Endometrial Stromal Sarcoma

KIRKLAND, QC, and MISSISSAUGA, ON, Dec. 21, 2023 /CNW/ - Merck (NYSE: MRK), known as MSD outside the United States and Canada, and Eisai announce that KEYTRUDA®, Merck's anti-PD-1 therapy, plus LENVIMA®, an orally available multiple receptor tyrosine kinase inhibitor discovered by Eisai, is now reimbursed with clinical criteria and conditions under the British Columbia, Alberta, Saskatchewan, Ontario, Quebec, Nova Scotia, New Brunswick, and Newfoundland drug plans, for adult patients with advanced endometrial carcinoma (EC) that is not microsatellite instability high (MSI-H) or mismatch repair deficient (dMMR), who have disease progression following prior platinum-based systemic therapy, and are not candidates for curative surgery or radiation. This announcement follows the notice of compliance issuance from Health Canada in July 2023 based on the results from the Phase 3 Study 309/KEYNOTE-775 trial, which evaluated KEYTRUDA® plus LENVIMA® versus chemotherapy (treatment of physician's choice of doxorubicin or paclitaxel) in patients with advanced endometrial carcinoma who had been previously treated with at least one prior platinum-based chemotherapy regimen in any setting. KEYTRUDA® plus LENVIMA® demonstrated statistically significant improvements in the dual primary endpoints of overall survival (OS) and progression-free-survival (PFS) compared to chemotherapy. "Each patient's journey is unique, and this particular indication addresses an important care gap as it targets individuals that are diagnosed in a late stage setting with limited treatment options," says Dr. Amit Oza, Head of the Division of Medical Oncology & Hematology, Professor of Medicine, University of Toronto, and Medical Director of the Cancer Clinical Research Unit at Princess Margaret Cancer Centre. "By having an additional therapeutic option in our toolbox, we are better able to tailor treatment plans according to individual needs, which can help improve health outcomes." These most recent developments are a result of the strategic collaboration between Merck and Eisai, whose collective mission is to help bring greater access to innovative medicines for patients in need. "Endometrial cancer is a serious and potentially life-threatening condition affecting many Canadians," says Patrick Forsythe, Country Manager, Eisai Canada. "We commend Health Canada and the health technology assessment organizations for supporting the approval and availability of KEYTRUDA® plus LENVIMA® to provide an additional treatment option in an area of oncology where cases are rising in this country." "This achievement is a result of the relentless work of our researchers and physicians, as well as the commitment of the patients who enroll in these clinical trials," says André Galarneau, Executive Director & Vice President, Oncology Business Unit at Merck Canada. "It is thanks to them that we can provide more treatment options to Canadians impacted by this disease." About STUDY 309/KEYNOTE-775 Study 309/KEYNOTE-775 is a Phase 3 multicenter, open-label, randomized, active-controlled trial that enrolled 827 patients with advanced EC previously treated with at least one prior platinum-based chemotherapy regimen in any setting, including in the neoadjuvant and adjuvant settings. The study excluded certain patients such as those with endometrial sarcoma, including carcinosarcoma, or patients who had active autoimmune disease or a medical condition that required immunosuppression. The primary efficacy outcome measures were OS and PFS as assessed by blinded independent central review (BICR) according to Response Evaluation Criteria in Solid Tumors Version (RECIST) v1.1. Secondary efficacy outcome measures included ORR as assessed by BICR. There were 697 patients with advanced EC that was not MSI-H or dMMR that were randomized 1:1 to receive pembrolizumab (200 mg intravenously every three weeks) plus lenvatinib (20 mg orally once daily or n=346 ) or investigator's choice, consisting of either doxorubicin (60 mg/m2 every three weeks; n=254) or paclitaxel (80 mg/m2 given weekly, three weeks on/one week off; n=97). Treatment with pembrolizumab plus lenvatinib continued until RECIST v1.1-defined progression of disease as verified by BICR, unacceptable toxicity, or for pembrolizumab, a maximum of 24 months or up to 35 administrations - whichever was longer. Administration of pembrolizumab plus lenvatinib was permitted beyond RECIST-defined disease progression if the treating investigator considered the patient to be deriving clinical benefit and the treatment was. The most common adverse events (reported in at least 30% of patients) among these patients receiving pembrolizumab and lenvatinib were hypothyroidism, hypertension, fatigue, diarrhea, musculoskeletal disorders, nausea, decreased appetite, vomiting, stomatitis, abdominal pain, weight loss, and urinary tract infection. About Endometrial Carcinoma