R&D Day - Theratech · R&D Day 2 Agenda Time Topic Presenter 12:00 Introduction Luc Tanguay...

R&D Day

Nasdaq MarketSite, New York

October 23, 2019

R&D Day

2

Agenda

Time Topic Presenter

12:00 Introduction Luc Tanguay

President and CEO, Theratechnologies

12:10 NAFLD/NASH – HIV Dr. Steven Grinspoon

Harvard Medical School

12:40 NASH – HIV: Review Christian Marsolais, PhD

Senior VP and CMO, Theratechnologies

12:50 Q&A : NASH – HIV Philippe Dubuc

Senior VP and CFO, Theratechnologies

13:00 Oncology Platform Richard Béliveau, PhD in Biochemistry

Université du Québec à Montréal

13:30 Oncology Platform: Review Christian Marsolais

13:40 Q&A Philippe Dubuc

13:55 Closing Comments/Adjournment Luc Tanguay

FORWARD-LOOKING INFORMATION

3

The following presentation contains statements that are considered forward-looking information (“FLI”) within themeaning of securities regulation.

The FLI in this presentation relates to future events or our future performance. The FLI are based on a number ofassumptions and are associated with a number of risks, uncertainties and other unknown factors that may causeour actual results, levels of activity, performance or achievements to be materially different from those implied bythe FLI. Such FLI reflects our current views with respect to future events and is given as at October 23, 2019. Weundertake no obligation and do not intend to update or revise the FLI contained in this presentation, except asrequired by law.

Certain assumptions made in preparing the FLI include, but are not limited to, the following: (1) sale of EGRIFTA®

and Trogarzo® will continue to grow over time; (2) the long-term use of EGRIFTA® and Trogarzo® will not changetheir known safety and efficacy profile; (3) EGRIFTA SVTM will be commercially available in the United States in thenext few weeks; (4) our relations with our suppliers of services will be conflict free; (5) data on the potential marketsize for multidrug resistant HIV-1 and NASH-HIV patients are accurate; (6) Trogarzo® will be reimbursed inEurope; (7) the bioequivalence study of the IV slow push formulation for Trogarzo® will be successful; (8) thedevelopment of EGRIFTA® for the treatment of NASH-HIV patients will be successful; (9) the research anddevelopment work conducted on our oncology platform will yield positive results; (10) our current and futureincome will be sufficient to fund our business plan; and (11) our strategies and business plan will not besubstantially modified.

The FLI in our presentations may not materialize; accordingly, investors should not place undue reliance on it. Werefer you to the “Risk Factors” section of our Annual Information Form dated February 20, 2019 available atwww.sedar.com, at www.theratech.com and as an exhibit to our Form 40-F available at www.sec.gov for adescription of the risks related to the conduct of our business.

EGRIFTA and EGRIFTA SV is a trademarks of Theratechnologies Inc.

Trogarzo is a registered trademark of TaiMed Biologics, Inc. under license to Theratechnologies Inc.

http://www.sedar.com/

http://www.theratech.com/

http://www.sec.gov/

Corporate Overview

THERATECHNOLOGIES

5

• Founded in 1993

• Headquartered in Montreal, Canada

• Listed on NASDAQ (THTX) and on the Toronto Stock Exchange (TH)

• Commercial-stage biopharmaceutical company

• North American and European presence

• Focus on Patients with Special Medical Needs

At a glance

THERATECHNOLOGIES

6

Corporate and commercial structure

FUNCTIONS

Head office (Canada and Europe) 39

Sales team (U.S.) 36

Reimbursement team (U.S.) 8

Medical Science Liaison (U.S.) 8

Medical Science Liaison (Europe) 3

Call center (U.S.) 11

Laboratories (Canada) 5

Total 110

Product

Indication

(Potential Indication)

Phase of Development Expected

2020 MilestonesPreclinical Phase 1 Phase 2 Phase 3 Commercial

THERATECHNOLOGIES

7

Portfolio

Co

mm

erc

ial

EGRIFTA®HIV-associated

lipodystrophy

EGRIFTA SV™HIV-associated

lipodystrophy

Trogarzo® MDR HIV-1


Reimbursement

approval on a country

by country basis

Develo

pm

en

t

EGRIFTA F8™HIV-associated

lipodystrophyBioequivalence study

Tesamorelin F8 NASH-HIV Initiating Phase III

Trogarzo® IV

slow push and IMMDR HIV-1 Bioequivalence study

TH-1902Triple Negative Breast

Cancer (TNBC)Initiating Ph 1

TH-1904 Ovarian Cancer Initiating Ph 1

Approved in E.U.

