Isofol Medical Ab · OMXSTO:ISOFOL
Isofol Medical Ab — Investor Presentation (April 2025)
39 slides from Isofol Medical Ab's investor presentation, April 2025
Slide 1: Corporate Presentation
Corporate Presentation April 2025 Petter Segelman Lindqvist, CEO
Slide 2: Disclaimer
Disclaimer Forward-looking statements This presentation of Isofol Medical AB (publ) ("Isofol") contains certain forward-looking statements with respect to certain of the company's current expectations and projections about future events. These statements, which sometimes use words such as "intend,"
Slide 3: Isofol: Oncology-focused biotech company listed on Nasdaq Stockholm
Isofol: Oncology-focused biotech company listed on Nasdaq Stockholm Arfolitixorin: aiming to improve the efficacy of standard chemotherapy regimens of solid tumors by replacing leucovorin as a next-generation folate, starting with Dr Roger Tell, Chief metastatic Medical Officer colorectal cancer
Slide 4: Management and Board
Management and Board Petter Dr. Roger Tell, MD Margareta Hagman Segelman Lindqvist Chief Medical Officer Chief Financial Officer Chief Executive Officer Jan-Eric Österlund Prof. Sten Nilsson, MD Dr. Helena Taflin, MD Dr. Alain Herrera, MD Lars Lind Chairman Board Director Board Director Board Direct
Slide 5: The basis of Isofol's value creation
The basis of Isofol’s value creation Arfolitixorin has potential to High medical High market significantly need potential improve patient outcomes 5
Slide 6: The basis of Isofol's value creation
The basis of Isofol’s value creation Arfolitixorin has potential to High medical High market significantly need potential improve patient outcomes 6
Slide 7: Metastatic colorectal cancer is a major medical problem worldwide
Isofol’s lead indication metastatic colorectal cancer is a major medical problem worldwide 154 000 53 000 86 % people annually are patient deaths per of patients with affected in the U.S. year in the metastatic disease die alone USA alone within five years Today’s treatments are insufficient. Ref: A
Slide 8: 5-FU Folate: backbone first-line treatment of metastatic colorectal cancer
The backbone first-line treatment of metastatic colorectal cancer and several other solid tumors is based on chemotherapy 95% of mCRC patients: 5-FU The chemo basis of cytostatic combinations (for example FOLFOX) + Folate Enhances the 5-FU-effect (today: leucovorin) arfolitixorin next-gen folate 8
Slide 9: 5-FU combined with folate is the backbone of first-line treatment
5-FU combined with folate is the backbone of first-line treatment of metastatic cancer for 95% of patiens Arfolitixorin replaces leucovorin which is used in almost all regimens Patient- groups: First Line treatments: 2L Addressable patient groups for arfolitixorin 3L 9
Slide 10: The basis of our value creation
The basis of our value creation Arfolitixorin has potential to High medical High market significantly need potential improve patient outcomes 10
Slide 11: Arfolitixorin does not require conversion and metabolization to become active
Arfolitixorin does not require conversion and metabolization to become active Leucovorin (prodrug) Multi-step conversion to MTHF driven by endogenous enzymes Effect Direct-acting: the active metabolite [6R]-MTHF in itself Arfolitixorin (active drug) resulting in higher levels of MTHF in tumor tissue
Slide 12: Mechanism of Action 5-FU + folate (simplified)
Mechanism of Action 5-FU + folate (simplified) 5-FU • Target: TS (thymidylate synthase – enzyme central to tumor cell DNA synthesis and FdUMP proliferation) • 5-FU is swiftly converted intracellularly to FdUMP and binds to TS forming a binary complex folate MTHF arfolitixorin • In the presence of fo
Slide 13: Previous phase III trial AGENT did not demonstrate superiority
Previous phase III trial AGENT did not demonstrate superiority but similar efficacy as the standard treatment as the selected dosing regimen was suboptimal Arfolitixorin was given in <50% lower dose than leucovorin Low dose → inaccurate comparison between arms Arfolitixorin was given 30 min after 5-
Slide 14: Now initiating a new clinical phase Ib/II study with an optimized dosing regimen
