Sonnet BioTherapeutics Announces That Its Proprietary Antibody Drug Conjugate (ADC) Platform is Available for Drug Discovery Partnerships with Potential for Producing Multiple Pipeline Drug Candidates
Sonnet BioTherapeutics (NASDAQ: SONN) announced the advancement of its proprietary Antibody Drug Conjugate (ADC) platform for drug discovery partnerships. The platform leverages the company's FHAB targeting domain and flexible docking peptides, offering controllable drug-antibody ratios (DAR).
Their initial proof-of-concept construct, SON-5010, demonstrated comparable performance to Kadcyla® and trastuzumab-MMAE in preclinical studies. SON-5010 comprises an anti-HER2-FHAB-anti-HER2 targeting scaffold linked to MMAE, showing similar tumor reduction activity at 10mg/kg in the BT-474 HER2+ carcinoma breast tumor mouse model.
The platform's key advantages include stable structural integrity, extended conjugation site flexibility, potential for enhanced tumor penetration, and the ability to select various payloads with different mechanisms of action for targeting cancer cells.
Sonnet BioTherapeutics (NASDAQ: SONN) ha annunciato il progresso della sua piattaforma proprietaria di Antibody Drug Conjugate (ADC) per partnership nella scoperta di farmaci. La piattaforma sfrutta il dominio di targeting FHAB dell'azienda e peptidi di docking flessibili, offrendo rapporti controllabili tra farmaco e anticorpo (DAR).
Il loro costrutto iniziale di prova di concetto, SON-5010, ha dimostrato prestazioni comparabili a quelle di Kadcyla® e trastuzumab-MMAE negli studi preclinici. SON-5010 comprende uno scaffold di targeting anti-HER2-FHAB-anti-HER2 collegato a MMAE, mostrando un'attività di riduzione tumorale simile a 10mg/kg nel modello murino di carcinoma mammario HER2+ BT-474.
I principali vantaggi della piattaforma includono un'integrità strutturale stabile, flessibilità prolungata nei siti di coniugazione, potenziale per una maggiore penetrazione tumorale e la possibilità di selezionare vari payload con diversi meccanismi d'azione per il targeting delle cellule tumorali.
Sonnet BioTherapeutics (NASDAQ: SONN) anunció el avance de su plataforma propietaria de Antibody Drug Conjugate (ADC) para asociaciones en el descubrimiento de fármacos. La plataforma aprovecha el dominio de targeting FHAB de la compañía y péptidos de acoplamiento flexibles, ofreciendo proporciones controlables de fármaco-anticuerpo (DAR).
Su constructo inicial de prueba de concepto, SON-5010, demostró un rendimiento comparable al de Kadcyla® y trastuzumab-MMAE en estudios preclínicos. SON-5010 comprende un andamiaje de targeting anti-HER2-FHAB-anti-HER2 vinculado a MMAE, mostrando una actividad similar de reducción tumoral a 10mg/kg en el modelo murino de carcinoma de mama HER2+ BT-474.
Las principales ventajas de la plataforma incluyen una integridad estructural estable, flexibilidad extendida en los sitios de conjugación, potencial para una mayor penetración tumoral y la capacidad de seleccionar diversos payloads con diferentes mecanismos de acción para el targeting de células cancerosas.
Sonnet BioTherapeutics (NASDAQ: SONN)는 약물 발견 파트너십을 위한 독점 항체 약물 접합체 (ADC) 플랫폼의 발전을 발표했습니다. 이 플랫폼은 회사의 FHAB 타겟팅 도메인과 유연한 도킹 펩타이드를 활용하여 약물-항체 비율(DAR)을 제어할 수 있습니다.
그들의 초기 개념 증명 구조인 SON-5010은 전임상 연구에서 Kadcyla® 및 trastuzumab-MMAE와 유사한 성능을 보여주었습니다. SON-5010은 MMAE에 연결된 anti-HER2-FHAB-anti-HER2 타겟팅 스캐폴드를 포함하며, BT-474 HER2+ 유방 종양 생쥐 모델에서 10mg/kg에서 유사한 종양 축소 활성을 나타냈습니다.
이 플랫폼의 주요 장점은 안정적인 구조적 무결성, 확장된 접합 부위 유연성, 향상된 종양 침투 가능성, 그리고 암세포를 타겟팅하기 위해 다양한 작용 메커니즘을 가진 다양한 페이로드를 선택할 수 있는 능력입니다.
