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New research suggests affron® saffron effectively normalized HPA-axis dysregulation, enhancing adaptation to stressful experiences MADRID, Jan. 24, 2024 /PRNewswire/ -- A new in vitro study sheds light to the stress relief effect of saffron (Crocus sativus L). The research highlights the ability of affron®, a standardized extract of saffron developed by Pharmactive Biotech Products to enhance resilience to occasional stress. Continue Reading Pharmactive’s Saffron Extract improves Resilience to Occasional Stress The new study, led by Chae-Young Kim PhD, and published November 2023 in the journal Nutrients, focuses on affron's role in regulating the hypothalamic–pituitary–adrenal (HPA axis). Results demonstrated significant improvements following repeated oral administration of the extract in stress model animal subjects. The stress signal The HPA axis is a vital brain signaling system involved in orchestrating responses to stress. It functions to assure survival in life-threatening situations, and its activation provides the energy for a "fight or flight" response. However, persistent activation of the HPA axis due to prolonged stress results in persistently elevated levels of the steroidal hormone glucocorticoids (cortisol in humans), which can have detrimental effects on overall health. The study involved 40 Wistar rats divided into four groups. Three groups were subjected to a series of standardised stress tests during the 4-week trial. Two of the groups were administered daily oral doses of affron at levels corresponding to 100mg/kg and 200mg/kg, respectively. The third group was subjected to stress without receiving affron, and the fourth group received no interventions at all as a control. Several stress-related parameters were evaluated, including hypothalamic gene expression and stress hormone levels. The two groups of affron treated rats showed marked decreases in the presence of arginine vasopressin and Corticotropin Releasing Factors (CRF) within the hypothalamus. These hormones play a pivotal role in triggering the release of other stress-related hormones, including adrenocorticotropic hormone (ACTH) from the pituitary gland, which in turn signals the adrenal glands to release cortisol (corticotropin in rodents). Serum concentration of these secondary hormones increased at first and then diminished by the third week, with a more pronounced reduction noted in the higher dose group. The high dose group also experienced a significant reduction in glucocorticoid receptor (GR) expression, reflecting a properly functioning negative feedback mechanism for orchestrating daily rhythms, managing stress responses, and facilitating adaptation to changing conditions. This effect avoids the known glucocorticoid receptor resistance that occurs due to the continuous release of glucocorticoids. The ability to mitigate this resistance through reduced GR expression demonstrates the body's effectiveness in managing stress. Saffron lightens the stress load "Chronic or excessive activation of the HPA axis and prolonged elevation of these hormones can contribute to the maladaptative response called allostatic overload—a state of cumulative strain wherein the body and mind get overwhelmed by constant anxiety or challenges, but don't have the time to recover," explains Inés Morán, PhD, Scientific Studies Manager at Pharmactive. "Beyond the mental overload, it can contribute to various health problems, such as metabolic diseases, and accelerate long-term wear and tear on the body's systems." Further examination of the affron treated rats showed they maintained high levels of Brain-Derived Neurotrophic Factor (BDNF) in the hypothalamus tissue, a protein that promotes brain plasticity, and eases the adaptation in response to life experiences by ensuring the growth, survival, and maintenance of nerve cells. The rats were also subject to a Sucrose Preference Test in which the three groups subjected to stress were observed to lose interest in sugar. Supplement with affron revived interest in sugar. "This outcome is significant, because extreme cases of anxiety or depression, can produce symptoms of anhedonia, which is a lack of interest and motivation for anything, including food," adds Morán. The renewed interest in sugar is evidence of a behavioural improvement due to the rebalanced levels of physiological regulators tested in the affron-treated groups. Current global challenges, such as political instabilities, pandemics, and economic upheavals, have brought the multifaceted impact of stress to the forefront. Simultaneously, the consumer demand for "better-for-you" solutions is fueling deeper exploration of botanicals and other natural agents for relief. Saffron is a distinguished botanical with a rich history of medicinal use. A series of studies previously confirmed the efficacy of affron across diverse populations (including adolescents) in alleviating stress, tension, and mood disturbances while enhancing mental well-being. "Despite the growing body of research on saffron's anti-stress properties, which includes six published studies of our proprietary, highly concentrated saffron extract, few studies have specifically investigated its role in normalizing the regulation of the HPA axis, a crucial system for stress modulation in the body," asserts Carlos Rodríguez, Communication Manager for Pharmactive. "Through ongoing research, we are unearthing more about saffron's benefits on cognitive well-being, and its mechanisms of action. We are realizing these extend beyond influencing serotonin expression but actually demonstrates a potential to boost resilience to occasional stress and prevent its detrimental impact on overall mental and physical health." About Pharmactive Pharmactive Biotech Products, SLU, is a Madrid-based pioneering biotechnology company that develops, and manufactures differentiated natural ingredients supported by science, such as damiana extract, pure saffron extract, and aged black garlic. The company's mission is to make a daily positive and significant impact on people's health and well-being through premium botanical ingredients backed by scientific studies and approved by ethics committees. Photo - SOURCE Pharmactive Biotech Products, S.L.

