Chemical Structure and Properties: Fenretinide (4-hydroxy(phenyl)retinamide; 4-HPR) is the active pharmaceutical ingredient (API) in SciTech’s ST-001 nanoFenretinide formulation. It is a synthetic retinoid derivative related to vitamin A (retinol). Fenretinide is a relatively small molecule (Chemical Formula: C26H33NO2; Molar Mass: 391.546 g/mol) that has been extensively studied and well characterized (PubChem CID: 5288209). It is very poorly soluble in water (Water Solubility: 0.00119 mg/mL).
McNeil Laboratories first developed fenretinide as an anti- cancer drug in the early 1980s. Subsequent drug studies by Johnson & Johnson (J&J), the National Cancer Institute (NCI) and others have generated a large body of data available for public use. These earlier studies demonstrate fenretinide’s safety and efficacy as an anti-cancer drug. A Significant History of Safety & Efficacy in Humans - Fenretinide’s performance has been well scrutinized in humans. Particularly noteworthy studies include the following: (1) Large breast cancer chemoprevention study (approx. 3000 patients, 5 year study) demonstrating fenretinide to be well tolerated in humans; (2) NCI case report confirming tumor response in an advanced cutaneous T-cell lymphoma patient (CTCL) - an early efficacy signal; (3) ASCO paper confirming therapeutic responses in the treatment of CTCL and angioimmunoblasticT cell lymphoma (AITL) that also highlights the shortcomings of the competition’s product, and (4) Phase II clinical study showing fenretinide to be well tolerated in patients with small cell lung cancer (SCLC) as well as a stabilization of the disease in 30%
of the patients.
McNeil and J&J have since abandoned fenretinide as a drug product due to its inherent poor solubility and low bioavailability - limitations successfully overcome by SciTech’s drug formulation product (ST-001 nanoFenretinide). Fenretinide is currently in the public domain and the NCI has specifically made the cGMP manufactured API available to SciTech gratis for further use and development.
Mechanism of Drug Action (MOA)
There is ample evidence in the scientific literature that demonstrates that fenretinide is cytotoxic and destroys cancer cells by inducing apoptosis (programmed cell death). The specific mechanism of fenretinide-induced apoptosis is still unknown; however, it has been shown that fenretinide generates several apoptosis-mediating agents such as ceramide (long chain fatty acid amide), reactive oxygen species (ROS), and ganglioside GD3 (a glycosphingolipid comprised of ceramide, oligosaccharide and sialic acid residues). The fact that fenretinide induces multiple apoptosis mediators has been the basis of predictions regarding its efficacy in so many different types of cancer. Given below is an animated representation of the mechanism of action for SciTech's lead anti-cancer drug ST-001 NanoFenretinde.
The recent discovery of fenretinide's immunotherapeutic effects provides an additional MOA for ST-001 nanoFenretinide; notably, its use as an immunotherapy cancer treatment..
The most common side effects reported with oral, lower dose fenretinide use include skin dryness and night-blindness, which are both reversible upon cessation of the fenretinide treatment; and, with subsequent intravenous higher doses of fenretinide additional side effects include elevated triglyceride blood levels.
Intellectual Property (IP)
SciTech Development is the co-inventor, co-owner and exclusive licensee of U.S. Patent No. 8,709,379 (issued April 29, 2014) titled “Liposomal Nanoparticles and
Other Formulations of Fenretinide for Use in Therapy and Drug Delivery”. The company holds international patent coverage in the major global oncology markets: Canada, Australia, New Zealand and the European Union (notably Great Britain, France, Germany and Switzerland). In addition to its patent protection, the company has a great deal of “know-how” regarding its ST-001 product manufacture, which it generally retains as trade secrecy. The company’s issued utility patent includes both composition of matter and methods of production claims. SciTech’s patent claims are both broad and specific thereby effectively blocking creative workaround strategies. SciTech has also received independent third-party evaluation providing an opinion on the freedom to operate (FTO) its intellectual property without infringing upon others.
SciTech has recently filed a provisional patent application titled "Use of Fenretinide Nanoparticles for Immunotherapeutic Cancer Treatment" (Application No. 62/769,822). Described in the application is a method to aid in the treatment of disease including Cutaneous T-Cell Lymphoma (CTCL) covering ST-001’s indirect immunotherapeutic capabilities that complement its already established direct cancer cell destruction capabilities.
GMP Validation & Manufacturing
Campbell University Pharmaceutical Production Plant.
Clinical trial sites identified
Protocol draft completed.
Strong Intellectual Property (IP)
Composition of Matter & Methods of Production claims are unique;
Patents issued: US, EU, Canada, Australia & New Zealand;
Avoids toxic components of the emulsion;
Claims are both broad and specific (blocks creative work-around);
IP anticipates applicability to other APIs.