Novel CML Treatment Scemblix Listed on PBS for Adult Patients

Chronic myeloid leukemia (CML) is a type of cancer that affects the blood and bone marrow, resulting in the overproduction of white blood (granulocytes), which can impede normal blood cell production and the body's ability to fight infections.2 It is estimated that each year in Australia, around 330 people will be diagnosed with CML, accounting for around 0.03% of all cancers diagnosed in the country.2

About Novartis Commitment to CML

Novartis has a long-standing scientific commitment to patients living with CML. For more than 20 years, our bold science has helped transform CML into a chronic disease for many patients. Despite these advancements, ^we're not standing still. We continue to research ways to target the disease, seeking to address the challenges with treatment resistance and/or intolerance that many patients face. Novartis also continues to reimagine CML care through its commitment to sustainable access for patients and collaboration with the global CML community.

About Scemblix^® (asciminib)

Scemblix is the first CML treatment that acts as a STAMP inhibitor, specifically targeting the ABL myristoyl pocket.4,5 This novel mechanism of action may help address resistance in patients with CML previously treated with two or

more TKIs and overcome mutations at the defective BCR:ABL¹ gene, which is associated with the over-production of leukaemic cells.4,5,12-18 While many patients will benefit from available TKI therapies, a significant proportion may experience intolerance or resistance to these treatments.6-11 It is estimated that over 25% of CML patients will switch TKIs at least once during their lifetime due to TKI intolerance or resistance.27 Scemblix represents an important development for patients who experience resistance and/or intolerance to currently available TKI therapies, and it is being studied across multiple treatment lines for CML-CP, both as a monotherapy and in combination.4,12-26 Specifically, the ASC4FIRST Phase III study (NCT04971226) evaluates Scemblix in newly diagnosed adult patients with Ph+ CML-CP vs. an investigator-selected TKI.20 In October 2021, the USFDA granted accelerated approval of Scemblix for adult patients with Ph+ CML-CP, previously treated with two or more TKIs based on MMR rate at 24 weeks, and full approval for adult patients with Ph+ CML-CP with the T315I mutation. In accordance with the Accelerated Approval Program, continued approval for the first indication may be contingent upon verification and description of clinical benefit from confirmatory evidence. The longer-term, 96- week efficacy and safety data have been shared with the FDA and are currently under evaluation through a priority review. Scemblix has received approval in several countries outside the US, including Japan, Switzerland, and the United Kingdom, for adult patients with Ph+ CML-CP with resistance or intolerance to at least two or more previous therapies.28

About Novartis

Novartis is improving the lives of more than 2.8 million patients across Australia and New Zealand through our medicines. By partnering with the healthcare system, we are working for patients to address their needs, and we are committed to accelerating patient access to life saving treatments and associated healthcare. We are reimagining medicine by using innovative science and technology to address challenging healthcare issues and our rich research pipeline has 200+ projects in development. We are transforming how clinical trials are run to increase patients' access to our industry-leading clinical trials footprint in Australia. We continue to work on improving our environment for diversity, equity and inclusion and being a family friendly employer. Every day our inspired, curious, unbossed, and integrity-driven culture unites our people and encourages leadership at every level.