Commercialized in US and Canada

Commercialized in the US

Commercialized in U.S

Our Approved Products

8

• EGRIFTA® (tesamorelin for injection)

• Only treatment approved for HIV-associated lipodystrophy

• New formulation to be launched before year-end

• Room temp, smaller needle, smaller injection volume

• Trogarzo® (ibalizumab-uiyk) injection

• Approved by the FDA on March 6, 2018

• Approved by the EMA on September 26, 2019

• Indicated for the treatment of patients with multidrug resistant HIV-1

Focusing on HIV niche markets

Consolidated Revenues (in 000 US$)

9

Quarterly revenues 2017-2019

0

2 000

4 000

6 000

8 000

10 000

12 000

14 000

16 000

18 000

Q1 Q2 Q3 Q4

2017 2018 2019

Product

Indication




THERATECHNOLOGIES

10

Portfolio

Co

mm

erc

ial

EGRIFTA®HIV-associated

lipodystrophy

EGRIFTA SV™HIV-associated

lipodystrophy



Reimbursement

approval on a country

by country basis

Develo

pm

en

t

EGRIFTA F8™HIV-associated

lipodystrophyBioequivalence study

Tesamorelin F8 NASH-HIV Initiating Phase III

Trogarzo® IV

slow push and IMMDR HIV-1 Bioequivalence study




Approved in E.U.

Commercialized in US and Canada

Approved in the US

Commercialized in U.S

Product

Indication




THERATECHNOLOGIES

11

Portfolio

Co

mm

erc

ial

Develo

pm

en

t Tesamorelin F8 NASH-HIV Initiating Phase III




Steven Grinspoon, M.D.Professor of MedicineHarvard Medical School

Steven Grinspoon, M.D.

13

• Professor of Medicine Harvard Medical School

• Chief, Metabolism Unit

• MGH Endowed Chair in Neuroendocrinology and Metabolism Director, Nutrition Obesity Research Center at Harvard

NAFLD – NASH in HIV

NAFLD/NASH: A Spectrum of Disease

15

Rinella, JAMA 2015

Courtesy of Dr. Steven Grinspoon

Prevalence in HIV in US

16

Prevalence: 35%

385,000 patients

Prevalence: 41%

451,000 patients

Prevalence: 21%

231,000 patients

NAFL NASH Fibrosis

Maurice et al., AIDS 2017; 31: 1621-1632

HIV Lipodystrophy

17

Brown, JCEM 2008

Joy, JAIDS 2008

Disproportionate Visceral Fat in HIV

Versus Controls with Similar BMI


Risk Factors in HIV for NAFLD/NASH

18

BMI

Waist circumference

Lipodystrophy

(Visceral Adipose Tissue

– VAT)

Diabetes /Glucose

Hypertension

Cholesterol

CD4 count

HCV co-infection

ART

ALT

AST

Maurice et al., AIDS 2017; 31: 1621-1632

Chalasani et al., 2007, 55(6); 2005-23

Coronel-Castillo, Exp Rev Gastro and Hepato, 2019,

Risk Factors for Fibrosis

19

HIV infection

(OR: 5.17)

Diabetes

(OR: 5.14)

Central obesity

(OR: 7.52)

Reduced HDL

cholesterol

(OR: 3.53)

BMI

(OR: 1.21)

Intrahepatic

triglyceride content

(OR: 1.10)

OR: Odd ratio

Lui et al., APT, 2016;44: 411-421

Leite and al., JIAPAIDS, 2015, 14 (5): 4663-68

Conclusion

20

• High prevalence of NAFLD/NASH in HIV population

• Visceral adipose tissue is a risk factor for NAFLD/NASH in HIV population

• HIV infection is a risk factor for development of fibrosis

• NAFLD/NASH is associated with significant comorbidities:

• CVD

• Diabetes

• All cause-mortality

Association between NAFLD/NASHand Growth Hormone

Relative GH Deficiency in HIV Lipodystrophy

22

Frequent Overnight Sampling GHRH-Arginine Stimulation Test

Rietschel et al, JCEM 2001

Koutkia et al, JCEM 2005

Low GH May Contribute to Hepatic Steatosis

in HIV

23

HIV Liver-Specific GHR KO Mice

*

*

*P < 0.05

Stanley et al, JAMA 2014

Liu et al, Diabetes 2016

Rationale for Use of GHRH vs GH

24

Hypothalamus

Somatostatin GHRH

Pituitary

GH

–

–

+–

++

Liver

IGF-1

Stomach

Ghrelin

Tesamorelin

25

• A minimally modified GHRH1-44 with trans 3-hexanoyl adduct on Tyr.

• Increases GH in a physiologic, pulsatile manner

Tesamorelin Reduces Visceral Fat in

Individuals with HIV and Abdominal Obesity

26

** P < 0.001 vs. placebo § P < 0.001 vs. baseline and vs. T-P

† P < 0.001 vs. baseline NEJM 2010, JCEM 2010

Tesamorelin Reduces Liver Fat in Individuals

with HIV and Abdominal Obesity

27

H2O

Lipid

1H MRS

Tesamorelin

(n = 28)

Placebo

(n = 22)

Age (years) 49 [46, 54] 53 [49, 58]

% Male 86 82

VAT (cm2) 208 ± 98 237 ± 127

SAT (cm2) 258 ± 116 256 ± 123

BMI (kg/m2) 28 [26, 33] 30 [27, 33]

Liver fat (%) 4.5 [2.0, 19.3] 6.2 [2.1, 20.6]Tesamorelin Placebo

-10

-5

0

5

Δ H

ep

ati

c L

ipid

-to

-Wate

r %

P = 0.004

Median, IQR

Stanley et al, JAMA 2014

Effect of Tesamorelin in NonalcoholicFatty Liver Disease in HIV:

A Randomized Trial

NAFLD/NASH Pharmacologic Pipeline

29

No therapies are currently FDA-approved

Connolly, J Clin Transl Hepatol 2018

Tesamorelin


Effect of Tesamorelin in HIV & NAFLD

30

Inclusion criteria

• Men and women 18-70 yrs

• HIV-infection and stable ART for ≥ 6 months

• Liver fat fraction ≥5% on MRS

• HCV antibody negative, or, if HCV antibody positive, successful therapy ≥1 year prior to baseline and undetectable HCV RNA.

• Females ≥50 yrs: negative mammogram within 1 year of baseline visit

• If use of Vitamin E ≥400 IU daily, stable dose for ≥6 months prior to study.


31

Exclusion criteria

• Heavy alcohol use defined as consumption (>20g daily for women or >30g daily for men)

• Use of insulin or thiazoledinediones (TZDs), or HbA1c ≥7%. Individuals with mild diabetes that is well-controlled with diet and/or oral anti-diabetic agents besides TZDs will be included. Use of oral anti-diabetics must have been stable for ≥6 months prior to study entry.

• Hepatitis B & active hepatitis C

• Known cirrhosis

• Fibrosis stage 4

• Chronic corticosteroid use except intermittent use of topical steroid creams

• Use of GH or GHRH within the past 1 year

• Active malignancy


32

Study design

Tesamorelin 2 mg SC daily

Open label Tesamorelin 2 mg

SC dailyPlacebo SC daily

Patients from 2 centers

(MGH and NIH)Randomization: 1:1

n=60

0 12 m 6 m

33

Editorial

Stanley, Fourman, The Lancet HIV 2019



34

Baseline characteristics

EGRIFTA® (n=31) PLACEBO (n=30)

Sex (N (%) Male) 24 (77.4%) 24 (80%)

Age (Y) 52 ± 8 54 ± 7

Duration of HIV infection 16 ± 9 18 ± 8

Current vitamin E use (N (%)) 2 (6.5%) 1 (3.3%)

Hepatic Fat (%) 12.9 ± 7.7 14.7 ± 9.0

NASH (N (%)) 10 (34.5%) 9 (31.0%)

