May 10, 2016 Q1 2016 Thank Financial you Results & Business Update
Q1 2016 Financial Results Prepared Remarks Q1 Update Tom Hughes, Ph.D., Chief Executive Officer Clinical Update Dennis Kim, M.D., Chief Medical Officer Financial Results Patty Allen, Chief Financial Officer Question and Answer Session Also available for Q&A Patrick Loustau, President Alicia Secor, Chief Commercial Officer 2
Forward Looking Statements These slides and the accompanying oral presentation contain forward-looking statements and information. The use of words such as may, might, will, should, expect, plan, anticipate, believe, estimate, project, intend, future, potential, or continue, and other similar expressions are intended to identify forward looking statements. For example, all statements we make regarding the initiation, timing, progress and results of our preclinical and clinical studies and our research and development programs, our ability to advance product candidates into, and successfully complete, clinical studies, the timing or likelihood of regulatory filings and approvals, and our expected cash, cash equivalents and marketable securities at year end are forward looking. All forward-looking statements are based on estimates and assumptions by our management that, although we believe to be reasonable, are inherently uncertain. All forward-looking statements are subject to risks and uncertainties that may cause actual results to differ materially from those that we expected. These statements are also subject to a number of material risks and uncertainties that are described in our most recent Annual Report on Form 10-K filed with the Securities and Exchange Commission, as updated by our future filings with the Securities and Exchange Commission, including without limitation, Zafgen s ability to obtain a release of the full clinical hold placed on the beloranib IND. Any forwardlooking statement speaks only as of the date on which it was made. We undertake no obligation to publicly update or revise any forward-looking statement, whether as a result of new information, future events or otherwise, except as required by law. 3 3
Q1 Update Tom Hughes, Ph.D. Chief Executive Officer
Recent Clinical Developments bestpws Phase 3 ZAF-311 Data in PWS Top-line results in January 2016; full data presentation at ENDO 2016 Beloranib achieved co-primary endpoints, with statistically significant and clinically meaningful improvements in hyperphagia-related behaviors and body weight Statistically significant reduction in total body mass and fat mass Improvements in lipids and markers of cardiometabolic risk Phase 2b ZAF-203 Data in Severe Obesity Complicated by Type 2 Diabetes Top-line results in February 2016 Achieved primary and key secondary endpoints Statistically significant and clinically meaningful improvements in body weight and glycemic control 5
Addressing the Beloranib Clinical Hold bestpws ZAF-311 Data ZAF-203 Data in Severe Obesity Complicated by Type 2 Diabetes Clinical and Non-clinical Risk Assessment Risk Mitigation Strategy Demonstrate Efficacy: Impact of Treatment, Clinical Relevance and Robustness of Effects Demonstrate Benefit/Risk from Full Program; Integrated AE Profile Risk Mitigation Proposal to Screen / Monitor / Mitigate Thrombotic Risk Next steps: Advancing toward discussions with the FDA 6
Clinical Update Dennis Kim, M.D. Chief Medical Officer
Positive Efficacy Results for bestpws and ZAF-203 bestpws ZAF-311 Phase 3 Data Prader-Willi Syndrome Achieved both co-primary endpoints, key secondary endpoints Statistically significant and clinically meaningful reduction in hyperphagiarelated behaviors and body weight Improvements in body fat composition, lipids and cardiometabolic risk factors Phase 2b ZAF-203 Data Severe Obesity with Type 2 Diabetes Achieved primary and key secondary endpoints Statistically significant and clinically meaningful improvements in body weight and glycemic control Improvements in body fat composition, lipids and cardiometabolic risk factors 8
bestpws ZAF-311 Pivotal Phase 3 Study Design Randomization Single-Blind Lead-in Blinded Controlled Treatment Primary Endpoint Placebo 2.4 mg Beloranib 1.8 mg Beloranib Placebo Optional Open Label Extension Study 2 0 Week 26 Co-primary endpoints: improvement in hyperphagia-related behaviors and body weight Secondary endpoints: body fat mass, LDL-c, HDL-c, C-reactive protein 107 patients randomized Baseline characteristics well-balanced among the three treatment groups Study population representative of general PWS population Placebo includes placebo low-volume and placebo high-volume. Subjects randomized to 2.4 mg beloranib and all subjects in the OLE received 1.8 mg beloranib for the first 4 weeks of treatment. All doses were administered twice-weekly by subcutaneous injection. 9
L S M e a n ± S E C h a n g e in H Q -C T T o ta l S c o re L S M e a n ± S E C h a n g e in H Q -C T T o ta l S c o re L S M e a n ± S E W e ig h t C h a n g e (% ) bestpws Study Achieves Co-Primary Efficacy Endpoints ITT Population (N=107) Statistically significant reduction in hyperphagia and body weight at both doses 5 5 HQ-CT Total Score 7.5 Body Weight 0-5 -1 0 0 0.4 5.0 * -6.34.2 1.7-5 p = 0.0 0 0 3 0.4-7.0 1.7 2.5 p = 0.0 0 0-6.3 1.7 *** -8.2 1.3 6.7 p = 0.0 0 0 3 p < 0.0 0 0 1 * ** 0.0 7.4-7.0 1.7-9.5 1.3 p = 0.0 0 0 1 p < 0.0 0 0 1-1 0 6.7 *** -2.5 * * 7.4 4.1-5.0-1 5 5.3 0 2 4 6 8 1 0 1 2 1 4 1 6 1 8 2 0 2 2 2 4 2 6 0 2 4 6 8 1 0 1 2 1 4 1 6 1 8 2 0 2 2 2 4 2 6-7.5 W e e 0k 2 4 6 8 1 0 1 2 1 4 1 6 1 8 2 0 2 2 2 4 2 6 W e e k W e e k P la c e b o (N = 3 4 ); B L W t= 1 0 0.9 k g ; B L H Q -C T = 1 5.0 1.8 m g B e lo ra n ib (N = 3 6 ); B L W t = 9 7.5 k g ; B L H Q -C T = 1 7.4 2.4 m g B e lo ra n ib (N = 3 7 ); B L W t= 1 0 5.7 k g ; B L H Q -C T = 1 8.3 *p<0.05, **p<0.01, ***p<0.0001 for change from baseline with beloranib vs. placebo. Analysis is implemented via a mixed model repeated measures (MMRM) model. 10
bestpws: Beloranib Produced Statistically Significant Improvements in Body Composition L S M e a n ± S E C h a n g e in M a s s (k g ) T o ta l B o d y M a s s F a t M a s s L e a n M a s s 5 3.4 2.6 0.7 0 0.5 0.7-5 -1 0 2.9 5.7 2.5 5.0 *p<0.05, **p<0.01, ***p<0.0001 for change from baseline with beloranib vs. placebo P la c e b o (N = 3 4 ) 1.8 m g B e lo ra n ib (N = 3 6 ) 2.4 m g B e lo ra n ib (N = 3 7 ) Baseline Total Mass (kg) Fat Mass (kg) Lean Mass (kg) Placebo 96.3 51.5 43.2 1.8 mg beloranib 91.5 47.6 42.2 2.4 mg beloranib 98.5 53.2 43.6 11
L S M e a n ± S E C h a n g e in bestpws: Beloranib Associated with Improvements in Markers of Cardiometabolic Risk L D L -C (m g /d L ) L S G e o m e tric M e a n ± S E C h a n g e in C R P (% ) L S M e a n ± S E C h a n g e in T o ta l C h o le s te r o l (m g /d L ) 1 0 LDL-Cholesterol 1 0 Total Cholesterol 0 1.8 0 1.3-1 0-2 0-3 0 0 2 4 6 8 1 0 1 2 1 4 1 6 1 8 2 0 2 2 2 4 2 6 W e e k 1.8 m g B e lo ra n ib (N = 3 6 ); B L = 9 4.9 m g /d L 2.4 m g B e lo ra n ib (N = 3 7 ); B L = 1 1 1.0 m g /d L * * P la c e b o (N = 3 4 ); B L = 9 6.9 m g /d L * * 2 0-1 8.4 4.3 * * -1 9.6 4.6 1 6.6 1 7.8 2.5 hs-crp -1 0-2 0-3 0 0 2 4 6 8 1 0 1 2 1 4 1 6 1 8 2 0 2 2 2 4 2 6 P la c e b o (N = 3 4 ); B L = 1 7 0.0 m g /d L W e e k 1.8 m g B e lo ra n ib (N = 3 6 ); B L = 1 6 6.3 m g /d L 2.4 m g B e lo ra n ib (N = 3 7 ); B L = 1 8 6.8 m g /d L * * * * * * * * * * -1 9.3 5.5 * * -1 8.5 5.4 1 7.2 1 8.0 0-2 0-4 0 *p<0.05, **p<0.01, ***p<0.0001 for change from baseline with beloranib vs. placebo -6 0-8 0-5 6.0 5 3.3 *** *** P la c e b o (N = 3 4 ); B L G e o m e tric M e a n 8.4 g /m L 1.8 m g B e lo ra n ib (N = 3 6 ); B L G e o m e tric M e a n 6.9 g /m L 2.4 m g B e lo ra n ib (N = 3 7 ); B L G e o m e tric M e a n 7.5 g /m L 12
Overview of Adverse Events (AE) and Serious Adverse Events (SAE) Related to Thrombosis Beloranib IND was placed on a full clinical hold by the FDA on December 2, 2015. Across nine clinical trials evaluating >500 patients, 11 patients had thrombotic events, of which five patients had SAEs. Thrombotic events to date seen only in patients randomized to beloranib. Study Dose Event Causality per Investigator ZAF-201 (completed) ZAF-203 (completed) ZAF-311 (completed) 1.2mg 2.4mg 2.4mg 2.4mg SAE of pulmonary embolism (PE); thrombophlebitis SAE of PE; Deep vein thrombosis (DVT) Moderate AE of thrombophlebitis superficial Mild AE of thrombophlebitis superficial Not related Not related Not related Not related 13 Additional Info Factor V Leiden mutation Gout attack and extended immobilization Varicose veins; Implanted contraceptive Implanted contraceptive 1.2mg SAE of PE Not related Implanted contraceptive; heart failure; systemic pulmonary inflammatory disease 1.8mg Moderate AE of DVT Related Discovered during VTE screening, 4 weeks after last dose of study drug. Two 8-hour flights occurring 3-4 weeks prior to VTE screening. 1.2mg 1.8mg Moderate AE of thrombophlebitis superficial Moderate AE of thrombophlebitis superficial; DVT Related Possibly related Discovered during VTE screening, 19 weeks after last dose of study drug. Ongoing medical history of bilateral superficial venous insufficiency Extended (6 hour) car ride 2.4mg Moderate AE of DVT Possibly related Androgel 1% transdermal patch 1.8mg 2.4mg SAE of PE; death; DVT confirmed upon autopsy SAE of PE; death; thrombophlebitis superficial Possibly related Probably related BMI 55 with multiple co-morbidities Ongoing thrombophlebitis superficial (prior history); treated with ASA 13
1Q16 Financial Results Patty Allen Chief Financial Officer
1Q 2016 Selected Financial Summary Balance Sheets As of March 31, 2016 As of March 31, 2015 As of December 31, 2015 Cash, Cash Equivalents and Marketable Securities $ 166.2M $ 234.2M $ 185.1M Total Assets $170.0M $ 236.7M $ 189.1M Statements of Operations Research & Development Expenses General & Administrative Expenses Quarter Ended March 31, 2016 Quarter Ended March 31, 2015 Quarter Ended December 31, 2015 $ 12.5M $ 10.2M $ 17.7M $ 5.4M $ 3.0M $ 5.5M Net Loss ($ 17.7)M ($ 13.5)M ($ 23.2)M Net Loss per Share ($0.65) ($0.53) ($0.85) Expect to end 2016 with greater than $100 million in cash Strong position to drive our programs forward Plan to provide more specific guidance following potential resolution of full clinical hold 15
Closing Remarks Tom Hughes, Ph.D. Chief Executive Officer
Q&A
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