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): June 21, 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)) |
Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§240.12b-2 of this chapter).
Emerging growth company x
If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. x
Item 7.01. Regulation FD Disclosure.
On June 15, 2017, Selecta Biosciences, Inc. (the “Company”) furnished a corporate slide presentation (the “June 15 Presentation”) providing additional data from the Company’s ongoing, open-label Phase 2 company-sponsored trial, which is assessing the safety, tolerability, pharmacokinetic and pharmacodynamics of SEL-212 in patients with elevated uric acid levels and symptomatic gout (the “Phase 2 Trial”).
The Company is now furnishing an updated corporate presentation (the “Updated Presentation”), which is attached to this Current Report on Form 8-K as Exhibit 99.1. In addition to incorporating information from the June 15 Presentation, the Updated Presentation includes, among other things, data with respect to Cohort 7 of the Phase 2 Trial, which were not contained in the June 15 Presentation.
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 8.01. Other Events.
The Updated Presentation amends (i) the number of patients enrolled in the Phase 2 Trial as of June 12, 2017 from 60 to 62 and (ii) the percentage of patients reporting a gout flare in the first month of treatment from 15% to 14% as a result of the increase in the number of patients.
Item 9.01. Financial Statements and Exhibits.
(d) Exhibits
Exhibit No. | Description | |||
99.1 | Corporate presentation of Selecta Biosciences, Inc. dated June 21, 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: June 21, 2017 | By: | /s/ Werner Cautreels, Ph.D. |
Werner Cautreels, Ph.D. | ||
President and Chief Executive Officer | ||
EXHIBIT INDEX
Exhibit No. | Description | |||
99.1 | Corporate presentation of Selecta Biosciences, Inc. dated June 21, 2017 | |||
June 21, 2017
Corporate Overview
Safe Harbor / Disclaimer
2
Any statements in this presentation about the future expectations, plans and prospects of Selecta Biosciences, Inc. (“the company”),
including without limitation, the progress of the Phase 1/2 clinical program of SEL-212, the potential of SEL-212 to treat severe gout
patients and resolve their debilitating symptoms, the ability of SVP-Rapamycin to induce immune tolerance against pegsiticase, the
ability of SEL-212 to improve acute symptoms during a short induction cycle, the ability of SEL-212 to be re-administered if severe
gout symptoms recur, whether the company will determine an appropriate dose of SEL-212 for a Phase 3, whether the company will
advance to a Phase 3 for SEL-212 at all, 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 enzyme therapy, gene therapy, oncology therapy, vaccines and treatments for allergies and autoimmune diseases, the
potential of the company’s two gene therapy product candidates to enable repeat administration, whether the company submits an
IND for its lead gene therapy program, MMA, in the first half of 2018, the company's expectations about receiving additional
payments from Spark Therapeutics, Inc. under the license agreement and/or the stock purchase agreement, 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
May 11, 2017, 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.
Immunogenicity is Now Recognized as a Serious
Challenge for Biologic Therapies
COMPROMISED EFFICACY
Anti-drug antibodies (ADAs)
neutralize therapeutic benefit
3
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
“Prophylactic immune tolerance induction should be strongly considered in patients who are at risk
of developing immune responses to ERT.”
– Amy Rosenberg, MD, Director, Division of Biotechnology Products Review and Research, FDA
IMAGINE IF
WE COULD…
1. Effectively treat many more
patients with existing biologics
2. Enable a new generation of novel
non-immunogenic biologics for
rare and serious diseases
4
The Key: Mitigate Anti-Drug Antibodies by
Inducing Regulatory T Cells
Naïve T cell
Lymph Node
B cell
Helper T cell
Dendritic cell
SVP-Rapamycin Biologic drug
Preventing ADAs
Inducing a tolerogenic
response to a biologic
drug (antigen)
Regulatory
T cell
Implementing the
message
Sending precise
instructions
Targeting
immune cells
• By dosing “free biologic”
separate from SVP-
Rapamycin, it distributes
broadly to desired sites of
action
• Some of the biologic co-
localizes with dendritic cells
that have taken up SVP-
Rapamycin
• The dendritic cells then
induce regulatory T cells
that circulate throughout the
body and suppress immune
responses against the
biologic (i.e. ADAs)
Potential to enable new therapies and improve efficacy/safety of existing biologics
5
Leveraging Nanoparticles to Deliver
Instructions to the Immune System
I.V. Injection
(6hr post-injection)
Spleen
Spleen harvested 24 hr after I.V.
