Cancer, COPD, asthma, and cardiovascular disease are among the most common and fastest-growing diseases worldwide. Millions die each year of these diseases, yet there remains an unmet medical need, due to the lack of effective treatments. Our portfolio addresses each disease. For oncology, VAL-001 is in clinical phase IIa as a pretreatment to chemotherapy for Non-Hodgkins Lymphoma. For COPD and asthma, Respiratorius has both RESP-1000 and RESP-2000 in preclinical phase. PET imaging is a growing diagnostic modality. RESP-3000 is a PET-tracer dedicated to perfusion diagnostics of coronary artery disease (CAD).
Christer Fåhraeus founded Respiratorius in 1999 to target COPD and severe asthma. Since its inception, about 90 million SEK has been invested into Respiratorius, which began with the development of a high-sensitive force measurement equipment (RESP-HSAT), assessing contractile forces of dissected human lung tissue. With the use of samples from about 200 individuals, we discovered how chemical substances affect bronchial smooth muscle, and then synthesized RESP-1000, which has a new mode of action and superior effect when compared to known bronchodilating substances. Respiratorius acquired Valcuria AB in 2012, including the rights to VAL-001, allowing for portfolio expansion with a clinical phase project.
In malignant lymphoma, diffuse large B-cell lymphoma (DLBCL) is the most frequent subtype (approximately 31%), with 3-4/100,000 annually in the EU. The median age of diagnosis is 65, and it is slightly more common in males than females. DLBCL is a heterogeneous group of diseases, with no common genetic or clinical features. Standard treatment was originally a multi-drug chemotherapy known as CHOP, while the addition of rituximab created a more recent international standard, R-CHOP. The problem lies in the following: as a starting point, 10-15% of patients do not respond to therapy. Of those who do respond, 40% will relapse – and once they have relapsed, will no longer respond to R-CHOP. For patients who relapse and those with refractory disease, treatment is expensive, difficult to tolerate, and includes side effects such as infections and cardiac toxicity. Elderly patients with DLBCL are often unable to tolerate treatment and, therefore, only palliative treatment remains. The current 5 year survival rate is approximately 60%.
VAL-001 is a combination of a histonedeacetylase inhibitor (HDACi) and a steroid, which, in preclinical experiments, shows increased effect on cell viability in combination with CHOP. In December 2013, the phase I study of VAL-001 was completed, establishing maximum tolerable dose (MTD) of VAL-001 in combination with R-CHOP. The MTD corresponded well with preclinical data and strong effects on evaluated biomarkers were achieved. In February 2014, the phase IIa study, a dose expansion of 20 patients on the MTD was initiated. In parallel with clinical development, work is in progress with a formulation of VAL-001.
COPD and Asthma (RESP-1000, RESP-2000)
Approximately 10% of the population over the age of 45 is affected by COPD, and an estimated 3 million die annually of the disease. The global asthma and COPD market was worth USD ~25M in 2010 and expected to reach USD ~27 M in 2017.
Respiratorius develops pharmaceuticals for COPD and severe asthma, focusing on a new class of substances with a superior ability to relax small airways compared to existing therapies. The substances use a new mechanism of action and are developed with new, world-leading, proprietary-force measurement equipment. The first clinical candidate, RESP-1000, shows broncho-relaxing and anti-inflammatory properties. A second series, RESP-2000 is also underway. During 2014 Respiratorius signed a license and development agreement with Cadila Pharmaceuticals Ltd for the RESP-1000 project.
Coronary Artery Disease (RESP-3000)
Coronary artery disease (CAD) is the leading cause of death in the USA, and imaging techniques are pivotal for diagnosis and prognosis. SPECT and PET are used for current evaluation of myocardial blood flow, but new and improved imaging agents are needed. Selective mitochondrial complex I (MC-1) inhibitors have demonstrated use as cardiovascular diagnostic agents, because of the high weight percentage of mitochondria in myocardia.
Respiratorius’s novel PET-tracer (RESP-3000) is a selective mitochondrial complex-1 (MC-1) inhibitor for myocardial perfusion imaging (MPI). The chemistry is optimized for 18F labeling, and data shows radiosynthesis yields >435 MBq and analytical radiochemical purity of 98%. A in-vivo proof-of-concept study was finalized with good results during 2014.