SPARC

The SON-1010 studies have together enrolled 61 subjects, to date, as dose escalation continues in SB101 and SB221 at higher levels Patients have received up to 25 cycles of SON-1010 as monotherapy and 10 cycles of SON-1010 with atezolizumab (Tecentriq®) without dose-limiting toxicity at any dose level Cytokine data reveals about 10-fold extended half-life for SON-1010 compared with rhIL-12 that induces prolonged and controlled IFNγ responses, with no evidence of cytokine release syndrome at any dose Clinical benefit was seen at four months post-initiation of dosing in 35% of evaluable patients (8/23) with advanced solid tumors PRINCETON, NJ / ACCESSWIRE / May 20, 2024 / Sonnet BioTherapeutics Holdings, Inc. (NASDAQ:SONN) (the "Company" or "Sonnet"), a clinical-stage company developing targeted immunotherapeutic drugs, announced today that the safety of SON-1010 dosing has been formally reviewed in both of the current Phase 1 clinical trials and the Company is now increasing the target dose of SON-1010 during dose escalation. SON-1010 is a proprietary version of recombinant human interleukin-12 (rhIL-12), configured using Sonnet's Fully Human Albumin Binding (FHAB®) 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). SB101 is a Phase 1 multiple-ascending dose (MAD) trial in adult patients with advanced solid tumors (NCT05352750) that commenced in Q2 2022 and is currently enrolling the sixth dose cohort. SB221 is a Phase 1b/2a dose-escalation and proof-of-concept study of the combination of SON-1010 with atezolizumab (in collaboration with Genentech, a member of the Roche Group), in a study focused on platinum-resistant ovarian cancer (PROC) (NCT05756907) that started in Q4 2023, now enrolling the fourth dose cohort. In addition, SON-1010 was studied in SB102, which was a Phase 1 single-ascending dose (SAD) trial in healthy volunteers (NCT05408572) that started in Q3 2022; the results were recently published (Kenney, et al, Frontiers in Immunology, 2024). Safety in both of the active cancer trials has been reviewed by their respective Safety Review Committees at each step during dose escalation. Both trials use 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 or related serious adverse events have occurred to date. The safety and toxicity pro 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. Of the 25 cancer patients dosed to date and evaluable for follow-up at this latest cutoff, 15 (60%) had stable disease at their first follow-up scan, 8 of whom were progressing at study entry. At four months follow-up, 8 of 23 evaluable patients remained stable at the second CT scan, suggesting clinical benefit of SON-1010 in 35% of the patients. "We have now dosed 18 cancer patients at increasing SON-1010 drug levels in the SB101 study, completed dosing in 31 healthy volunteers in SB102, and are rapidly filling the dose-escalation cohorts with 12 subjects enrolled in the first four cohorts of the SB221 combination study," said Richard Kenney, M.D., Sonnet's Chief Medical Officer. "The overall safety and toxicity pro SON-1010, primarily including local reactions, headache, myalgia, and fatigue, mimics the published experience with rhIL-12, which prompted us to raise the target dose to enhance potential efficacy. The SB102 study allowed us to generate clean data for the pharmacokinetic (PK) and pharmacodynamic (PD) analyses, enabling simulation of the effect of multiple doses with the help of a continual reassessment model of PK and PD. This modeling suggests target-mediated drug disposition (TMDD), which supports the mechanism of the FHAB being directed to tumor tissue. The combination of SON-1010 with atezolizumab may benefit from the ability of IL-12 to turn ‘cold' tumors ‘hot', which upregulates the amount of PD-L1 in the TME." 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. One patient in Part 1 of SB221 with uterine sarcomas received 8 cycles of the SON-1010/atezolizumab combination therapy every 3 weeks before progressing; another two have received 8 and 10 cycles, respectively, and are continuing on the study. The stable AE profiles despite dose escalation led us to reevaluate the target dose, so the Company has added groups in both studies to evaluate 1200 ng/kg SON-1010 as a maintenance dose (the molar equivalent of 800 ng/kg rhIL-12). Finally, Part 2 of the SB221 combination study has been trimmed to remove the monotherapy arm. "The findings to date in these two trials represent significant progress for the SON-1010 molecule", said Robert Wenham, M.D., Chair, Department of GYN Oncology at Moffitt Cancer Center and the Lead Principal Investigator for SB221. "Multiple strategies to present IL-12 safely have been tried over the past two decades with little evidence of improved tolerability in humans, yet the preclinical models continue to suggest that induction of IFNγ in the TME can activate an effective anti-tumor response. This also results in the local induction of PD-L1. Adding a cohort to increase the target MTD of SON-1010, an extended PK molecule that is concentrated in the TME, is the right approach at this stage. This will provide a chance to study the safety of SON-1010 monotherapy in SB101, and then in combination with atezolizumab in SB221, along with the clinical effect of the combination on PROC in a limited set of subjects in the expansion cohort later this year. Defining the best dose for SON-1010 is required to allow a direct randomized comparison of the strategy with the standard of care therapy in Part 2." "We are very pleased with the data we are seeing at these higher dose levels of SON-1010, with safety and tolerability being well within expected levels, as well as displaying SON-1010 extended PK/PD, tumor targeting, and clinical activity during treatment," said Pankaj Mohan, Ph.D., Sonnet Founder and Chief Executive Officer. "Research on rhIL-12 in humans has been hindered by toxicity for decades. We believe that the IL-12 component in SON-1010 is presented in a way that is safer, due to the longer half-life, and it is concentrated in the tumor, due to the recurrent binding of the FHAB-associated albumin to SPARC in the TME. It is important to note that many of these patients have been fighting their cancers for a very long time and have exhausted all approved treatment regimens available to them, so seeing tumor shrinkage at any dose is both difficult to achieve and encouraging for future results. We are excited to continue testing the impact of SON-1010 in combination with atezolizumab at these higher dose levels in patients with PROC, who represent a significant unmet medical need, and we expect to have a further update early next year." 