Biolipox AB

Founded in June 2000 by two professors from Sweden's Karolinska Institute, Biolipox AB is focusing on the role of arachidonic acid in inflammation, and looking to develop an improved family of respiratory and anti-inflammatory drugs.

New Opportunities in Respiratory and Anti-inflammatory Diseases

Founded in June 2000 by two professors from Sweden's Karolinska Institute (KI), Biolipox AB is focusing on the role of arachidonic acid in inflammation, and looking to develop an improved family of respiratory and anti-inflammatory drugs.

Arachidonic acid is an essential, un-saturated fatty acid synthesized by most tissues. It has a wide range of actions and is converted by the body into regulatory molecules such as prostaglandins, thromoboxanes and leukotrienes, all of which play a crucial role in inflammatory disorders. Some prostaglandins are involved in the cascade leading to the pain, heat and swelling associated with inflammation, while leukotrienes are known to trigger allergy and asthma symptoms.

There is no shortage of therapeutics tackling inflammatory conditions mediated by products of, or related to, arachidonic acid's activities. Merck & Co. Inc. 's montelukast (Singulair), Abbott Laboratories Inc. 's zileuton (Zyflo) and AstraZeneca PLC's zafirlukast (Accolate) block the activity of leukotrienes, for example; blockbuster pain/inflammation drugs celecoxib (Celebrex) and rofecoxib (Vioxx) work through inhibiting cyclooxygenase 2 (Cox-2), an enzyme involved in the conversion of arachidonic acid into prostaglandins and thromboxanes. Corticosteroids such as beclomethasone or fluticasone decrease the body's immune response, and are also effective in reducing pain and inflammation. Although these products represent a multi-billion dollar market, they nevertheless offer varying degrees of efficacy and can cause a number of side effects.

Biolipox aims to improve on these current approaches to respiratory and inflammatory disorders. CEO Carl-Johan Dalsgaard, a partner at Swedish venture firm HealthCap and former head of the pain control therapeutic area at AstraZeneca PLC, reveals that the company's scientists have discovered a number of new substances derived from arachidonic acid which they believe play an important part in inflammation, particularly in the respiratory tract. Dalsgaard won't give away details of the nature of these substances, but he contends that they could lead to the development of a safer family of drugs because "unlike corticosteroids, which affect a number of pathological and physiological functions, our substances will be more specific in action." By identifying the enzyme inhibitors and receptor ligands of these substances, Biolipox hopes to develop treatments that cause fewer side effects than corticosteroids and are more efficacious than leukotriene receptor antagonists, the newest class of oral asthma drugs. Dalsgaard also claims that such products may have potential as a first line therapy for asthma together with bronchorelaxants.

Along with its arachidonic acid program, Biolipox hopes to make use of nitric oxide (NO)-releasing drug-discovery technologies to help build its portfolio of oral allergy and asthma therapies. Again, Dalsgaard won't discuss details about the specific molecules being explored, but he does say that the two technologies offer scope for development as either stand-alone or combined drug therapies. He believes that combining the two technologies should provide Biolipox with a broad technology platform of high-risk and low-risk projects across a wider portfolio of drugs.

NO is an endogenous substance which in low concentrations counteracts inflammation. It is a signaling module involved in the control of a broad spectrum of physiological processes including inflammation. When combined with non-steroidal anti-inflammatory drugs (NSAIDs), low doses of NO have been shown to significantly reduce gastrointestinal toxicity without compromising the anti-inflammatory and analgesic properties of NSAIDs. Further, the substance works without the cardiovascular risks associated with Cox-2s. NO technology confers one other important therapeutic benefit: the facility to stimulate physiologic pathways that protect against NSAID-induced damage.

Biolipox's researchers have been working on NO-based drug-enhanced therapeutic projects in collaboration with France's Nicox SA since 2001 [See Deal]. (See: "NicOx: Challenging the Cox-2s?" In Vivo Europe Rx, November 2002 (Also see "NicOx: Challenging the Cox-2s?" - In Vivo, 1 Nov, 2002.).) Although AstraZeneca, which is developing NicOx's late-stage NO-product for arthritis, recently reported disappointing trial results, Dalsgaard claims this has no impact on the Biolipox program. (See: "NicOx/AstraZeneca: Transparency vs. Partnering Etiquette," In Vivo Europe Rx, April 2003 (Also see "NicOx/AstraZeneca: Transparency vs. Partnering " - In Vivo, 1 Apr, 2003.).) The failing related only to a lack of statistically significant reduction in the incidence of gastric ulcers in AstraZeneca's trials, Dalsgaard points out. "Our aim is not to reduce existing gastrointestinal side effects, but to add the anti-inflammatory effect of the donated NO. As our parent compounds are not NSAIDs, they do not carry the risk of gastrointestinal bleeding." The results to date are encouraging, and, contends Dalsgaard, "we have no reason to believe that this will not work."

Biolipox's short-term goal is to "explore new pathways and develop a new portfolio of products," points out Dalsgaard, using the company's own 50,000-compound library to generate hits. One new program involves the development of Eoxin inhibitors for asthma and other inflammatory diseases, including hay fever. Discovered by Biolipox's scientific founders, these new metabolites are based on arachidonic acid technology. The company has identified a target and is testing its own new chemical entities, the most advanced of which is in lead optimization.

Dalsgaard notes that one of Biolipox's drug candidates has already entered clinical trials; further details of which will be released sometime this year. He claims that Biolipox can run both pre-clinical and clinical trials in respiratory and inflammatory diseases.

The majority of the start-up's research is carried out at the KI, as well as in collaboration with a group of independent pharma professionals who between them have contacts in the chemical community, a scientific grounding in arachidonic acid technology and experience in the respiratory field. Besides the KI, Biolipox has further collaborations with Uppsala University and the Biomedical Centre, Firestone Institute of Respiratory Health and Axovan AG [See Deal], a Swiss drug discovery company focused on G-Protein Coupled Receptors. Biolipox has signed licensing agreements with the KI, but so far no deals have been struck with pharma companies. When its programs progress beyond preclinical trials, Biolipox will seek a worldwide partner to secure global market coverage.

Dalsgaard holds that Biolipox's wide range of drug candidates designed to address the multiple pathways of asthma, the size of the market, and the growing need for improved drugs in this field all work in the company's favor. Most importantly, Biolipox's focus on arachidonic acid has equipped the start-up with a host of "completely novel targets," and new applications. He adds that the company has intellectual property rights for the Eoxin pathway, the NO technology and around specific NO-donating compounds through its collaborative work with NicOx as well as composition of matter patents.

Starting out with €450,000 of seed financing from HealthCap, Biolipox has to date raised more than €26 million through three investment rounds. Investors include Apax Partners (UK and France), Sofinnova Partners, Crédit Lyonnais Private Equity, and Auriga Partners. Between them, these backers hold more than 84% of the start-up's shares.

--by Debbie Legall