AMRIF BV is a biopharmaceutical company focussed on innovative therapies using the RESCAP® platform technology in chronic (inflammatory) disorders. It was founded in 2013 as a sister company of Alloksys Life Sciences BV (a company using the RESCAP® focused to acute inflammatory conditions). AMRIF’s technology are phosphatase compounds, that are active/involved in Attenuation Modulation and Restoration of Immune Functionality. For drug development, AMRIF will use proprietary IP and attract specific IP and know-how from third parties. Preclinical development programs (including safety and proof of principle studies in relevant in vitro, animal and human models) are executed in cooperation with academic institutes, medical centers and partnering biotech companies. Early product candidates (if possible after phase I or II) will be out-licensed to pharma parties for subsequent further (clinical) development. The revenues of drug development will fuel future development of innovative therapeutic entities.
The lead product of AMRIF is hRESCAP® (recombinant human alkaline phosphatase) as developed under an ETB (Euroean Trans Bio) project in cooperation with CEVEC Pharma (Cologne, Germany), using CEVECs proprietary CAP9 cell technology and GMP-produced at GenIBET (Oeiras, Portugal). hRESCAP is a protein with a prolonged plasma residence time, compatible with chronic disease management. Costs of Goods of this product are, compared to other biologicals produced on other host-cell lines, favorable due to the fact that marginal dosages are needed (mgs of RESCAP per total bodyweight rather than mgs per kilogram bodyweight used for many of e.g. anti-Rheumatoid Arthritis biologicals). Intravenously administrated hRESCAP has passed phase I clinical trials successfully in human volunteers. hRESCAP is found to be safe and does not trigger adverse clinical events. Partners in this study were, performed in July/August 2013 TNO (Zeist), VUMC (Amsterdam) and Centre for Human Drug Research, Leiden The Netherlands (CHDR). Both orphan disease projects are being targeted as well as in blockbuster diseases.
Ectophosphatases are enzymes that act on the outside of cells and and act, among others, to dephosphorylate compounds, that act as triggers to the immune system. These triggers can derive from both the external environment (stranger signals, like the bacterial LPS-toxin) but also from inside the body itself, like nucleotides. These nucleotides, when present in the extracellular milieu, function as “danger” signal. In our vision, the superfamily of ecto-phosphatases plays a yet “undiscovered” role in the immune defense system. The recently described role of extracellular adenosine as key signaling moiety with a central anti-inflammatory is in agreement with the mechanism of action of this superfamily of ectophosphatases. Interestingly however, there is ample evidence that alkaline phosphatases also play an important role in the maintenance of physiological barriers, like the gastro-intestinal barrier, the blood brain barrier, the placental barrier and the respiratory barrier where, in healthy persons, the ectophosphatases are highly expressed. AMRIF’s interest in developing the therapeutic applications linked to these barriers, since deficiencies in functionality have been identified and supplementation with specific ectophosphatases has been demonstrated to be effective in animal models. Thus, ectophosphatases have a distinctive mechanism of action and are an integral part of the nature’s defense system to prevent initiation and aggravation of inflammatory conditions. Hence the MOA of ecto-phosphatases are different from other anti-inflammatory compounds like corticosteroids, NSAIDS, cox inhibitors, TNFa blockers or DMARDS. Additional Mechanism of Action towards diabetes and metabolic syndrome have recently described, underlining the pluriform functionality and applicability of RESCAP for different diseases.
Beneficial clinical effects of Alkaline Phosphatase were shown in various, mostly inflammation driven and ischemia driven diseases and clinical conditions; open cardiac surgery, inflammatory bowel disease and septic shock (treatment of acute renal failure in septic shock patients) and rheumatoid arthritis. Also preclinical proof of principle with the RESCAP platform was obtained in diseases ranging from MS, CF, diabetes, metabolic syndrome, cancer and skin/wound repair. The latter programs are developed in concert with USA-based biotech companies. Thus, pending financing, POC Phase 2 clinical trials using our RESCAP platform technology are being planned in patients suffering from Neurodegenerative diseases like Parkinson and ALS, as well as in patients suffering from RA and diabetes. Independent business-units of AMRIF will be set-up towards specific therapeutic applications. Upon successful clinical trials and or transfer to third parties, AMRIF will initiate further development in other therapeutic applications enabled by the RESCAP platform technology.
Investors are welcomed to participate in AMRIF or to participate in the development of specific therapeutic indications applying our RESCAP platform technology in separated business units under the umbrella of AMRIF.
• Identify and demonstrate pre-clinical efficacy of the specific RESCAP compatible therapeutic indications like NDD, RA, ALS, CF, MS, Asthma/COPD, diabetes.
• Maintain a low overhead and “virtual operating structure” by outsourcing (CMO/CRO).
• Marketing & Sales by major- or niche pharma players in the respective fields.
• After initial investment funding subsequent revenues come from e.g. milestone-payments and subsequently royalties on net sales.
New modalities or applications will be protected by proprietary patents. Patent protection will be pursued and precedes scientific publications in the field. Where needed exclusive patents will be in-licensed from third parties on specific fields of interest.
Current patents of AMRIF:
• Recently a patent was granted on Alkaline Phosphatase endogenous
induction: Brands et al., 2009, Method for increasing the Activity of the
Immune System of a mammal at Risk of Inflammatory Diseases.
US2011052560 EP2252324, granted in the US and EU
• A novel patent on the rescue function of alkaline phosphatase as
generator of anti-inflammatory adenosine (Feb 2011, EPO 11154667.7)
has been in-licensed from Alloksys Life Sciences BV: Alkaline Phosphatase
as systemic rescue moiety to combat inflammatory disorders: Alkaline
phosphatase mediated generation of Extracellular Adenosine, as an
Alternative Pathway to modulate anti-inflammatory responses under excessive pro-inflammatory insult conditions.
• AMRIF, through its cooperation with its partners Zoltan Laboratories,
Essential Skin Care, Cancure Labs in USA and Cevec Pharma in Germany
has full access to respective IP in diabetes, skin diseases, oncology and
The above patent portfolio covers about 80 % of all IP on therapeutic applications of Alkaline Phosphatase