Improving Life Transforming Value

Transcription

1 Improving Life Transforming Value 2017 Marcum MicroCap Conference June 16, 2017

2 Forward-Looking Statements This presentation contains forward-looking statements made pursuant to the safe-harbor provision of the U.S. Securities Litigation Reform Act of 1995, which reflect our current expectations regarding future events. Forward-looking statements may include, but are not limited to statements preceded by, followed by, or that include the words expects, believes, intends, anticipates, and similar terms that relate to future events, performance, or our results. Forward-looking statements involve known risks and uncertainties, many of which are discussed under the caption Key Information - Risk Factors in our most recent Annual Report on Form 20-F filed with the relevant Canadian securities regulatory authorities in lieu of an annual information form and with the U.S. Securities and Exchange Commission ( SEC ). Such statements include, but are not limited to, statements about the timing of, and prospects for, regulatory approval and commercialization of our product candidates, statements about the status of our efforts to establish a commercial operation and to obtain the right to promote or sell products that we did not develop and estimates regarding our capital requirements and our needs for, and our ability to obtain, additional financing. Known and unknown risks and uncertainties could cause our actual results to differ materially from those in forward-looking statements. Such risks and uncertainties include, among others, our now heavy dependence on the success of Macrilen and the continued availability of funds and resources to successfully complete the submission of an NDA without undue delay with respect to Macrilen and, in the event the FDA approves Macrilen, to successfully launch the product, the rejection or non-acceptance of any new drug application by one or more regulatory authorities and, more generally, uncertainties related to the regulatory process, the ability of the Company to efficiently commercialize one or more of its products or product candidates (including, in particular, Macrilen ), the degree of market acceptance once our products are approved for commercialization (including, in particular, Macrilen ), our ability to take advantage of business opportunities in the pharmaceutical industry, our ability to protect our intellectual property, the potential of liability arising from shareholder lawsuits and general changes in economic conditions. Investors should consult the Company s quarterly and annual filings with the Canadian and U.S. securities commissions for additional information on risks and uncertainties. Given these uncertainties and risk factors, readers are cautioned not to place undue reliance on these forward-looking statements. We disclaim any obligation to update any such factors or to publicly announce any revisions to any of the forward-looking statements contained herein to reflect future results, events or developments, unless required to do so by a governmental authority or applicable law. 2

3 Focused on Developing Shareholder Value Æ Impending FDA submission of Macrilen NDA; potential approval year-end Æ Adequate liquidity and resources to fund operations through expected Macrilen approval Æ ~$17.8 million unrestricted cash and cash equivalents at end of Q1; no third party debt Æ Expected average operating cash use rate of between ~$1.7 million and $1.9 million/month for the remainder of 2017 (down approximately 22% compared to the first quarter) Æ Approximately 14.3 million Common Shares outstanding Æ Experienced leadership with strong record of increasing shareholder value 3

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5 Macrilen (macimorelin) Oral ghrelin receptor agonist for assessing Adult Growth Hormone Deficiency (AGHD) Represents a disruptive advance to the Gold Standard of assessing AGHD Expected to file New Drug Applications with FDA in Q FDA approval expected year-end Upon approval, will be the only FDA-approved drug for assessing AGHD o Granted orphan drug status o Patented through 2027 Significant market expansion opportunity for traumatic brain injury (TBI) patients at risk of developing AGHD 5

6 1956/57 -- Development of Gold-Standard in ETT 6

7 Pharmacologic Response Agents Pharmacologic agents (i.e., drugs ) specifically intended to elicit a physiological response in order to confirm the presence or absence of a disease or condition. Regulatory approval and oversight in the U.S. is via an NDA or ANDA Regulatory approval and oversight in Europe is via an MAA Typically, PRAs are used instead of traditional medical procedures or PRAs represent advances in the medical evaluation of a disease or condition. 7

8 Pharmacologic Response Agents (PRAs) Examples of existing marketed PRAs (NDA approved drugs) in the U.S. : Lexiscan - cardiac evaluation/stress test Thyrogen - determination of thyroid cancer Tubersol & Aplisol - determination of tuberculosis Kinevac - gall bladder/pancreas evaluation Amyvid - plaque density evaluation in Alzheimer s disease Cortrosyn - evaluation of adrenal gland insufficiency 8