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 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 pro not only IL-12, but a variety of potent immunomodulators that can be added 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 will be 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 and the recommended Phase 2 dose (RP2D) using monthly subcutaneous injections of SON-1010. 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 FHAB platform. About the SB221 Phase 1b/2a Trial SB221 is a global Phase 1b/2a multicenter, dose-escalation and randomized proof-of-concept study to assess the safety, tolerability, PK, PD, and efficacy of SON-1010 administered subcutaneously (SC), either alone or in combination with atezolizumab given intravenously (IV). The study is designed in Part 1 to rapidly establish the maximum tolerated dose (MTD) of the combination in patients with advanced solid tumors at the lower dose levels. The focus shifts to PROC at higher dose levels using small dose-escalation groups with expansion of the dataset at the recommended Phase 2 dose (RP2D). This would be followed in Part 2 by an assessment in patients with PROC of the potential for improved efficacy of the combination versus the standard of care. Both companies look forward to this collaboration as an opportunity to improve outcomes for patients with ovarian cancer. 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 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 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. Tecentriq® (atezolizumab) is a registered trademark of Genentech, a member of the Roche Group. 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 the Company's 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. Sonnet BioTherapeutics Investor Contact Jack Yauch Solebury Strategic Communications 862-754-1024 jyauch@soleburystrat.com SOURCE: Sonnet BioTherapeutics Holdings, Inc. View the original press release on accesswire.com

PRINCETON, NJ / ACCESSWIRE / February 29, 2024 / Sonnet BioTherapeutics Holdings, Inc., (NASDAQ:SONN) a clinical-stage company developing targeted immunotherapeutic drugs for cancer, announced today the publication of clinical data on SON-1010 in Frontiers in Immunology. SON-1010, Sonnet's lead proprietary monofunctional compound, combines the company's fully-human albumin-binding (FHAB) construct with single-chain interleukin 12 (IL‑12). The paper, entitled "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", demonstrated safety and tolerability up to 300 ng/kg as a single ascending dose. In the B16F10 melanoma model, a single dose of SON-1010 results in a marked reduction of tumor growth that was concomitant with increased IFNg, along with augmented immune cell numbers and activity in the tumor microenvironment (TME). The study of SON‑1010 in healthy volunteers, called SB102 (NCT05408572), was first announced in July 2022 and was done in parallel with the ongoing SB101 study in cancer patients (NCT05352750). The results from SB102 provide the initial ‘desensitizing dose' for further dose escalation of the maintenance dose in SB101, to establish the maximum tolerated dose for this molecule. "The publication of these data is an important milestone for Sonnet that provides additional scientific validation of our FHAB technology." said Pankaj Mohan, Ph.D., Founder and CEO of Sonnet. "The SB102 study was designed to elucidate the PK and PD of SON-1010 in normal, healthy volunteers, and shows that the drug is safe in the dose range tested, while also providing an appreciably extended half-life. When combined with checkpoint inhibitors, we hypothesize that the targeted immune enhancing components of the SON-1010 mechanism have the potential to turn cold tumors hot. We also believe that our pipeline, which includes compounds with bifunctional combinations of Interleukins 15 and 18, could potentially prove useful in combination with cell-based therapies. We are diligently pursuing these applications, as well." While doses above 100 ng/kg were tolerated, participants generally experienced more treatment-emergent adverse effects (TEAEs) than those receiving the lowest dose of 50 ng/kg. All TEAEs were transient and were consistent with published experience using recombinant IL‑12. More precise pharmacokinetic (PK) and pharmacodynamic (PD) data can be obtained using this non-genotoxic cancer therapy in healthy individuals, without a background of immunosuppression. PK analysis showed two-compartment elimination in SB102 with a mean half-life of 104 hours, compared with one-compartment elimination in SB101, which correlated with prolonged but controlled and dose-related increases in IFNg. This is evidence for target-mediated drug disposition (TMDD), which implies delivery to and retention of SON-1010 in tumor tissue. There were minimal responses with other cytokines and no evidence of cytokine release syndrome. "IL-12 has been studied in healthy