Modufolin (arfolitixorin) / Isofol Medical, Solasia - LARVOL DELTA

Isofol includes first patient in a clinical phase Ib/II study of arfolitixorin (Isofol Medical Press Release) - "Isofol Medical AB...announces that the first patient has been included in the clinical phase Ib/II study of the drug candidate arfolitixorin as a new potential treatment of metastatic colorectal cancer....The study will be conducted in two stages, where the initial phase Ib part will assess the benefit/risk profile of escalating doses in a new dosing regimen that is expected to increase the efficacy further as compared to previously conducted trials."

Trial status • Colorectal Cancer

A Clinical Study of Arfolitixorin in Patients With mCRC (clinicaltrials.gov) - P1/2 | N=60 | Recruiting | Sponsor: Isofol Medical AB | Not yet recruiting ➔ Recruiting

Enrollment open • Colorectal Cancer • Oncology • Solid Tumor

A Clinical Study of Arfolitixorin in Patients With mCRC (clinicaltrials.gov) - P1/2 | N=60 | Not yet recruiting | Sponsor: Isofol Medical AB

New P1/2 trial • Colorectal Cancer • Oncology • Solid Tumor

Isofol announces the presentation of a post-hoc analysis of the phase III study AGENT at the 2025 ASCO GI symposium (Isofol Medical Press Release) - P3 | N=490 | AGENT (NCT03750786) | Sponsor: Isofol Medical AB | "Results from the analysis, in which the expert committee excluded patients who were not treated in compliance with the study protocol, show a numerical difference in objective response rate (ORR) in favor of arfolitixorin based on a remaining group of 225 patients...The study further pointed out regional differences. In North America, the incremental efficacy of arfolitixorin was significant (arfolitixorin: 85.7% ORR; leucovorin: 45.5% ORR; p<0.017; based on 47 patients). Notably, in all regions excluding Japan, arfolitixorin showed a 15.9 percentage points statistically significant higher response rate compared to leucovorin (arfolitixorin: 62.1% ORR; leucovorin: 46.2% ORR; p<0.026; based on 172 patients)."

P3 data • Colorectal Cancer

The importance of treatment handling and compliance on overall response rate in a phase III study of metastatic colorectal cancer: Post-hoc per protocol analyses of the AGENT trial. (ASCO-GI 2025) - P3 | " In a randomized, multicenter, multinational, phase III study, patients were randomized to receive either arfolitixorin (n=245) or leucovorin (n=245) with 5-fluorouracil (5-FU), oxaliplatin and bevacizumab as a first-line treatment. In the AGENT trial, 46% of the included patients met per protocol compliance for treatment handling. In this cPP population, there was a non-significant, but clinically relevant, increase in the overall response rate in the arfolitixorin compared to the leucovorin arm. Notably, in all regions excluding Japan, the overall response rate was higher for arfolitixorin, with statistical significance."

Clinical • Compliance • Metastases • P3 data • Retrospective data • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

Isofol and its partner Solasia plan to expand the upcoming clinical trial of arfolitixorin to Japan (Isofol Medical Press Release) - "Isofol Medical AB...today announces that its partner Solasia Pharma K.K. (Solasia) has made a directional decision to include Japanese patients in the phase II part of the upcoming phase Ib/II trial of arfolitixorin in metastatic colorectal cancer...Isofol and its Japanese license partner Solasia are strongly committed to developing arfolitixorin as a new potential treatment for colorectal cancer. Isofol has submitted a clinical trial application, CTA, to the German regulatory agency, BfArM, for an upcoming clinical phase Ib/II trial and is expected to initiate the first part of the trial in the first half of 2025....Alongside the initiation of the first part of the clinical trial (phase Ib), which is conducted at Charité – Universitätsmedizin Berlin in Europe, Isofol and Solasia have agreed to engage in joint preparations for the second part of the study (phase II). The aim is to enroll patients in Japan in 2026."

New P1/2 trial • Colorectal Cancer

Isofol provides an operational update during investor meeting (Isofol Medical Press Release) - "Isofol Medical AB...will provide an operational update during today’s investor meeting. The company will present its evidence platform that forms the basis for the upcoming clinical study with drug candidate arfolitixorin, the intended study design for the phase Ib/II study, as well an update on the commercial potential of arfolitixorin...The evidence platform gathers the extensive arfolitixorin dataset generated in pre-clinical and clinical studies, and the conclusions can be summarized as follows: Arfolitixorin has already shown efficacy in an extensive phase III study; Higher doses with a new administration regimen are expected to lead to better efficacy; Higher doses can most likely be given without affecting the safety profile....The design and preliminary endpoints will be presented at the investor meeting."

