Sonnet BioTherapeutics Completes Enrollment in Phase 1 Study of SON-1010 (IL12-FHAB) as a Monotherapy (SB101) for the Treatment of Solid Tumors

Rhea-AI Summary

Sonnet BioTherapeutics (NASDAQ: SONN) has completed enrollment and initiated dosing in its Phase 1 SB101 clinical trial of SON-1010 (IL12-FHAB) for advanced solid tumors. The study enrolled 24 subjects, with topline safety data expected in Q4 2024. SON-1010 is a targeted immune activation cancer therapy designed to turn 'cold' tumors 'hot'. Key points:

• No dose-limiting toxicities reported to date
• Majority of adverse events mild and transient
• One patient with endometrial sarcoma showed stable disease for almost 2 years
• Controlled induction of interferon gamma observed
• No indication of potential for cytokine release syndrome

Positive

• Completed enrollment and initiated dosing in Phase 1 SB101 clinical trial
• No dose-limiting toxicities reported to date
• One patient with endometrial sarcoma showed stable disease for almost 2 years
• Controlled induction of interferon gamma observed without cytokine release syndrome potential

Negative

• Topline safety data not expected until Q4 2024
• No partial responses achieved according to RECIST criteria

Clinical Research Analyst

The completion of enrollment in Sonnet BioTherapeutics' Phase 1 study for SON-1010 is a significant milestone. This IL-12 based immunotherapy shows promise in treating solid tumors by potentially converting "cold" tumors to "hot" ones. Key points:

• 24 subjects enrolled, with topline safety data expected in Q4 2024
• No dose-limiting toxicities reported so far, with mostly mild adverse events
• One patient with endometrial sarcoma showed stable disease for almost 2 years
• Controlled induction of interferon gamma observed, without signs of cytokine release syndrome

While these early results are encouraging, it's important to await the final safety data and potential efficacy signals. The extended stable disease in one patient is promising, but larger studies will be needed to confirm SON-1010's therapeutic potential.

Oncology Specialist

SON-1010's approach of using a modified IL-12 to target the tumor microenvironment is innovative. The "desensitizing" first dose strategy to mitigate IL-12's known toxicities is clever, potentially allowing for higher maintenance doses. The observed stable disease in an endometrial sarcoma patient for almost two years is noteworthy, as these tumors are often aggressive. However, it's important to note that:

• Single-patient responses can be outliers
• The lack of a partial response by RECIST criteria suggests tumor shrinkage
• The controlled IFNγ induction without significant increases in other inflammatory cytokines is encouraging for safety

While promising, we need to see consistent responses across more patients and tumor types to fully assess SON-1010's potential impact on solid tumor treatment.

Financial Analyst

From a financial perspective, Sonnet BioTherapeutics' progress with SON-1010 is positive but should be viewed cautiously:

• Completing enrollment is a de-risking event, potentially increasing investor confidence
• The expected topline data in Q4 2024 provides a clear catalyst for the stock
• Early safety data and the stable disease case are encouraging, but not definitive for commercial success
• As a NASDAQ-listed company (SONN), positive trial results could significantly impact stock price

However, investors should consider that many Phase 1 successes don't translate to later-stage trials or commercial viability. The company's cash position and burn rate will be important factors to watch, as further trials and potential commercialization will require substantial funding. Overall, while promising, it's too early to predict SON-1010's market potential or impact on Sonnet's valuation.

SON-1010 is a targeted immune activation cancer therapy designed to turn ‘cold’ tumors ‘hot’

Topline safety data of SB101 Phase 1 study expected by Q4 2024

PRINCETON, NJ, Sept. 18, 2024 (GLOBE NEWSWIRE) -- Sonnet BioTherapeutics Holdings, Inc. (the “Company” or “Sonnet”) (NASDAQ: SONN), a clinical-stage company developing targeted immunotherapeutic drugs, today announced the completion of enrollment and initiation of dosing in its Phase 1 SB101 clinical trial of SON-1010 (IL12-F_HAB) in adult patients with advanced solid tumors. The Company expects to report topline data from this study in Q4 2024.

