The American Diabetes Association estimates that there are currently 23.6 million diabetics in the U.S. (7.8% of the total population, including 17.9 million diagnosed cases, 5.7 million undiagnosed, and 57 million pre-diabetics. Diabetes results in an estimated $174 billion in costs from diagnosed cases of diabetes in the U.S. (2007).[More...]

On a global scale, the International Diabetes Federation (IDF) estimates 285 million diabetics worldwide in 2010. I have outlined some investing opportunities in this article, with a focus on emerging small / micro-cap companies from across the world which are developing innovative therapeutics, diagnostics, and monitoring products to improve the treatment outcomes for the growing, global diabetes epidemic.

Epinex Diagnostics, Inc. (privately held) is dedicated to the development of innovative point-of-care technologies using rapid diagnostic tests. Epinex has developed a proprietary platform for rapid tests that apply existing immunoassay strips and biosensors to create unique quantitative diagnostic tests, focused on a significant initial market opportunity for a new type of diabetes monitoring test that measures glycated albumin (G1a), with an expected FDA 510(k) filing in early 2010 seeking marketing clearance as a Class 2 medical device for an expected review period of 90 days. My 13-page profile report and the most recent corporate profile for Epinex are available to view or download at the BioMedReports.com research downloads section or at the ProActive News Room landing page for Epinex.

Novo Nordisk (NYSE: NVO) is based in Denmark and represents the largest (market cap of US$39.5 billion), globally diversified play on diabetes care, deriving over 73% of total revenue (US$5.6 million / US$7.6 million) during the first nine months of 2009 from this business segment. During the first three quarters of 2009, NVO posed total and diabetes care segment sales growth of 15% (Danish kroner) and 11% (local currencies).

NVO expects to receive formal feedback from the FDA during 4Q09 for its pending Victoza (liraglutide is a once-daily human GLP-1 analogue) New Drug Application (NDA) seeking U.S. marketing approval for the treatment of type 2 diabetes in adults. In early July, the European Commission granted marketing authorization for liraglutide. Victoza is used once-daily via subcutaneous injection, and the drug is a synthetic glucagon-like peptide-1 (GLP-1) that works by stimulating insulin release when glucose levels become high.

Another company awaiting a FDA decision for a new diabetes care product is MannKind Corp. (NASDAQ: MNKD), which submitted its NDA in mid-March that is seeking FDA approval of Afresa (insulin monomer human rDNA origin) Inhalation Powder and the AFRESA Inhaler for the treatment of adults with type 1 or type 2 diabetes. The FDA issued a standard, 10-month review for the NDA, with a decision expected in mid-January 2010. Afresa is an ultra rapid-acting form of insulin (achieving peak levels within 12-14 minutes to mimic the normal physiological release of insulin in healthy individuals) that is delivered through an inhaler rather than the typical route of injection by a syringe.

In early October, MNKD announced that it would not be able to sign a partnership deal for Afresa by year-end as it awaits the pending FDA decision, stating that the Company and potential partners will be better able to address appropriate deal terms and structure once the label for Afresa is clarified. In November 2007, Pfizer (NYSE: PFE) agreed to a settlement with Nektar Therapeutics (NASDAQ: NKTR) that included a one-time payment of $135 million to the latter after Exubera (the first FDA-approved inhaled insulin product) failed to generate meaningful sales despite a significant investment by Pfizer.

In early May, Amylin Pharma (NASDAQ: AMLN), Eli Lilly (NYSE: LLY), and Alkermes (NASDAQ: ALKS) announced that a NDA was filed seeking FDA approval of exenatide (Byetta LAR) as a once-weekly formulation for type 2 diabetes which is administered by subcutaneous injection, with a FDA decision expected in early 2010. Byetta is currently approved for use as a twice-daily injection for patients with Type 2 diabetes and is classified as an incretin that exhibits many of the same actions as GLP-1 (glucagon-like peptide-1) which act by stimulating insulin release when glucose levels become high.

