IMMUNOMEDICS, INC.2).pdf · Immunomedics’ Next Generation ADC Technology Platform 1. Reduced toxicity 2. Greater dose of drug to tumor 3. Opportunity for long-term, repeated treatments

IMMUNOMEDICS, INC.

Advanced Antibody-Based Therapeutics

Oncology

Autoimmune Diseases

Jefferies 2015 Global Healthcare Conference

Peter P. Pfreundschuh, VP Finance and CFO

2

This presentation, in addition to historical information, contains certain forward-looking statements made pursuant to the Private Securities Litigation Reform Act of 1995. Such statements may involve significant risks and uncertainties, and actual results could differ materially from those expressed or implied herein. Factors that could cause such differences include, but are not limited to, new product development (including clinical trials outcome and regulatory requirements/actions); competitive risks to marketed products; forecasts of future operating results; availability of required financing and other sources of funds on acceptable terms, if at all; as well as those discussed in the Company's filings with the Securities and Exchange Commission.

Forward-Looking Statements

• Multiple late-stage opportunities in underserved markets

– Lead candidate represents potential next generation Lupus treatment

– Cancer programs focused on unmet need in difficult-to-treat tumors

– Two Phase 3 candidates and two Phase 2 candidates

• Next 18 months could be transformational

– Epratuzumab pivotal Phase 3 topline results expected in 1H15

– Initial IMMU-132 & IMMU-130 Phase 2 results very encouraging; evaluating Phase 3 strategy• Supports antibody-drug conjugate (ADC) technology platform• Valuable assets for partnering

– 90Y-clivatuzumab tetraxetan Phase 3 trial in pancreatic cancer expected to complete patient enrollment in 2016• Potentially first self-commercialized product, if approved

– Several additional ADCs identified to continue pipeline progress

3

Highlights

4

Research/Preclinical Phase 1 Phase 2 Phase 3

90Y-clivatuzumab tetraxetan

3+-line advanced pancreatic cancer Complete Phase 3 enrollment in 2016

Epratuzumab (humanized anti-CD22)

Systemic lupus erythematosus (SLE) Top-line data 1H15

Antibody-drug conjugates

IMMU-132: anti-TROP-2-SN-38 for metastatic solid tumors

IMMU-130: anti-CEACAM5-SN-38 for mCRC

Milatuzumab (anti-CD74) for cancer and autoimmune diseases

Multiple compounds for cancer and autoimmune diseases

Veltuzumab (anti-CD20) for cancer and autoimmune diseases

Other product candidates

Broad Pipeline of Antibody-Based Therapies

• A chronic autoimmune disease with no cure– ~650,000 patients diagnosed with primary SLE (systemic lupus

erythematosus) in the U.S. and E.U.*– ~$1 billion estimated size in major pharmaceutical markets**– Moderate to severe SLE represent ~70% of cases***

• SLE is caused when a patient’s immune system attacks normal, healthy tissue– Can attack heart, joints, skin, lungs, liver, kidneys, and CNS– Unexpected “flares” – Most common in women under 35

Key market needs:1. Control of flares to allow normal organ function and improve QoL2. Reduction in use of corticosteroids and other drugs3. Minimal side effects to allow chronic use

5 Sources: *NIH Diagnoses Data; **Systemic lupus erythematosus - 2014, Decision Resource, December 2014; ***New Harvard Guide to Women’s Health 2004

Lupus Market Opportunity

6

Common Lupus Treatments

Immunosuppressive to help control flares

Wide range of uses

Long-term effects of systemic immunosuppression, including increased potential for:• Diabetes

• Obesity

• High blood pressure

• Cataracts

• Osteoporosis

Contraindicated for pregnancy

First new lupus therapy in 50 years (approved 2011)

Reduces number of flares

No reduction in use of corticosteroids

Blackbox warning for mortality

Corticosteroids Benlysta

• Target doses demonstrated promising efficacy and safety

– Statistically significant higher responder rates vs. placebo (Total cycle = 2400mg)

– Safety profile similar to placebo

• Encouraging multi-year open-label extension experience

– Lupus disease activity maintained or further reduced

– Reduced dependence on corticosteroids

– No new safety signals observed in extended use

– Improved measures of health-related quality of life

7

Epratuzumab Phase 2 Summary

How Epratuzumab Is Designed to Work

• Lupus is caused by B-cells producing auto-antibodies that attack normal tissue

• In Blood publication, epratuzumab was shown to reduce B cells by 30-40% and connect B cells with an effector cell

