Sonnet BioTherapeutics Expands Phase 1 SB101 Trial to Evaluate Combination of SON-1010 with Trabectedin in Certain Sarcomas
Sonnet BioTherapeutics (NASDAQ:SONN) announced the expansion of its Phase 1 SB101 clinical study of SON-1010 to evaluate its combination with trabectedin in soft-tissue sarcoma patients. The expansion follows successful monotherapy dose escalation and will explore SON-1010's immune-oncology impact at the maximum tolerated dose of 1200 ng/kg.
The study will enroll up to 18 patients with unresectable, metastatic liposarcoma or leiomyosarcoma. Enrollment is expected to complete in H1 2025, with topline safety data anticipated in H2 2025. The trial's primary outcomes include safety, tolerability, pharmacokinetics, and pharmacodynamics of SON-1010.
SON-1010, Sonnet's proprietary version of IL-12, is configured using the FHAB platform to extend half-life and bioactivity. The company believes combining SON-1010 with trabectedin could enhance local immune response in the tumor microenvironment and potentially improve treatment outcomes for soft-tissue sarcoma patients.
Sonnet BioTherapeutics (NASDAQ:SONN) ha annunciato l'espansione del suo studio clinico di Fase 1 SB101 relativo a SON-1010 per valutare la sua combinazione con trabectedin in pazienti affetti da sarcoma dei tessuti molli. L'espansione segue un incremento di dose della monoterapia di successo e esplorerà l'impatto immuno-oncologico di SON-1010 alla massima dose tollerata di 1200 ng/kg.
Lo studio recluterà fino a 18 pazienti con liposarcoma o leiomiosarcoma non operabili e metastatici. Il reclutamento dovrebbe concludersi nel primo semestre del 2025, con dati di sicurezza attesi nel secondo semestre del 2025. Gli esiti principali della sperimentazione includono sicurezza, tollerabilità, farmacocinetica e farmacodinamica di SON-1010.
SON-1010, la versione proprietaria di Sonnet di IL-12, è configurato utilizzando la piattaforma FHAB per estendere la emivita e la bioattività. L'azienda ritiene che la combinazione di SON-1010 con trabectedin possa migliorare la risposta immunitaria locale nell'ambiente tumore e potenzialmente migliorare i risultati del trattamento per i pazienti con sarcoma dei tessuti molli.
Sonnet BioTherapeutics (NASDAQ:SONN) anunció la expansión de su estudio clínico de Fase 1 SB101 relacionado con SON-1010 para evaluar su combinación con trabectedin en pacientes de sarcoma de tejidos blandos. La expansión sigue un escalonamiento de dosis en monoterapia exitoso y explorará el impacto inmuno-oncológico de SON-1010 a la dosis máxima tolerada de 1200 ng/kg.
El estudio inscribirá hasta 18 pacientes con liposarcoma o leiomiosarcoma metastásico y no resecable. Se espera que la inscripción se complete en la primera mitad de 2025, con datos de seguridad generales anticipados para la segunda mitad de 2025. Los resultados primarios del ensayo incluyen seguridad, tolerabilidad, farmacocinética y farmacodinámica de SON-1010.
SON-1010, la versión propietaria de Sonnet de IL-12, está configurado utilizando la plataforma FHAB para extender la vida media y la bioactividad. La compañía cree que combinar SON-1010 con trabectedin podría mejorar la respuesta inmune local en el microambiente tumoral y potencialmente mejorar los resultados del tratamiento para pacientes con sarcoma de tejidos blandos.
Sonnet BioTherapeutics (NASDAQ:SONN)는 SON-1010의 1상 SB101 임상 연구 확장을 발표하여 연부조직 육종 환자에서 trabectedin과의 병용 요법을 평가할 예정입니다. 이번 확장은 성공적인 단독 요법 용량 확대에 이어 진행되며, 최대 허용 용량인 1200 ng/kg에서 SON-1010의 면역 종양학적 영향을 살펴볼 것입니다.
이 연구는 절제가 불가능한 전이성 지방 육종 또는 평활근 육종 환자 최대 18명을 등록할 예정입니다. 등록은 2025년 상반기 중에 완료될 것으로 예상되며, 2025년 하반기에는 안전성 데이터의 주요 결과가 예상됩니다. 이 시험의 주요 결과에는 SON-1010의 안전성, 내약성, 약리학적 동태 및 약리학적 작용이 포함됩니다.