Fibrosis (N (%)) 14 (48.3%) 11 (37.9%)

Stage 1 4 (13.8%) 5 (17.2%)

Stage 2 6 (20.7%) 4 (13.8%)

Stage 3 4 (13.8%) 2 (6.9%)

At baseline:

Mean HFF: 13.8 ± 8.4%

33% with histologic diagnosis of NASH

43% had fibrosis Stage 1 or higher

Effect of Tesamorelin on Hepatic Fat

35

Tesamorelin Placebo-8

-6

-4

-2

0

2

Ab

so

lute

ch

an

ge

in liv

er

fat, % P = 0.009

-0.0 ± 4.1

-4.7 ± 6.6

Tesamorelin Placebo-60

-40

-20

0

20

Re

lativ

e c

ha

ng

e in

liv

er

fat, % P = 0.02

-32 ± 54

5 ± 42

Tesamorelin Placebo0

10

20

30

40

He

pa

tic

ste

ato

sis

< 5

%

at 1

2 m

on

ths

P = 0.007

35

4

Mean ± SEM Courtesy of Dr. Steven Grinspoon

Effect of Tesamorelin on ALT in Participants

with ALT > 30 U/L at Baseline

36

Mean ± SEMCourtesy of Dr. Steven Grinspoon


37

Effect on fibrosis progession after 12 months of Tx

10,5

37,5

0

5

10

15

20

25

30

35

40

Fibrosis progression

Pe

rce

nta

ge

of p

atie

nts

(%

)

EGRIFTA Placebo

P=0.004


38

Effect on visceral adiposity and SAT after 12 months of Tx

-35

11

-40

-30

-20

-10

0

10

20

Visceral adiposity Subcutaneous fat

Tre

atm

en

t e

ffe

ct (c

m2

)

Tx effect:

-35 (-66, -4)

p=0.03

Tx effect:

11 (-19, 41)

p=0.46

Association of hepatic fat reduction with NAS

score improvement

39

• 29% decrease in liver fat is associated ≥ 2 point change in histological NAS score*

• Phase II results:

*Patel et al., Therapeutic Advances in Gastroenterology 2016 9;692-701

60%

16%

0%

10%

20%

30%

40%

50%

60%

70%

Patient with relative liver fat reduction of > 30%

Tesamorelin

Placebo


40

Effect on other parameters after 12 months of Tx

Tx effect P

ALT, U/L -7 (-15, 1) 0.09

GGT, U/L -19 (-13, 4) 0.10

IGF-1 117 (76, 157) < 0.0001

TG, mg/dL 23 (-7, 53) 0.12

HDL-C, mg/dL 3 (-1, 6) 0.17

LDL-C, mg/dL -5 (-21, 11) 0.54

CRP, mg/L -4.7 (-9.2, -0.2) 0.04

Tx effect P

Adiponectin, ng/mL 222 (-225, 669) 0.32

Fasting glucose, mg/dL 4 (-5, 13) 0.40

HbA1c, % 0.2 (-0.1, 0.5) 0.29

CD4+ T cells (cells/mm3) 17 (-60, 95) 0.65

CD8+ T cells (cells/mm3) -18 (-113, 77) 0.70

Log HIV viral load

(copies/mL)

0.18 (-0.25, 0.62) 0.41

Even though there was an expected increase of

IGF-1.

No subject had IGF-1 Z score over the pre-

specified dose reduction threshold (Z-score > 3).

Effect of Tesamorelin on Fasting Plasma

Glucose by Treatment Group

41

0 3 6 9 120

50

100

150

200

Months

Pla

sm

a g

luc

os

e (m

g/d

L) Tesamorelin

Placebo


Adverse Events by Treatment Group

42


Summary

43

• Low concentration of GH is associated with an increase of the visceral adipose tissue and liver fat (+fibrosis).