• Designed to cause the transfer of B-cell antigens (including CD22) to the effector cell– The process is called

trogocytosis or “shaving”

• Without CD22, the B cells die (apoptosis)

8

• Double-blind, dose-ranging study in moderate to severe SLE

• Primary endpoint: Clinical activity response index at 12 weeks

– Index emphasizes BILAG; also includes SLEDAI, physician global assessment and treatment failure status

9 Wallace DJ, et al. Ann Rheum Dis. 2014 Jan;73(1):183-90

Open-Label Extension(all pts: 1200mg q2w x2 in 12 week treatment cycles)

Screening/Lead-in

N = 227 Primary Endpoint

0 Week 4 Week 8Week -2 1 2 3 Week 12

Minimum disease activity: ≥1 organ BILAG A, or ≥2 organs BILAG B

Treatment Phase

Ran

do

miz

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n

Dose Arm 4: 400mg q2w, wk: 0,2 (n=38)

Dose Arm 2: 1200mg q2w, wk: 0,2 (n=37)

Dose Arm 5: 1800mg q2w, wk: 0,2 (n=38)

Dose Arm 1: 600mg qw, wk: 0,1,2,3 (n=37)

Dose Arm 3: 100mg q2w, wk: 0,2 (n=39)

Placebo (n=38)

Phase 2b EMBLEM Study Design

• Statistically significant reduction in lupus disease activity versus placebo at 12 weeks with 2400mg treatment cycle (600mg qw)

– Combined 2400mg cycle arms (600mg qw + 1200mg q2w) produced a 12 week response rate of 43.2% (p = 0.02)

10 Wallace DJ, et al. Ann Rheum Dis. 2014 Jan;73(1):183-90.

p = 0.07

Doses selected for Phase 3 (EMBODY)

Response Rate at 12 Weeks

40.5%,

30.8%

23.7%

21.1%

45.9 %, p = 0.03Epratuzumab 600mg qw (n=37)

Epratuzumab 1200mg q2w (n=37)




Placebo (n=38)

26.3%

Results Point to Optimal Doses

• All open-label extension (OLE) patients received epratuzumab1200mg q2w x2 in 12-week treatment cycles

• Number of responders observed by week:

• No new safety signals were observed during the extension period

• Patients reported meaningful improvements in a number of health-related quality-of-life (HRQoL) measures

11 Presented at EULAR 2013 Congress

EMBLEM group OLE Screen Week 24 Week 48 Week 72 Week 96 Week 108

Placebo (n = 35) 9 13 14 17 15 12

Epratuzumab (n = 168) 57 59 60 62 55 58

Total (N = 203) 66 72 74 79 70 70

Treatment Responses Improved Through OLE

12 Presented at EULAR 2013 Congress

Median corticosteroid dose during EMBLEM open-label extension

Patients using <7.5mg/day rose from 36.5% to 58.0%

Reduced Steroid Use

• Two identical, double-blind, placebo-controlled registration studies in moderate to severe SLE

• Trial design highly similar to Phase 2b and its Open-Label Extension Trials

• Primary endpoint: Clinical activity response index at 48 weeks– Trials are fully enrolled – Top-line data expected 1H 2015

13

Screening/Lead-in

N = 1,560 Primary Endpoint

Cycle 1(Week 0)

Cycle 2(Week 12)

Cycle 3(Week 24)

Week -2 Week 48

Minimum disease activity: ≥1 organ BILAG A, or ≥2 organs BILAG B

Arm 1: 600mg qw x4 per 12 week cycle

Arm 2: 1200mg q2w x2 per 12 week cycle

Placebo

Cycle 4(Week 36)

Ran

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Phase 3 Design (EMBODY 1 & 2)

• Partnered with UCB worldwide

– Clinical and commercial milestones of up to $300 million

– Escalating double-digit tiered royalty on sales (mid-teens to mid-twenties)

– Development and commercialization funded by UCB

– Immunomedics retains global rights to all oncology indications

• UCB is a global leader in autoimmune and CNS disorders

– Ideal partner with experience in commercialization of products for autoimmune diseases

• Intend to submit marketing application in 2H15

14

Commercialization Plan

• Potential characteristics of difficult-to-treat tumors

– Not responsive to prior therapies– Protected by surrounding layer of connective tissue– Often become metastatic

• Components of IMMU’s antibody-drug conjugation platform (ADC)