Endometrial carcinoma (endometrial cancer) begins in the inner lining of the uterus, and makes up more than 95% of all uterine cancer cases. In 2023, an estimated 8,500 Canadian women will be diagnosed with uterine cancer, with a greater tendency to develop in women over the age of 50. Symptoms of endometrial cancer can include abnormal vaginal bleeding, pain during intercourse, difficult or painful urination and pain in the pelvic area. About KEYTRUDA® (pembrolizumab) KEYTRUDA® is an anti-PD-1 therapy that works by helping increase the ability of the body's immune system to help detect and fight tumour cells. KEYTRUDA® is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes which may affect both tumour cells and healthy cells. KEYTRUDA® was first approved in Canada in 2015 and currently has indications in several disease areas, including advanced renal cell carcinoma, bladder cancer, non-small cell lung carcinoma, primary mediastinal B-cell lymphoma, classical Hodgkin lymphoma, colorectal cancer, endometrial carcinoma, esophageal cancer, triple-negative breast cancer, melanoma, and head and neck squamous cell carcinoma. About LENVIMA® (lenvatinib) LENVIMA®, discovered and developed by Eisai, is an orally available multiple receptor tyrosine kinase inhibitor that selectively inhibits the kinase activities of vascular endothelial growth factor (VEGF) receptors VEGFR1 (FLT1), VEGFR2 (KDR), and VEGFR3 (FLT4). LENVIMA® inhibits other kinases that have been implicated in pathogenic angiogenesis, tumor growth, and cancer progression in addition to their normal cellular functions, including fibroblast growth factor (FGF) receptors FGFR1-4, the platelet derived growth factor receptor alpha (PDGFRα), KIT, and RET. In syngeneic mouse tumor models, LENVIMA® decreased tumor-associated macrophages, increased activated cytotoxic T cells, and demonstrated greater antitumor activity in combination with an anti-PD-1 monoclonal antibody compared to either treatment alone. About Merck At Merck, known as MSD outside of the United States and Canada, we are unified around our purpose: We use the power of leading-edge science to save and improve lives around the world. For more than 130 years, we have brought hope to humanity through the development of important medicines and vaccines. We aspire to be the premier research-intensive biopharmaceutical company in the world – and today, we are at the forefront of research to deliver innovative health solutions that advance the prevention and treatment of diseases in people and animals. We foster a diverse and inclusive global workforce and operate responsibly every day to enable a safe, sustainable, and healthy future for all people and communities. For more information about our operations in Canada, visit and connect with us on LinkedIn and X @MerckCanada. About Eisai Eisai's Corporate Concept is "to give first thought to patients and the people in the daily living domain, and to increase the benefits that healthcare provides." Under this Concept [also known as our human health care (hhc) Concept], we aim to effectively achieve social good in the form of relieving anxiety over health and reducing health disparities. With a global network of R&D facilities, manufacturing sites and marketing subsidiaries, we strive to create and deliver innovative products to target diseases with high unmet medical needs, with a particular focus in our strategic areas of Neurology and Oncology. In addition, our continued commitment to the elimination of neglected tropical diseases (NTDs), which is a target (3.3) of the United Nations Sustainable Development Goals (SDGs), is demonstrated by our work on various activities together with global partners. For more information about Eisai, please visit (for global headquarters: Eisai Co., Ltd.), us.eisai.com (for U.S. headquarters: Eisai Inc.) or (for Europe, Middle East, Africa, Russia, Australia, and New Zealand headquarters: Eisai Europe Ltd.), and connect with us on X, formerly known as Twitter (for U.S. and global), and LinkedIn (for U.S. and EMEA). Forward-Looking Statement of Merck & Co., Inc., Rahway, N.J., USA This news release of Merck & Co., Inc., Rahway, N.J., USA (the "company") includes "forward-looking statements" within the meaning of the safe harbor provisions of the U.S. Private Securities Litigation Reform Act of 1995. These statements are based upon the current beliefs and expectations of the company's management and are subject to significant risks and uncertainties. There can be no guarantees with respect to pipeline candidates that the candidates will receive the necessary regulatory approvals or that they will prove to be commercially successful. If underlying assumptions prove inaccurate or risks or uncertainties materialize, actual results may differ materially from those set forth in the forward-looking statements. Risks and uncertainties include but are not limited to, general