Incorporated in California as well as in Europe, Regulon Inc. is a private biopharmaceutical company committed to the discovery and development of anticancer biopharmaceuticals based on its proprietary liposome encapsulation platform technology for more than 10 years.
Technology
The company has developed a unique liposome encapsulation technology applicable to drugs, small molecules, peptides, proteins and viruses aiming at improving human lives and reducing the side effects of chemotherapy known to exacerbate the quality of life of cancer patients. The firm has successfully applied this technology to encapsulate two members of the platinum family of anticancer drugs, cisplatin and oxaliplatin. Platins are the cornerstone of modern chemotherapy, as they have been commonly applied in the effective treatment of the majority of tumor indications for the last 30 years. Despite their well-documented efficacy, however, platinum treatment, almost invariably, results in pronounced toxicity against the patient's kidneys, nerves, bone marrow, gastrointestinal tract, hearing system and most other vital organs. Thus, generating platins of lower toxicity and / or higher efficacy (higher therapeutic index) is an unmet medical need in cancer chemotherapy. The company’s technology has successfully addressed this need and has already shown clinical proof of concept in humans in advanced Phase III studies.
Regulon’s world-wide patented nanotechnology increases the efficacy of current block-buster anticancer drugs, while significantly reducing their serious side-effects on patients. Regulon’s unique liposome encapsulation technology can use most of the 1000 FDA-approved drugs and wrap these into liposomes thus generating branded names of off-patent drugs.
Furthermore, the technology lends itself to gene therapy applications, e.g. for cancer immunotherapy based on a liposomally encapsulated virus carrying the human IL-12 gene. This is a breakthrough in molecular medicine because it allows a number of potential gene therapy treatments to be delivered to patients.
In addition to cancer treatment, the technology can be used against viral infections (such as AIDS and hepatitis) as well as fungal, protozoan and bacterial infections to deliver liposomal antibiotics to the inflammatory area; in addition, the technology has applications in cardiovascular disease, arthritis and autoimmune diseases where alterations of the inflammatory tissue vasculature also enable targeting with Regulon’s nanoparticles as carriers of the appropriate drug. See more under: Attachment: Regulon Business & Technology.ppt
Product Pipeline
Lipoplatin™
The inception and implementation into clinical practice of our lead nanotechnology product, Lipoplatin, integrating our cutting edge patented technology, has reduced the severe side effects of cisplatin in patients. Lipoplatin is concentrated into tumors and metastases at phenomenal levels after intravenous injection to patients while sparing most normal tissues of side effects. Lipoplatin has shown highly promising Phase III results and is now a candidate drug for treatments of lung and pancreatic cancers, soon to seek marketing authorization in these indications (2011), with breast, and gastric cancers planned as our next targets. Lipoplatin started its clinical development in 2001 and was promoted in 2005 into Phase III clinical trials in Germany and Greece. More recently (October 1, 2009) a Phase III pivotal trial was approved by EMEA using Lipoplatin as first line treatment against lung adenocarcinoma following the orphan drug status in 2007 against pancreatic cancer by EMEA (Attachment: Orphan drug designation of Lipoplatin against pancreatic cancer by EMEA); completion of these two studies is anticipated to lead to centralized marketing authorization (MA) for all 27 EU countries. Data from clinical studies so far predict an easy MA process without obstacles as the drug has proven non-inferior to the queen of chemotherapy, cisplatin, but also superior in cancer subtypes and, in all cases, with statistically significant lower side effects.
A milestone achievement of Regulon is that Lipoplatin is being used as first-line treatment against the world’s largest cancer indication, Non-Small Cell Lung Cancer (NSCLC) under the name Nanoplatin. One Phase III interim analysis was successfully completed from an investigator-led clinical study in Greece, meeting the non-inferiority goals of the study and demonstrating a lower toxicity profile, sufficient to warrant registration. The data drawn from another Phase III study in Greece show that Nanoplatin met the non-inferiority goals with statistically significant lowering of side effects and an improved quality of life. Lipoplatin is anticipated to demonstrate a high efficacy in theh nos-squamoue histological subtype of NSCLC manly including adenocarcinoma (70% of NSCLC).
Upon marketing authorization of Lipoplatin / Nanoplatin by EMEA (anticipated in 2011) medical oncologists will be tempted to use the drug in all indications of cisplatin also including testicular, ovarian, head & neck, cervical, urinary bladder, hepatocellular, esophageal, colorectal, gastric, breast and several other cancers comprising ~50% of all human malignancies. It should be emphasized here that most of these cancers are adenocarcinomas where Lipoplatin is showing its high efficacy.
Distribution rights for Lipoplatin have already been sold in several markets; the Company received upfront payments and 40% from future sales. It will not develop a sales force, remain the small-medium size enterprise (SME) and sell distribution rights to large or local Pharmaceutical Companies collecting 40% royalties from sales.
Lipoxal™
The company achieved a further breakthrough with its second compound, a liposomal oxaliplatin, Lipoxal. Oxaliplatin, marketed as Eloxatin by Sanofi-Aventis, is an off-patent drug (2006) used to treat colorectal cancer, constituting 11% of all cancers worldwide, and generated $1.9 billion in sales in 2005. The company’s Lipoxal has significantly reduced all toxicities of oxaliplatin in a completed and published Phase I study. As part of this Phase I study, it was also determined that 2 out of 4 patients (50%) with stomach cancer who failed to respond to earlier chemotherapy achieved partial response. Therefore the company plans to initiate several Phase II clinical trials to test this compound as first line treatment against gastric cancer and plans to apply for orphan drug status (orphan indication in EU and USA, major cancer in Asia).
