UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549
FORM 8-K
CURRENT REPORT
Pursuant to Section 13 or 15(d) of
the Securities Exchange Act of 1934
Date of report (Date of earliest event reported): January 9, 2017
SELECTA BIOSCIENCES, INC.
(Exact name of registrant as specified in its charter)
Delaware | 001-37798 | 26-1622110 | ||
(State or other jurisdiction of incorporation or organization) | (Commission File Number) | (I.R.S. Employer Identification No.) | ||
480 Arsenal Way
Watertown, MA 02472
(Address of principal executive offices) (Zip Code)
(617) 923-1400
(Registrant’s telephone number, include area code)
N/A
(Former Name or Former Address, if Changed Since Last Report)
Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions
o | Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425) |
o | Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12) |
o | Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b)) |
o | Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c)) |
Item 7.01. Regulation FD Disclosure.
Selecta Biosciences, Inc. (the “Company”) from time to time presents and/or distributes to the investment community at various industry and other conferences slide presentations to provide updates and summaries of its business. A copy of its current corporate slide presentation is attached to this Current Report on Form 8-K as Exhibit 99.1. The Company undertakes no obligation to update, supplement or amend the materials attached hereto as Exhibit 99.1.
The information in Item 7.01 of this Form 8-K, including Exhibit 99.1 attached hereto, shall not be deemed “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended (the “Exchange Act”) or otherwise subject to the liabilities of that section, nor shall it be deemed incorporated by reference in any filing under the Securities Act of 1933, as amended, or the Exchange Act, except as expressly set forth by specific reference in such a filing.
Item 9.01. Financial Statements and Exhibits.
(d) Exhibits
Exhibit No. | Description | |||
99.1 | Corporate slide presentation of Selecta Biosciences, Inc. dated January 2017 | |||
SIGNATURES
Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.
SELECTA BIOSCIENCES, INC. | ||
Date: January 9, 2017 | By: | /s/ Werner Cautreels, Ph.D. |
Werner Cautreels, Ph.D. | ||
President and Chief Executive Officer | ||
EXHIBIT INDEX
Exhibit No. | Description | |||
99.1 | Corporate slide presentation of Selecta Biosciences, Inc. dated January 2017 | |||
January 2017
Corporate Presentation
Safe Harbor / Disclaimer
Any statements in this presentation about the future expectations, plans and prospects of Selecta Biosciences, Inc. (“the
company”), including without limitation, statements regarding the development of its pipeline, the company's expectations about
receiving payments from Spark Therapeutics, Inc. under the license agreement, the progress of the Phase 1/2 clinical program
of SEL-212 including the number of centers in the Phase 2 clinical trial of SEL-212 and the announcement of data, conference
presentations, the ability of the company’s SVP platform, including SVP-Rapamycin, to mitigate immune response and create
better therapeutic outcomes, the potential treatment applications for products utilizing the SVP platform in areas such as gene
therapy and oncology, any future development of the company’s discovery programs in peanut allergy and celiac disease, the
sufficiency of the company’s cash, cash equivalents, investments, and restricted cash and other statements containing the
words “anticipate,” “believe,” “continue,” “could,” “estimate,” “expect,” “hypothesize,” “intend,” “may,” “plan,” “potential,” “predict,”
“project,” “should,” “target,” “would,” and similar expressions, constitute forward-looking statements within the meaning of The
Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by such forward-
looking statements as a result of various important factors, including, but not limited to, the following: the uncertainties inherent
in the initiation, completion and cost of clinical trials including their uncertain outcomes, the availability and timing of data from
ongoing and future clinical trials and the results of such trials, whether preliminary results from a particular clinical trial will be
predictive of the final results of that trial or whether results of early clinical trials will be indicative of the results of later clinical
trials, the unproven approach of the company’s SVP technology, potential delays in enrollment of patients, undesirable side
effects of the company’s product candidates, its reliance on third parties to manufacture its product candidates and to conduct
its clinical trials, the company’s inability to maintain its existing or future collaborations or licenses, its inability to protect its
proprietary technology and intellectual property, potential delays in regulatory approvals, the availability of funding sufficient for
its foreseeable and unforeseeable operating expenses and capital expenditure requirements, substantial fluctuation in the price
of its common stock, a significant portion of the company’s total outstanding shares have recently become eligible to be sold
into the market, and other important factors discussed in the “Risk Factors” section of the company’s Quarterly Report on Form
10-Q filed with the Securities and Exchange Commission, or SEC, on November 10, 2016, and in other filings that the company
makes with the SEC. In addition, any forward-looking statements included in this presentation represent the company’s views
only as of the date of its publication and should not be relied upon as representing its views as of any subsequent date. The
company specifically disclaims any obligation to update any forward-looking statements included in this presentation.
2
Pioneering Precision Immune System Communication
for Rare and Serious Diseases
Clinical-Stage Company focused on addressing the
immunogenicity caused by biologic treatments
Lead Program in Phase 2 with initial data expected
in the first half of 2017
Upside Potential with immune stimulating programs being
developed via non-dilutive funding
Proprietary Product Pipeline based on antigen-specific
immune modulating technology platform
Significant Partnership & Licensing Potential for
enzyme therapies, gene therapies, oncology, etc.
3
The Experts Agree Immunogenicity is a Serious
Challenge to Biologic Therapy Development
COMPROMISED EFFICACY
Anti-drug antibody
(ADA) formation neutralizes
therapeutic benefits
4
UNPREDICTABLE
RESPONSE
Changed PK/PD through
drug-ADA interaction
SAFETY RISK
Hypersensitivity reactions
can impact patients
I M M U N O G E N I C I T Y ’ S I M P A C T
“For the gene therapies
today in clinical
development that apply
AAV-vectors systemically,
no repeat dose is possible
due to neutralizing
antibodies.”
– Federico Mingozzi, PhD
INSERM, France
“Immunological
responses are a
significant risk in CRIM-
negative infantile Pompe
disease; thus induction of
immune tolerance in the
naive setting should
strongly be considered.”
– Priya Kishnani, MD ea
Duke University
“Hemophilia A
patients with
inhibitors to Factor
VIII replacement
therapy are the
hardest and most
expensive patient
group to treat.”
