On February 19, 2025 Sonnet BioTherapeutics Holdings, Inc. (the "Company" or "Sonnet") (NASDAQ: SONN), a clinical-stage company developing targeted immunotherapeutic drugs, reported its plans to advance the development of its proprietary Antibody Drug Conjugate (ADC) platform which was designed to circumvent many of the technical challenges associated with ADCs (Press release, Sonnet BioTherapeutics, FEB 19, 2025, View Source [SID1234650381]). Additionally, the Company announced the release of a Virtual Investor "What This Means" segment to discuss plans for its ADC platform.
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"In order to increase our value proposition to cancer patients, in addition to our existing FHAB platform we have developed a bolt-on ADC platform that takes advantage of our FHAB targeting domain and flexible docking peptides, which offer controllable DAR capacity," commented Pankaj Mohan, Ph.D., Founder and Chief Executive Officer of Sonnet. "Further, we believe our ADC platform is differentiated from other ADCs by stable structural integrity, extended conjugation site flexibility, potential for enhanced tumor penetration and retention with the FHAB domain, and potential to select and conjugate one of several possible payloads having different mechanisms of action (MOA) for killing cancer cells. With a plug-and-play ADC platform, we could generate a number of ADC candidates, and thus, we are seeking value-driven discovery partnerships."
The initial proof-of-concept (POC) construct was designated as SON-5010, which is produced through a two-step process whereby the targeting scaffold and payload domains are either expressed and purified from mammalian cells or chemically synthesized, respectively, and then joined to create the final ADC conjugate using a chemical linkage process. The SON-5010 ADC construct is comprised of an anti-HER2-FHAB-anti-HER2 targeting scaffold linked to a docking peptide that has 3 equally spaced lysine residues which serve as conjugation sites for monomethyl auristatin E (MMAE), a synthetic antineoplastic agent that disrupts the microtubule network and suppresses cell proliferation and mitosis, including G2/M arrest. This initial SON-5010 ADC was used in a head-to-head comparison with an approved product, Kadcyla, which has a very similar anti-HER2 targeting domain and linker chemistry but is conjugated with a different toxin payload known as mertansine (DM1) and a trastuzumab-MMAE complex, consisting of a humanized anti-HER2 receptor monoclonal antibody with the same linker chemistry and 3x MMAE DAR payload as SON-5010.
John Cini, Ph.D., Co-Founder and Chief Scientific Officer commented, "Sonnet is excited about the early POC data shown by this novel plug-and-play, non-IgG ADC format that incorporates Sonnet’s albumin binding scFv into the targeting scaffold. The binding of albumin in this particular ADC format provides the differentiated potential for accumulation of the FHAB-ADC complex into the tumor. The SON-5010 ADC was produced with the same linker chemistry and MMAEx3 as in trastuzumab (Herceptin) and has shown in vitro human serum stability at 37oC and similar cellular cytotoxicity results. In a direct in vivo comparison with Kadcyla and Herceptin at 10mg/kg in the BT-474 HER2+ carcinoma breast tumor mouse model, SON-5010 demonstrated similar tumor reduction activity and no detectable toxicity. The potential diverse application of Sonnet’s ADC platform could be applied with a wide variety of linkers and toxins, resulting in complete controllable DAR. Further, Sonnet’s ADC platform has the ability to show bispecific or tri-specific tumor targeting capability when associated with the FHAB scFv, which could potentially improve its ADC clinical efficiency."
Dr. Stephen McAndrew, Ph.D., Chief Business Officer commented, "We believe this ADC platform differentiates itself by offering the potential for flexibility around multiple targeting scaffolds, controllable DARs and choice of payload. We plan to continue global prosecution of our intellectual property around this ADC platform while we seek discovery partnership opportunities aimed at developing proprietary ADC drug candidates."