• In the HIV population, Tesamorelin

• Significantly decreases the liver fat

• Significantly decreases the fibrosis progression

• Already approved for visceral fat reduction in lipodystrophy, likely to also benefit the large number of HIV patients with NAFLD/NASH

• Tesamorelin has a good and well documented safety profile

HIV NASH Regulatory Strategy

Tesamorelin in HIV NAFLD/NASH –

Regulatory Strategy

45

• Drugs in development for NASH

• Have not included HIV patients

• Did not show conclusive results for this patient population

• Disease’s etiology is different from the general population due to HIV risk factors

• Tesamorelin safety profile is well established

• Impossible to conduct large trials to assess impact on Clinical Events in HIV

• Tesamorelin can address an unmet medical need


Regulatory Strategy

46

• FDA Guidelines:

• Identifying therapies that will slow the progress of, halt, or reverse NASH and NAFLD will address an unmet medical need

• Endpoints:

• Decrease in fibrosis of at least 1 with no negative impact on NASH

• Normalization of NASH score with no negative impact on fibrosis


Regulatory Strategy

47

• Clinical Phase III trial

• Patient population: presence of fibrosis with a score of at least 1 and NASH of 4 or more

• Endpoints:

• Normalization of liver fat (˂5%) with

• Delayed progression in fibrosis with no negative impact on NASH, or

• Delayed progression in NASH with no negative impact on fibrosis

• In Silico mathematical modeling of long term reduction of clinical events

Next Steps – Tesamorelin in HIV NAFLD/NASH

48

• Request for Type C meeting submitted to the FDA

• Request for Scientific Advice with EMA to be submitted at the beginning of November

• Complete Bioequivalence studies for F8 formulation

• Complete discussion with regulatory agencies

• Initiate Phase 3 program

Q&A NASH – HIV

TARGETED ONCOLOGYPLATFORM

Dr. Richard BéliveauProfessor Emeritus of BiochemistryUniversité du Québec à Montréal

Need for a new approach in cancer treatment

52

Chemotherapy is a key therapeutic approach to treat cancer, but it is limited by side effects:

• More than 95% anticancer drugs administered through classical chemotherapy is unfortunately taken up within healthy tissues, whereas only 2-5% effectively reaches tumors

First-line treatments

53

Chemotherapy drugs and side effects

Chemotherapy drugs

• Doxorubicin

• Pegylated liposomal doxorubicin

• Paclitaxel

• Nab-paclitaxel

• Capecitabine

• Gemcitabine

• Vinorelbine

• Cyclophosphamide

• Carboplatin

• Docetaxel

• Cisplatin

• Epirubicin

Common side effects

• Myelosuppression

• Neutropenia

• Nausea and vomiting

• Sore mouth and throat

• Alopecia

• Diarrhea

• Constipation

• Fatigue

• Loss of appetite

• Treatment-induced menopause

• Cognitive changes

• Nervous system damage

• Fertility problems

Targeted Oncology Platform

54

• New oncology platform

• Potential to link a number of different cytotoxic and other anticancer agents

• Lower risk program

• Peptide-Anticancer Drug Conjugates for targeted therapies

• Targeting Sortilin receptor (receptor overexpressed in cancer cells)

• Targets cancer cells with virtually no impact on normal cells

• Brings cytotoxics to the cancer cells without inducing neutropenia and other AEs, weight loss.

• Can lead to the development of a number of cancer drugs

Receptor-mediated Cancer Treatment

Why Sortilin as a new target in cancer therapy?

55

• Sortilin overexpression in tumors, compared to healthy tissue

• Clinical patients survival correlated with Sortilin expression

• Scavenger receptor involved in import-export of peptides: ideal candidate for drug internalization of peptide-drug conjugates

• Ligands with known sequences allow creation of an ideal synthetic ligand with drug conjugation capability

Discovery and role of Sortilin

56

Functions:

• Transmembrane scavenger receptor

• Involved in internalization and trafficking of ligands

from the plasma membrane, to the endocytic

pathway and to lysosomes for degradation

• Considered as one of the cells own shuttle system

In cancer:

• Receptor involved in cancer cell survival, invasion

and progression

• High Sortilin expression has been associated with

poor prognosis in different cancers

Sortilin’s role in cancer development

58

• Associated with cancer stem cells expansion

• Progranulin-induced breast cancer stem cell propagation in vivo

• Involved in intercellular communication

• Transfer of genetic and protein material to control angiogenesis

• Release and transfer of exosomes

• Regulates adaptive phenotypes in solid tumor

• Increased upon low oxygen tension

• Increased in metastases and local cancer cell infiltration

Treatment of Sortilin Positive Cancers

59

Sortilin expression in cancers

• Associated with ovarian and breast cancers aggressiveness:

• 90-100% of ovarian cancers

• 79% of invasive ductal breast cancer (60% in TNBC)

• Increased expression as a function tumor grade (I to IV)

• Other cancers expressing Sortilin:

• Endometrial (90%)

• Lung (65%)

• Melanoma (90-100%)

• Urothelial (70%)

• Colorectal (30%)

• Pancreatic (30%)

Classic Chemotherapy

60

Drug efflux

Doxorubicin Docetaxel MaytansineINTERSTITIUM

PLASMA

MEMBRANE

CYTOPLASM

MDR1

PASSIVE DIFFUSION

• Low specificity

• Many unwanted side effects

• Drug efflux by MDR1 leading to low drug concentrations

Theratechnologies’ Oncology Platform

61

A molecular Trojan horse

Receptor-mediated internalization

• High specificity

• Less side effects

• Bypasses MDR1 leading to high drug concentrations

Intracellular

Drug Release

Lysosomal

Degradation

Receptor

RecyclingInternalization

SORTILIN

Theratechnologies peptide conjugates

Binding Endocytic-Vesicle

Formation

MDR1

Treatment of Sortilin Positive Cancers

62

• First-in-class peptide family

• 17 AA linear synthetic peptide specific for Sortilin

• Conjugation cytotoxics at selected drug-peptide ratio

• Combination treatment with other pharmacological approaches

Cleavable linker: DMG

(dimethyl-glutaryl)

Peptide

Drug

(Doxorubicin)

Doxorubicin-Theratechnologies peptide conjugate (TH1904)

TH1904: Doxorubicin conjugate in Ovarian Cancer

64

Cancer Incidence Mortality Rate (%)

Breast 1 384 155 275 008 20

Uterus 288 387 73 854 26

Cervix 530 232 224 747 42

Ovary 224 747 140 163 62

Incidence of Major Cancers in Women

(worldwide)

Ovarian cancer

65

SORTILIN Expression in Human Ovarian Cancers by IHC

Healthy ovary Primary ovarian cancer Ovarian metastasis Healthy ovary Primary ovarian cancer Ovarian metastasis

In Vivo Validation

66

Preferential tumor targeting

TH1904 (Ovarian Cancer)

Ovarian tumor vs healthy ovary

Healthy Ovary Tumor0

1000

2000

3000

4000

5000

6000

7000

8000

Doxorubicin

DoxKA

Tissues

Accu

mu

latio

n (n

g/g

of t

issu

e) • High accumulation in ovarian tumor

• Low accumulation in healthy ovary tissueTH1904

In Vitro Characterization and Validation

67

Bypass MDR efflux pump


• In contrast to Doxorubicin, TH1904 is unaffected by the MDR inhibitor Cyclosporin A (CsA)

• Bypassing MDR1 efflux pump leads to increased TH1904 accumulation

Uptake in MDCK-MDR-positive cells

Doxorubicin TH1904

0

5

10

15

20

- + - + CsA

Upta

ke (

fmol/m

g o

f pro

tein

)

In Vivo Validation

68

ES-2 Ovarian Cancer model

Delta tumor volume post-treatments

Day-14 PT

Vehicle Doxorubicin DoxKA0

25

50

75

100

125

150

43%

97%

Tum

or

volu

me incre

ase (

%)

*18 mg/kg/week TH1904 is equivalent to the Doxorubicin MTD (6 mg/kg/week)

TH 1904

TH1904: Tumor Growth Inhibition

69

Second Ovarian Tumor Model (SKOV3)

• Mice treated with Doxorubicin received 5 treatments at 3 mg/kg/bi-weekly (MTD)

• Mice treated with TH1904 received 7 treatments at an equivalent dose of Doxorubicin

0 2 4 6 8 10 12 14 16 18 20 220

100

200

300

400

500

600

700

800

900

1000

1100

Tx1 Tx2 Tx3 Tx4 Tx5 Tx6*

Vehicle

Doxorubicin

DoxKA

Tx7*

Days Post-Treatment

Tum

or

Volu

me

(mm

3)