– David Scott, PhD
Uniformed Services
University
“Clinical trial results point to a
direction in targeted cancer
therapy, whereby improved
clinical responses might occur
through combining
immunotoxin therapy with
immune modulation.”
– Raffit Hassan, MD ea
Uniformed Services University
“Prophylactic immune tolerance induction should be strongly considered in patients who are at risk of developing immune
responses to ERT.”
– Amy Rosenberg, MD, Director of the FDA’s Office of Biotechnology Products
R&D
Failures
Clinical Trial
Failures
Limited Market
Uptake
5
Current patient population
Potential patient population for biological drugs
Enable new
technologies
Enhance
existing drugs
Rescue failed
drugs
Expand
patient use
Enable new
classes of drugs
Our Mission: Unlocking the Full Potential of Biologics
SVP Technology
Today’s Target Patient Population for Biologic Drugs
IMAGINE IF
WE COULD…
1. Effectively treat many more
patients with existing biologics
2. Enable a host of new disease
treatments for patients with
rare and serious conditions
6
The Key: Precise Communication
with the Immune System
Targeting
immune
cells
Sending
precise
instructions
Implementing
the message
Eliciting an
amplified response
Taken up by
dendritic cells,
which initiate
and regulate
immune responses
Deliver a message
of immune tolerance
or activation by
controlled release of
immunomodulator
inside the immune cell
Activate antigen-
specific T cells
Induce regulatory T
cells to mitigate
undesired immune
responses
7
Mitigating the Formation of Anti-Drug Antibodies
by Inducing Regulatory T Cells
8
Potential to enable new therapies and improve efficacy/safety of existing biologics
Regulatory T cell
Naïve T cell
Lymph Node
B cell
Helper T cell
Targeting
immune
cells
Dendritic cellSending
precise
instructions
Implementing
the messageTolerogenic
Response to
Biologic Drug
(Antigen)
Prevention of ADAs
SVP-Rapamycin Biologic drug
Platform Designed to be Utilized Broadly
9
IMMUNE TOLERANCE SVP
Encapsulated
Rapamycin
Encapsulating
Nanoparticle
PLA+PLA-PEG
Targeted
Immunotoxins AntibodiesViral VectorsEnzymes
SVP-Rapamycin’s preclinical, clinical and manufacturing data can
be applied across a broad range of product candidates
10
Example of Immune System Education
Advate-Specific ADAs
Day 0 7 14 21 28 57 81 123 143 187
Advate Advate Advate Advate Advate
T im e (D a y s )
A
n
ti
-F
V
II
I
a
n
ti
b
o
d
y
(
µ
g
/m
l)
0 5 0 1 0 0 1 5 0 2 0 0
0
2 0
4 0
6 0
8 0
*******
Teach + Treat Treat
Empty Nanoparticle + Advate
or
SVP-Rapamycin + Advate
SVP
Rapamycin
Advate
SVP-Rapamycin
Empty NP Advate
Empty NP
Antigen specificity
A
n
ti
-P
h
iX
1
7
4
A
b
(
O
D
)
E m p ty N P S V P
0 .0
0 .2
0 .4
0 .6
0 .8
1 .0
Antigen-Specific Tolerance Maintained for Over Five Months in Hemophilia A Mice
SEL-212
Refractory and chronic
tophaceous gout
Methylmalonic Acidemia
(MMA) - Anc80 Vector
Ornithine
Transcarbamylase (OTC)
Deficiency – AAV Vector
Significant Platform Building Opportunity
Therapeutic
Enzymes
Gene
Therapy
Oncology
• Myozyme (Pompe)
• IgA Protease
• Other ERT
• Additional Anc80
programs
• Other gene therapies
• Gene editing
• Immunotoxins
• Antibody drug
conjugates
• Factor VIII
• Anti-TNF antibodies
• Bispecific antibodies
Proprietary programs accelerate development, increase value, enable expansion
Other
Biologics
C U R R E N T P R O P R I E T A R Y P I P E L I N E
(proprietary, collaborations and/or licenses)
P O T E N T I A L E X P A N S I O N
11
Product Candidate Selection Framework
Immunogenicity Barrier for target drug/candidate that has
underlying potential for efficacy
Rare and Serious Disease with a high unmet need
Clear Clinical and Regulatory Path based upon the strength of
pre-clinical data and established clinical endpoints
Ownership of a biologic product/candidate that can be combined
with SVP to generate a solid ROI
12
Immune Tolerance Pipeline
Indication Description Preclinical Phase 1 Phase 2
Proprietary ADA Mitigation Programs
Refractory Gout
SVP-Rapamycin
co-administered with
pegsiticase (SEL-212)
Methylmalonic Acidemia
(MMA)
SVP-Rapamycin
co-administered with
Anc80 vector
Ornithine
Transcarbamylase
Deficiency (OTC)
SVP-Rapamycin
co-administered with
AAV vector
ADA Mitigation Program Collaboration
Mesothelioma &
Pancreatic Cancer
SVP-Rapamycin
co-administered with
LMB-100
ADA Mitigation Program License
Hemophilia A
SVP-Rapamycin licensed
for FVIII gene therapy
13
Therapeutic Enzymes
Potential to treat many rare and serious diseases with
enzyme replacement and microbial enzyme therapies
High immunogenicity seen in response to virtually all
enzyme replacements for lysosomal storage diseases