References

1. 1. Scemblix https://www.guildlink.com.au/gc/ws/nv/cmi.cfm?product=nvcsceor10722
   2. Leukaemia Foundation. (n.d.). Chronic myeloid leukaemia. Leukaemia Foundation.https://www.leukaemia.org.au/blood-cancer/leukaemia/chronic-myeloid-leukaemia/
   3. Leukaemia Foundation. (2020). State of the nation: Blood cancer in Australia. https://www.leukaemia.org.au/wp-content/uploads/2020/06/State-of-the-Nation-Blood-Cancer-in- Australia_Leukaemia-Foundation.pdf
   4. Scemblix Summary of Product Characteristics, 2022.
   5. Rea D, et al. A Phase 3, Open-Label, Randomized Study of Asciminib, a STAMP Inhibitor, vs Bosutinib in CML After≥ 2 Prior TKIs. Blood. 2021. DOI: 10.1182/blood.2020009984. PMID: 34407542.
   6. Flis S, et al. Chronic myelogenous leukemia, a still unsolved problem: pitfalls and new therapeutic possibilities. Drug Des Devel Ther. 2019;13:825-843.
   7. Akard LP, et al. The "Hit Hard and Hit Early" Approach to the Treatment of Chronic Myeloid Leukemia: Implications of the Updated National Comprehensive Cancer Network Clinical Practice Guidelines for Routine Practice. Clin Adv Hematol Oncol. 2013;11(7):421-432.
   8. Cortes JE, et al. Long-term bosutinib for chronic phase chronic myeloid leukemia after failure of imatinib plus dasatinib and/or nilotinib. Am J Hematol. 2016;91(12):1206-1214.
   9. Cortes JE, et al. Ponatinib efficacy and safety in Philadelphia chromosome–positive leukemia: Final 5-year results of the phase 2 PACE trial. Blood. 2018;132(4):393-404.
   10. Garg RJ, et al. The use of nilotinib or dasatinib after failure to 2 prior tyrosine kinase inhibitors: long-term follow-up. Blood. 2009;114(20):4361-4368
   11. Steegmann JL., et al. European LeukemiaNet recommendations for the management and avoidance of adverse events of treatment in chronic myeloid leukaemia. Leukemia. 2016;30:1648-1671.
   12. Wylie AA, et al. The allosteric inhibitor ABL001 enables dual targeting of BCR–ABL1. Nature. 2017;543(7647):733-737.
   13. Schoepfer J, et al. Discovery of Asciminib (ABL001), an Allosteric Inhibitor of the Tyrosine Kinase Activity of BCR-ABL1. J Med Chem. 2018;61(18):8120-8135.
   14. Hughes TP, et al. Asciminib in Chronic Myeloid Leukemia after ABL Kinase Inhibitor Failure. N Engl J Med. 2019; 381(24):2315-2326.
   15. Hughes TP, et al. Expanded Phase 1 Study of ABL001, a Potent, Allosteric Inhibitor of BCR-ABL, Reveals Significant and DurableResponses in Patients with CML-Chronic Phase with Failure of Prior TKI Therapy. Poster presented at: ASH Annual Meeting & Exposition; Dec. 5, 2016.
   16. Ottmann OG, et al. ABL001, a Potent, Allosteric Inhibitor of BCR-ABL, Exhibits Safety and Promising Single- Agent Activity in a Phase I Study of Patients with CML with Failure of Prior TKI Therapy. Blood. 2015;126(23):138.
   17. Mauro MJ, et al. Combination of Asciminib Plus Nilotinib (NIL) or Dasatinib (DAS) in Patients (PTS) with Chronic Myeloid Leukemia(CML): Results from a Phase 1 Study. Poster presented at: EHA Annual Meeting; June 15, 2019.
   18. Cortes JE, et al. Combination Therapy Using Asciminib Plus Imatinib (IMA) in Patients (PTS) with Chronic Myeloid Leukemia (CML):Results from a Phase 1 Study. Poster presented at: EHA Annual Meeting; June 15, 2019.
   19. ClinicalTrials.gov. 2017. Study of Efficacy of CML-CP Patients Treated with ABL001 Versus Bosutinib, Previously Treated With 2 or More TKIs. [online] Available at: https://clinicaltrials.gov/ct2/show/NCT03106779.
   20. ClinicalTrials.gov. 2021. A Study of Oral Asciminib Versus Other TKIs in Adult Patients With Newly Diagnosed Ph+ CML-CP. [online] Available at: https://clinicaltrials.gov/ct2/show/NCT04971226.
   21. ClinicalTrials.gov. 2014. A Phase I Study of Oral ABL001 in Patients With CML or Ph+ ALL. [online] Available at: https://clinicaltrials.gov/ct2/show/NCT02081378.
   22. ClinicalTrials.gov. 2018. Study of Efficacy And Safety Of Asciminib In Combination With Imatinib In Patients With Chronic Myeloid Leukemia In Chronic Phase (CML-CP). [online] Available at: https://clinicaltrials.gov/ct2/show/NCT03578367.
   23. ClinicalTrials.gov. 2021. Study of Efficacy and Safety of CML-CP Patients Treated With Asciminib Versus Best Available Therapy,Previously Treated With 2 or More Tyrosine Kinase Inhibitors. [online] Available at: https://clinicaltrials.gov/ct2/show/NCT04795427.
   24. ClinicalTrials.gov. 2021 Asciminib Treatment Optimization in ≥ 3rd Line CML-CP. [online] Available at: https://clinicaltrials.gov/ct2/show/NCT04948333
   25. ClinicalTrials.gov. 2021. Study to Determine the Dose and Safety of Asciminib in Pediatric Patients With Chronic Myeloid Leukemia [online] Available at: https://clinicaltrials.gov/ct2/show/NCT04925479
   26. ClinicalTrials.gov. 2020. Asciminib in Monotherapy for Chronic Myeloid Leukemia in Chronic Phase (CML- CP) With and WithoutT315I Mutation (AIM4CML). [online] Available at: https://clinicaltrials.gov/ct2/show/NCT04666259
   27. Steegmann JL, Baccarani M, Breccia M, et al. European LeukemiaNet recommendations for the management and avoidance of adverse events of treatment in chronic myeloid leukaemia. Leukemia. 2016
   28. Novartis. (2022, January 20). Novartis' Scemblix, a novel mechanism of action, approved by European Commission for adult patients with chronic myeloid leukemia [Press release]. https://www.novartis.com/news/media-releases/novartis-scemblix-novel-mechanism-action-approved- european-commission-adult-patients-chronic-myeloid-leukemia