Lonza 2024

Swiss-based ADC Therapeutics, an oncology-drug development company specializes in the development of antibody drug conjugates (ADCs), and Freenome, a biotech company pioneering the a multiomics platform for early cancer detection through a routine blood draw, have entered a biomarker development collaboration in which ADC Therapeutics will use Freenome’s platform to identify patients who are most likely to respond to treatment with loncastuximab tesirine, also known as ADCT-402.

Loncastuximab tesirine is comprised of a humanized monoclonal antibody that binds to human CD19, conjugated through a linker to a pyrrolobenzodiazepine (PBD) dimer toxin. Once bound to a CD19-expressing cell, loncastuximab tesirine is internalized into the cell where enzymes release the PBD-based payload. CD19 is a clinically validated target for the treatment of B-cell malignancies. The PBD-based warhead has the ability to form highly cytotoxic DNA interstrand cross-links, blocking cell division and resulting in cell death.

Ongoing research
Loncastuximab tesirine is currently investigated in a pivotal Phase II clinical trial in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL)*, a Phase Ib clinical trial in combination with ibrutinib in patients with R/R DLBCL or mantle cell lymphoma (MCL) and a Phase Ib clinical trial in combination with durvalumab in patients with R/R DLBCL, MCL or follicular lymphoma. The U.S. Food and Drug Administration granted orphan drug designation to ADCT-402 for the treatment of relapsed or refractory DLBCL and MCL.

Platform technology
Freenome’s platform characterizes tumor heterogeneity and systemic immune response to identify signatures from blood of DLBCL patients participating in ADC Therapeutics’ pivotal Phase II clinical trial. The multiomics approach will allow ADC Therapeutics to consider a broad range of DNA, RNA and protein markers in developing a biomarker signature.

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The technology integrates assays for cell-free DNA, methylation, and proteins with advanced computational biology and machine learning techniques to identify additive signatures that improve the accuracy for early cancer detection given the molecular subtypes of cancer are heterogeneous in nature. This strategy incorporates a multidimensional view of both tumor- and immune-derived signatures that enables the early detection of cancer, instead of relying only on tumor-derived markers, which may miss the early signs of cancer

“[The] partnership with ADC Therapeutics validates our unique multiomics platform and its potential to help biopharmaceutical companies develop innovative cancer therapies for patients in need,” said Gabe Otte, Chief Executive Officer of Freenome.

“Our platform can help biopharma partners refine biomarker development and potentially de-risk and accelerate drug development by characterizing patients likely to respond to therapy. In addition, given that ADCT-402 is targeting a hematological malignancy, this partnership highlights the potential of our platform to provide tumor and immune signatures for hematological cancers in addition to solid tumors. Combined with the ongoing development of our early cancer screening test, we are moving closer to our goal of helping physicians and patients navigate precision health by identifying cancer at its earliest stages when treatments can be most effective,” added Otte.

“We are excited to leverage Freenome’s unique platform to potentially enhance our identification and understanding of the patients who are most likely to benefit from treatment with ADCT-402, which has been demonstrating significant single-agent clinical activity in a broad population of patients with relapsed or refractory diffuse large B-cell lymphoma in our pivotal Phase II clinical trial,” noted Patrick van Berkel, Senior Vice President of Research and Development at ADC Therapeutics.

“This partnership adds to our ongoing biomarker research efforts, which we believe will be advantageous as we continue to advance the clinical development of ADCT-402,” Van Berkel concluded.

Clinical trials*
Study to Evaluate the Efficacy and Safety of Loncastuximab Tesirine in Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma – NCT03589469
Safety and Antitumor Activity Study of Loncastuximab Tesirine + Ibrutinib in Diffuse Large B-Cell or Mantle Cell Lymphoma – NCT03684694
Safety and Antitumor Activity Study of Loncastuximab Tesirine and Durvalumab in Diffuse Large B-Cell, Mantle Cell, or Follicular Lymphoma – NCT03685344

The companies did not disclosed financial terms of the collaboration.

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