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All about the drug candidate arfolitixorin
and related information

STRATEGY

Isofol has initiated a a stepwise process, together with several external experts, to continue developing the drug candidate arfolitixorin. Through a cost-effective and risk-minimizing process, step-by-step evaluations will be carried out. The strategy is based on Isofol being constantly prepared to reassess the plans based on the outcomes in the sequential activities and the company will continuously communicate the results from the activities. The Company will not commit to any investment in extensive clinical studies or preparation for commercialization until the analytical results of the stepwise process are complete and it is verified that arfolitixorin has the potential to achieve expected results. The focus is on establishing the clinical effect. Our assessment is that the planned activities can be financed with existing funds.

Step 1: In-depth analyses of data from the phase III study

An in-depth analysis of data from the Phase III study AGENT has been made during the first half of 2023. The results from the analysis support the hypothesis that a different dose and administration regimen has the potential to improve the efficacy of the company’s drug candidate arfolitixorin.

The main conclusions of the evaluation in step 1 are:

• The chosen dose and the administration regime of two bolus doses likely resulted in that the concentration of arfolitixorin in the patients’ blood was too low to deliver a sufficiently high amount of active substance into the tumor.
• The consequence of the low dose, in comparison with the control group with standard treatment, was not justified because the control group was treated with a higher dose.
• PK modeling and review of available safety data show that it is likely possible to administer arfolitixorin at a higher dose than that evaluated in the AGENT study and that a different dose and administration regimen could probably have improved the drug candidate’s efficacy.

Based on these conclusions, Isofol has decided to continue the development of arfolitixorin according to this three-step process. Read the press release >>

Step 2: Laboratory study to document the effect of different doses

Step 2 has been initiated and concerns time- and cost-effective laboratory studies. The aim is to document the effect of arfolitixorin in different doses and administration forms in combination with 5-FU. These tests are preformed in collaboration with external research laboratories and have gradually been extended to cell lines and organoids also outside the area of colorectal cancer. Collaborations are currently taking place with a research laboratory in Norway and one in the USA.

The first results received were from a limited number of tests in cell lines and organoids from pancreatic tumors and cell lines from colorectal tumors. Different doses have been tested, including a higher dose of arfolitixorin than that used in the AGENT study. The results of the initial experiments in pancreatic tumor cell lines and organoids show no additional effect of either arfolitixorin or leucovorin. The tests on cell lines from colorectal cancer tumors showed no additional effect. Read the press release >>

Additional results originate from tests on organoids from tumors in the colon and rectum showed additional effects of arfolitixorin in two of a total of five organoids studied, an effect that was not seen with leucovorin. The additional effect was shown as an enhancement of the response to the chemotherapy drug 5-FU, both in terms of reducing tumor size and the ability to induce cell death. In three out of five organoid tests, however, no additional effect of any of the folates in combination with 5-FU was seen. Data from the laboratory tests will undergo bioinformatics analyses to identify molecular patterns associated with folate sensitivity. These analyses may provide further support in the construction of a hypothesis for the continued development of arfolitixorin. Read the press release >>

Complementary studies of arfolitixorin’s effect on organoids are planned to be carried out during the first quarter of 2024.

Step 3: A small clinical trial with a carefully selected dosing regimen

An overall assessment and positive signals from step 2 will be the basis to conduct a smaller clinical efficacy study with carefully selected dose and administration form in step 3. The results will be used as a basis for discussions with relevant pharmaceutical authorities regarding the further development plan, and may also increase the attractiveness of the project among potential licensees in the pharmaceutical industry. It is currently difficult to estimate the costs and time required for this type of efficacy study, but the company’s current assessment is that its existing financial means will be sufficient.

Last updated 05-20-2024