PYY

Jay Galeota, CEO and President, Kallyope Over the past year, obesity treatments have become the focus of intense media attention and discussion in healthcare — particularly incretin-based injectable therapies including glucagon-like peptide-1 (GLP-1) agonists such as Wegovy and Zepbound. This attention has highlighted how much more is needed to address the global obesity epidemic: a greater understanding of the disease, a broader focus on the diversity of the patient population, and most of all, the great need for new therapeutic classes that can benefit the many underserved patients living with obesity. As a clinical-stage biotechnology company discovering and developing novel, oral small-molecule therapeutics for diseases with high unmet needs, Kallyope has a major focus on obesity as one of the most significant chronic health conditions currently facing humanity. With estimates that more than one billion people around the world are currently living with obesity, the disease is linked to 3-5 million deaths per year and is now classified as a global epidemic by the World Health Organization. In the United States alone, the prevalence of obesity — defined as an individual with a body mass index (BMI) of 30 kg/m2 or more — has increased significantly since the 1990s, with 41.9 percent of adults and 19.7 percent of children currently considered obese. The health consequences are enormous: obesity is a risk factor for conditions including heart disease, stroke, osteoarthritis and certain types of cancer, and is the leading risk factor for developing Type 2 diabetes mellitus (T2DM), with obese people more than 80 times more likely to develop the disorder than individuals with a BMI of 22 or less. Despite these staggering numbers, it is estimated that only two percent of people with obesity in the United States receive medical treatment with therapeutics, due in part to limitations such as tolerability, cost, supply disruptions, reimbursement, and patient and practitioner resistance to the use of injectables. In this regard, to address this massive unmet need, there is an imperative to identify safe, easy-to-use, well-tolerated oral agents that are effective for weight loss through differentiated mechanisms of action - both as stand-alone medicines and in combination with other drugs. New therapies with the potential to deliver meaningful weight loss and glycemic efficacy will help enable the widespread treatment needed to have a material impact on public health. Kallyope is focused on innovative approaches to developing therapeutics that can address the limitations of current treatments and meet patients’ needs more broadly. The company’s lead clinical development program is focused on obesity and T2DM and is currently in a Phase 2a clinical trial evaluating two therapeutic regimens - K-757 as a monotherapy, and K-757 and K-833 in combination. K-757 and K-833 are drugs known as oral nutrient receptor agonists, which enhance the body’s natural metabolic signals to stimulate the secretion of multiple appetite-suppressing satiety hormones, or incretins. These include GLP-1, and several other well-validated gut hormones capable of regulating appetite and glucose, such as glucose-dependent insulinotropic polypeptide (GIP), cholecystokinin (CCK), Peptide YY (PYY), and oxyntomodulin (OXM), the latter of which is known to increase energy expenditure. The mechanism of action for oral nutrient receptor agonists mimics the increase of the natural appetite-suppressing hormones that is seen after bariatric surgery – leveraging the body’s natural capacity to regulate appetite (vs. synthetic hormones), which is fundamentally different from the GLP-1 agonists now on the market. K-757 and K-833 are the only known oral nutrient receptor agonists being studied for the treatment of obesity, and Kallyope anticipates that this approach will be beneficial for both weight loss and glycemic control and may be easier to take and better tolerated vs. GLP-1s. The Phase 1 clinical program for K-757 and K-833 demonstrated weight loss and established proof of concept as a combination therapy for T2DM. Preclinical data also support the potential for K-757 and K-833 to be used in combination with existing GLP-1 agonists and for weight loss maintenance following GLP-1 agonist treatment. As there is no one-size-fits-all therapeutic approach capable of stopping the obesity epidemic, these results mark an encouraging milestone in treating patients more comprehensively. The population of people living with obesity is highly diverse and only beginning to be understood, and it is essential to have differentiated options available to address patients’ varying needs. Still, there is more that must be done, as this is an epidemic in need of innovative solutions that go well beyond drug discovery. Understanding patient and community risk factors, implementing rigorous screening resources, educating the public and policymakers on the specifics of the condition, and new therapeutic interventions will all be critical in fighting the obesity epidemic. It is vital for physicians, scientists, insurers and the general public to have a better insight into what obesity is and why it is so difficult to manage. One of the