IMMUNOMEDICS, INC.
Advanced Antibody-Based Therapeutics
Oncology
Autoimmune Diseases
February 2015
Forward-Looking Statements
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.
2
Highlights
• 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 data for pancreatic cancer
expected in 2016
• Potentially first self-commercialized product, if approved
– Several additional ADCs identified to continue pipeline progress
3
Broad Pipeline of Antibody-Based Therapies
Research/Preclinical
Phase 1
Phase 2
Phase 3
Epratuzumab (humanized anti-CD22)
Systemic lupus erythematosus (SLE)
90Y-clivatuzumab
Top-line data 1H15
tetraxetan
3+-line advanced pancreatic cancer
Complete Phase 3 enrollment 2H15
Antibody-drug conjugates
IMMU-132: anti-TROP-2-SN-38 for metastatic solid tumors
IMMU-130: anti-CEACAM5-SN-38 for mCRC
Other product candidates
Veltuzumab (anti-CD20) for cancer and autoimmune diseases
Milatuzumab (anti-CD74) for cancer and autoimmune diseases
Multiple compounds for cancer and autoimmune diseases
4
Lupus Market Opportunity
• A chronic autoimmune disease with no cure
– ~650,000 patients diagnosed with primary SLE (systemic lupus
erythematosus) in the U.S. and E.U.*
– 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.
2.
3.
5
Control of flares to allow normal organ function and improve QoL
Reduction in use of corticosteroids and other drugs
Minimal side effects to allow chronic use
Sources: *NIH Diagnoses Data; **New Harvard Guide to Women’s Health 2004
Common Lupus Treatments
Corticosteroids
ü Immunosuppressive to help
control flares
ü Wide range of uses
ü First new lupus therapy in 50
years (approved 2011)
ü Reduces number of flares
û Long-term effects of systemic
immunosuppression, including
increased potential for:
û No reduction in use of
corticosteroids
û Blackbox warning for mortality
•
•
•
•
•
Diabetes
Obesity
High blood pressure
Cataracts
Osteoporosis
û Contraindicated for pregnancy
6
Benlysta
Epratuzumab Phase 2 Summary
• Target doses demonstrated promising efficacy and safety
– Statistically higher responder rates vs. placebo (Total cycle = 2400mg)
– Safety profile similar to placebo
• Encouraging multi-year open-label extension experience
–
–
–
–
7
Responder rates maintained or further reduced
Reduced dependence on corticosteroids
No new safety signals observed in extended use
Improved measures of health-related quality of life
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
–
•
8
The process is called
trogocytosis or “shaving”
Without CD22, the B cells die
(apoptosis)
Phase 2b EMBLEM Study Design
•
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
N = 227
Dose Arm 1: 600mg qw, wk: 0,1,2,3 (n=37)
Screening/
Lead-in
Dose Arm 2: 1200mg q2w, wk: 0,2 (n=37)
Randomization
Minimum
disease
activity:
≥1 organ
BILAG A, or
≥2 organs
BILAG B
Primary Endpoint
Dose Arm 3: 100mg q2w, wk: 0,2 (n=39)
Dose Arm 4: 400mg q2w, wk: 0,2 (n=38)
Dose Arm 5: 1800mg q2w, wk: 0,2 (n=38)
Open-Label Extension
Placebo (n=38)
Week -2
9
Source: ACR 2010 Wallace
0
1
2
3 Week 4
Treatment Phase
(all pts: 1200mg q2w x2 in
12 week treatment cycles)
Week 8
Week 12
Results Point to Optimal Doses
•
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)
Response Rate at 12 Weeks
45.9 %, p = 0.03
Epratuzumab 600mg qw (n=37)
40.5%, p = 0.07
Epratuzumab 1200mg q2w (n=37)
Epratuzumab 100mg q2w (n=39)
Epratuzumab 400mg q2w (n=38)
Epratuzumab 1800mg q2w (n=38)
Placebo (n=38)
10
Source: ACR 2010 Wallace
30.8%
26.3%
23.7%
21.1%
Doses selected for
Phase 3 (EMBODY)
Treatment Responses Improved Through OLE
11
•
All open-label extension (OLE) patients received epratuzumab
1200mg q2w x2 in 12-week treatment cycles
•
Number of responders observed by week:
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
•
No new safety signals were observed during the extension period
•
Patients reported meaningful improvements in a number of healthrelated quality-of-life (HRQoL) measures
Presented at EULAR 2013 Congress
Reduced Steroid Use
Median corticosteroid dose during EMBLEM open-label extension
Patients using <7.5mg/day rose from 36.5% to 58.0%
12
Presented at EULAR 2013 Congress
Phase 3 Design (EMBODY 1 & 2)
•
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
N = 1,560
Primary Endpoint
Minimum
disease
activity:
≥1 organ
BILAG A, or
≥2 organs
BILAG B
Week -2
13
Randomization
Screening/
Lead-in
Cycle 1
(Week 0)
Arm 1: 600mg qw x4 per 12 week cycle
Arm 2: 1200mg q2w x2 per 12 week cycle
Placebo
Cycle 2
(Week 12)
Cycle 3
(Week 24)
Cycle 4
(Week 36)
Week 48
Commercialization Plan
• Partnered with UCB worldwide
– Clinical and commercial milestones of up to $300 million
– Escalating double-digit tiered royalty on sales (mid-teens to midtwenties)
– 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
ADC Products - Targeting Difficult-to-Treat Tumors
•
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
Immunomedics’ Next Generation ADC Technology Platform
1. Reduced toxicity
2. Greater dose of drug to tumor
3. Opportunity for long-term, repeated treatments
15
What Makes IMMU’s ADCs Different?