– Highly specific MAb that is targeted to cancer cells– Specially designed “payload” drug that delivers a concentrated dose to the

tumor – A linker designed to release the payload at the tumor site

15

Immunomedics’ Next Generation ADC Technology Platform

1. Reduced toxicity

2. Greater dose of drug to tumor

3. Opportunity for long-term, repeated treatments

ADC Products - Targeting Difficult-to-Treat Tumors

• Unique approach to ADC therapeutics for cancer

– Highly cancer-specific antibodies based on 30 years of experience– Utilize moderately potent payloads: increased therapeutic index

• Proprietary linker for rapid payload release at or inside tumor

– High drug-to-antibody ratio (~7.6:1)

• SN-38 payload

– Active metabolite with more potency than its parent compound, irinotecan (a commonly used chemotherapy)

– ADCs’ unique chemistry avoids low solubility and selectively deliversSN-38 to the tumor

• Two ADCs completed Phase 2: IMMU-132 and IMMU-130

16

What Makes IMMU’s ADCs Different?

IMMU-132 delivers up to 135-fold more SN-38 to Capan-1 xenografts

than irinotecan

17

Keep in mind these facts:

• Mice convert irinotecan to SN-38 more efficiently than humans.

• Mice were given 22-fold more SN-38 equivalents with the irinotecan dose than the IMMU-132 dose, yet IMMU-132 delivers 135-fold more SN-38.

0 2 4 4 8 7 2

1 0 2

1 0 3

1 0 4

1 0 2

1 0 3

H o u rs

SN

-38

(n

g/g

)

IMM

U-1

32

-tre

ate

d a

nim

als

SN

-38

(ng

/g)

Irin

ote

ca

n-tr

ea

ted

an

ima

ls

IM M U -1 3 2 : S N -3 8

Ir in o te c a n -tre a te d : S N -3 8

AUClast (µg/g·h)

Irinotecan-treated IMMU-132-treated

0.40 54.25

Up to 135x Higher Delivery of SN-38

IMMU-132: Increased Payload Potency

Presented at World ADC San Diego 2014

• Mechanism of action– Binds TROP-2, which is highly expressed on many epithelial cancer

cells– IMMU-132 is internalized into the tumor cells before SN-38 is released

• Phase 1/2 clinical trial design – Conducted in patients with relapsed/refractory metastatic cancers:

breast, lung, esophageal, ovarian, prostate, lung, colorectal, others• U.S. Fast Track designation in triple-negative breast, non-small cell and small cell

lung cancers• U.S. Orphan Drug status in small-cell lung and pancreatic cancers

– Dosing on days one and eight of 21-day cycle

• Encouraging results from Phase 1/2 reported – Mild and manageable toxicity at recommended doses – Numerous objective responses or long-term disease stabilization in

heavily pretreated patients; including patients previously treated with topoisomerase inhibitors

– Multiple treatment cycles administered18

IMMU-132 Targets a Variety of Solid Tumors

19

Numberof Patients

% ORR1 % Disease Control Clinical BenefitPR + SD > 4 mo

Clinical BenefitPR + SD > 6 mo

TNBC 46 26% 74% 63% 46%

NSCLC 19 32% 74% 59%

SCLC 20 30% 55% 55% 37%

EAC 16 13% 56% 44%

1 Objective response rate (%ORR) = (Complete response + partial response)/number of patients.

Note: Clinical benefit and ORR do not include any patient currently pending, starting dose at 18 mg/kg , or who

received less than three doses and terminated early due to death or disease progression. Clinical benefit

calculations do not include patients with stable disease that have not been dosed > 4 months and > 6 months.

Meaningful responses in patients having multiple prior therapies, Phase 1 / 2 clinical trials

IMMU-132: Summary Efficacy (Patients with at least one post-baseline CT)

Presented at 2015 Annual Meeting of the American Association for Cancer Research in Philadelphia, PA, April 2015