Injection of fluorescent NPs
SVP Antigen
SVP
Macrophages
Dendritic cells
B cells
6
7
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
Zhang et al., Cell Immunol, 2016
Proprietary program(s) Potential program(s)
8
SEL-212 for Chronic Severe Gout
Commercially attractive
Rare disease
Rapid ADA onset
Clear endpoint
Adult patients
Single
Treatment
Chronic
Treatment
Adult
Patients
Cancer
Patients
Pediatric
Patients
Oncology
(LMB-100)
Enzyme Replacement Therapy
(Pompe Disease)
Gene Therapy
(MMA and OTC)
+
Treatment
Cycle
+
+
+
Plan for SVP Immune Tolerance
Platform Expansion
Ongoing Ph2 trial also
will inform clinical
programs for other
product candidates
SEL-212 for Chronic
Severe Gout
Selecta’s Lead Product Candidate: SEL-212
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 inhibitory antibodies in
~60% of patients and carry risk for anaphylaxis
Rare and Serious Disease
▪ ~160,000 adults with chronic 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
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
10
Substantial Unmet Need for Chronic Severe
Gout Patients
11
Tophi Significantly Increase Mortality Risk3
No/not
diagnosed tophi
8.3
3.1
5.2 4.7
0.5
Patients
Rx treated
Primary
care, endo,
nephro,
other
Rheumatologists
U.S. Gout Patients (million)1
530,000
370,000
Estimated SEL-212 Target Patient Population1
Gout treated by
rheumatologists
Est. SEL-212
patient pool
Un-diagnosed
or no Rx
treatment
Gout
prevalence
160,000
(1) IMS, Desk Research, Selecta rheumatologist interviews,
Crystal patient registry
(2) Lim SY et al, Trends in Gout and Rheumatoid Arthritis
Hospitalizations in the United States, JAMA, June 2016
(3) Vincent Z et al, Predictors of Mortality in People with Recent Onset of
Gout: A Prospective Observational Study, J. Rheumatol, 2017
Gout Admissions Now Exceed RA2
What is Chronic Severe Gout?
(1) IMS, Desk Research
(2) Selecta rheumatologist interviews, Crystal patient registry
(3) Choi HK et al, Tophaceous Gout and the Risk of Mortality: A General
Population-Based Study, ACR, Sept. 2016
(4) Zhu Y, et al, Comorbidities of gout and hyperuricemia in the US
general population: NHANES 2007-2008, Am J Med, July 2012
12
• ~50,000 U.S. gout patients are refractory to standard
therapies and most have existing “tophi”1
• Over 100,000 additional patients have tophaceous
gout and remain symptomatic2
• Tophi are hidden or disfiguring inflammatory nodules
of crystallized uric acid that form in severe gout
patients
- Tend to form primarily in joints and tissues
- Source of recurrent flares and debilitating pain
that cannot be treated effectively by simply
lowering sUA to <6 mg/dL
- Shown to significantly increase morbidity and
mortality if left untreated3,4
Visible tophi
Hidden uric acid deposits
Uric acid
deposits
Resolving Tophi and Uric Acid Deposits
with Monthly Uricase Treatments
13
6.8
6.0
Seru
m
U
ri
c
A
c
id
(
m
g
/d
L
)
Time
Transition from uricase
to oral therapies
Before1 After1
Uric acid deposits
Calcium deposits
Very low sUA levels enable
rapid tophi resolution
12-24 week treatment cycle
(1) Arujo EG et al, Tophus resolution with pegloticase:
