Modufolin®

Modufolin® has the potential to replace all
folate drugs used in cancer treatment

What is Modufolin?

FOLATE-BASED THERAPIES ARE THE MOST COMMONLY USED CANCER DRUGS TODAY

As part of their cancer treatments, more than 500 000 patients are treated with folate-based therapies annually, in the US, Europe and Japan – more than any other single cancer drug. Modufolin® (chemical name: [6R]-5,10-methylenetetrahydrofolate abbreviated MTHF). Isofol’s clinical lead candidate is Modufolin® (chemical name of active metabolite: [6R]-5,10-methylenetetrahydrofolate abbreviated as MTHF), a novel folate-based therapy developed to increase the efficacy and reduce the side effects of antimetabolites used in cancer treatment. It is the key active metabolite of all clinically used folate-based drugs today, including leucovorin and levoleucovorin, and therefore does not require metabolic activation to exert its action.

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Situation today

A MAJORITY OF PATIENTS DO NOT FULLY BENEFIT FROM THEIR FOLATE-BASED THERAPIES TODAY

All current folate-based therapies used in cancer treatment are prodrugs that need multiple activation steps into an active metabolite (MTHF) to exert their actions. Isofol has shown that a few genes determine cancer patients’ ability to activate these prodrugs. By purifying the key active metabolite of all the marketed folate-based prodrugs, Isofol has created a product that does not require metabolic activation to exert its action. Against this background, Modufolin® may be beneficial regardless of the patient’s genetic ability to activate folates and thus holds the potential to replace the folates used in cancer treatment today.

Development pipeline

How far have we come?

Development Status

NCT ID Research Preclin Phase 1 Phase 2 Phase 3 NDA Submission MAA
Colorectal Cancer
01681472 ICO-CC-002, Pharmacockinetics and pharmacodynamics investigation of Modufolin® in Plasma, Tumor and Adjacent Mucosa in Patients with Colon Cancer. See details.
Completed
02244632 ICO-CC-005, Phase I/II Modufolin® in Combination with 5-Fluorouracil Alone or Together with Oxaliplatin or Irinotecan in Colorectal Cancer
Ongoing-Recruiting
01397305 ISO-MC-091, An extended Feasibility Phase I/II Study of Modufolin® and Pemetrexed Single Agent, Given as Neoadjuvant Treatment in Patients With Resectable Rectal Cancer. See details.
Completed
Osteosarcoma
02383901 ICO-MTX-OB1, A Retrospective Non-intervention Study to Characterize Folate Rescue Treatment in Osteosarcoma Patients Treated With HDMTX (FORTO)
Results available 2016
01987102 ICO-MTX-003, Phase I/II open label dose titration and tolerability in Osteosarcoma
Ongoing - Recruiting

Clinical Studies

WE ARE CURRENTLY IN PHASE I/II CLINICAL STUDIES
FOR BOTH HDMTX RESCUE AND COLORECTAL CANCER

ISO-MTX-003

ISO-MTX-003 (NCT01987102) is a Phase I/II open-label, multicenter
clinical trial designed to identify the Modufolin® dose with most favorable safety prospect and confirmed ability to mitigate HDMTX induced toxicity during treatment of osteosarcoma patients. This is the first study in which HDMTX rescue with Modufolin® is investigated. The study is currently ongoing.

ISO-CC-002

ISO-CC-002 (NCT01681472) is a Phase I/II single-center, blinded, randomized, pharmacokinetic and pharmacodynamic investigation with two doses of Modufolin® compared to levoleucovorin in tumor tissue, adjacent mucosa and plasma for patients with colon cancer admitted for resection of the colon. The study is completed.

ISO-MC-091

ISO-MC-091 (NCT01397305) is a Phase I/II single-center, open-label, feasibility extended study of pemetrexed single agent with Modufolin® given to chemo-naïve patients with newly diagnosed operable rectal cancer. The study is currently ongoing but approaching completion and the last patient is undergoing treatment.

ISO-CC-005

ISO-CC-005 (NCT02244632) is a Phase I/II, single center, open label study aiming to identify the safety and tolearability of a dose range of Modufolin® in combination with the routine doses of 5-FU and oxaliplatin in patients with colon cancer, stage IV. The study is being initiated at Östra Hospital, Gothenburg, Sweden. The results will be used to define the dose to be documented as efficacious in a blinded multicentre trial in patients with colon cancer, stage IV.

Folate Development

FOLATES WERE
DISCOVERED IN THE 1930’s

Folates are derivatives of folic acid (vitamin B9) and the discovery of their effects were made almost 80 years ago, in 1931. A scientist by the name of Lucy Wills demonstrated that anemia could be reversed during pregnancy with brewer’s yeast. A few years later, it was scientifically proven that folates were the corrective substance class. Early on it was recognized that the active metabolites of folates were essential for numerous bodily functions, such as the ability to stimulate cell growth. Folates are essential for life and reduced folates are the natural source of vitamin B9 found in a variety of foods, most often, in leafy green vegetables, dried beans, and peas. They are critical for cell growth inside the human body.

 

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