Clinical protocol • New P1/2 trial • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

Isofol announces that an investigator-initiated study of arfolitixorin has been published in BJC Reports (Isofol Medical Press Release) - P1/2 | N=30 | Modelle 001 (NCT04126655) | "Isofol Medical...announces that the investigator-initiated Modelle study, evaluating the effect of the drug candidate arfolitixorin at tissue level, has been published in the scientific journal BJC Reports...Modelle is an investigator-initiated study conducted at Sahlgrenska University Hospital in collaboration with Norrlands University Hospital and co-financed by Isofol...The study evaluated different doses of arfolitixorin and its ability to enhance the tumor-inhibiting effect of 5-FU-based chemotherapy. The effect was measured as inhibition of thymidylate synthase (TS), an enzyme that drives tumor cell growth and is thus an important target in cancer treatment....The results showed that giving arfolitixorin resulted in significantly higher concentrations of the active substance in liver metastatic tissue compared to the given dose of the standard of care treatment leucovorin. Further, an increased inhibition of TS was shown..."

P1/2 data • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

Increased potentiation of 5-fluorouracil induced thymidylate synthase inhibition by 5,10-methylenetetrahydrofolate (arfolitixorin) compared to leucovorin in patients with colorectal liver metastases; The Modelle-001 Trial. (PubMed, BJC Rep) - "The Modelle-001 Trial demonstrated significantly higher levels of MeTHF in metastases following Arfo compared to LV. This resulted in a greater increase TS inhibition in metastases although not statistically significant."

Journal • Colorectal Cancer • Oncology • Solid Tumor • TYMS

Isofol announces that an abstract has been accepted for presentation at ASCO GI 2025 (Isofol Medical Press Release) - "Isofol Medical AB...announces that an abstract with results from a post hoc-analysis of the company’s Phase III-study AGENT has been accepted by ASCO GI, which takes place in San Francisco, US, between January 23-25th, 2025....The results show the importance of adherence to the study protocol and that a higher protocol compliance would likely increase the efficacy of arfolitixorin and thus, as previously communicated, support the company’s new development plan."

Retrospective data • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

A Late Breaking Abstract concerning arfolitixorin will be presented at ENA 2024 today (Isofol Medical Press Release) - "The poster describes a dose-dependent cytotoxic effect and increased activity of arfolitixorin at higher doses in combination with 5-FU...The studies evaluated the effect of arfolitixorin and leucovorin in combination with 5-FU based chemotherapy in patient-derived colorectal cancer tumoroids. The results show that arfolitixorin displays a potent, dose-dependent cytotoxic effect and increased activity in 5-FU-treated tumoroids that, at higher doses, is higher than with today’s standard treatment leucovorin. The effect was most marked in the tumoroids that were most resistant to 5-FU....'The conclusions from the preclinical studies support our hypothesis of a suboptimal arfolitixorin dose regime in the phase III clinical trial AGENT. This contributed to not achieving a sufficiently high efficacy to establish superiority to leucovorin in the ITT population.'"

Preclinical • Trial status • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

Dose-dependent cytotoxicity of arfolitixorin, a direct-acting folate, versus leucovorin with 5-fluorouracil in patient-derived colorectal cancer tumoroids (PDTs) (EORTC-NCI-AACR 2024) - P3 | "In the Phase 3 study ISO-CC-007 (NCT03750786), ARF showed efficacy comparable to LEU, however, the primary endpoint of demonstrating superiority was not achieved, possibly due to the dose being suboptimal for a cellular response.Material and methods The activity of 5FU, LEU, levoleucovorin (LLEU), ARF, and combinations thereof, were assessed in a panel of two CRC cell lines and 20 PDTs. These findings support that suboptimal dosage in the ISO-CC-007 trial contributed to insufficient efficacy. Further clinical development at higher doses could enhance the standard of care for patients, and a Phase 1/2 clinical trial based on this approach is currently being planned."

Clinical • Late-breaking abstract • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

Isofol announces that a Late Breaking Abstract has been accepted by ENA 2024 (Isofol Medical Press Release) - "Posters qualified for Late Breaking Abstracts at ENA are, according to the congress guidelines, those that describe the latest advances that will change daily clinical practice....The abstract was produced in cooperation with Oncosyne AS and Akershus University Hospital in Oslo, Norway, and is based on the preclinical studies that were conducted earlier this year, whose conclusions support the company’s clinical development plan."

Late-breaking abstract • Preclinical • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

Isofol strengthens the outlook for further extending the patent protection of its drug candidate arfolitixorin (Isofol Medical Press Release) - "Isofol Medical AB...announces positive outcomes of a preliminary patentability report on a new international product patent application for arfolitixorin, submitted under the PCT (Patent Cooperation Treaty). If granted, the patent could significantly strengthen and prolong arfolitixorin’s intellectual property protection internationally...The application, which has been filed under the Patent Cooperation Treaty, covers pharmaceutical compositions comprising arfolitixorin in the form of stable lyophilizates for use in clinical settings....The ensuing patents will have an expected expiry in the mid- 2040s, and span across Isofol’s key markets, including but not limited to the United States, Europe and Japan. Given its scope, potential geographic coverage and long duration, this patent is deemed to be of high importance for Isofol and its partners."

