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Non-Confidential Overview
November 2017
CAELUMBIOSCIENCES
Forward Looking Statements
2
Statements in this presentation that are not descriptions of historical facts are forward‐looking statements
within the meaning of the “safe harbor” provisions of the Private Securities Litigation Reform Act of 1995.
We have attempted to identify forward‐looking statements by terminology including “anticipates,”
“believes,” “can,” “continue,” “could,” “estimates,” “expects,” “intends,” “may,” “plans,” “potential,” “predicts,”
“should,” or “will” or the negative of these terms or other comparable terminology. Forward‐looking
statements are based on management’s current expectations and are subject to risks and uncertainties that
could negatively affect our business, operating results, financial condition and stock price. Factors that could
cause actual results to differ materially from those currently anticipated are risks relating to: results of
research and development activities; uncertainties relating to preclinical and clinical testing; our growth
strategy; our ability to obtain, perform under and maintain financing and strategic agreements and
relationships; our dependence on third party suppliers; our ability to obtain, perform under and maintain
financing and strategic agreements and relationships; our ability to attract, integrate, and retain key
personnel; the early stage of products under development; our need for substantial funds; government
regulation; patent and intellectual property matters; and competition. We expressly disclaim any obligation
or undertaking to update or revise any statements contained herein to reflect any change in our
expectations or any changes in events, conditions or circumstances after the date of this presentation.
About Us
3
Caelum Biosciences is a clinical stage biotechnology companydeveloping treatments for rare and life-threateningconditions. Caelum’s lead asset, CAEL-101, is a novelpioneering antibody in Phase 1b clinical trials that is beingdeveloped for patients with Amyloid Light chain (AL)Amyloidosis.
Michael Spector, CEO
Potential Best-in-Class Antibody developed to clear amyloid deposits
Sustained clinically significant organ activity even after a single dose
Well-tolerated with no dose limiting toxicity
Rationally designed antibody clears both human AL λ and κ in preclinical studies
Ph1b ongoing - last patient dosed; expect results 2017
Preparing for Phase 3
Broad protection through IP and Orphan Drug and Biologics exclusivity
CAEL-101 Opportunity Overview in AL Amyloidosis
4
Amyloid Fibrils Formation in Tissue
5
Misfolded protein
AL Amyloidosis
patients
Misfolded proteins
collect together
Collection of
misfolded protein
creates Amyloid fibrils
Plasma Cells
Plasma
Cells
Produce
Proteins
Normal Protein
Bone
marrow
produce
plasma
cell
Bone
Amyloid Fibrils
deposit
in tissues
Normal Plasma Protein Cell Production
Mechanism of Amyloid Formation in Tissues
AL Amyloidosis Impact on Organs & Tissue
60%-80% of patients - leads to end-stage
kidney disease
65%-75% of patients - leads to heart failure
and high mortality
20%-45% of patients - peripheral neuropathy
leading to pain, numbness, and weakness
6
5%-35% - Other organs
AL Amyloidosis Opportunity: High Unmet Need and Large
Market Opportunity
7 Source: Kumar et al, Mayo Clinic Proc, 2011 86(1):12-8.
• 1 Year Mortality: 47%
• 5 Year Mortality: 72%
• Median Mortality: 1.5 Years
• Wall Street Analysts estimate a prevalent patient population of 30,000 – 40,000 patients split evenly between the U.S. and EU.
