Kura Oncology, Inc. · NASDAQ:KURA
Kura Oncology — Technical Presentation (June 2024)
10 slides from Kura Oncology's technical presentation, Jun 21, 2024
Slide 1: Menin Inhibitor Ziftomenib Induces Insulin Production in a Rat Model of T2DM
TM 845-P The Menin Inhibitor Ziftomenib Induces Insulin Production and Improves Insulin Sensitivity in a Rat Model of Type 2 Diabetes Mellitus (T2DM) Asako McCloskey1, Yahu Liu1, Xingjuan Wang2 and Francis Burrows1 1Kura Oncology, Inc., San Diego, CA 2WuXi AppTec (Hong Kong) Limited June 21, 2024
Slide 2: Disclosures
Disclosures • Asako McCloskey (Presenter), Yahu A. Liu (Co-Author), and Francis Burrows (Co-Author) • Employed by Kura Oncology, Inc.; own stock of Kura Oncology, Inc.; patents and/or patent applications with Kura Oncology, Inc. • Xingjuan Wang (Co-Author) • Employed by WuXi AppTec (Hong Kong) Limit
Slide 3: Background
Background • Menin is a scaffold protein known to regulate epigenetic gene expression in several cell types. Genetic menin loss (MEN1 syndrome) is associated with insulinemia due to upregulated pancreatic β-cell proliferation. • Inhibiting menin could be a viable option to enhance pancreatic functio
Slide 4: Study Design
Study Design ZDF male rats (obese, fa/fa) • Wait for T2DM development Birth (12-13 weeks old) Day 0 Day 6 Day 12 Day 21 Day 27 • Av 4h FBG = 23 mM (414 mg/dL) Start dosing 4h FBG 4h FBG 4h FBG 4h FBG Insulin Insulin Insulin Insulin %HbA1C %HbA1C %HbA1C %HbA1C OGTT c-peptide • Vehicle: QD, PO • Zifto
Slide 5: Reduces Blood Glucose and HbA1C Levels and Improves Insulin Sensitivity
Ziftomenib Reduces Blood Glucose and HbA1C Levels and Improves Insulin Sensitivity Ziftomenib significantly reduced 4h fasting blood glucose (FBG) levels and %HbA1C within 27 days of treatment; FBG level for the zifto group approached the healthy BG threshold. 4h fasting blood glucose HOMA-IR 35 500
Slide 6: Stimulates Insulin Production
Ziftomenib Stimulates Insulin Production Ziftomenib significantly increased serum insulin and c-peptide levels, indicating significant improvement to steady-state β-cell function 4h fasting Insulin c-peptide on Day27 HOMA-B 25 5000 **** ns **** *** 2500 ns c-peptide pmol/L 20 4000 ns insulin (ng/mL)
Slide 7: Improves Postprandial Glucose Control
Ziftomenib Improves Postprandial Glucose Control Ziftomenib significantly reduced blood glucose during the glucose challenge after 27 days of treatment OGTT AUC (OGTT) AUC(0-180min)mmol/L.min 60 8000 Blood Glucose (mmol/L) vehicle 6000 40 * ziftomenib **** 4000 semaglutide ns ns **** 20 **** **** **
Slide 8: Ziftomenib Reduces FBG and Improves Insulin Production in Advanced Disease Model
In Model of More Advanced Disease, Ziftomenib Reduces FBG and Improves Insulin Production with Continued Effects during Wash-out Period Ziftomenib maintained meaningful activity during the wash-out period, suggesting restoration of β-cell mass zifto 0.5x mpk or 1x mpk, QD, for 42 days Wash-out (2 we
Slide 9: Stimulates β-cell Proliferation in Human Pancreatic Islet Microtissues
Ziftomenib Stimulates β-cell Proliferation with Minimal Effects on Non-β-cells in Human Pancreatic Islet Microtissues Ziftomenib stimulated the proliferation of β-cells specifically in both donor samples • Ziftomenib: 1x (nM) or 5x (nM) • Harmine: 10 µM (only used in STD, toxic under GTX) • Prolifer
Slide 10: Conclusions
Conclusions • Ziftomenib induced β-cell proliferation in human islet microtissues. Induction of non- β-cell proliferation was not detectable, indicating menin is a viable therapeutic target for β-cell mass specific expansion. • Ziftomenib treatment showed consistent progressive improvement in both i