Most are foreign to the patient’s immune system and
can provoke immune responses
No alternative/rescue therapies for patients developing
ADAs in most cases
Enzyme Therapy’s Immunogenicity Challenges
ADAs known to negatively impact therapeutic half-life,
activity, cellular localization and/or safety
15
Developing SEL-212: The First Non-Immunogenic
Uricase Enzyme Product Candidate
Immunogenicity Barrier
▪ Uricase is highly effective in breaking down uric acid deposits, but is foreign to the
human immune system, causing immunogenicity
▪ Two approved products (Krystexxa and Elitek) cause neutralizing antibodies in
~60% of patients and carry risk for anaphylaxis
Rare and Serious Disease
▪ ~160,000 adults with severe gout treated by U.S. rheumatologists
▪ Debilitating flares and joint-damaging arthritis caused by uric acid deposits; risk of
renal and cardiovascular disease
Clear Clinical Path
▪ Krystexxa approved with less than 500 patients dosed from phase 1-3
▪ Primary endpoint: serum uric acid level reduction – a robust FDA/EMA-approved
biomarker endpoint – can be seen rapidly upon dosing, easy to measure,
maintenance strongly correlated with low/negative ADA titers
▪ Adult patient population with rapid enrollment potential
Ownership
▪ In-licensed pegsiticase in 2014; combined with SVP-Rapamycin to form SEL-212
16
No/not
diagnosed tophi
Severe Gout is a Rare and Serious Disease
with Substantial Unmet Needs
8.3
3.1
5.2 4.7
0.5
US Gout
Patients
Rx Treated
Primary
Care, Endo,
Nephro,
Other
Rheum*
Gout Patient Stocks (million)1
530,000
370,000
Estimated SEL-212 Target Patient Population1
US Gout treated at
Rheum
Est. SEL-212
patient pool
Un-
diagnosed or
no Rx
treatment
US Gout
Prevalence
* Rheumatologists see estimated 10% of treated gout patients
(1) Source: IMS, Desk Research, Selecta Rheum interviews, Crystal
patient registry
(2) Includes an estimated 50,000 patients with chronic refractory gout
(3) Source: HK Choi JAMA 2016
Gout
Rheumatoid arthritis
Gout Hospitalizations and Cost Per Patient Have Surpassed RA Hospitalizations3
Costs per patient
$58,003
$55,988
$34,457
$83,101
Gout
Rheumatoid
Arthritis
2001 2011
160,0002
17
SEL-212 Phase 1/2 Clinical Program
Status
Phase 1b
Phase 1a
Phase 2
Patient visits
complete
Data presented in
December 2016
Trial complete
Both goals
achieved
Patient dosing
started in
October 2016
Objective
Demonstrate that
SEL 212:
Mitigates ADAs
Enables
prolonged control
of uric acid
Define effective
dose of
pegsiticase
Demonstrate
formation of
ADAs
Demonstrate
safety, tolerability
and ability to
reduce serum uric
acid after multiple
doses of SEL-212
Trial Design
• n = 63
• Single dose of SEL-212
• Patients with hyperuricemia
• n = 22
• Single dose of pegsiticase
• Patients with hyperuricemia
• n = 36+
• 3 monthly doses of SEL-212;
then 2 of pegsiticase alone
• Symptomatic gout patients with
hyperuricemia
18
Phase 1b Multicenter U.S. Clinical Trial
19
Clinicaltrials.gov NCT02648269
*Excludes exploratory group of 5 patients at 0.03 mg/kg SEL-212
0.5 mg/kg SVP-Rapamycin
0.3 mg/kg SVP-Rapamycin
0.1 mg/kg SVP-Rapamycin
0.03 mg/kg SVP-Rapamycin
0.3 mg/kg SEL-212
0.03 mg/kg SEL-212
Pegsiticase alone
0.15 mg/kg SEL-212
0.1 mg/kg SEL-212
N=5
N=7
N=7
N=7
N=7
N=5
N=5
N=5*
N=5+5
Pegsiticase alone
(0.4mg/kg)
Single ascending dose
of SVP-Rapamycin
Single ascending dose
of SVP-Rapamycin
combined with 0.4
mg/kg pegsiticase
20
0
2
4
6
8
1 0
0
2
4
6
8
1 0
0
2
4
6
8
1 0
S
e
ru
m
U
ric
A
cid
(
m
g
/d
L
)
0
2
4
6
8
1 0
0
2
4
6
8
1 0
Day
0 7 14 21 30
Loss of control over
serum uric acid
levels by day 14
No effect on serum
uric acid levels
Dose-dependent
reduction in serum
uric acid levels
0.03 mg/kg SVP-Rapamycin
0.4 mg/kg Pegsiticase
0.10 mg/kg SVP-Rapamycin
0.4 mg/kg Pegsiticase
0.4 mg/ kg Pegsiticase only
0.03, 0.1, 0.3 mg/kg
SVP-Rapamycin only
0.30 mg/kg SVP-Rapamycin
0.4 mg/kg Pegsiticase
Clinical Activity of SVP-Rapamycin + Pegsiticase
0
2
4
6
8
1 0
0.15 mg/kg SVP-Rapamycin
0.4 mg/kg Pegsiticase
N = 5
N = 15
N = 5
N = 10
N = 5
N = 5
Current unaudited data
20
21
0
2
4
6
8
1 0
0
2
4
6
8
1 0
S
e
ru
m
U
ric
A
cid
(
m
g
/d
L
)
0
2
4
6
8
1 0
0
2
4
6
8
1 0
0.03 mg/kg SVP-Rapamycin
0.4 mg/kg Pegsiticase
0.10 mg/kg SVP-Rapamycin
0.4 mg/kg Pegsiticase
0.4 mg/ kg Pegsiticase only
0.03, 0.1, 0.3 mg/kg
SVP-Rapamycin only
0.30 mg/kg SVP-Rapamycin
0.4 mg/kg Pegsiticase
0
2
4
6
8
1 0
0.15 mg/kg SVP-Rapamycin
0.4 mg/kg Pegsiticase
0
2
4
6
8
1 0
0 7 14 21 30 37 44 51
No emergence
of new ADAs*
* Patients in the 0.1, 0.15 and 0.3 mg/kg groups with <0.1 mg/dL uric acid levels at day 21 were invited on a
voluntary basis to return for additional observations after 30 days.