industry conditions and competition; general economic factors, including interest rate and currency exchange rate fluctuations; the impact of the global outbreak of novel coronavirus disease (COVID-19); the impact of pharmaceutical industry regulation and health care legislation in the United States and internationally; global trends toward health care cost containment; technological advances, new products and patents attained by competitors; challenges inherent in new product development, including obtaining regulatory approval; the company's ability to accurately predict future market conditions; manufacturing difficulties or delays; financial instability of international economies and sovereign risk; dependence on the effectiveness of the company's patents and other protections for innovative products; and the exposure to litigation, including patent litigation, and/or regulatory actions. The company undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise. Additional factors that could cause results to differ materially from those described in the forward-looking statements can be found in the company's Annual Report on Form 10-K for the year ended December 31, 2022 and the company's other filings with the Securities and Exchange Commission (SEC) available at the SEC's Internet site ( ). Please see the product monograph for KEYTRUDA® (pembrolizumab) at: Please see the product monograph for LENVIMA® (lenvatinib) at: Media Inquiries: Merck: Mediacanada@merck.com / Eisai: Michele Randazzo, (551) 427-6722, Michele_Randazzo@eisai.com Investor Contacts: Merck: Peter Dannenbaum, (732) 594-1579; Damini Chokshi, (732) 594-1577 / Eisai Co., Ltd., Investor Relations: +81-(0) 3-3817-5122 SOURCE Merck Canada Inc. Company Codes: NYSE:MRK

PRINCETON, NJ / ACCESSWIRE / December 14, 2023 / Sonnet BioTherapeutics Holdings, Inc. (NASDAQ:SONN) ("Sonnet" or the "Company"), a biopharmaceutical company developing innovative targeted biologic drugs focused on oncology, announced today its financial results for the fiscal year ended September 30th, 2023 and provided a business update. "Sonnet has had a very productive year, exemplified by important achievements across our pipeline. The successful completion of the Phase 1 SB102 study with SON-1010 in healthy volunteers, combined with the initial data reported from the Phase 1 SB101 study in cancer patients propelled us forward into receiving FDA Investigational New Drug (IND) acceptance for the Phase 1b/2a SB221 combination study of SON-1010 with Roche's atezolizumab, in platinum-resistant ovarian cancer (PROC)," commented Pankaj Mohan, Ph.D., Founder and CEO. "Our efforts to advance our pipeline continue and are accompanied by Janssen's ongoing evaluation of SON-1010, SON-1210 and SON-1410 in combination with certain proprietary cell therapy assets. We are also working diligently to complete enrollment of the first portion of the Phase 1b SB211 study of SON-080 in chemotherapy-induced peripheral neuropathy (CIPN), with the hope of having early safety data available during the first quarter of 2024. We also expect to be able to share safety data from the SB102 and SB221 studies of SON-1010 during the first half of the year. In all, 2024 should be another exciting year for the company." Fiscal Year 2023 and Recent Corporate Updates Announced Collaboration Agreement with Roche: On January 9, 2023, Sonnet announced a collaboration agreement with Roche for the clinical evaluation of SON-1010 with atezolizumab. The companies have entered into a Master Clinical Trial and Supply Agreement (MCSA), along with ancillary Quality and Safety Agreements, to study the safety and efficacy of the combination of SON-1010 and atezolizumab in a platinum-resistant ovarian cancer (PROC) patient setting. Further, the companies will provide SON-1010 and atezolizumab, respectively, for use in the Phase 1b/Phase 2a combination safety, dose-escalation, and efficacy study (SB221). On August 16, Sonnet announced that the FDA accepted the Investigational New Drug application (IND) for the use of SON-1010 in ovarian cancer, authorizing the companies to move forward with the SB221 trial. Sonnet is pleased to provide the following updates on its pipeline assets: SON-1010 (IL12-FHAB): In January 2023, Sonnet announced data from SB102, a single-ascending dose (SAD) Phase 1 clinical trial designed to carefully study the pharmacokinetics (PK) and pharmacodynamics (PD) of SON-1010 in preparation for combination studies. Typical dose-related increases were seen with SON-1010 in the serum after subcutaneous (SC) administration. Drug levels peaked at about 11 hours and the mean elimination half-life (t½) after the 150 ng/kg dose of SON-1010 was 112 hours, compared to 12 hours for rhIL-12 given SC, as reported in the literature. In April, Sonnet presented additional data from the SB101 study of SON-1010 at the 2023 AACR Annual Meeting. SB101 is a SAD trial in adult