• It is estimated that there are approximately 3,000 – 4,000 new cases of AL amyloidosis annually in the United States, though actual incidence is likely higher as a result of under-diagnosis; a recent epidemiology study is illustrative (see next slide)
• An approved, successful therapy could represent a >$1.5B opportunity
Case Study: Underdiagnosis of AL Amyloidosis in England
8 1Pinney et. al.; Systemic amyloidosis in England: an epidemiological study; BJH 2013
National
Amyloidosis
Centre
Incidence of AL Amyloidosis by region
0 1.000.50
Correct diagnosis following referral appears to be a function of proximity to specialist center: Suggests that AL
Amyloidosis may be widely underdiagnosed
RegionPopulation (in
mm)
Incidence based on
newly diagnosed
caes at NAC1
Incidence
Reference to
London
England 51.4 0.52 71%
1 – East of England 5.7 0.56 77%
2 – East Midlands 4.4 0.47 64%
3 – London 7.7 0.73 100%
4 – Northeast 2.6 0.07 10%
5 – Northwest 6.8 0.35 48%
6 – South Central 4 0.64 88%
7 – Southeast Coast 4.3 0.55 75%
8 – Southwest 5.2 0.47 64%
9 – West Midlands 5.4 0.64 88%
10 – Yorkshire and the
Humber5.2 0.42 58%
Day-1 Day-14
Amyloid fibril suspensions sourced from human postmortem
samples were injected into mice to form amyloidomas. Mice
received either no treatment or 11-1F4 (CAEL-101).
Untreated Mice
CAEL-101
Treated Mice
Day-14Day-1
CAEL-101 expedites the clearance of AL amyloidoma in a
human PDx mouse model
9
CAEL-101: Rationally designed antibody
that clears both ALλ and κ deposits
Source: Hrncic et al, Am J Path 2000
CAEL-101 removes amyloidomas in mice bearing human
ALΚ & λ fibrils
10
1415
14
21
2425
28
4 4
89
17
24
28
0
5
10
15
20
25
30
κ-1 κ-2 λ-1 λ-2 λ-3 λ-4 λ-5
Days
Un
til C
leara
nce
Single Dose1 3
Untreated 11-1F4
Notes: Days until clearance of untreated vs 11-1F4 treated human amyloidoma deposits injected subcutaneously into mice
1. 100μg at day 0 2. 100 μg at days 0,2,4,6 . 11-1F4 are mAb designation
Source: Hrncic et al, Am J Path 2000
NT NT NT
24
2625
28
NT NT NT
9 9
67
0
5
10
15
20
25
30
κ-1 κ-2 λ-1 λ-2 λ-3 λ-4 λ-5
Days
Un
til C
leara
nce
Multiple Doses2 3
Untreated 11-1F4
CAEL-101-Mediated Clearance of Human ALκ and ALλ Amyloidomas in Mice
• GMP-grade amyloid fibril-reactive human IgG1 Fc chimeric mAb CAEL-101 was produced by NCI’s Biological Resource Branch for a Phase 1a/b trial
• Open-label, dose-escalation Phase 1a/b study of CAEL-101 (NCT02245867)
• Patients with relapsed or refractory AL Amyloidosis
• Primary Objective:
• Establish the maximum tolerated dose (up to 500 mg/m2) of CAEL-101
• Secondary Objectives:
• Demonstrate reduction in amyloid burden, as evidenced by decrease in affected organomegaly, and/or improved organ function
• Determine the pharmacokinetics of CAEL-101 when given as a single IV infusion (phase 1a) or as a series of weekly IV infusions (phase 1b)
• To determine the difference between 250mg/m2 and 500mg/m2
• https://clinicaltrials.gov/ct2/show/NCT02245867
Phase 1a/b Study of CAEL-101 (11-1F14) in Patients with AL
Amyloidosis presented at ASH 2016
11
Palladini et al reported a strong
correlation between reduction in amyloid
free light chains and survival in patients
treated with front line chemotherapy.
Cardiac morbidity is the major
determinant of survival in these patients
generally, and changes in cardiac function
after therapy can be reliably assessed
using the cardiac biomarker N-terminal
natriuretic peptide type B (NT-proBNP).
Changes in amyloid free light chain and
NT-proBNP predicted survival as early as 3
months after treatment initiation.
The international AL amyloidosis expert community is in agreement that the N-terminal fragment of the probrain natriuretic
peptide (NT-proBNP) is analytically validated and clinically qualified as a biomarker for use as a surrogate end point for survival
in patients with AL amyloidosis. (G Merlini et al, Leukemia, 2016)
12
NT-proBNP Associated with Survival in Amyloidosis Patients:
Potential for Surrogate Endpoint
CAEL-101 binds to
Liver and Bone
Amyloid Fibrils
Wall, JS et al. Blood. 2010 Sep 30;116(13):2241-4.