a prospective dual-energy CT study, RMD Open, 2015 For illustrative purposes only
Uric acid solubility limit
FDA-approved endpoint
Oral therapies
14
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
N = 5
N = 15
N = 5
N = 10
N = 5
N = 5
Phase 1b Demonstrates SEL-212’s Clinical
Activity for ≥30 Days
Day 14
+
IMVACS 2016 Presentation
Phase 1b Trial Shows Correlation Between
ADA Titers, Pegsiticase Activity and sUA
15
0 5 1 0 1 5 2 0 2 5 3 0
0
3
6
9
1 2
0 5 1 0 1 5 2 0 2 5 3 0
0
3
6
9
1 2
0 5 1 0 1 5 2 0 2 5 3 0
0
3
6
9
1 2
0 5 1 0 1 5 2 0 2 5 3 0
0
3
6
9
1 2
S
e
ru
m
u
ri
c
a
cid
(
m
g
/d
L
)
0 5 1 0 1 5 2 0 2 5 3 0
1 0
- 1
1 0
0
1 0
1
1 0
2
1 0
3
0 5 1 0 1 5 2 0 2 5 3 0
1 0
- 1
1 0
0
1 0
1
1 0
2
1 0
3
0 5 1 0 1 5 2 0 2 5 3 0
1 0
- 1
1 0
0
1 0
1
1 0
2
3
0 5 1 0 1 5 2 0 2 5 3 0
1 0
- 1
1 0
0
1 0
1
1 0
2
S
e
ru
m
p
e
g
s
iticase
ac
ti
vit
y
(m
U
/m
L)
0 5 1 0 1 5 2 0 2 5 3 0
1 0
1
1 0
2
1 0
3
1 0
4
1 0
5
0 5 1 0 1 5 2 0 2 5 3 0
1 0
1
1 0
2
1 0
3
4
5
0 5 1 0 1 5 2 0 2 5 3 0
1 0
1
1 0
2
1 0
3
4
5
0 5 1 0 1 5 2 0 2 5 3 0
1 0
1
1 0
2
1 0
3
1 0
4
1 0
5
A
n
ti
-u
ri
c
a
s
e
I
g
G
tit
e
r
Days post-infusion
Pegsiticase only
Pegsiticase +
0.1 mg/kg
SVP-Rapamycin
Pegsiticase +
0.15 mg/kg
SVP-Rapamycin
Pegsiticase +
0.3 mg/kg
SVP-Rapamycin
7 of 10
4 of 5
N=5
N=10
N=5
N=5
4 of 5
7 of 10
+
Serum Uric AcidPegsiticase PDAnti-Uricase ADA
Clinicaltrials.gov NCT02648269
Clinical Objectives of SEL-212 Program
Phase 1b
Phase 1a
Phase 2
Demonstrate that SEL 212:
Mitigates ADAs
Enables prolonged control of
uric acid for >30 days
Define effective monthly dose
of pegsiticase
Demonstrate rapid formation
and kinetics of ADAs
Demonstrate SEL-212’s safety,
tolerability and ability to reduce
serum uric acid after multiple
doses
• n = 63
• Single ascending dose of SEL-212
• Hyperuricemic patients
• n = 22
• Single ascending dose of pegsiticase
• Hyperuricemic patients
• n = 62
• 3 monthly doses of SEL-212 +
2 monthly doses of pegsiticase alone
• Symptomatic & hyperuricemic patients
16
+
Nearly 100 patients now dosed with SEL-212
+
Clinicaltrials.gov NCT02464605
Clinicaltrials.gov NCT02648269
Clinicaltrials.gov NCT02959918
Unaudited data as of June 12, 2017; amended following on-site reviews
Clinicaltrials.gov NCT02959918
Trial Completion
Phase 2 Trial Overview
17
• Patients with symptomatic gout and serum uric acid levels >6 mg/dL
• Safety, tolerability and pharmacokinetics of multiple doses of
SEL-212 and pegsiticase alone
• Reduction of serum uric acid levels
• Reduction of ADA levels
• Multiple ascending dose cohorts
• Control cohorts: pegsiticase alone every 28 days for up to five doses
• All other cohorts: SEL-212 every 28 days for three doses followed
by two doses of pegsiticase alone
• Dosing stopped upon loss of sUA control at Days 21 after a dose
• Expected by the end of 2017
• 62 patients dosed at 11 active U.S. clinical sites
Enrollment Criteria
Primary/Secondary
Endpoints
Design
Dosing
Stopping Rules
As of June 12
Unaudited data as of June 12, 2017; amended following on-site reviews
Clinicaltrials.gov NCT02959918
18
Status of Phase 2 Trial Cohorts
Cohort
Treatment Weeks 0, 4, 8 Treatment Weeks 12 + 16
Status