Sonnet BioTherapeutics (NASDAQ: SONN) a annoncé l'avancement de sa plateforme propriétaire de Antibody Drug Conjugate (ADC) pour des partenariats dans la découverte de médicaments. La plateforme exploite le domaine de ciblage FHAB de l'entreprise et des peptides de docking flexibles, offrant des ratios contrôlables de médicament-anticorps (DAR).
Leur premier construct de preuve de concept, SON-5010, a montré des performances comparables à celles de Kadcyla® et trastuzumab-MMAE dans des études précliniques. SON-5010 comprend un échafaudage de ciblage anti-HER2-FHAB-anti-HER2 lié à MMAE, montrant une activité de réduction tumorale similaire à 10mg/kg dans le modèle murin de carcinome mammaire HER2+ BT-474.
Les principaux avantages de la plateforme incluent une intégrité structurelle stable, une flexibilité prolongée des sites de conjugaison, un potentiel d'amélioration de la pénétration tumorale et la capacité de sélectionner divers payloads avec différents mécanismes d'action pour cibler les cellules cancéreuses.
Sonnet BioTherapeutics (NASDAQ: SONN) hat den Fortschritt seiner proprietären Antibody Drug Conjugate (ADC) Plattform für Partnerschaften in der Arzneimittelentdeckung bekannt gegeben. Die Plattform nutzt den FHAB-Targeting-Domäne des Unternehmens und flexible Docking-Peptide, die kontrollierbare Verhältnisse von Arzneimittel zu Antikörper (DAR) bieten.
Ihr anfänglicher Proof-of-Concept-Konstrukt, SON-5010, zeigte in präklinischen Studien eine vergleichbare Leistung zu Kadcyla® und trastuzumab-MMAE. SON-5010 besteht aus einem anti-HER2-FHAB-anti-HER2-Targeting-Gerüst, das mit MMAE verbunden ist, und zeigt eine ähnliche Tumorreduktionsaktivität bei 10mg/kg im BT-474 HER2+ Karzinom-Mausmodell.
Die wichtigsten Vorteile der Plattform umfassen stabile strukturelle Integrität, erweiterte Flexibilität der Konjugationsstellen, Potenzial für verbesserte Tumordurchdringung und die Möglichkeit, verschiedene Payloads mit unterschiedlichen Wirkmechanismen zur gezielten Bekämpfung von Krebszellen auszuwählen.
- Platform shows comparable efficacy to established drugs (Kadcyla® and trastuzumab-MMAE) in preclinical studies
- SON-5010 demonstrated similar tumor reduction activity with no detectable toxicity in mouse models
- Platform offers flexible payload capacity and controllable drug-antibody ratios
- Technology enables potential for multiple targeting capabilities (bi-specific or tri-specific)
- Platform is still in early development stage with only preclinical data available
- Requires partnerships for further development, indicating potential resource limitations
Insights
Sonnet BioTherapeutics has unveiled a potentially game-changing Antibody Drug Conjugate (ADC) platform that addresses several critical limitations in current ADC development. The platform's initial proof-of-concept, SON-5010, has demonstrated comparable efficacy to Kadcyla® in HER2+ breast cancer models - a significant achievement considering Kadcyla's established market position and proven clinical success.
The platform's technological advantages are particularly noteworthy: the flexible payload capacity and controllable drug-antibody ratios (DAR) could enable more precise drug delivery and potentially reduced side effects. The integration of Sonnet's FHAB domain for enhanced tumor targeting represents a unique differentiator in the competitive ADC landscape.
The ADC market is experiencing rapid growth, with major pharmaceutical companies actively seeking innovative platforms. Sonnet's "plug-and-play" approach could be particularly attractive for potential partners, as it offers:
- Flexible targeting scaffolds for multiple cancer types
- Controllable drug loading capacity
- Choice of different toxic payloads
- Potential for bi-specific or tri-specific targeting
The comparable performance to Kadcyla® in preclinical studies, without detected toxicity, positions Sonnet's platform as a serious contender in the ADC space. The company's strategy to pursue discovery partnerships could accelerate platform validation while preserving capital - a important consideration given their current market capitalization of
However, investors should note that while the preclinical data is promising, the path to commercialization remains long and capital-intensive. The success of partnership discussions and the platform's ability to generate multiple viable drug candidates will be critical metrics to watch.
