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): April 10, 2018
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 April 10, 2018, Selecta Biosciences, Inc. (the “Company”) announced new data from its ongoing Phase 2 Company-sponsored trial of SEL-212, for the treatment of chronic severe gout, which is assessing single ascending dose safety, pharmacokinetic and pharmacodynamics of SEL-212 in patients with elevated uric acid levels. The full text of the press release issued in connection with the announcement is furnished as Exhibit 99.1 to this Current Report on Form 8-K.
The Company will present the presentation poster furnished as Exhibit 99.2 to this Current Report on Form 8-K, which contains new data from patients receiving up to 0.15 mg/kg of SVP-Rapamycin with 0.2 or 0.4 mg/kg of pegsiticase from the Phase 2 trial at the Pan American League of Associations for Rheumatology (PANLAR) 2018 Congress in Buenos Aires, Argentina on April 10, 2018.
In connection with the issuance of the press release, the Company is holding a public conference call and webcast on April 10, 2018, at 8:30 a.m. ET, during which the Company will provide the investor presentation attached as Exhibit 99.3 to this Current Report on Form 8-K. The Company undertakes no obligation to update, supplement or amend the materials attached hereto as Exhibit 99.3.
The information furnished under this Item 7.01, including Exhibits 99.1, 99.2 and 99.3 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
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: April 10, 2018 | By: | /s/ Werner Cautreels, Ph.D. |
Werner Cautreels, Ph.D. | ||
President and Chief Executive Officer | ||
Exhibit 99.1
Selecta Biosciences Presents Positive New Data from Ongoing Phase 2 Trial of SEL-212, in Development for Chronic Severe Gout, at PANLAR 2018 Congress
• | 3-month Phase 2 data indicate SEL-212 (SVP-Rapamycin + pegsiticase) product profile may provide better and more sustained serum uric acid control, fewer flares, and less frequent dosing compared with recent data reported with the current FDA-approved uricase therapy. |
• | Data from patients receiving five doses of SEL-212 expected to be presented at Q3 medical conference |
• | Phase 3 trial planned to begin in 2018 |
• | Company to host conference call and live webcast today at 8:30 am ET |
Watertown, Mass., April 10, 2018 - Selecta Biosciences, Inc. (NASDAQ: SELB), a clinical-stage biopharmaceutical company focused on unlocking the full potential of biologic therapies by avoiding unwanted immune responses, today presented new data from patients receiving SEL-212 for the treatment of chronic severe gout at the Pan American League of Associations for Rheumatology (PANLAR) 2018 Congress in Buenos Aires, Argentina.
SEL-212 is designed to be the first non-immunogenic version of uricase, which would allow for the effective and safe administration of multiple doses with concurrent mitigation of anti-drug antibodies (ADAs) against the pegsiticase enzyme. The data reported today at PANLAR consisted of patients that received three monthly doses of SEL-212, up to 0.15 mg/kg of SVP-Rapamycin in combination with 0.2 or 0.4 mg/kg of pegsiticase, followed by two monthly doses of pegsiticase alone. Approximately 75% of evaluable patients maintained serum uric acid level control below 6 mg/dl during the initial three months of therapy with concurrent mitigation of ADAs against the pegsiticase enzyme. Furthermore, 91% of patients dosed with pegsiticase alone in month four after the initial three monthly doses of SEL-212 maintained serum uric acid control demonstrating the potential of SVP technology for the induction of immune tolerance.
“We are very pleased by the clinical activity seen in the data presented today at PANLAR, not only in SEL-212’s ability to control serum uric acid levels but also in the reduced incidence of gout flares compared to the current FDA-approved uricase. We believe that SEL-212 has the potential to change the treatment paradigm for patients with chronic severe gout since there remains a high unmet need for a monthly-dosed therapy that can provide better and sustained serum uric acid control in these patients. Today’s reported data show that approximately 75% of evaluable patients maintained serum uric acid control through three months,” said Werner Cautreels, Ph.D., President and CEO of Selecta. “We plan to present data from patients receiving five monthly SEL-212 doses at an upcoming medical meeting in the third quarter of this year. We expect these results will expand the 3-month SEL-212 clinical activity shown in today’s PANLAR data across the entire 5-month treatment period of the Phase 2 trial. This will position us well to execute on our Phase 3 trial, which is expected to start later this year. Importantly, the new 4-month PANLAR data provide further evidence that our SVP-Rapamycin platform has the ability to induce immune tolerance, with 91% of evaluable patients maintaining serum uric acid level control after being dosed with pegsiticase only in month three versus 17% who receive pegsiticase without previously receiving the three-monthly doses of SEL-212. We believe this evidence of immune tolerance to a highly
1
immunogenic enzyme has positive implications for the overall platform and its potential for combination with other immunogenic biologic therapies.”
