Everyday humans are confronted with a plethora of rewards competing for their attention. Nevertheless, to obtain a goal or reward, humans often need to invest effort. When humans are confronted with the challenge to integrate costs of action such as the effort of walking to one's favorite lunch place with its anticipated benefits (i.e., eating one's favorite meal), accumulating evidence suggest that humans might "go with the gut". Ghrelin is a stomach-derived hormone and the only known circulating peptide that stimulates appetite. At the same time, patients with major depressive disorder report deficits in motivated behavior which are oftentimes accompanied by changes in appetite and weight. Based on a wealth of accruing evidence from animal studies, the investigators suggest that the gut acts as an important arbitrator in effort allocation by signaling the energy level of the body. Within this physiological framework, ghrelin is thought to signal a short-term energy deficit to increase reward responsivity and willingness to work for reward as compensatory (allostatic) means. Here, the investigators propose to conduct a follow-up study (to NCT05318924) with subcutaneous administration of ghrelin vs. saline in patients with major depressive disorder and healthy control participants. During each visit, participants will receive a subcutaneous administration of either ghrelin or saline and perform an effort allocation task where they have to exert physical effort to obtain food and monetary rewards. The investigators hypothesize that ghrelin will increase the motivation to exert effort for rewards. The goal of this follow-up study is to test that the motivational effects of ghrelin are similar in patients with depression and healthy control participants. Furthermore, participants resting energy expenditure will be estimated before and after the administration. In line with a role of ghrelin as an energy deficit signal, the investigators expect ghrelin to decrease energy expenditure. During each visit, participants will answer questions about their current mood and physiological state. The investigators hypothesize that ghrelin increases mood state and hunger while decreasing satiety.

Start Date02 Sep 2024

Sponsor / Collaborator

University Hospital Tuebingen

NCT05726240 / Not yet recruitingPhase 2IIT

Multicentre Randomized Trial of Ghrelin in Anterior Circulation Ischemic Stroke Treated With Endovascular Thrombectomy. A Randomized Phase 2 Trial

About half of the patients with acute ischemic stroke treated with endovascular thrombectomy (EVT) remain dependent on the help of others or die in the first 90 days. We hypothesize that treatment with ghrelin, started in the first six hours after stroke onset, improves early recovery and long-term functional outcome in these patients. Ghrelin is a naturally occurring hormone and mildly excitatory neurotransmitter also known as the 'hunger hormone.' Treatment with acylated ghrelin consistently improved functional and histological recovery in in vitro and in vivo models of ischemic stroke.

Start Date01 Oct 2023

Sponsor / Collaborator-

NCT05318924 / RecruitingPhase 1/2IIT

Will Work for Reward: Effects of Ghrelin Administration on Dopamine and Effort

Ghrelin is a stomach-derived hormone and the only known circulating peptide that stimulates appetite. Animal studies have conclusively shown that ghrelin increases dopaminergic neurotransmission and, thereby, enhances effort. However, similar evidence on the putative role of ghrelin in humans is still lacking. Here, the investigators propose to conduct a [11C]-raclopride PET/MR study after intravenous administration of ghrelin vs. saline in healthy individuals. First, during an intake visit, the investigators will assess fasting blood levels of hormones involved in appetitive behavior such as ghrelin, leptin, and insulin. In addition, the investigators will conduct a set of tasks that have been associated with dopamine function (i.e., effort and reinforcement learning). Second, the investigators will assess the effects of intravenous administration of ghrelin on dopamine signaling using a double-blind randomized cross-over design. To this end, participants will be infused with ghrelin (vs. saline) while we determine dopamine release (via PET imaging) and assess cerebral blood flow and functional connectivity at rest (via concurrent MR imaging). Furthermore, the investigators will conduct an instrumental motivation task (IMT) where participants have to exert physical effort to obtain rewards. Based on preclinical studies and indirect evidence from human studies, the investigators hypothesize that ghrelin will increase dopamine release in the striatum and that this will, in turn, lead to an increase in the willingness to work for rewards. Moreover, the investigators expect that ghrelin-induced dopamine release will be associated with an elevated tracking of reward utility in the mesolimbic circuit during the IMT, which is known to be associated with response vigor. Collectively, the proposed project would provide a unique resource to test an important link between the gut and the brain in the regulation of appetitive behavior. If ghrelin were to enhance effort expenditure for rewards via dopamine signaling in humans, then restoring sensitivity to ghrelin might be the more promising therapeutic approach compared to antagonizing the ghrelin receptor.

