DT-7012 / Domain Therap - LARVOL DELTA

Study of DT-7012 as a Single Agent and in Combination With an Immune Checkpoint Inhibitor in Participants With Advanced Solid Tumors (clinicaltrials.gov) - P1/2 | N=125 | Recruiting | Sponsor: Domain Therapeutics Australia Pty Ltd | N=60 ➔ 125

Checkpoint inhibition • Enrollment change • Monotherapy • Oncology • Solid Tumor

Domain Therapeutics Doses First Patients in Phase I/II Trial of DT-7012 Targeting CCR8 in Solid Tumors (PRNewswire) - "The DOMISOL study is an open-label, multicenter Phase I/II, first-in-human dose-escalation and cohort-expansion trial evaluating the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary anti-tumor activity of DT-7012 in adult patients with selected advanced solid tumors. The trial is being conducted in Australia, with initial clinical sites including Peninsula and Southeast Oncology (PASO) and Cabrini Health in Melbourne. Additional centers are expected to come online in the coming months."

Trial status • Solid Tumor

CITY: A Phase 1, Multicenter, Open-label, Prospective, First-in-human Dose-escalation Clinical Trial of Domain Therapeutics' Anti-CCR8 Monoclonal Antibody (DT-7012) in Patients With Relapsed or Refractory Cutaneous T-cell Lymphomas (CTCL) (clinicaltrials.gov) - P1 | N=30 | Not yet recruiting | Sponsor: Assistance Publique - Hôpitaux de Paris

First-in-human • New P1 trial • Cutaneous T-cell Lymphoma • Dermatology • Hematological Malignancies • Lymphoma • Mycosis Fungoides • Non-Hodgkin’s Lymphoma • Oncology • Peripheral T-cell Lymphoma • Sezary Syndrome • T Cell Non-Hodgkin Lymphoma

Study of DT-7012 as a Single Agent and in Combination With an Immune Checkpoint Inhibitor in Participants With Advanced Solid Tumors (clinicaltrials.gov) - P1/2 | N=60 | Recruiting | Sponsor: Domain Therapeutics Australia Pty Ltd | Not yet recruiting ➔ Recruiting

Checkpoint inhibition • Enrollment open • Monotherapy • Oncology • Solid Tumor

Domain Therapeutics Presents Novel Data Addressing Key Challenges in Oncology at AACR 2025 (PRNewswire) - ""Domain Therapeutics...today announces new clinical and preclinical data for its key oncology programs... DT-7012....details preclinical and benchmark data highlighting the sophisticated profile of DT-7012, a Treg depleting anti-CCR8 monoclonal antibody. The study highlighted that DT-7012: Demonstrates a broad pattern of CCR8 binding, high affinity to CCR8, and potent effector functions, enabling effective targeting and selective depletion of CCR8+ Tregs in patient samples. Maintains functional efficacy, preserving antagonistic activities (ADCC/ADCP) even under high concentrations of the CCR8 ligand CCL1 and effectively blocking CCL1-induced receptor internalization....These preclinical findings support the advancement of DT-7012 into Phase I/II trials, anticipated to start in 2025."

Preclinical • Trial status • Solid Tumor

Comprehensive characterization of DT-7012, a differentiated CCR8-depleting antibody for the treatment of solid tumors (AACR 2025) - "DT-7012 exhibits high-affinity binding to CCR8, potent Fc-mediated effector functions, and selective depletion of CCR8+ Tregs in NSCLC patient samples as well as a good safety profile. These findings highlight the therapeutic potential of DT-7012 as a novel strategy to enhance anti-tumor immunity and support its upcoming clinical development."

Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CCR8

Study of DT-7012 As a Single Agent and in Combination with an Immune Checkpoint Inhibitor in Participants with Advanced Solid Tumors (clinicaltrials.gov) - P1/2 | N=60 | Not yet recruiting | Sponsor: Domain Therapeutics SA

New P1/2 trial • Oncology • Solid Tumor

Characterization of DT-7012, a highly differentiated anti-CCR8 mAb clinical candidate (SITC 2024) - "The binding and killing activity of DT-7012 was specific to CCR8 and CCR8+ cells, without affecting the other immune cell populations, suggesting a good safety profile of the Domain's candidate. Conclusions These data demonstrate major competitive advantages over the competitive anti-CCR8 mAbs currently in clinical development making DT-7012 a potential novel best-in-class anti-CCR8 mAb candidate."

Clinical • Lung Cancer • Oncology • Solid Tumor • CCR8

Domain Therapeutics Strengthens Its Intellectual Property for Its Series of Treg Depleting anti-CCR8 Antibodies, Including Best-in-class Candidate DT-7012 (Businesswire) - "Domain Therapeutics...announces the publication of three international PCT patent applications....These patents will significantly strengthen the Company’s intellectual property protection for its series of tumor-infiltrating regulatory T cells (Tregs) depleting antibody-dependent cell-mediated cytotoxicity/ phagocytosis (ADCC/ADCP) anti-CCR8 antibodies, including DT-7012, a novel drug candidate with best-in-class potential compared to other clinical-stage CCR8 antibodies."

