Tesamorelin Clinical Data Overview Jean-Claude Mamputu, PhD Senior Medical Advisor, Theratechnologies

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Mechanism of Action of Tesamorelin EGRIFTA (tesamorelin for injection) is a Synthetic Analogue of Human Growth Hormone-Releasing Factor (GRF) EGRIFTA stimulates the pituitary to synthesize and

2 Mechanism of Action of Tesamorelin EGRIFTA (tesamorelin for injection) is a Synthetic Analogue of Human Growth Hormone-Releasing Factor (GRF) EGRIFTA stimulates the pituitary to synthesize and secrete growth hormone In vitro, EGRIFTA binds and stimulates human GRF receptors with similar potency as the natural GRF EGRIFTA EGRIFTA binds to receptor Receptor Growth Hormone Release of growth hormone Copyright All Rights Reserved. Property of Theratechnologies Inc.

3 Growth Hormone (GH) Regulation and Physiology + GHRH - Somatostatin (-) GH Growth Muscle Mass IGF-I Synthesis Lipolysis

4 Rietschel et al. J Clin Endocrinol Metab Growth Hormone Secretion is Reduced in HIV-Related Lipodystrophy

Phase 3 Clinical Studies of EGRIFTA TM (tesamorelin for injection) Main Phase (Weeks 0-26) Extension Phase (Weeks 26-52) EGRIFTA TM 2:1 Randomization EGRIFTA TM Randomization (3:1 ratio for Study 1)

5 Phase 3 Clinical Studies of EGRIFTA TM (tesamorelin for injection) Main Phase (Weeks 0-26) Extension Phase (Weeks 26-52) EGRIFTA TM 2:1 Randomization EGRIFTA TM Randomization (3:1 ratio for Study 1) (1:1 ratio for Study 2) (E-E)* PLACEBO (E-P) Placebo EGRIFTA TM (P-E) *E-E= EGRIFTA (tesamorelin for injection) for weeks 0-26 and EGRIFTA for weeks E-P= EGRIFTA for weeks 0-26 and placebo for weeks P-E= Placebo for weeks 0-26 and EGRIFTA for weeks Copyright All Rights Reserved. Property of Theratechnologies Inc. Falutz et al. J Clin Endocr Metab

6 Inclusion and Exclusion Criteria Main Inclusion Criteria HIV+ male or female patient, years Waist circumference 95 cm (37.4 inches) and a waist-to-hip ratio 0.94 for men and waist circumference 94 cm (37.0 inches) and waist-to-hip ratio 0.88 for women Fasting blood glucose (FBG) <150 mg/dl (<8.33 mmol/l) Stable antiretroviral regimen for 8 weeks prior to randomization For inclusion into the extension phase, patients must have completed the main phase with (FBG) 150 mg/dl Main Exclusion Criteria BMI 20 kg/m 2 Type 1 diabetes, type 2 diabetes if previously treated with insulin or with oral hypoglycemic or insulin sensitizing agents History of malignancy Hypopituitarism. Copyright All Rights Reserved. Property of Theratechnologies Inc. Falutz et al. J Clin Endocr Metab

7 Study Endpoints Primary study endpoint Percentage change from baseline in visceral adipose tissue (VAT) vs placebo at week 26 VAT and changes in VAT were assessed using CT Scans at L4-L5 vertebral level Secondary study endpoints Patient-reported outcomes related to body image Triglycerides Ratio of total cholesterol to HDL cholesterol IGF-1 levels Safety parameters Other Endpoints Waist circumference Abdominal subcutaneous tissue (SAT) Trunk fat Lean body mass Copyright All Rights Reserved. Property of Theratechnologies Inc. Falutz et al. J Clin Endocr Metab

8 Baseline Characteristics (combined studies: 0-26 weeks) Tesamorelin (N=543) Placebo (N=263) P-value Age (y) 48 ± 7 48 ± 8 NS Gender (Male/Female) 465 / / 43 NS Ethnic Origin (W/AA/H) 418 / 71 / / 34 / 25 NS BMI (kg/m 2 ) 29 ± 4 29 ± 4 NS Viral Load, undetectable (%) NS CD4 cell count (cells/mm 3 ) 603 ± ± 281 NS W: White/Caucasian; AA: African American/Black; H: Hispanic. Data are Mean ± SD. NS: Not significant. Falutz et al. J Clin Endocr Metab