Start Date21 Feb 2022

Sponsor / Collaborator

University Hospital Tübingen

[+1]

100 Clinical Results associated with Lenomorelin

100 Translational Medicine associated with Lenomorelin

100 Patents (Medical) associated with Lenomorelin

2,016

Literatures (Medical) associated with Lenomorelin

01 Dec 2024·Environmental Pollution

Ghrelin alleviated TiO2 NPs-induced inhibition of endochondral osteogenesis and promoted longitudinal growth of long bones in juvenile rats via Wnt/β-catenin signaling pathway

Article

Author: Sun, Leke ; Feng, Lihua ; Chen, Xiangxiang ; Shi, Weihong ; Xu, Hengyi ; Liu, Yang ; Xia, Yanan ; Lang, Yuanyuan

Titanium dioxide nanoparticles (TiO₂ NPs) are widely used in children's daily necessities and foods, and their health hazards to children have attracted particular attention. Childhood is a critical time for accelerated bone growth and development. Current studies revealed that TiO₂ NPs exposure causes bone damage in juvenile rats; however, the underlying mechanism is unknown. Ghrelin is a polypeptide hormone that is considered to be a candidate factor for regulating bone growth and development. In this research, 3-week-old juvenile male rats were administered 0, 100 or 200 mg/kg TiO₂ NPs and 50 μg/kg ghrelin for 4 weeks to explore the underlying mechanism of TiO₂ NPs-induced bone damage, and the protective effect of ghrelin. Our results revealed that TiO₂ NPs resulted in decreased synthesis of bone growth-related hormones, disturbed bone metabolism, and destruction of bone structure. Further mechanism studies showed that TiO₂ NPs inhibited Wnt/β-catenin pathway, reduced collagen synthesis, inhibited chondrocyte proliferation and differentiation, promoted chondrocyte apoptosis, and inhibited endochondral osteogenesis, ultimately leading to long bone longitudinal growth retardation and osteoporosis. Ghrelin alleviated the negative effects of TiO₂ NPs-induced bone growth in juvenile rats by upregulating the Wnt/β-catenin signaling pathway. This study provided a reference for the clinical treatment of growth retardation and idiopathic short stature in juvenile children caused by environmental pollutants.

01 Nov 2024·Molecular Pharmacology

Ghrelin Modulates Voltage-Gated Ca²⁺Channels through Voltage-Dependent and Voltage-Independent Pathways in Rat Gastric Vagal Afferent Neurons

Article

Author: Holmes, Gregory M ; Herold, Paul B ; Ruiz-Velasco, Victor ; Stella, Salvatore L ; Goudsward, Hannah J

The orexigenic gut peptide ghrelin is an endogenous ligand for the growth hormone secretagogue receptor type 1a (GHSR1a). Systemic ghrelin administration has previously been shown to increase gastric motility and emptying. While these effects are known to be mediated by the vagus nerve, the cellular mechanism underlying these effects remains unclear. Therefore, the purpose of the present study was to investigate the signaling mechanism by which GHSR1a inhibits voltage-gated Ca²⁺ channels in isolated rat gastric vagal afferent neurons using whole-cell patch-clamp electrophysiology. The ghrelin pharmacological profile indicated that Ca²⁺ currents were inhibited with a log (Ic₅₀) = -2.10 ± 0.44 and a maximal inhibition of 42.8 ± 5.0%. Exposure to the GHSR1a receptor antagonist (D-Lys3)-GHRP-6 reduced ghrelin-mediated Ca²⁺ channel inhibition (29.4 ± 16.7% vs. 1.9 ± 2.5%, n = 6, P = 0.0064). Interestingly, we observed that activation of GHSR1a inhibited Ca²⁺ currents through both voltage-dependent and voltage-independent pathways. We also treated the gastric neurons with either pertussis toxin (PTX) or YM-254890 to examine whether the Ca²⁺ current inhibition was mediated by the Gα _i/o or Gα _q/11 family of subunits. Treatment with both PTX (Ca²⁺ current inhibition = 15.7 ± 10.6%, n = 8, P = 0.0327) and YM-254890 (15.2 ± 11.9%, n = 8, P = 0.0269) blocked ghrelin's effects on Ca²⁺ currents, as compared with control neurons (34.3 ± 18.9%, n = 8). These results indicate GHSR1a can couple to both Gα _i/o and Gα _q/11 in gastric vagal afferent neurons. Overall, our findings suggest GHSR1a-mediated inhibition of Ca²⁺ currents occurs through two distinct pathways, offering necessary insights into the cellular mechanisms underlying ghrelin's regulation of gastric vagal afferents. SIGNIFICANCE STATEMENT: This study demonstrated that in gastric vagal afferent neurons, activation of GHSR1a by ghrelin inhibits voltage-gated Ca²⁺ channels through both voltage-dependent and voltage-independent signaling pathways. These results provide necessary insights into the cellular mechanism underlying ghrelin regulation of gastric vagal afferent activity, which may benefit future studies investigating ghrelin mimetics to treat gastric motility disorders.

