This is a Phase 1b/2a, open-label, adaptive-design outpatient study to assess the safety, tolerability, and PK/PD of SON-1010 in combination with atezolizumab administered to patients with advanced solid tumors (Part 1) and patients with Platinum-resistant Ovarian Cancer (Part 2)

Start Date15 Sep 2023

Sponsor / Collaborator

Sonnet BioTherapeutics, Inc.

[+1]

NCT05408572

/ CompletedEarly Phase 1

A Phase 1, Randomized, Adaptive-Design, Dose-Escalation Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of SON-1010 (IL12-FHAB) in Healthy Adults

SB102 is a randomized, double-blind, single center, placebo-controlled study in healthy adults starting with sentinel participants at each dose level to carefully assess the safety, tolerability, PK, and PD of SON-1010.

Start Date27 Jul 2022

Sponsor / Collaborator

Sonnet BioTherapeutics, Inc.

NCT05352750

/ Active, not recruitingPhase 1

A Phase 1, Dose-Escalation Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of SON-1010 (IL12-FHAB) in Adult Patients With Advanced Solid Tumors.

This is a Phase 1, first-in-human, open-label, adaptive-design outpatient study to assess the safety, tolerability, and PK/PD of SON-1010 administered to patients with advanced solid tumors.

Start Date20 Apr 2022

Sponsor / Collaborator

Sonnet BioTherapeutics, Inc.

100 Clinical Results associated with SON-1010

100 Translational Medicine associated with SON-1010

100 Patents (Medical) associated with SON-1010

Literatures (Medical) associated with SON-1010

Frontiers in immunology

A phase I trial of SON-1010, a tumor-targeted, interleukin-12-linked, albumin-binding cytokine, shows favorable pharmacokinetics, pharmacodynamics, and safety in healthy volunteers

Article

Author: Cini, John K ; Kuan, Isabelle ; Lickliter, Jason ; Ryan, Philip J ; Polasek, Thomas M ; Chawla, Sant P ; Kenney, Richard T ; Dexter, Susan ; DaFonseca, Manuel ; Bingham, Justus

Background:

The benefits of recombinant interleukin-12 (rIL-12) as a multifunctional cytokine and potential immunotherapy for cancer have been sought for decades based on its efficacy in multiple mouse models. Unexpected toxicity in the first phase 2 study required careful attention to revised dosing strategies. Despite some signs of efficacy since then, most rIL-12 clinical trials have encountered hurdles such as short terminal elimination half-life (T½), limited tumor microenvironment targeting, and substantial systemic toxicity. We developed a strategy to extend the rIL-12 T½ that depends on binding albumin in vivo to target tumor tissue, using single-chain rIL-12 linked to a fully human albumin binding (FHAB) domain (SON-1010). After initiating a dose-escalation trial in patients with cancer (SB101), a randomized, double-blind, placebo-controlled, single-ascending dose (SAD) phase 1 trial in healthy volunteers (SB102) was conducted.

Methods:

SB102 (NCT05408572) focused on safety, tolerability, pharmacokinetic (PK), and pharmacodynamic (PD) endpoints. SON-1010 at 50-300 ng/kg or placebo administered subcutaneously on day 1 was studied at a ratio of 6:2, starting with two sentinels; participants were followed through day 29. Safety was reviewed after day 22, before enrolling the next cohort. A non-compartmental analysis of PK was performed and correlations with the PD results were explored, along with a comparison of the SON-1010 PK profile in SB101.

Results:

Participants receiving SON-1010 at 100 ng/kg or higher tolerated the injection but generally experienced more treatment-emergent adverse effects (TEAEs) than those receiving the lowest dose. All TEAEs were transient and no other dose relationship was noted. As expected with rIL-12, initial decreases in neutrophils and lymphocytes returned to baseline by days 9-11. PK analysis showed two-compartment elimination in SB102 with mean T½ of 104 h, compared with one-compartment elimination in SB101, which correlated with prolonged but controlled and dose-related increases in interferon-gamma (IFNγ). There was no evidence of cytokine release syndrome based on minimal participant symptoms and responses observed with other cytokines.

Conclusion:

SON-1010, a novel presentation for rIL-12, was safe and well-tolerated in healthy volunteers up to 300 ng/kg. Its extended half-life leads to a prolonged but controlled IFNγ response, which may be important for tumor control in patients.

Clinical trial registration:

https://clinicaltrials.gov/study/NCT05408572, identifier NCT05408572.

