NPY2R

CINCINNATI--( BUSINESS WIRE )--CinFina Pharma, a CinRx portfolio company dedicated to advancing a portfolio of high-impact treatment options for obesity and metabolic diseases, today announced the initiation of the Phase 1 MAD clinical trial for CIN-110, a novel, highly selective PYY 3-36 analog for the treatment of obesity. This Phase 1 MAD clinical trial aims to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics and immunogenicity of CIN-110 in adults with obesity. The initiation of this MAD trial follows the ongoing SAD study, where CIN-110 was well-tolerated with noteworthy reductions in caloric intake and body weight. The SAD study will be used to inform dosing decisions in the current MAD study. “ To date, CIN-110 has demonstrated very strong safety and pharmacokinetic profiles in its single dose study, as well as encouraging pharmacodynamic data,” said Mary Bond, M.S., M.B.A., Chief Translational Science Officer of CinRx Pharma. “ We are excited to see this promising asset advance into this next clinical assessment where we will gain an even greater understanding of its potential to provide a safe and effective obesity treatment option for physicians and their patients.” As a potent and highly selective PYY 3-36 analog with an extended half-life, CIN-110 has the potential to be durable and well-tolerated without the significant nausea and emesis seen in previous attempts to develop PYY-focused therapies. PYY 3-36 is an endogenous hormone secreted from endocrine L-cells in the gut in response to food, particularly fat ingestion, acting as a selective agonist of the neuropeptide Y2 receptor (Y2R) and safely decreasing food intake by reducing appetite. About CIN-110 Phase 1 MAD Study: The multiple ascending dose (MAD) study is designed as a randomized, placebo-controlled clinical trial that will investigate the safety, tolerability, pharmacokinetics, pharmacodynamics and immunogenicity of CIN-110 delivered subcutaneously (SC) in study subjects with obesity over 12 weeks. Trial participants are males and females, ages 18-55, with a body mass index between 30.0 and 44.9 kg/m2. The study is planned to include multiple cohorts, each with 12 subjects randomized in a 3:1 ratio to receive SC CIN-110 or a matched placebo, respectively. About CinFina Pharma: CinFina Pharma, a CinRx portfolio company, is expanding the treatment options for obesity and its associated comorbidities with a pipeline of therapeutic candidates designed to be safe, tolerable and durable to help people lose weight and keep it off to improve their overall health. CinFina’s four therapeutic candidates are naturally occurring peptides engineered for prolonged activity which send signals in the body to control insulin secretion or feelings of satiety. Learn more at www.CinFina.com . About CinRx Pharma: CinRx Pharma is a biotech company advancing a diverse portfolio of high-impact medicines through clinical development with a unique hub-and-spoke business model. CinRx’s approach combines financing with the efficient progression of therapeutic candidates within its portfolio, each managed by CinRx’s central infrastructure and operating team. Current CinCos address areas of high unmet medical need including metabolic, gastrointestinal and oncology. Differentiated by an asset selection process agnostic to therapeutic area, a strategic CRO partnership, and insights from thousands of development programs, CinRx identifies, funds and accelerates promising drugs with the potential to have the highest impact on patients’ quality of life. CinRx Pharma is headquartered in Cincinnati, Ohio. For more information, please visit www.CinRx.com or follow the company on X and LinkedIn .

CIN-110 is a potent and highly selective large molecule peptide YY (PYY3-36) with an extended half-life being developed as a monotherapy and co-administration agent to induce satiety, reduce appetite and impact glucose metabolism CIN-110 is the second therapeutic in CinFina’s metabolic portfolio to reach the in-human clinical trial milestone CINCINNATI--(BUSINESS WIRE)-- CinFina Pharma, a CinRx portfolio company dedicated to advancing a portfolio of high-impact treatment options for obesity and metabolic diseases, today announced the U.S. Food and Drug Administration (FDA) has cleared the company’s Investigational New Drug Application (IND) for CIN-110, a PYY3-36 analog, allowing the first in-human clinical study to proceed. With the commencement of the trial, CinFina also announced the first cohort of participants has been dosed. The trial will evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics and immunogenicity of CIN-110 in a randomized, double-blind, placebo-controlled, single ascending dose study in otherwise healthy subjects with obesity. “Despite the emergence of new medicines to help address the obesity epidemic, there remains an unmet medical need for therapeutics that are well tolerated for long-term treatment,” said Dr. Jon Isaacsohn, Founder and Chief Executive Officer at CinRx Pharma. “As demonstrated by promising preclinical efficacy data, CIN-110 has the potential to meet these needs and provide important therapeutic advantages to patients in monotherapy and combination settings, including durability of weight loss. We look forward to continuing to explore its safety and tolerability profiles in this important Phase 1 study.” CIN-110 is a stable and long-acting analog of PYY3-36 being developed both as a monotherapy and co-administration agent for obesity. PYY3-36 is an endogenous hormone secreted in the gut, which activates the neuropeptide Y2 receptor (Y2R) to reduce appetite and food intake. Unlike prior attempts at developing a PYY focused therapeutic, CIN-110 is uniquely designed to limit severe nausea and emesis and still deliver on the promise of effective, long-term weight loss. CIN-110 selectively binds and activates Y2R, the target for native PYY3-36. Pharmacodynamic evaluation of CIN-110 demonstrated that repeat subcutaneous dosing leads to significant reduction of food intake and body weight in obese, non-human primates and rodents. Additionally, data shows CIN-110 led to an improvement of glucose homeostasis and insulin sensitivity in animal models. The toxicology program results indicated that CIN-110 was well tolerated with no adverse findings noted in either non-human primates or rodents. The results from the preclinical efficacy and safety studies support the progression of CIN-110 to human clinical trials. “The preclinical program of CIN-110 underscores the potential for PYY to be a differentiated approach to treat obesity. This uniquely engineered molecule holds promise to expand the current therapeutic paradigm beyond GLP-1s with its selectivity, potency and half-life extension,” said Brian Murphy, M.D., Chief Medical Officer at CinRx Pharma. About CinFina Pharma: CinFina Pharma, a CinRx portfolio company, is expanding the treatment options for obesity and its associated comorbidities with a pipeline of therapeutic candidates designed to be safe, tolerable, and durable to help people lose weight and keep it off to improve their overall health. CinFina’s four therapeutic candidates are naturally occurring peptides engineered for prolonged activity which send signals in the body to control insulin secretion or feelings of satiety. Learn more at . About CinRx Pharma: CinRx Pharma is a biotech company advancing a diverse portfolio of high-impact medicines through clinical development with a unique hub-and-spoke business model. CinRx’s approach combines financing with the efficient progression of therapeutic candidates within its portfolio, each managed by CinRx’s central infrastructure and operating team. Current CinCos address areas of high unmet medical need including metabolic, gastrointestinal, and oncology. Differentiated by an asset selection process agnostic to therapeutic area, a strategic CRO partnership, and insights from thousands of development programs, CinRx identifies, funds and accelerates promising drugs with the potential to have the highest impact on patients’ quality of life. CinRx Pharma is headquartered in Cincinnati, Ohio. For more information, please visit or follow the company on X and LinkedIn.

Researchers have for the first time identified the genetic pathway between the heart and brain tied to fainting. They found that vagal sensory neurons trigger fainting, laying a foundation for addressing fainting-related disorders. Nearly 40 percent of people experience syncope, or fainting spells, at least once in their lives. These brief losses of consciousness, whether brought by pain, fear, heat, hyperventilation or other causes, account for a significant portion of hospital emergency room visits. Yet the exact root mechanisms at play when people "pass out" largely have remained a mystery. Publishing a new report in Nature, University of California San Diego researchers, along with colleagues at The Scripps Research Institute and other institutions, have for the first time identified the genetic pathway between the heart and brain tied to fainting. One of their unique approaches was to think of the heart as a sensory organ rather than the longstanding viewpoint that the brain sends out signals and the heart simply follows directions. School of Biological Sciences Assistant Professor Vineet Augustine, the paper's senior author, applies a variety of approaches to better understand these neural connections between the heart and brain. "What we are finding is that the heart also sends signals back to the brain, which can change brain function," said Augustine. Information resulting from the study could be relevant to better understanding and treating various psychiatric and neurological disorders linked with brain-heart connections, the researchers note in their paper. "Our study is the first comprehensive demonstration of a genetically defined cardiac reflex, which faithfully recapitulates characteristics of human syncope at physiological, behavioral and neural network levels." Augustine, along with Biological Sciences Staff Research Associate Jonathan Lovelace and Graduate Student Jingrui Ma, the first authors of the paper, and their colleagues studied neural mechanisms related to Bezold-Jarisch reflex (BJR), a cardiac reflex first described in 1867. For decades researchers have hypothesized that the BJR, which features reduced heart rate, blood pressure and breathing, may be associated with fainting. But information lacked in proving the idea since the neural pathways involved in the reflex were not well known. The researchers focused on the genetics behind a sensory cluster known as the nodose ganglia, which are part of the vagus nerves that carry signals between the brain and visceral organs, including the heart. Specifically, vagal sensory neurons, or VSNs, project signals to the brainstem and are thought to be associated with BJR and fainting. In their search for a novel neural pathway they discovered that VSNs expressing the neuropeptide Y receptor Y2 (known as NPY2R) are tightly linked to the well-known BJR responses. Studying this pathway in mice, the researchers were surprised to find that when they proactively triggered NPY2R VSNs using optogenetics, a method of stimulating and controlling neurons, mice that had been freely moving about immediately fainted. During these episodes they recorded from thousands of neurons in the brains of the mice, as well as heart activity and changes in facial features including pupil diameter and whisking. They also employed machine learning in several ways to analyze the data and pinpoint features of interest. Once NPY2R neurons were activated, they found, mice exhibited rapid pupil dilation and the classic "eye-roll" seen during human fainting, as well as suppressed heart-rate, blood pressure and breathing rate. They also measured reduced blood flow to the brain, an area of collaboration with Professor David Kleinfeld's laboratory in the UC San Diego Departments of Neurobiology and Physics. "We were blown away when we saw how their eyes rolled back around the same time as brain activity rapidly dropped," the researchers reported in a paper summary. "Then, after a few seconds, brain activity and movement returned. This was our eureka moment." Further testing showed that when NPY2R VSNs were removed from mice, the BJR and fainting conditions vanished. Previous studies had shown that fainting is caused by a reduction in brain blood flow, which the new study also found to be true, but the new evidence indicated that brain activity itself could be playing an important role. The findings therefore implicate the activation of the newly genetically identified VSNs and their neural pathways not only with BJR, but more centrally in overall animal physiology, certain brain networks and even behavior. Such findings were difficult to tease out previously because neuroscientists study the brain and cardiologists study the heart, but many do so in isolation of the other. "Neuroscientists traditionally think the body just follows the brain, but now it is becoming very clear that the body sends signals to the brain and then the brain changes function," said Augustine. As a result of their findings, the researchers would like to continue tracking the precise conditions under which vagal sensory neurons are triggered into action. "We also hope to more closely examine cerebral blood flow and neural pathways in the brain during the moment of syncope, to better understand this common but mysterious condition," they note. They also hope to use their research as a model to develop targeted treatments for fainting-associated conditions.