01 Oct 2024·Journal of Nuclear Medicine

Design, Synthesis, and Preclinical Evaluation of a High-Affinity¹⁸F-Labeled Radioligand for Myocardial Growth Hormone Secretagogue Receptor Before and After Myocardial Infarction

Article

Author: Hou, Jinqiang ; Prato, Frank S ; Dhanvantari, Savita ; Kovacs, Michael ; Yu, Lihai ; Biernaski, Heather ; Prato, Frank S. ; Hicks, Justin ; Sykes, Jane ; Sullivan, Rebecca ; Wisenberg, Gerald ; Thiessen, Jonathan D. ; Butler, John ; Luyt, Leonard G ; Luyt, Leonard G. ; Dharmakumar, Rohan ; Wilk, Benjamin ; Thiessen, Jonathan D

The peptide hormone ghrelin is produced in cardiomyocytes and acts through the myocardial growth hormone secretagogue receptor (GHSR) to promote cardiomyocyte survival. Administration of ghrelin may have therapeutic effects on post-myocardial infarction (MI) outcomes. Therefore, there is a need to develop molecular imaging probes that can track the dynamics of GHSR in health and disease to better predict the effectiveness of ghrelin-based therapeutics. We designed a high-affinity GHSR ligand labeled with ¹⁸F for imaging by PET and characterized its in vivo properties in a canine model of MI. Methods: We rationally designed and radiolabeled with ¹⁸F a quinazolinone derivative ([¹⁸F]LCE470) with subnanomolar binding affinity to GHSR. We determined the sensitivity and in vivo and ex vivo specificity of [¹⁸F]LCE470 in a canine model of surgically induced MI using PET/MRI, which allowed for anatomic localization of tracer uptake and simultaneous determination of global cardiac function. Uptake of [¹⁸F]LCE470 was determined by time-activity curve and SUV analysis in 3 regions of the left ventricle-area of infarct, territory served by the left circumflex coronary artery, and remote myocardium-over a period of 1.5 y. Changes in cardiac perfusion were tracked by [¹³N]NH₃ PET. Results: The receptor binding affinity of LCE470 was measured at 0.33 nM, the highest known receptor binding affinity for a radiolabeled GHSR ligand. In vivo blocking studies in healthy hounds and ex vivo blocking studies in myocardial tissue showed the specificity of [¹⁸F]LCE470, and sensitivity was demonstrated by a positive correlation between tracer uptake and GHSR abundance. Post-MI changes in [¹⁸F]LCE470 uptake occurred independently of perfusion tracer distributions and changes in global cardiac function. We found that the regional distribution of [¹⁸F]LCE470 within the left ventricle diverged significantly within 1 d after MI and remained that way throughout the 1.5-y duration of the study. Conclusion: [¹⁸F]LCE470 is a high-affinity PET tracer that can detect changes in the regional distribution of myocardial GHSR after MI. In vivo PET molecular imaging of the global dynamics of GHSR may lead to improved GHSR-based therapeutics in the treatment of post-MI remodeling.

News (Medical) associated with Lenomorelin

13 Jul 2023

·www.globenewswire.com

Aeterna Zentaris Outlines Progress on Development Pipeline Programs and Provides Corporate Update