Pegsiticase SVP-Rapamycin Pegsiticase
1 0.2 mg/kg None 0.2 mg/kg Enrollment terminated
2 0.4 mg/kg None 0.4 mg/kg Enrollment terminated
3 0.2 mg/kg 0.05 mg/kg 0.2 mg/kg Dosing completed
4 0.4 mg/kg 0.05 mg/kg 0.4 mg/kg Dosing completed
5 0.2 mg/kg 0.08 mg/kg 0.2 mg/kg Dosing completed
6 0.4 mg/kg 0.08 mg/kg 0.4 mg/kg Ongoing
7 0.2 mg/kg 0.1 mg/kg 0.2 mg/kg Ongoing
8 0.4 mg/kg 0.1 mg/kg 0.4 mg/kg Ongoing
9+ Under design Planned
Unaudited data as of June 12, 2017; amended following on-site reviews
Clinicaltrials.gov NCT02959918
19
Minimal Effective Dose of SEL-212 Now Defined
0 1 2 3 4 5 6 7 8 9 1 0 1 1 1 2 1 3 1 4 1 5 1 6 1 7 1 8 1 9 2 0
0
3
6
9
1 2
SU
A
(m
g/d
L)
0 1 2 3 4 5 6 7 8 9 1 0 1 1 1 2 1 3 1 4 1 5 1 6 1 7 1 8 1 9 2 0
0
3
6
9
1 2
SU
A
(m
g/d
L)
0 1 2 3 4 5 6 7 8 9 1 0 1 1 1 2 1 3 1 4 1 5 1 6 1 7 1 8 1 9 2 0
0
3
6
9
1 2
SU
A
(m
g/d
L)
0 1 2 3 4 5 6 7 8 9 1 0 1 1 1 2 1 3 1 4 1 5 1 6 1 7 1 8 1 9 2 0
0
3
6
9
1 2
W e e k s
SU
A
(m
g/
dL
) 0 1 2 3 4 5 6 7 8 9 1 0 1 1 1 2 1 3 1 4 1 5 1 6 1 7 1 8 1 9 2 0
0
3
6
9
1 2
0 1 2 3 4 5 6 7 8 9 1 0 1 1 1 2 1 3 1 4 1 5 1 6 1 7 1 8 1 9 2 0
0
3
6
9
1 2
0 1 2 3 4 5 6 7 8 9 1 0 1 1 1 2 1 3 1 4 1 5 1 6 1 7 1 8 1 9 2 0
0
3
6
9
1 2
W e e k s
0 1 2 3 4 5 6 7 8 9 1 0 1 1 1 2 1 3 1 4 1 5 1 6 1 7 1 8 1 9 2 0
0
3
6
9
1 2
0.2 mg/kg
None
Single patient
5 patients
Dosing ongoing Dosing ongoing
Cohort terminated for loss of
efficacy and patient safety
Cohort terminated for loss of
efficacy and patient safety
Single
patient
Single
patient
Pegsiticase Dose
0.4 mg/kg
S
V
P
-Rapa
m
y
cin
Dos
e
0.05
0.08
0.1
8 patients 8 patients
Excludes data points after dosing is stopped or stopping rules are met
Unaudited data as of June 12, 2017; amended following on-site reviews
Clinicaltrials.gov NCT02959918
20
Cohort 6: Minimal Effective Dose of SEL-212
• Sustained reduction
of sUA after two
injections of
pegsiticase alone
suggests induction
of immune tolerance
• Cohort being
expanded to 10
evaluable patients
# Stopping rules met (sUA level >1 mg/dL at 21 days after dosing)
Unaudited data as of June 12, 2017; amended following on-site reviews
Clinicaltrials.gov NCT02959918
0 7 1 4 2 1 2 8 3 5 4 2 4 9 5 6 6 3 7 0 7 7 8 4 9 1 9 8 1 0 5 1 1 2 1 1 9 1 2 6 1 3 3 1 4 0
0
2
4
6
8
1 0
1 0
2
1 0
3
1 0
4
1 0
5
0 7 1 4 2 1 2 8 3 5 4 2 4 9 5 6 6 3 7 0 7 7 8 4 9 1 9 8 1 0 5 1 1 2 1 1 9 1 2 6 1 3 3 1 4 0
0
2
4
6
8
1 0
1 0
2
1 0
3
1 0
4
1 0
5
0 7 1 4 2 1 2 8 3 5 4 2 4 9 5 6 6 3 7 0 7 7 8 4 9 1 9 8 1 0 5 1 1 2 1 1 9 1 2 6 1 3 3 1 4 0
0
2
4
6
8
1 0
1 0
2
3
4
5
0 7 1 4 2 1 2 8 3 5 4 2 4 9 5 6 6 3 7 0 7 7 8 4 9 1 9 8 1 0 5 1 1 2 1 1 9 1 2 6 1 3 3 1 4 0
0
2
4
6
8
1 0
1 0
2
3
4
5
0 7 1 4 2 1 2 8 3 5 4 2 4 9 5 6 6 3 7 0 7 7 8 4 9 1 9 8 1 0 5 1 1 2 1 1 9 1 2 6 1 3 3 1 4 0
0
2
4
6
8
1 0
1 0
2
3
4
5
0 7 1 4 2 1 2 8 3 5 4 2 4 9 5 6 6 3 7 0 7 7 8 4 9 1 9 8 1 0 5 1 1 2 1 1 9 1 2 6 1 3 3 1 4 0
0
2
4
6
8
1 0
1 0
2
3
4
5
0.4 mg/kg Pegsiticase +
0.08 mg/kg SVP-Rapamycin
0.4 mg/kg
Pegsiticase
114-0001
107-0004
111-0002
110-0008
106-0035
104-0010
Days
S
e
ru
m
U
ric
A
cid
(
m
g
/d
L
)
A
n
ti-U
ricas
e
A
n
ti
b
o
d
y
T
it
e
r
#
Patient #
21
Cohort 7: 0.2 mg/kg of Pegsiticase +
0.1 mg/kg of SVP-Rapamycin