N = 5
N = 15
N = 5
N = 10
N = 5
N = 5
Clinical Activity of SVP-Rapamycin + Pegsiticase
Day
Current unaudited data
21
Uric acid
(mg/dL)
ADA
(Titer)
108-0010 7 1080
103-0015 6 9720
104-0032 1.9 1080
109-0012 6.3 1080
104-0036 8.8 9720
Day 30
Subject
number
Day 30 Anti-Uricase Antibody and Serum Uric
Acid Levels
Uric acid
(mg/dL)
ADA
(Titer)
107-0027 <0.1 Neg
107-0028 <0.1 Neg
104-0050 <0.1 Neg
104-0060 <0.1 120
103-0019 <0.1 Neg
Day 30
Subject
number
Neg = Negative
Uric acid
(mg/dL)
ADA
(Titer)
107-0018 <0.1 Neg
107-0021 <0.1 Neg
104-0027 6.1 29160
108-0008 <0.1 120
102-0005 <0.1 Neg
111-0018 <0.1 120
111-0022 8.6 360
111-0028 <0.1 Neg
111-0029 6.4 9720
106-0004 <0.1 Neg
Day 30
Subject
number
Pegsiticase alone
0.1 mg/kg
SVP-Rapamycin
+ Pegsiticase
0.3 mg/kg
SVP-Rapamycin
+ Pegsiticase
Uric acid
(mg/dL)
ADA
(Titer)
11-0043 <0.1 Neg
111-0045 <0.1 Neg
104-0091 <0.1 Neg
104-0094 <0.1 Neg
111-0049 2.5 720
Day 30
Subject
number0.15 mg/kg SVP-Rapamycin
+ Pegsiticase
SVP-Rapamycin-treated patients negative for anti-uricase IgG were also negative for anti-PEG antibodies
Current unaudited data
22
Phase 1a and Phase 1b Safety Overview
Current unaudited data
• Pegsiticase only
- Generally well tolerated at all dose levels
• SVP-Rapamycin alone
- 17x dose range tested to determine maximum tolerated dose (MTD)
- At 0.5 mg/kg, two SAEs (stomatitis)
- Known side effect of rapamycin
- Resolved without further issue
- Set 0.3 mg/kg as MTD
• SEL-212 (combination of SVP-Rapamycin and pegsiticase)
- Generally well tolerated at clinically active dose levels (0.1, 0.15 and 0.3 mg/kg)
- At 0.1 mg/kg there were two SAEs
- Patient with grade 2 rash led to classification of SAE due to ER visit;
resolved without further issue
- Second SAE classified as not related to study drug by medical monitor
- No SAEs at 0.15 and 0.3 mg/kg
23
“3 + 2” Dosing
Phase 2 Trial Ongoing with Initial Data
Expected in 1H17
1 29 57 85 113Days
Cohort 1
Cohort 2
Cohort 3
Cohort 4
0.2 mg/kg Pegsiticase 0.2 mg/kg Pegsiticase
0.4 mg/kg Pegsiticase 0.4 mg/kg Pegsiticase
0.05 mg/kg SVP-Rapamycin + 0.2 mg/kg Pegsiticase 0.2 mg/kg Pegsiticase
0.05 mg/kg SVP-Rapamycin + 0.4 mg/kg Pegsiticase 0.4 mg/kg Pegsiticase
Enrolling 36+ Patients in up to 15 U.S. Centers
Primary Endpoints: Safety and tolerability of multiple doses of SEL-212 and pegsiticase alone
Reduction of serum uric acid levels
Secondary Endpoints: Reduction in uricase-specific ADAs and pegsiticase-specific ADAs
Exploratory Endpoints: Change in tophi volume as measured by DECT imaging
Gout flares
Additional cohorts to receive higher doses of SVP-Rapamycin followed by pegsiticase alone
24
Gene Therapy
AAV-based gene therapy is maturing but restricted by
several types of immunogenicity, limiting application breadth
2. Cellular immune responses associated with loss of
transgene expression observed in recently reported
hemophilia B trials, limiting maximum tolerated dose
1. Pre-existing antibodies to AAV vector are an
exclusion criteria for up to 50% of patients in most
trials
3. Re-dosing is not possible due to the formation of ADAs
limiting the duration of treatment effect and the number of
diseases with viable products
Gene Therapy’s Immunogenicity Challenges
26
Mitigating AAV Immunogenicity and Enabling
Repeat Dosing in Mice…
Serum Factor IX
Expression
0 2 0 4 0 6 0
0
5 0 0 0
1 0 0 0 0
1 5 0 0 0
2 0 0 0 0
2 5 0 0 0
D a y s
A
n
ti
-
A
A
V
8
A
n
ti
b
o
d
y
T
it
e
r
Anti-AAV8
Antibody Titer
0
20000
40000
60000
80000
100000
120000
140000
160000
180000
200000
34 41 54
Human
F
IX
(
n
g
/ml
)
Days post injection
tNP/tNP
NP/tNP
SVP-Rapamycin
Empty NP
34 41 54
Days
H
u
m
an
F
IX
(ng
/m
l)
0
4000
8000
12000
16000
20000
SVP-Rapamycin
Empty Nanoparticle
SVP or Empty NP
AAV -Luciferase AAV8-Factor IX
Day 0 21 54
SVP or Empty NP
S
V
P
E
m
p
ty
N
P
-1
0
1
2
3
4
5
C
D
8
m
R
N
A
L
e
v
e
ls
(
C
t
)
CD8 T cell Liver
Infiltrates
S
V
P
E
m
p
ty
N
P
0
5
1 0
1 5
2 0 **
A
L
T
a
c
t
iv
it
y
(
m
U
/
m
L
)
Serum ALT
Enzyme Levels
Inhibiting Li er
Inflammation with First Dose
AAV8
SVP or Empty NP
0Day
Enabling Repeat Dosing
by Preventing ADAs
Data generated in collaboration with Dr. Federico Mingozzi
27
…and Non-Human Primates
1) Control NP
2) SVP-Rapamycin
3) SVP-Rapamycin
AAV8-GAA AAV8-human Factor IX
Day 0 Day 30 Day 45
Screen d-12 d3 d15 d45N
eu
trali
z
ing
An
tibod
y
T
it
e
r
AAV8-Specific ADAs
Control NP
SVP-Rapamycin
SVP-Rapamycin
Day 45 Serum Human Factor IX
Hu
m
a
n
F
a
ct
o
r
IX
(n
g
/m
l)
SVP SVP Control NP
Data generated in collaboration with Dr. Federico Mingozzi
28
N
o
d
e
p
le
t i
o
n
C
D
2
5
d
e
p
le
t i
o
n
0
5 0 0 0
1 0 0 0 0
1 5 0 0 0
2 0 0 0 0
* *
a
n
t
i-
A
A
V
8
I
g
G
(
n
g
/
m
L
)
Depletion of Regulatory T Cells with Anti-CD25
Antibody Restores Anti-AAV8 Antibody Response
N
o
D
e
p
le
t i
o
n
C
D
2
5
D
e
p
le
t i
o
n
0
11 0 0 4
21 0 0 4
31 0 0 4
41 0 0 4
C
D
2
5
+
C
D
4
S
p
l
e
n
i
c
T
c
e
l
l
s
AAV8
Day 0 32
4x1012 vg/kg AAV8 4x1012 vg/kg
SVP-Rapamycin +
19 20 21
Anti-CD25 antibody
Splenic CD25+ CD4 T cells Anti-AAV8 Antibody
Data generated in collaboration with Dr. Federico Mingozzi
