ADC Therapeutics and Mitsubishi Tanabe Pharma Corporation have signed an exclusive license agreement for the development and commercialization of loncastuximab tesirine (ADCT-402; Zynlonta®; ADC Therapeutics), a CD19-directed antibody-drug conjugate (ADC). Underv the terms of the agreement, ADC Therapeutics will receive US $ 30 million upfront payment, up to US $ 205 million in milestones. and double-digit royalties based on net sales in Japan.
ADC Therapeutics will also receive royalties ranging in percentage from the high teens to the low twenties based on net sales of the product in Japan.
Mitsubishi Tanabe Pharma will conduct clinical studies of loncastuximab tesirine in Japan and will have the right to participate in any global clinical studies of the product by bearing a portion of the costs of the study.
Approval
Patients diagnosed with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who do not respond to or who have progressive disease after salvage therapies generally have a poor prognosis. In clinical trials loncastuximab tesirine demostrated encouraging results.[1]
Based on these results, the U.S. Food and Drug Administration (FDA) approved loncastuximab tesirine in April 2021 for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) after two or more lines of systemic therapy, including DLBCL not otherwise specified, DLBCL arising from low-grade lymphoma and also high-grade B-cell lymphoma.
“This license agreement with Mitsubishi Tanabe Pharma, a leader in the Japanese pharmaceutical industry, expands our global footprint in an important geography, and furthers our goal to make loncastuximab tesirine available globally to patients,” said Chris Martin, PhD, Chief Executive Officer of ADC Therapeutics.
“We are excited to bring together our expertise in ADCs with Mitsubishi Tanabe Pharma’s extensive experience in Japan where there is significant unmet need for a safe and effective therapy for patients with relapsed or refractory DLBCL.”
“Mitsubishi Tanabe Pharma is delighted to collaborate with ADC Therapeutics, a leader in the field of antibody drug conjugates, to develop and commercialize loncastuximab tesirine in Japan,” said Hiroaki Ueno, Ph.D, Chief Executive Officer of Mitsubishi Tanabe Pharma Corporation.
“We will try to improve the quality of life of patients suffering from cancer with the use of ADC Therapeutics’ novel anti-CD19 ADC, loncastuximab tesirine,” Ueno concluded
Meachnism of Action
Loncastuximab tesirine consists of a pyrrolobenzodiazepine (PBD) DNA-alkylating warhead covalently attached via a cleavable linker to an anti-CD19 antibody that binds to B cells.[2] Once bound to a CD19-expressing cell, loncastuximab tesirine is internalized by the cell, where enzymes release the PBD payload, that binds to DNA minor groove with little distortion, remaining less visible to DNA repair mechanisms. This ultimately results in cell cycle arrest and tumor cell death.
Highlights of Prescription Information
Loncastuximab tesirine (Zynlonta®; ADC Therapeutics) (Prescribing Information)
Reference
[1] Caimi PF, Ai W, Alderuccio JP, Ardeshna KM, Hamadani M, Hess B, Kahl BS, Radford J, Solh M, Stathis A, Zinzani PL, Havenith K, Feingold J, He S, Qin Y, Ungar D, Zhang X, Carlo-Stella C. Loncastuximab tesirine in relapsed or refractory diffuse large B-cell lymphoma (LOTIS-2): a multicentre, open-label, single-arm, phase 2 trial. Lancet Oncol. 2021 Jun;22(6):790-800. doi: 10.1016/S1470-2045(21)00139-X. Epub 2021 May 11. PMID: 33989558.
[2] Lee A. Loncastuximab Tesirine: First Approval. Drugs. 2021 Jul;81(10):1229-1233. doi: 10.1007/s40265-021-01550-w. PMID: 34143407.
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