Sonnet BioTherapeutics Reports Encouraging Data from Phase 1b/2a Clinical Trial of SON-080 in Chemotherapy-Induced Peripheral Neuropathy (CIPN) That Support Advancement into Phase 2 Study

Rhea-AI Summary

Sonnet BioTherapeutics (NASDAQ:SONN) reported encouraging data from its Phase 1b/2a clinical trial of SON-080 for Chemotherapy-Induced Peripheral Neuropathy (CIPN). The study showed that SON-080 was well-tolerated at both 20 µg and 60 µg doses, with no evidence of pro-inflammatory cytokine response. Pain and quality of life survey results suggest potential rapid improvement of peripheral neuropathy symptoms and post-dosing durability compared to placebo. Sonnet intends to seek a partnership to initiate a Phase 2 clinical trial of SON-080 in Diabetic Peripheral Neuropathy (DPN), a larger, high-value indication with unmet medical need. The company believes this data bridges the historical safety database and is foundational for advancing SON-080 to Phase 2, evaluating its neuroprotective and neuro-regenerative effects in DPN.

Positive

• SON-080 was well-tolerated at both 20 µg and 60 µg doses in the Phase 1b trial
• Pain and quality of life survey results suggest potential rapid improvement of peripheral neuropathy symptoms
• Data indicates post-dosing durability of effects compared to placebo
• No evidence of pro-inflammatory cytokine response observed
• Company plans to advance to Phase 2 clinical trial for Diabetic Peripheral Neuropathy (DPN)

Negative

• One patient in the low-dose group developed severe fatigue and stopped dosing after one month
• Injection site erythema was the most prominent treatment-related adverse event
• Headache, dizziness, and chills were reported infrequently in the high-dose group
• Company needs to seek partnership to support initiation of Phase 2 clinical trial

Insights

Medical Research Analyst

The recent data from Sonnet BioTherapeutics regarding the Phase 1b/2a clinical trial for SON-080 in Chemotherapy-Induced Peripheral Neuropathy (CIPN) is highly significant. The fact that the treatment was well-tolerated with no pro-inflammatory cytokine response is important for its continued development. Peripheral neuropathy caused by chemotherapy is debilitating and lacks effective treatments. The potential for SON-080 to not only be safe but also improve symptoms is a strong signal for moving into Phase 2 trials. Additionally, the results demonstrated sustainability in symptom improvement post-treatment, aligning with preclinical data showing neuro-regenerative effects of low-dose Interleukin-6 (IL-6).

For retail investors, this indicates a potential breakthrough in a high-need area, which could substantially increase the drug's market value if further trials are successful. The intention to seek a partnership for Phase 2 trials in Diabetic Peripheral Neuropathy (DPN) opens another avenue with significant market potential due to the high prevalence of diabetes-related neuropathy.

Short-term implication: Expect an increase in interest and potential stock price movement as the company prepares for Phase 2.

Long-term implication: Successful Phase 2 trials could position SON-080 as a leading treatment for both CIPN and DPN, dramatically improving its market capitalization.

Financial Analyst

Sonnet BioTherapeutics' announcement of positive Phase 1b results for SON-080 has significant financial implications. Firstly, the safety and tolerability findings de-risk the asset, making it more attractive to potential partners. The company's plan to seek a partnership for further development is a strategic move to share costs and minimize financial risk. Diabetic Peripheral Neuropathy (DPN) presents a larger market opportunity compared to CIPN, due to the higher number of diabetes patients globally. This strategic pivot could lead to increased investor confidence and potentially higher stock valuations as the company advances towards Phase 2.

For investors, this news suggests that Sonnet is on a prudent path towards capitalizing on a high-value market segment while mitigating development risks through partnerships. The potential for rapid market growth in the DPN segment offers a substantial upside.

Short-term implication: Increased investor interest and potential stock price increase due to de-risking and strategic focus on a larger market.

Long-term implication: Successful partnerships and Phase 2 results could lead to significant revenue growth and stock price appreciation over the next few years.

Oncology Doctor

The Phase 1b trial results for SON-080 are promising from a clinical perspective. Chemotherapy-Induced Peripheral Neuropathy (CIPN) is a severe, often chronic side effect that significantly impacts patients' quality of life. The reported safety and tolerability of SON-080, along with its potential to improve pain and quality of life, mark a hopeful advance in CIPN management. The use of low-dose IL-6 to stimulate peripheral nerve growth aligns with current scientific understanding and the durability of symptom improvement hints at a potentially transformative treatment option.