25

5- 0

22

11

1- 0

29

25

5- 0

08

25

5- 0

25

25

2- 0

04

11

1- 0

18

25

5- 0

18

25

2- 0

09

25

5- 0

05

25

4- 0

12

25

5- 0

19

25

4- 0

17

25

2- 0

07

25

2- 0

01

11

1- 0

06

25

4- 0

19

11

1- 0

30

18

1- 0

04

25

5- 0

21

25

5- 0

27

25

4- 0

16

11

1- 0

13

25

5- 0

11

25

2- 0

10

25

5- 0

23

25

5- 0

29

20

4- 0

05

25

5- 0

24

25

5- 0

26

25

4- 0

09

25

2- 0

03

11

1- 0

02

25

5- 0

15

25

5- 0

04

25

5- 0

10

11

1- 0

33

20

4- 0

09

- 1 0 0

- 8 0

- 6 0

- 4 0

- 2 0

0

2 0

4 0

6 0

8 0

1 0 0

Be

st

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- 2 9 . 9 %

6 p a t i e n t s w i t h P D a r e n o t s h o w n b e c a u s e t h e y h a d a n e w l e s i o n

o r p r o g r e s s i o n o f n o n - t a r g e t l e s i o n s

L y m p h n o d e w a s s i n g l e t a r g e t le s io n t h a t d e c r e a s e d t o < 1 0 m m a t 1 s t a s s e s s m e n t ,

a n d w i t h d is a p p e a r a n c e o f 2 n o n - t a r g e t le s io n s , t h e p t i s c o n s id e r e d C R

20

IMMU-132: Best Response from TNBC Patients46 assessable, 21 continuing treatments 07 Apr 2015

Objective response (CR + PR) = 26%Disease control (CR + PR + SD) = 74%

CBR* [CR + PR + (SD > 6 mo)] = 17/37 (46%)CBR* [CR + PR + (SD > 4 mo)] = 27/43 (63%)

53 patients enrolled; 3 have not had their first assessment; 3 excluded because ≤2 doses given; 1

excluded because of 18 mg/kg starting dose.

*CBR, clinical benefit ratio.


(CR) = 2

(PR) = 10

(SD) = 22

(PD) = 12

Median prior chemotherapies = 4 (range, 1 – 11)

20

6- 0

06

18

1- 0

33

20

6- 0

17

25

2- 0

11

18

1- 0

40

11

1- 0

16

20

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20

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18

25

4- 0

13

20

6- 0

19

25

4- 0

14

25

4- 0

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20

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2 p t s w i t h P D n o t s h o w n b e c a u s e

t h e y h a d n e w le s io n .

s q u a m o u s c e l l h i s t o p a t h o l o g y ,

a l l o t h e r s a d e n o c a r c i n o m a

21

IMMU-132: Best Response from NSCLC Patients19 assessable 07 Apr 2015


CBR* [CR + PR + (SD > 4 mo)] = 10/17 (59%)

25 patients enrolled; 5 have not had their first assessment; 1 excluded because ≤2 doses given.



(CR) = 0

(PR) = 6

(SD) = 8

(PD) = 5

Median prior therapies = 3 (range, 1 – 8)

22

IMMU-132: Best Response from SCLC Patients20 assessable 07 Apr 2015


CBR* [CR + PR + (SD > 6 mo)] = 7/19 (37%)CBR* [CR + PR + (SD > 4 mo)] = 11/20 (55%)

22 patients enrolled; 1 excluded because ≤2 doses given; 1 excluded because of 18 mg/kg starting dose.



(CR) = 0

(PR) = 6

(SD) = 5

(PD) = 9

Median prior therapies = 2.5 (range, 1 – 7)

23

IMMU-132: Best Response from EAC Patients16 assessable 07 Apr 2015


CBR* [CR + PR + (SD > 4 mo)] = 7/16 (44%)

18 patients enrolled; 1 excluded because ≤2 doses given; 1 excluded because of 18 mg/kg starting dose.



(CR) = 0

(PR) = 2

(SD) = 7

(PD) = 7

24

• Camptosar (irinotecan) US Prescribing Information (USPI) “boxed warnings”

– Early and late forms of diarrhea can occur (Grades 3 & 4: 38%)

– Severe myelosuppression may occur (Neutropenia: Grades 3 & 4: 31%)

• No anti-antibody responses detected to-date, even after repeated dosing

• Minimal dose delays; 15%-16% of patients required dose reductions

Grade 3 Grade 4

Neutropenia 22 (18%) 7 (6%)

Anemia 7 (6%) 0

Fatigue 6 (5%) 0

Diarrhea 4 (3%) 0

Febrile neutropenia 3 (2%) 2 (2%)

Note: Grade 2 Alopecia N = 25 (20%)

Grade 3 Lymphopenia, WBC count decreased, and vomiting – 2 patients each

Grade 3 Asthenia, dizziness, and UTI – 1 patient each

Adverse events (Grades 3 and 4): Starting dose of 8 or 10 mg/kg (N=123)