Treatments: equimolar Doxorubicin doses

(3 mg/kg/bi-weekly, IV)

SKOV-3 Ovarian Tumor Growth

TH1904

Vehicle Doxorubicin DoxKA0

25

50

75

100

125

150

¯41%

¯77%

Tum

or

volu

me incre

ase (

%)

TH1904

In Vivo Benefits

70


• In humans, Doxorubicin limit lifetime cumulative dose (<550 mg/m²) to reduce risk of cardiotoxicity

• Less accumulation of TH1904 in the heart suggests better cardiotoxicity profile compared to Doxorubicin

Reducing side effects

Heart

Doxorubicin DoxKA0

500

1000

1500

2000

Treatment

Accu

mu

latio

n (n

g/g

of t

issu

e)

TH1904Doxorubicin

In Vivo Benefits

71

TH1904 Conjugate (Ovarian Cancer)


TH1904

In contrast to Doxorubicin, TH1904

does not induce the expression of the myocardial pro-

inflammatory interleukin-6 (IL-6)

Cumulative doses injected into mice:

• Doxorubicin: 15-20 mg/kg

• TH1904: 72-180 mg/kg (Eq. Doxo: 24-60 mg/kg)

In Vivo Benefits

72



Untreated Doxorubicin TH1904

After 2 treatments

• No weight loss observed for TH1904 treated mice

In Vivo Benefits

73



• No significant effect of TH1904 on white blood cell counts (ex. Lymphocytes)

Vehicle Doxorubicin TH19040

2

4

6

8

Treatments

Lym

phocyte

s (

10

9/L

)

Higher normal limit

Lower normal limit

Lymphocytes counts after 3 treatments

TH1902: Docetaxel conjugate in Triple Negative Breast Cancer

Breast cancer

75

• Association between SORT1 expression and clinico-pathological parameters in breast

cancer

Breast cancer Sortilin +

PATHOLOGIC TYPES

- Invasive ductal carcinoma 79%

- Invasive lobular carcinoma 54%

BREAST CANCER SUBTYPES

- Luminal A 66%

- Luminal B 73%

- HER2+ 79%

- TNBC 59%

Overall,

in breast cancers,

expression of

SORT1 is about

66%vs

10-15%for HER2

expression

SORT1 expression

Triple-Negative Breast Cancer

76

• Most lethal form of breast cancer

• More frequently diagnosed in younger women (<40 years old)

• Higher risk of earlier relapse (42% will have rapid relapses within 5-10 years)

• Median survival from the time of developing metastases rarely >1 year

• Lack ER, PR and HER2 – no targeted therapies available

• Endocrine therapy and anti HER2 treatments are not effective

TNBC Patients

77

• TNBC patients with metastases in lymph nodes and high sortilin expression have a poorer

prognostic in ‘‘Relapse Free Survival’’

0 24 48 72 96 120 144 168 192 2160.2

0.4

0.6

0.8

1.0

1.2

(n = 161)

Time (months)

Fra

ctio

n s

urv

iva

l in

all

TN

BC

pa

tien

ts

Low Sortilin

High Sortilin

0 24 48 72 96 1200.2

0.4

0.6

0.8

1.0

1.2

(n = 72)

Time (months)

Fra

ctio

n s

urv

ival in

TN

BC

patie

nts

with

lym

ph

no

de

me

tasta

se

s

Low Sortilin

High Sortilin

ALL TNBC PATIENTS(n=161)

PATIENTS WITH LYMPH NODE METS(n=72)

Breast cancer

78

SORTILIN Expression in Breast Cancers

Normal

adjacent tissue

Infiltrating

duct carcinoma

Lymph Node

Metastasis carcinoma

In Vivo Validation

79

TH1902 (Triple-Negative Breast Cancer)

• Mice treated with Docetaxel received 3 treatments at 15mg/kg/week (MTD)

• Mice treated with TH1902 received 5 treatments at an equivalent dose of Docetaxel

0 5 10 15 20 25 30 35 40 45 50 55 60 65 700

200

400

600

800

Tx1 Tx2 Tx3 Tx4* Tx5*

Vehicle

Docetaxel (15 mg/kg, MTD)

DoceKA (1 eq.)