• sUA remains
controlled
in a majority of
patients following
repeat doses
• One patient withdrew
consent after
experiencing
cholecystitis (not
related to study
drug)
• One patient
experienced an
infusion reaction and
fully recovered
Patient withdrew consent
# Stopping rules met (sUA level >1 mg/dL at 21 days after dosing)
* SAE (infusion reaction)
Unaudited data as of June 12, 2017; amended following on-site reviews
Clinicaltrials.gov NCT02959918
0.2 mg/kg Pegsiticase +
0.1 mg/kg SVP-Rapamycin
0.2 mg/kg
Pegsiticase
Patient #
114-0004
111-0004
103-0018
104-0014
106-0039
105-0001
114-0007
104-0019
104-0024
104-0020
S
e
ru
m
U
ric
A
cid
(
m
g
/d
L
)
A
n
ti-U
ricas
e
A
n
ti
b
o
d
y
T
it
e
r
0 7 1 4 2 1 2 8 3 5 4 2 4 9 5 6 6 3 7 0 7 7 8 4 9 1 9 8 1 0 5 1 1 2 1 1 9 1 2 6 1 3 3 1 4 0
0
2
4
6
8
1 0
1 0 2
1 0 3
1 0 4
1 0 5
2
3
4
5
0 7 1 4 2 1 2 8 3 5 4 2 4 9 5 6 6 3 7 0 7 7 8 4 9 1 9 8 1 0 5 1 1 2 1 1 9 1 2 6 1 3 3 1 4 0
0
2
4
6
8
1 0
1 0 2
3
4
5
2
3
4
5
0 7 1 4 2 1 2 8 3 5 4 2 4 9 5 6 6 3 7 0 7 7 8 4 9 1 9 8 1 0 5 1 1 2 1 1 9 1 2 6 1 3 3 1 4 0
0
2
4
6
8
1 0
1 0 2
3
4
5
2
3
4
5
0 7 1 4 2 1 2 8 3 5 4 2 4 9 5 6 6 3 7 0 7 7 8 4 9 1 9 8 1 0 5 1 1 2 1 1 9 1 2 6 1 3 3 1 4 0
0
2
4
6
8
1 0
1 0 2
3
4
5
2
3
4
1 0 5
0 7 1 4 2 1 2 8 3 5 4 2 4 9 5 6 6 3 7 0 7 7 8 4 9 1 9 8 1 0 5 1 1 2 1 1 9 1 2 6 1 3 3 1 4 0
0
2
4
6
8
1
1 0 2
3
4
5
2
3
4
5
0 7 1 4 2 1 2 8 3 5 4 2 4 9 5 6 6 3 7 0 7 7 8 4 9 1 9 8 1 0 5 1 1 2 1 1 9 1 2 6 1 3 3 1 4 0
0
2
4
6
8
1
1 0 2
3
4
5
114-0009
♦
#
Days
*
♦
22
Cohort 8: 0.4 mg/kg of Pegsiticase +
0.1 mg/kg of SVP-Rapamycin
• sUA remains
controlled
in a majority of
patients following
repeat doses
• Two patients met
stopping rules
• One of these
patients was
inadvertently re-
dosed; experienced
an infusion
reaction and fully
recovered
0.4 mg/kg Pegsiticase +
0.1 mg/kg SVP-Rapamycin
0.4 mg/kg
Pegsiticase
Patient #
104-0018
110-0015
103-0020
104-0017
106-0054
106-0045
107-0008
103-0019
111-0008
104-0023
0 7 1 4 2 1 2 8 3 5 4 2 4 9 5 6 6 3 7 0 7 7 8 4 9 1 9 8 1 0 5 1 1 2 1 1 9 1 2 6 1 3 3 1 4 0
0
2
4
6
8
1 0
1 0 2
1 0 3
1 0 4
1 0 5
2
3
4
5
0 7 1 4 2 1 2 8 3 5 4 2 4 9 5 6 6 3 7 0 7 7 8 4 9 1 9 8 1 0 5 1 1 2 1 1 9 1 2 6 1 3 3 1 4 0
0
2
4
6
8
1 0
1 0 2
3
4
5
2
3
4
5
0 7 1 4 2 1 2 8 3 5 4 2 4 9 5 6 6 3 7 0 7 7 8 4 9 1 9 8 1 0 5 1 1 2 1 1 9 1 2 6 1 3 3 1 4 0
0
2
4
6
8
1 0
1 0 2
3
1 0 4
1 0 5
2
3
4
5
0 7 1 4 2 1 2 8 3 5 4 2 4 9 5 6 6 3 7 0 7 7 8 4 9 1 9 8 1 0 5 1 1 2 1 1 9 1 2 6 1 3 3 1 4 0
0
2
4
6
8
1 0
1 0 2
3
4
5
2
3
4
5
0 7 1 4 2 1 2 8 3 5 4 2 4 9 5 6 6 3 7 0 7 7 8 4 9 1 9 8 1 0 5 1 1 2 1 1 9 1 2 6 1 3 3 1 4 0
0
2
4
6
8
1
1 0 2
3
4
5
2
3
4
5
S
e
ru
m
U
ric
A
cid
(
m
g
/d
L
)
A
n
ti-U
ricas
e
A
n
ti
b
o
d
y
T
it
e
r
# *
#
# Stopping rules met (sUA level >1 mg/dL at 21 days after dosing)
* SAE (infusion reaction) due to protocol deviation
Unaudited data as of June 12, 2017; amended following on-site reviews
Clinicaltrials.gov NCT02959918
Days
23
• Urate lowering therapies typically increase the incidence of flares at the
beginning of therapy
• Data indicate SEL-212 lowers flares compared to pegsiticase alone
0 . 0 5 0 . 0 8 0 . 1
0
2 0
4 0
6 0
% P a t i e n t s w i t h f l a r e i n m o n t h s 1 - 3