•
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 delivers SN-38 to
the tumor
•
16
Two ADCs completed Phase 2: IMMU-132 and IMMU-130
IMMU-132: Increased Payload Potency
Up to 135x Higher Delivery of SN-38
SN-38 (ng/g)
IMMU-132-treated animals
SN-38 (ng/g)
Irinotecan-treated animals
AUClast (µg/g·h)
Irinotecan-treated
IMMU-132-treated
0.40
54.25
IMMU-132 delivers up to 135-fold
more SN-38 to Capan-1 xenografts
than irinotecan
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.
17
IMMU-132 Targets a Variety of Solid Tumors
•
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 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
•
18
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 administered
IMMU-132-01: Summary Efficacy
(Patients1 with at least one post-baseline CT)
Meaningful responses in patients having multiple
prior therapies, Phase I / II clinical trials
1
Number of
Pts
% ORR1
% Disease
Stabilization
Clinical Benefit
PR + SD > 4 mo
Clinical Benefit
PR + SD > 6 mo
TNBC
23
30%
70%
52%
40%
NSCLC
7
43%
86%
43%
43%
SCLC
13
23%
39%
31%
31%
CRC
26
4%
58%
46%
24%
%ORR = (CR+PR)/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 SD
that have not been dosed > 4 months and > 6 months.
19
IMMU-132-01 Patients with TNBC
Best response (N = 31 assessable)
Disease stabilization (CR + PR + SD) = 71% (22/31)
11
10
25 29
50
25 08
50
25 05
50
11 18
10
25 18
40
25 12
20
25 01
50
25 19
40
11 17
10
18 06
10
25 04
50
25 21
40
11 16
10
25 13
50
20 11
40
25 05
50
25 15
40
11 09
10
25 02
50
25 04
50
20 10
400
9
Best Response (% change from baseline)
ORR = 23% (7/31)
CBR* (PR + SD > 4 mo) = 54%
CBR* (PR + SD > 6 mo) = 39%
44 pts enrolled, 31 assessable on 07Jan15. 13 pts not included: 9, too early for 1st assessment; 2
received ≤2 doses, 1 received 18 mg/kg, 1 received XRT to relieve pain in region of TL.
*CBR, clinical benefit ratio.
20
Source: World ADC San Diego, Oct-2014
IMMU-132: Mild, Predictable and Manageable Toxicity
Adverse events (Grades 3 and 4): Starting dose of 8 or 10 mg/kg (N=123)
Grade 3
Grade 4
22 (18 %)
7 (6%)
Anemia
7 (6 %)
0
Fatigue
6 (5 %)
0
Diarrhea
4 (3 %)
0
Febrile neutropenia
3 (2 %)
2 (2 %)
Neutropenia
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
• Camptosar (irinotecan) US Prescribing Information (USPI) “boxed warnings”
– Early and late forms of diarrhea can occur (Grade 3&4: 31 %)
– Severe myelosuppression may occur (Neutropenia Grade 3&4: 26-31 %)
• No anti-antibody responses detected to-date, even after repeated dosing
• Minimal dose delays; 15% dose reductions
21
Source: World ADC San Diego, Oct-2014
IMMU-130 in Metastatic Colorectal Cancer
22
•
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
IMMU-130 Best Response Data (N=26)*
IMMU-130-01
23
IMMU-130-02
Every other week
Twice weekly
Once weekly
PR = 1
SD = 4
PD = 7
PR = 1
SD = 6
PD = 3
PR = 0
SD = 3
PD = 1
Disease Control
5/12 (42%)
Disease Control
7/10 (70%)
Disease Control
3/4 (75%)
* Presented at 2014 ASCO annual meeting.
90Y-Clivatuzumab Tetraxetan: Phase 3 for PC
• 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 2H2015
• Product patent-protected
24
Phase 1b: Initial Experience in Refractory PC
• 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:
100
100%
90 Y-clivatuzumab tetraxetan +
gemcitabine (Arm A)
90 Y-clivatuzumab tetraxetan monotherapy (Arm B)
80
80%
Median survival Arm A = 3.9 months
Median survival Arm B = 2.8 months
p = 0.020
60
60%
40
40%
20
20%
0%
0
25
5
10 Months
90Y-Clivatuzumab Tetraxetan P3 Design (PANCRIT-1)
• 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
Randomization
N = 440
Cycle 1
26
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 2
Cycle 3
Cycle 4
Cycle 5
Cycle 6
(max)
Financial Highlights (As of December 31, 2014)
Basic shares outstanding
Market capitalization
Debt
27
93 million
$447 million
-
Cash, cash equivalents and marketable
securities
$21 million
Forecast FY 2015 annual cash burn
(6/30/15)
$41 million
Meaningful Upcoming Anticipated Milestones
Program
Expected
Timing
Epratuzumab
Phase 3 top line data in SLE
1H15
IMMU-132 &
IMMU-130
Additional Phase 2 data
2015
Phase 3 clinical program decision
2H15
Phase 3 top line data in 3+-line pancreatic cancer
2016
IMMU-132
90Y-clivatuzumab
tetraxetan
28
Event