Applying Our Technology to Cytokines
We have applied our technology to several cytokines by encapsulating them into protective microparticles that dramatically improve shelf-life and are easily and safely administered orally, intranasally, or even injected directly into a tumor. Drugs are then released slowly over time directly into the specific tissue or organ.
The science behind EXStaM (Patent Pending)
The microparticles themselves are made of poly-lactic acid (PLA), or poly-(D, L-lactic-co-glycolic)-acid (PLGA), copolymers. These copolymers are already used in several Food and Drug Administration (FDA) approved therapeutic devices, owing to biodegradability and biocompatibility. The unique process that allows efficient encapsulation and commercial scale production of labile biologics is made possible by our proprietary EXStaM technology.
NGoXIM™, TreXTAM™ and ATRAXiM™
Our two lead products are NGoXIM™ and TrexTAM™. NGoXIM™ contains the particulate formulation of the potent immune-stimulating cytokine Interleukin-12 (GneX12™) in combination with a proprietary antigen. TrexTAM™ consists of two active ingredients, the multi-functional cytokine Transforming Growth Factor beta (TGFβ) and the vitamin A derivative all-trans retinoic acid (ATRA). ATRAXiM™ is the ATRA component alone.
NGoXIM™ is aimed at the prevention of gonorrhea, one of the most commonly reported bacterial infections in the US, with an estimated incidence of over 800,000 annual cases. The orchestration of innate and adaptive immune responses normally leads to the clearance of infections; however, many bacteria – including Neisseria gonorrheae – survive by perturbing the host’s immune response and preventing the development of protective immunity. No vaccine for gonorrhea currently exists – the treatment depends entirely on antibiotics. However, the steady development of widespread antibiotic resistance has led to serious concerns that gonorrhea could soon become impossible to treat with available methods. TherapyX has teamed up with Intravacc, the Institute for Translational Vaccinology; an experienced non-profit R&D component of the Dutch Royal Ministry of Health that optimizes vaccine technologies – to develop the world’s first prophylactic vaccine against gonorrhea.
Innovating Solutions with Encapsulated Immunomodulatory Biologics
We have demonstrated that prophylactic vaccination with NGoXIM™ can achieve long-lasting cross-protection from multiple strains of N. gonorrheae (1). Separately, we have shown that mucosal treatment of mice with the adjuvant component of NGoXIM™, i.e. GneX12™, rapidly clears established gonorrheae infection and induces protective immunity within the host, something that has never been demonstrated before in any species (2, 3). As a result, TherapyX has been awarded multiple SBIR grants amounting to over $4,000,000 to support IND-enabling preclinical efficacy and pharmacology and toxicity studies related to the development of NGoXIM™. It has been vetted through the FDA and will soon move into non-human primates studies.
The Future of NGoXIM™
At present, NGoXIM™remains focused on the prevention of genital tract infection. However, our studies suggest that the adjuvant component (GneX12™) alone may be effective as a novel therapeutic vaccine for antibiotic-resistant gonorrheae, and separately as an intratumoral immune therapeutic against some of the most challenging and unmet medical needs of our time, such as pancreatic cancer.
TrexTAM™ is aimed at the treatment of inflammatory bowel disease (IBD) and Systemic Lupus Erythematosus (SLE).
The two most common forms of IBD are ulcerative colitis (UC) and Crohn’s disease (CD), and nearly 1.5 million Americans suffer from a form of IBD. Despite recent progress, most patients with IBD are still treated with general medications that exert a mainly anti-inflammatory or suppressive effect on the mucosal immune system. Although biologic agents directed against the proinflammatory cytokine TNFα are a relatively new and effective treatment, 30% of patients will not respond to induction therapy, and of those who initially respond, 50% will cease to respond within a year. In addition, these biologic agents are often not cost-effective and can lead to rare but serious side effects. There is an urgent and unmet need for unique, effective treatments.
SLE is a serious autoimmune condition that affects over 1.5 million Americans. It most often strikes young women between the ages of 15 and 44. There is no cure and only one new drug, an injectable with risks and serious side effects, has won FDA approval in the last 50 years. Other treatments focus on improving quality of life through controlling symptoms and minimizing flare-ups. There is an urgent, unmet need for more effective and convenient treatments. Strong pre-clinical data suggest that TrexTAM™ could be the world’s first successful immune therapy to treat SLE.
How TrexTAM™ Works
TrexTAM™ is an oral combinatorial product containing the potent cytokine Transforming Growth Factor beta (TGFβ) and the vitamin A derivative all-trans retinoic acid (ATRA). We believe that these two active agents in TrexTAM™ work synergistically to suppress harmful inflammatory processes through the generation and stabilization of regulatory T cells.
As a result of our preclinical proof-of-principle in several animal models (4), our team at TherapyX has been awarded multiple NIH SBIR grants worth over $5,000,000 to develop TrexTAM™. Here at TherapyX, we strive to revolutionize the way inflammatory disease is treated.
The Future of TrexTAM™
At present, TrexTAM™ remains in development as an oral treatment for active Crohn’s disease and Lupus. Efficacy and toxicology results will drive product development into the clinic. Independent studies in rodents suggest that ATRAXiM™, the ATRA component of the combinatorial product, may have separate application as a stand-alone oral treatment to prevent organ fibrosis. The company is also exploring its potential in other orphan indications. Since ATRA is already an approved pharmaceutical, ATRAXiM™ may be also be eligible for an FDA accelerated approval pathway.