9 Baseline Characteristics (combined studies: 0-26 weeks) (Cont d) Tesamorelin (N=543) Placebo (N=263) P-value IGF-1 (ng/ml) 154 ± ± 69 NS Fasting Glucose (mg/dl) 98 ± ± 16 NS TG (mg/dl) 245 ± ± 144 NS WC at Screening (cm) 105 ± ± 9 NS VAT (cm 2 ) 182 ± ± 87 NS SAT (cm 2 ) 231 ± ± 123 NS Limb Fat (kg) (by DEXA) 7.3 ± ± 4.4 NS Data are Mean ± SD. NS: Not significant. Falutz et al. J Clin Endocr Metab

10 Percent Tesamorelin decreases visceral adipose tissue (VAT) and preserves subcutaneous adipose tissue (SAT) Percent Week 26 Week ** VAT SAT -20 VAT SAT Tesamorelin Placebo T-T T-P P-T Data are Mean ± SEM; **P<0.001 vs. Placebo; P<0.001 vs. Baseline and vs. T-P; P<0.001 vs. Baseline. Falutz J. et al. J Clin Endocr Metab. 2010;95:4291.

11 cm cm Tesamorelin significantly reduces waist circumference Week 26 Week ** Waist Circumference -4.0 Waist Circumference Tesamorelin Placebo T-T T-P P-T Data are Mean ± SEM. **P<0.001 vs. Placebo. P<0.001 vs. Baseline and vs. T-P. P<0.001 vs. Baseline. Falutz J. et al. J Clin Endocr Metab. 2010;95:4291.

12 Falutz J. et al. J Clin Endocr Metab. 2010;95:4291. Tesamorelin improves lipid profile (Week 26)

An atherogenic was defined as TGs 75 th percentile plus HDL-C 25 th percentile (Wyszynski DF et al.

13 Tesamorelin decreases triglycerides in patients with atherogenic dyslipidemia Data are mean ± SEM. **, p=0.01 for tesamorelin ALP(+) vs. tesamorelin ALP(-). An atherogenic was defined as TGs 75 th percentile plus HDL-C 25 th percentile (Wyszynski DF et al. Am J Cardiol. 2005), while an ALP(-) pattern included patients with TGs median plus HDL-C median at baseline Falutz J. et al. CROI 2009.

14 Tesamorelin synergizes with fibrates to decrease triglycerides (% change from baseline) 10.0 Falutz J. et al. CAHR 2016

15 mg/l μg/ml ng/ml ng/ml Tesamorelin Improves inflammatory markers PAI tpa P= P= CRP 1.5 Adiponectin P= P=0.03 Data are Mean ± SEM. Tesamorelin Placebo Stanley T. et al. AIDS 2011;25:1281.

16 Change from baseline Tesamorelin improves belly appearance distress Towards Encouraging or Less Distress P=0.002 ** 10 8 ** Placebo Tesamorelin Data are mean ± SEM. **, P < vs. Baseline for the within group comparison; displayed p-value is for the between group comparisons. A positive change indicates improvement in belly appearance distress. Falutz J. et al. J Clin Endocr Metab. 2010;95:4291.

Change in Glucose Parameters at Week 26 (Combined Studies) Baseline Change from Baseline to Week 26 Parameter Tesamorelin (N=543) Placebo (N=263) Tesamorelin (N=543) Placebo (N=263) Mean ± SD Fasting

17 Change in Glucose Parameters at Week 26 (Combined Studies) Baseline Change from Baseline to Week 26 Parameter Tesamorelin (N=543) Placebo (N=263) Tesamorelin (N=543) Placebo (N=263) Mean ± SD Fasting glucose (mmol/l) 5.45 ± ± ± ± hr OGTT glucose (mmol/l) 6.26 ± ± ± ± 2.37 Insulin (pmol/l) ± ± ± ± HOMA-IR 5.5 ± ± ± ± 7.09 HbA 1c (%) 5.3 ± ± ± ± Statistically significantly different between the tesamorelin and placebo groups (p=0.0004). Falutz J. et al. J Clin Endocr Metab. 2010;95:4291.