Highlights progress, recent developments and upcoming key milestonesCompany continues to build growing body of data across pipeline, advancing towards first in human studiesStrong financial position with cash projected to fund operations and advancement of priority pipeline programs into 2025 TORONTO, ONTARIO, July 13, 2023 (GLOBE NEWSWIRE) -- Aeterna Zentaris Inc. (NASDAQ: AEZS) (TSX: AEZS) (“Aeterna” or the “Company”), a specialty biopharmaceutical company developing and commercializing a diversified portfolio of pharmaceutical and diagnostic products, today provided an update on its therapeutic and diagnostic development pipeline programs and outlined upcoming key milestones. “We are encouraged by our significant progress across all of our active development programs, and based on the prioritization of our pipeline, have strengthened our focus on our diagnostic and therapeutic programs as we execute on key decision points,” commented Dr. Klaus Paulini, Chief Executive Officer of Aeterna. “Additionally, in our ongoing DETECT clinical trial, we are making significant progress regarding patient recruitment and believe we are well-positioned to continue building momentum towards completion of the study by year’s end. Further, based upon our active outreach and discussions, we expect to secure an alternate development and commercialization partner for Macrilen® for the U.S. and Canada.” Therapeutics Development Pipeline Update Autoimmunity Modifying ("AIM") Biologicals: Targeted, highly specific autoimmunity modifying fusion proteins for the potential treatment of neuromyelitis optica spectrum disorder ("NMOSD") and Parkinson's disease (“PD”) AIM Biologicals represent a unique platform technology with the potential to address the cause and not only the symptoms of auto-immune and inflammatory, neurodegenerative disorders at early stages. This approach is based on induction of selective and highly target-specific immune de-sensibilization based on the natural concept of feto-maternal tolerance. Dr. Paulini added, “We have received encouraging feedback from our collaborator and scientific advisor on the NMOSD indication, Dr. Michael Levy, Research Director of the Division of Neuroimmunology & Neuroinfectious Disease at Massachusetts General Hospital. Dr. Levy shares our vision that presenting antigens on soluble HLA-G fusion proteins is a promising, novel approach to induce antigen specific immune tolerance among NMOSD and PD patients. Together, we look forward to furthering the development of this program.” Recent Highlights Demonstrated positive pre-clinical proof-of-concept in various in-vitro and in-vivo models.In-depth profiling of a limited set of candidates for potential use in clinical development.Confirmed AIM Biologicals’ mechanism of action and efficacy in ex-vivo studies in human blood samples from both NMOSD and PD patients. Next Steps Evaluation of manufacturing strategy and initiation of production of selected development candidates.Ongoing compilation of a comprehensive pre-clinical data package for scientific advice meetings with regulatory authorities, expected to take place in the near future. Delayed Clearance Parathyroid Hormone ("DC-PTH", AEZS-150) Fusion Proteins: Potential treatment for chronic hypoparathyroidism AEZS-150 is a fusion protein of PTH [1-34] coupled to a modified human growth-hormone binding protein (GHBP). Preclinical results so far indicate the potential for maintaining regular calcium and phosphate levels in blood longer and more consistently than with current treatments. This project aims to address this debilitating orphan disease, which is currently without satisfactory treatment options, with weekly instead of daily injections. “There is a major unmet need for physiological parathyroid hormone replacement in patients with hypoparathyroidism, either congenital or acquired from neck surgery, who have an impaired quality of life and increased morbidity and mortality on current therapy. DC-PTH will address this unmet need,” commented Prof. Richard Ross, MD, FRCP, Department of Oncology and Metabolism at Sheffield University (UK). “Aeterna has made great progress in the manufacturing process development of AEZS-150 and repeating validation studies in models of hypoparathyroidism required before undertaking trials in patients.” Recent Highlights Detailed profiling of AEZS-150 through in-vitro studies and in-vivo models of hypoparathyroidism.Established a master cell bank for a cell line expressing AEZS-150 in good yield.Continued progress in the development of a production process suitable for larger scale GMP manufacturing. Next Steps Meet with regulatory authorities to determine the development path forward; Company expects such a meeting in Q4/2023, and as outcome, an abbreviated safety and toxicology program as the active principle ([1-34]-PTH fragment) is already approved and in use.Initiate IND-enabling preclinical studies in 2024. Macimorelin Therapeutic (AEZS-130): Ghrelin agonist in development for the treatment of ALS (Lou Gehrig's disease) Amyotrophic Lateral Sclerosis (ALS) is a debilitating and deadly orphan disease, and those who suffer from this terminal condition have few treatment options. Macimorelin’s (AEZS-130) multiple modes of action should have the potential to improve the quality of life for these patients. Recent Highlights Successful development of an alternative formulation suitable for use in ALS.Accumulating data for positive effects of AEZS-130 treatment on survival of motor-neurons.Continued assessment of AEZS-130 in transgenic mouse ALS models and in human patient-derived neuron cultures.Completion of initial toxicology and safety studies to support clinical development as a therapeutic, in addition to the already existing body of safety and toxicology data from our macimorelin diagnostic development. Next Steps Following achievement of proof-of-concept, the Company will seek to have a scientific advice meeting with regulatory authorities to discuss program development next steps.Completion of toxicology and safety studies to support treatment over prolonged periods. Diagnostics Development and Commercialization Update Macimorelin Diagnostic: Approved and commercialized