Frontiers in Immunology

SON-1010: an albumin-binding IL-12 fusion protein that improves cytokine half-life, targets tumors, and enhances therapeutic efficacy

Article

Author: McAndrew, Stephen J ; Cini, John K ; Boohaker, Rebecca ; Lapi, Suzanne E ; Brody, Rich ; Eraslan, Rukiye-Nazan ; Dexter, Susan ; Mohan, Pankaj ; Kenney, Richard T ; Rezac, Darrel J

Background:

Cytokines have been promising cancer immunotherapeutics for decades, yet only two are licensed to date. Interleukin-12 (IL-12) is a potent regulator of cell-mediated immunity that activates NK cells and interferon-γ (IFNγ) production. It plays a central role in multiple pathways that can enhance cancer cell death and modify the tumor microenvironment (TME). Attempts to dose rIL-12 were initially successful but IFNγ toxicity in Phase 2 complicated further development in the late 1990s. Since then, better dosing strategies have been developed, but none have achieved the level of cancer control seen in preclinical models. We set out to develop a novel strategy to deliver fully functional IL-12 and other biologics to the TME by binding albumin, taking advantage of its ability to be concentrated and retained in the tumor.

Methods:

Single-chain variable fragments (scFv) were identified from a human phage display library that bound human, mouse, and cynomolgus macaque serum albumin, both at physiologic and acidic conditions. These were taken through a series of steps to identify strongly binding molecules that don’t interfere with the normal physiology of albumin to bind FcRn, giving it prolonged half-life in serum, along with SPARC/GP60, which allows albumin to target the TME. A final molecule was chosen and a single mutation was made that minimizes the potential for immunogenicity. This fully human albumin-binding (FHAB®) domain was characterized and manufacturing processes were developed to bring the first drug candidate into the clinic.

Results:

Once identified, the murine form of mIL12-FHAB was studied preclinically to understand its mechanism of action and biodistribution. It was found to be much more efficient at blocking tumor growth compared to murine IL-12, while stimulating significant IFNγ production with minimal toxicity. SON-1010, which uses the human IL-12 sequence, passed through all of the characterization and required toxicology and is currently being studied in the clinic.

Conclusions:

We identified and developed a platform technology with prolonged half-life that can target IL-12 and other immune modulators to the TME. Safety and efficacy are being studied using SON-1010 as monotherapy and in combination with checkpoint blockade strategies.

News (Medical) associated with SON-1010

15 Oct 2025

·www.globenewswire.com

Evaluation of SON-1010 Using a Patient-Derived Tumoroid Platform to Support an Ongoing Phase 1 Study in Patients with Sarcoma

HOUSTON, Oct. 15, 2025 (GLOBE NEWSWIRE) -- Sonnet BioTherapeutics Holdings, Inc. (NASDAQ:SONN) is collaborating with Spanios on a non-clinical study using New Alternate Methodologies (NAM)-based patient-derived tumoroid (PDT) platforms that emulate the tumor microenvironment (TME) ex vivo to evaluate the effect of SON-1010 (IL-12-FHAB) in soft tissue sarcoma. The study aims to speed up the development of treatments for patients with rare and difficult-to-treat cancers. This study utilizes Spanios’ advanced patient-derived tumoroid COMPASS platform, which is engineered to closely replicate the TME, along with physiological oxygenation that can influence cancer progression and treatment response. In contrast to conventional preclinical models—often based on animal testing and less representative of human biology—patient-derived tumoroids preserve the distinct genetic and environmental attributes of individual tumors. By replicating the different pH and oxygen concentrations ex-vivo, using our COMPASS platform with our NAM-based methodology, we seek to enhance the understanding of SON-1010’s efficacy against cancer cells. This approach is anticipated to yield more accurate and dependable predictions regarding the clinical performance of SON-1010 therapy. Through the integration of these innovative techniques, Sonnet intends to expedite the development of effective therapies for multiple rare and difficult-to-treat cancers, ultimately providing new options for patients with limited treatment paradigms. “We wanted to try this innovative approach that evaluates physiologically relevant tumoroids,” said Raghu Rao, PhD, Sonnet’s Interim CEO, “to see how SON-1010 might impact the organoid growth and other readouts. This platform has the potential to be used with any type of solid tumor for rapid evaluation of the effects of new drugs and combinations.” About Sonnet Bio Sonnet BioTherapeutics 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 Company’s technology utilizes a fully human single chain antibody fragment (scFv) that binds to and "hitch-hikes" on human serum albumin (HSA) for transport to the TME. 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. For additional information about Sonnet, please visit Sonnet BioTherapeutics, Inc. (SONN). Bhuvanesh Dave, PhD, Co-Founder and CEO of Spanios noted, “We are excited to collaborate with the uniquely insightful and developmentally effective team at Sonnet to advance therapeutic research for solid tumors. By combining our expertise, resources, and innovative platforms, we continue to deliver on our mission of identifying, discovering, and delivering effective treatments to rare and difficult to treat cancer indications.” About Spanios Spanios was established with the objective of accelerating the discovery, identification, and development of oncology drugs for rare and challenging cancers. By enabling the ex-vivo recreation of human solid tumors and their microenvironment, Spanios eliminates reliance on traditional animal models that often lack predictive accuracy. In response to the dynamic requirements of onco-therapeutic research, Spanios has developed the proprietary patient-derived tumoroid (PDT) platform, COMPASS (Custom Organoid Modelling Platform for Accurate and Speedy Solutions). This robust set of models offers reliable clinical outcome prediction through precision-focused preclinical research. The three tiers of COMPASS, each relevant to human biology and translation, expedite drug discovery by prioritizing efficacy. For additional information about Spanios, please visit www.spanioslab.com. Bhuvanesh Dave, PhD; Co-Founder & CEO, bhuvanesh.dave@spanioslab.com www.spanioslab.com

