Diffuse large B-cell lymphoma
Credit: CoRus13 via Wikimedia Commons

Freenome’s multiomics platform, designed to improve early cancer detection from a routine blood draw, will be used by ADC Therapeutics to develop biomarkers for ADC’s pivotal-phase lymphoma drug candidate ADCT-402 (loncastuximab tesirine), through a collaboration whose value was not disclosed.

The Freenome platform is designed to identify tumor- and immune-derived signatures rather than just tumor-derived markers, which the company reasons may miss the early signs of cancer. The platform integrates assays for cell-free DNA, methylation, and proteins with advanced computational biology and machine learning techniques—a multiomics approach that according to ADC Therapeutics will allow it to consider a variety of DNA, RNA and protein markers in developing a biomarker signature.

ADC Therapeutics plans to use Freenome’s platform to identify patients deemed most likely to respond to treatment with ADCT-402, an antibody drug conjugate (ADC) consisting 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, ADCT-402 is internalized into the cell where enzymes release the PBD-based warhead. ADC Therapeutics says CD19 is an ideal target for an ADC approach, since it is highly expressed in a range of B-cell hematological tumors, including certain types of lymphoma and leukemia, while its expression in healthy tissue is restricted.

The FDA has granted its orphan drug designation to ADCT-402 for the treatment of diffuse large B-cell lymphoma (DLBCL) and mantle cell lymphoma (MCL).

ADC is evaluating ADCT-402 in a pivotal Phase II trial (NCT03589469) in patients with relapsed or refractory (R/R) DLBCL. The study is estimated to enroll 140 patients, with an estimated primary completion date of February 22, 2020.

Funding an eventual Biologics License Application (BLA) for ADCT-402 was among the priorities identified by ADC Therapeutics when it announced the final close of a $103 million financing expansion that brought the total gross proceeds of the Series E round to $303 million. The financing catapulted ADC to No. 2 on Clinical OMICs sister publication GEN’s A-List of Top 10 Young Companies in the Money, January–July 2019.

ADCT-402 is also being evaluated in two Phase I trials. One trial is assessing the drug candidate in combination with the Pharmacyclics (AbbVie)/Janssen Biotech (Johnson & Johnson) co-marketed drug Imbruvica® (ibrutinib) in patients with R/R DLBCL or MCL (NCT03684694). The other trial is studying ADCT-402 in combination with AstraZeneca’s marketed anticancer treatment Imfinzi® (durvalumab) in patients with R/R DLBCL, MCL or follicular lymphoma (NCT03685344).

“Our partnership with ADC Therapeutics validates our unique multiomics platform and its potential to help biopharmaceutical companies develop innovative cancer therapies for patients in need,” Freenome CEO Gabe Otte said in a statement. “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.

Otte added that the collaboration also highlights the potential of Freenome’s platform to provide tumor and immune signatures for blood cancers in addition to solid tumors.

Added 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.”

“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,” van Berkel added.

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