Swedish firm Alligator Bioscience and Seattle-based Aptevo Therapeutics have agreed to co-develop ALG.APV-527, a bispecific antibody for tumor-directed immunotherapy, which is based on Alligator’s first-generation bispecific antibody ATOR-1016. The new candidate targets both 4-1BB, a tumor necrosis factor receptor (TNFR) family co-stimulatory receptor on activated T cells, and an undisclosed tumor antigen that the firms say is overexpressed in multiple different tumor types. ALG.APV-527 has been developed under a prior material transfer agreement between the companies, using Aptevo’s Adaptir® protein therapeutics technology platform and Alligator’s Alligator-Gold® antibody library. 

“Our collaboration with Alligator Bioscience has unlocked tremendous synergies, enabling us to capitalize on our companies' respective expertise in therapeutic antibody engineering,” said Marvin L. White, president and CEO of Aptevo. “The addition of a 4-1BB bispecific candidate expands and diversifies Aptevo's portfolio while demonstrating the flexibility of our Adaptir platform in addressing novel mechanisms of action, in addition to redirected T-cell cytotoxicity.”

Under the terms of the agreement, Alligator and Aptevo will jointly own and equally shoulder the costs of developing ALG.APV-527 through to the end of Phase II clinical development. The partners may then decide to either out-license the candidate or continue further development separately or in partnership. The deal includes an option for the firms to develop a second bispecific antibody candidate based on the same novel mechanism of action, which would also be jointly owned and funded by Aptevo and Alligator.

The co-stimulatory receptor 4-1BB plays a key role in modulating and augmenting the immune response to cancer by promoting the activation, expansion, and enhanced effector function of tumor-specific T cells, Alligator and Aptevo explain. The firms believe that an immunotherapeutic that targets 4-1BB could have potential utility against a broad range of tumor types, including breast, cervical, non-small-cell lung, prostate, renal, gastric, colorectal, and bladder.

“Our technology platform enables the generation of highly functional antibodies with optimal stability and manufacturing properties, merged into an exceptional bispecific antibody using Aptevo's Adaptir platform, added Per Norlén, M.D., Ph.D., CEO at Alligator Bioscience.  “With five immuno-oncology programs currently in development, each with first- or best-in-class potential, this partnership with Aptevo allows us to further build on the promise of bispecific therapeutics for tumor-directed immunotherapy.”

Aptevo was spun out of Emergent BioSolutions in 2016 to exploit the modular Adaptir platform for developing immune-oncology candidates, including antibody-sized, multispecific molecules that can bind up to four targets. The firm says Adaptir candidates can be designed to offer different mechanisms of action, including redirected T-cell-mediated cytotoxicity, signal blockade of multiple receptors, and the delivery of engineered cytokines to immune system components. Aptevo’s clinical pipeline is headed by otlertuzumab (previously TRU-016; anti-CD37), a humanized monospecific Adaptir molecule, which is in Phase II development as combination therapy for chronic lymphocytic leukemia (CLL) and in Phase I/Ib clinical studies for treating subtypes of non-Hodgkin’s lymphoma (NHL). The firm’s Phase I-stage candidate MOR209/ES414 is a humanized bispecific Adaptir molecule designed to bind to prostate-specific membrane antigen (PSMA) and CD3 in prostate cancer. MOR209/ES414 is being co-developed with MorphoSys.

Alligator is exploiting its Alligator-Gold and Find® technology platforms to develop tumor-directed immunotherapies, including mono- and bispecific antibodies. Last month, the firm reported moving its 4-1BB antibody candidate ATOR-1017 into preclinical development.

In March, Alligator reported completing a Phase I dose-escalation study evaluating intratumoral and intravenous administration of ADC-1013 in patients with 10 different tumor types. ADC-1013 is a human, monospecific agonistic immunoglobulin G1 (IgG1) antibody, which is designed to target the co-stimulatory receptor CD40 and trigger the activation of T cells that then attack the tumor.

In August 2015, Alligator exclusively licensed ADC-1013 to Janssen Biotech, which started a second Phase I study with ADC-1013 in October 2016.

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