SON-1010는 Sonnet의 IL-12 독점 버전으로, FHAB 플랫폼을 사용하여 반감기와 생물학적 활성을 연장하도록 구성되어 있습니다. 회사는 SON-1010과 trabectedin의 병합이 종양 미세 환경에서 국소 면역 반응을 촉진하고 연부조직 육종 환자의 치료 결과를 개선할 수 있다고 믿고 있습니다.
Sonnet BioTherapeutics (NASDAQ:SONN) a annoncé l'expansion de son étude clinique de Phase 1 SB101 concernant SON-1010 afin d'évaluer sa combinaison avec trabectedin chez des patients atteints de sarcome des tissus mous. L'expansion intervient après une escalade de dose monothérapie réussie et explorera l'impact immuno-oncologique de SON-1010 à la dose maximale tolérée de 1200 ng/kg.
Cette étude inscrira jusqu'à 18 patients avec liposarcome ou léiomyosarcome non opérable et métastatique. L'inscription est prévue pour se terminer au premier semestre de 2025, avec des données de sécurité clés anticipées pour le second semestre 2025. Les résultats primaires de l'essai comprennent la sécurité, la tolérance, la pharmacocinétique et la pharmacodynamique de SON-1010.
SON-1010, la version propriétaire de Sonnet d'IL-12, est configuré à l'aide de la plateforme FHAB pour prolonger la demi-vie et la bioactivité. La société est convaincue que la combinaison de SON-1010 avec trabectedin pourrait améliorer la réponse immunitaire locale dans le microenvironnement tumoral et potentiellement améliorer les résultats du traitement pour les patients atteints de sarcome des tissus mous.
Sonnet BioTherapeutics (NASDAQ:SONN) gab die Erweiterung seiner Phase-1-Studie SB101 zu SON-1010 bekannt, um die Kombination mit Trabectedin bei Patienten mit Weichgewebesarkomen zu bewerten. Die Erweiterung folgt auf eine erfolgreiche Dosissteigerung der Monotherapie und wird die immunonkologische Wirkung von SON-1010 bei der maximal tolerierten Dosis von 1200 ng/kg untersuchen.
Die Studie wird bis zu 18 Patienten mit inoperablem, metastasierendem Liposarkom oder Leiomyosarkom einschließen. Mit der Einschreibung wird bis zur ersten Hälfte von 2025 gerechnet, während die Spitzenwerte zur Sicherheit in der zweiten Hälfte von 2025 erwartet werden. Die primären Ergebnisse der Studie umfassen Sicherheit, Verträglichkeit, Pharmakokinetik und Pharmakodynamik von SON-1010.
SON-1010, die proprietäre Version von Sonnet von IL-12, wurde mit der FHAB-Plattform konfiguriert, um die Halbwertszeit und Bioaktivität zu verlängern. Das Unternehmen ist der Ansicht, dass die Kombination von SON-1010 mit Trabectedin die lokale Immunantwort im Tumormikromilieu verbessern und möglicherweise die Behandlungsergebnisse für Patienten mit Weichgewebesarkomen verbessern könnte.
- Successful completion of monotherapy dose escalation phase
- Maximum tolerated dose established at 1200 ng/kg
- No new safety concerns reported to date
- Potential synergistic effect with trabectedin in treating soft-tissue sarcomas
- Topline safety data not expected until H2 2025
- initial enrollment of only 18 patients
- Requires further Phase 2 studies to establish efficacy
Insights
The expansion of SONN's Phase 1 SB101 trial represents a strategic advancement in sarcoma treatment. The combination of SON-1010 with trabectedin targets an identified market opportunity in soft-tissue sarcoma (STS), particularly following trabectedin's recent approval as second-line therapy. The 1200 ng/kg MTD established for SON-1010 provides a clear dosing framework for the combination study.
The trial design is robust, with 18 patients planned for enrollment - a number specifically chosen to detect statistical significance in RECIST responses. The alternating dosing schedule with trabectedin's 21-day cycles demonstrates careful consideration of potential drug interactions and optimal timing for immune response.
Most notably, targeting earlier-stage patients could yield better outcomes than typical Phase 1 trials, as these patients' immune systems are likely more responsive. The combination's mechanism of action - trabectedin's macrophage activation complemented by SON-1010's NK and T cell stimulation - presents a scientifically sound approach to enhancing anti-tumor response.