9 Pharmacologic Response Agents Product Indication, DX Use Type Molecule Corp 2016_Sales $ LEXISCAN Stress test Vasodilation Regadenoson ASTELLAS $602,000,000 THYROGEN Thyroid cancer Secretagogue FDA approved NDAs of PRAs Annual U.S. Revenues of ~ $1 Billion Thyroid Stimulating Hormone SANOFI $93,776,831 TUBERSOL Tuberculosis Antigen, Protein Tuberculin Test SANOFI $81,260,165 APLISOL Tuberculosis Antigen, Protein Tuberculin Test ENDO $61,304,962 AMYVID PET imaging for Alzheimer s Radioactive Binding to Amyloid Plaque Florbetapir LILLY $14,996,800 CORTROSYN & two Generics Adrenal insufficiency Stimulatory Cosyntropin AMPHASTAR MYLAN NOVARTIS $9,504,697 9

10 Growth Hormone Growth hormone (GH, somatotropin) is a peptide hormone synthesized, stored, and secreted by the pituitary gland. GH is a potent regulator of lipid, sugar and protein metabolism stimulating growth, cell reproduction, and cell regeneration. GH secretion is regulated by neuroendocrine hormones released by the hypothalamus (e.g. GHRH), various physiologic stimuli incl. exercise and sleep, as well as Ghrelin. GH is critical to health throughout life. Häggström, Mikael. "Medical gallery of Mikael Häggström 2014". Wikiversity Journal of Medicine 1 (2). 10

11 Growth Hormone Deficiency (GHD) Consequences of GHD Pediatric Growth failure; delayed physical maturation Adult Diminished lean body mass; poor bone density; numerous physical and psychological symptoms Major causes Primary method of confirming diagnosis of GHD Gold Standard Estimated annual number of tests in U.S. Idiopathic; also, radiotherapy for childhood cancer Provocative testing; e.g.: Insulin Tolerance Test (ITT) Pituitary tumors; radiotherapy for head and neck tumors; traumatic brain injury Provocative testing; e.g.: Insulin Tolerance Test (ITT) ~ 40,000* ~ 40,000* * Source: Navigant

12 Benefits of Growth Hormone Treatment in Adults Significant clinical benefits in body composition and exercise capacity Significant clinical benefits in skeletal integrity Improvement of several cardiovascular surrogate outcomes, including endothelial function, inflammatory cardiovascular biomarkers, lipoprotein metabolism, carotid intima-media thickness, and aspects of myocardial function Improvement of quality of life in most patients 12

13 ~1965 Assessing Growth Hormone Deficiency Insulin Tolerance Test ( ITT ) Medical Procedure (Not FDA Approved or FDA Regulated) Physician Supervision 2 Hours Up to several Hours Fasted Patient Initial Blood Draw Hypoglycemia induced via Insulin IV administration Multiple blood draws and monitoring of blood glucose levels Continued medical supervision Note The ITT procedure must be undertaken with great care and generally requires a physician to be in attendance at all times during the administration of the procedure. 13

14 Macrilen - A potent pharmacologic stimulator of GH release Macrilen (macimorelin acetate) is an orally-active ghrelin receptor agonist that induces a fasting patient s GH secretion in a similar way as ghrelin (GH secretion). Upon stimulation by Macrilen GH is released from the pituitary gland into the circulation. Stomach Ghrelin + Macrilen + Pituitary Gland Growth hormone (GH) Stimulated GH levels are measured in blood for the assessment of growth hormone deficiency (GHD). GH assay 14

15 Assessing AGHD with Macrilen vs the ITT Macrilen -- Pharmacologic Response Agent (NDA) No Physician Supervision Required Initial Blood Draw Patient Drinks Solution 1 Hour 1-2 blood draws No patient restrictions or necessary care Insulin Tolerance Test ( ITT ) Medical Procedure Physician Supervision 2 Hours Up to several Hours Fasted Patient Initial Blood Draw Hypoglycemia induced via Insulin IV administration Multiple blood draws and monitoring of blood glucose levels Continued medical supervision 15

16 Macrilen -- Confirmatory Phase 3 Trial Design Pivotal Phase 3 Study Open-label, randomized, 2-way crossover Extension Study (EU only) N= 30 Patients ITT Macrilen TM Macrilen TM ITT Macrilen TM Macrilen TM Primary Objective Validation of macimorelin for the diagnosis of AGHD, using the ITT as comparator Co-Primary Efficacy Variables Percent Negative Agreement and Percent PositiveAgreement Patients Patients with suspected GHD (low high risk) and healthy subjects Sites: 21 in EU; 5 in U.S. 16