Patent • Cutaneous T-cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor • T Cell Non-Hodgkin Lymphoma

Domain Therapeutics and Chime Biologics announce manufacturing agreement to advance novel anti-CCR8 antibody for cancer immunotherapy (PRNewswire) - "Domain Therapeutics...and Chime Biologics...announce the signing of a manufacturing service agreement for the production of Domain's best-in-class Treg depleting anti-CCR8 antibody candidate, DT-7012....Under the terms of the agreement, Chime Biologics will ensure stable cell line development (CLD) and DT-7012 candidate manufacturing to support clinical trials in strategic countries....Phase I clinical studies of DT-7012 are expected to start in early 2025 for solid tumors and mid-2025 for cutaneous T-cell lymphoma (CTCL)."

Licensing / partnership • New P1 trial • Cutaneous T-cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor • T Cell Non-Hodgkin Lymphoma

Domain Therapeutics Awarded Hospital-University Research in Health (RHU) SPRINT Consortium Grant to Progress Its Proprietary CCR8 Antibody Candidate to the Clinic (Businesswire) - "Domain Therapeutics...today announces it has been awarded a grant as part of the Hospital-University Research in Health (RHU) SPRINT consortium. The €30 million consortium project will be supported by a nearly €10 million grant from the Agence Nationale de la Recherche (ANR) as part of the France2030 investment plan, shared between the academic and private partners to progress precision medicines, including moving Domain’s DT-7012 to the clinic...The SPRINT project aims to revolutionize the management of patients with CTCL and deliver a new cure paradigm as a standard-of-care....Domain’s target is a highly strategic approach to derive efficient novel immunotherapies that increase the clinical success rate of treatments in non-responding patients with cancer, and the Company expects to start a Phase I study of DT-7012 by mid-2025."

Financing • New P1 trial • Cutaneous T-cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor • T Cell Non-Hodgkin Lymphoma

Domain Therapeutics announces nomination of best-in-class CCR8 antibody candidate, DT-7012, further strengthening its unique portfolio of GPCR-targeting immunotherapies (GlobeNewswire) - "Domain Therapeutics...today announces the nomination of a novel drug candidate, DT-7012, an anti-CCR8 monoclonal antibody depleting tumor-infiltrating regulatory T cells (Tregs), with best-in-class potential and an initial positioning that will enable fast-track development and accelerated market access.... Domain has discovered a unique collection of anti-hCCR8 antibodies and nominated DT-7012 as a differentiated best-in-class Treg-depleting CCR8 antibody candidate. Unlike most competitors, DT-7012 is able to i) preserve CCR8-modulation capacity in presence of high concentrations of CCR8 in the tumor microenvironment and to ii) recognize different forms of CCR8 having different post-translational modifications. With cell line generation currently ongoing, the Company expects to start a Phase I study of DT-7012 by mid-2025."

New P1 trial • Pipeline update • Preclinical • Oncology

Beyond CCR8: key epitopes targeting dynamic CCR8 conformational states and a diversity of monoclonal antibodies to modulate the tumor microenvironment for the treatment of cancers (SITC 2022) - "In parallel, treatment of tumor-bearing mice with cell-depleting anti-CCR8 antibody indeed eradicated established tumors with induction of potent tumor-specific effector/memory T cells...Up to date, targeting selective CCR8 epitopes mimicking dynamic conformational CCR8 stage according to CCR8 positive cell subset or activation cellular state will be a key issue and differentiate therapeutic approach for the TME modulation in the treatment of cancer. Moreover, the use of depleting anti-CCR8 mAb with enhanced cytotoxic activity (i.e., ADCC, CDC, ADCP) can also reduce the number of CCR8 immune suppressive cells in a tumor."

Biomarker • IO biomarker • Tumor microenvironment • Oncology • ARRB1 • CCR8

Domain Therapeutics presents new data on its EP4R and CCR8 antagonists at 2022 SITC Annual Meeting (GlobeNewswire) - "Domain Therapeutics presents new data on its EP4R and CCR8 antagonists at 2022 SITC Annual Meeting....The preclinical data being presented on Domain’s immuno-oncology candidate, DT-9081, shows that the drug candidate was able to demonstrate strong anti-tumor effects in two cancer models with notable synergies with immune checkpoint inhibitors to induce long lasting complete responses.....Domain is also presenting preclinical proof-of-principle data on its CCR8 depleting-antibody program, which represents an attractive target from which to derive novel immunotherapies. Data from the studies shows that treatment with a depleting anti-mCCR8 antibody in monotherapy was able to translate into robust anti-tumor activity in multiple models, with induction of a potent and long-lasting tumor-specific memory effect."

Preclinical • Oncology • Solid Tumor

Domain Therapeutics to present new data on its EP4R and CCR8 antagonists at 2022 SITC Annual Meeting (GlobeNewswire) - "Domain Therapeutics...will present data on its proprietary GPCR programs at the Society for Immunotherapy of Cancer (STIC) Annual Meeting, taking place on 8-12 November 2022 in Boston, US. Domain will present two posters on its oral small molecule EP4R antagonist, DT-9081. The first poster will highlight preclinical data illustrating the synergy of DT-9081 in combination with immune checkpoint inhibitors in different cancer models. The second poster will focus on the clinical trial design for the upcoming Phase I clinical study, which is expected to start before the end of the year....Domain will also present a poster on its CCR8 depleting-antibody program illustrating key differentiating properties of its patent-protected proprietary series of antibodies targeting CCR8."

Clinical protocol • New P1 trial • Preclinical • Oncology • Solid Tumor