as test for adult growth hormone deficiency and in clinical Phase 3 development for childhood-onset growth hormone deficiency ("CGHD") testing. Aeterna is currently conducting its pivotal Phase 3 safety and efficacy study AEZS-130-P02 (the “DETECT-trial”) evaluating macimorelin for the diagnosis of Childhood Onset Growth Hormone Deficiency (“CGHD”). Most clinical sites in the U.S. as well as European countries are open for patient recruitment. Recent Highlights Phase 3 Study: Significant progress made with DETECT patient recruitment also by engagement of an additional Clinical Research Organization (CRO). Currently three new countries (Armenia, Slovakia, and Turkey), have ongoing DETECT clinical trial application activities and almost half the foreseen subjects have meanwhile concluded the trial.Macimorelin Commercialization: Having regained full rights to Macrilen® for the U.S. and Canada from Novo Nordisk in May 2023, the Company is actively focused on identifying an alternate development and commercialization partner for Macrilen® for U.S. and Canada. “We continue to manage our cash responsibly with a balanced de-risked development approach, which we believe enables us to optimize the Company's capital and human resources,” added Giuliano La Fratta, Chief Financial Officer of Aeterna. “We remain focused on advancing our programs to their next phase of development, guided by the data and financial risk/reward as we do so. Based on our current projections, we believe the Company has the ability to meet its currently anticipated cash needs into 2025.” About Aeterna Zentaris Inc. Aeterna Zentaris is a specialty biopharmaceutical company developing and commercializing a diversified portfolio of pharmaceutical and diagnostic products focused on areas of significant unmet medical need. The Company's lead product, macimorelin (Macrilen®; Ghryvelin™), is the first and only U.S. FDA and European Commission approved oral test indicated for the diagnosis of adult growth hormone deficiency (AGHD). The Company is leveraging the clinical success and compelling safety profile of macimorelin to develop it for the diagnosis of childhood-onset growth hormone deficiency (CGHD), an area of significant unmet need. Aeterna Zentaris is dedicated to the development of its therapeutic asset and has established a pre-clinical development pipeline to potentially address unmet medical needs across a number of indications, including neuromyelitis optica spectrum disorder (NMOSD), Parkinson's disease (PD), hypoparathyroidism and amyotrophic lateral sclerosis (ALS; Lou Gehrig's disease). For more information, please visit www.zentaris.com and connect with the Company on Twitter, LinkedIn and Facebook. Forward-Looking Statements This press release contains statements that may constitute forward-looking statements within the meaning of U.S. and Canadian securities legislation and regulations, and such statements are made pursuant to the safe-harbor provision of the U.S. Securities Litigation Reform Act of 1995. Forward-looking statements are frequently, but not always, identified by words such as "expects," "aiming", "anticipates," "believes," "intends," "potential," "possible," and similar expressions. Such statements, based as they are on current expectations of management, inherently involve numerous risks, uncertainty and assumptions, known and unknown, many of which are beyond our control. Forward-looking statements in this press release include, but are not limited to, those relating to Aeterna's expectations regarding: its preclinical and clinical studies, its ability to secure regulatory approvals for Macrilen™, its efforts to obtain a development and commercialization partner for Macrilen™ in the U.S. and Canada and the ability to meet its currently anticipated cash needs into 2025. Forward-looking statements involve known and unknown risks and uncertainties, and other factors which may cause the actual results, performance or achievements stated herein to be materially different from any future results, performance or achievements expressed or implied by the forward-looking information. Such risks and uncertainties include, among others, our reliance on the success of the DETECT clinical trial in the European Union and U.S. for Macrilen™ (macimorelin) in CGHD; results from our ongoing or planned pre-clinical studies and our DETECT clinical trial under development may not be successful or may not support advancing the product further in pre-clinical studies, to human clinical trials or regulatory approval; our ability to raise capital and obtain financing to continue our currently planned operations; our now heavy dependence on the success of Macrilen™ (macimorelin) and related out-licensing arrangements and the continued availability of funds and resources to successfully commercialize the product; the global instability due to the global pandemic of COVID-19 and the war in the Ukraine, and their unknown potential effect on our planned operations; our ability to enter into out-licensing, development, manufacturing, marketing and distribution agreements with other pharmaceutical companies and keep such agreements in effect; and our ability to continue to list our common shares on the NASDAQ. Investors should consult our quarterly and annual filings with the Canadian and U.S. securities commissions for additional information on risks and uncertainties, including those risks discussed in our Annual Report on Form 20-F and annual information form, under the caption "Risk Factors". Given the uncertainties and risk factors, readers are cautioned not to place undue reliance on these forward-looking statements. We disclaim any obligation to update any such factors or to publicly announce any revisions to any of the forward-looking statements contained herein to reflect future results, events or developments, unless required to do so by a governmental authority or applicable law. No securities regulatory authority has either approved or disapproved of the contents of this news release. The Toronto Stock Exchange accepts no responsibility for the adequacy or accuracy of this release. Investor Contact: Jenene ThomasJTC TeamT (US): +1 (833) 475-8247E: aezs@jtcir.com