29
Developing a Repeat Dose Gene Therapy for
Ornithine Transcarbamylase (OTC) Deficiency
Immunogenicity Barrier
▪ Infants require treatment prior to metabolic crisis to avoid CNS effects; retreatment
likely needed as patients grow
▪ Repeat gene therapy dosing impossible due to neutralizing antibodies to viral capsid
▪ Cellular immune responses to the liver are an additional potential barrier
Rare and Serious Disease
▪ Inborn error of metabolism; largest disease in urea cycle disorders
▪ No effective treatment today; causes accumulation of toxic ammonia levels
in 1 in 15,000-60,000 worldwide1
▪ Onset in early infancy; significantly reduces life expectancy
Clear Clinical Path
▪ Engineered AAV vector optimized for primates
▪ Contracted development with Genethon and Intl. Centre for Genetic Engineering and
Biotech: animal models, transgene optimization and vector development expertise
▪ Clinical endpoints: OTC enzyme, ammonia and urea levels
Ownership
▪ Proprietary AAV-based gene therapy combined with SVP-Rapamycin
1. Source: NIH
30
Developing the Only Known Gene Therapy
Candidate for Methylmalonic Acidemia (MMA)
Immunogenicity Barrier
▪ Infants require treatment prior to metabolic crisis to avoid CNS effects; retreatment
likely needed as patients grow
▪ Repeat gene therapy dosing impossible due to neutralizing antibodies to viral capsid
▪ Cellular immune responses to the liver are an additional potential barrier
Rare and Serious Disease
▪ Inborn error of metabolism; largest disease in family of acidemias
▪ No effective treatment today; causes methylmalonic acid accumulation
in 1 in 25,000-48,000 worldwide1
▪ Onset in early infancy; significantly reduces life expectancy
Clear Clinical Path
▪ Anc80 designed to have limited cross-reactivity with pre-existing AAV antibodies
▪ Collaboration with NIH and Mass Eye & Ear: Access to validated animal models,
gene therapy development expertise and patients
▪ Clinical endpoints include: Methylmalonyl-CoA mutase and MMA levels
Ownership
▪ Proprietary Anc80-based gene therapy combined with SVP-Rapamycin
1. Source: NIH
31
License Agreement with Spark Therapeutics
32
• Announced in December 2016
• Provides Spark Therapeutics with exclusive
worldwide rights to Selecta's SVP platform
technology for up to five gene therapy targets.
• Initial focus on combination of SVP with SPK-8011, Spark’s clinical
Hemophilia A gene therapy program
• Among the largest gene therapy and SMID-cap to SMID-cap biotech deals
announced to date
• Subject to the terms of the license agreement, Spark agreed to pay to
Selecta:
– $30 million of cash payments and investments in Selecta equity, of which $15
million has already been paid
– Up to $430 million in milestone payments for each target
– Mid-single to low-double-digit royalties on worldwide annual net sales of any
resulting commercialized gene therapy
Oncology
Biologic therapies required to target tumor cells and mount
a strong attack
ADA issues common upon initial treatment cycle
Several intermittent treatment cycles usually
required to halt or reverse tumor growth
Clinical trial use of global immunosuppressants may
not be sufficiently effective to prevent ADAs
Oncology’s Immunogenicity Challenges
34
Developing a Highly Potent Recombinant
Pseudomonas Immunotoxin Targeting Mesothelin
Benefit from Immunogenicity Removal
▪ LMB-100 induces neutralizing antibodies upon first dose in almost all patients, limiting
dosing to one administration cycle; insufficient to control tumor
▪ Global immunosuppressants ineffective in vast majority of patients
▪ SVP allows 3+ treatment cycles in pre-clinical models, restoring LMB-100 benefits
Rare and Serious Disease
▪ All mesotheliomas (~3,000 annual U.S. diagnoses1) and pancreatic cancers (~50,000)
express mesothelin; high percentage of ovarian, lung, breast cancers
▪ Certain solid tumors remain hard to treat and have remained evasive to
immunotherapy approaches
Clear Clinical Path
▪ LMB-100 and SVP-Rapamycin both in the clinic today in separate trials
▪ LMB-100 in NCI-sponsored clinical trials of mesothelioma and pancreatic cancer
▪ Clinical studies combining LMB-100 and SVP-Rapamycin may focus on overall and
progression free survival and anti-LMB-100 antibodies
Ownership
▪ Collaboration ongoing; now in licensing discussions
1. Source: American Cancer Society
35
Preclinical Data Supports the Benefits of
SVP-Rapamycin + LMB-100 Combination Therapy
Prevents formation of
anti-drug antibodies
Restores LMB-100’s
anti-tumor response
SVP alone does not
accelerate tumor growth
SVP-Rapamycin LMB-100
T u m o r G r o w t h
D a y s s i n c e t u m o r i n o c u l a t i o n
T
u
m
o
r
s
iz
e
(
m
m
3
)
0 1 0 2 0 3 0
0
5 0 0
1 0 0 0
1 5 0 0
S a l in e
S V P - R a p a m y c in
- 1 0 - 5 0 5 1 0 1 5 2 0
5 0 0
1 0 0 0
1 5 0 0
2 0 0 0
2 5 0 0
D a y s s i n c e t u m o r i n o c u l a t i o n
T
u
m
o
r
s
i
z
e
(
m
m
3
)
L M B - 1 0 0
S a l i n e
L M B - 1 0 0 + S V P
T u m o r G r o w t h
A n t i - L M B - 1 0 0 A n t i b o d y T i t e r
w e e k
D
il
u
t
io
n
f
a
c
t
o
r
0 2 4 6 8
0
5 0 0 0
1 0 0 0 0