17 Macrilen Confirmatory Phase 3 Trial Results did not meet both pre-defined equivalence criteria for Macrilen success Negative Agreement: 93.94% (CI: 85.20%, 98.32%) Positive Agreement: 74.32% (CI: 62.84%, 83.78%) Under the study protocol, performance of Macrilen TM was considered acceptable if the lower bound of the two-sided 95% confidence interval for the primary efficacy variables is 75% or higher for Percent Negative Agreement and 70% or higher for the Percent Positive Agreement Secondary endpoint: (acceptance criteria not defined) Overall agreement: % (CI: 76.38%, 89.29%) 17

18 Macrilen Confirmatory Trial Conclusions from data analysis Macrilen stimulates the pituitary gland effectively to secrete growth hormone This stimulation was consistently more pronounced than the stimulation achieved with the ITT (in about 80% of all cases, peak growth hormone levels following the administration of Macrilen were equal to or higher than those observed during the ITT). The Macrilen test performed well in the study: Sensitivity (87%) and Specificity (96%) of the Macrilen TM test were satisfactory. Data of the previous study (82% sensitivity, 92% specificity) could be reproduced. The co-primary endpoint negative agreement, which is considered as the more relevant endpoint, was met, demonstrating that the Macrilen test provides medical benefit. The co-primary endpoint positive agreement was not met. 18

19 Macrilen Confirmatory Trial Conclusions from data analysis In the repeatability extension part of the study, conducted upon request from the EMA, Macrilen results proved to be highly reproducible. 94% reproducibility (32 out of 34 cases at the pre-defined cut-off point) Reproducibility of the ITT, which was not investigated in this study, appears worse than the Macrilen test as demonstrated by a high number of nonevaluable ITTs in the study Study results can be further optimized by modulation of the predefined cut-off point of 2.8 ng/ml. Any cut-off point for Macrilen between 4.6 ng/ml and 8.6 ng/ml would have resulted in a positive study outcome in that both protocol-defined co-primary endpoints would have been met. Increasing the cut-off point when comparing to the ITT outcome is justified by the more powerful stimulation of Macrilen as compared to the ITT (pre-defined cut-off point of 5.1 ng/ml) 19

20 Macrilen - Repeatability Subject disposition AGHD likelihood Group A: High B: Intermediate C: Low Total N N N N All subjects Match between first and second MAC test Repeatability per protocol: 32 matching out of 34 RS01-06, Gr C: 1 st test: positive; 2 nd test negative, but 1 st test had no PK results (fake case by dosing error ) 20

21 Macrilen - Evaluability of Macrilen and ITT ITT Macrilen 21

22 Macrilen Confirmatory Trial Robustness Macrilen was found to be a more robust test than ITT, since only 1 out of 153 Macrilen tests needed to be repeated to become evaluable (compared to 28 out of 157 for the ITT) Reproducible outcome of the Macrilen test upon planned repetition in the repeatability study (34 tests) is further evidence of its robustness Macrilen stimulation of growth hormone release more pronounced than the ITT In about 80% of all cases, peak growth hormone levels following the administration of Macrilen were equal to or higher than those observed during the ITT 22

23 Macrilen -- Peak GH concentrations after Macrilen and ITT MAC ITT MAC ITT MAC ITT MAC ITT 23

24 Macrilen - Continued Progress March 6: received EMA concurrence with Pediatric Investigational Plan enabling EU filing March 29: Successful FDA meeting regarding confirmatory trial results addressing deficiencies in previous CRL July 2017: Expected to submit NDA to FDA October 2017: Expected to submit MAA to EMA Year-end 2017: Potential FDA approval Early 2018: Potential U.S. Commercial Launch 24

25 Target Market Assuming ~40,000 annual AGHD stimulatory/confirmatory tests Majority are patients with brain injury due to a tumor itself or treatment (surgery, radiation, chemo) thereof Pediatric GHD patients transitioning into adulthood Traumatic brain injury (TBI) due to accidents Idiopathic causes Approximately 2,500 ENDOs (~1,000 represent >70% of AGHD tests) 150 pituitary/neuroendocrine centers 200 to 300 additional large hospitals 13 Defense and Veterans Brain Injury Centers (DVBIC) providing TBI care for active and retired military 25

26 Macrilen Marketing Objective To rapidly establish Macrilen as the new adult growth hormone deficiency confirmatory test standard, thereby disrupting the current market by displacing current tests (ITT/GST) and capturing >50% of the market within 2-3 years of commercial launch. 26

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28 Focused on Value & Growth Development Transform Aeterna Zentaris from development stage to a profitable, commercially operating specialty biopharmaceutical company through: Working towards successful development and commercialization of Macrilen Pursuing further portfolio additions 28

29 Improving Life Transforming Value June, 2017