Slide 1: Medivir Q3 Report 2023 & Fostrox Development Update
MEDIVIR Q3 REPORT 2023 & FOSTROX DEVELOPMENT UPDATE
Slide 2: Important notice
Important notice You must read the following before continuing. The following applies to this document and the information provided in this presentation by Medivir AB (publ) (the “Company”) or any person on behalf of the Company and any other material distributed or statements made in connection wit
Slide 3: Today's presenters
Today’s presenters Jens Lindberg Dr. Pia Baumann Magnus Christensen CEO CMO CFO Dr. Jeff Evans ▪ Professor of Translational Cancer Research, University of Glasgow. ▪ Lead of the Glasgow Experimental Cancer Medicine Centre (ECMC) and National Clinical Lead of the NHS Scotland Cancer Research Network.
Slide 4: Financial summary Q3, 2023
Financial summary Q3, 2023 Consolidated Income Statement, summary Q3 Q1 - Q3 Full year (SEK m) 2023 2022 2023 2022 2022 Net turnover 0.8 1.1 3.2 2.1 4.4 Other operating income 0.2 0.8 1.1 1.6 1.8 Total income 1.0 2.0 4.3 3.8 6.2 Other external expenses -18.1 -11.1 -52.4 -53.3 -69.1 Personnel costs -
Slide 5: Broad pipeline with focus on in-house program fostrox
Broad pipeline with focus on in-house program fostrox IN-HOUSE PROGRAM – FOSTROX PROJECT DISEASE AREA PATIENT POPULATION PRE-CLIN PH 1 PH 2 PH 3 NEXT EVENTS Fostrox HCC Monotherapy (Proof-of-Concept) ▪ Fostrox + Lenvima data read-out Fostrox + Lenvima ▪ Fostrox + Lenvima ph 2b initiation Fostrox + K
Slide 6: Fostrox + Lenvima update agenda
Placeholder agenda Fostrox + Lenvima® update Phase 1b/2a data update & comparison with SoC HCC today & tomorrow Fostrox + Lenvima in a future clinical context Fostrox moving forward Target segment & path to get there with speed 6 Slide
Slide 7: Fostrox + Lenvima – Key take-aways from today's update
Fostrox + Lenvima – Key take-aways from today’s update Fostrox + Lenvima shows consistently improved efficacy compared with Lenvima alone Continued development for fostrox + Lenvima in 2nd line HCC with Accelerated Approval intent 2027 2nd line HCC post Tecentriq® + Avastin® lacks approved treatment
Slide 8: Fostrox + Lenvima – HCC background and phase 1b/2a clinical data in 2nd line HCC
Fostrox + Lenvima – HCC background and phase 1b/2a clinical data in 2nd line HCC Slide 8
Slide 9: Advanced HCC is an underserved disease with high need of new treatment options
Advanced hepatocellular carcinoma (HCC) is an underserved disease with high need of new treatment options • HCC is an underserved disease where only surgery and liver transplantation provides hope of long-term survival1,2 • The majority (80%) are diagnosed with advanced HCC with a 5-y survival < 20%
Slide 10: HCC – current preferred treatment algorithm provides opportunity for fostrox
HCC – current preferred treatment algorithm provides opportunity for fostrox HCC Treatment Algorithm Very Early/Early Intermediate Advanced Terminal stage (0/A) stage (B) stage (C) stage (D) 1L systemic therapy 20% Tecentriq + Avastin SoC ▪ IV chemotherapy currently not used in HCC, primarily due to
Slide 11: Fostrox – unique, liver targeted treatment inducing tumor selective cell death
Fostrox – unique, liver targeted treatment inducing tumor selective cell death without impacting vital liver functions Pro-drug tail Active substance - troxacitabine Pro-drug approach enables oral administration and Cytotoxic with high cell achieves >100-fold liver killing selectivity of tumor targe
Slide 12: Fostrox differentiated MoA in HCC; synergistic combination with Lenvima
Fostrox use of differentiated MoA in HCC; provides synergistic combination possibility with Lenvima (TKI) Liver directed, cytotoxic prodrug Angiogenesis inhibitor Fostrox – Rapid conversion in liver to active metabolite Lenvima induces lack of oxygen in tumors leading to increased activity of fostro
Slide 13: Phase 1b/2a study fully recruited with >50% of patients still on treatment
Phase 1b/2a study fully recruited with >50% of patients still on treatment Fostrox + Lenvima phase 1b/2a dose expansion study – 21 patients dosed Fostrox + Lenvima 40 mg • Advanced Treatment until inoperable Fostrox + Lenvima Progressive Disease Fostrox + Lenvima HCC RP2D – 30 mg1 (PD) 30 mg (n=3) (
Slide 14: Majority of patients followed for ≥12 weeks, enabling robust evaluation in 2L HCC
Majority of patients followed for ≥12 weeks (18 of 21), enabling a robust evaluation in 2L HCC Phase 1b/2a – focus of today’s data presentation Key patient characteristics (18 patients) ▪ 15 sites in Spain, the UK, South Korea ▪ 100% progressed (tumor growth) on prior treatment ▪ Primary Endpoint: S
