Pipeline

260 ODhfMThTRVBULmpwZw==The main focus of the company is to develop highly effective anticancer drugs for the global market. The company will build a distinctive portfolio of botanical and plant-derived anti-cancer drugs from compounds different from those currently used in the oncology industry.

Cordycepin (3′-deoxyadenosine)

Cordycepin is Rainforest Pharmacal’s lead compound that it is advancing into Phase I/II trials in TdT-positive refractory leukemia patients. Cordycepin (3′-deoxyadenosine) is a novel purine nucleoside antimetabolite found in the parasitic fungus Cordyceps miltaris. In vitro and in vivo studies of Cordycepin have reported numerous biological activities, including the inhibition of cell proliferation, induction of apoptosis, inhibition of platelet aggregation, inhibition of cell migration and invasiveness, and inhibition of inflammation.

In mice, Cordycepin can reduce tumor formation in a model of metastasis and has therefore been proposed as a cancer drug. The effect of Cordycepin on RNA polymerases has been shown to be relatively minor. In contrast, Cordycepin strongly inhibits mRNA polyadenylation, presumably by causing chain termination after it has been incorporated as Cordycepin triphosphate. At high doses Cordycepin inhibits incorporation of labeled uridine into mRNA, but not into its precursor hnRNA, indicating that the export, processing, or stability of transcribed mRNA is inhibited, rather than primary
synthesis.

Cordycepin has displayed cytotoxicity against some leukemic cell lines in vitro. Because it can be converted to an inactive metabolite by adenosine deaminase, Cordycepin must be
administered with an adenosine deaminase inhibitor (e.g., pentostatin) in order to be effective. In addition to anti-cancer activities, Cordycepin has demonstrated very potent anti-oxidant and antiinflammatory activities.

Cordycepin Clinical Development Plan

Complete Phase I/II trial of Cordycepin in TdT-positive refractory leukemia within the next 36 months:

  • dreamstime_xl_56565749Q4 2016 – Re-activate the Investigational New Drug (IND) application for Cordycepin and meet with the FDA.
  • Q4 2016 – Partner with an experienced contract manufacturing organization (CMO) that can support Cordycepin formulation development, stability studies, and production of clinical trial materials.
  • Q3 2017 through Q2 2019 – Conduct Phase I/II trial of Cordycepin.
    Rainforest Pharmacal will re-initiate the Phase I/II study of Cordycepin plus Pentostatin in refractory TdT-positive leukemia patients to determine MTD and pharmacokinetics efficacy and safety at MTD. We anticipate a study design of approximately 24 patients for dose-escalation and up to 20 patients for the dose-expansion stage. Three sites are planned for the doseescalation stage and two additional site will be added for dose-expansion to ensure efficient patient accrual. We expect the study to be completed in 18 months.

Amitosin

Amitosin is a rainforest plant extract shown to be safe and effective. A positive key factor developing these products is the plant is fast growing and hardy. If the production of  he drugs requires utilizing the natural plant source the company will be able to produce a  ufficient resource for worldwide distribution.

24 ODIwMDc5MTAuanBnInitial in vitro studies of Amitosin have demonstrated antitumor activities. The laboratory of Potu N. Rao, Ph.D, Department of Developmental Therapeutics, The University of Texas MD Anderson Cancer Center (MDACC) in Houston, Texas, concluding that Amitosin is more effective in blocking RNA synthesis than DNA synthesis or protein synthesis. This indicates that Amitosin has a drug has the potential to stop the growth of cancer. Similarly, a report from Dr. Jonathan L. Hartwell, Head of the Natural Products Section at the National Cancer Institute (NCI) concluded that Amitosin showed “significant activity” in multiple cell lines. Additional pre-clinical testing on Amitosin is necessary to isolate, identify, and develop theactive ingredients.

Phase I clinical trials will begin upon completion of the pre-clinical studies.

Amitosin Research Roadmap

Rainforest Pharmacal believes that the prior research will allow for discovery and comprehensive testing of one or more compounds with patent potential. Based on the searchable patents and patent applications as well as published technical literature, it appears that plant extracts—specifically those from the Plant “A” species—are novel and potentially patentable in the US, provided they can be characterized physiochemically to illustrate in sufficient detail the inherent differences from the large variety of extracts from other species in the Plant “A” genus which are known in the art. Since the art teaches that the various Plant “A” species vary widely in chemical component make-up, the possibility of a novel component spectrum seems reasonable.

Once intellectual property has been secured, Rainforest Pharmacal will embark on a full drug development program of Amitosin including nonclinical toxicology in rodents and
canines, with long-term animal studies designed to detect carcinogenic potential, particularly evidence of kidney and/or urinary bladder injury during the studies and/or at necropsy. Other planned studies include drug-induced forward mutations in an in vitro mouse lymphoma model (L5178Y) and effects on clastogenesis in an in vivo mouse micronucleus assay. Chromosomal aberration assays will also be conducted (sister chromatid exchange in vivo and Ames test in vitro). Male animals will be studied for product effects on spermatogenesis and female animals will be evaluated for decreased fertility, fetal toxicity or embryolethality.

Upon completion of the non-clinical studies, Rainforest Pharmacal will move forward with the clinical development of Amitosin. We anticipate the completion of the non-clinical studies to occur within the next 36 months and to initiate the Phase 1 dose-finding clinical trial in 2019.