This trial expansion carries significant market implications. With a micro-cap valuation of
The parallel development of SON-1010 in ovarian cancer (SB221 trial) with Genentech collaboration provides additional value potential and risk diversification. The expected safety data readouts in H2 2025 for the trabectedin combination and Q1 2025 for the ovarian cancer trial represent near-term catalysts that could impact valuation.
The focus on second-line STS treatment aligns with market demands, addressing an established need while potentially offering improved outcomes through immunotherapy enhancement. This positions SONN for potential partnership opportunities, particularly if the combination demonstrates superior efficacy to trabectedin monotherapy.
SON-1010, after receipt of data suggesting clinical benefit when administered as a monotherapy in patients with advanced solid tumors, enters combination evaluation with trabectedin (Yondelis®) with the potential to improve trabectedin’s therapeutic window in soft-tissue sarcoma patients
Combined mechanisms have the potential to enhance progression-free survival (PFS) in some of the largest cohorts of patients with soft-tissue sarcoma
Topline safety data of the combination of SON-1010 with trabectedin is expected in H2 calendar year 2025
Sonnet management discusses what this expansion means in a Virtual Investor “What This Means” segment; Access here
PRINCETON, NJ, Jan. 21, 2025 (GLOBE NEWSWIRE) -- Sonnet BioTherapeutics Holdings, Inc. (NASDAQ:SONN) (the "Company" or "Sonnet"), a clinical-stage company developing targeted immunotherapeutic drugs, announced today an expansion of its Phase 1 SB101 clinical study of SON-1010 (IL12-FHAB) in adult patients with advanced solid tumors to add a new cohort to evaluate the effect of SON-1010 in combination with trabectedin (Yondelis®), following the successful completion of monotherapy dose escalation. This expansion will explore the immune-oncology impact of SON-1010 at the maximum tolerated (MTD) dose of 1200 ng/kg in combination with trabectedin, which is an approved chemotherapeutic drug for certain advanced soft-tissue sarcomas (STS). Patients with STS could potentially benefit from an enhanced local immune response in the tumor microenvironment (TME). Enrollment in this cohort is underway and is expected to be completed in H1 calendar year 2025. Topline safety data of the combination with trabectedin is expected in H2 calendar year 2025; no new safety concerns have been reported to date. Additionally, the Company announced the release of a “What This Means” segment to discuss the expansion of the Phase 1 clinical study which is now available here.
“The Sarcoma Oncology Center is pleased to have been able to enroll most of the patients in Sonnet’s Phase1 SB101 study to date, with the majority of the patients having STS,” commented Dr. Sant Chawla, Principal Investigator at the Sarcoma Oncology Center in Santa Monica, California. “Additionally, as we have contributed to the development of trabectedin over the years, we were excited to see its approval in early 2024 as a monotherapy in the second-line treatment for two of the most common types of sarcoma — liposarcoma and leiomyosarcoma. While the trabectedin approval was based on several clinical trials in sarcoma, we believe a large unmet need remains for the treatment of STS. We believe that combining trabectedin with SON-1010 has the potential for a natural synergistic effect of the two mechanisms of action.”
The Company expects to enroll up to 18 patients with unresectable, metastatic liposarcoma or leiomyosarcoma in this open-label, single-arm expansion cohort. The patients will be treated with SON-1010 in combination with the standard 21-day trabectedin cycles, alternating the dosing of the two drugs. This number of subjects may be needed to see a statistical benefit in the response using the standard RECIST paradigm. The primary outcome measures for the Phase 1 SB101 trial are the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of SON-1010 and to establish the MTD, which has been set at 1200 ng/kg. The Company believes the results of this expansion cohort could position SON-1010 for a larger Phase 2 study that could establish the combination of SON-1010 and trabectedin as a new and potentially improved treatment for STS.
“The ability to assess earlier-stage patients is an exciting opportunity to evaluate the potential for SON-1010 to turn ‘cold’ tumors ‘hot’,” said Richard Kenney, M.D., Sonnet's Chief Medical Officer. “Most Phase 1 studies in the oncology space are done in patients with advanced disease, whose immune systems may not respond optimally after multiple types of chemotherapy. Trabectedin’s approval as a single agent second-line therapy in STS provides access to patients at an earlier stage with an underlying immune response that may be more robust.”
“The Sonnet team has been studying the efficacy and safety of SON-1010 as a single agent, which has thus far suggested clinical benefit when administered as a monotherapy in patients with advanced solid tumors,” said Pankaj Mohan, Ph.D., Sonnet Founder and Chief Executive Officer. “Further, we believe this synergy could improve the response in a serious type of cancer at an earlier stage of disease, which could open up another potential opportunity for partnering.”
