Company Presentation June 2016

Transcription

1 Company Presentation June 2016

2 Millendo Therapeutics Highlights Establishing a leading endocrine company Pipeline of first-in-class, disease-modifying, clinical-stage therapeutics for endocrine diseases caused by hormone dysregulation Worldwide rights to all programs Four indications with high unmet medical needs and substantial sales potentials MLE NK3R antagonist in Phase 2 Polycystic ovary syndrome (PCOS) ATR ACAT1 inhibitor in Phase 2 Congenital adrenal hyperplasia (CAH) in Phase 2 Adrenocortical carcinoma (ACC) in Phase 1 Endogenous Cushing s syndrome (CS) preparing for Phase 2 Strong leadership and expertise in endocrine drug development Supported by well-recognized investor base CONFIDENTIAL 2

3 Building a Leading Endocrine Company Rapid build to date with significant data readouts near-term Fast Start Founded in 2012 as Atterocor, Inc. Closed $15M Series A financing Established preclinical proof of concept for ATR-101 Strong founders, advisors and semi-virtual team established Company Building Advancing pipeline of firstin-class, disease-modifying therapeutics In-licensed MLE4901 for PCOS from AstraZeneca $62M Series B financing Initiating three Phase 2 trials & Phase 1 expansion cohort Completing management team and drug development capabilities Key Data Readouts Efficacy data from MLE4901 in PCOS and ATR-101 in all three indications (CAH, CS, ACC) and preparation for pivotal studies Continue to attract product opportunities in the endocrine space Drive to create a fullyintegrated pharmaceutical company focused on endocrine diseases Build company profile and financial position CONFIDENTIAL 3

4 Millendo Clinical Pipeline Four clinical programs in endocrine diseases of hormone dysregulation CONFIDENTIAL 4

5 MLE4901

6 MLE4901 for Polycystic Ovary Syndrome (PCOS) Potential first-in-class, first-in-disease, oral PCOS treatment Market: PCOS, the most common endocrine disease in women, with no approved therapies Potential use in other diseases of GnRH hyperpulsatility Potential >$1B WW peak revenues Data to date: Clear proof of mechanism in Phase 2a study in PCOS patients Well-tolerated in multiple Phase 1 and Phase 2 studies to date (~200 subjects) Next steps: Initiate Phase 2b trial in 2016 CONFIDENTIAL 6

7 Polycystic Ovary Syndrome No approved therapies for the most common endocrine disease in women Affects 5-15% of women Growing awareness and diagnosis $4B in annual healthcare costs (NIH 2012 estimate) Variety of clinical symptoms Including menstrual dysfunction, androgen excess and metabolic syndrome Major cause of infertility issues No approved therapies Current treatments used off-label and directed at managing symptoms, not at resolving disease Driven by underlying endocrine abnormalities Neuroendocrine basis for disease is GnRH hyperpulsatility in the hypothalamus NKB/NK3R signaling contributes significantly to the control of pulsatile GnRH neurosecretion CONFIDENTIAL 7

8 MLE4901 Mechanism of Action NK3R central role in PCOS recently established CONFIDENTIAL 8

9 MLE4901 Phase 2a Study Strong proof of mechanism in PCOS MLE mg QD Screening MLE mg BID MLE mg BID Placebo Follow-up Days -60 to -2 Days 1 to 28 Day 42 ± 3 Double-blind, randomized, placebo-controlled study in women aged years with PCOS as documented by ultrasound scan, with elevated free testosterone (>85% of ULN) and <6 menstrual cycles per year N = 65; n = 14-16/group Primary objective was to determine change from baseline of Luteinizing Hormone (LH) AUC (0-8) at Day 7 in comparison to placebo CONFIDENTIAL 9

10 MLE4901 Phase 2a Data Provide Clear Proof of Mechanism Changes seen in multiple variables: LH, pulse frequency, LH:FSH ratio, T Primary endpoint was achieved Dose dependent reduction; highly statistically significant at top dose Extensive secondary endpoints (plus post-hoc analyses) are consistent with broad effect on disease hr*iu/l LH AUC 0-8 * Evidence for exposure/response relationship for key pharmacodynamic parameters Well-tolerated; no SAEs attributed to study drug Results align with MOA and provide high likelihood of symptomatic improvement Day 7 Geometric LS Mean Placebo 20 mg QD 20 mg BID 40 mg BID Primary Endpoint (all subjects enrolled) * 40 mg bid vs. placebo p< CONFIDENTIAL 10

11 MLE4901: Potential to Uniquely Address Breadth of PCOS Symptoms Versus Available Off-Label Treatments Menstrual dysfunction Excess androgens Metabolic symptoms Fertility MLE Oral contraceptives + + Metformin +/- + Spironolactone (anti-androgen) + Clomifene + CONFIDENTIAL 11

12 ATR-101

13 ATR-101 for Orphan Endocrine Diseases Novel MOA has potential to address multiple serious adrenal diseases Target: Potent, selective inhibitor of ACAT1 targets adrenal excess steroidogenesis and overproliferation Indications: Congenital adrenal hyperplasia (CAH), adrenocortical carcinoma (ACC), endogenous Cushing s syndrome (CS) Data to date: Targeted effects on adrenal cortex and inhibition of adrenal steroid production in animal studies Status: Good safety profile in Phase 1 patients at exposures consistent with preclinical efficacy Ongoing Phase 2 trial in CAH and Phase 1 trial in ACC patients Next steps: Initiate Phase 2 study in CS Initiate expansion cohort of Phase 1 ACC study CONFIDENTIAL 13

14 Orphan Adrenal Diseases Serious conditions with limited to no treatment options ATR-101: ACAT1 inhibitor Highly selective effects on the adrenals Inhibition of adrenal steroid production at low doses Induces apoptosis at much higher doses Congenital Adrenal Hyperplasia (CAH) Medical need: Cortisol deficiency requires life-long treatment; leads to testicular tumor and hyperandrogenism Prevalence: 20-30,000 patients in the U.S. ATR -101 rationale: Reduction of androgens by blocking adrenal steroid precursors Cushing s Syndrome (CS) Medical need: Control of excess cortisol in refractory Cushing s syndrome (all types) Prevalence: ~20,000 cases in the U.S. ATR -101 rationale: ATR-101 acts directly in adrenals lowering cortisol, upstream of steroid biosynthesis Adrenocortical Carcinoma (ACC) Medical need: Aggressive endocrine tumor (<20% 5-yr survival), typically producing excess steroids Prevalence: ~1,000 patients in the U.S., with ~600 new patients diagnosed each year ATR -101 rationale: Apoptosis via disruption of cholesterol homeostasis CONFIDENTIAL 14

15 ATR-101 Targets Starting Point of Adrenal Steroid Synthesis Steroidogenesis upregulated in ACC, CAH & CS Adrenal Cancer Most pathways frequently elevated, particularly cortisol X X Congenital Adrenal Hyperplasia Inactive CYP21A2 leading to elevated androgens & precursors Cushing s syndrome Elevated cortisol CONFIDENTIAL 15

16 Broad ATR-101 Reduction of Steroids and Intermediates Effects demonstrated at modest exposures in canines Significant reduction particularly in androgen intermediates, such as 17OH-progesterone, that are in excess in CAH patients Change after 14d ATR-101 Pathway Steroid Basal ACTH-stim CONFIDENTIAL 16

17 Promising Efficacy in Canine Cushing s Syndrome Reduction of cortisol levels in 90% of subjects Veterinary clinical study in companion dogs with naturally-occurring Cushing s syndrome (similar features to human disease) 10 subjects: 7 pituitary and 3 adrenal Cushing s syndrome Primary endpoint: ACTH-stimulated cortisol levels Results presented at ENDO 2015 Langois, Michigan State University CONFIDENTIAL 17

18 High-Dose ATR-101 Causes Apoptosis Activity due to disruption of cholesterol homeostasis Increase in Free Cholesterol ER Stress and Activation of UPR Induction of Apoptosis In Vitro Potent Adrenolytic Effects Across Species In vivo adrenal cortex effects Cortical atrophy Increased apoptosis Vacuolization Effects seen at relevant pharmacologic doses in dogs, monkeys, guinea pigs, rabbits LaPensee et al, Endocrinology 2016, 157: CONFIDENTIAL 18

19 ATR-101 Phase 1 Study in ACC Patients Study ongoing with top adrenal cancer centers Advanced adrenocortical carcinoma patients who have failed or declined mitotane and platinum-based chemotherapy 3+3 dose escalation followed by expansion cohort Patients receiving benefit allowed to stay on drug No safety concerns in subjects so far Current cohorts have reached exposures of interest Expansion cohort will provide assessment of efficacy Efficacy bar is exceptionally low: mitotane provides only 2 months PFS Successful Phase 1 trial could enable proceeding directly to a pivotal study Current Centers CONFIDENTIAL 19

20 Multiple Clinical Milestones Driving News Flow Opportunity to demonstrate proof of concept across four indications MLE4901 PCOS In-license from AstraZeneca Initiate Phase 2b study ATR-101 Congenital adrenal hyperplasia FDA Type C meeting Initiate Phase 2 study ATR-101 Adrenal cancer Reach target exposure range in dose escalation Initiate expansion cohort of Phase 1 study ATR-101 Cushing s syndrome Orphan drug designation Initiate Phase 2 study CONFIDENTIAL 20

21 Series B Financing of $62M Completed December 2015 Led by New Enterprise Associates with other top-tier investors Significant financing provides long runway and enables clinical proof of concept across four indications CONFIDENTIAL 21

22 Millendo Management and Board of Directors Team with relevant and successful drug development expertise Management Julia Owens, PhD CEO & Co-founder Pharis Mohideen, MD CMO Stephen Hunt, PhD CSO Jeff Brinza SVP Administration & GC Thomas Hoover VP Commercial Strategy Marianne Plaunt, PhD VP Clinical Operations Andrew Spencer, PhD VP Preclinical R&D Jennifer Minai Sr. Director, Finance & Admin Board of Directors Carol Gallagher, PharmD Partner, New Enterprise Associates Jamie Topper, MD, PhD General Partner, Frazier Healthcare Tracy Saxton, PhD Investment Director, Roche Venture Fund Randy Whitcomb, MD Independent Director Julia Owens, PhD CEO, Millendo Therapeutics CONFIDENTIAL 22

23 Millendo is Poised to Become a Significant Endocrine Player Novel agents in diseases with unmet needs and little innovation Building a specialty company in endocrine diseases of hormone dysregulation Novel treatments that Will be first-in-class and disease modifying Have significant market potential Indications marked by Complicated symptoms, yet clear biological basis Few/no approved treatments Interested and engaged treating physicians Team with Aligned capabilities and experience Strong thought leader relationships CONFIDENTIAL 23

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