Patent • Patent expiry • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

ISOFOL ANNOUNCES NEW PRECLINICAL DATA SUPPORTING THE PREVIOUSLY COMMUNICATED CLINICAL DEVELOPMENT PLAN FOR ARFOLITIXORIN (Isofol Medical Press Release) - "Isofol Medical AB...today announces results from two preclinical studies that support the dose-response relationship for arfolitixorin. These positive data further strengthen the hypothesis behind the design of the clinical Phase Ib/II study in patients with colorectal cancer that Isofol plans to conduct in collaboration with one of Europe’s leading university hospitals, Charité – Universitätsmedizin Berlin...The preclinical studies were conducted by Oncosyne AS in collaboration with Akershus University Hospital in Oslo, and at the Surgical Oncology Laboratory (SOL) at Sahlgrenska University Hospital in Gothenburg, respectively. Both studies show that increased doses of arfolitixorin in combination with 5-FU lead to significantly higher efficacy. The studies also investigated the addition of PLP (the active form of vitamin B6) and with the analysis methods applied, neither found any additive efficacy in combination with arfolitixorin."

Clinical protocol • Preclinical • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

ISOFOL ANNOUNCES A POST HOC PER-PROTOCOL ANALYSIS OF THE AGENT STUDY, FURTHER SUPPORTING ARFOLITIXORIN’S CONTINUED CLINICAL DEVELOPMENT (Isofol Medical Press Release) - P3 | N=490 | AGENT (NCT03750786) | Sponsor: Isofol Medical AB | "Isofol Medical AB...announced today that an external committee of experts has performed a post hoc per-protocol analysis of the clinical phase III study AGENT that shows new results in favor of arfolitixorin...Results from the analysis, in which the expert committee excluded patients who were not treated in compliance with the study protocol, show a numerical difference in objective response rate (ORR) in favor of arfolitixorin (arfolitixorin: 59.3 % ORR; leucovorin: 51.5 % ORR; p<0.23). Thus, the study shows a non-significant difference between the arms in favor of arfolitixorin of 7.8 percentage points based on a remaining group of 225 patients....The conclusions from the per-protocol post hoc analysis will support the design of the phase Ib/II study that is expected to be initiated before the end of 2024 and the upcoming dialogues with relevant authorities."

Clinical protocol • New P1/2 trial • P3 data • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

Final analysis of the Greek cohort of the AGENT phase III study arfolitixorin in metastatic colorectal cancer (ESMO-GI 2024) - P3 | "This study presents the final analysis focusing on the Greek patient subpopulation. Patients with mCRC were randomized to receive arfolitixorin (Arm A: 120 mg/m2 given as two intravenous bolus doses) or leucovorin (Arm B: 400 mg/m2 as a single intravenous infusion), both in combination with 5-FU, oxaliplatin, and bevacizumab... The AGENT trial did not demonstrate clinical superiority of arfolitixorin over leucovorin in first-line therapy for mCRC. Nonetheless, this analysis suggests potential benefits associated with arfolitixorin in the Greek population, possibly influenced by regional and genetic factors. Limitations, including the small sample size, warrant cautious interpretation of these findings."

Metastases • P3 data • Colorectal Cancer • Fatigue • Gastrointestinal Cancer • Hematological Disorders • Oncology • Pain • Solid Tumor • BRAF • KRAS

Arfolitixorin: An unmet need in the management of metastatic colorectal cancer. (PubMed, J Pak Med Assoc) - No abstract available

Journal • Metastases • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

ISOFOL AND CHARITÉ SIGN COLLABORATION AGREEMENT ON FURTHER CLINICAL DEVELOPMENT OF ARFOLITIXORIN (Isofol Medical Press Release) - "Isofol Medical AB...announced today that the company has signed a collaboration agreement with...hospital Charité Universitätsmedizin in Berlin, and Professor Sebastian Stintzing, for the further clinical development of arfolitixorin. The collaboration includes strategic planning of the clinical development of arfolitixorin in general and the design of the clinical phase Ib/II study in particular....the collaboration will include strategic discussions on the continued development and evaluation of completed preclinical and clinical studies as well as planning for future ones. This includes, for example, the design of a possible future clinical phase III study as well as discussions and agreements on the design of the planned clinical phase Ib/II study to complete the synopsis and study protocol. The parties have agreed on the objective to carry out the clinical phase Ib/II study at Charité, with an estimated initiation before the turn of the year 2024/2025."