Phase 1

01 May 2025

·www.sonnetbio.com

Sonnet Chief Medical Officer, Richard Kenney, M.D., to Present at the 6th Annual Cytokine-Based Drug Development Summit

PRINCETON, N.J., May 01, 2025 (GLOBE NEWSWIRE) -- Sonnet BioTherapeutics Holdings, Inc. (NASDAQ:SONN) (the "Company" or "Sonnet"), a clinical-stage company developing immunotherapeutic drugs targeting the tumor microenvironment (TME), today announced it will present at the 6th Annual Cytokine-Based Drug Development Summit being held May 15-16, 2025 in Boston, MA. Details of the presentation are as follows: Title: Managing Toxicity Caused by The Over Expression of Cytokines to Widen the Therapeutic Window Session: Understanding Toxicity Challenges & Improving Safety Profiles to Widen the Therapeutic Window Speaker: Richard Kenney, M.D., Chief Medical Officer of Sonnet Date and Time: Thursday, May 15, 2025 at 11:15 AM ET As part of the session, Dr. Kenney will discuss: Exploring the strategy behind the introduction of receptor bias to reduce toxicity and improve efficacy; Key strategies for optimizing cytokine potency and mitigating their inherent toxicity while considering the role of the therapeutic index in determining the clinical efficacy and safety of cytokine-based therapies; and Examining whether toxicity is the primary limiting factor in achieving therapeutic benefit and considering alternative factors that may influence the ‘therapeutic window’. For more information, please visit the Summit website here. 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, certain types of sarcoma, 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) (NCT05756907). The Company is also evaluating its second program using this platform, 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. 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: JTC Team, LLC Jenene Thomas 908-824-0775 SONN@jtcir.com Released May 1, 2025

Immunotherapy

16 Apr 2025

·www.sonnetbio.com

Sonnet Releases Virtual Investor "What This Means" Segment

- Raghu Rao, Interim Chief Executive Officer and Dr. Richard Kenney, Chief Medical Officer, of Sonnet discuss the recently announced safety data related to SON-1010 - Watch the "What This Means" video here PRINCETON, N.J., April 16, 2025 (GLOBE NEWSWIRE) -- Sonnet BioTherapeutics Holdings, Inc. (NASDAQ:SONN) (the "Company" or "Sonnet"), a clinical-stage company developing immunotherapeutic drugs targeted to the tumor microenvironment (TME), today announced that members of the Sonnet management team participated in a Virtual Investor "What This Means" segment. As part of the segment, Raghu Rao, Interim Chief Executive Officer and Dr. Richard Kenney, Chief Medical Officer, discussed the recently announced positive safety results of SON-1010 (IL12-FHAB) at the highest dose combined with atezolizumab being evaluated in the Phase 1b/2a clinical trial in adult patients with advanced solid tumors or platinum-resistant ovarian cancer (PROC) (the SB221 study). Mr. Rao and Dr. Kenney also provided insight into next steps for the program. The Virtual Investor "What This Means" segment featuring Sonnet is now available here. 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, certain types of sarcoma, 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) (NCT05756907). The Company is also evaluating its second program using this platform, 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. 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: JTC Team, LLC Jenene Thomas 908-824-0775 SONN@jtcir.com Released April 16, 2025