Now initiating a new clinical phase Ib/II- study with an optimized dosing regimen Arfolitixorin Optimized dose Treatment-naïve replacing and administration patients with leucovorin in based on metastatic combination with previously colorectal cancer. 5-FU based generated data. chemotherapy. 14
Slide 15: Strategic development collaboration with one of the world's leading hospitals
Strategic development collaboration with one of the world’s leading hospitals Prof. Dr. med. Sebastian Stintzing Head of the Department of Hematology, Oncology and Cancer Immunology (CCM) Principal investigator 15
Slide 16: Collaboration with global top experts reinforces the clinical program
Isofol’s collaboration with global top experts reinforces the viability of the clinical program Sebastian Stintzing Heinz-Josef Lenz Takayuki Yoshino Frits Peters Prof. Dr. med. MD Professor MD Professor MD PhD. Professor Head of the Clinic for Hematology, Associate Director for Clinical Research Or
Slide 17: Comprehensive dataset de-risks the continued clinical program
Comprehensive dataset de-risks the continued clinical program ISO-CC-002 (Phase I/II) Tumor homogenate studies ISO-CC-005 (Phase I/II) Cell line experiments The AGENT study (Phase III) Tumoroid studies Post hoc-analysis of the AGENT study Tissue-level study 17
Slide 18: Comprehensive dataset de-risks the continued clinical program (1/3)
Comprehensive dataset de-risks the continued clinical program (1/3) ISO-CC-002 (Phase I/II) Tumor homogenate studies ISO-CC-005 (Phase I/II) Cell line experiments The AGENT study (Phase III) Tumoroid studies Post hoc-analysis of the AGENT study Modelle study Phase I/II-studies indicate that the drug
Slide 19: Comprehensive dataset de-risks the continued clinical program (2/3)
Comprehensive dataset de-risks the continued clinical program (2/3) ISO-CC-002 (Phase I/II) Tumor homogenate studies ISO-CC-005 (Phase I/II) Cell line experiments The AGENT study (Phase III) Tumoroid studies Post hoc-analysis of the AGENT study Tissue-level study • Global, randomized phase III-study
Slide 20: Analyses identify main reasons for AGENT outcome: suboptimal dosing regimen
Analyses identify the main reasons for the AGENT trial outcome: suboptimal dosing regimen Arfolitixorin was given in <50% lower dose than leucovorin Low dose → inaccurate comparison between arms Arfolitixorin was given 30 min after 5-FU bolus, in contrast to leucovorin that was given before which is
Slide 21: Comprehensive dataset de-risks the continued clinical program (3/3)
Comprehensive dataset de-risks the continued clinical program (3/3) ISO-CC-002 (Phase I/II) Tumor homogenate studies ISO-CC-005 (Phase I/II) Cell line experiments The AGENT study (Phase III) Tumoroid studies Post hoc-analysis of the AGENT study Tissue-level study Recent studies strengthen the eviden
Slide 22: Tumoroid studies support the dose-response relationship
Tumoroid studies provide further support for the dose-response relationship Presented at ENA 2024 as Late-Breaking Abstract The figure shows response for increasing doses of arfolitixorin (10, 20 and 40 μM). The dose- response relationship is evident, and the conclusion is that ”arfolitixorin activi
Slide 23: Tumor homogenate studies add support for the dose-response relationship
Tumor homogenate studies add additional support for the dose-response relationship dUr*concentration by group Effect of folate dosage on dUr* concentration ✱✱✱✱ in matching tumor homogenates ✱✱✱✱ ✱✱✱✱ ns 30000 dUr concentration (pmol/g) 25000 dUr concentration (pmol/g) Arfo 93% of arfolitixorin- 250
Slide 24: The Modelle-001 trial adds to the body of evidence
The Modelle-001 trial, conducted on tumor samples from live patients, adds to the body of evidence Median TS inhibition was highest in the group receiving the highest dose of arfolitixorin, supporting the dose-response relationship. Taflin, H. et. al. (2024). Increased potentiation of 5-fluorouracil
Slide 25: Stable evidence platform for the continued development
Stable evidence platform for the continued development 1 Arfolitixorin has already shown efficacy in an extensive Phase 3 study with a suboptimal dosing regimen. 2 Higher doses given earlier in time is expected to lead to better efficacy. 3 Higher doses can most likely be given without affecting the