Clinical protocol • Licensing / partnership • New P1/2 trial • Trial initiation date • Oncology • Solid Tumor

ISOFOL’S JAPANESE PARTNER SOLASIA INTENSIFIES ITS COMMITMENT TO THE CLINICAL DEVELOPMENT OF ARFOLITIXORIN (Isofol Medical Press Release) - "Isofol Medical AB...today announces that the company’s collaboration partner, the Japanese pharmaceutical company Solasia Pharma K.K...has confirmed its continued strong commitment in the development of arfolitixorin. Solasia will contribute with its expertise and participate in defining the detailed design of the clinical development program presented by Isofol today....Solasia will participate in the ongoing process to define the details of the development program led by Isofol and discuss development schedules, clinical trial designs and related matters."

Clinical protocol • Licensing / partnership • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Sarcoma • Solid Tumor

ISOFOL PRESENTS A CLINICAL DEVELOPMENT PLAN FOR ARFOLITIXORIN (Isofol Medical Press Release) - "Isofol Medical AB...today presents the company’s continued strategy and clinical development program for the drug candidate arfolitixorin. The board and management, together with external experts, have evaluated the available data for arfolitixorin and decided to conduct a clinical phase I/II study to document the efficacy and safety of a new dose regimen. Isofol’s goal is to reach a read-out of top-line data with its current financial resources. The plan will be presented during an investor meeting today, Tuesday, March 19...The preliminary design of the phase I/II study, which will be discussed with relevant regulatory authorities, will start with a phase I part in which ascending doses of arfolitixorin in different administration forms (intravenous bolus injection/short infusion) will be evaluated to ensure safety and tolerability, while also performing an initial efficacy evaluation....the first patient is expected to be included in the study before the end of 2024."

Clinical protocol • New P1/2 trial • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

ISOFOL MEDICAL AB (PUBL) PUBLISHES YEAR-END REPORT, JANUARY – DECEMBER 2023 (Isofol Medical Press Release) - "Isofol Medical AB...announces that they have received an abstract from the investigator-initiated academic study, Modelle 001, that was conducted with arfolitixorin. Isofol will review the full results when they are published, likely in the spring of 2024."

P1/2 data • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

ISOFOL HAS RECEIVED THE FIRST RESULTS FROM LABORATORY TESTS OF ARFOLITIXORIN (Isofol Medical Press Release) - "Isofol Medical AB...announces today that the company has received the first results from the laboratory tests of arfolitixorin which are performed ahead of a potential decision to continue the clinical development of the drug candidate. Data generated so far from the first experiments show no difference in additional effect of arfolitixorin compared to leucovorin. Higher doses of arfolitixorin than was used in the AGENT study have been tested, but with no better effect. Further laboratory tests are ongoing and full results from the preclinical evaluation are expected to be delivered in early 2024....The results of the initial experiments in pancreatic tumor cell lines and organoids show no additional effect of either arfolitixorin or leucovorin."

Preclinical • Trial status • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Solid Tumor

ISOFOL’S BOARD OF DIRECTORS DECIDES TO INITIATE THE PLANNING OF CLINICAL STUDIES AND WILL ANNOUNCE A STRATEGIC DEVELOPMENT PLAN ON MARCH 19 (Isofol Medical Press Release) - "Isofol Medical AB...has been engaged in intensive strategy work since the new Board of Directors and management took office in January. The Board of Directors has decided today to prepare a new development program for arfolitixorin, with the goal of initiating new clinical studies as soon as possible. The company intends to present details of the strategic direction on March 19, along with holding an investor meeting...The initial focus will be to conduct small scale trials in a time- and cost-efficient manner, powered to prove the value of arfolitixorin compared to standard of care. Planning is currently underway and further details will be announced on 19 March....In parallel with this, Isofol continues to analyze data from the AGENT study and will perform additional laboratory studies with the primary goal of optimizing the design of the new clinical program."

Clinical • Trial status • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

ISOFOL PRESENTS ADDITIONAL RESULTS FROM LABORATORY TESTS WITH ARFOLITIXORIN SHOWING SUPPLEMENTARY EFFECTS (Isofol Medical Press Release) - "Isofol Medical AB...announces today that the company has received additional results from the laboratory tests conducted with arfolitixorin ahead of a potential decision on the drug candidate’s continued clinical development. The results show interesting supplementary effects of arfolitixorin in two of a total of five evaluated organoids from colorectal cancer tumors. These findings are positive for Isofol and the company will implement additional bioinformatic analysis to identify potential patterns...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....The tests are carried out in collaboration with external research laboratories in Norway and the USA and have been gradually extended to cell lines and organoids..."

Preclinical • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor