Multiple Myeloma Research Foundation MMRF News and Updates PMMNG Meeting March 11, 2017 Mary DeRome Multiple Myeloma Research Foundation

Progress for Myeloma Patients 10 40 3 % × DRUGS IMPROVEMENT 5 IN -YEAR LIFE SPAN IN THE LAST DECADE SURVIVAL FOR PATIENTS

MMRF/MMRC Founded in 1998 Funds worldwide research Builds myeloma community Partners with MMRC Founded in 2004 Supports 25 institutions Conducts tissue banking Facilitates phase I/II trials

MMRF Precision Medicine Model

Data Analysis: MMRF Researcher Gateway CoMMpass℠ data is available through our open-access platform—the MMRF Researcher Gateway—to drive discoveries. Integrates clinical, laboratory, genomic data; advanced visualization, analytics Enables population stratification, biomarker and target discovery Enables researchers to connect, and share analyses, results, insights Incorporates existing data sets; definitive MM research resource

Testing Hypotheses A new model, the Translational Network of Excellence, was established to accelerate findings from preclinical research to the clinic. Network priorities: New targets/drugs validation Immune efforts MM-related malignancies Minimal Residual Disease (MRD)

Moving to the Clinic: MMRC By integrating 25 leading centers, the MMRC has performed over 73 trials with more than 35 agents.

MMRF CoMMpass STUDY AS CORNERSTONE Longitudinal Clinical Data and Molecular Profiling COMPLETED ENROLLMENT: 1,200+ newly diagnosed patients DURATION: ~10 years SITES: 75 Community and Academic Cancer Centers INDUSTRY PARTNERS: Takeda, Amgen, Janssen, BMS Centralized Molecular Tests Flow cytometry & BRAF mutations RNA sequencing expression analysis Whole exome DNA sequencing Whole genome chromosome analysis Cytospin slides for FISH Biorespository of PBMNC, plasma Tumor

PATIENT questions we’ve been able to answer Should I do a transplant?

PATIENT questions we’ve been able to answer Should I be on 3 drugs?

PATIENT questions we’ve been able to answer I have del17p. Am I high risk?

PATIENT QUESTIONS WE MUST ANSWER What treatment (combination) should I start on? should I stay on? Can we prevent this disease?

No Two Patients Are The Same Integrative analyses using CoMMpass data will help identify patients at greater risk of progression and optimize their treatment

Additional Data for Relapsed Patients The MMRF continues to build the data bank with clinical- grade sequencing of 500 relapsed patients. CD138 Enrichment/ library prep Exome capture processing Sequencing HiSeq rapid mode Report generation and review Sample receipt Sequence analysis Day 0 Days 1–3 Day 4 Days 5–6 Days 6–8 Day 9 ONCOSEQ 1700

“Actionable” Alterations in MM MMRF PM efforts have identified molecular alterations for which there are drugs in the clinic KRAS and NRAS (40%) BRAF (8%) CDKN2C and CCND1 (18%) PI3K-AKT (5%) FGFR3 IGF1R and ALK IDH1/2 MyD88 (3%) Others (11%)

Beyond Single Hypothesis Testing: Master Protocols Functional High Risk Patients RAF/RAS mutations t(11;14) IPD Profiling for alterations (NCT02884102) No detectable “actionable” alterations IPD +Immune checkpoint MAPKi + IPD IDH activating mutations IDHi CCND1 activating alteration CDKi PI3K/AKT activating alterations AKTi BCLi+ IPD BCLi FGFR3 activating alterations FGFRi

Precision Medicine Trials The MMRC is launching precision medicine trials using the information we have gathered from our MMGI and CoMMpass initiatives MDM2 – 17p deletion B-raf/MEK – mutations in Ras pathway genes FGFR3 – activating mutations in a growth receptor The MMRC has also opened 4 trials to date to test new immune agents such as PDL-1, Elotuzumab, and CD38 Mabs and is collaborating with other institutions on additional immune agent trials

IBRANCE® (palbociclib) Machine Learning -GNS New insights on high risk disease are emerging from analyses with GNS and were presented at last upcoming ASH meeting in Dec. IBRANCE® (palbociclib) dinaciclib AT7519 OTS167