PARIS, France I September 07, 2023 I Corteria Pharmaceuticals (“Corteria”), a biopharmaceutical company specialized in the development of transformative therapies for unaddressed heart failure subpopulations, today announced an oversubscribed €65M ($71M [1] ) Series A co-led by US investment firm OrbiMed and EU-based leading investment firm Jeito Capital, with the participation of all existing seed investors (Kurma Partners, Fountain Healthcare Partners, V-Bio Ventures, Invivo Capital, Omnes Capital). As a result, Erez Chimovits from OrbiMed and Andreas Wallnoefer from Jeito Capital will join the board of Directors of Corteria. The funding will be used to advance Corteria’s cardiovascular pipeline into the clinic. Heart failure is a serious disease with a prevalence of more than 60 million patients globally and still growing. Corteria’s innovative approach is centered on selecting therapeutic targets involved in the worsening and acute forms of human heart failure, as well as a stratification strategy to identify specific subgroups that are most likely to benefit from the treatments. These forms of heart failure are widespread, life-threatening, and not directly addressed by the current standards of care. Corteria was founded in 2021 by Sanofi’s former head of cardiovascular research, Philip Janiak, and Marie-Laure Ozoux, former cardiovascular project leader at Sanofi, around two cardiovascular programs in-licensed from Sanofi. [2] Since then, Corteria’s pipeline has expanded rapidly and comprises today three first-in-class therapies that are highly differentiated as they produce multi-organ benefits, acting on the kidneys, the heart, and the vessels: The lead asset for Worsening Heart Failure is expected to enter the clinic in early 2024. “This financing marks a major milestone in our mission to bring therapies to heart failure subpopulations with high unmet needs,” said Philip Janiak, Founder and President of Corteria Pharmaceuticals. “ We are extremely grateful to Jeito and OrbiMed as our new investors for their trust in our science and team and to our existing investors for their support and commitment since inception. We are looking forward to working all together to develop next generation transformative therapeutics.” Andreas Wallnoefer, Partner at Jeito Capital, said: “Despite current treatments, heart failure is a progressing disease that impacts severely the lives of many patients and remains one of the leading causes of mortality worldwide. Corteria focuses on translating important therapeutic innovation in cardiology into clinical practice. Our investment in Corteria reflects Jeito’s commitment to address significant unmet needs in the realm of cardiology. We are excited to join forces with Corteria’s dedicated team to develop a portfolio of medicines with important clinical benefit for patients.” “We are proud to have been involved with Corteria since its early days and impressed with the progress made to date. The company is now at a turning point of entering the clinic with its lead asset early next year and validating its unique positioning in well-defined heart failure subpopulations with high unmet medical needs. Kurma Partners is pleased to continue supporting the company during this key step that we hope will bring transformative clinical outcome for patients,” said Thierry Laugel, Managing Partner at Kurma Partners, and Chairman of the board of Corteria. About OrbiMed OrbiMed is a healthcare investment firm, with over $17 billion in assets under management. OrbiMed invests globally across the healthcare industry through a range of private equity funds, public equity funds, and royalty/credit funds. OrbiMed’s team of over 100 professionals is based in New York City, San Francisco, Shanghai, Hong Kong, Mumbai, Herzliya, and other key global markets. www.orbimed.com About Jeito Capital Jeito Capital is a global leading Private Equity company with a patient benefit driven approach that finances and accelerates the development and growth of ground-breaking medical innovation. Jeito empowers and supports managers through its expert, integrated, multi-talented team and through the investment of significant capital to ensure the growth of companies, building market leaders in their respective therapeutic areas with accelerated patients’ access globally, especially in Europe and the United States. Jeito Capital has €534 million under management and a rapidly growing portfolio of investments. Jeito Capital is based in Paris with a presence in Europe and the United States. For more information, please visit www.jeito.life or follow @Jeito_life on Twitter or LinkedIn . About Corteria Pharmaceuticals Founded in 2021, Corteria Pharmaceuticals is a privately held biopharmaceutical company developing first-in-class drugs in heart failure subpopulations. Despite some improvements in the management of this serious disease, the prevalence of heart failure keeps increasing with more than 60 million patients worldwide. Corteria’s strategy involves innovative patient stratification and target selection based on human evidence and a better understanding of disease biology in patients with a focus on worsening and acute heart failure and right heart failure. More information available at: www.corteriapharma.com [1] Applying a 1.0886 EUR/USD exchange rate as of 30 August 2023 (Banque de France) rounded to $71M [2] CRF2 peptide agonist and AVP neutralizing monoclonal antibody programs [3] Corticotropin-releasing hormone receptor 2 SOURCE: Corteria Pharmaceuticals

The Company’s Nelivabon Program Pairs Novel Compound with Companion Diagnostics to Treat MDD patientsMUNICH, Germany, June 20, 2023 (GLOBE NEWSWIRE) -- HMNC Brain Health (‘‘HMNC’’ or the ‘‘Company’’), a global clinical-stage biopharmaceutical company pioneering the development of personalized therapies in psychiatry, announced today that the first patient has been enrolled in the Olive trial, a randomized, double-blind, placebo-controlled trial in more than 300 patients with Major Depressive Disorder (MDD) conducted in eight countries in Europe. The Olive trial is a crucial component of the Nelivabon program, aimed at developing BH-200, a potent vasopressin V1b receptor antagonist, for improved treatment of patients with MDD who have underlying HPA-axis (Hypothalamus‐pituitary‐adrenal axis) dysfunction. The neuropeptide vasopressin plays a critical role in coordinating hormonal and behavioral adaptation to stress, and its elevated activity in the brain following repeated stressors may increase anxiety and depressive symptoms. BH-200 directly targets the HPA-axis dysfunction and has demonstrated promising tolerability in previous clinical trials. The Olive trial will evaluate the efficacy and safety of BH-200 in depressed patients. Moreover, it will test the predictive capabilities of the V1b polygenic score, which the company aims to eventually develop into a companion diagnostic for BH-200. As this genetic in-vitro diagnostic test is still under development, the Olive trial will recruit every patient regardless of genetic status, and a post-hoc analysis will be performed. The hypothesis is that patients with a high V1b polygenic score, which is estimated to be around 30% of the population, will benefit the most from BH-200. ‘‘The initiation of the Olive trial for the Nelivabon program marks an important milestone in our pursuit of providing innovative and personalized treatments for patients suffering from stress-axis-related MDD,’’ said Dr. Maximilian Doebler, Chief Business Officer of HMNC Brain Health. ‘‘We remain committed to advancing our clinical research pipeline to address unmet needs in mental health care and ultimately bring new treatment options to patients suffering from mental health disorders such as MDD.’’ ‘‘The development of the predictive companion diagnostic as part of the Nelivabon program reflects HMNC Brain Health's focus on targeted and personalized treatments. By identifying patients with a specific dysfunction of the HPA-axis, the program aims to provide tailored and efficient treatment options, furthering the company's goal of delivering personalized healthcare solutions,’’ said Dr. Hans Eriksson, Chief Medical Officer of HMNC Brain Health. ‘‘The commencement of our Phase 2 study is a crucial step in validating the safety and efficacy of this innovative treatment strategy. We are very confident that our precision psychiatry approach for the treatment of MDD will prove its noteworthy potential addressing a large patient population.’’ If the Nelivabon program receives clinical validation, it could represent a significant advancement in the treatment of stress-axis-related MDD, a potential breakthrough in mental health treatment, supporting HMNC Brain Health’s commitment to innovation. The initial results of the Olive trial are expected in H2 2024. ABOUT HMNC BRAIN HEALTH HMNC Brain Health (HMNC Holding GmbH) is a global precision psychiatry biopharma company pioneering the development of personalized therapies powered by predictive companion diagnostics, leading to higher remission rates. The Company develops a unique pipeline for targeting both Major Depressive Disorder (MDD) and Treatment-Resistant Depression (TRD). The Company has presence in both Germany and the US and is backed by a renowned global VC, several family offices, and a strategic healthcare investor. The Company now enters the next stage of its development with a large-scale licensing and fundraising agenda. ABOUT THE NELIVABON PROGRAM The Nelivabon program is focused on developing BH-200, a vasopressin V1b receptor antagonist, to treat Major Depressive Disorder (MDD) related to dysfunction in the human body's stress system, called HPA-axis (Hypothalamus‐pituitary‐adrenal axis). BH-200 targets the elevated activity of vasopressin in the brain caused by repeated stressors, potentially reducing anxiety and depressive symptoms. The neuropeptide vasopressin coordinates hormonal and behavioral adaptation to stress, but repeated stressors can cause an overactive vasopressin system that leads to an increase in anxiety and the development of depressive symptoms. To identify depressed patients with underlying dysfunction of the HPA-axis, who may benefit from treatment with BH-200, the program includes a matching molecular diagnostic test. While the diagnostic test is still in early development, data stemming from this trial is expected to significantly improve its accuracy. BH-200 has shown to be well-tolerated in clinical trials. The program is entering a Phase-II proof-of-concept study in H1 2023 and once clinically validated, could represent an efficient treatment option for patients suffering from stress-axis-related MDD. Media contacts (U.S.):Anne Donohoe+1212.896.1265hmncbrain@kcsa.com Investor Contacts (U.S.):Sophia Bashford+1 347-487-6788sbashford@kcsa.com