intraperitoneally. For B-D, statistics were analyzed by t-test, *p<0.05 ****p<0.0001"

Genito-urinary Cancer • Melanoma • Oncology • Renal Cell Carcinoma • Solid Tumor • CD8 • IL12A • IL2 • STAT4 • STAT5

Cullinan Oncology Provides Corporate Update and Reports Third Quarter 2022 Financial Results (GlobeNewswire) - "Portfolio Highlights...CLN-617...Cullinan Oncology remains on track to file an Investigational New Drug (IND) application in the first half of 2023; CLN-978...Cullinan Oncology remains on track to file an IND application in the first half of 2023....R&D Expenses: Research and development (R&D) expenses were $19.7 million for the third quarter of 2022, compared to $26.4 million for the prior quarter....The decrease in R&D expenses was primarily related to a decrease in chemistry, manufacturing, and control activities for zipalertinib, CLN-619 and CLN-617 and the initiation of expense reimbursement for zipalertinib due to the collaboration agreement with Taiho Oncology, Inc. in the third quarter."

Commercial • IND • Oncology

CLN-617 is an IL-2/IL-12 fusion protein with a collagen-anchoring domain that induces potent systemic anti-tumor immunity upon intra-tumoral administration (AACR 2022) - "Our human lead candidate CLN-617 is produced at high titers in CHO cells and is currently in IND enabling studies.We have demonstrated that the use of collagen-binding domains for tumor retention enables safe and effective delivery of a combination of IL-2 and IL-12 in a single multifunctional molecule. The strong anti-tumor efficacy of mCLN-617 as a monotherapy and significant deepening of responses in combination with checkpoint blockade, together with a favorable tolerability profile, supports future clinical development of CLN-617."

Oncology • IL12A • IL2

Cullinan Oncology Provides Corporate Update and Reports Fourth Quarter and Full Year 2021 Financial Results (GlobeNewswire) - “Cullinan will provide a regulatory update on CLN-081 on March 28th, 2022….A more extensive preclinical characterization of CLN-049 has been published in the Journal for Immunotherapy of Cancer (JITC)…Initial clinical data are expected by mid-2023; The trial design includes parallel evaluation of CLN-619 as a monotherapy and in combination with checkpoint inhibitor therapy in separate modules. Initial clinical data are expected by mid-2023; [for CLN-617 and CLN-978] Cullinan expects to submit INDs for both programs by the end of the first half of 2023.”

EGFR exon 20 • IND • P1 data • Regulatory • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Cullinan Oncology to Present Data Demonstrating Breadth and Progress of Its Immuno-Oncology Portfolio at AACR 2022 (GlobeNewswire) - "Data for the following programs will be presented: (i) Preclinical characterization of CLN-049 and demonstration of its antitumor activity in AML models; (ii) Preclinical data evaluating the ability of CLN-619 to functionally restore the MICA/MICB-NKG2D axis...; (iii) Preclinical data demonstrating robust anti-tumor activity of CLN-617, locally in injected tumors and systemically in uninjected tumors; (iv) Preclinical characterization of CLN-978, a novel CD19/CD3-bispecific construct with extended serum half-life and high potency against target cells expressing very low levels of CD19; (v) Preclinical data assessing Opal, an earlier stage immuno-oncology program designed to simultaneously block the PD-1/PD-L1/2 axis and conditionally activate the 4-1BB/CD137 pathway on T cells."

Preclinical • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

Cullinan Oncology Provides Corporate Update and Reports Second Quarter 2021 Financial Results (GlobeNewswire) - “CLN-081…intends to provide a clinical and regulatory update in Q4 2021…Cullinan intends to initiate a first-in-human (FIH) trial of CLN-619 in 2H 2021…Cullinan intends to initiate a FIH trial of CLN-049 in 2H 2021…CLN-617, a fusion protein combining two potent antitumor cytokines, IL-2 and IL-12, in a single molecule with a collagen-binding tumor retention domain for the treatment of solid tumors. IND-enabling studies are planned to commence in the 2H 2021.”

New trial • Trial status • Acute Myelogenous Leukemia • Hematological Malignancies • Lung Cancer • Non Small Cell Lung Cancer • Oncology

Cullinan Oncology Reports Full Year 2020 Financial Results and Business Highlights (GlobeNewswire) - “Cullinan Amber’s lead program, CLN-617, is a fusion protein uniquely combining in a single agent two potent antitumor cytokines, IL-2 and IL-12, with a collagen-binding domain for the treatment of solid tumors…Cullinan expects to submit an IND for CLN-617 in 2022; Cullinan expects to submit an IND for CLN-978 in 2022.”

IND • Oncology • Solid Tumor