1 5 0 0 0
L M B - 1 0 0
L M B - 1 0 0 + S V P
L M B - 1 0 0
S V P
36
Immune Tolerance Pipeline
Indication Description Preclinical Phase 1 Phase 2
Proprietary ADA Mitigation Programs
Refractory Gout
SVP-Rapamycin
co-administered with
pegsiticase (SEL-212)
Methylmalonic Acidemia
(MMA)
SVP-Rapamycin
co-administered with
Anc80 vector
Ornithine
Transcarbamylase
Deficiency (OTC)
SVP-Rapamycin
co-administered with
AAV vector
ADA Mitigation Program Collaboration
Mesothelioma &
Pancreatic Cancer
SVP-Rapamycin
co-administered with
LMB-100
ADA Mitigation Program License
Hemophilia A
SVP-Rapamycin licensed
for FVIII gene therapy
37
Upside Potential With Selecta’s Allergy,
Autoimmune and Immune Activation Pipeline
Indication Description Preclinical Phase 1 Phase 2
Allergies and Autoimmune Programs
Peanut Allergy
SVP-adjuvant and
SVP-food allergen
Celiac Disease
SVP-Rapamycin and
SVP-gluten
Type 1 Diabetes
SVP-Rapamycin and
SVP-insulin
Immune Activation Programs
Smoking Cessation &
Relapse Prevention
SVP-adjuvant and
SVP-nicotine (SEL-070)
HPV-associated Cancer
SVP-adjuvant and
SVP-HPV antigen
(SEL-701)
Malaria
SVP-adjuvant and
SVP-malaria antigens
38
Q3 Financial Overview
For the Quarter Ended
(In thousands, except share and per share data)
September 30,
2016
September 30,
2015
Grant & Collaboration Revenue $1,048 $1,607
Research & Development Expenses 6,021 5,483
General & Administrative Expenses 2,495 2,195
Net Loss Attributable to Common Stockholders ($7,728) ($7,561)
Net Loss Per Basic Share ($0.43) ($3.50)
Wtd. Avg. Common Shares Outstanding – Basic & Diluted 18,108,014 2,159,658
As of
(In thousands)
September 30,
2016
June 30,
2016
Cash, Cash Equivalents, Marketable Securities, Restricted Cash $79,927 $85,271
39
January 2017
SVP Peanut Allergy Program
Safe Harbor / Disclaimer
Any statements in this presentation about the future expectations, plans and prospects of Selecta Biosciences, Inc. (“the
company”), including without limitation, statements regarding the development of its pipeline, the company's expectations about
receiving payments from Spark Therapeutics, Inc. under the license agreement, the progress of the Phase 1/2 clinical program
of SEL-212 including the number of centers in the Phase 2 clinical trial of SEL-212 and the announcement of data, conference
presentations, the ability of the company’s SVP platform, including SVP-Rapamycin, to mitigate immune response and create
better therapeutic outcomes, the potential treatment applications for products utilizing the SVP platform in areas such as gene
therapy and oncology, any future development of the company’s discovery programs in peanut allergy and celiac disease, the
sufficiency of the company’s cash, cash equivalents, investments, and restricted cash and other statements containing the
words “anticipate,” “believe,” “continue,” “could,” “estimate,” “expect,” “hypothesize,” “intend,” “may,” “plan,” “potential,” “predict,”
“project,” “should,” “target,” “would,” and similar expressions, constitute forward-looking statements within the meaning of The
Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by such forward-
looking statements as a result of various important factors, including, but not limited to, the following: the uncertainties inherent
in the initiation, completion and cost of clinical trials including their uncertain outcomes, the availability and timing of data from
ongoing and future clinical trials and the results of such trials, whether preliminary results from a particular clinical trial will be
predictive of the final results of that trial or whether results of early clinical trials will be indicative of the results of later clinical
trials, the unproven approach of the company’s SVP technology, potential delays in enrollment of patients, undesirable side
effects of the company’s product candidates, its reliance on third parties to manufacture its product candidates and to conduct
its clinical trials, the company’s inability to maintain its existing or future collaborations or licenses, its inability to protect its
proprietary technology and intellectual property, potential delays in regulatory approvals, the availability of funding sufficient for
its foreseeable and unforeseeable operating expenses and capital expenditure requirements, substantial fluctuation in the price
of its common stock, a significant portion of the company’s total outstanding shares have recently become eligible to be sold
into the market, and other important factors discussed in the “Risk Factors” section of the company’s Quarterly Report on Form
10-Q filed with the Securities and Exchange Commission, or SEC, on November 10, 2016, and in other filings that the company
makes with the SEC. In addition, any forward-looking statements included in this presentation represent the company’s views
only as of the date of its publication and should not be relied upon as representing its views as of any subsequent date. The
company specifically disclaims any obligation to update any forward-looking statements included in this presentation.
