Attached files
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| EX-99.3 - EXHIBIT 99.3 - SELECTA BIOSCIENCES INC | exhibit993selectapanl6d9.htm |
| EX-99.1 - EXHIBIT 99.1 - SELECTA BIOSCIENCES INC | exhibit991_pressrelease.htm |
| 8-K - 8-K - SELECTA BIOSCIENCES INC | selectabiosciences8k_prese.htm |
Pegsiticase
Pegsiticase
• Uricases have been shown to be very effective in significantly
reducing serum uric acid levels in patients with chronic severe gout
• Uricases are highly immunogenic, compromising their safety and
efficacy
• Pegsiticase is a pegylated uricase enzyme that is being developed
in combination with SVP-Rapamycin to mitigate its immunogenicity
SVP-Rapamycin
Rapamycin
PLA, PLA-PEG
SVP
Macrophages
Dendritic cells
B cells
6 hr post IV injection of fluorescent
nanoparticles in mice
• SVP-Rapamycin is a biodegradable
nanoparticle that encapsulates
rapamycin, an mTOR inhibitor
• Intravenous injection of SVP-
Rapamycin results in selective
accumulation in the spleen and liver,
where it is endocytosed by dendritic
cells (DC) and macrophages
• SVP-Rapamycin is designed to be co-administered with
biologic drugs to prevent the formation of ADAs through the
induction of immune tolerance and thus enable sustained
therapeutic activity of the biologic
Background
Mitigation
of
Immunogen
icity with
Tolerogenic
Nanoparticl
es
Spleen
SVP-Rapamycin Pegsiticase RegulatoryT cell
Naïve T cell
B cell
Helper
T cell
Dendritic cell
Naïve T cell
Induction of
tolerogenic
dendritic cells
Immune tolerance mediated by
regulatory T cells
Prevention
of ADAs
• SEL-212 is a combination drug comprised of pegsiticase and SVP-Rapamycin
• The co-administration of SVP-Rapamycin and pegsiticase is designed to induce the
formation of regulatory T cells that prevent the formation of ADAs against
pegsiticase and enable sustained reduction of serum uric acid (sUA) levels
•SEL-212 has been generally well tolerated at clinically active doses
following >300 administrations
•Fifteen SAEs reported in the ongoing Phase 2 trial:
• Seven were reported not to be or unlikely to be related to study drug
• Eight infusion reactions:
• Four in cohorts receiving pegsiticase alone or pegsiticase in combination
with the lowest dose of SVP-Rapamycin, as anticipated
• Two due to protocol deviations related to dosing errors
• Two during a repeat dose of SEL-212 in higher (0.1 – 0.15 mg/kg) dose
cohorts
•None occurred after treatment period 2
•All SAEs were successfully treated without further issues
Safety
Abstract
SVP-Rapamycin
SEL-212
Ongoing Phase 2
• SEL-212 has the potential to provide significant improvement in the treatment of patients with chronic severe gout
• Current data of high SVP Rapamycin dose cohorts show ~75% of patients achieve sUA levels <6 mg/dL after 3 months of
combination therapy
• Low incidence of anti-drug antibodies
• Low rate of gout flares
• Convenient monthly administration
• Generally well tolerated at clinically active dose levels and infusion reactions associated with repeat dosing were reduced
with increasing doses of SVP-Rapamycin.
• Current data support monthly doses of SVP-Rapamycin in combination with pegsiticase in Phase 3
• SEL-212 provides clinical proof of concept for SVP-Rapamycin’s potential to mitigate immunogenicity for a wide range of
biologic therapies where ADAs may be a limiting factor for efficacy or approvability
Conclusions
We thank all of the patients that participated in these clinical trials. We are very grateful to the clinical trial site investigators, their staff and the entire Selecta SEL-212 project team
70%*
Phase 1b
SEL-212/201 clinical trial design – Multiple Ascending Dose
Study description
• Evaluate the safety, pharmacokinetics, pharmacodynamics and immunogenicity of
repeated monthly IV infusions of SEL-212 in patients with symptomatic gout and
elevated serum uric acid (sUA) levels (>6 mg/dL)
• Cohorts of patients administered three q28 day IV infusions of 0.2 or 0.4 mg/kg
pegsiticase in combination with ascending doses of SVP-Rapamycin followed by two
q28 day IV infusions of 0.2 or 0.4 mg/kg pegsiticase alone
• Monitored for safety, uric acid levels, uricase pharmacodynamic activity, and anti-
uricase-antibodies (ADAs)
• Male or female subjects ages 21 to 75 inclusive
• Patients with established or symptomatic gout (≥1 tophus, ≥ 1 gout flare in last 6
months, or chronic gouty arthropathy) with hyperuricemia (> 6mg/dL sUA)
• Average sUA at enrollment/screening: 8.2 mg/dL
Introduction: Pegylated uricases are a promising but highly immunogenic therapy
for severe gout. Preclinical studies have shown the ability of synthetic vaccine
particles containing rapamycin (SVP-R) to inhibit the formation of ADAs against
pegsiticase, a pegylated uricase1. Here we report data on the safety,
immunogenicity and activity of SEL-212, a novel combination therapy consisting of
a pegsiticase and SVP-Rapamycin, in an ongoing Phase 2 trial.
Objectives: Evaluate the ability of repeated monthly doses of SEL-212 to mitigate
the immunogenicity of pegsiticase and enable sustained control of serum uric acid
(sUA) levels in gout patients.
Methods: Patients with symptomatic gout and elevated sUA (≥6mg/dL) were
treated with fixed doses of pegsiticase (0.2mg/kg or 0.4mg/kg) alone or co-
administered with SVP-Rapamycin (0.05 to 0.15mg/kg). SEL-212 was infused in
28-day cycles x3 doses followed by challenge with pegsiticase alone on 28-day
cycles x2 doses. Safety, tolerability, sUA, and ADAs were monitored.
Results: In the ongoing Phase 2 study, the majority of patients receiving 0.1-0.15
mg/kg SVP-Rapamycin administered with either 0.2 or 0.4 mg/kg pegsiticase
showed low or no ADAs and maintained low sUA levels after 3 monthly doses of
SEL-212, indicating sustained activity with repeated doses of SEL-212. Currently
patients are being dosed with 0.15 mg/kg SVP-Rapamycin, a dose level which
enabled control of sUA levels in patients in Phase 1b. SEL-212 was generally well
tolerated and associated with a low rate of gout flare rates compared to those
treated with pegsiticase alone.
Conclusion: SVP-Rapamycin showed a dose-dependent reduction in ADAs and
enabled sustained control of sUA with repeated dosing of SEL-212. SVP-
Rapamycin is a promising approach to prevent the formation of ADAs against
immunogenic biologic therapies.
References: 1Kishimoto TK, et al., Nature Nanotechnol. (2016) 11:890-899.
Low Incidence of Gout Flares with SEL-212 Treatment
Percent patients with gout flare by treatment month
% Patients with sUA <6 mg/dL during Combination Treatment
Dose-Dependent Reduction of sUA after Single Dose of SEL-212
Six Monthly Combination Doses of SEL-212
Clinical Development Plan
Unmet Medical Needs in Chronic Severe Gout
• Persistent reduction in Serum Uric Acid levels (sUA)
• Ability to complete full therapy cycles
• Monthly dosing
• Gout flare reduction
• Elimination of tophi
• Avoidance of “off-label” and global immunosuppressive therapies
Clinicaltrials.gov NCT02959918
Individual Patient Data - Ongoing 0.15 mg/kg SEL-110 + 0.2 or 0.4 mg/kg Pegsiticase Cohorts
0.15 mg/kg SVP-Rapamycin + 0.4 mg/kg Pegsiticase
0.4 mg/kg Pegsiticase +
0.15 mg/kg SVP-Rapamycin
0.4 mg/kg
Pegsiticase
Patient
107-0017
106-0073
111-0012
111-0013
111-0015
110-0026
106-0077
110-0028
106-0079
107-0021
110-0030
103-0028
115-0002
0
2
4
6
8
1 0
1 0 2
1 0 3
1 0 4
1 0 5
0
2
4
6
8
1 0
1 0 2
3
4
5
0
2
4
6
8
1 0
2
1 0 2
3
4
5
0 1 0 2
3
4
5
2
4
6
8
0
1
1 0 2
3
4
5
2
4
6
8
0
1
1 0 2
3
4
5
2
4
6
8
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
2
4
6
8
1 0
1 0 2
1 0 3
1 0 4
1 0 5
S
er
um
U
ric
A
ci
d
(m
g/
dL
)
A
G
Week
A
nti-U
ricase A
ntibody Titer
A
F
F
Patient
106-0084
117-0003
106-0086
103-0022
111-0018
103-0025
111-0019
110-0034
104-2026
106-0092
106-0093
102-0024
104-2021
0.2 mg/kg Pegsiticase +
0.15 mg/kg SVP-Rapamycin
0.2 mg/kg
Pegsiticase
0.15 mg/kg SVP-Rapamycin + 0.2 mg/kg Pegsiticase
1 0 2
1 0 3
1 0 4
1 0 5
1 0 2
3
4
5
1 0 2
3
4
5
1 0 2
3
4
5
1 0 2
3
4
5
1 0 2
3
4
5
0 1 2 3 4 5 6 7 8 9 1 0 1 1 2 1 3 1 4 1 5 1 6 1 7 1 8 9 2 0
1 0 2
1 0 3
1 0 4
1 0 5
S
e
ru
m
U
ri
c
A
ci
d
(
m
g
/d
L
)
Week
A
nti-U
rica
se
A
ntib
o
d
y T
ite
r
E
A
F
D
Ser
um
Ur
ic A
cid
(m
g/d
L)
0.03 mg/kg
0.4 mg/kg
0.1 mg/kg
0.4 mg/kg
0.4 mg/kg
0.3 mg/kg
0.4 mg/kg
0.15 mg/kg
0.4 mg/kg
0
2
4
6
8
1 02
4
6
8
1 0
0
2
4
6
8
1 0
0
2
4
6
8
1
2
4
6
8
1
N = 5
N = 5
N = 10
N = 5
N = 5
Days
Sin
gle
Do
se
0%
70%
100%
100%
20%
% Patient sUA
< 6mg/dL at Day 30
0 7 14 21 30
Pegsiticase SVP-Rapamycin
A Stopping rules met F Withdrawal of ConsentD Withdrawn due to protocol deviation G SAE; non-study drug relatedE Discontinuation due to infusion reaction
Primary Clinical Endpoint:
Serum uric acid < 6 mg/dl
measured at month 3 and 6
DETERMINATION OF DOSE REGIMEN TO TAKE INTO PHASE 3 PHASE 3 PROGRAM WITH DEFINED DOSE REGIMEN
Phase 2 Dose Ranging
Five monthly injections
Matrix approach to find
best doses of the two
components:
• SVP-Rapamycin
• Pegsiticase
(Planned N ~ 140)
Phase 1 a
Dose Finding
Pegsiticase
(N= 22)
6 Monthly Combination Injections of SEL-212
Phase 1 b
Dose Finding
SVP-Rapamycin
+/- pegsiticase
(N= 63)
Phase 2 Clinical Data of SEL-212 in Symptomatic Gout Patients:
Monthly Dosing of a Pegylated Uricase (Pegsiticase) with SVP-
Rapamycin Enables Sustained Reduction of Serum Uric Acid
Levels by Mitigating Formation of Anti-Drug Antibodies
Earl Sands1, Alan Kivitz2, Wesley DeHaan1, Lloyd Johnston1, Takashi Kei Kishimoto1
1Selecta Biosciences, Watertown, MA USA; 2Altoona Center for Clinical Research, Altoona, PA USA
1 1 2 3 4 5
0
2 0
4 0
6 0
% o
f Pa
tien
ts w
/Fla
re
Pegsiticase
Alone SEL-212
50%
25.5%
19.0%
4.4%
13.2%
3.6%
month
0.2 or 0.4 mg/kg
Pegsiticase
%
Pts.
SUA
<
6 m
g/
dL
75% (9/12)
Week
Patients evaluable at 12 weeks who received a
full first dose and completed treatment cycle 1
0.2 or 0.4 mg/kg
0.15 mg/kg
SEL-212
Unaudited data reported as of April 2, 2018
Pegsiticase
SVP- apamy in
0.2 or 0.4 mg/kg
Pegsiticase
17% (1/6)
0.15 mg/kg SVP-Rapamycin +
0.2 or 0.4 mg/kg Pegsiticase
%
Pt
s.
SU
A
<6
m
g/
dL
Week
0 1 2 3 4 5 6 7 8 9 1 0 1 1 1 2
0
5 0
1 0 0
0 1 2 3 4
0
5 0
1 0 0
Clinicaltrials.gov NCT02648269
Unaudited data reported as of April 2, 2018
Unaudited data reported as of April 2, 2018
Unaudited data reported as of April 2, 2018
Unaudited data reported as of April 2, 2018