greatest challenges in treating obesity is the immense social bias against people who have it, with people thinking of the disease as a “lifestyle choice” that reflects negatively on those living with it, rather than as a chronic disease like diabetes or high blood pressure, where long-term medical management may be appropriate. Beyond the standard recommendation for lifestyle changes, patients are often left with little to no guidance on how to materially address their obesity. It is important to prioritize improved education on obesity for healthcare professionals and convey a sense of urgency in expanding obesity research. Changing our society’s perception of obesity is the key here. If, together as an industry we can accomplish that, we will create an environment receptive to the development and introduction of novel therapeutics in which our efforts to combat this growing epidemic can be most effective. 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K-757 and K-833 are first in a new class of oral agents, known as nutrient receptor agonists, that target the body’s natural physiology to secrete appetite-suppressing hormones NEW YORK--(BUSINESS WIRE)--Kallyope, Inc., a clinical stage biotechnology company discovering and developing novel, oral small-molecule therapeutics for diseases with high unmet need, today announced the initiation of their Phase 2 trial evaluating K-757 and K-833, new oral nutrient receptor agonists being studied for obesity and Type 2 diabetes. The trial, K-757 P006, aims to demonstrate the weight-loss efficacy, safety, and tolerability of these novel agents for patients with obesity, a growing epidemic in the United States. Weight loss can play an important role in helping patients living with obesity to manage serious health consequences including Type 2 diabetes, cardiovascular disease, and high cholesterol. While new therapeutics are now available for the treatment of obesity and diabetes, only two percent of patients with obesity in the U.S. receive medical treatment.1 The availability of effective, easy to use, and well tolerated oral agents will be an important step forward in addressing this unmet need more broadly. “There is a clear and present urgency for oral, easier to use, better tolerated, widely accessible, and low-cost solutions to address the enormous unmet patient need that obesity represents,” said Jay Galeota, president and CEO, Kallyope. “Today, there are many barriers to weight-loss treatment for people with obesity, including high costs, supply disruptions, issues with tolerability of present drugs, and patient and practitioner resistance to the use of injectables. It has been well demonstrated that oral treatments are highly preferred both by patients and physicians. A therapeutic with the potential to deliver meaningful weight loss and glycemic efficacy with GI tolerability, simple titration, lower cost, and improved patient access compared to many available agents will help enable the widespread treatment needed to have material impact on public health. K-757 and K-833 represent a first-in-class oral approach that may greatly enhance treatment options for people affected by obesity and Type 2 diabetes.” “It is critical that we identify novel therapies that are safe, well tolerated, and effective for weight loss, both as stand-alone medicines and to work in combination with other drugs,” said Brett Lauring, M.D., Ph.D., Chief Medical Officer, Kallyope. “The population of people living with obesity is highly diverse and only beginning to be understood, and there is a need for multiple agents in multiple classes in order to address their different needs.” “In a major milestone, the Kallyope team has successfully advanced these first-in-class molecules from discovery to the clinic,” said Nancy Thornberry, founding CEO and chair, Research and Development, Kallyope. “The mechanism of action for K-757 and K-833 is fundamentally different from the GLP-1 agonists now in the market. Research indicates that our approach may mimic the hormone release that occurs with bariatric surgery, which many consider the gold standard for sustainable weight loss. We anticipate that this approach will be beneficial for both weight loss and glycemic control and may be easier to take and to tolerate than GLP-1s.” K-757 and K-833 are new oral nutrient receptor agonists that enhance the body’s natural metabolic signals to stimulate the secretion of multiple appetite-suppressing satiety hormones, including GLP-1, and several other well validated satiety hormones, such as PYY and CCK. This is similar to the effect on these natural appetite-suppressing hormones that is seen after bariatric surgery. They are the only known oral nutrient receptor agonists being studied for the treatment of obesity. About Obesity Obesity is a common, serious, and costly chronic disease of adults and children. Obesity afflicts nearly a billion people around the world and is linked to between 3 and 5 million deaths per year. Traditionally, obesity has been treated with diet and exercise and, more recently, surgery and drugs, yet the global prevalence of obesity has increased markedly in recent decades. It is estimated that 42.5 percent of adults in the United States – more than 100 million people – are living with obesity,2 and more than 35 million adults live with Type 2 diabetes.3 The NIH projects that the number of U.S adults with Type 2 diabetes will skyrocket to nearly 55 million by 2030,4 and it is estimated that nearly half of U.S. adults will be obese.5 About Kallyope Kallyope, a clinical stage biotechnology company, is leveraging its proprietary Klarity™ therapeutic platform to discover and develop novel, oral small-molecule therapeutics in areas with high unmet medical need, including diabetes and obesity, gastrointestinal disease, and neurological disorders. _______________________ 1 Unique non-diabetes patients via Trilliant Health Analysis, via STAT and American Society for Metabolic and Bariatric Surgery 2 Prevalence of Overweight, Obesity, and Severe Obesity Among Adults Aged 20 and Over: United States, 1960–1962 Through 2017–2018 3 Centers for Disease Control and Prevention. National Diabetes Statistics Report website 4 Diabetes 2030: Insights from Yesterday, Today, and Future Trends 5 Projected U.S. State-Level Prevalence of Adult Obesity and Severe Obesity

Proprietary Ionic Liquids platform is advancing towards one of i2o’s main goals of producing oral biologics and peptides; an innovation that originated in Harvard’s labs under Dr. Samir Mitragotri Acquired multiple cardiometabolic assets including long-acting GLP-1s, Amylin, Glucagon and PYY that hold significant promise as combination therapies in diabetes, obesity and related indications Acquired ITCA 650 and the Medici™ Implant Platform, an investigational twice-yearly implantable GLP-1 for type 2 diabetes, recently granted a public hearing before an FDA Advisory Committee BOSTON--(BUSINESS WIRE)-- i2o Therapeutics, Inc. today announced the appointment of Kurt Graves as Chairman, President and CEO. He was previously Executive Chairman of the Board, a position he held since August 2021. Mr. Graves succeeds i2o co-founder and CEO Ravi Srinivasan, Ph.D., who is pursuing other leadership opportunities within the life sciences field. While i2o has been actively advancing the ionic liquids technology in pre-clinical work on its lead GLP-1 asset, in parallel the company has completed a series of corporate and strategic transactions including: A $46 million Series A financing with top-tier biotech investors. An acquisition and integration of proprietary pipeline assets in the cardiometabolic space from Intarcia Therapeutics including long-acting GLP-1s, Amylin, Glucagon and PYY. The combination of long-acting GLP-1s and the other peptides noted hold significant potential to redefine the standards of care in diabetes, obesity, and related indications. An acquisition and integration of ITCA 650 and the Medici implant technology platform which is an investigational twice-yearly implantable GLP-1 for type 2 diabetes and was recently granted a public hearing on September 21 before an FDA Advisory Committee. The public hearing was granted by the Commissioner’s Office and FDA’s Chief Scientist. i2o has also entered into a new 4-year sponsored research and licensing agreement with the Mitragotri Lab at Harvard University to further strengthen its IP and leadership position in the Ionic Liquid space where additional ionic liquid uses and applications are being advanced. A recent publication in the Lancet has estimated at the current pace that ~1.3 billion people will be living with diabetes by 2050 – a leading cause of death and disability worldwide. The authors concluded, “Diabetes will be a defining disease of this century,” and that “the world has underestimated the true scale and threat the disease poses…representing an urgent call to course correct.” “The cardiometabolic assets and novel delivery platforms we have at i2o are important at a time when global policy and health officials are increasingly concerned by soaring diabetes and obesity prevalence rates and the massive implications that poor glucose and weight control will have on healthcare systems, societies, and global economies for decades to come,” said Kurt Graves, Chairman, President and CEO of i2o Therapeutics. “At i2o, our ultimate goal is to be an important part of the novel GLP-1 based combination products and innovative drug delivery solutions that are needed to raise the standards of care, address widespread unmet needs around poor control and poor adherence, and to help remove the barriers to access, affordability, and supply that are needed to help millions of patients.” Mr. Graves has provided leadership to several highly innovative biotech and global pharmaceutical companies over the last 30 years. He has previously served as Chairman, President and CEO of Intarcia Therapeutics, former Chairman of Radius Health, former Executive Chairman of i2o Therapeutics, and as a Board member at Achillion Pharmaceuticals until it was acquired, and at Seres Health. He was also E&Y’s New England Entrepreneur of the Year in 2015. Previously, Mr. Graves served as EVP, Head of Corporate Development, Strategic Drug Development and Program Management and Head of Commercial at Vertex Pharmaceuticals. Prior to that, he was at Novartis Pharmaceuticals for nearly 10 years, most recently as the Global Head of the General