42
Rationale for Selecta’s Peanut Allergy Program
Growing Unmet Need: Prevalence has increased ~4-fold
over last 20 years, affecting 1.4% of children in US
Potential Life-Threatening Anaphylactic Responses
Expansion Opportunities: Potential to address other
allergies by combining SVP-Rapamycin with SVP-
encapsulated allergens
High Unmet Need: No available therapies; only
approach today is peanut avoidance
43
Crude Peanut
Extract (CPE)
R848
Treating Allergies with Synthetic Vaccine
Particles (SVP) by Inducing Immune Switching
SVP-Immune Switching Particles
SVP-CPE & SVP-R848
SVP-R848 was generally well
tolerated in a phase 1 clinical
nicotine vaccine trial for smoking
cessation
SVP Allergy Program*
• Immunology of allergies
• Th2 effector T cell mediated disease with
generation of allergen-specific IgE antibodies that
cause mast cell activation
• Th2 to Th1 switch mechanism promotes the
formation of innocuous allergen-specific IgG
antibodies while reducing IgE antibodies
• SVP approach
• Robust switch mediated by SVP-R848, which
encapsulates potent Th1 polarizing adjuvant R848
(Resiquimod) leading to a strong IgG response
while minimizing off-target effects
• Encapsulated Crude Peanut Extract (SVP-CPE) to
elicit an antigen-specific response and shield patient
from systemic exposure to peanut allergen
• Approach could be replicated for other food and air-
borne allergies
SVP-R848SVP-CPE
44
* Based on preclinical data
45
Ara h6
Lane Sample
1 MW standards
2 CPE lot #1
4 CPE lot #2
6 SVP-CPE (lot #1)
8 SVP-CPE (lot #1)
10 SVP-CPE (lot #2)
12 SVP-CPE (lot #2)
Ara h1
1 2 3 4 5 6 7 8 9 10 11 12
Ara h2
Ara h3
SVP Encapsulation of Crude Peanut Extract
Reproducibly Maintains Representation of Major Allergens
CPE
#1
CPE
#2
SVP-CPE #1 SVP-CPE #2
Major peanut allergen proteins contained in Crude Peanut Extracts (CPE):
Ara h1, Ara h2, Ara h3, and Ara h6
45
Therapeutic SVP Treatment Inhibits Systemic
Anaphylaxis in Peanut Allergy Models
T i m e a f t e r c h a l l e n g e ( m i n )
T
e
m
p
e
ra
tu
re
(
C
)
0 1 0 2 0 3 0 4 0 5 0 6 0 7 0 8 0 9 0 1 0 0
3 0
3 1
3 2
3 3
3 4
3 5
3 6
3 7
3 8
3 9
CPE challenge of SVP-treated and untreated mice
0 7 40 47 61 82 103
0.5 mg CPE
+ alum (i.p.)
SVP-R848 & SVP-CPE,
SVP-R848 or SVP-Empty (s.c.) CPE i.n.
Prime Treatment Challenge
**** **** **** ***
A
n
a
p
h
y
l
a
c
t
i
c
s
c
o
r
e
S
V
P
-E
m
p
ty
S
V
P
-R
8
4
8
S
V
P
-C
P
E
&
S
V
P
-R
8
4
8
N
o
n
-a
ll
e
rg
ic
m
ic
e
0
1
2
3
Systemic Anaphylaxis
46
Body Temperature
Non-allergic mice
SVP-CPE & SVP-R848
SVP-R848
SVP-Empty
CPE dose: <1µg in SVP-CPE
46
Activity of SVP in a Peanut-Specific
Cutaneous Anaphylaxis Model
T im e a fte r c h a lle n g e (m in )
E
a
r
th
ic
k
n
e
s
s
;
c
h
a
ll
e
n
g
e
-m
o
c
k
(
m
m
)
0 2 0 4 0 6 0 8 0
-0 .0 5
0 .0 0
0 .0 5
0 .1 0
0 .1 5
0 .2 0
0 .2 5
* * * * * * * * * * /* * * * * /* *
0 7 40 47 61 82 104
CPE + alum (i.p.) Nanoparticle treatment (s.c.) CPE challenge (i.d)
• SVP-CPE & SVP-R848 but not SVP-R848 inhibits peanut-specific cutaneous anaphylaxis and IgE
• <1µg of CPE encapsulated in SVP combined with SVP-R848 sufficient for therapeutic efficacy
Peanut-specific cutaneous
anaphylaxis
Correlation of cutaneous anaphylaxis and
peanut-specific IgE
No treatment
SVP-R848
SVP-CPE & SVP-848
No sensitization
SVP-CPE &
SVP-R848
SVP-R848
Ig E O D m a x (d 1 0 1 )
M
a
x
l
o
c
a
l
in
fl
a
m
m
a
ti
o
n
(
m
m
)
0 1 2 3 4
0 .0
0 .1
0 .2
0 .3
p = 0 .0 0 1 2
I g E O D m a x ( d 1 0 1 )
M
a
x
l
o
c
a
l
in
fl
a
m
m
a
ti
o
n
(
m
m
)
0 1 2 3 4
0 . 0
0 . 1
0 . 2
0 . 3
p = 0 . 8 7
47
SVP-CPE Does Not Induce Anaphylaxis Even at
>50x Higher Dose than Required for Efficacy
0 15 30 50 70 90
28
30
32
34
36
38
40
T im e a f te r c h a l le n g e (m in )
T
e
m
p
e
ra
tu
re
(
C
)
* * * *
* * * *
* * * * * * * *
* * * *
0 15 3 5 70 90
32
34
36
38
40
T im e a fte r c h a lle n g e (m in )
* * * *
* * * *
15 3 50 70 90
28
30
32
34
36
38
40
T im e a fte r c h a lle n g e (m in )
S a lin e
F r e e C P E , 5 0 g
S V P -C P E , 5 0 g
C h a lle n g e
* * * *
* * * *
* * *
* *
CPE-sensitized mice consecutively challenged with free CPE vs. SVP-CPE
Day 32 Day 38 Day 47
5 mice/group
0 7 32 38
47
0.5 mg CPE
+ alum (i.p.) SVP-CPE vs free CPE (s.c.)