patients with advanced solid tumors that commenced in the second quarter of 2022 and is currently enrolling the final dose cohort. Of the 15 patients from SB101 who were evaluable for follow-up at this latest cutoff, 9 had stable disease at the first follow-up scan, 4 of which were already progressing at study entry. At the four-month follow-up, 5 of 14 patients remained stable at the second scan, suggesting clinical benefit of SON-1010 in 36% of patients. As an example, the first patient dosed, who has an aggressive endometrial sarcoma, had target tumor shrinkage with complete resolution of ascites at one point and has been clinically stable for over a year. SON-1010 has been safe and tolerable at all doses tested to date. Adverse events have generally been mild/moderate and transient in nature, with no study discontinuations for safety reasons. In addition, adverse effects have been less numerous and less intense with subsequent doses. Comparison of the PK curves between the two studies suggests that SON-1010 may be targeting tumors, as it was designed to do. Cytokine analysis following each dose revealed controlled and prolonged induction of interferon gamma (IFNγ) that peaked at 24 to 48 hours and returned to baseline after 2 to 4 weeks, which may improve tumor control. A small increase in IL-10 was observed with each dose, as might be expected in response to IFNγ. There was either a minimal or no signal for IL-1β, IL-6, IL-8, and TNFα and no indication of any potential for cytokine release syndrome (CRS) at these doses. Safety data from final dose escalation in the SB101 study are expected during the first half of 2024. Following FDA acceptance of the IND in August, Sonnet launched the SB221 study with several patients currently being dosed. This trial consists of a modified 3+3 dose-escalation design in Part 1 to establish the maximum tolerated dose (MTD) of SON-1010 with a fixed dose of atezolizumab. Clinical benefit in PROC will be confirmed in an expansion group to establish the recommended Phase 2 dose. Part 2 of the study will then investigate SON-1010 monotherapy, its use in combination with atezolizumab, or the standard of care (SOC) for PROC in a randomized comparison to show proof-of-concept (POC). Initial safety data from Part 1 of the SB221 study are expected during the first half of 2024. In September 2023, Sonnet announced the completion of two independent in vivo proof-of-concept (POC) studies to show the biodistribution of interleukin-FHAB molecules to the tumor microenvironment (TME), using labs with expertise in radiolabeling biologics and in vivo biodistribution analysis. The labs employed different radiolabeling methodologies (99mTc or 89Zr) for mIL-12 and mIL12-FHAB. The two studies were completed using the B16F10 mouse melanoma model to measure the accumulation of radiolabeled product and tumor volume inhibition over various time points. Both studies indicated that mIL12-FHAB had significantly higher tumor accumulation, 2.5-4.7 times higher on average at the longer time points, and increased retention when compared to mIL-12. Accumulation was demonstrated in tumors compared to normal mice, and was transient in liver, kidney, and other organs, as expected. Importantly, radiolabeled mIL12- FHAB also demonstrated measurable accumulation in the draining lymph nodes. Overall, these findings have important implications for therapeutic applications of any mono-(ILx-FHAB) or bi-functional (ILx-FHAB -ILy) molecules demonstrating enhanced tumor targeting and accumulation, as well as the potential for improved efficacy that could lead to a variety of drug candidates. SON-1210 (IL12-FHAB-IL15): In February 2023, Sonnet announced data from two successfully completed IND-enabling toxicology studies with SON-1210 in non-human primates. The compound elicited no serious adverse events in repeat, subcutaneous dosing and was well-tolerated using dosing levels at least 50x higher than the highest anticipated human clinical dose level. Sonnet is prepared to initiate the regulatory authorization process for SON-1210, pending the outcome of any partnering activity. SON-1410 (IL18-FHAB-IL12): Cell line development and process development are ongoing, with early experimental drug supply suitable for formulation and analytical method development activities. After some delays in 2023, activities will continue into 2024 with the potential to generate a drug suitable for preclinical studies and subsequent human studies. SON-080 (low-dose IL-6): Enrollment of the first portion of the SB211 study in CIPN is nearing completion, which should position the DSMB to complete its review of the preliminary safety data during the first calendar quarter of 2024. John Cini, Ph.D., Sonnet's CSO and Co-founder commented on the fiscal year's R&D accomplishments, saying, "The biodistribution data we announced in September further confirmed the ability of the FHAB technology to