Diabetes care companies in the Asia /Pacific region include Terumo Corp. (TYO: 4543) (OTC: TRUMY.PK) and Takeda Pharma (TYO: 4502) (OTC: TKPHY.PK). Terumo manufacturers medical devices / equipment such as insulin syringes while Takeda markets diabetes drug Actos with continued development of alogliptin as an experimental drug for Type 2 diabetes as both a single agent and in combination with Actos. In late June, Takeda received a Complete Response Letter (CRL) from the FDA for alogliptin, which is a selective dipeptidyl peptidase IV (DPP-4) inhibitor under investigation for the treatment of type 2 diabetes as an adjunct to diet and exercise that will require a cardiovascular safety study prior to possible FDA approval.

In September, Vivus Inc. (NASDAQ: VVUS) announced positive results from two final, Phase 3 pivotal 56-week studies, EQUIP (OB-302) and CONQUER (OB-303), evaluating the safety and efficacy of Qnexa (phentermine + topiramate) in more than 3,750 patients across 93 sites. The EQUIP and CONQUER studies met all primary endpoints by demonstrating statistically significant weight loss with all three doses of Qnexa, as compared to placebo. Patients taking Qnexa also achieved significant improvements in cardiovascular and metabolic risk factors including blood pressure, lipid levels, and Type 2 diabetes. Vivus expects to file a NDA before year-end and has an ongoing Phase 2 study evaluating Qnexa in Type 2 diabetics.

Access Pharma (OTC: ACCP.OB) has developed a nano-polymer drug delivery system for the oral administration of large molecules such as insulin, human growth hormone (hGH), and erythropoietin (EPO). This drug delivery technology involves coating a nano-particle with a B12 analog (cobalamin) that binds to intrinsic factor in the gut and triggers binding to cellular receptors which absorb the entire package, resulting in 1,000 to 1,000,000-fold increases in absorption through the gut of large molecule drugs typically administered by injection.

Licensing discussions are expected to formalize for the Company's basal (long-acting) oral insulin product following the mid-June announcement that two bio-pharmaceutical companies will conduct preclinical, animal studies before proceeding to more formal negotiations. The results of these preclinical studies will be made public, including one North American biotech company and one European biotech company. Access is providing the oral insulin while the two interested companies will conduct one animal study each (including a rat and dog model) with data expected before year-end.

Other investment opportunities related to diabetes care include (1) Unilife Medical Solutions (OTC: UNIFF.PK) (ASX: UNI.AX) (Unitract safety syringes, contract medical device manufacturing); (2) West Pharmaceutical Services (NYSE: WST) (syringe component manufacturer); (3) Retractable Technologies (AMEX: RVP) (VanishPoint safety syringes); (4) CPEX Pharma (NASDAQ: CPEX) (Nasulin is an experimental intranasal insulin product candidate); (5) Emisphere (OTC: EMIS.OB) (plans to change development focus to an oral formulation of a GLP-1 analog rather than continuing to pursue development of oral insulin).

The market for all diabetes monitoring products is the largest medical diagnostics market in the world at $12.4 billion in 2000 and estimated to grow to a level of $27 billion by 2010, representing a 12% CAGR (compound annual growth rate). The diabetes testing market includes diversified, global healthcare giants and smaller niche players, including those outlined below.

Johnson & Johnson (NYSE: JNJ) (LifeScan - One Touch), Abbott Labs (NYSE: ABT) (FreeStyle), Becton Dickinson (NYSE: BDX) (BD Diagnostics), Roche (OTC: RHHBY.PK) (Accu-Chek), Bayer (OTC: BAYRY.PK) (Ascenscia), Bio-Rad Labs (NYSE: BIO), Home Diagnostics (NASDAQ: HDIX), Insulet Corp. (NASDAQ: PODD), Echo Therapeutics (OTC: ECTE.OB), Trinity Biotech (NASDAQ: TRIB), and DexCom (NASDAQ: DXCM).