Pankaj Mohan, Founder and Chief Executive Officer of Sonnet commented, “This milestone is an important step forward in our development program for SON-1010 as a monotherapy. We are encouraged by the data seen to date demonstrating safety and tolerability being well within expected levels. We are hopeful that we will continue to see extended PK/PD, tumor targeting and clinical activity during treatment. We remain committed to bringing this trial to completion and we expect to report topline safety data in Q4 2024.”

SB101 is the Company’s open-label, adaptive-design dose-escalation study to assess the safety, tolerability, and PK/PD of SON-1010 administered to patients with advanced solid tumors. The study enrolled 24 subjects. Primary outcome measures for the study are to evaluate the safety and tolerability of SON-1010 and establish the maximum tolerated dose (MTD) of SON-1010.

SON-1010 is the Company’s proprietary version of recombinant human interleukin-12 (rhIL-12), configured using Sonnet’s Fully Human Albumin Binding (F_HAB^®) platform, which extends the half-life and activity of the IL-12 component due to binding native albumin in the serum and targets the tumor microenvironment (TME) by strongly binding gp60 and Secreted Protein Acidic and Rich in Cysteine (SPARC).

As previously announced, the safety of SON-1010 was reviewed by the Safety Review Committee at each step during dose escalation. The trial uses a ‘desensitizing’ first dose to take advantage of the known tachyphylaxis with rhIL-12, which minimizes toxicity and allows higher maintenance doses. No dose-limiting toxicities have occurred to date. The safety and toxicity profile that has developed is typical for a Phase 1 oncology trial, with the majority of adverse events (AEs) being reported as mild. All have been transient, with no evidence of cytokine release syndrome.

As previously announced, one patient with progressive endometrial sarcoma receiving SON-1010 monotherapy in SB101 had stable disease (SD) for almost 2 years before progressing - her ascites had resolved and tumors had shrunk at one point but she never reached a partial response (PR) by Response Evaluation Criteria in Solid Tumors (RECIST) rules. Cytokine analysis following each dose in that study revealed controlled and prolonged induction of interferon gamma (IFNγ) that peaked at 24 to 48 hours and returned to baseline within 2 to 4 weeks. A small increase in IL-10 was observed with each dose as expected in response to IFNγ. There was either a minimal or no signal for IL-1β, IL-6, IL-8, and TNFα, and there was no indication of any potential for cytokine release syndrome (CRS) at these doses.

For more information about the SB101 Phase 1 trial in adult patients with advanced solid tumors visit www.clinicaltrials.com and reference identifier NCT05352750.

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 was selected to bind albumin both at normal pH, as well as at the acidic pH typically found in the TME. The F_HAB 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 for 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 SB101 Phase 1 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 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, should establish the MTD 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 pharmacokinetics (PK), pharmacodynamics (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 F_HAB 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-F_HAB, 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-F_HAB-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. Sonnet is currently seeking partnership opportunities to support a Phase 2 trial.

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
833-475-8247
SONN@jtcir.com

Source: Sonnet BioTherapeutics Holdings, Inc.
Released September 18, 2024

FAQ

What is the purpose of Sonnet BioTherapeutics' SON-1010 Phase 1 trial?

The SON-1010 Phase 1 trial (SB101) aims to assess the safety, tolerability, and pharmacokinetics/pharmacodynamics of SON-1010 in adult patients with advanced solid tumors, and to establish the maximum tolerated dose.

How many subjects were enrolled in the SON-1010 Phase 1 trial (SONN)?

The Phase 1 SB101 clinical trial of SON-1010 enrolled 24 subjects with advanced solid tumors.

When does Sonnet BioTherapeutics expect to report topline data for the SON-1010 trial?

Sonnet BioTherapeutics (SONN) expects to report topline safety data from the SON-1010 Phase 1 trial in Q4 2024.

What were the key safety findings in the SON-1010 Phase 1 trial so far?

No dose-limiting toxicities have occurred to date in the SON-1010 trial. The majority of adverse events were reported as mild and transient, with no evidence of cytokine release syndrome.

Has SON-1010 shown any clinical activity in the Phase 1 trial (SONN)?

One patient with progressive endometrial sarcoma receiving SON-1010 monotherapy had stable disease for almost 2 years, with resolved ascites and shrinking tumors, but did not reach a partial response by RECIST criteria.