Phase 3

05 Apr 2023

·www.globenewswire.com

Aeterna Zentaris Provides Update on Macrilen® (Macimorelin), Reiterates Advancement of Pediatric DETECT Trial

U.S. sales of Macrilen® for adult use to be temporarily discontinued as of May 23, 2023, while DETECT trial continues in order to expand the opportunity for pediatric usage of Macrilen®Sales and commercialization efforts continue to move forward in European Economic Area and UK under recent agreement with PharmanoviaUnited States Patent and Trademark Office (“USPTO”) has issued a Notice of Allowance for Aeterna’s U.S. patent application related to use of macimorelin for Assessing Growth Hormone Deficiency in Children TORONTO, ONTARIO, April 05, 2023 (GLOBE NEWSWIRE) -- Aeterna Zentaris Inc. (NASDAQ: AEZS) (TSX: AEZS) (“Aeterna” or the “Company”), a specialty biopharmaceutical company developing and commercializing a diversified portfolio of pharmaceutical and diagnostic products, today announced that sales of Macrilen® (macimorelin) will be temporarily discontinued in the United States commercial market for the diagnosis of adult growth hormone deficiency (“AGHD”), effective May 23, 2023 and until anticipated re-launch with an alternate commercialization partner. This temporary action follows the August 29, 2022 announced decision by Aeterna’s former North American commercialization partner Novo Nordisk Healthcare AG (“Novo Nordisk”) to end its license agreement for this product in North America. The Company is actively seeking alternate development and commercialization partners for Macrilen® (macimorelin) in the US and other territories currently not partnered. The decision to temporarily discontinue sales of Macrilen® in the United States does not have any impact on the sales and commercialization efforts in the UK and European Economic Area. On March 16, 2023, Aeterna announced that Pharmanovia, a global lifecycle management healthcare company, had acquired the exclusive rights and license to commercialize GHRYVELIN™ (macimorelin’s brand name in the UK and European Economic Area) in the territory for the diagnosis of Adult Growth Hormone Deficiency (AGHD) and, if approved, for Childhood Onset Growth Hormone Deficiency (CGHD) from the Company's previous EEA and UK partner, Consilient Health. “We remain confident in macimorelin’s value and effectiveness for the diagnosis of AGHD,” said Dr. Klaus Paulini, Chief Executive Officer of Aeterna. “We believe that our partnership with Pharmanovia and the patent issued by the USPTO (see more information below) are additional indications of macimorelin’s medical and commercial potential. We remain focused on a commercialization path for North America that will capture not only this value, but the further opportunities we believe exist in the ongoing DETECT trial, as we continue in discussions with possible commercialization partners in North America. At the same time, we continue to move forward with our commercialization partners for the EEA, the UK and other territories already partnered.” USPTO Issues Notice of Allowance for Aeterna U.S. Patent Application for Macimorelin The Company also announced today that the USPTO has issued a Notice of Allowance for Aeterna’s U.S. patent application No. 17/375,709 titled, “Use of Macimorelin in Assessing Growth Hormone Deficiency in Children.” The Company anticipates the issue of the formal registration of this U.S. patent application in the coming months. AEZS-130-P02 (the "DETECT-trial"), Aeterna’s pivotal Phase 3 safety and efficacy study evaluating macimorelin for the diagnosis of CGHD, remains ongoing. Most clinical sites in the U.S. as well as European countries are open for patient recruitment. “We believe the potential opportunities for expanded commercial success will increase as we move closer to completing our DETECT trial and potential approval for the diagnosis of CGHD,” Dr. Paulini continued. Dr. Paulini concluded, “We are pleased to have received further commercial validation of the potential of the use of macimorelin for the diagnosis of CGHD with the notice of allowance received for our U.S. patent. We remain optimistic about the progress made in our DETECT trial and are laser focused on our efforts to successfully execute on our plans in order to meet the anticipated completion of enrollment at the end of this year. At the same time, we remain committed to exploring all strategic options for our macimorelin asset in North America and territories not currently partnered.” About Macimorelin (Macrilen®; GHRYVELIN™) Macimorelin is marketed under the brand name GHRYVELIN™ (macimorelin) in the UK and European Economic Area and Macrilen® in the United States for the diagnosis of adult growth hormone deficiency (AGHD). In addition, Aeterna Zentaris is currently conducting a pivotal Phase 3 safety and efficacy study AEZS-130-P02 (also referred to as the "DETECT-trial") evaluating macimorelin for the diagnosis of childhood-onset growth hormone deficiency (CGHD). Macimorelin (Macrilen®; GHRYVELIN™), a ghrelin agonist, is an orally active small molecule that stimulates the secretion of growth hormone from the pituitary gland. Stimulated growth hormone levels are measured in blood samples after oral administration of macimorelin for the assessment of AGHD. Approval of macimorelin was granted by the FDA in 2017 and by the EMEA in 2019, based on Phase III data showing that oral macimorelin provides accuracy comparable to that of standard insulin tolerance testing (ITT), but has a more favorable safety profile compared to ITT. Oral macimorelin also reduces false positive test results, helping to avoid unnecessary treatment of patients. About Aeterna Zentaris Inc. Aeterna Zentaris is a specialty biopharmaceutical company developing and commercializing a diversified portfolio of pharmaceutical and diagnostic products focused on areas of significant unmet medical need. The Company's lead product, macimorelin (Macrilen™; Ghryvelin®), is the first and only U.S. FDA and European Commission approved oral test indicated for the diagnosis of adult growth hormone deficiency (AGHD). The Company is leveraging the clinical success and compelling safety profile of macimorelin to develop it for the diagnosis of childhood-onset growth hormone deficiency (CGHD), an area of significant unmet need. Aeterna Zentaris is dedicated to the development of its therapeutic asset and has established a pre-clinical development pipeline to potentially address unmet medical needs across a number of indications, including neuromyelitis optica spectrum disorder (NMOSD), Parkinson's disease (PD), hypoparathyroidism and amyotrophic lateral sclerosis (ALS; Lou Gehrig's disease). For more information, please visit www.zentaris.com and connect with the Company on Twitter, LinkedIn and Facebook. Forward-Looking Statements This press release contains statements that may constitute forward-looking statements within the meaning of U.S. and Canadian securities legislation and regulations, and such statements are made pursuant to the safe-harbor provision of the U.S. Securities Litigation Reform Act of 1995. Forward-looking statements are frequently, but not always, identified by words such as "expects," "aiming", "anticipates," "believes," "intends," "potential," "possible," and similar expressions. Such statements, based as they are on current expectations of management, inherently involve numerous risks, uncertainty and assumptions, known and unknown, many of which are beyond our control. Forward-looking statements in this press release include, but are not limited to, those relating to Aeterna's expectations regarding: its ability to secure a commercialization partner in North America and to re-launch sales of Macrilen® in the United States, its expectations for the timing of completion and success of the DETECT-trial, the potential for macimorelin to be approved for the treatment of CGHD and other statements related to the clinical, regulatory or commercial success of macimorelin (Macrilen®; GHRYVELIN™). Forward-looking statements involve known and unknown risks and uncertainties, and other factors which may cause the actual results, performance or achievements stated herein to be materially different from any future results, performance or achievements expressed or implied by the forward-looking information. Such risks and uncertainties include, among others, we may not be successful in finding a commercialization partner for Macrilen® in North America or other territories not currently partnered, we may not be able to re-launch sales of Macrilen® in the United States, our reliance on the success of the DETECT-trial in CGHD; results from our ongoing or planned pre-clinical studies and our DETECT-trial may not be successful or may not support advancing the product further in pre-clinical studies, to human clinical trials or regulatory approval; our ability to raise capital and obtain financing to continue our currently planned operations; our now heavy dependence on the success of macimorelin (Macrilen®; GHRYVELIN™) and related out-licensing arrangements and the continued availability of funds and resources to successfully commercialize the product; the global instability due to the global pandemic of COVID-19 and the war in the Ukraine, and their unknown potential effect on our planned operations; our ability to enter into out-licensing, development, manufacturing, marketing and distribution agreements with other pharmaceutical companies and keep such agreements in effect; and our ability to continue to list our common shares on the NASDAQ. Investors should consult our quarterly and annual filings with the Canadian and U.S. securities commissions for additional information on risks and uncertainties, including those risks discussed in our Annual Report on Form 20-F and annual information form, under the caption "Risk Factors". Given the uncertainties and risk factors, readers are cautioned not to place undue reliance on these forward-looking statements. We disclaim any obligation to update any such factors or to publicly announce any revisions to any of the forward-looking statements contained herein to reflect future results, events or developments, unless required to do so by a governmental authority or applicable law. No securities regulatory authority has either approved or disapproved of the contents of this news release. The Toronto Stock Exchange accepts no responsibility for the adequacy or accuracy of this release.Investor Contact: Jenene ThomasJTC TeamT (US): +1 (833) 475-8247E: aezs@jtcir.com