extend therapeutic half-life and potentiate tumor targeting, which, combined with the clinical data we presented at AACR in April, position the platform as a differentiated approach for developing next-generation, cytokine-based oncologic drugs. We are excited about the opportunity to continue to highlight our pipeline assets at upcoming medical conferences and through the publication of peer-reviewed articles that elucidate our findings." Financings Completed: On February 10, 2023, we closed a public offering of common stock and certain warrants for net proceeds of $13.6 million through the issuance and sale of 530,222 shares of our common stock and, to certain investors, pre-funded warrants to purchase 101,090 shares of common stock, and accompanying common warrants to purchase up to an aggregate of 1,262,618 shares of our common stock. The public offering price of each share of common stock (or pre-funded warrant in lieu thereof) and accompanying common warrant was $23.76. On June 30, 2023, we closed a registered direct offering of common stock (and common stock equivalents in lieu thereof) and a concurrent private placement of certain common stock warrants for net proceeds of $1.9 million through the issuance and sale of 166,363 shares of our common stock and, to certain investors, pre-funded warrants to purchase 60,909 shares of common stock, and accompanying common warrants to purchase up to an aggregate of 227,272 shares of our common stock. The offering price of each share of common stock (or pre-funded warrant in lieu thereof) and accompanying common warrant was $9.90. On October 26, 2023, we closed a public offering of common stock and certain warrants for net proceeds of $4.1 million through the issuance and sale of 1,306,250 shares of our common stock and, to certain investors, pre-funded warrants to purchase 1,537,500 shares of common stock and accompanying common warrants to purchase up to an aggregate of 5,687,500 shares of our common stock. The public offering price of each share of common stock (or pre-funded warrant in lieu thereof) and accompanying common warrant was $1.60. Fiscal Year Ended September 30, 2023 Financial Results Jay Cross, CFO, elaborated on Sonnet's performance, saying, "We are very pleased with the progress we made this year in an otherwise challenging environment for small biotechnology companies. We will continue to closely monitor our operating expenses, and we are happy to share the preliminary approval we recently received to sell up to $4.8 million of our New Jersey state net operating losses." As of September 30, 2023, Sonnet had no debt and $2.27 million cash on hand, which excludes net proceeds of $4.1 million from the October financing. Sonnet believes its cash at September 30, 2023, together with the $4.1 million net proceeds from the October financing, will fund its projected operations into March 2024. In addition, Sonnet expects to receive a $0.8 million net cash refund from the research and development tax incentive program in Australia and recently received preliminary approval of its application to sell up to $4.8 million of its New Jersey state net operating losses through the Technology Business Tax Certificate Transfer Program, subject to execution of such sale, which together Sonnet believes will extend the funding of its projected operations into the third calendar quarter of 2024. Research and development expenses were $11.8 million for the year ended September 30, 2023, compared to $21.4 million for the year ended September 30, 2022. The decrease of $9.6 million was primarily due to the establishment of cost savings by transitioning product development activities to cost advantaged locations such as India and Australia, by reducing expenditures on tertiary programs such as SON-3015, which has been placed on a development hold, and suspending antiviral development related to SON-1010, as well as a decrease in share-based compensation expense. General and administrative expenses were $7.1 million for the year ended September 30, 2023, compared to $8.6 million for the year ended September 30, 2022. The decrease of $1.5 million relates primarily to a decrease in share-based compensation, legal and business development expenses, as we are managing expenses for liquidity purposes and are tightening our focus on the research and development projects we have assessed to have the greatest near-term potential. 