As I wrote last week, Echo Therapeutics announced positive results in a pilot clinical study for its needle-free Symphony Transdermal Continuous Glucose Monitoring (tCGM) System as a non-invasive, wireless, transdermal solution for monitoring blood sugar levels when used in conjunction with the needle-free Prelude SkinPrep System. The Prelude SkinPrep has been licensed to Ferndale Pharma in North America + UK for the enhanced delivery of its topical lidocaine skin-numbing agent (LMX4), with a FDA 510(k) submission expected during 1Q10 for potential marketing clearance while the Symphony tCGM will be evaluated in a pivotal trial that is expected to begin by late February 2010 with a FDA PMA submission expected to follow.

Coming soon is a premium service offered in collaboration with Investars YOU for full access to a global database of over 1,000 stocks which are organized and managed within my 23 ProActive HavRx stock indexes. This service will allow investors to create custom portfolios, personalized exchange-traded funds (ETFs), and generate investment ideas based on their personal preferences, beliefs, and opinions through specialized stock indexes that are organized and targeted toward a wide variety of themes.

The BioMedReports.com FDA Calendar service includes a database with over 400 entries of (1) pending new drug, biological agent, or medical device new product decisions at the FDA (e.g. NDA, BLA, 510k, PMA, sNDA, and sBLA filings); (2) pending new submissions to the FDA; (3) pending complete response letter (CRL) re-submissions to the FDA; and (4) pending clinical trial results.

Disclosure: Long ACCP.OB, Epinex Diagnostics (privately held)

 

The news today follows the successful transfer of the automated assembly system for the Unitract 1mL Syringes into its designated clean room in accordance with previously announced schedules. Prior to transferring the automated assembly system into the clean room, it was required to pass a series of operational tests designed to validate its performance in areas such as running speeds and product quality. These tests were successfully completed, with the automated assembly system now rated at up to 90% of efficiency. Unilife will continue to work towards achieving the optimum productivity rate for this assembly system of about  40 million units per year.

Unilife will now begin to build inventory to fulfill current and anticipated orders for its Unitract 1mL Syringes, which has already received key regulatory certifications for use in major markets such as the U.S., Canada, Europe, and Australia. Commercial release of the Unitract 1mL Syringes is expected to occur during 4Q09 once product aging studies have been completed and Unilife will promote the products at key industry events in the U.S. and Europe. Unilife is currently in discussions with a number of global pharmaceutical and healthcare companies that are interested in the Unitract 1mL Syringes.

The Company's product line-up of safety syringes are sold under the Unitract brand and allow users to control the speed of automatic needle retraction through a fully integrated safety syringe to nearly eliminate the risk of needle-stick injuries and disease transmission for healthcare providers. Unilife has a fully-owned U.S. subsidiary through its acquisition of Integrated BioSciences, which is located near Harrisburg, PA, and employs the majority of the Company's staff (50) at a FDA registered manufacturing facility for the large-scale production of medical devices. This facility produces the Unitract safety syringes and also handles contract manufacturing of medical devices for healthcare and pharmaceutical companies.

The Company's strategic partner for exclusive manufacturing and distribution of sharps safety products is Shanghai Kindly Enterprise Development Group (KDL). This facility currently produces Unitract 1mL syringes and MedPro blood collection safety devices using semi-automated assembly systems developed and qualified by Unilife. KDL is the second largest medical device manufacturer in China and has two-thirds market share of the Chinese needle market, manufacturing over 5 billion needles and 600 million syringes per year.

The major business partner for Unilife is Sanofi-Aventis (NYSE:SNY), which is the largest buyer of pre-filled syringes in the world for injectable products such as the blood thinner Lovenox and influenza vaccines such as Fluzone marketed by the Company. Last July, Unilife and SNY agreed to a five-year exclusive licensing agreement for the Unilife Pre-Filled syringe. SNY paid a €10 million exclusivity fee the right to purchase the syringes over the next five years and also agreed to finance Unilife's plans for expanding manufacturing capacity for the syringes (with a first-year production target of 40 million units by early 2011).