Days Post-Treatment

Tu

mo

r V

olu

me

(m

m3)

MDA-MB-231 xenografts study(IV administration)

TH1902

Tx4* Tx5*

TH1902

80

Eradication of breast tumors (IP administration)

Residual tumor burden

0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42 44 46 48 50 52 54 56 58 60 62 64 66 68 70 72 74 76 78

-20

-10

0

10

20

30

40

50

Vehicle

Docetaxel

KBA106

Days (post-treatments)

Lu

min

esce

nce

In

ten

sity (x1

06 R

FU

)

TH1902

Vehicle Docetaxel TH1902

Day-1

4 P

TD

ay-7

4 P

T

TH1902 treated mice:

• Luminescence is undetectable in 6/6 mice 46 days after last treatments

1 day in mice =

1 month in human

TH1902

81

Eradication of breast tumors

TH1902 treated mice:

• Luminescence is undetectable in 6/6 mice 46 days after last treatments

Docetaxel TH1902-100

0

100

200

300

400

Tum

or

lum

inescence p

rogre

ssio

n(%

of D

ay 0

level)

*

TH1902 Potent efficacy against TNBC

82

Strong inhibition of MDA-MB231 tumor growth at low dose

0 5 10 15 20 25 30 35 400

200

400

600

800

1000

Days Post-Treatment

Tum

or

Volu

mes (

mm

3)

Docetaxel (3.75 mg/kg,1/4 MTD)

TH1902 (8.75 mg/kg)

Vehicle

83

• After a single injection at MTD, Docetaxel induced a drastic reduction in neutrophil count

• Even after six TH1902 treatments at an equivalent Docetaxel dose, neutrophil count remained within normal limits

Docetaxel MTD: 15 mg/kg/week; 3 cycles

TH1902Docetaxel

0 1 3 6 0 1 3 60.0

0.5

1.0

1.5

2.0

(Number of treatments)

Docetaxel DoceKA

NANeutropenia

Ne

utro

ph

ils (1

09/L

)

TH1902Docetaxel

Absence of neutropenia after TH1902 treatment

Effect on body weight after 3 cycles (Day 19)

84

• Docetaxel : MTD 15 mg/kg/week

• TH1902 : Equivalent dose

Vehicle Docetaxel TH190280

90

100

110

*

Treatments

Weig

ht

(% o

f D

ay-0

)

Advantages of Theratechnologies’ Oncology Platform

85

INCREASED

EFFICACY

BETTER

TOLERABIILITY

TARGETED

THERAPY

FLEXIBLE

PLATFORM

Advantages of Theratechnologies’ Oncology Platform

86

Specifically targeting known drugs already tested in millions of patients

drastically reduces the risk of unfortunate surprises in

translating animal studies to human patients

Showing old drugs new tricks…

THANK YOU

Oncology Platform

88

Summary

1 Business model: Clinical POC in ovarian and TNBC cancers, large unmet medical

needs

2 Novel proprietary peptides for the targeted delivery of known and novel cancer

therapies

3 Use of well known cytotoxics, doxorubicin and docetaxel to reduce the development

risk

Oncology Platform

89

Summary

4 Targeted cancer treatment on Sortilin, a novel target involved in cellular

internalization/trafficking and cancer cells, over-expressed in several cancers

5 Initiation of Phase I studies in 2020

6 Targeting clinical Proof-of-Concept in humans in 2021

Q&A Oncology

Conclusion

THERATECHNOLOGIES

92

• Major turnaround in the last five years

• Grew from $4M in royalties and amortized revenues to over $60M in sales for the past 12 months

• Developed commercial activities in the USA

• Expanded to the EU

• Developed and gained approval for a new formulation: EGRIFTA SV

• Built an R&D pipeline

• Active on M&A

• Acquisition of Trogarzo commercial rights in the USA and the EU

• Acquisition of the Oncology Platform

Conclusion

THERATECHNOLOGIES

93

• Well positioned for significant growth

• Short term with Egrifta SV and Trogarzo in the USA

• Mid term with Trogarzo in the EU

• Longer term with our pipeline in NASH and in Oncology

Conclusion

THANK YOU

R&D Day - Theratech · R&D Day 2 Agenda Time Topic Presenter 12:00 Introduction Luc Tanguay...

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