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 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 Sonnet BioTherapeutics Holdings, Inc. Consolidated Balance Sheets September 30, 2023 2022 Assets Current assets: Cash and cash equivalents $ 2,274,259 $ 3,052,879 Prepaid expenses and other current assets 1,677,396 1,643,743 Income tax receivable 786,574 717,305 Total current assets 4,738,229 5,413,927 Property and equipment, net 33,366 46,211 Operating lease right-of-use asset 193,689 256,594 Deferred offering costs 49,988 113,280 Other assets 414,206 - Total assets $ 5,429,478 $ 5,830,012 Liabilities and stockholders' deficit Current liabilities: Related party notes $ - $ 748 Accounts payable 2,201,999 4,752,340 Accrued expenses and other current liabilities 3,230,922 3,193,972 Current portion of operating lease liability 73,048 51,328 Deferred income 18,626 166,431 Total current liabilities 5,524,595 8,164,819 Operating lease liability, net of current portion 130,863 203,912 Total liabilities 5,655,458 8,368,731 Commitments and contingencies Stockholders' deficit: Common stock, $0.0001 par value: 125,000,000 shares authorized; 1,750,426 and 251,955 issued and outstanding at September 30, 2023 and 2022, respectively 175 25 Additional paid-in capital 110,017,598 88,872,315 Accumulated deficit (110,243,753 ) (91,411,059 ) Total stockholders' deficit (225,980 ) (2,538,719 ) Total liabilities and stockholders' deficit $ 5,429,478 $ 5,830,012 See 10-K filed today for notes to consolidated financial statements Sonnet BioTherapeutics Holdings, Inc. Consolidated Statements of Operations Years ended September 30, 2023 2022 Collaboration revenue $ 147,805 $ 349,943 Operating expenses: Research and development 11,814,690 21,444,019 General and administrative 7,125,732 8,575,283 Total operating expense 18,940,422 30,019,302 Loss from operations (18,792,617 ) (29,669,359 ) Foreign exchange loss (40,077 ) (52,482 ) Net loss $ (18,832,694 ) $ (29,721,841 ) Per share information: Net loss per share, basic and diluted $ (18.14 ) $ (150.52 ) Weighted average shares outstanding, basic and diluted $ 1,038,188 $ 197,462 See 10-K filed today for notes to consolidated financial statements SOURCE: Sonnet BioTherapeutics Holdings, Inc. View the original press release on accesswire.com

Demonstrated that P2B001 provides benefits comparable with commercially used doses of marketed pramipexole-ER (PramiER) while minimizing associated daytime sleep–related and dopaminergic side effects associated P2B001 provided superior efficacy on motor symptoms and activities of daily living, compared to each of its individual components The convenient dosing of P2B001, as a no-titration, once-daily single pill, may be a valuable option for patients, neurologists, and particularly non-specialists who are often the only physicians treating PD patients REHOVOT, Israel, Nov. 09, 2023 (GLOBE NEWSWIRE) -- Pharma Two B Ltd., a private, late-stage pharmaceutical company, today announced that data from a Phase 3 study evaluating P2B001, a fixed, low-dose extended-release (ER) combination of pramipexole 0.6 mg and rasagiline 0.75 mg, were published in Movement Disorders. Results from the international, multicenter, randomized, double-blind parallel-group study evaluated the safety and efficacy of P2B001 in patients with early Parkinson’s disease compared to its components and to commercial doses of the dopamine agonist pramipexole (mean 3.2 mg per day). The study included 544 untreated patients with Parkinson’s disease who were randomized (2:2:2:1) to treatment with P2B001, its individual components (pramipexole-ER 0.6 mg or rasagiline-ER 0.75 mg), or marketed PramiER individually titrated to optimal dose (1.5-4.5 mg). “The present study demonstrates that each component contributes to the benefits of P2B001, and that it provides benefits comparable to commercially used doses of Pramipexole ER but with a reduced frequency of sleep-related and dopaminergic adverse events," said C. Warren Olanow, M.D., FRCPC, Chairman Emeritus of the Department of Neurology and Professor Emeritus in the Department of Neuroscience at the Mount Sinai School of Medicine in New York City. Further, he stated that “P2B001 is a once-a-day treatment that requires no titration. As such, if approved, P2B001 represents an important consideration for initiating treatment in patients with early PD.” “P2B001 represents a novel and easy-to-use therapeutic approach, as there has been a clear unmet need for a once-daily treatment that has demonstrable efficacy and safety, requires no titration and has a lower incidence of excessive daytime sleepiness, a commonly reported side effect among people with PD, often caused by dopamine agonist treatment,1-3” said Robert Hauser, M.D., M.B.A., Director, Parkinson’s Disease & Movement Disorders Center, University of South Florida. The primary endpoint was change from baseline to week 12 in Unified Parkinson’s Disease Rating Scale (UPDRS) parts II and III comparing P2B001 to its individual components. The key secondary endpoint was the change from baseline to week 12 in the Epworth Sleepiness Scale (ESS) for P2B001 versus the titrated dose of commercially available PramiER. The change from baseline in total UPDRS (primary endpoint) showed that P2B001 was significantly superior to each of its individual components demonstrating that each contributed to the P2B001 benefit. Least squares mean (LSM) (standard