Distribution of CAEL-101 Antibody Binding
13
Radiolabeled
CAEL-101
Wall’s work shows that CAEL-101 successfully binds AL amyloid.
CAEL-101 Phase 1a/1b Organ Response Rates to Date
14
Renal Response Phase 1a
& 1b (n=8)
Cardiac Response Phase
1a & 1b (n=8)
Overall Responders
Best Organ Response
Phase 1a Phase 1b
12 Weeks
4 Weekly Doses
8 Weeks
Single Dose
63%Responders
70%
Responders
5/8 Patients
7/10 Patients
Responder Stable Progressor
>30% and >300
pg/ml decrease
in NT-proBNP
>30% and >300
pg/ml decrease in
NT-proBNP
63% 25% 12.5%
5/8
2/4 from Phase 1a
3/4 from Phase 1b
Patients
2/8Patients
1/8
Responder Stable Progressor
75% 25% 0%
6/8 Patients
2/4 from Phase 1a
4/4 from Phase 1b
2/8 Patients
>30% decrease
in proteinuria or a
decrease to <0.5
g/24 hours
>25% worsening
in eGFR
PATIENT 3 PROFILE
❖ Refractory λ AL Amyloidosis
❖ Baseline NT-proBNP approx. 13,000 ng/L
❖ Previous treatments: 1
❖ Best Hematologic response to chemotherapy: VGPR
❖ No Organ response to chemotherapy
❖ Persistently elevated NT-proBNP
❖ NYHA Class III
Organ response to CAEL-101
❖ NYHA Class I
❖ NT-proBNP Reduction to below 4,000 ng/L
Cardiac response (NT-proBNP) in a patient during Phase 1a/b
clinical trial of CAEL-101 antibody
15
Marked and Sustained Cardiac Response After Initial Dose of
CAEL-101
0
2,000
4,000
6,000
8,000
10,000
12,000
14,000
Mar-2015 Jun-2015 Sep-2015 Dec-2015 Mar-2016
NT
pro
-BN
P (
ng
/L)
Started
Phase 1a
CAEL-101 Started
Phase 1b
CAEL-101Wk
4Wk
8
Wk
5
Wk
8
Wk
12
PATIENT 7 PROFILE
❖ Refractory λ AL Amyloidosis
❖ Baseline 24-hr urine protein in mg/24hr: approx. 10,000
❖ Previous treatments: 6
❖ No Organ response to chemotherapy
❖ Persistence of significant proteinuria
Organ response to CAEL-101
❖ 24 hour urine protein in mg/24 hr: approx. 3,000
24 hour urine protein in a patient before and during
Phase 1a/b clinical trial of CAEL-101 antibody
16
Marked and Progressive Renal Response After Initial Dose of
CAEL-101
0
2,000
4,000
6,000
8,000
10,000
12,000
Apr-2015 Jul-2015 Oct-2015 Jan-2016 Apr-2016
24
hr
uri
ne p
rote
in (
mg
/24
hr)
Started
Phase 1a
CAEL-101Wk
5
Wk
8
Wk
12
Wk
8
Wk
4
Started
Phase 1b
CAEL-101
• Treatment with CAEL-101 is well tolerated and safe
• No drug-related grade 4 or 5 AEs or dose-limiting toxicity up to an MTD of 500mg/m2
• CAEL-101 is clinically efficacious and rapid-acting
• Early and sustained organ response even as a single infusion, or as a weekly infusion for 4 weeks: 70% response after 4 weekly doses
• Cardiac, Renal, GI, Skin and Soft tissue responses observed
• CAEL-101 represents a novel and promising adjunct to the treatment of AL Amyloidosis
• Safely promotes amyloid resolution in 67% of the patients to date
• Leads to improvement in organ function
Summary Clinical Data CAEL-101
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• Phase1b study in 2017: Awaiting final data report and PK analysis
• Finalize Phase 3 plan and prepare for trial launch
• Strategic Manufacturing Agreement with Patheon Biologics for clinical trial and commercial manufacturing
Next Steps
18
19
Broad exclusivity through IP and regulatory protection
Phase 3 to commence in 2018
Organ activity independent of light chain sub-type
Marked and sustained responses even after a single dose
No dose-limiting toxicity
Promising Phase 1a/1b data; results anticipated in 2017
Pioneering, rationally designed antibody
Strategic cGMP manufacturing agreement in place
Experienced Leadership Team
CAEL-101 Summary
20
Key Leadership
Lindsay Rosenwald, M.D. - Executive Chairman
Dr. Rosenwald has almost 25 years of experience as a biotechnology entrepreneur, including the
founding and recapitalization of numerous public and private biotechnology and life sciences
companies. In addition to serving as Caelum’s Executive Chairman, Dr. Rosenwald is Chairman,
President and CEO of Fortress Biotech, Caelum’s parent company. Dr. Rosenwald is also a Co-Portfolio
Manager and Partner at Opus Point Partners Management, LLC, a life-science focused asset
management firm. Before moving into his current positions, Dr. Rosenwald served as Chairman of
Paramount BioCapital, Inc. Dr. Rosenwald received an M.D. from Temple University School of Medicine
and a B.S. in finance from Pennsylvania State University.