18 AEs 5% and Occurring More Frequently in Tesamorelin-Treated Patients (Combined Studies) Main Phase (0-26 Weeks) T (N=543) P (N=263) Extension Phase (27-52 Weeks) T-T (N=246) T-P (N=135) Patients with Adverse Events n (%) 425 (78.3) 187 (71.1) 154 (62.6) 81 (60.0) Injection site reactions Injection site erythema 46 (8.5) 7 (2.7) 3 (1.2) 0 Injection site pruritus 41 (7.6) 2 (0.8) 5 (2.0) 0 GH-related events Arthralgia 72 (13.3) 29 (11.0) 14 (5.7) 8 (5.9) Pain in extremity 33 (6.1) 12 (4.6) 8 (3.3) 1 (0.7) Peripheral edema 33 (6.1) 6 (2.3) 5 (2.0) 0 Myalgia 30 (5.5) 5 (1.9) 3 (1.2) 0 Falutz J. et al. J Clin Endocr Metab. 2010;95:4291.

20 Proportion of Responders and Non Responders at Week 26 Intent-to-treat population, last observation carried forward analysis - Tesamorelin: 57.4% responders* - Placebo: 29.3% responders Per-protocol population, observed case analysis - Tesamorelin: 68.8% responders* - Placebo: 32.6% responders *The proportion of responders and non-responders is statistically different between the tesamorelin and placebo groups in both analyses (p< 0.001)

21 Change in VAT (%) Changes in VAT: Responders vs. Non Responders 15,0 5,0-5,0-15,0-25,0-35,0 VAT Responders VAT VAT Non-Responders No statistical analyses were performed to compare Responders vs Non-Responders Per protocol- Observed Case analysis. Data are Mean ± SEM

22 VAT Profile over 26 Weeks (Responders vs. Non Responders) cm cm 2 (10%) cm cm cm 2 (-27%) 110 Baseline Week 13 Week 26 Responders Non-Responders Per protocol- Observed Case analysis. Data are Mean ± SEM

23 cm Waist Circumference Profile over 26 Weeks (Responders vs. Non Responders) cm cm cm cm 98 Baseline Week 13 Week 26 Responders Non-Responders Per protocol- Observed Case analysis. Data are Mean ± SEM

24 Change (mg/dl) Changes in Lipids Parameters at Week 26 (Responders vs. Non Responders) Total Chol. Non-HDL Chol. Triglycerides P=0.014 P= P=0.005 VAT Responders Per protocol- Observed Case analysis. Data are Mean ± SEM VAT Non-Responders

25 Change from Baseline Towards Encouraging or Less Distress 20 Change in Belly Appearance Distress at Week 26 (Responders vs. Non-Responders) P< VAT Responders VAT Non-Responders Per protocol Observed case analysis; Data are mean ± SEM. Displayed P-values are for the between group comparisons

26 Changes in Glucose Parameters at Week 26 (Responders vs. Non-Responders) Parameter Responders (N= 229) Baseline N-responders (N=98) Mean ± SD Change from Baseline to Week 26 Responders (N= 229) N-responders (N=98) Fasting glucose (mg/dl) 5.4 ± ± ± ± hr OGTT glucose (mmol/l) 6.3 ± ± ± ± 2.4 Insulin (pmol/l) ± ± ± ± 93.8 HOMA-IR 5.38 ± ± ± ± 4.26 HbA 1c (%) 5.26 ± ± ± ± p< 0.05 Responders vs N-responders per protocol Observed Case MK Nov/09

28 Predictors of Response to Tesamorelin Treatment Mangili A. et al., PLoS One 2015.

29 Predictors of Response to Tesamorelin Treatment (Cont d) Mangili A. et al., PLoS One 2015.

30 Conclusions EGRIFTA has a unique mechanism of action as it works by stimulating the production of endogenous growth hormone EGRIFTA resulted in statistically significant reductions in VAT and WC at week 26, sustained through week 52 Treatment effect related to duration of treatment and seen as early as 13 weeks GH-related AEs and injection site reactions were more frequent with EGRIFTA Patients with baseline MetS, elevated TG levels, or white race were most likely to experience reductions in VAT after 6 months of treatment Please see EGRIFTA (tesamorelin for injection) full Prescribing Information, Patient Information and Patient Instructions for Use for full disclosure. Copyright All Rights Reserved. Property of Theratechnologies Inc.