IMMU-132: Mild, Predictable and Manageable Toxicity


• Mechanism of action

– Binds to CEACAM5 on colorectal and other tumor cells

– SN-38 is released locally from IMMU-130 for diffusion into tumor cells

• Two Phase 1 clinical trials

– Multiple dosing schedules evaluated

• Phase 2 clinical trial

– Enrolled relapsed/refractory metastatic colorectal cancer patients previously treated with one or more irinotecan regimens, some refractory to irinotecan regimens

– Patient follow-up continuing in 1H15

25

IMMU-130 in Metastatic Colorectal Cancer

26

IMMU-130-01 IMMU-130-02

Every other week Twice weekly Once weekly

PR = 1

SD = 4

PD = 7

Disease Control

5/12 (42%)

PR = 1

SD = 6

PD = 3

Disease Control

7/10 (70%)

PR = 0

SD = 3

PD = 1

Disease Control

3/4 (75%)

IMMU-130: Best Response Data (N=26)

Presented at 2014 ASCO and 2014 AACR

• Labeled with 90Y for potential first-in-class therapy

– Designed to selectively deliver radiation to pancreatic tumor tissue

– Under investigation in combination with low dose gemcitabine for enhanced activity

• Orphan Drug designation in the United States and EU

• Fast Track status with FDA

• Highly specific antibody targeting mucin antigen

– Does not bind to normal pancreas tissue or pancreatitis while reactive to ~85% of pancreatic cancers

• Global randomized, double-blind, Phase 3 study; completion of enrollment expected in 2016

• Product patent-protected

27

90Y-Clivatuzumab Tetraxetan: Phase 3 for PC

28

• Open label study in patients with metastatic pancreatic cancer who had received two or more prior therapies

– Study regimen: 6.5 mCi/m2 90Y-clivatuzumab tetraxetan qw x3 +/- low dose gemcitabine (200 mg/m2 qw x4)

• Encouraging overall survival trends with minimal toxicity of the combination therapy

Patients Alive at 3, 6, 9 and 12 Months

Final data presented at 2014 ASCO

Phase 1b: Initial Experience in Refractory PC

N 3 Months 6 Months 9 Months 12 Months

Arm A 29 14 (48%) 10 (34%) 6 (21%) 3 (10%)

Arm B 29 10 (34%) 3 (10%) 1 (3%) 0 (0%)

0

2

4

6

8

10

12

14

16

3 Months 6 Months 9 Months 12 Months

Nu

mb

er o

f P

atie

nts

Y-clivatuzumab tetraxetan + gemcitabine (Arm A)90

Y-clivatuzumab tetraxetan monotherapy (Arm B)90

• Double-blind, placebo-controlled, registration study in advanced pancreatic cancer patients who had received two or more prior therapies

– Prior therapy must include gemcitabine

• Primary endpoint: Overall survival

29

N = 440

Ran

do

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atio

n

Arm 1: 6.5mCi/m2 90Y-clivatuzumab tetraxetan qw x3 + 200mg/m2 gemcitabine qw x4 per 7-week cycle (n=293)

Arm 2: Placebo qw x3 + 200mg/m2 gemcitabine qw x4 per 7-week cycle (n=147)

Cycle 1 Cycle 3 Cycle 4 Cycle 5Cycle 2 Cycle 6(max)

90Y-Clivatuzumab Tetraxetan P3 Design (PANCRIT-1)

30

Financial Highlights (As of March 31, 2015)

Basic shares outstanding 93 million

Market capitalization $358 million

Debt (convertible senior notes) $100 million

Cash, cash equivalents and marketable securities $106 million

Forecast FY 2015 annual cash burn (6/30/15) $42 million

31

Program EventExpected

Timing

Epratuzumab Phase 3 top line data in SLE 1H15

IMMU-132 & IMMU-130

Additional Phase 2 data 2015

IMMU-132 Phase 3 clinical program decision 2H15

90Y-clivatuzumab tetraxetan

Complete Phase 3 enrollment in 3+-line pancreatic cancer 2016

Meaningful Upcoming Anticipated Milestones

Documents

IMMUNOMEDICS, INC.2).pdf · Immunomedics’ Next Generation ADC Technology Platform 1. Reduced toxicity 2. Greater dose of drug to tumor 3. Opportunity for long-term, repeated treatments