Sompharmaceuticals S.A. is a biopharmaceutical company based at the Biopôle in Epalinges-Lausanne, Switzerland focused on developing novel anti-tumor somatostatin analogue (SSA) peptide medicines and diagnostics for patients with rare diseases, which have unmet medical needs and major market opportunities. These include growth hormone producing pituitary tumors (acromegaly), Cushing’s Disease and malignant, neuroendocrine hormone producing intestinal and pancreatic tumors (NETs) that are resistant or poorly controlled with currently available SSA treatments, octreotide and lanreotide.
The Company’s lead candidate therapy, G02113, is a dual-receptor specific, SSA which has enhanced affinity for the two somatostatin subtype receptors (SSTR) 2 and 5 that control hormone released from the above mentioned tumors. G02113 is designed to overcome the limited efficacy of available SSAs.
Currently the Company has established proof-of-concept in animals and in experiments on human pituitary adenoma biopsies with its lead peptide G02113. The Company is currently conducting formal regulatory studies to facilitate the first-in-man exposure to the lead therapeutic in a Phase I/IIa clinical study in the first half of 2015.
Company Achievements and Development Milestones
G02113 has demonstrated enhanced specific binding to two key SSTRs 2 and 5 that control tumoral hormone production, and marked suppression of GH and prolactin secretion in rat pituitary cells a well-established preclinical model for the screening of SSAs [Moore et al, J Med. Chem. 2005]. Successful synthesis and manufacturing of >97% purity G02113 was achieved by two independent peptide manufacturers in the UK and the US. EU and US Orphan Drug Designation submissions which would allow market exclusivity for 7 years in the US and 10 years in EU and Japan are on-going. In order to support the development of G02113, a grant was awarded in June 2013 by the CTI (Commission for Technology Innovation) a Swiss Federal Agency for CHF540,000. Other applications to various grant awarding bodies including the EU are pending.
The Company has completed acute and chronic rat proof-of-concept and pharmacological studies. These studies have confirmed that the SSTR binding affinity of G02113 is associated with a desirable biological effect profile. Of note unlike pasireotide, G02113 does not cause hyperglycemia and thus provide optimal control for patients unresponsive or poorly responsive to existing SSAs. Also G02113 inhibited GH and IGF-1 significantly in healthy rats, in a manner that was also different from pasireotide, indicating that the profile of G02113 is one that could compete aggressively with that of all existing somatostatin analogs. Additionally, the Company has established proof-of-concept in experiments on several human pituitary adenoma biopsies with its lead peptide.
Following a pre-IND meeting with the FDA in December 2012, the Company is preparing to initiate a first in man Phase I clinical trial program with a subcutaneous injectable, immediate release formulation under an IND in 2014 followed by a Phase II study using a patented optimized controlled release injectable formulation in patients with active acromegaly, who are resistant or sub-optimally controlled with octreotide. Subsequently, Phase II clinical studies will be initiated in patients with malignant NETs such as carcinoid syndrome who are poorly controlled with SSAs due to primary resistance or disease progression. Phase III studies for both indications could then be initiated with the involvement of a large pharmaceutical partner or alone with additional funding.
The Company recently closed its Series A Financing Round after raising 1.1.M CHF (900K Euros). The Company now seeks and additional 11.7 M Euros in two tranches to finance the clinical phases.
Disease Targets and Markets: Acromegaly and Malignant NETs
Acromegaly is a debilitating, life-threatening, rare endocrine disease characterized by excess production of growth hormone (GH) that occurs almost exclusively as a result of a tumor in the pituitary gland located at the base of the brain.
With a median prevalence of 1.2 per 10,000 (40,507 patients in the US) acromegaly is a recognized Orphan Disease in both the EU and US. Treatment includes surgical removal of the tumor, radiotherapy and pharmaceutical treatment. Current SSAs, octreotide and lanreotide are the standard-of-care first-line medical therapy for surgical failures followed by the GH antagonist Somavert (Pegvisomant) in case of resistance or poor GH control.
NETs are a family of rare hormone producing cancers of the digestive tract. The most frequent is a major subtype called carcinoid tumor that causes severe diarrhea, hypotension, flushing and cardiac damage due to excessive release of hormones. The prevalence of NETs in the US is 103,312 cases. Surgical excision of the tumor is not possible in most cases due to the presence of distant metastases (often in the liver).
Main pharmaceutical therapies used for symptom control of carcinoid tumors and NETs are the SSAs octreotide and lanreotide, a similar class to that of G02113, which together generate sales of approximately $1.9Bn per year. Some patients with carcinoids will experience tumor stabilization during SSA treatment. G02113 is designed to enhance symptom control, prolong tumor size stabilization and delay the time to disease progression to a greater extent than the two available SSAs.
Cushing’s disease is a rare hormone disorder. Recent statistics indicate that annual incidence is somewhere between 1 and 10 new cases per million and is 3 times more common in women than in men. Cushing’s disease is the specific form of Cushing’s syndrome caused by a pituitary adenoma (usually a microadenoma) that secretes excessive levels of the hormone ACTH. Approximately 15% of pituitary adenomas are ACTH secreting. In Cushing’s disease, the feedback inhibition normally exerted by cortisol on corticotropin-releasing hormone (CRH) and ACTH production ceases to have an effect. The normally tightly regulated hypothalamic-pituitary-adrenal (HPA) axis is no longer effective, therefore the pituitary adenoma continues to release ACTH and the adrenal glands release cortisol continuously in response. Excess production of cortisol by the adrenals results in the characteristic clinical features of Cushing’s syndrome and has effects on several biochemical systems. G02113 binds to the SSTR receptors present on the adenoma reducing secretion of ACTH which in turn will reduce the excess secretion of cortisol by the adrenals resulting in symptom control of the disease.
Unmet Medical Need and Scientific Rationale for a Next Generation SSA, G02113
In acromegaly or NETs, the relative proportions somatostatin receptors SSTR2 and 5 expressed by the tumors are variable but important. For tumors that express less SSTR2 or have undergone octreotide-induced SSTR2 down-regulation, octreotide is less likely to produce hormonal control and tumour size control (in NETs) or tumor shrinkage (acromegaly). In these situations, the addition of enhanced SSTR5 action via an agonist such as G02113, can add hormone suppression and tumor stabilization that is unachievable by octreotide or lanreotide alone. This potentiation of effect occurs because SSTR5 acts synergistically with SSTR2 to enhance its inhibitory effects, while potentially having its own suppressive or anti-tumor activities. In the case of G02113, the affinity for SSTR2 is similar to that of octreotide, thus covering the 40% of patients that do respond adequately to octreotide and lanreotide, while its enhanced affinity for SSTR5 may control the remaining 60% of patients who are not appropriately controlled or resistant in terms of hormonal production and potentially tumor stabilization or shrinkage. Thus, G02113 may represent an effective therapy for a significant proportion of the 60% of patients, indeed may be all, of the patients available for pharmaceutical intervention.
Further, G02113 does not lead to hyperglycemia and diabetes in animal studies, unlike pasireotide/Signifor
This profile of G02113 means that it could also represent a superior compound to Signifor/pasireotide in the approved indication of Cushing’s Disease, where hormonal reductions that are not complicated by worsening diabetes would represent a superior clinical/commercial proposition.
Alan G. Harris, MD, PhD – Chairman
John Watson – CEO
4/29/14: 750,000CHF – Series A
10/15/13: 100,000CHF – Foundation for Technological Innovation (Switzerland)
6/15/13: 540,000CHF – Commission for Technology Innovation (Switzerland)
Murray Goodman, PhD (deceased)
Division of Physical Sciences