Building on proven targeting of the FHAB domain, Sonnet’s ADC platform offers flexible payload capacity and controllable drug-antibody ratios (DAR)
An epidermal growth factor receptor 2 (HER2) ADC construct designated – SON-5010 showed similar activities as compared with Kadcyla® and also trastuzumab-MMAE, in a preclinical study
Company’s ADC Platform offers the potential for novel ADCs with homogeneous structural integrity, tumor targeting domain, interchangeability of toxin payloads and flexible conjugation site usage
Management releases “What This Means” segment discussing its ADC platform; Access here
PRINCETON, N.J., Feb. 19, 2025 (GLOBE NEWSWIRE) -- Sonnet BioTherapeutics Holdings, Inc. (the “Company” or “Sonnet”) (NASDAQ: SONN), a clinical-stage company developing targeted immunotherapeutic drugs, today announced 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. Additionally, the Company announced the release of a Virtual Investor “What This Means” segment to discuss plans for its ADC platform, which is now available here.
“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.”
About Sonnet BioTherapeutics Holdings, Inc.
Sonnet is an oncology-focused biotechnology company with a proprietary platform for developing targeted biologic drugs with single or bifunctional action. Known as FHAB (Fully Human Albumin-Binding), the technology utilizes a fully human single chain antibody fragment (scFv) that binds to and "hitch-hikes" on human serum albumin (HSA) for transport to target tissues. Sonnet's FHAB was designed to specifically target tumor and lymphatic tissue, with an improved therapeutic window for optimizing the safety and efficacy of immune modulating biologic drugs. FHAB platform is the foundation of a modular, plug-and-play construct for potentiating a range of large molecule therapeutic classes, including cytokines, peptides, antibodies, and vaccines.
Sonnet’s lead program, SON-1010, or IL-12-FHAB, is in development for the treatment of advanced solid tumors, certain types of sarcoma, and platinum-resistant ovarian cancer (PROC). SON-1010 is being evaluated in an ongoing Phase 1/2a study through a Master Clinical Trial and Supply Agreement with Roche in combination with atezolizumab (Tecentriq®) for the treatment of PROC. The Company is also evaluating its second product candidate, SON-1210, an IL12-FHAB-IL15 for solid tumors, in collaboration with the Innovative Immuno-Oncology Consortium (IIOC), and plans to commence an investigator-initiated and funded Phase 1/2a study for the treatment of locally-advanced or metastatic pancreatic ductal adenocarcinoma (PDAC).
The Company’s SON-080 program is a low dose of rhIL-6 in development for Chemotherapy-Induced Peripheral Neuropathy (CIPN) and Diabetic Peripheral Neuropathy (DPN). SON-080 demonstrated encouraging results in a Phase 1b/2a clinical trial, being well tolerated with no evidence of a pro-inflammatory cytokine response. In October 2024, Sonnet announced a license agreement with Alkem Laboratories, Inc. who will assume responsibility for advancing development of the SON-080 program into a Phase 2 study in DPN in India.
Forward-Looking Statements
This press release contains certain forward-looking statements within the meaning of Section 27A of the Securities Act of 1933 and Section21E of the Securities Exchange Act of 1934 and Private Securities Litigation Reform Act, as amended, including those relating to, the Company's product development, the Company's cash runway clinical and regulatory timelines, market opportunity, competitive position, possible or assumed future results of operations, business strategies, potential growth opportunities and other statements that are predictive in nature. These forward-looking statements are based on current expectations, estimates, forecasts and projections about the industry and markets in which we operate and management's current beliefs and assumptions.
These statements may be identified by the use of forward-looking expressions, including, but not limited to, "expect," "anticipate," "intend," "plan," "believe," "estimate," "potential," "predict," "project," "should," "would" and similar expressions and the negatives of those terms. These statements relate to future events or our financial performance and involve known and unknown risks, uncertainties, and other factors which may cause actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements. Such factors include those set forth in the Company's filings with the Securities and Exchange Commission. Prospective investors are cautioned not to place undue reliance on such forward-looking statements, which speak only as of the date of this press release. The Company undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise.
Investor Relations Contact:
JTC Team, LLC
Jenene Thomas
908-824-0775
SONN@jtcir.com
FAQ
What are the key features of Sonnet's new ADC platform announced in February 2024?
How did SONN's SON-5010 perform compared to Kadcyla in preclinical trials?
What is the composition of Sonnet's SON-5010 ADC construct?
What are the potential advantages of SONN's ADC platform over existing technologies?