West Pharmaceutical Services (NYSE:WST) supplies medical device components to a variety of companies in the healthcare sector. WST is a PA-based company with a market cap over $1B with over 20 manufacturing facilities on a global basis. Unilife has a development agreement with WST for the provision of specialist components such as seals for Unitract products.

The industrialization agreement with SNY for Unilife Ready-to-Fill Syringe (RTFS) announced on 6/30/09 included the following features outlined below and also allows Unilife to move forward with discussions that include other potential customers that are interested in the Company's prefilled syringes.

(1) Period of Industrialization Program: The program was originally intended to be completed by the end of 2011, but it is proceeding ahead of schedule so that both parties have agreed to bring its scheduled completion date forward to the end of 2010.

(2) Payment of March Quarterly Milestone: Following the completion of designated milestones during the quarter ending 3/30/09, Unilife received a milestone payment of A$3.5 million (€2 million). Unilife has now received a total of A$9.5 million (€5 million) in quarterly milestone payments since the commencement of the program. With the program proceeding as scheduled, Unilife has issued to SNY an invoice for the delivery of milestones attained during the quarter ended 6/30/09.

(3) Selection of Automated Assembly Supplier: Unilife has completed due diligence on potential qualified international suppliers for the development of the high-volume automated assembly system.

(4) Scheduled Production Capacities: Unilife is scheduled to commence supply of the RTFS by the end of 2010. Initial supply of the RTFS by Unilife will utilize a fully automated assembly system that will have a targeted annual capacity of more than 40 million units. The design of this first line will also be used to develop a higher-volume automated assembly system scheduled to be completed by the end of 2011. This high-volume automated assembly system is anticipated to have an annual production capacity greater than 100 million units. Unilife has a target production plan for the RTFS of about 400 million units per year beyond 2014.

(5) RTFS Production Facility: Unilife has conducted a review of opportunities within Europe for the establishment of a manufacturing facility suitable for the high-volume production of the RTFS and has decided to instead centralize its manufacturing activities within PA. The centralization of RTFS production activities within PA is expected to reduce the Company's operational costs, further optimize its supply chain activities, and place Unilife in a more favorable international location to supply the RTFS to all of its anticipated customers.

Earlier this year, Unilife announced plans to relocate its global headquarters into a building being occupied by fully-owned subsidiary Integrated BioSciences in Lewisberry, PA. The Company also appointed a U.S.-based chief financial officer, Mr. Daniel Calvert, around the same time as part of plans to apply for listing on a U.S. stock exchange and expanding the number of people at the manufacturing plant in Lewisberry (near Harrisburg) to around 100 while retaining a small R&D team in Sydney, Australia.

The rapid expansion of Unilife will soon become more apparent to U.S. investors as the Company expects to list for trading here later in the year. Also, the extensive partnership with SNY provides Unilife with the necessary capital to expand its U.S. manufacturing capacity and will provide a major source of demand for the Company's pre-filled syringes by late 2010 with a production target of 40 million units per year at that time.

Disclosure: No positions

More than two billion prefilled syringes are currently used each year on a global basis and pharmaceutical companies are making the switch to products such as Unilife's safety syringe which are compliant with needle-stick prevention laws (e.g. Federal Needlestick Prevention Act, 2000). Key differentiating features of Unilife's fully-integrated (within the barrel of the syringe) safety syringes include the following:

1.) a passive needle retraction system that is activated inside the body

2.) healthcare providers / shot administrators control the speed of needle retraction

3.) auto-disabling prevents re-use or tampering with used syringes

The market opportunity for prefilled syringes includes 50 drugs (primary anti-coagulant / hematology medications, vaccines, and other biological agents) that are delivered by injection, including an estimated 3 billion prefilled syringes in use by 2012. Unilife has a distinct advantage with a disruptive technology since there are currently no prefilled syringes to deliver medications with fully-integrated safety features so pharmaceutical companies must add these features - which adds to production / shipping costs and increases the overall packaging size by up to 60%, resulting in both waste disposal and marketing issues.