For patients, this means a possible reduction in the debilitating effects of CIPN, allowing them to complete cancer treatments with better tolerability. If the Phase 2 trials confirm these benefits, SON-080 could become a widely adopted therapy, significantly impacting patient care standards.

Short-term implication: Positive trial results increase optimism among clinicians and may influence early adoption if FDA approval is eventually granted.

Long-term implication: Should long-term safety and efficacy be confirmed, SON-080 could set a new treatment standard for CIPN, positively impacting patient outcomes and healthcare practices.

• Data indicates that SON-080 was well-tolerated at both doses, with no evidence of a pro-inflammatory cytokine response
• Pain and quality of life survey results suggest the potential for rapid improvement of peripheral neuropathy symptoms and post-dosing durability with both doses, compared to placebo controls
• Sonnet intends to seek a partnership to support initiation of a Phase 2 clinical trial of SON-080 in Diabetic Peripheral Neuropathy (DPN), a mechanistically synergistic and larger, high-value indication with unmet medical need
• Management highlights data findings in a Virtual Investor “What This Means” segment

PRINCETON, N.J., July 24, 2024 (GLOBE NEWSWIRE) -- Sonnet BioTherapeutics Holdings, Inc. (the “Company” or “Sonnet”) (NASDAQ:SONN), a clinical-stage company developing targeted immunotherapeutic drugs, today announced encouraging data from the Phase 1b portion of its Phase 1b/2a clinical trial evaluating SON-080 for the treatment of CIPN (the “SB211 study”). The SB211 study is a double-blind, randomized, controlled trial of SON-080 conducted at two sites in Australia in patients with persistent CIPN using a new proprietary version of recombinant human Interleukin-6 (rhIL-6) that builds upon previous work with atexakin alfa. The goal of the Phase 1b portion of the SB211 study was to confirm safety and tolerability before continued development in Phase 2. As previously announced in March 2024, a data and safety monitoring board reviewed the unblinded safety and tolerability of SON-080 in the first nine patients and concluded that the symptoms were tolerable in the initial patients and the study could proceed to Phase 2. Additionally, the Company participated in a Virtual Investor “What This Means” segment to further discuss the Phase 1b data and highlight what this means for its development program moving forward. Click here to access the segment.

CIPN is a common side effect of many chemotherapeutic drugs that induce peripheral nerve damage. CIPN can last for weeks to years after treatment has ended and patients with CIPN often experience discomfort that can result in persistent, unbearable pain, as well as motor and autonomic dysfunction that may limit the duration of their cancer treatment. Conventional pain medications and opioids are often ineffective against peripheral neuropathy, creating a significant unmet need for new treatment options. Low dose IL-6 has been shown to stimulate peripheral nerve growth in preclinical models, thereby ameliorating motor and sensory functions and normalizing the associated pain or sensation disturbance of neuropathy.

“We believe this highly encouraging data bridges the large atexakin alfa historical safety database in cancer patients and is foundational in advancing the development of SON-080 to a Phase 2 study evaluating the neuroprotective and neuro-regenerative effects in DPN,” said Pankaj Mohan, Ph.D., Sonnet Founder and Chief Executive Officer. “IL-6 is often dysregulated in diabetic patients, suggesting there is disease modifying potential for the application of rhIL-6 in DPN. Given the high prevalence of neuropathy in diabetes and the commensurate industry interest in this market, we have prioritized DPN as the best potential indication for Phase 2 development. We intend to seek a partnership to move the asset forward towards commercialization."

A total of 9 patients were randomized between two different SON-080 dose groups and placebo in this portion of the study. The treatment period was 12 weeks long and patients were followed-up for an additional 12 weeks.

The Phase 1b data demonstrated SON-080 was well-tolerated at both 20 µg and 60 µg/dose, which was about 10-fold lower than the maximum tolerated dose (MTD) for IL-6 that was established in previous clinical evaluations. Injection site erythema was the most prominent treatment-related adverse event irrespective of the dose of SON-080, and was transient and mild in all but one case at each dose, where it was moderate. Fatigue was reported occasionally and was more prominent at the higher dose. One patient who developed severe fatigue and stopped dosing after one month was in the low-dose group. Headache, dizziness, and chills were reported infrequently in the high-dose group; all were mild apart from a single moderate event with each symptom. All other adverse events were infrequent and mild.

"These data suggest possible benefits in humans with various types of peripheral neuropathy due to cancer and diabetes. Interleukin-6 has been extensively studied in cancer patients in the past, so the use of SON-080 in CIPN was expected to provide a similar adverse event profile at low doses," commented Richard Kenney, M.D., Sonnet's Chief Medical Officer. "We now have a further understanding of the adverse event profile and the opportunity to look at preliminary efficacy trends. We look forward to initiating a Phase 2 study with a partner in the much larger DPN indication."