SON-1010 is the Company’s proprietary version of recombinant human interleukin-12 (rhIL-12), configured using genetic fusion to Sonnet's Fully Human Albumin Binding (FHAB®) platform, which extends the half-life and bioactivity of the IL-12 component due to binding native albumin in the serum. Albumin naturally targets the TME by strong binding to gp60 and Secreted Protein Acidic and Rich in Cysteine (SPARC). The majority of patients enrolled to date in the Phase 1 SB101 trial have STS, which has a known potential for an enhanced response to immunotherapy.
Trabectedin is an alkylating DNA-binding agent that was approved as a second-line treatment in early 2024 for patients with unresectable, metastatic liposarcoma or leiomyosarcoma who have received a prior anthracycline-containing regimen. It is also known to activate tumor macrophages into a pro-inflammatory phenotype. The Company believes that SON-1010 has the potential to complement that activity by activating the NK and T cells in the TME to secrete more interferon-gamma (IFNγ) which is considered to be important for anti-tumor control.
For more information about the Phase 1 SB101 trial in adult patients with advanced solid tumors visit www.clinicaltrials.gov and reference identifier NCT05352750.
SON-1010 is also being evaluated in a Phase 1b/2a dose-escalation and proof-of-concept study (SB221) in combination with SON-1010 and atezolizumab (Tecentriq®) (in collaboration with Genentech, a member of the Roche Group), which is focused on platinum-resistant ovarian cancer (PROC) (NCT05756907). Enrollment remains ongoing and an update on safety at the MTD in that trial is expected in Q1 calendar year 2025.
About SON-1010
SON-1010 is a candidate immunotherapeutic recombinant drug that links unmodified single-chain human IL-12 with the albumin-binding domain of the single-chain antibody fragment A10m3. This single-chain antibody fragment was selected to bind albumin both at normal pH, as well as at the acidic pH typically found in the TME. The FHAB technology targets tumor and lymphatic tissue, providing a mechanism for dose sparing and an opportunity to improve the safety and efficacy profile of not only IL-12, but a variety of potent immunomodulators that can be linked using the platform. Interleukin-12 can orchestrate a robust immune response to many cancers and pathogens. Given the types of proteins induced in the TME, such as the Secreted Protein and Rich in Cysteine (SPARC) and glycoprotein 60 (GP60), several types of cancer, such as non-small cell lung cancer, melanoma, head and neck cancer, sarcoma, and some gynecological cancers are particularly relevant to this approach. SON-1010 is designed to deliver IL-12 to local tumor tissue, turning ‘cold' tumors ‘hot' by stimulating IFNγ, which activates innate and adaptive immune cell responses and increases the production of Programed Death Ligand 1 (PD-L1) on tumor cells.
About the Phase 1 SB101 Trial
This first-in-human study is primarily designed to evaluate the safety of multiple ascending doses of SON-1010 in cancer patients and is being conducted at several sites across the United States. While the optimal dose is unknown at this stage, the potential to target the tumors, the extended PK mechanism, and our preclinical data suggest the therapeutic dose may be lower compared to native human IL-12. The study, utilizing a standard 3+3 oncology design in at least five cohorts, established the MTD at 1200 ng/kg using subcutaneous injections of SON-1010 every 3 to 4 weeks. The primary endpoint explores the safety and tolerability of SON-1010, with key secondary endpoints intended to measure PK, PD, immunogenicity, and anti-tumor activity. This study will form the basis for potential combinations with other types of immunotherapies and the future development of bispecific candidates using the FHAB platform.
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 solid tumors and ovarian cancer. SON-1010 is being evaluated in an ongoing Phase 1/2a study through a Master Clinical Trial and Supply Agreement, along with ancillary Quality and Safety Agreements, with Roche in combination with atezolizumab (Tecentriq®) for the treatment of platinum-resistant ovarian cancer (PROC). The Company is also evaluating its second program, SON-1210, an IL12-FHAB-IL15 for solid tumors, in collaboration with the Sarcoma Oncology Center to commence an investigator-initiated and funded Phase 1/2a study for the treatment of pancreatic cancer.
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 an India 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.
Forward-Looking Statements
This press release contains certain forward-looking statements within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934 and Private Securities Litigation Reform Act, as amended, including those relating to the outcome of the Company’s clinical trials, the Company's cash runway, the Company's product development, 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:
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FAQ
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