%
P
a
t
ie
n
t
s
w
it
h
f
la
r
e
s
S V P - R a p a m y c i n ( m g / k g )
+ P e g i s t i c a s e
P
e
g
i s
t i
c
a
s
e
a
l o
n
e
1 1 2 3
0
2 0
4 0
6 0
% P a t i e n t s w i t h f l a r e b y m o n t h
%
P
a
t
ie
n
t
s
w
it
h
f
la
r
e
s
S V P - R a p a m y c i n
+ P e g i s t i c a s e
P
e
g
i s
t i
c
a
s
e
a
l o
n
e
Results to Date Suggest Reduction in Flare
Frequency During SEL-212 Therapy
Unaudited data as of June 12, 2017; amended following on-site reviews
Clinicaltrials.gov NCT02959918
Phase 2 Safety Overview
24
• SEL-212 has been generally well tolerated at clinically active doses
following repeated administrations
• Eight SAEs reported to date in the trial:
- Seven infusion reactions, four of which were in cohorts receiving pegsiticase
alone or pegsiticase in combination with the lowest dose of SVP-Rapamycin,
as expected, and two of which were due to protocol deviations related to
dosing errors
- One was for a patient with history of gall stones who experienced cholecystitis
(inflammation of gall bladder caused by impacted gall stones), which was
determined not to be related to study drug
• All SAEs were successfully treated and resolved without further issues
Unaudited data as of June 12, 2017; amended following on-site reviews
Clinicaltrials.gov NCT02959918
25
Phase 2 Adverse Events
Cohort Entire
Study
1 2 3 4 5 6 7 8
N(%) 62 3 3 9 10 6 10 11 10
≥ 1TEAE 50(80.1) 3 2 8 7 5 8 8 9
≥ SAE 8 1 1 2 0 0 1* 1#, 1 1*
Death 0 0 0 0 0 0 0 0 0
Discontinuation
due to TEAE
9 1 1 2 0 0 1*, 1 1#, 1 1*
Specific TEAEs
Infusion reaction 8(12.9) 1 1 2 0 0 1*, 1 1 1*
Gout flare 13(21.0) 3 0 2 2 1 2 1 2
Hyperglycemia1 7(11.3) 0 0 2 0 2 1 1 1
Hypertriglyceridemia1 7(11.3) 0 0 1 0 3 1 1 1
Infection1 11(17.7) 0 1 5 1 0 1 1 2
Tachycardia1 3(4.8) 0 0 2 0 0 1 0 0
Headache1 8(12.9) 0 0 0 3 0 1 2 2
Hypophosphatemia1 4(6.5) 0 0 4 0 0 0 0 0
Stomatitis or oral
lesion1
3(4.8) 0 0 0 0 1 0 0 2
Leukopenia1 8(12.9) 0 0 2 0 2 1 1 2
# Determined not to be related to study drug. Patient underwent a
cholecystectomy
*Patient incorrectly dosed; protocol deviation
(1) Observed at single data points, transient in nature and mild or
moderate
Unaudited data as of June 12, 2017; amended following on-site
reviews
Clinicaltrials.gov NCT02959918
Oncology
Developing a Highly Potent Recombinant
Pseudomonas Immunotoxin Targeting Mesothelin
Benefit of Immunogenicity Mitigation
▪ LMB-100 induces inhibitory 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
▪ Initial repeat dose data from ongoing SEL-212 Phase 2 bodes well for this application
Rare and Serious Disease
▪ Virtually 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
▪ In discussions with NCI regarding a Phase 1b trial for the combination treatment
Ownership
▪ In-licensed LMB-100 from NCI in April 2017
▪ $50,000 upfront fee; up to $9.25 million in milestones; low single-digit royalties
1. Source: American Cancer Society
27
Immunotoxin LMB-100
• LMB-100: Pseudomonas exotoxin A linked
to antibody Fab targeting mesothelin
• Currently in Phase 1 clinical trials
• Efficacy is limited by immunogenicity after
one or two cycles in most patients
Ira Pastan, M.D.