Approximately 25% of the patient population treated with SEL-212 in the ongoing Phase 2 trial experienced gout flares during the first month after treatment with continued reduction of gout flare rates over months two to five. This low rate of gout flares appears to be in contrast with higher incidence of gout flares reported in clinical trials involving other urate lowering therapies.
SEL-212 has been generally well tolerated at clinically active doses following repeated administrations in the trial. There have been 15 serious adverse events (SAEs) reported, seven of which were reported to be not related or unlikely to be related to study drug, seven were infusion reactions that were previously reported by the company in its June 2017 data readout, and one infusion reaction in the most recent cohorts. No infusion reactions have been reported after treatment period 2. All SAEs were successfully treated without further issues.
Conference Call Reminder
The company will host a conference call via live webcast today at 8:30am ET. The live webcast of the presentation can be accessed via the Investors & Media section of the company’s website, http://selectabio.com. Individuals may also participate in the live call via telephone by dialing (844)-845-4170 (domestic) or (412) 717-9621 (international) and may access a teleconference replay for one week by dialing (877) 344-7529 (domestic) or (412) 317-0088 (international) and using confirmation code 10118839.
About Selecta Biosciences, Inc.
Selecta Biosciences, Inc. is a clinical-stage biopharmaceutical company that is focused on unlocking the full potential of biologic therapies by mitigating unwanted immune responses. Selecta plans to combine its tolerogenic Synthetic Vaccine Particles (SVP™) with a range of biologics for rare and serious diseases that require new treatment options. The company’s current proprietary pipeline includes SVP-enabled enzyme, oncology and gene therapies. SEL-212, the company’s lead product candidate in Phase 2, is being developed to treat severe gout patients and resolve their debilitating symptoms, including flares and gouty arthritis. A Phase 1 trial is ongoing for a combination therapy consisting of SVP-Rapamycin and LMB-100 (Selecta’s SEL-403 product candidate) for the treatment of patients with malignant pleural or peritoneal mesothelioma. Selecta’s proprietary gene therapy product candidates are being developed for rare inborn errors of metabolism and have the potential to enable repeat administration. The use of SVP is also being explored in the development of vaccines and treatments for allergies and autoimmune diseases. Selecta is based in Watertown, Massachusetts. For more information, please visit http://selectabio.com and follow @SelectaBio on Twitter.
Forward-Looking Statements
Any statements in this press release about the future expectations, plans and prospects of Selecta Biosciences, Inc. (“the company”), including without limitation, statements regarding 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 or otherwise mitigate immunogenicity, the ability of SEL-212 to allow for the effective and safe administration of multiple doses with concurrent mitigation of anti-drug antibodies (ADAs) against the pegsiticase enzyme, the ability of SEL-212 to provide better and more sustained serum uric acid control, fewer flares, and less frequent dosing compared with recent data reported with the current FDA-approved uricase therapy, whether results from patients receiving five monthly combination doses of SEL-212 will expand the three-month SEL-212 clinical activity data across the entire five-month
2
treatment period of the Phase 2 trial, when the company will report further data from the Phase 2 trial, whether the FDA approves the company’s plan to provide combination therapy of SEL-212 for the entire treatment period, whether the data from patients receiving five monthly combination doses of SEL-212 will support the company’s plans for its Phase 3 trial, when the company will advance to a Phase 3 for SEL-212 (if at all), whether SEL-212 has the potential to change the treatment paradigm for patients with chronic severe gout and address the unmet needs of these patients, the company’s ability to unlock the full potential of biologic therapies by mitigating unwanted immunogenicity, the ability of the company’s SVP platform, including SVP-Rapamycin, to induce immune tolerance and its potential for combination with other immunogenic biologic therapies, the company’s plan to apply its SVP platform to a range of biologics and rare diseases, 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, statements regarding the progress of the Phase 1 trial for SEL-403, the potential of the company’s gene therapy product candidates to treat rare inborn errors of metabolism and enable repeat administration, the potential of the SVP-Rapamycin platform generally, 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 Annual Report on Form 10-K filed with the Securities and Exchange Commission, or SEC, on March 15, 2018, and in other filings that the company makes with the SEC. In addition, any forward-looking statements included in this press release 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 press release.
3
Contact Information:
John Leaman, MD
Selecta Biosciences, Inc.
617-231-8081
jleaman@selectabio.com
Sarah McCabe
Selecta Biosciences, Inc.