Slide 26: Findings are integrated in the design of the new study
The findings are integrated in the design of the new study, increasing the likelihood of positive outcomes o Higher dose → higher efficacy. o Earlier start, extended administration time → Phase Ib/II study: optimizing conditions for synergistic interaction with 5-FU and effective TS inhibition, ensu
Slide 27: Study design
Study design Phase 1b: Phase 2 (randomized): Dose escalation Dose optimization Five dose levels up to 500 mg/m2 Maximum tolerated dose (MTD) Intravenous short infusion (up to 20 patients) One dose level below MTD 28
Slide 28: Study high-level timetable
Study high-level timetable Phase 2 Regulatory Phase 1b results approval results and and dose of study dose selection selection Phase 1b (2025) Phase 2 (2026) Initiation of Top line- Top line- patient results results ecruitment 29
Slide 29: Study endpoints
Study endpoints Phase 1b: Phase 2: Dose escalation Dose optimization • Objective response (ORR) • Safety and • Progression free survival (PFS) tolerability • Overall survival (OS) • Pharmacokinetics • Safety and tolerability • Effect read-out (ORR, • Pharmacokinetics PFS) • ctDNA • Biopsy analyses 3
Slide 30: The basis of our value creation
The basis of our value creation Arfolitixorin has The unmet potential to High market medical need is significantly potential high improve patient outcomes 31
Slide 31: The market for treatment of metastatic colorectal cancer
The market for treatment of metastatic colorectal cancer 6 billion USD 7.3 billion USD Current market size for Expected market size in pharmaceutical treatments 2032 32
Slide 32: 5-FU + folate will remain the backbone treatment for decades to come
5-FU + folate will remain the backbone treatment for decades to come “I think we are going to get “It is inconceivable to smarter and find more think that 5-FU backbone actionable mutations, but I do will not be the mainstay not think this will impact the care, it is a very effective 1L SoC” drug wi
Slide 33: Suite of patents provide strong intellectual property protection
Suite of patents provide for strong intellectual property protection • Substance and formulation • Patents for clinical use owned and patents owned and managed by managed by Isofol Merck*, covered by the license • New dose regimen patent filed in agreement with Isofol 2025, expiring no earlier than
Slide 34: Blockbuster potential in lead indication in the U.S. alone
Blockbuster potential in lead indication in the U.S. alone, additional opportunities to add Blockbuster opportunity • Sales potential exceeding USD 1 bn per year at peak) in mCRC in the U.S. alone* • 60000-70000 addressable patients, significant price premium Additional markets ex-U.S to be added •
Slide 35: The basis of our value creation
The basis of our value creation Arfolitixorin has The unmet potential to High market medical need is significantly potential high improve patient outcomes 36
Slide 36: Recent newsflow (Q1 2025 to date) illustrates progress
The recent newsflow (Q1 2025 to date) illustrates progress across the board • Evidence platform finalized: Analyses from previous studies concluded (including post hoc, per protocol study), preclinical studies performed and guiding the design of the upcoming study • Regulatory approval to start ph I
Slide 37: The Isofol opportunity in short
The Isofol opportunity in short: Focusing on areas in oncology of high medical need The amount of data available de-risks the clinical program, efficacy already demonstrated. All CMC in place. A next-gen version of an established mechanism of action with widespread clinical use: facilitates market a
Slide 38: Our goal: To improve the prognosis for millions of cancer patients
Our goal: To improve the prognosis for millions of cancer patients and thereby create significant value for patients and their families, shareholders and society at large. 39
Slide 39: Isofol Medical AB (publ)
Isofol Medical AB (publ) Biotech Center Arvid Wallgrens Backe 20 SE-413 46 Göteborg, Sweden [email protected] www.isofolmedical.com © ISOFOL MEDICAL AB (publ) Company Presentation, April 2025. ISO-44, rev 16