BioWorld International Correspondent
Italy’s first major biotechnology start-up of the year is a spinout from the Milan research unit of F. Hoffmann-La Roche Ltd. BioXell SpA, which was formed at the beginning of January, held a public launch last week and disclosed its first-round funding of EUR22 million (US$19.3 million).
MPM Capital, Index Ventures and Life Science Partners all backed the new company, which, CEO and co-founder Francesco Sinigaglia told BioWorld International, has a post-money valuation of EUR40 million.
Roche, of Basel, Switzerland, retains a 17 percent stake in BioXell, which currently has programs in septic shock, secondary hyperparathyroidism and benign prostatic hyperplasia. Its lead compound, BXL628, has completed Phase I trials in the latter indication and is expected to enter Phase II trials before the year’s end.
Sinigaglia was the founder and scientific director of Roche Milano Ricerche, which focused on chronic inflammatory diseases and autoimmunity. The other co-founders of BioXell are Chief Scientific Officer Luciano Adorini, who is vice president of the Italian Society for Immunology, and Chairman Michael Steinmetz of MPM Capital.
All of the staff of the Roche unit has transferred into the new company, which has 30 people based in Milan, its center for pharmacology and clinical development. In addition, a second Roche lab, a four-person medicinal chemistry unit based in Nutley, N.J., has been included in the new structure as a wholly owned subsidiary, BioXell Inc.
BioXell has two principal technology platforms, both in the immunology field. It is developing TREM receptors (triggering receptor expressed on myeloid cells) as targets for therapeutic intervention in septic shock. Its programs in secondary hyperparathyroidism and benign prostatic hyperplasia are part of a wider research effort into vitamin D3 analogues, which act via nuclear receptors and have a range of cell cycle and immunomodulatory effects. BioXell has inherited from Roche a patent portfolio covering more than 200 vitamin D3 analogues in total.
Benign prostatic hyperplasia is a novel indication for vitamin D3 therapy, Adorini said. In vitro work with cells taken from patients with the condition indicates that it plays a role in the phosphorylation of certain receptors for growth factors that are involved in prostate growth. A treatment strategy based on this approach would bypass problems with impotence and reduced libido associated with current anti-androgen therapy, he said.
Secondary hyperparathyroidism arises primarily in patients undergoing kidney dialysis. Chronic renal failure results in the loss of a key enzyme, 1-alpha-hydroxylase, which is required to catalyze the conversion of vitamin D3 from its inactive to its active form. This, in turn, leads to uncontrolled production of parathyroid hormone and osteomalacia due to the inability to absorb calcium. Analogues have been administered for the past 20 years the market is worth an estimated US$600 million, Adorini said but BioXell aims to develops new compounds with superior efficacy and reduced toxicity. Two, BXL353 and BXL490, are in advanced preclinical development. One will be selected for Phase I clinical trials before the year’s end.
Its TREM receptor program derives from work scientific collaborator Marco Colonna, of Washington University in St. Louis, carried out at the Basel Institute of Immunology. It was published in the April 26, 2001, issue of Nature in a paper titled “TREM-1 amplifies inflammation and is a crucial mediator of septic shock.”
The TREM-1 receptor is expressed on monocytes and granulocytes and is involved in mediating the release of inflammatory chemokines and cytokines. In animal models of microbial sepsis, injection of a soluble form of the TREM-1 receptor prevents septic shock, presumably by mopping up the ligands that would otherwise cause it. “The ligands are not known yet. What you do is block the ligands, basically,” Sinigaglia said. The company is developing soluble fusion proteins that incorporate the receptor domain of TREM-1 as potential therapies. But it also is working to identify the ligands that bind to and activate the receptor, with a view to developing antagonists.
“Now we are trying to find a suitable corporate partner to further develop the septic shock program, which is a particularly difficult indication for a small biotechnology company,” Sinigaglia said. “We are discussing it with several pharmaceutical companies. Certainly, Roche is one.”