+1-212-362-1200
sarah@sternir.com
4
New SEL-212 Phase 2 Data
Presented at PANLAR
April 10, 2018
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,
statements regarding 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 or otherwise mitigate immunogenicity, the ability of SEL-212 to improve
acute symptoms during a short induction cycle, whether the company participates in an End-of-Phase 2 meeting for SEL-212 in mid-2018 or at all, the ability of SEL-
212 to mitigate anti-drug antibodies, enable repeat dosing, achieve better and more sustained serum uric acid control and reduce gout flares, the ability of SEL-212 to
be re-administered if severe gout symptoms recur, whether results from patients receiving five monthly combination doses of SEL-212 will expand the three-month
SEL-212 clinical activity data across the entire five-month treatment period of the Phase 2 trial, when the company will report further data from the Phase 2 trial,
whether the FDA approves the company’s plan to provide combination therapy of SEL-212 for the entire treatment period, whether the data from patients receiving five
monthly combination doses of SEL-212 will support the company’s plans for its Phase 3 trial, whether the patient population for a Phase 3 for SEL-212 has a rapid
enrollment potential, when the company will advance to a Phase 3 for SEL-212 (if at all), whether SEL-212 has the potential to address the unmet needs of gout
patients, whether SEL-212 holds billion dollar potential, the ability of the company’s SVP platform, including SVP-Rapamycin, to mitigate immune response and induce
immune tolerance, the potential of the SVP-Rapamycin platform generally, 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, undesirab le 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 o ther important factors discussed in the
“Risk Factors” section of the company’s Annual Report on Form 10-K filed with the Securities and Exchange Commission, or SEC, on March 15, 2018, 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.
SEL-212 Phase 2 Overview and Summary of
New Data Presented at PANLAR
3
Phase 2 Trial Overview for new data presented at PANLAR
• Enrollment Criteria: Patients with symptomatic gout and serum uric acid (sUA) >6 mg/dl
• Primary/Secondary Endpoints:
• Safety, tolerability and pharmacokinetics of multiple doses of SEL-212 (SVP-Rapamycin + pegsiticase) and pegsiticase
alone
• Control of sUA levels
• Reduction in anti-drug antibody (ADA) levels
• Dosing (Cohort 10,11,12): SEL-212 every 28 days for three doses (months 0, 1 and 2) followed by two doses of pegsiticase
alone (months 3 and 4)
Summary of new data presented at PANLAR
• 3-month data show SEL-212 product profile provides:
• Mitigation of ADAs enabling repeat dosing and sustained serum uric acid control: ~74% of patients with sUA <6
mg/dl
• Low flare rate in the first month : 37% for new SEL-212 Cohorts; 26% for all SEL-212 Cohorts in the trial
• Less frequent dosing: Monthly compared to weekly/bi-weekly dosing for FDA-approved uricase
• 4-month data, of evaluable patients dosed at month 3 with pegsiticase alone, provide evidence for the ability of the
SVP platform to induce immune tolerance in a clinical setting with a highly immunogenic enzyme
SEL-212 Clinical Development Plan
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)
Current Stage of SEL-
212 Development
4
5
74%; (14/19)
0.2 or 0.4 mg/kg Pegsiticase
Patients evaluable at 12 weeks who received a full
first dose and completed treatment cycle 1
0.2 or 0.4 mg/kg
0.125 or 0.15 mg/kg
SEL-212
Pegsiticase
SVP-Rapamycin
0.2 or 0.4 mg/kg
Pegsiticase
17% (1/6)
Week
%
P
ts.
S
U
A
<6
mg
/d
L
Pegsiticase + SVP-Rapamycin
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 5 6 7 8 9 1 0 1 1 1 2
0
5 0
1 0 0
0 1 2 3 4 5 6 7 8 9 1 0 1 1 1 2
0
5 0
1 0 0
%
P
ts.