Head, Molecular Biology Section
National Cancer InstituteLMB-100
Anti-mesothelin Fab Pseudomonas exotoxin A
domain III with mutated B
cell epitopes
Mesothelin is overexpressed
on many solid tumors
Mesothelioma (~100%)
Pancreatic cancer (~100%)
Ovarian cancer (70%)
Lung cancer (50%)
Breast cancer (34%)
Gastric cancer
28
Clinical Activity of LMB-100 Precursor in
Mesothelioma
Day 12 3 months 15 months
Before treatment 1.6 months 8 months
Patient 5
• Widely metastatic
peritoneal
mesothelioma
• Survived 32
months
Patient 3
• Extensive pleural
mesothelioma
• Survival >64
months (still alive)
S
u
m
o
f
ta
rg
e
t
le
s
io
n
s
(
c
m
)
Months after treatment
S
u
m
o
f
ta
rg
e
t
le
s
io
n
s
(
c
m
)
Months after treatment
The patients able to receive 4 or more cycles showed major anti-tumor response
Hassan, Pastan et al. Cancer Research (2014)
However, immunogenicity limited treatment to 1 or 2 cycles for most patients despite
concomitant use of immunosuppressive therapy
6 Treatment Cycles
4 Treatment Cycles
29
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
i
z
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
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
30
W e e k
A
n
ti
-L
M
B
-1
0
0
I
g
G
(
g
/m
l)
0 2 4 6 8
0
1 0 0
2 0 0
3 0 0
4 0 0
L M B -1 0 0
S V P
L M B -1 0 0
L M B -1 0 0 + S V P
A n ti-L M B -1 0 0 A n tib o d y
Data generated in collaboration with Dr. Ira Pastan, NCI
Gene Therapy
Selecta’s Proprietary Gene Therapy Programs
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 Diseases
▪ Two inborn error of metabolism: Methylmalonic Acidemia (MMA) and Ornithine
Transcarbamylase (OTC) Deficiency
▪ MMA affects 1 in 25,000-48,0001; OTC deficiency affects 1 in 15,000-60,000 worldwide1
▪ Onset in early infancy; significantly reduces life expectancy
Clear Clinical Path
▪ Targeting IND for lead gene therapy program, MMA, in the first half of 2018
▪ 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
▪ Two proprietary gene therapies utilizing AAV and Anc80 + SVP-Rapamycin
1. Source: NIH
32
Benefits of ADA Avoidance in Gene Therapy
Inhibiting Liver
Inflammation from First
Dose
Allowing for Repeat
Dosing
Enabling Dose Titration
S V P E m p ty N P
-1
0
1
2
3
4
5
C
D
8
m
R
N
A
(
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
ct
iv
ity
(
m
U
/m
L
)
Serum ALT Enzyme Levels
+ AAV8
SVP or Empty NP
0Day
SVP or Empty NP
+ AAV8-Luc AAV8-Factor IX
Day 0 21 54
SVP or Empty NP
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
T
it
e
r
Anti-AAV8 Antibody Titer
Serum Factor IX Expression
Data generated in collaboration with Dr. Federico Mingozzi, Genethon
0
40000
80000
120000
160000
200000
34 41 54
Hu
m
an
F
IX
(
n
g/
m
l)
Days
SVP-Rapamycin
Empty NP
0
1 0 0 0
2 0 0 0
3 0 0 0
4 0 0 0
H
u
m
a
n
F
IX
(
n
g
/
m
L
)
S in g le d o s e 5 e 9 A A V 8 -F IX + S V P
S p lit d o s e 2 X 2 .5 e 9 A A V -F IX + S V P
5e9 AAV8-FIX +SVP
2.5e9 AAV8-FIX +SVP
Day 0 10
2.5e9 AAV8-FIX+SVP
30
FIX Expression after split dose
33
0 5 0 1 0 0 1 5 0 2 0 0
0