Slide 15: Improved clinical benefit across key efficacy endpoints in latest interim update
Improved clinical benefit across key efficacy endpoints in latest interim update of fostrox + Lenvima Investigator review1 (RECIST 1.1) Fostrox + Lenvima (n=18) Overall response rate (ORR) 22% • Study ongoing, data continues to mature as >50% of patients still on treatment Disease Control Rate (DCR)
Slide 16: 22% Overall Response Rate; more than two third of patients with tumor reduction
22% Overall Response Rate (ORR); more than two third of patients with tumor reduction* (Investigator review RECIST 1.1) Best % change from baseline in target lesion size (n=18) Fostrox + Lenvima n=18 40% ORR 22% 30% Best Percentage Change from Partial Response, PR 22% 20% 16% Stable disease, SD 56%
Slide 17: Early & durable anti-tumor activity with longest patient on treatment 14 months
Early & durable anti-tumor activity with longest running patient still on treatment after 14 months* (Investigator review RECIST 1.1) 40% Change in total target lesion tumor size since baseline 30% Progressive 20% Disease Change since baseline 10% 0% -10% -20% Partial -30% Response -40% Slide 17 *Pr
Slide 18: Good safety & tolerability profile with fostrox + Lenvima
Good safety & tolerability profile with fostrox + Lenvima* and lower than expected dose modifications Discontinuation and dose modifications Encouraging safety with Fostrox + Lenvima ▪ No unexpected new safety events Only 10% of patients discontinue due to fostrox adverse events ▪ Adverse events tra
Slide 19: Independent review of phase 1b cohorts shows 50% ORR with 1 complete response
Independent review of phase 1b dose escalation cohorts shows 50% ORR with 1 complete response (CR) Phase 1b fostrox + Lenvima dose escalation cohorts1; Independent Review – mRECIST ▪ 1 of 6 patients achieved Complete Response (CR), no signs of viable tumor ▪ Achieving complete tumor response is rare
Slide 20: First prospective study to evaluate Lenvima in 2nd line HCC
The first, prospective study to evaluate clinical efficacy & safety of Lenvima in 2nd line HCC Non-randomised, open-label, multi-center study evaluating Lenvima in 1st & 2nd line HCC patients1 Patients with advanced HCC suitable for Lenvima Primary Endpoint: • 1st line or 2nd line post Tecentriq + A
Slide 21: Indirect comparison; similar patient characteristics in both studies
Indirect comparison; similar patient characteristics in fostrox + Lenvima study & Lenvima study in 2nd line HCC Key patient characteristics Fostrox + Lenvima2 Lenvima1 (n=18) (n=12) 2nd line/3rd line patients* 83% / 17% 100% / 0% ECOG status (0/1) 67% / 33% 92% / 8% Extrahepatic metastases ≥56% 42%
Slide 22: Indirect comparison; comparable tolerability, no new safety events
Indirect comparison; Fostrox + Lenvima study with comparable tolerability, no new safety events vs Lenvima study Safety & tolerability Fostrox + Lenvima2 Lenvima1 (n=18) (n=12) ≥ Grade 3 AEs 61% 67% Dose modifications Lenvima 50% 92% Discontinuations due to AEs 17% 25% 1Kobayashi et al., Clinical Ca
Slide 23: Fostrox + Lenvima shows consistently improved clinical benefit versus Lenvima alone
Fostrox + Lenvima study shows consistently improved clinical benefit compared with Lenvima study alone Indirect comparison – Independent review (mRECIST) Fostrox + Lenvima2 (n=6) Lenvima1 (n=12) CR 17% 0% ORR 50% 17% DCR (at 6 weeks) 83% 75% Indirect comparison – Investigator Review (RECIST 1.1) Fos
Slide 24: Indirect comparison of PFS/TTP reinforces improved clinical benefit
Indirect comparison of Progression free survival (PFS)/Time to progression (TTP) reinforces improved clinical benefit Median PFS/TTP* Median PFS/TTP* Median Treatment Duration Lenvima (PFS) Fostrox + Lenvima (TTP) Lenvima (PFS) Fostrox + Lenvima (TTP) Lenvima Fostrox + Lenvima 5.1 4.7 4.9 months3 mo
Slide 25: HCC treatment today & tomorrow; Fostrox + Lenvima in a future clinical context
HCC treatment today & tomorrow; Fostrox + Lenvima in a future clinical context Dr. Jeff Evans Slide 25
Slide 26: Epidemiology of Hepatocellular Carcinoma
Epidemiology of Hepatocellular Carcinoma Hepatology, Volume: 73, Issue: S1, Pages: 4-13, First published: 22 April 2020, DOI: (10.1002/hep.31288) Slide 26
Slide 27: Where we have come from (before 2008)
Where we have come from (before 2008) HCC Early Stage Intermediate Stage Advanced Stage End Stage Surgical treatments TACE New Agents Local ablation (30%) (50-60%) (10%) Potentially Curative Treatments Randomized trials BSC 5-yr survival: 50-70% Median survival if untreated: 6-16 mo Survival< 3 mo S
Slide 28: BCLC staging and treatment strategy in 2022