32 Rationale and Hypothesis Humans: Patients with pituitary growth hormone deficiency (GHD) have a higher prevalence of NAFLD and NASH than the general population Replacement of GH reduces transaminases and improves histological findings Hypothesis: Tesamorelin will reduce liver fat in association with reductions in VAT. Adams LA et al. Hepatology. 2004; 39: Ichikawa T et al. Gut. 2003; 52:914.

33 H e p a tic L ip id -to -W a te r % Tesamorelin decreases liver fat C h a n g e in L iv e r F a t p = % 0-40% -5 T e s a m o re lin P la c e b o Bars show median, error bars IQR. Tesamorelin: -2.0 [-6.4, 0.1]; Placebo: 0.9 [-0.6, 3.7] Stanley T. et al. JAMA 2014.

34 Correlations between Changes in VAT, Hepatic Fat, and Metabolic Variables A Visceral Adipose Tissue (cm 2 ) C AST (U/L) P Hepatic Lipid-to-Water Percent T T P B = 0.31, P = = 0.50, P = Log10 Triglyceride HOMA-IR Tesamorelin Placebo Hepatic Lipid-to-Water Percent 0.8 r = 0.33, P = 0.03 D r = 0.52, P = T T P P Visceral Adipose Tissue Area (cm 2 ) Stanley T. et al. JAMA Visceral Adipose Tissue Area (cm 2 )

36 Diabetic Retinopathy Relationship between serum IGF-1 levels and development of diabetic retinopathy still controversial A large cross-sectional study (N=225) found no association between serum IGF-1 and diabetic retinopathy 1 Increased serum levels of IGF-1 not associated with an increased risk of diabetic retinopathy in a longitudinal study (N-480, 6.2 years of follow-up) 2 1 Payne JF et al., Molecular Vision 2011; 2 Chen HS et al., Eur J Clin Invest 2012.

37 Safety of Growth Hormone (GH) (1) Since 2012, new data have emerged on the potential risk of cancer in patients receiving GH Mortality data from parallel investigations in Belgium, The Netherlands and Sweden show that none of the patients died from cancer or from a CVD 1 No increase increased risk of mortality or incidence of cancer, stroke, or myocardial infarction in adult GHdeficient patients who had previously received pediatric GH treatment (The Hypopituitary Control and Complications Study, a prospective observational study (N= 10,190, US, Canada, and 14 Europeans countries) 2 1 Savendahl L. et al. JCEM 2012; 2 Mo D. et al. Pituitary 2014.

38 Safety of Growth Hormone (GH) (2) Pediatric Endocrine Society Drug and Therapeutics Committee: GH therapy can be safely administered without concerns about an increased risk for neoplasia 1 A statement from the European Society of Paediatric Endocrinology (ESPE), the Growth Hormone Research Society (GRS), and the Pediatric Endocrine Society (PES) concluded that the evidence from the follow-up of thousands of children and adults over tens of thousands of patient years 2 1 Raman J. et al. J Clin Endocrinol Metab. 2015;100: ; 2 Allen D.B. et al..eur J Endocrinol 2016.

39 Safety of Growth Hormone (GH) (3) ENDO 2016: Debate on the safety of GH: Dr. Jean-Claude Carel (Paris, France) vs. Dr. Ron Rosenfeld (Los altos, CA, USA) 1 : Dr. Carel (PI of the French SAGhE study): Risks of long-term GH are plausible, but there is a long way to go before we fully evaluate the longterm safety of GH treatment. The risk of cancer and CVD is debatable. It s difficult to demonstrate causality. Dr. Rosenfeld: GH is safe. I think methodological limitations of the SAGhE study should be recognized. Interpretation of data may not be correct. Mortality is not increased when adjusted for birth weight. The rhgh population differed from the general population in birth weight and birth length. Limitations of the French SAGhE study include: small number of observations, heterogeneous population, failure to reproduce findings outside of France, lack of appropriate control group. 1 ENDO 2016 Endocrine Debates: Are there long-term risks in pediatric growth hormone treatment? Boston, April 2, 2016.

FULL PRESCRIBING INFORMATION: CONTENTS*

FULL PRESCRIBING INFORMATION: CONTENTS* HIGHLIGHTS OF PRESCRIBING INFORMATION These highlights do not include all the information needed to use EGRIFTA safely and effectively. See full prescribing information for EGRIFTA. EGRIFTA (tesamorelin