S
U
A
<6
mg
/d
L
Week
Unaudited data reported as of April 02, 2018 | Clinicaltrials.gov NCT02959918
New Phase 2 Data at 3 Months Show 74% of Patients
With Control of SUA <6 mg/dl
Patients Dosed With 0.125 mg/kg of SVP-Rapamycin + 0.4 mg/kg of
Pegsiticase
6
Unaudited data reported as of April 02, 2018 | Clinicaltrials.gov NCT02959918
Patient
S
e
ru
m
U
ric
A
cid
(
m
g
/d
L
)
F
E
A
D
D
Week
G
106-0060
106-0061
111-0009
102-0019
107-0012
112-0002
112-0001
107-0014
111-0010
111-0011
117-0005
110-0031
107-0022
107-0024
H
A
n
ti-U
ric
a
s
e
A
n
ti
b
o
d
y
T
it
e
r
Pegsiticase Alone Pegsiticase + SVP-Rapamycin
0.125 mg/kg
0.4 mg/kg
Withdrawn due to protocol deviation Discontinuation due to infusion reaction Withdrawal of consent
Discontinuation due to TEAE SAE; non-study drug related
Stopping rules met A D E F
G H
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
1 0 2
3
4
5
0
2
4
6
8
1
1 0 2
3
4
5
0
2
4
6
8
1
1 0 2
3
4
5
0
2
4
6
8
1
1 0 2
3
4
5
8
1
0
2
4
6
1 0 2
3
4
5
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
Patients Dosed With 0.15 mg/kg of SVP-Rapamycin + 0.2 mg/kg of
Pegsiticase
7
Unaudited data reported as of April 02, 2018 | Clinicaltrials.gov NCT02959918
Patient
S
e
ru
m
U
ric
A
cid
(
m
g
/d
L
)
Week
A
n
ti-U
ric
a
s
e
A
n
ti
b
o
d
y
T
it
e
r
0.15 mg/kg
0.2 mg/kg
Withdrawn due to protocol deviation Discontinuation due to infusion reaction Withdrawal of consent Stopping rules met A D E F
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
E
A
F
D
Pegsiticase Alone Pegsiticase + SVP-Rapamycin
0
2
4
6
8
1 0
1 0 2
1 0 3
1 0 4
1 0 5
2
3
4
5
0
2
4
6
8
1 0
1 0
2
3
4
5
0
2
4
6
8
1
1 0 2
3
4
5
2
3
4
5
0
2
4
6
8
1
1 0
2
3
4
5
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
Patients Dosed With 0.15 mg/kg of SVP-Rapamycin + 0.4 mg/kg of
Pegsiticase
8
Unaudited data reported as of April 02, 2018 | Clinicaltrials.gov NCT02959918
S
e
ru
m
U
ric
A
cid
(
m
g
/d
L
)
Week
A
n
ti-U
ric
a
s
e
A
n
ti
b
o
d
y
T
it
e
r
0.15 mg/kg
0.4 mg/kg
Stopping rules met A Withdrawal of consent F SAE; non-study drug related G
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
Patient
A
G
A
F
F
Pegsiticase Alone Pegsiticase + SVP-Rapamycin
0
2
4
6
8
1 0
1 0 2
1 0 3
1 0 4
1 0 5
2
3
4
5
0
2
4
6
8
1 0
1 0
8
1 0
2
2
3
4
5
0
2
4
6
1 0 2
3
4
5
8
1
2
3
4
5
0
2
4
6
1 0
2
3
4
5
8
1
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
1 1 2 3
0
2 0
4 0
6 0
9
Percent patients with gout flare by treatment month
%
o
f
P
a
ti
e
n
ts
w
/Fl
a
re
SEL-212*
50%
month
Unaudited data reported as of April 02, 2018 | Clinicaltrials.gov NCT02959918
%
o
f
P
a
ti
e
n
ts
w
/Fl
a
re
Pegsiticase
Alone
37%
26%
5%
Pegsiticase 0.2 or 0.4 mg/kg with SVP-Rapamycin 0.125 or 0.15 mg/kg; Patients evaluable at 12
weeks who received a full first dose and completed treatment cycle 1
*
New PANLAR Data Continue to Show Low Overall
Incidence of Gout Flares
SEL-212 Continues to Show Low Overall Incidence
of Gout Flares In Total Phase 2 Patient Population
10
Percent patients with gout flare by treatment month
1 1 2 3 4 5
0
2 0
4 0
6 0
%
o
f
P
a
ti
e
n
ts
w
/Fl
a
re
Pegsiticase
Alone SEL-212
50%
26%
19%
4%
13%
4%
month
Unaudited data reported as of April 02, 2018 | Clinicaltrials.gov NCT02959918
SEL-212 Safety For the Total Phase 2 Patient
Population
11
•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
Unaudited data reported as of April 02, 2018 | Clinicaltrials.gov NCT02959918
12
SEL-212 PANLAR Data Compared to KRYSTEXXA® Data+
SEL-212 (12 weeks) KRYSTEXXA® (16 weeks)
74%++ 44%
42% 52%
3 monthly injections 3 weekly followed by
7 bi-weekly injections
