D3 receptor

The first-in-human Phase 1 clinical study will evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamic profile of ENX-104 in healthy volunteers SAN DIEGO, Sept. 18, 2024 (GLOBE NEWSWIRE) -- Engrail Therapeutics, a precision neuroscience company focused on the development of transformational therapies to improve the lives of patients, today announced initiation of a Phase 1 single ascending dose clinical study for ENX-104 in healthy volunteers. ENX-104 is a potent and selective dopamine D2/D3 receptor antagonist designed to enhance dopamine neurotransmission by preferential autoreceptor inhibition at low doses. The lead indication for ENX-104 is the treatment of major depressive disorder (MDD) characterized by anhedonia (aMDD). Anhedonia is the inability to experience pleasure in normally pleasurable activities and is a core symptom of MDD that is largely unresponsive to currently approved antidepressants. “Dysregulation of dopamine in the reward centers of the brain is believed to underlie anhedonia which is experienced by 60-70% of MDD patients. ENX-104 provides a novel and targeted approach to enhancing dopamine modulation and represents a potential new therapeutic modality for the treatment of patients with aMDD,” said Vikram Sudarsan, PhD, chief executive officer of Engrail. “The initiation of this Phase 1 study is a significant step forward for ENX-104 and an important milestone for Engrail as our second clinical-stage program.” The ENX-104 Phase 1 study is a randomized, double-blind, placebo-controlled single ascending dose clinical study that is expected to enroll up to 48 healthy adult volunteers. The primary objective is to evaluate the safety and tolerability of ENX-104 after a single oral administration of increasing doses in separate cohorts. Each dose cohort will include 8 subjects, with 6 subjects randomized to ENX-104 and 2 to placebo. The study is also designed to measure pharmacokinetics and explore the pharmacodynamic effects of ENX-104 on biomarkers associated with changes in dopamine neurotransmission in order to ascertain target engagement. About ENX-104ENX-104 is a potent dopamine D2/D3 receptor antagonist in development for major depressive disorder (MDD) characterized by anhedonia (aMDD). Dysregulated dopaminergic neurotransmission, particularly in brain reward systems, is believed to underlie anhedonia, a hallmark symptom of MDD. ENX-104 was designed to directly modulate dopaminergic transmission in brain reward systems by increasing dopamine release via potent antagonism of presynaptic D2/D3 autoreceptors at low doses. ENX-104 is in Phase 1 clinical development. About Engrail TherapeuticsEngrail is a clinical-stage pharmaceutical company with a rich pipeline of precision-targeted neuroscience programs designed to improve the lives of patients with neuropsychiatric and neurodevelopmental diseases. ENX-102, a next-generation GABAA positive allosteric modulator, is in Phase 2 clinical development for the treatment of generalized anxiety disorder. ENX-104, a potent dopamine D2/D3 receptor antagonist, is in Phase 1 clinical development for the treatment of major depressive disorder characterized by anhedonia. Additional programs in development are intended to address significant unmet medical needs for the treatment of posttraumatic stress disorder, anxiety-, mood- and stress-related disorders and rare neurological conditions. At Engrail, we apply precision chemistry and pharmacology to develop transformative medicines for patients who are underserved by existing treatments. For more information, visit engrail.com. Media Contact:Anil Vootkur, PharmDEngrail Therapeuticsanil@engrail.com

Biotech accelerator CinRx Pharma has secured an additional $73 million in financing to support its existing spinouts, created via its hub-and-spoke business model, as well as to pursue new programmes in areas with high unmet medical need. The latest infusion of capital, which brings its total funding to $176 million, was raised from prior investors including industry insiders and high-net-worth individuals. The new funding will enable CinRx to “replicate our proven asset selection process to identify and accelerate more promising new programs with high potential to impact patients’ quality of life,” according to Jon Isaacsohn, chief executive of CinRx Pharma.Seven CinCosTo date, CinRx has created seven portfolio companies  – so-called "CinCos" – of which five  are focused on cardiovascular, metabolic or gastrointestinal disorders. Most notably, hypertension drug developer CinCor was acquired by AstraZeneca last year for $1.3 billion upfront. The other four spinouts – CinFina, CinDome, CinPhloro and vTv Therapeutics – are focused on treatments for obesity, gastroparesis, irritable bowel syndrome and hypoglycaemia, respectively. CinFina’s four-candidate pipeline was in-licensed from Johnson & Johnson’s Jassen Pharmaceuticals unit and comprises two obesity assets in Phase I testing, along with a pair of preclinical programmes. CinDome’s lead candidate is deudomperidone (CIN-102), a dopamine D2/D3 agonist in a Phase II study of adults with diabetic gastroparesis; data are due next year.CinPhloro was built to develop CIN-103, a small molecule, pulsatile-release formulation of phloroglucinol modified to require less frequent dosing. The candidate is in a Phase II trial in patients with irritable bowel syndrome with diarrhoea, which is expected to wrap in 2025.The most advanced programme belongs to vTv Therapeutics, whose TTP399 – an oral, small molecule, liver selective glucokinase activator – is in a Phase III study as an adjunct therapy to insulin to manage hypoglycaemia in patients with type 1 diabetes.