Michael Spector - President and Chief Executive Officer
Mr. Spector was named President and Chief Executive Officer of Caelum in January 2017. Previously, Mr.
Spector served as Senior Vice President, Global Commercial Operations at Iroko Pharmaceuticals. Earlier in
his career, he spent 15 years at GlaxoSmithKline in multiple senior management positions, including Vice
President and General Manager of GlaxoSmithKline South Africa, where he led the overall business
strategy and was elected to run the South African Pharmaceutical Manufacturers Association. Mr. Spector
holds an M.B.A. from Rider University in Lawrenceville, N.J. and a B.S. in biology from the University of
Pittsburgh. He also serves on the Board of Directors of Jacaranda Health, a nonprofit organization that
seeks to transform maternal and neonatal healthcare in East Africa.
Elisabeth Leiderman, M.D., M.B.A. – Vice President, Corporate Development
Dr. Leiderman has 20 years of experience working in the healthcare industry. Since January 2017, Dr.
Leiderman has served as Vice President and Head of Corporate Development at Caelum which is a
subsidiary of Fortress Biotech. Prior to joining industry, Dr. Leiderman worked as a Healthcare Investment
Banker, where she most recently was an Executive Director at Nomura Securities. She spent close to 10
years on Wall Street and held prior roles at UBS and Credit Suisse. She has covered life science companies
and advised clients on M&A, Equity and Debt transactions. Dr. Leiderman earned her B.A. at The
University of Pennsylvania, her M.D. from Sackler Medical School at Tel-Aviv University and her MBA from
The Wharton School. Dr. Leiderman is an employee of Fortress Biotech and provides services to Caelum
Biosciences pursuant to a Management Services Agreement between Fortress Biotech and Caelum
Biosciences.
Suzanne Lentzsch, M.D., Ph.D. – Scientific Advisory Board Chair
Professor of Medicine at College of Physicians and Surgeons, Columbia University
Director, Multiple Myeloma and Amyloidosis Service Columbia Univ Medical Center
Dr. Lentzsch is Professor of Medicine and the Director of the Multiple Myeloma and Amyloidosis Service at
New York Presbyterian Hospital/ Columbia University Medical Center, New York. After receiving her
degrees from the Humboldt University/ Charité Berlin, Germany, she completed her residency and
fellowship at Humboldt University and a research fellowship, studying the mechanism of action of
thalidomide and its derivatives in multiple myeloma, in the Jerome Lipper Multiple Myeloma Center under
the mentorship of Dr Kenneth Anderson at the Dana-Farber Cancer Institute, Boston. Dr. Lentzsch was
recruited in August 2004 to the University of Pittsburgh and the University of Pittsburgh Cancer Institute.
Her translational research focuses on the identification of novel targets for the treatment of Multiple
Myeloma, Multiple Myeloma bone disease and amyloidosis. Her innovative research in amyloidosis
resulted in a series of translational clinical trials, including the establishment of new treatments for
relapsed AL amyloidosis in a multicenter trial investigating bendamustine.