volunteers in the past and has shown great promise in animal models of cancer treatment for decades, yet developmental progress in human trials has typically been hindered by toxicity before the therapeutic dose can be reached." said Richard Kenney, M.D., Sonnet's Chief Medical Officer. "Extending the PK by binding to the neonatal Fc receptor (FcRn), combined with targeting retention in the TME through binding to gp60 and SPARC, contributes to TME localization of SON-1010. This may be the key to enhancing the therapeutic window and inducing successful immune responses in the TME, as the PD will also be extended to allow better activation of immune cell penetration and replacement of immune inhibitors." The manuscript can be accessed through the following link: About SON-1010 SON-1010 is an immunotherapeutic drug candidate that links unmodified single-chain human IL-12 with the albumin-binding domain of the single-chain antibody fragment FHAB. The FHAB single chain was selected to bind well at normal pH, as well as at an acidic pH that is typically found in the tumor microenvironment (TME). The FHAB technology targets tumor and lymphatic tissue, providing a mechanism for dose-sparing, enhanced pK, and an opportunity to improve the safety and efficacy pro IL-12. A variety of other potent immunomodulators can be combined with the platform to orchestrate a robust immune response to many cancers and pathogens. Given the types of proteins induced in the TME, such as Secreted Protein Acidic and Rich in Cysteine (SPARC), several types of cancer such as non-small cell lung cancer, melanoma, colorectal cancer, 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, with the intention of turning ‘cold' tumors ‘hot' by stimulating IFNg, which activates both innate and adaptive immune cells in the TME, as well as increasing the production of Programed Death Ligand 1 (PD-L1) on tumor cells. 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 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 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. Sonnet BioTherapeutics Investor Contact: Jack Yauch Solebury Strategic Communications 862-754-1024 jyauch@soleburystrat.com SOURCE: Sonnet BioTherapeutics, Inc. View the original press release on accesswire.com

CARLSBAD, Calif., Oct. 18, 2023 /PRNewswire/ -- Advanced Biologics (known commercially as Biologica Technologies), a California-based company known for their innovative biologic solutions, announced today their successful merger with Isto Biologics, a global leader in regenerative and autologous therapies. The merger will seamlessly integrate Advanced Biologics' proprietary products into Isto's esteemed and growing portfolio of allografts found within their Influx™ line. "We are thrilled for our entire Advanced Biologics/Biologica team to join forces with Isto Biologics, said Amit Govil, President of Advanced Biologics. "This merger brings together the clinical, commercial, and research-driven expertise of both companies' and a shared commitment to help patients heal faster." Advanced Biologics has maintained a commercial partnership with Isto Biologics since 2020, catalyzed by the development of Isto's Integrative Bone Matrix, SPARC™. SPARC is a novel inductive bone matrix that stemmed from Advanced Biologics' proprietary tissue processing method used in their well-known allograft, OsseoGen®. SPARC is known for its increased levels of osteoinductive, chemotactic, angiogenic and proliferative growth factors. The integration of Advanced Biologics' product commercialization initiatives into Isto's growing allograft portfolio provides a unique opportunity to help patients heal faster and enable both customer bases to benefit from the broadened product set. "Over the past four years, our collaboration with Advanced Biologics has been impressive," said Harry Holiday, Chairman of the Board at Isto Biologics and Managing Director at Thompson Street Capital Partners (TSCP). "Investing in Advanced Biologics and embarking on this strategic combination amplifies both Isto's and Advanced Biologics' comprehensive biologics portfolios, paving a path forward for continued growth and patient healing." "With this merger, our combined team is now elevated with greater clinical expertise and deeper customer support to provide our surgeon champions with the best products available on the market," said Don Brown, CEO of Isto Biologics. About Advanced Biologics/Biologica Technologies Advanced Biologics (ABC) is a 3-time, Orthopedics This Week - New Technology Award winning biologics company focused on developing innovative and clinically relevant biologic solutions across a wide degree of medical specialties. To better serve customers, Advanced Biologics created Biologica Technologies in 2015 as a separate, stand-alone company to serve as the sales, marketing and clinical research group. Advanced Biologics' core proprietary technology offers the ability to access intracellular growth factors (GFs) found within allograft tissue. ProteiOS® growth factor and OsseoGEN® cellular bone matrix are among the first products based on the technology and possess the highest concentration of GFs within their respective biologic categories. The company is privately-held and headquartered in Carlsbad, CA. About Isto Biologics Isto Biologics is a leading biologics and cellular therapy company in the orthopedic space. Isto Biologics is focused on Helping Patients Heal Faster™ through innovative solutions for bone regeneration and cell-based therapies. The company's flagship product offerings include the market-leading Magellan® Autologous Platelet Separator, and bone-growth products including InQu® Bone Graft Extender & Substitute, and the Influx™ product family. For more information, visit istobiologics.com SOURCE Advanced Biologics