Products and
Pipeline

Overview^1-2

- Ixazomib is an oral proteasome inhibitor that can be administered weekly at a fixed dose

- The ixazomib clinical development program, called the TOURMALINE program, is investigating ixazomib as a potential treatment option across the myeloma treatment paradigm, as treatment in the relapsed/refractory setting, and as post-ASCT and post-induction maintenance

MOA^2-7

- Ixazomib inhibits the β5 site of the proteasome core

- Proteasome inhibition has direct effects on both malignant plasma cells and the MM cell microenvironment through:

• Inhibition of cytokine secretion
• Suppression of adhesion molecule expression
• Inhibition of angiogenesis
• Apoptotic pathways

- Studies have shown that malignant cells, including multiple myeloma cells, appear to be susceptible to proteasome inhibition

- Ixazomib has been shown to inhibit growth and induce apoptosis in cancer cells

- Preclinical studies of ixazomib have shown antitumor effects in multiple myeloma, including activity in mouse xenograft models and synergy with other myeloma therapies. Ixazomib has effects on the bone marrow microenvironment, including promotion of osteoblastogenesis

Clinical Trials

The following are currently ongoing Takeda sponsored trials.

Study Name

A National, Prospective, Non-interventional Study of NINLARO in Real World Clinical Practice

Study Name

An Open-Label, Single-Arm, Multicenter Study to Evaluate the Effectiveness and Safety of Ixazomib (NINLARO^®) in Combination With Lenalidomide and Dexamethasone (IRD) in Patients With Multiple Myeloma Previously Receiving a Bortezomib-Based Induction Regimen (US MM-6)

Study Name

An Open-label, Single-Arm, Multicenter Study to Evaluate the Efficacy and Safety of Ixazomib in Combination With Lenalidomide and Dexamethasone in Patients With Relapsed and/or Refractory Multiple Myeloma Initially Treated With an Injection of Proteasome Inhibitor-Based Therapy

Study Name

A Phase 3, Randomized, Placebo-Controlled, Double-Blind Study of Oral Ixazomib Maintenance Therapy After Initial Therapy in Patients With Newly Diagnosed Multiple Myeloma Not Treated With Stem Cell Transplantation

References

1. Gupta N, et al. Br J Clin Pharmacol. 2015;79:789-800.

2. NINLARO (ixazomib) US Prescribing Information.

3. Hideshima T, et al. Mol Cancer Ther. 2011;11/1;10(11): 2034-2042.

4. Kupperman E, et al. Cancer Res. 2010;70:1970-1080.

5. Chauhan D, et al. Clin Cancer Res. 2011;17:5311-5321.

6. Duncan K, et al. Blood Cancer J. 2013;35:e165.

7. Garcia-Gomez A, et al. Clin Cancer Res. 2014;20:1542-1554.

Disclaimers

Efficacy and safety of these products, for the uses identified within, are currently under investigation. Regulatory approval of any of these products or uses is dependent on the completion of the study programs and review by regulatory authorities. The clinical trial information is available at www.clinicaltrials.gov *Marketed products have received approval in one or more jurisdictions.