Phase 3License out/inDrug Approval

17 Mar 2023

·www.pharmaceutical-technology.com

Pharmanovia signs licence deal for Aeterna Zentaris’ Ghryvelin

AGHD affects two to three people in 10,000 with significant morbidity risk. Credit: Priscilla Du Preez / Unsplash. Pharmanovia and Aeterna Zentaris have entered an exclusive licensing agreement for the latter’s medicine Ghryvelin (macimorelin). Under the deal, Pharmanovia will acquire the exclusive rights and license to commercialise Ghryvelin in the EEA and the UK from Consilient Health. Ghryvelin is used for the diagnosis of Adult Growth Hormone Deficiency (AGHD), a rare and serious condition, as well as for Childhood Onset Growth Hormone Deficiency (CGHD), if approved. Macimorelin is marketed under the brand name Ghryvelin in the EEA and the UK. It is a ghrelin agonist, an orally active small molecule that has been designed to stimulate the secretion of growth hormone from the pituitary gland. Pharmanovia CEO Dr James Burt said: ‘’Endocrinology is the largest of our four core therapy areas and the in-licensing of this important novel medicine, the second in-licensing deal of a novel medicine in almost as many weeks, speaks to our ability to in-licence novel, complementary products in the therapeutic settings we support. “We are well placed to use the knowledge and the platform we’ve built through our current endocrinology work to ensure that more patients get the diagnosis they need for this rare and serious condition. “Furthermore, today’s announcement presents a rare opportunity to license in a medicine that naturally synergises with one of the core growth products in our current portfolio.” The company stated that the new licensing agreement expands its existing endocrinology portfolio. According to Pharmanovia, AGHD affects two to three people in 10,000 with significant morbidity risk and reduced quality of life.