The Quality-of-Life Questionnaire-CIPN twenty-item scale (QLQ-CIPN20), a validated survey designed to assess cancer patients’ experience of symptoms and functional limitations related to CIPN, was used as the primary indicator of response. While the number of patients in each group was small, a trend toward improved scores within a month of starting therapy was seen for both dose groups as compared to placebo in the overall scores. This greater improvement with SON-080 persisted after the 12 weeks of therapy had stopped, while the placebo group scores returned to baseline. These results are in line with the preclinical model insights with low dose IL-6, although further work with larger clinical groups is needed to substantiate this trend.

Multiple cytokines were studied as part of the safety evaluation. There was no demonstrable drug effect on any of these inflammatory cytokine serum levels during or after therapy with SON-080. However, there was a dose-related increase in serum amyloid alpha that persisted during therapy, which returned to baseline once treatment was stopped. An expert consultant concluded that the degree of amyloid elevation seen in this study for 12 weeks should be benign.

For more information about the SB211 study, visit clinicaltrials.gov and reference identifier NCT05435742.

About SON-080 as a Therapeutic Drug Candidate

SB211 studied a low dose of rhIL-6 called SON-080 that has an amino acid sequence identical to the native molecule. The trial targets serum levels similar to those induced with moderate exercise, which triggers the natural healing of nerves, muscle, and bone. As a pleiotropic cytokine, native IL-6 participates in several physiological processes, including tissue repair, glucose homeostasis, and the innate immune response at lower levels, but it can result in acute pathological inflammation at higher serum levels. Preclinical models of CIPN and DPN show that low dose rhIL-6 has the potential to stimulate nerve regrowth to re-establish normal sensations, thereby reducing pain and normalizing some of the physiological conditions that had deteriorated due to nerve degeneration. Early versions of rhIL-6, including Serono’s atexakin alfa and others, have been tested in hundreds of patients with cancer, diabetes, idiopathic aplastic anemia, and in healthy controls, showing a maximum tolerated dose of 10 µg/kg three times a week (TIW). The IL-6-related fever, nausea, and vomiting that were prominent adverse events at doses over 2.5 µg/kg TIW were substantially reduced at lower doses.

About the SB211 Phase 1b/2a Trial

The SB211 study was primarily designed to evaluate the safety, PK, PD, and initial efficacy of two dose levels of SON-080 compared to placebo. The drug is self-administered subcutaneously three times a week in patients with CIPN lasting at least 3 months after chemotherapy. The study was conducted at multiple sites in Australia, in a blinded fashion, comparing SON-080 to placebo. The primary endpoint explores the safety and tolerability of SON-080, with key secondary endpoints intended to measure PK, PD, and immunogenicity. Preliminary efficacy is being explored using standardized quality of life and pain questionnaires over the course of the trial.

About Sonnet BioTherapeutics Holdings, Inc.

Sonnet BioTherapeutics is an oncology-focused biotechnology company with a proprietary platform for innovating biologic drugs of single or bifunctional action. Known as F_HAB (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 F_HAB 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. F_HAB 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.

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 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, Inc.

FAQ

What were the key findings of Sonnet BioTherapeutics' Phase 1b/2a trial for SON-080 in CIPN?

The trial showed that SON-080 was well-tolerated at both 20 µg and 60 µg doses, with no evidence of pro-inflammatory cytokine response. Pain and quality of life survey results suggested potential rapid improvement of peripheral neuropathy symptoms and post-dosing durability compared to placebo.

What is Sonnet BioTherapeutics' (SONN) next step for SON-080 after the Phase 1b/2a trial?

Sonnet intends to seek a partnership to initiate a Phase 2 clinical trial of SON-080 in Diabetic Peripheral Neuropathy (DPN), which is a larger, high-value indication with unmet medical need.

What were the main adverse events reported in the SON-080 trial for CIPN?

The most prominent treatment-related adverse event was injection site erythema. Fatigue was reported occasionally, more prominently at the higher dose. Headache, dizziness, and chills were reported infrequently in the high-dose group.

How did SON-080 perform in the Quality-of-Life Questionnaire-CIPN twenty-item scale (QLQ-CIPN20)?

While the patient groups were small, a trend toward improved scores within a month of starting therapy was seen for both dose groups compared to placebo. This improvement persisted after the 12 weeks of therapy had stopped, while placebo group scores returned to baseline.