BZB Group

OSD

EXECUTIVE SUMMARY

The OSD: Oral Synchronous Drug Delivery System

March 2003

The company

Delivery Therapeutics Ltd (DT), an Israeli biotechnology company, has developed a proprietary technology enabling an efficient oral delivery of poorly absorbed drugs, mainly protein drugs and poorly-water soluble drugs.  The company was founded by Prof. Avri Rubinstein and Prof. Michael Friedman of The Hebrew University of Jerusalem, Faculty of Medicine, School of Pharmacy. Both scientists possess a worldwide reputation in the field of oral drug delivery.  DT is based in the Naiot Technological Center, a business and R&D incubator for biotechnological and high-tech startups.  Naiot is affiliated with the Ofer Brothers Group, Israel’s largest private enterprise.

The Challenge

Oral delivery of drugs is the preferred mode of administration in pharmacy since it makes use of the only body organ designed to absorb – the gastrointestinal (GI) tract. The organ is complex and the anatomic and physiologic characteristics of its various components differ from each other. The understanding of these biological parameters is the key for a rational design of plain as well as advanced dosage forms. This is true especially now since extraordinary advances have occurred in drug design approach and the nature of drugs: from small, stable organic molecules to high molecular weight, potent peptides or nucleotides.

Protein drugs: Recent developments in biotechnology have resulted in a number of powerful new protein therapies for many previously untreatable conditions, including hepatitis C, multiple sclerosis, hormonal disorders and different cancers. Typical examples of such drugs include: insulin, calcitonin, erythropoietin, interferons, tumor necrosis factor, superoxide dismutase and GnRH.

Difficulties associated with the oral delivery of protein drugs: These drugs are prominent in their susceptibility to proteolysis in the lumen and cannot be ingested orally unless protected properly (by protease inhibitors). Moreover, being large charged molecules, they need assistance to pass through the gut wall (absorption enhancers).

In the past 20 years the attempts in the field of oral delivery of protein drugs have been focused in either identifying new enhancers/enzyme inhibitors, or developing sustained release methods and platforms. As a result some new approaches, such as nasal delivery systems have been marketed. However, no attempt has been made to optimize the release of the protein probes and the auxiliary molecules physiologic-wise into of the fluids of the intestinal tube in a rational manner. As will be described below synchronization, which has not been tested before, is a practical solution to this problem.  

Non-protein drugs share the above hurdle, namely poorly water-soluble drugs (a drug molecule must be in a solution prior to penetrating the gut wall) and drugs that are pumped back from the gut wall by efflux pumps located at the membrane of the epithelial cells.

DT’s solution

Combining the understanding of GI physiology and the acquaintance with industrial pharmacy, DT has developed a novel approach to increase the bioavailability of protein drugs, poorly absorbed drugs and drugs susceptible to efflux pumping incidents. This approach has been tested over 4 years in a variety of biological models and resulted in the design of the oral synchronous delivery system (OSD).

The OSD  technology

            The OSD proprietary (patent allowed in Israel, patent pending in the USA)  matrix is a tailor-made platform, capable of synchronizing the release process of drug(s) together with functional additives such as absorption enhancers (AE); enzyme inhibitors (PI), and efflux pump inhibitors [e.g. p-glycoprotein (pGP)], over a predetermined time interval along specific locations in the intestine. In other words: the matrix is designed to cause a concomitant release of two ingredients or more and “forces” them to stay together, while traveling down the gut.

The concomitant release provided by the OSD allows continuous action of the functional adjuvant (absorption enhancer, enzyme inhibitor, or solubilizing agent) throughout the whole length of the intestine, or at pre-designed intestinal segments over predetermined time slots. The outcome is an improved bioavailability of the drug of interest compared with the bioavailability accomplished when administered in non-synchronous carriers (Figure 1).

Figure 1:  Depicted description of the OSD mode of action.

Proof of concept example – oral calcitonin

Salmon calcitonin (sCT) has been tested with the OSD. The therapeutic uses of sCT, a 32-amino acid hormone available commercially for over 25 years, are the long-treatment of Paget's disease and the short-term relief of some hypercalcemia conditions (e.g., malignant hypercalcemia). Studies indicate that sCT can be absorbed from the digestive tract. If properly formulated its clinical potential could be further explored (e.g. in the context of osteoporosis) and its commercial benefit dramatically improved.

In a set of pre-clinical studies performed in beagle dogs, three OSD platforms of sCT, sodium decanoate (absorption enhancer) and bacitracin (protease inhibitor) were tested against control formulation (containing similar ingredients, without the ability to synchronize their release). A significant increase in the oral bioavailability of sCT after OSD administration was observed (Figure 2).

At a latter stage the OSD sCT platform was tested in primates. The preliminary results indicate a considerable absorption of sCT from the formulations tested.