+Krystexxa results from “Initial Clinical Study to determine whether a tolerizing regimen of pegloticase can increase frequency of subjects having sustained
lowering of serum urate.” Kenneth E. Saag, Mitchell Finemann, Alan Kivitz, Herbert Baraf, Roy Fleishmann, Arthur Kavanaugh, and Peter Lipsky; ACR Poster
2017
Unaudited SEL-212 data reported as of April 02, 2018 | Clinicaltrials.gov NCT02959918
Category
sUA control
Gout flare %
Dosing regimen
++ Defined as % of evaluable patients at 12 weeks with sUA <6 mg/dl who received a full first dose and completed treatment cycle 1
Phase 3 Initiation Expected in 2018
Primary Clinical Endpoint:
Serum uric acid < 6 mg/dl
measured at month 3 and 6
6 Monthly Combination Injections of SEL-212
SEL-212 PHASE 3 PROGRAM+
• Data expected in
third quarter from
patients receiving
five combination
doses of SEL-212
• Phase 3 trial
expected to begin
in 2018
13
+Will include placebo controlled trials; potentially positive controlled trials (e.g., Head to Head with KRYSTEXXA®)
Preclinical Studies Demonstrate Induction of Antigen-
Specific Immune Tolerance by SVP-Rapamycin
Preclinical mechanism of action studies
• Antigen-specific1, 2, 5
• Induction of tolerogenic DCs in vivo2
• Induction of antigen-specific Tregs in vivo1, 2, 4
• Biodistribution of SVP-Rapamycin to antigen-
presenting cells in the spleen1, 2, 3
• Free rapamycin does not induce immune tolerance2
• Reversal of tolerance by depletion of Tregs5
• Transfer of tolerance from SVP-Rapa-treated mice
to naïve mice3, 4, 5
14
SVP-Rapamycin
Pegsiticase
Regulatory T cell
Naïve T cell
B cell
Helper
T cell
Dendritic cell (DC)
Induction of
tolerogenic DC
Immune suppression mediated
by regulatory T cells
Naïve T cell
1. Maldonado et al., PNAS, 2015, 112(2):E156-65
2. Kishimoto et al, Nature Nanotech, 2016, 11(10):890-899
3. Mazor et al., PNAS, 2018,115(4):E733-E742
4. LaMothe et al. Frontiers Immunol, 2018, 9:281
5. Amine et al., Mol Therapy, 2016, 24, Suppl 1, S34,
15
0
5 , 0 0 0
1 0 , 0 0 0
S p l e n o c y t e s R e c e i v e d
A
n
t
i-
L
M
B
-
1
0
0
t
it
e
r
Cell number - 107 107 107 107
LMB-100 - - + - +
SVP-Rapa - - - + +
PBS - +
Transfer of Tolerance from Treated Mice to Naïve Mice
CONFIDENTIAL
4 5
TREATED
DONOR
+/-LMB-100
+/- SVP
1 3 Week
Week
NAÏVE
RECIPIENT LMB-100
Transfer splenocytes
LMB-100
+/-LMB-100
+/- SVP
Mazor et al., PNAS 2018
T cells from mice treated with SVP-Rapamycin and LMB-100 are able to transfer
tolerance to naïve mice that have never been exposed to SVP-Rapamycin
Anti-LMB-100 Antibody Titer
16
Unaudited data reported as of April 02, 2018 | Clinicaltrials.gov NCT02959918
Current Phase 2 Data Provides Evidence for Immune
Tolerance Induction
0 1 2 3 4 5 6 7 8 9 1 0 1 1 1 2
0
5 0
1 0 0
0.2 or 0.4 mg/kg
0.125 or 0.15 mg/kg
SEL-212
Pegsiticase
SVP-Rapamycin
Patients evaluable at 16 weeks who received a
full first dose and completed treatment cycle 1
Week
%
P
ts.
S
U
A
<6
mg
/d
L
Pegsiticase + SVP-Rapamycin
Weeks after dose of
pegsiticase alone
0.2 or 0.4 mg/kg Pegsiticase
0 1 2 3 4 5 6 7 8 9 1 0 1 1 1 2 1 3 1 4 1 5 1 6
0
5 0
1 0 0
0.2 or 0.4 mg/kg Pegsiticase
0.2 or 0.4 mg/kg
Pegsiticase
Treatment naïve patients after
1 dose of pegsiticase alone
0 1 2 3 4 5 6 7 8 9 1 0 1 1 1 2
0
5 0
1 0 0
%
P
ts.
S
U
A
<6
mg
/d
L
SEL-212-treated patients with
control of sUA at 12 weeks after
1 dose of pegsiticase alone
91%
17%
91% of patients who make it to week 12
sustain control of sUA through 16 weeks
We thank all of the patients that participated in our clinical
trials. We are very grateful to the clinical trial site
investigators and their staff.
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