Platform Technology

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Celsus Therapeutics is a biopharmaceutical drug development company focused on the development of novel non steroidal anti-inflammatory drugs.

Celsus’s lead products are first-in-class, novel, non-steroidal, synthetic anti-inflammatory drugs termed Multi-Functional Anti-Inflammatory Drugs (MFAID) focus on one of the most sought after pharmaceutical targets in inflammation research: the sPLA2 family.

This extracellular family of enzymes are a universal early trigger in all in the inflammatory diseases studied that hydrolyses phospholipids on the cell membrane into two key inflammatory precursors: arachidonic acid (AA) and lysophospholipids (LysoPL).

  • AA is metabolized via the cyclooxygenase (COX) and lipoxygenase (LOX) pathways to produce large families of eicosanoids; many of them are involved in the development of numerous pathological conditions, especially in inflammation related processes. These include Prostaglandins, Thromboxanes and Leukotrienes.
  • LysoPL induce white cell activation and extravasation, activate cell activation (by lyso phosphatidylserine in particular) , induce tissue damage, such as gastric ulceration , and act as growth factors (especially lyso phosphatidic acid), to induce proliferation of cancer cells and tumor metastasis . Furthermore, LysoPL are also the precursors of platelet activating factor (PAF), possibly the most potent mediator of inflammatory processes .

The key to successfully controlling this “universal inflammatory trigger” has been demonstrated by the past clinical failures of several pharmaceutical companies. It can be summarized as follows:

  1. Inhibit of the entire sPLA2 family, not just one or two of its isomers.
  2. Do not interfere with the cPLA2 family, a related group of enzyme which are located inside the cell (unlike the sPLA2) and which have a vital homeostatic role (unlike sPLA2) which must not be interfered with.

Celsus’s MFAIDs were designed and synthesized to overcome these two critical, and previously insurmountable, problems and represent not just a single molecule but an entire new genus of compounds, each different but with a similar mechanism of action.

MFAID have shown in vitro and in vivo efficacy in numerous models and patients including: a pilot Phase II clinical study in allergic rhinitis, a phase I/IIa clinical study in eczema, allergic bronchitis (a model for asthma) in rats, intestinal inflammation (IBD) in rats and mice, endotoxin induced cytokine production by lung microvascular endothelial cells, and endotoxin-induced sepsis, as well as unpublished data in cardiovascular cell-proliferation, and cystic fibrosis (performed at Columbia University and funded by the Cystic Fibrosis Foundation). Patient and animal safety studies to-date have shown no treatment emergent adverse effects and the drugs can be administered via numerous routes including topical, inhaled, systemic and oral (for IBD).

 

Figure 1: Mechanism of action of MFAIDs – interference with sPLA2 hydrolysis of cell surface phospholipids and subsequent inhibition of the production of Arachidonic Acid (AA) and Lysophospholipids (LysoPL). MFAIDs cannot be internalized and therefore act exclusively on the sPLA2 family without interfering with the homeostatic role of the cPLA2 family.

Core areas of interest and clinical programs:

Celsus is currently focusing on several major pathology areas: dermatology, respiratory, ophthalmology and gastro-intestinal inflammatory diseases. Our secondary areas include osteoarthritis, angiogenesis, cardiovascular, central nervous systems, and cancer conditions.

Dermatology

  • A first-in-man topical academic Phase IIa study for contact dermatitis was successfully completed in Israel and a larger follow-up study was initiated in April 2010 (n=80).

Respiratory

  • A fully ICH-compliant Phase IIa nasal spray study on allergic rhinitis patients has been recently completed with demonstrated clear improvement in biochemical and clinical markers and excellent safety results.
  • Published data in standard industry animal model in asthma (rat ovalbumin allergic bronchitis model) showing amelioration in symptoms, histology and inflammatory mediators.
  • Pre-clinical program in cystic fibrosis generated positive data in CF cell lines.

Inflammatory Bowel Disease

  • A pre-clinical program in IBD has demonstrated efficacy of MFAID orally administered in the standard industry animal model.

Ophthalmology

  • Ophthalmology (dry eye and SAC). Positive data on guinea pig allergic conjunctivitis model (with steroid comparator) as well as safe ocular toxicology profile.

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Figure 2: current developmental stage for Celsus’s drugs