BCLC staging and treatment strategy in 2022 28
Slide 29: Systemic Therapy uHCC
Systemic Therapy uHCC First Atezoliumab + Durvalumab +/- Sorafenib Lenvatinib Line Bevacizumab Tremelimumab Second Sorafenib Sorafenib Cabozantinib Ipi + Line Lenvatinib Cabozantinib Nivo Ramucirumab Cabozantinib Ramucirumab Regorafenib Regorafenib Regorafenib 29 Durvalumab, durvalumab+tremelumaband
Slide 30: High unmet need remains in 2nd line HCC
While significant advances have been made in the 1st line HCC, high unmet need remains in 2nd line No approved systemic 2nd line treatment options post 1st Treatment guidelines* highlights significant unmet line standard of care (SoC) medical need in 2nd line advanced HCC ▪ 1st line SoC in HCC: immu
Slide 31: Fostrox + Lenvima: novel combination aligned with current and future 2nd line HCC SoC
Fostrox + Lenvima: novel combination in development aligned with current and future 2nd line HCC SoC Treatment algorithm in advanced HCC Ongoing studies in 2nd line HCC post Tecentriq + Avastin 1st line Fostrox + TKI IO Tecentriq (anti-PDL1) + Avastin (VEGFi/TKI) Lenvima monotherapy combinations 2nd
Slide 32: Synergy in mechanism of action – how fostrox could provide further benefit
Standard of care treatment - synergy in mechanism of action – how could fostrox provide further benefit Inhibiting growth factor signaling Blocking negative immune-checkpoints Inducing DNA-damage and cell death • Current systemic therapy in advanced HCC uses multikinase inhibitors (MKIs), or combine
Slide 33: Cancer in the liver is different; controlling the primary tumor is critical
Cancer in the liver is different; controlling the primary tumor in the liver is critical in HCC of HCC patients has an underlying cirrhosis in Up to 80% the liver, negatively impacting ability to tolerate anti-tumor treatments1,2 Progression in HCC is unique as it primarily occurs locally in the liv
Slide 34: TACE; a frequently used alternative provides diminishing returns
TACE (local chemoembolization); a frequently used alternative to reduce primary tumor burden in HCC provides diminishing returns ▪ TACE is the general standard of care for patients with intermediate-stage HCC (i.e. BCLC stage B)1 ▪ However, despite consensus between international guidelines on when
Slide 35: Potential of Systemic Anti-Cancer Agents across the HCC landscape
Potential of Systemic Anti-Cancer Agents (SACT) across the HCC landscape Eligible for local Not eligible for surgery Eligible for surgery1 interventions, not or local interventions1 surgery1 Liver transplant TACE 1L: SACT Tumor RFA resection 2L: SACT PEI Systemic Anti-Cancer Agents have potential as
Slide 36: Pivotal phase 2b with Accelerated Approval intent is the next step
Pivotal phase 2b with Accelerated Approval intent is the next approriate step Slide 36
Slide 37: Pivotal phase 2b; randomized design with PFS as primary endpoint
Pivotal phase 2b; randomized design with PFS as primary endpoint to enable accelerated approval 2027 Phase 2b: randomized, double-blind study design with Master Protocol for phase 2b & confirmatory phase 3 Key factors supporting accelerated approval process Primary Endpoint: Fostrox 30 mg + • PFS Le
Slide 38: Fostrox – Major commercial opportunity with no approved treatments
Fostrox – Major commercial opportunity in a patient population with no approved treatments Slide 38
Slide 39: First-to-market opportunity in 2nd line HCC market worth $2.4bn annually by 2028
First-to-market opportunity for fostrox in 2nd line HCC market worth $2.4bn annually by 2028 Significant market growth* driven primarily by As medical treatments improve, NASH/NAFLD induced HCC 2nd line treatment duration will increase significantly* 4 000 US Europe 5 Japan China RoW 2L treated ▪ US
Slide 40: Summary
Summary Slide 40
Slide 41: Fostrox + Lenvima – Potential to transform 2nd line HCC
Fostrox + Lenvima – Potential to transform 2nd line HCC Fostrox + Lenvima shows consistently improved efficacy compared with Lenvima alone Continued development for fostrox + Lenvima in 2nd line HCC with Accelerated Approval intent 2027 2nd line HCC post Tecentriq® + Avastin® lacks approved treatmen
Slide 42: Q/A
Q/A Slide 42
Slide 43: Fostrox + Lenvima – Potential to transform 2nd line HCC
Fostrox + Lenvima – Potential to transform 2nd line HCC Fostrox + Lenvima shows consistently improved efficacy compared with Lenvima alone Continued development for fostrox + Lenvima in 2nd line HCC with Accelerated Approval intent 2027 2nd line HCC post Tecentriq® + Avastin® lacks approved treatmen
Slide 44: Thank You!
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