In mid-August, Unilife announced that it has commenced U.S. production of the UnitractTM 1mL Insulin Syringe at its FDA-registered manufacturing facility in Pennsylvania. The Company's automated assembly system is now rated at up to 90% of efficiency and Unilife will continue to work towards achieving the optimum productivity rate for this assembly system of about 40 million units per year. Unilife will now begin to build inventory to fulfill current and anticipated orders for its Unitract 1mL Syringes, which has already received key regulatory certifications for use in major markets such as the U.S. (FDA), Canada, Europe (CE Mark), and Australia.

Commercial release of the Unitract 1mL Syringes is expected to occur during 4Q09 once product aging studies have been completed and Unilife will promote the products at key industry events in the U.S. and Europe. Unilife is currently in discussions with a number of global pharmaceutical and healthcare companies that are interested in the Unitract 1mL Syringes. The Company also recently announced a pair of upcoming presentations at pharmaceutical trade shows in Europe to showcase its safety syringe technology and products.

The Company's strategic partner for exclusive manufacturing and distribution of sharps safety products is Shanghai Kindly Enterprise Development Group (KDL). This facility currently produces Unitract 1mL syringes and MedPro blood collection safety devices using semi-automated assembly systems developed and qualified by Unilife. KDL is the second largest medical device manufacturer in China and has two-thirds market share of the Chinese needle market, manufacturing over 5 billion needles and 600 million syringes per year. In addition, Unilife has a development agreement with PA-based West Pharmaceutical Services (NYSE:WST) for the provision of specialist components such as seals for Unitract products.

The key strategic business partner for Unilife is Sanofi-Aventis (NYSE:SNY), which is the largest buyer of pre-filled syringes in the world for injectable products such as the blood thinner Lovenox and influenza vaccines such as Fluzone marketed by the Company (Griffin Securities estimates that SNY purchases 40% of all pre-filled syringes on a global basis). Last July, Unilife and SNY agreed to a five-year exclusive licensing agreement for the Unilife Pre-Filled syringe. SNY is paying US$38M for the right to negotiate purchase of the RTFS (ready-to-fill syringe), consisting of fees and milestone-based industrialization payments with ongoing negotiations for exclusivity agreements by therapeutic class (e.g. blood thinners, vaccines, etc.).

The industrialization agreement with SNY for Unilife Ready-to-Fill Syringe (RTFS) announced mid-year allows Unilife to move forward with discussions that include other potential customers that are interested in the Company's prefilled syringes (with an additional agreement expected in early 2010). This key partnership with SNY provides Unilife with the necessary capital to expand its U.S. manufacturing capacity and will provide a major source of demand for the Company's pre-filled syringes by late 2010 with a production target of 40 million units per year at that time.

The program was originally intended to be completed by the end of 2011, but it is proceeding ahead of schedule so that both parties have agreed to bring its scheduled completion date forward to the end of 2010 (an entire year ahead of schedule). Unilife is scheduled to commence supply of the RTFS by the end of 2010. Initial supply of the RTFS by Unilife will utilize a fully automated assembly system that will have a targeted annual capacity of more than 40 million units. The design of this first line will also be used to develop a higher-volume automated assembly system scheduled to be completed by the end of 2011.

This high-volume automated assembly system is anticipated to have an annual production capacity greater than 100 million units and Unilife has a target production plan for the RTFS of about 400 million units per year beyond 2014. In addition, the centralization of RTFS production activities within Central PA is expected to occur in 2010 and will reduce the Company's operational costs, further optimize its supply chain activities, and place Unilife in a more favorable international location to supply the RTFS to all of its anticipated customers while leveraging the Company's strong, mutually beneficial relationship with the PA government due to the generation of high quality jobs in the state.

Earlier this week, Unilife announced this week that it has accepted a $5.2 million offer of assistance from the Commonwealth of Pennsylvania to support the creation of 241 new jobs within York County. The Company's expansion plans in Central PA include the proposed redomiciliation from Australia to the U.S., obtaining a NASDAQ listing for the stock, and the establishment of a major new global headquarters + manufacturing facility.

Unilife also announced this week that it has commenced the filing of international trademarks for UnifillTM, which will become the market brand for its portfolio of ready-to-fill safety syringes. The product previously referred to on a pre-commercial basis as the Unilife Ready-to-Fill Syringe (or Unilife Prefilled Syringe) will now be marketed as the Unifill syringe. Unilife has developed the Unifill brand to help the Company effectively market its expanding range of injectable drug delivery products designed for use by pharmaceutical companies.

Last week, Unilife announced that CEO Alan Shortall 479,800 shares of the Company's stock on the open market at an average price of A$1.026 per share and the CEO has authorized his broker to purchase additional shares that will bring the total number of shares purchased to over 500,000. Mr. Shortall commented that he elected to purchase the shares in the open market rather than participate in the Company's recently announced private placement (conducted at a 7.7% discount to the market price at the time) as a sign of confidence to shareholders

In early October, Unilife announced an A$42.1M capital raise (consisting of an A$32.1M private placement to institutional investors + A$10M fully underwritten share purchase plan to existing, eligible shareholders at the same price of A$0.85 per share) to accelerate the expansion of its operational capabilities, production facilities, and equipment requirements in the U.S., in addition to completing the industrialization of the Unilife Ready-to-Fill Syringe. Unilife also plans to expedite the commercialization of additional pipeline products with other interested major pharmaceutical companies with whom the Company is currently in discussions. Finally, the proceeds of the capital raise will ensure adequate cash reserves leading to the redomiciliation in the U.S. and planned NASDAQ listing for the stock.

The Company announced that it received significant interest in recent months from both U.S. / Australian investors and other industry stakeholders for its strategic and operational strategies and the Board determined that it was in the best interests of shareholders to act upon this strong interest prior to its anticipated NASDAQ listing to ensure the Company has sufficient cash reserves to support and accelerate significant business expansion activities which it expects to undertake within the United States.

Since I first wrote about Unilife in early April, the US-listed Pink Sheet ADR (UNIFF.PK) has experienced an exponential rise in both share price (from below 25 cents to the one dollar range) and trading volume as investors recognize the significant potential of the Company's niche strategy focused on safety syringes. The bullish sentiment by investors for Unilife is warranted given its disruptive safety syringe technology, relocation plans to the U.S. / NASDAQ stock listing next year, partnership with Sanofi, recent capital raise, and an additional deal expected next year.

Click here for the ProActive News Room landing page for Unilife, which includes a compilation of digital media coverage links for the Company and several recent reports and presentations, including those outlined below.

Unilife Medical (OTC: UNIFF.PK): Griffin Securities 8/19/09

Unilife Medical (OTC: UNIFF.PK): Sept. 2009 Presentation

Unilife Medical (OTC: UNIFF.PK): CCZ Equities 10/13/09

Disclosure: No positions

Friday was a milestone in the evolution of the ongoing financial crisis. No, not the employment data, which was execrable (and prompted Goldman to raise their unemployment rate forecast to an eye-watering 8.5%.) In fact, Friday was notable because it was the first time in quite a while that Macro Man can recall being bored at the office. It seems as if markets have mentally shut down and are content to limp into the end of the year. Liquidity has certainly dried up amongst many of the products that Macro Man trades, and declining volumes in a number of exchange-traded assets also bear testament to a lack of engagement. Moreover, the ever-reliable blog traffic indicator has shown a reasonable decline in eyeballs from the panicky markets of a month ago. As always, that is perhaps explainable by the dearth of quality of the commentary in this space...but nevertheless it would appear to indicate a waning interest in the day-to-day saga of the financial[More...]