5 0 0
1 0 0 0
1 5 0 0
2 0 0 0
D a y s
M
M
A
(
M
)
A n c 8 0 -h A A T -M u t4 5 e 1 2 V G
A A V 8 -h A A T -M u t4 5 e 1 2 V G
Anc80/synMUT Proof of Concept
in Mouse Model of MMA at ASGCT 2017
Anc80 or AAV8 Retro
Orbital injection
Reducing MMA Levels
With Anc80 and AAV8
Increasing Weight Gain
Following Treatment
0
5
10
15
20
25
30
35
AAV2/Anc80L65-hAAT-synMUT4-RBG AAV2/8-hAAT-synMUT4-RBG No treatment
Weight Gain in 12 days (%)
** (P = 0.036)
NS (P = 0.44)
(N=3) (N=3) (N=3)
Anc80 AAV8 No Tx
Per
c
en
t
w
eight gai
n
Preventing Anti-Anc80
Antibodies with SVP-
Rapamycin
A
n
t
i-
A
n
c
8
0
I
g
G
(
O
D
4
5
0
-
5
7
0
)
0 .0
0 .5
1 .0
1 .5
2 .0
D a y 7
D a y 1 2
D a y 1 9
D a y 2 8
1 0 5 0 1 0 0
S V P -R a p a m y c in (g )
0
Data generated in collaboration with Dr. Charles Venditti, NIH, and Dr. Luk Vandenberghe, Mass Eye & Ear
Anti-Anc80 Antibodies
34
Day 0 19 20 21 32
0 1 28
Demonstration of the Role of Regulatory T Cells
Data generated in collaboration with Dr. Federico Mingozzi, Genethon
Effect can be Transferred to a Recipient T Reg Depletion Negates Effect
a
n
ti
-A
A
V
8
I
g
G
(
g
/m
L
)
E m p ty N P S V P
0
5
1 0
1 5
2 0
* * *
Anti-AAV8 IgG levels in recipient mice (Day +14)
DONOR
AAV8-Luc +/- SVP
0 14Day
Day
RECIPIENT
AAV8-hFIX
AAV8-Luc +/- SVP
PRIME
Anti-CD25
Treg Depletion
CHALLENGE
Anti-AAV8 IgG levels (Day 32)
** P < 0.01, *** P < 0.001
Transfer splenocytes
0
1 0
2 0
3 0
4 0
5 0
***
a
n
ti
-A
A
V
8
I
g
G
(
n
g
/m
L)
**
S V P -R a p a m y c in
T re g d e p le t io n
+ +
++- -
- -
35
Indication Description Preclinical Phase 1 Phase 2
Proprietary ADA Mitigation Programs
Chronic Severe Gout
SVP-Rapamycin
co-administered with
pegsiticase (SEL-212)
Mesothelioma &
Pancreatic Cancer*
SVP-Rapamycin
co-administered with
LMB-100
Methylmalonic Acidemia
(MMA)
SVP-Rapamycin
co-administered with
Anc80 vector
Ornithine
Transcarbamylase
Deficiency (OTC)
SVP-Rapamycin
co-administered with
AAV vector
ADA Mitigation Program License
Hemophilia A
SVP-Rapamycin licensed
for FVIII gene therapy
Immune Tolerance Pipeline
36
* LMB-100 is currently being investigated in two Phase 1 clinical trials at the National Cancer Institute (NCI): one of LMB-100 alone in Mesothelioma and one
of LMB-100 in combination with nab-paclitaxel in Pancreatic Cancer. Selecta and NCI are currently in discussions regarding a planned Phase 1b clinical trial
to evaluate multiple cycles of LMB-100 in combination with SVP-Rapamycin.
Q1 Financial Overview
For the Quarter Ended
(In thousands, except share and per share data)
March 31,
2017
March 31,
2016
Grant & Collaboration Revenue $137 $2,088
Research & Development Expenses 11,044 6,648
General & Administrative Expenses 3,875 2,381
Net Loss Attributable to Common Stockholders ($15,134) ($9,832)
Net Loss Per Basic Share ($0.82) ($4.52)
Wtd. Avg. Common Shares Outstanding – Basic & Diluted 18,474,227 2,175,037
As of
(In thousands)
March 31,
2017
December 31,
2016
Cash, Cash Equivalents, Marketable Securities, Restricted Cash $68,919 $84,535
37
