At DAMIAN, we want to help patients by creating something tangible. We focus our expertise on the diagnosis, localization and treatment of aldosterone-dependent conditions.
Identified in 1956, Primary Aldosteronism is a hormonal disorder that produces significant negative outcomes and has no targeted treatment. DAMIAN aims to change that.
The Disease
The adrenal glands help maintain blood pressure and organ perfusion through the controlled secretion of the hormone aldosterone. Primary Aldosteronism (PA) is a disorder that occurs when adrenal production of aldosterone is no longer controlled. This overproduction of aldosterone leads to water and sodium retention and potassium loss. This can result in irreversible structural damage to the blood vessels and manifest as chronic high blood pressure. Untreated, PA can lead to an increased risk of stroke, myocardial infarction, and chronic kidney disease.
dexfadrostat phosphate (DP13): Our Investigational Drug
The aldosterone synthase inhibitor dexfadrostat phosphate (DP13) is a first-of-its-kind treatment for primary aldosteronism (PA) that medically targets the cause of the disease. DAMIAN successfully completed its Phase I Clinical Trial evaluating the pharmacological properties of dexfadrostat phosphate in healthy volunteers. The safety and efficacy of dexfadrostat phosphate was investigated across Europe in a Phase II Trial, becoming the first clinical trial to demonstrate clinical efficacy in patients with PA without raising safety concerns.
Currently available therapies have no impact on the cause of PA i.e., the overproduction of aldosterone. In contrast, dexfadrostat phosphate selectively inhibits the enzyme responsible for aldosterone production, thus directly reducing the amount of aldosterone in the body.
DP14: Our Diagnostic Tool
The diagnostic pathway for PA is complex, requiring specialist expertise, particularly the detection of a unilateral tumor which is not always successful. The introduction of DP14, a unique PET tracer currently in the research phase, has the potential to image and localize aldosterone-producing benign tumors without the need for specialist surgery and with a higher success rate.
Future Directions
DAMIAN is committed to helping patients by finding treatment solutions wherever they exist. Remaining true to its mission, DAMIAN continues to identify and evaluate additional therapeutic opportunities or diagnostic solutions in other aldosterone-dependent conditions.
Professor of Internal Medicine, University of Torino, Italy
PA Expert and DP13C201 Principal Investigator
DAMIAN announces publication of phase 2 data of dexfadrostat phosphate in patients with primary aldosteronism
A new open-access publication
DAMIAN announces online publication of the primary data from clinical study DP13C201 in eClinical Medicine, a Lancet journal. The clinical phase 2 study assessed whether dexfadrostat phosphate, a novel aldosterone synthase inhibitor taken orally once a day for 8 weeks, could provide biochemical and clinical benefit in patients with primary aldosteronism (PA) diagnosed, according to the Endocrine Society Clinical Practice Guidelines. The study also evaluated the effect of dexfadrostat phosphate on ambulatory diastolic blood pressure, office systolic and diastolic blood pressure, serum potassium and urinary aldosterone content as well as cortisol levels.
Structural and clinical characterization of CYP11B2 inhibition by dexfadrostat phosphate
A new open-access publication
The final three steps of the biosynthetic pathway of aldosterone are catalyzed by CYP11B2, also known as aldosterone synthase. Hence, inhibiting aldosterone synthase is a targeted mechanism for new therapeutic compounds aimed at reducing aldosterone production. In a new publication by Pignatti et al. the authors reveal that the novel aldosterone synthase inhibitor, dexfadrostat phosphate, aligns with the catalytic moiety of CYP11B2 but not CYP11B1, a related enzyme in the biosynthetic pathway of cortisol. Additionally, both in vitro and clinically, dexfadrostat phosphate demonstrated significant inhibition of CYP11B2 vs. CYP11B1 and did not change basal cortisol levels. Importantly, dexfadrostat phosphate inhibits the final steps in aldosterone biosynthesis, leading to dose-dependent reductions in aldosterone in healthy volunteers.
Pignatti et al., Journal of Steroid Biochemistry and Molecular Biology. 2023; 235.
Doi: 10.1016/j.jsbmb.2023.10640. Online ahead of print.
DAMIAN announces publication in the British Journal of Clinical Pharmacology of phase 1 data of dexfadrostat phosphate in healthy volunteers
Today DAMIAN announces the publication of study DP13C101, a phase 1 study evaluating the efficacy and safety of dexfadrostat phosphate in healthy volunteers in the British Journal of Clinical Pharmacology.
Dexfadrostat phosphate is a novel aldosterone synthase inhibitor (ASI), which acts to directly control the production of aldosterone at its origin. “By inhibiting the 3 enzymatic conversions mediated by aldosterone synthase, dexfadrostat phosphate was shown to demonstrate a dose-dependent reduction of the aldosterone-to-renin ratio (ARR, a marker of sodium retention) without affecting the adrenal stress response or the hypothalamic-pituitary-gonadal axis.”
DAMIAN announced in October 2022 the successful completion of a phase 2 study evaluating dexfadrostat phosphate in patients with primary aldosteronism. The study met both its primary endpoints (ARR, ambulatory systolic blood pressure reduction) with high statistical significance following 8 weeks of once-daily treatment. The study also demonstrated a good safety and tolerability profile.
Mulatero et al., Brit J Clinical Pharmacol. 2023 Mar 13; doi: 10.1111/bcp.15713. Online ahead of print
DAMIAN announces dexfadrostat phosphate achieves high efficacy in PA patients
DAMIAN announces new data from the Phase II trial in patients with primary aldosteronism (PA), that showed the investigational compound dexfadrostat phosphate effectively reduced both aldosterone-to-renin ratio (ARR) and ambulatory systolic blood pressure (aSBP). The trial met both primary endpoints with high significance.
https://dampha.s3.us-east-2.amazonaws.com/assets/uploads/damian-press-release-phase-2-data.pdf
DAMIAN receives research grant from Innosuisse
Innosuisse awards third Swiss research grant to DAMIAN to support the further development of its new research project DP20. The new funding supports a collaboration between DAMIAN and its three research partners: Fachhochschule Nordwest Schweiz, ETH Zurich and the University of Bern.
DAMIAN initiates Phase II study of dexfadrostat phosphate (DP13)
DAMIAN enrolls the first patients in its multinational Phase II study of dexfadrostat phosphate in patients with Primary Aldosteronism (NCT04007406; EUDRACT# 2019-000919-85).
DAMIAN conducts Phase I study of dexfadrostat phosphate (DP13)
DAMIAN executes its Phase I proof-of-concept, double-blind, safety and tolerability study of dexfadrostat phosphate in healthy volunteers (NCT03046589). The Phase I study successfully completed in September 2018.
Pre-Investigational New Drug (IND) meeting with FDA
The full clinical development plan for dexfadrostat phosphate (DP13) in Primary Aldosteronism was discussed with FDA in a Pre-IND meeting, including advice on Phase III design and registration endpoints.
DAMIAN receives grant from the Swiss Commission for Technology and Innovation
The Swiss Commission for Technology and Innovation (CTI) awarded DAMIAN with a grant to support the DP14 diagnostic tracer project. The Commission promotes science-based innovation in the interests of industry and society in Switzerland. Funding allocation is based on competitive applications and allows small companies the ability to work with research partners to test and develop their ideas.
DAMIAN clinical plan affirmed by the Foundation for Therapeutic Research
The Lausanne-based Foundation for Therapeutic Research awards a grant for the development of new therapeutic principles in cardiovascular disease to the University of Torino to investigate dexfadrostat phosphate (DP13). The grant supports the Phase I clinical trial of dexfadrostat phosphate, the first-in-class aldosterone synthase inhibitor from DAMIAN.
DAMIAN incorporated in Switzerland
In 2015, DAMIAN was incorporated in Zug, Switzerland with the goal to deliver a targeted medicine to patients with Primary Aldosteronism. Subsequently, the mission of DAMIAN was expanded to find treatment solutions for aldosterone-dependent conditions, wherever they exist.