error) treatment difference between P2B001 and pramipexole ER (PPX-ER 0.6 mg) was –2.66 ± 0.85 points (p = 0.0018), and between P2B001 and rasagiline ER (RAS-ER 0.75 mg) was –3.30 + 0.85 points (p = 0.0001). The change from baseline to week 12 in total UPDRS score between P2B001 and PramiER (individually titrated to optimal dose; mean, 3.2 mg/day) was not significantly different (–8.35 ± 0.86 vs. 7.98 ± 0.60; p = 0.7197). Analysis of the key secondary endpoint (change from baseline to week 12 in the ESS score) demonstrated no worsening in the sleepiness scale with P2B001 treatment, whereas optimized doses of PramiER (mean dose, 3.2 mg) caused significant worsening in ESS. LSM difference between groups was –2.66 ± 0.43 (p < 0.0001). P2B001 was generally well tolerated and showed fewer sleep-related and dopaminergic adverse events in comparison to commercially used doses of pramipexole ER. "We are grateful to the patients, families and clinicians who have contributed to this study as we look to deliver a new, convenient treatment option for patients with early Parkinson’s disease,” said Dan Teleman, CEO of Pharma Two B. “We look forward to moving P2B001 forward towards an NDA submission to make this potential treatment option available to patients.” About P2B001 P2B001 is an investigational, novel, fixed-dose, extended-release combination of pramipexole and rasagiline (0.6 mg/0.75 mg), both at low doses that are not commercially available. Marketed pramipexole and rasagiline are currently indicated for the treatment of Parkinson’s disease (as monotherapy and adjunct therapy for early and more advanced patients). P2B001 is being developed for potential use as a first-line therapy for people with Parkinson’s disease. Extended release rasagiline is a new and proprietary formulation of rasagiline developed by Pharma Two B. Pharma Two B owns worldwide-granted patents for both pharmaceutical composition and method of treatment with P2B001, which are expected to remain in effect until January 2033. About Pharma Two B Pharma Two B is a private, late-stage pharmaceutical company established in 2008 in Rehovot, Israel. Our mission is to improve patients’ quality of life by developing innovative, value-added combination drugs for neurological disorders, with a clear unmet need, that are based on previously approved oral drugs and that may offer meaningful clinical benefits, as well as improved safety and enhanced convenience through easier administration. Our company is led by a highly experienced team in Parkinson’s disease, supported by top-tier scientific and clinical key opinion leaders and backed by a dedicated group of investors. For more information, please visit: . Forward-Looking Statements Some of the statements made herein constitute forward-looking statements. These statements relate to future financial and other performance or anticipated plans and are identified by words such as “will,” “expect,” “could,” “if,” “expected,”” “anticipate,”” look forward,” “believe,” “potential,” “propose” and “continue” or negative variants of such terms. These and similar forward-looking statements discuss the company’s future expectations and plans. The company operates in a very competitive and rapidly changing environment. New risks emerge from time to time. Given these risks and uncertainties, the company cautions against placing undue reliance on these forward-looking statements. These statements are only estimates of future performance. Actual performance or events may not meet such expectations or estimates and may, in fact, differ materially. Although the company believes that the expectations reflected in the forward-looking statements made herein are reasonable, the company cannot and does not guarantee future results, levels of activity, performance or achievements. Moreover, the company does not assume any responsibility for the accuracy and completeness of such forward-looking statements in the future. The company does not plan and, subject to applicable law, undertakes no obligation to update any of the forward-looking statements made herein after the date hereof in order to conform such statements to actual results. Amara AW, Chahine LM, Caspell-Garcia C, et al. Longitudinal assessment of excessive daytime sleepiness in early Parkinson’s disease. JNeurol Neurosurg Psychiatry. 2017;88(8):653-662. doi:10.1136/jnnp-2016-31502 Suzuki K. Current update on clinically relevant sleep issues in Parkinson’s disease: a narrative review. J Parkinsons Dis. 2021;11(3):971-992. doi: 10.3233/JPD-202425 Avorn J, Schneeweiss S, Sudarsky LR, et al. Sudden uncontrollable somnolence and medication use in Parkinson disease. Arch Neurol. 2005;62(8):1242-1248. doi: 10.1001/archneur.62.8.1242 CONTACT INFORMATION Dan Teleman CEO Pharma Two B Ltd. Cell + 972-54-550-0804 Email: dan@pharma2b.com U.S. media contact: Cali Mangel Director Cell: 215-694-1577 Email: Cali.Mangel@calciumco.com