Financing brings total funds raised to $176M to advance diverse portfolio of high-impact medicines and expand efforts to additional high unmet needs Current portfolio of CinCos include two clinical-stage obesity therapeutics, two Phase 2 gastrointestinal programs and several pre-clinical programs CINCINNATI--(BUSINESS WIRE)-- CinRx Pharma, a hub-and-spoke biotech accelerating high-impact medicines, today announced the closing of a $73 million financing, bringing the total funds raised to $176 million. Participants in the round include prior investors comprised of industry insiders and high-net-worth individuals. To date, CinRx has launched five companies (“CinCos”) focused primarily on cardiovascular, metabolic and gastrointestinal conditions. In addition to its company creation function, CinRx has forged several CINergy partnerships with existing companies. CinRx plans to use the funds to advance development of its existing portfolio programs and assets to expand in key areas of high unmet medical need. “Our early financings totaling $103 million supported the construction and progression of our seven-company portfolio. Notably, this included the formation, advancement and exit of CinCor Pharma ahead of its $1.8 billion acquisition, underscoring the success of our incredibly effective team and validation of our efficient business model,” said Dr. Jon Isaacsohn, Founder and Chief Executive Officer at CinRx Pharma. “With this infusion of capital, we will continue rapid advancement of existing programs and replicate our proven asset selection process to identify and accelerate more promising new programs with high potential to impact patients’ quality of life.” CinRx’s portfolio of CinCos are managed by a lean team of scientific, technical and drug development experts with decades of experience treating patients and supporting thousands of clinical development programs. Each CinCo was created through a rigorous asset selection process to identify novel therapies with the potential to address significant unmet medical needs and meaningfully reduce disease burden for patients. CinCor Pharma was created to advance baxdrostat (CIN-107), a highly selective, oral small molecule inhibitor of aldosterone synthase for the treatment of hypertension and other cardiorenal conditions from a license agreement with Roche in 2019. CinRx led the clinical design and execution of baxdrostat, and was responsible for CinCor’s successful Series A and Series B financings to fund its early development through its $194 million IPO in 2022. In early 2023, CinCor was acquired by AstraZeneca in a deal worth $1.3 billion upfront and an additional $500 million in biobucks. CinFina Pharma is developing a pipeline of four therapies, in-licensed from Janssen Pharmaceuticals, aimed at providing safe, tolerable and durable options for treating obesity. In March 2024, CinFina announced the dosing of the first patients in a Phase 1 trial of CIN-110, a PYY analog. Upcoming milestones include initiation of a Phase 2 study evaluating CIN-109, a novel GDF-15 molecule focusing on body composition and lean body mass preservation, with and without semaglutide. Additional preclinical development is ongoing to support Investigational New Drug (IND) application submissions for CIN-209 and CIN-210, which are both dual-agonists utilizing GLP-1 therapy in combination with the aforementioned mechanisms of action. CinDome Pharma is developing deudomperidone (CIN-102) as a potential safe, chronic treatment for gastroparesis. Deudomperidone is a novel formulation of a well-known dopamine D2/D3 agonist, domperidone. In May 2023, CinDome presented encouraging QT study data at the 2023 Digestive Disease Week (DDW) Conference. CinDome recently raised $40 million in a Series B financing from Perceptive Advisors and CinRx, and is actively enrolling the Phase 2 envision3D study for adults with diabetic gastroparesis, expected to read out in 2025. CinPhloro Pharma is progressing CIN-103, a small molecule for the long-term management of irritable bowel syndrome with diarrhea (IBS-D). CIN-103 is a pulsatile-release formulation of phloroglucinol, an approved therapy in select countries outside of the U.S., modified for sustained exposure and less frequent dosing. In February 2024, CinPhloro dosed the first patients in the Phase 2 enviva study to evaluate the safety, efficacy and tolerability of CIN-103 for IBS-D. CinPhloro is actively enrolling the enviva study, which is expected to complete in 2025. 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.