Isofol Medical Ab · OMXSTO:ISOFOL
Isofol Medical Ab — Investor Presentation (November 2024)
48 slides from Isofol Medical Ab's investor presentation, November 2024
Slide 1: Investor meeting November 2024
Investor meeting November 2024
Slide 2: Petter Segelman Lindqvist, CEO
Petter Segelman Lindqvist CEO 2
Slide 3: Agenda
Agenda Evidence platform and Petter Segelman Lindqvist CEO basis for clinical studies Clinical study design Roger Tell CMO Market outlook Petter Segelman Lindqvist CEO 3
Slide 4: 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 5: Arfolitixorin has an important role to play
Arfolitixorin has an important role to play Petter Segelman Lindqvist, CEO Dr Roger Tell, Chief Medical Officer
Slide 6: The basis of our value creation
The basis of our value creation Arfolitixorin has the potential to High medical High market significantly need potential improve patient outcomes 6
Slide 7: Colorectal cancer remains a major medical problem
Colorectal cancer remains a major medical problem 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: American Society of Clinical Oncology (ASC
Slide 8: The backbone treatment of metastatic colorectal cancer remains unchanged
The backbone treatment of metastatic colorectal cancer remains unchanged 5-FU The basis of cytostatic combinations (for example FOLFOX) + Folate Pharmaceutical that enhances the 5-FU-effect (leucovorin) arfolitixorin next-gen folate Improved first-line treatments offer greatest potential to improve
Slide 9: Arfolitixorin does not require conversion to be active
Arfolitixorin does not require conversion to be active Leucovorin Endogenous enzymes Effect Arfolitixorin Direct-acting Effect 9
Slide 10: Comprehensive dataset enhances prospects for success in upcoming study
Comprehensive dataset enhances prospects for success in upcoming study 10
Slide 11: Comprehensive dataset as a basis for the next step
Comprehensive dataset as a basis for the next step 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 11
Slide 12: Comprehensive dataset as a basis for the next step
Comprehensive dataset as a basis for the next step 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 candidate is saf
Slide 13: Comprehensive dataset as a basis for the next step
Comprehensive dataset as a basis for the next step 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 III-study showed comparable efficacy to leucovorin
Slide 14: Comprehensive dataset as a basis for the next step
Comprehensive dataset as a basis for the next step 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 (liver metastases) Recent studies strengthens the evidence
Slide 15: Stable evidence platform for continued development
Stable evidence platform for continued development 1 Arfolitixorin has already shown efficacy in an extensive Phase 3 study. 2 Higher doses with a new administration regimen should lead to better efficacy. 3 Higher doses can most likely be given without affecting the safety profile. 15
Slide 16: The evidence platform 1/3
The evidence platform 1/3 1 Arfolitixorin has already shown efficacy in an extensive Phase 3 study. o The ITT analysis of the Phase 3 study AGENT showed arfolitixorin is efficacious in line with leucovorin → demonstrated that the drug is active and has an effect already at the selected dosing regime
Slide 17: AGENT: A post-hoc per protocol analysis show better effect even with the selected dose
AGENT: A post-hoc per protocol analysis show better effect even with the selected dose When excluding subjects Significantly higher Result cleared from with study protocol proportion of reduced 5-FU subjects with reduced deviations, arfolitixorin doses in Japan compared to 5-FU doses show shows sign
Slide 18: The evidence platform 2/3
The evidence platform 2/3 2 Higher doses with a new administration regimen should lead to better efficacy. o Analyses shows that the dose regimen probably did not provide sufficient conditions for synergistic action between 5-FU and arfolitixorin. The dose was too low and was not given in an optimal
Slide 19: Was the dose regimen in AGENT optimal?