Prime Challenge
CPE
SVP-CPEFree CPE
• <1µg of CPE encapsulated in SVP was sufficient for therapeutic efficacy in peanut allergy models
• To demonstrate the safety of SVP-CPE, a >50 times higher dose of CPE (50µg) was administered
• SVP-CPE was safe at 50µg of CPE whereas 50µg of free CPE led to anaphylaxis in sensitized animals
48
A Non-Human Primates (NHP) Model of Allergy:
Background Information
• Goal to translate findings in rodents to non-human primates (NHP)
• No NHP peanut allergy available
• However, NHPs that are naturally allergic to Ascaris suum, a parasite, are
available. The Ascaris model was used to validate findings of the work done
in mice with peanut allergies
– Encapsulation of Ascaris (SVP-Ascaris) using the same method as for
SVP-CPE
– Intranasal challenge with Ascaris results in constriction of nasal passage
– Nasal constriction measured by acoustic rhinometry
– NHPs have been used by Sanofi to test various therapeutics in multiple
allergy studies over many years
– After 8-11 weeks, NHPs are expected return to a baseline allergic state
(~20-30% of normal rhinometry after i.n. challenge)
– Once back at baseline, NHPs are made available for a new treatment
cycle
49
Intranasal ascaris challenge followed by acoustic rhinometry. Measurements Days: -14, 63, 77, 98 & 119
Subcutaneous Treatment: (Days 0, 7, 14, & 42) with SVP-R848 or SVP-Ascaris & SVP-R848
D
Day: -14 0 7 14 42 49 63 70 77 84 98 105 119 126
Weeks post treatment 1 3 4 5 6 8 9 11 12
Study Design for NHP Model of
Ascaris-Mediated Allergic Rhinitis
Colony of 12 ascaris-allergic NHPs
Latin square design with 4 treatment groups. Each group of NHPs
rotated through all treatments in successive cycles (4 cycles)
• High dose 60 µg SVP-R848
• High dose 60 µg SVP-R848 + nanoparticle-encapsulated Ascaris extract (SVP-Ascaris)
• Low dose 12µg SVP-R848
• Low dose 12 µg SVP-R848 + nanoparticle-encapsulated Ascaris extract (SVP-Ascaris)
Repeated Ascaris challenge to assess durability of treatment
50
SVP-Treated NHPs Showed Improved Rhinometry
Scores at 5 Weeks After Treatment
M in im u m C r o s s -S e c tio n a l A re a
%
o
f
P
re
-a
s
c
a
ri
s
c
h
a
ll
e
n
g
e
A
re
a
[R
8 4
8
6 0
u g
]
[R
8 4
8
6 0
u g
] D
a y
6
3
[R
8 4
8
6 0
u g
] D
a y
7
7
[R
8 4
8
6 0
u g
/a
s c
6
u g
]
[R
8 4
8
6 0
u g
/a
s c
6
u g
] D
a y
6
3
[R
8 4
8
6 0
u g
/a
s c
6
u g
] D
a y
7
7
[R
8 4
8
1 2
u g
]
[R
8 4
8
1 2
u g
] D
a y
6
3
[R
8 4
8
1 2
u g
] D
a y
7
7
[R
8 4
8
1 2
u g
/a
s c
6
u g
]
[R
8 4
8
1 2
u g
/a
s c
6
u g
] D
a y
6
3
[R
8 4
8
1 2
u g
/a
s c
6
u g
] D
a y
7
7
0
2 0
4 0
6 0
8 0
1 0 0
V o lu m e
%
o
f
P
re
-a
s
c
a
ri
s
c
h
a
ll
e
n
g
e
V
o
lu
m
e
[R
8 4
8
6 0
u g
]
g ]
a y
6
3
[R
8 4
8
6 0
u g
] D
a y
7
7
[R
8 4
8
6 0
u g
/a
s c
6
u g
]
/
g ]
a y
6
3
[R
8 4
8
6 0
u g
/a
s c
6
u g
] D
a y
7
7
[R
8 4
8
1 2
u g
]
[
g ]
a y
6
3
[R
8 4
8
1 2
u g
] D
a y
7
7
[R
8 4
8
1 2
u g
/a
s c
6
u g
]
[
/a
s c
6
u g
]
a y
6
3
[R
8 4
8
1 2
u g
/a
s c
6
u g
] D
a y
7
7
0
2 0
4 0
6 0
8 0
1 0 0
BL w3 w5
60 µg
SVP-R848
60 µg
SVP-R848
+
SVP-Ascaris
12 µg
SVP-R848
12 µg
SVP-R848
+
SVP-Ascaris
BL w3 w5 BL w3 w5 BL w3 w5
• Nasal airway constriction in
response to intranasal
ascaris challenge was
measured at baseline (BL)
• NHPs received 4 treatments
with nanoparticles and then
challenged with ascaris i.n.
at 3 weeks (3w) and 5
weeks (5w) after the last
treatment
51
After 3 Cycles, SVP-Treated NHPs Remained
Allergy Free for >8 Months
Ascaris extract
R848
SVP-R848SVP-Ascaris
• In previous studies, NHPs typically
returned to baseline levels (~20-30% of
pre-ascaris challenge) by 8-11 weeks
after treatment
• After Cycle 1, majority of NHPs returned
to baseline levels
• After Cycle 2, NHPs only returned to 50%
of pre-ascaris challenge levels at week
14, with considerable variability
• After Cycle 3, NHPs are refractory to
repeated ascaris challenge, with 90% of
normal nasal area measured after i.n.n
ascaris challenge at 35 weeks after last
treatment
Cycle 1
Week 11
Cycle 2
Week 14
Cycle 3
Week 19
Cycle 3
Week 24
Cycle 3
Week 29
Cycle 3
Week 35
Weeks post treatment
52
Target Profile and Differentiation of SVP in
Peanut Allergies
Treatable
population
Safety
• Mild to moderate cases
• Treatment success rate decreases with age
of patients
• Children preferred target group
De-sensitization
• Anaphylaxis and patient drop out from some
clinical trials observed
Onset and
duration of
effect
• ~12 months to onset—requiring daily
application
• Effects wears off after stopping
treatment
Product
• Administration orally or via skin
• Passive change in immune response
• Daily dosing
Selecta (SVP Immune Switching)
• Moderate to severe cases
• MoA has potential to reverse disease in all
patients of children & adults (active immune
modulation)
• SVP-R848 well tolerated in clinical nicotine
vaccine trial for smoking cessation
• Short treatment period could lead to better
compliance
• Designed for immediate onset after 3-5 s.c.
injections
• Potential medium to long duration as a result of
prolonged switch of immune response
• Nanoparticle encapsulated with peanut antigen
and adjuvant injected s.c.
• Active switch from Th2 to Th1 response
• Vaccine like prime + boost dosing
53