Nonexclusive distribution rights for this second product have already been sold in two minor markets.
LipoVIL12
The firm’s third product is a first-in-class gene therapy product for cancer immunotherapy based on a liposomally encapsulated virus carrying a human interleukin gene. It has finished a Phase I study, representing the first official international protocol using a liposomal virus. The liposomal encapsulation evades the immune system and allows repetitive administration of the virus without inducing immune response, thus opening new avenues in molecular medicine. This represents a breakthrough in molecular medicine because it allows a number of potential gene therapy treatments to be delivered to patients. The compound is moving successfully to Phase II testing in the immunotherapy of a variety of cancers.
Intellectual Property
Regulon’s technology platform is protected by a broad array of issued and applied patents with additional liposomal drugs in the pipeline.
Competition
Regulon has demonstrated its ability to compete effectively large Pharmaceutical Companies as for example Sequus/Alza/J&J on their liposomal cisplatin also known as SPI-77. Lipoplatin has shown a high efficacy in NSCLC compared to 5% efficacy of SPI-77 in NSCLC, data that resulted in its discontinuation in 2007. The great number of other nanotechnology anticancer products emerging in various research institutions or Biotech and Pharmaceutical Companies are mostly at preclinical or early clinical stage; one out of 100 of these will reach the market in the next 10 years. Lipoplatin has demonstrated its virtues since 2001 when it was promoted into Phase I human studies; currently, it is at late Phase III with data expected to give marketing authorization, first in EU, and then in all world markets.
Advantages over current state of the art and pharmaco-economic benefits
Regulon foresees its customers (oncologists and other clinicians) will readily accept the lead product at the expense of naked cisplatin for the following reasons. Firstly, the lead product can be delivered on an outpatient basis, thereby obviating the costly 24-hour hospitalization required for cisplatin. Secondly, the product commands less frequent usage of expensive hematopoietic factors such as EPO and GM-CSF. Thirdly, the lead product greatly attenuates key cisplatin toxicities, such as renal damage and impairment of glomerular filtration, its use helps reduce hospital costs associated with the management of cisplatin’s toxicities, such as hemodialysis for the treatment of patients with kidney damage and even more expensive treatments for neuropathies. All-together the lead product affords significant benefits for oncologists and other clinicians (key customer benefit) as well as for healthcare payers (key governmental / pharmaco-economic benefit).
It also gives a better quality of life to the patient and a significant extension in the overall survival, something important for the health insurance system. For young patients with testicular cancer where the disease can be completely cured with cisplatin, applying the liposomal cisplatin to target the tumor will avoid long term toxicity in these patients.
Potential Market
The US remains the largest pharmaceutical market in the world recording sales of $279bn in 2007 and contributing 42% of global pharmaceutical market sales. The global cancer market will be worth over USD 50bn in 2009. Global sales of cancer drugs will grow at a compounded annual rate of 12 to 15 percent, reaching USD 75bn to USD 80bn by 2012. According to IMS, the top 20 anticancer drugs generated sales of USD 20bn across the seven major markets (USA, Japan, Germany, UK, France, Italy & Spain) in 2005. Similarly, global sales of the cytostatics class grew 10% in the twelve months after July 2005 to reach USD 20bn in July 2006. Cytotoxics of the platinum family, which include cisplatin, carboplatin and oxaliplatin, contributed around USD 3.5bn (17%) of global cytostatics sales.
Management and attorneys
Teni Boulikas, Ph.D, is Founder, President and CEO of Regulon, Inc (USA) and of Regulon AE (Hellas). Dr. Boulikas is the company founder and has been responsible for the development of Lipoplatin™. (see Biographical sketch of Teni)
Teni Boulikas, Ph.D.
Chairman of the Board, Regulon Inc. (USA)
Afxentiou 7, Alimos, Athens 17455, Greece
Cellular: +30-6937-255-067;
Direct: +30-210-9847-995
Main Office: +30-210-9858-454
Fax: +30-210-9858-453
E-mail: teni@regulon.org
www.regulon.org
The Senior Management Team
Teni Boulikas, Ph.D., Founder, Chairman of the Board / CEO, R&D drug discovery California and Athens
Theodoros Pitsiolis, Financial
Stavros Kottaridis, Ph.D. Member BOD, Coordinator of Phase III in Hellas
Ioannis Tsogas, Ph.D. , in Chemistry, Member BOD, Production Manager, Lipoxal
Ted (Leftheris) Doukas, Senior VP, Business Development based in USA
Christos Karanikas, M.D. Chief Medical Officer, Regulatory Affairs
Maria Karabatzaki, M.D. Chief Medical Officer, Regulatory Affairs
Yannis Barbayannis, Chemical Engineer, Chief Operating Officer based in Athens
Regulon uses the corporate attorney services of Michael Madda at Baker and MacKenzie in Palo Alto, California and the services of Antoinette Konski in California as well as Mrs. Alkisti Malamis in Greece for patents. Timothy Wong and Matt Chavez, CPAs are the accountants of the Corporation based in California. KPMG in California, Zurich and Athens are the auditors for the financial statements. The audited statements, under IFRS, for the period 2005-2008 are expected to become available by the end 2009.