Was the dose regimen in AGENT optimal? Mechanism of action 5-FU + folate AGENT study a) 5-FU is swiftly metabolized intracellularly to FdUMP, which o Arfolitixorin was given in <50% lower dose than leucovorin. binds to the target enzyme TS (central to tumor cell proliferation) o Arfolitixorin was gi
Slide 20: The evidence platform 2/3
The evidence platform 2/3 2 Higher doses with new administration regimen should lead to better efficacy. o Analyses show that the dose regimen probably did not provide sufficient conditions for synergistic action between 5-FU and arfolitixorin. The dose was too low and not administered in an optimal
Slide 21: Tumor homogenate studies
Tumor homogenate studies 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- 25000 LV 20000 treated samples had 20000 15000 higher dUr lev
Slide 22: Tumoroid studies
Tumoroid studies 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 activity is positively correlated with drug concentration”. Studi
Slide 23: Modelle-study
Modelle-study 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 induced thymidylate synthase inhibition by 5,10-methylenetetrahydrofolate (arfolitix
Slide 24: The evidence platform 3/3
The evidence platform 3/3 3 Higher doses can most likely be given without affecting the safety profile. o Available safety data from clinical studies and PK simulations show that it is possible to administer significantly higher doses of arfolitixorin while maintaining the safety profile. o Studies
Slide 25: Stable evidence platform for continued development
Stable evidence platform for continued development 1 Arfolitixorin has already shown efficacy in an extensive Phase 3 study. 2 Higher doses with a new administration regimen should lead to better efficacy. 3 Higher doses can most likely be given without affecting the safety profile. 25
Slide 26: The findings are actionable and integrated in the design of the new study
The findings are actionable and integrated in the design of the new study, increasing the likelihood of positive outcomes o Higher dose → higher efficacy o Longer injection time with earlier start → Phase Ib/II study: optimizing conditions for synergistic interaction and safety, and decreases the ne
Slide 27: Dr Roger Tell, Chief Medical Officer
Dr Roger Tell Chief Medical Officer 27
Slide 28: The design of the clinical phase 1b/2-study – an overview
The design of the clinical phase 1b/2- study – an overview Dr Roger Tell, Chief Medical Officer
Slide 29: The path to approval
The path to approval • No proven superiority compared to leucovorin (in ITT-population). AGENT • Analyses shows that a suboptimal dosing regimen was used. Phase 3 • Dose-response relationship established (ex. patient-derived tumoroids). • Primary endpoint in phase 1b is to define a safe (higher) dos
Slide 30: The clinical phase 1b/2-study
The clinical phase 1b/2-study Optimized dose Treatment-naïve Arfolitixorin in and administration patients with combination with based on metastatic 5-FU based previously colorectal cancer. chemoterapy. generated data. 30
Slide 31: Study design
Study design Phase 1b: Phase 2: Dose escalation Dose optimization Five dose levels Maximum tolererated dose (MTD) up to 500 mg/m2 (~20 patients) Intravenous short infusion One dose level below MTD (up to 20 patients) (~20 patients) 31
Slide 32: 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 33: Next step (March 2024)
Next step (March 2024) Decision on study Additional results sites and principal from preclinical investigator studies Interactions with Clinical trial regulatory application (CTA) authorities 33
Slide 34: Next step (November 2024)
Next step (November 2024) Clinical trial Clinical trial application (CTA) to application (CTA) BfArM approved Interactions with Study initiation at regulatory trial center and authorities recruitment of first patient(s) 34
Slide 35: Overall timetable
Overall 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 recruit results results ment 35
Slide 36: Strategic development collaboration
Strategic development collaboration Prof. Dr. med. Sebastian Stintzing Head of the Department of Hematology, Oncology and Cancer Immunology (CCM) 36
Slide 37: Slide 37
Slide 38: The market potential for arfolitixorin
The market potential for arfolitixorin Petter Segelman Lindqvist, CEO Dr Roger Tell, Chief Medical Officer
Slide 39: The basis of our value creation
The basis of our value creation Arfolitixorin has The unmet the potential to High market medical need is significantly potential high improve patient outcomes 39
Slide 40: 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 40
Slide 41: 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 Patient- groups: First Line treatments: 2L Adressable patient groups for arfolitixorin 3L 41
Slide 42: 5-FU combined with folate will remain the mainstay of treatment
5-FU combined with folate will remain the mainstay of treatment “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 within
Slide 43: Favorable competitive landscape
Favorable competitive landscape 5-FU-based 5-FU+folate-based treatment remain chemotherapy is expected to remain the mainstay of treatment One of few Arfolitixorin innovations Potential to replace leucovorin and significantly enhance the efficacy of 5-FU therapy 43
Slide 44: The U.S. market alone indicates high commercial potential
The U.S. market alone indicates high commercial potential for arfolitixorin Blockbuster potential: ~1 billion USD* * Gross revenue in the U.S. The estimate is based on market research and analysis conducted by Back Bay Life Science Advisors in October 2024 44
Slide 45: Large patient population and favourable pricing generates blockbuster potential
Large patient population and favourable pricing generates blockbuster potential Total US Population Price: Significant premium Incidence of CRC Market penetration Annual mCRC patient population Adressable … Patients with unresectable mCRC, eligible to population: No of treatment cycles receive 5-FU
Slide 46: Additional markets and indications could be added
Additional markets and indications could be added All relevant markets ex-U.S. • Japan, Canada, Europe • Additional regions Potential indication extensions in colorectal cancer • Adjuvant / neoadjuvant treatment Potential additional indications in other forms of cancer / solid tumors • For example p
Slide 47: The basis of our value creation
The basis of our value creation Arfolitixorin has The unmet the potential to High market medical need is significantly potential high improve patient outcomes 47
Slide 48: We are convinced that arfolitixorin has the potential to revolutionize treatment
We are convinced that arfolitixorin has the potential to revolutionize the treatment of colorectal cancer. 48
Isofol Medical — Investor Presentation (November 2024) on 6ix