The above results, supported by extensive data obtained from in vitro and rodent studies conducted in the past six years (see Additional Information), will enable the assembly and optimization of  a prototype (6-8 month)  to be tested in pilot human clinical trials. The trials are expected to begin following the capital raising during 2003.

Figure 2:    Mean sCT plasma levels after oral administrations of a non-synchronized sCT capsule (filled circles), and three types of OSD of sCT (designed to function at different durations). Shown are the mean values of 3 studies.

Market opportunity

Modified release  (MR) oral drug-delivery systems are extremely attractive constituencies in the drug market. In the year 2000 the drug delivery business totaled $13.8 billion in the USA alone. It is expected to grow some 98% to $27.4 billion in 2005 (BCC).

The global market for protein and poorly soluble drugs is currently valued at $47 billion according to Technology and Business Review. According to Scrip, there are approximately 40 macromolecular drugs currently on the market with forecasted 2002 sales of $18-19 billion. These are expected to soar to $30-40 billion by 2006, attributed to both approval of new drugs, currently in the pipeline, and the introduction of new drug delivery technologies, part of which will augment macromolecular drug penetration.

Competitive edge of the OSD

Improved bioavailability, efficacy and safety.

For protein drugs: improved shelf stability.

Generic technology, easy to scale up.

Applicable to a variety of drugs.

Investment Opportunity

DT is looking for an equity investment that will (a) enable it to complete pilot human clinical trials for its oral calcitonin technology, (b) secure 4-5 strategic partnership agreements, and (c) strengthen and broaden its IP basket.

DT is a unique investment opportunity due to its:

-Breakthrough OSD platform technology with multiple applications

- Multi-billion dollar markets

-Strong management team with key experienced people the areas of business, technology, business development and marketing/sales.

-The technology has a strategic added value to large firms in the pharmaceutical

  industry

-World-renowned scientists with extensive experience in the field of oral drug

  delivery and industrial pharmacy

- Extensive pipeline of additional drug delivery applications

 

 Business Strategy

Based on the large amount of data accumulated with sCT, the immediate goal of DT is to perform pilot clinical trials with its OSD of this drug.

DT has identified a list of potential molecules with (a) oral absorption problems, (b) market potential, (c) aimed at chronic treatment.

Expected revenues will come from: (a) out-licensing self-developed products, (b) tailor made developments.

A desired agreement with a potential partner will be the one in which (a) the partner will finance a mile-stone based research program which will last up to pilot clinical trials, (b) The partner will be responsible for conducting clinical trials and manufacturing and marketing, (c) the partner will receive worldwide exclusivity on the product developed (d) DT will receive royalty payments calculated on the basis of  the product(s) sales.

DT’s Management staff

Professor Michael Friedman (Co-Founder and Chief Technology Officer) is Professor of Pharmacy Science at the Hebrew University in Jerusalem Faculty of Medicine at the School of Pharmacy. He is also the Dean of Academic Affairs at the School of Pharmacy. Previously he was the Dean of the Department. Professor Friedman has extensive experience in the field of oral drug delivery and industrial pharmacy. He has published over 110 scientific articles, reviews and book chapters and applied and received 21 international patents.

Professor Abraham (Avri) Rubinstein (Co-Founder and Chief Technology Officer) is Professor of Pharmacy Science at the Hebrew University in Jerusalem, Faculty of Medicine at the School of Pharmacy. He is the current Department Dean. Professor Rubinstein has extensive experience in the field of oral drug delivery. He has published over 60 scientific articles, reviews and book chapters and over 70 published abstracts in international conferences.

Ms. Tali Sivan (Chief Executive Officer) was a Co-Founder and CEO of Enzymotec Ltd, a biotechnology company. She led the company through its inception and its major efforts in converting technical ideas to products and markets. Her former position was Vice President for business development at Enzymotec.

Ms. Sivan received her Master of Business Administration (MBA) from the Technion, Israel Institute of Technology, School of Management and her Master of Science (MSc), in Biology also from the Technion.   

Additional information

Baluom M., Friedman M. and Rubinstein A.
The importance of intestinal residence time of absorption enhancer on drug absorption and implication on formulative considerations.
Int. J. Pharm., 176: 21-30, 1998.

Baluom M., Friedman M., Assaf P., Haj-Yehia A. I. and Rubinstein A.
Synchronous release of sulpiride and sodium decanoate from HPMC matrices: a rationale approach to enhance sulpiride absorption in the rat intestine.
Pharm. Res., 17: 1071-1076, 2000.

Baluom M., Friedman M. and Rubinstein A.
Improved intestinal absorption of sulpiride in rats with synchronized oral delivery systems.
J. Contr. Rel., 70: 139-147, 2001.

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Last modified: 03/16/04