License out/inDrug Approval

100 Deals associated with Lenomorelin

External Link

KEGG	Wiki	ATC	Drug Bank
-	Lenomorelin	-	DB11895

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Anorexia Nervosa	Phase 3	JP	Asubio Pharma Co. Ltd.	-
Muscular Atrophy	Phase 3	-	University of California San Diego	-
Muscular Atrophy	Phase 3	JP	KineMed, Inc.	-
Muscular Atrophy	Phase 3	-	Oxeia Biopharmaceuticals, Inc.Startup	-
Muscular Atrophy	Phase 2	-	Biopharma Forest Inc.	-
Pulmonary Disease, Chronic Obstructive	Preclinical	GT	Daiichi Sankyo, Inc.	15 May 2008
Pulmonary Disease, Chronic Obstructive	Preclinical	AR	Daiichi Sankyo, Inc.	15 May 2008
Pulmonary Disease, Chronic Obstructive	Preclinical	HN	Daiichi Sankyo, Inc.	15 May 2008
Pulmonary Disease, Chronic Obstructive	Preclinical	US	Daiichi Sankyo, Inc.	15 May 2008
Pulmonary Disease, Chronic Obstructive	Preclinical	CL	Daiichi Sankyo, Inc.	15 May 2008

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04558346 (Corporate Publications) Manual	Phase 2	Brain Concussion	-	OXE103	ekjdjyqnzo(xcoemfusnq) = Promising interim results show potential for OXE103 as an effective treatment for concussion iislacbrqy (qbfjuiuizg )	Positive	03 Aug 2022
DDW2022	Not Applicable	-	-	ghrelin (Fasted rats)	kqgyptukrj(msprtoglve) = a significant increase in c-Fos expression was observed by ghrelin administration only in fasted rats yrckbqvvuv (uvfjfsmgfr ) View more	-	23 May 2022
				ghrelin (Non-fasted rats)
DDW2022	Not Applicable	-	-	Ghrelin	(ohvdddwoyw) = vuonsnopru jlwdrfjdsw (rjqurzbjwx ) View more	-	23 May 2022
				GLP-1	(ohvdddwoyw) = gmpjllsjgn jlwdrfjdsw (rjqurzbjwx ) View more
DDW2022	Not Applicable	-	-	Ghrelin	(ygtchlrqvi) = ryurdsvgyk qjvxsqzmsn (pbyrzcddnd ) View more	-	23 May 2022
				GLP-1	(ygtchlrqvi) = deoddbogpo qjvxsqzmsn (pbyrzcddnd ) View more
DDW2022	Not Applicable	-	-	ghrelin (Fasted rats)	dvxmuoomyf(chcjyeqbti) = a significant increase in c-Fos expression was observed by ghrelin administration only in fasted rats dixpwytzhc (gbmeeljlhl ) View more	-	23 May 2022
				ghrelin (Non-fasted rats)
DDW2022	Not Applicable	-	-	Ghrelin	(pqeakwojfq) = ldahqycauu nepgmqxteu (mecxbscqyj ) View more	-	23 May 2022
				GLP-1	(pqeakwojfq) = qzpnklgluv nepgmqxteu (mecxbscqyj ) View more
DDW2022	Not Applicable	-	-	ghrelin (Fasted rats)	mdneprzagq(upfvieqhay) = a significant increase in c-Fos expression was observed by ghrelin administration only in fasted rats woaergcemq (qrvykgpado ) View more	-	23 May 2022
				ghrelin (Non-fasted rats)
DDW2022	Not Applicable	-	-	ghrelin (Fasted rats)	gaoadcaaln(affltzgnkn) = a significant increase in c-Fos expression was observed by ghrelin administration only in fasted rats coifwjkzmw (jefbemrhem ) View more	-	23 May 2022
				ghrelin (Non-fasted rats)
DDW2022	Not Applicable	-	-	ghrelin (Fasted rats)	modcblteum(fynnixrwom) = a significant increase in c-Fos expression was observed by ghrelin administration only in fasted rats jmhjduvhey (udevylrgxx ) View more	-	23 May 2022
				ghrelin (Non-fasted rats)
DDW2022	Not Applicable	-	-	Ghrelin	(rlvhrnuucx) = hnosjohcii okqwldujzx (tjwcfppvef ) View more	-	23 May 2022
				GLP-1	(rlvhrnuucx) = fqpwgkekjg okqwldujzx (tjwcfppvef ) View more

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