ImmunotherapyClinical Study

100 Deals associated with SON-1010

R&D Status

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Advanced Malignant Solid Neoplasm	Phase 2	United States	Hoffmann-La Roche Ltd.	15 Sep 2023
Advanced Malignant Solid Neoplasm	Phase 2	United States	Sonnet BioTherapeutics, Inc.	15 Sep 2023
Advanced Malignant Solid Neoplasm	Phase 2	Australia	Sonnet BioTherapeutics, Inc.	15 Sep 2023
Advanced Malignant Solid Neoplasm	Phase 2	Australia	Hoffmann-La Roche Ltd.	15 Sep 2023
Platinum-Resistant Ovarian Carcinoma	Phase 2	United States	Sonnet BioTherapeutics, Inc.	15 Sep 2023
Platinum-Resistant Ovarian Carcinoma	Phase 2	United States	Hoffmann-La Roche Ltd.	15 Sep 2023
Platinum-Resistant Ovarian Carcinoma	Phase 2	Australia	Sonnet BioTherapeutics, Inc.	15 Sep 2023
Platinum-Resistant Ovarian Carcinoma	Phase 2	Australia	Hoffmann-La Roche Ltd.	15 Sep 2023
Soft Tissue Sarcoma	Phase 1	United States	Sonnet BioTherapeutics, Inc.	20 Apr 2022

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT05352750 (SB101, AACR2026)	Phase 1	Locally Advanced Soft Tissue Sarcoma	18	SON-1010 1200 ng/kg + SON-1010 1200 ng/kg	zpdidzojsl(uwejfsqgdm) = vkeuvcrewy locsenazsc (qcoqkmrskh ) View more	Positive	21 Apr 2026
NCT05352750 (SB101, ESMO2025)	Phase 1	Soft Tissue Sarcoma	20	SON-1010	hmqtuahzsa(kalpucthzd) = wuxiiavmze pwtbfwmrdl (zaunsvhyru ) View more	Positive	17 Oct 2025
NCT05352750 (SB101, ESMO2025)	Phase 1	Soft Tissue Sarcoma	20	SON-1010 + Trabectedin	hmqtuahzsa(kalpucthzd) = huxaifaqch pwtbfwmrdl (zaunsvhyru ) View more	Positive	17 Oct 2025
NCT05352750 (SB101, GlobeNewswire \| Company_Website) Manual	Phase 1	Solid tumor	24	SON-1010	urezkunzto(bhjgtwskky) = shxldhcono ufjcladklo (cwefedvbnj ) View more	Positive	09 Dec 2024
SB101 (NEWS)	Not Applicable	Ovarian Epithelial Carcinoma	61	SON-1010	oatrusuloq(mzvjjlkteg) = iguncxuxxr euqnnonevm (sbhzmrpgqi )	Positive	20 May 2024
SB101 (NEWS)	Not Applicable	Ovarian Epithelial Carcinoma	61	SON-1010+阿替利珠单抗	-	Positive	20 May 2024
NCT05408572 (SB102, Literature \| Pubmed \| Front Immunol) Manual	Phase 1	-	-	SON-1010	kjxuzrtpuf(itvalnvgar) = two-compartment elimination in SB102 with mean T½ of 104 h, compared with one-compartment elimination in SB101 vqieogwvqk (ioikmpbcec )	Positive	29 Feb 2024
AACR2023 Manual	Not Applicable	HR-positive/HER2-low Solid Tumors	11	SON-1010	uwxpkqpdbu(qlrhyhoapf) = thbatgvcvy ioxxzrirms (gvzffqmiqn ) View more	Positive	14 Apr 2023
AACR2023 Manual	Not Applicable	HR-positive/HER2-low Solid Tumors	11	SON-1010 (the first 3 dose cohorts)	eassefclmj(etvomrfkmq) = qjhhytokve ihvhebmnzo (ztgjtkdvir )	Positive	14 Apr 2023
NCT05352750 (SB101, Corporate Publications) Manual	Phase 1	Neoplasms	12	SON-1010	pflxbjtvun(xwgjpobzil) = mild/moderate, transient in nature, and have all been tolerable yyhdinafgv (wgbhjjnonk )	Positive	02 Nov 2022

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