and Specialty Medicines Business and the first Global Chief Marketing Officer for the Pharmaceuticals division. Earlier in his career, at Merck and Astra-Merck for nearly 10 years, he worked on multiple cardiovascular and GI medicines and led the GI Business Unit responsible for developing and commercializing Prilosec®, Nexium® and Prilosec OTC®. About i2o Therapeutics i2o Therapeutics is a private biotechnology company that was founded in 2019 to exploit the versatile properties of ionic liquids for producing oral biologics and peptides. i2o has also acquired wholly owned proprietary peptides with an intent to advance novel therapies for serious cardiometabolic diseases. As a complement to the oral ionic liquids approach, i2o also owns the rights to a sustained delivery system (small osmotic implants - Medici™) that enables just twice-yearly maintenance dosing of chronic medications. With this scope of platform technologies and proprietary peptides, i2o’s initial aim is to form strategic partnerships and to advance meaningful innovations that achieve a new standard of care for patients suffering from T2DM, Obesity, and related diseases. Over time, i2o’s platforms will also be leveraged for other opportunities and collaborations. Forward Looking Statements This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, such as statements regarding the application and use of Ionic Liquids (ILs) technology in the development therapeutics for cardio-metabolic diseases, inflammatory diseases, and other partnered and target indications, the efficacy and safety of oral biologic products and combination peptides, patient delivery experience and compliance, the integration of acquired assets with our IL-platform, oral combination of a GLP-1 and other co-agonist peptides, our scientific collaborations with pharmaceutical companies and the potential outcomes of such collaborations, our planned preclinical and clinical programs and studies, the use of proceeds our from our Series A financing, and the potential commercialization of our products and partnership as compared to existing treatment options, among others. Statements in this press release that are not statements of historical fact are considered forward-looking statements, which are usually identified by the use of words such as “aims”, “anticipates,” “believes,” “continues,” “goal,” “could,” “estimates,” “scheduled,” “expects,” “intends,” “may,” “plans,” “potential,” “predicts,” “indicate,” “projects,” “seeks,” “should,” “will,” “strategy,” and variations of such words or similar expressions. Statements of past performance, efforts, or results of our preclinical and clinical trials, about which inferences or assumptions may be made, can also be forward-looking statements and are not indicative of future performance or results. Forward-looking statements are neither forecasts, promises nor guarantees, and are based on the current beliefs of i2o Therapeutics’ management as well as assumptions made by and information currently available to i2o Therapeutics. Such information may be limited or incomplete, and i2o Therapeutics’ statements should not be read to indicate that it has conducted a thorough inquiry into, or review of, all potentially available relevant information. Such statements reflect the current views of i2o Therapeutics with respect to future events and are subject to known and unknown risks, including business, regulatory, economic and competitive risks, uncertainties, contingencies and assumptions about i2o Therapeutics, including, without limitation, (i) the risks and uncertainties associated with the regulatory submission, review and approval process, (ii) the ability of i2o Therapeutics to continue its planned preclinical and clinical development of its development programs, and the timing and success of any such continued preclinical and clinical development and planned regulatory submissions, (iii) i2o Therapeutics’ ability to retain and hire key personnel, (iv) i2o Therapeutics’ ability to obtain additional financing to fund its operations and complete the development and commercialization of its various product candidates, (v) i2o Therapeutics’ ability to successfully commercialize its product candidates and uncertainties around regulatory reviews and approvals, (vi) i2o Therapeutics’ ability to scale its manufacturing and commercial supply operations for its product candidates and future approved products, (vii) i2o Therapeutics’ ability to obtain, maintain, protect and enforce patent protection and other proprietary rights for its product candidates and technologies, and (viii) the unknown future impact of the COVID-19 pandemic on certain clinical trials or their milestones and/or i2o Therapeutics’ business operations or operating expenses. i2oTherapeutics cautions you not to place undue reliance on any forward-looking statements, which speak only as of the date hereof. i2o Therapeutics does not undertake any duty to update any forward-looking statement or other information in this press release, except to the extent required by law. View source version on businesswire.com: Contacts Lauren Arnold MacDougall Advisors Larnold@macdougall.bio Source: i2o Therapeutics, Inc. View this news release online at: