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): March 27, 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.
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 (the “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 | |||
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: March 27, 2018 | By: | /s/ Werner Cautreels, Ph.D. |
Werner Cautreels, Ph.D. | ||
President and Chief Executive Officer | ||
Needham Presentation
Nasdaq: SELB
March 27, 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, the progress of
the Phase 1/2 clinical program of SEL-212, whether the company participates in an End-of-Phase 2 meeting for SEL-212 in mid-2018 or at all, the potential of SEL-212 to treat
severe gout patients and resolve their debilitating symptoms, the ability of SVP-Rapamycin to mitigate unwanted immunogenicity and unlock the full potential of biologic
therapies, whether higher level doses of SVP-Rapamycin or SEL-212 will show increased clinical activity and durability in line with the Phase 1b, 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
company will determine an appropriate dose regimen of SEL-212 for the Phase 3, 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 will lower the incidence of flares, whether SEL-212 holds billion dollar potential, the ability of the
company’s SVP platform, including SVP-Rapamycin, to mitigate immune response and create better therapeutic outcomes or to improve the efficacy or safety of existing
biologics, whether the SVP platform enables the biologic to be distributed broadly to desired sites of action, 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 future
collaborations or licenses based on the ability of SVP-Rapamycin, the potential of the SVP-Rapamycin platform, generally, statements regarding progress of the Phase 1 trial
for SEL-403, whether preclinical data regarding SVP-Rapamycin and LMB-100 will be predictive of clinical trial results for SEL-403, whether the company files an IND for SEL-
302 in 2019, 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 into mid-2019 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 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.
Corporate Overview
3
• Clinical-stage company applying proprietary Synthetic Vaccine Particle (SVP™) platform
to mitigate unwanted immunogenicity and unlock the full potential of biologic therapies
• Expect to begin Phase 3 in 2018 with SEL-212 (SVP-Rapamycin + pegsiticase) for
chronic severe gout
• Dosed first patient in Phase 1 trial of SEL-403 (SVP-Rapamycin + LMB-100) for
mesothelioma
• Proprietary gene therapy candidates in preclinical development
• License agreement in place with Spark Therapeutics, with additional potential for
collaborations and licenses in a range of therapeutic areas
Immunogenicity is Well Recognized as a Serious
Challenge for Biologic Therapies
4
COMPROMISED EFFICACY
Anti-drug antibodies (ADAs)
neutralize therapeutic benefit
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
“With the explosion of biologic
products on the market and in
research pipelines, we’ve
become very concerned about
the effectiveness and safety of
these drugs.”
– Amy Rosenberg, MD, Director,
Division of Biotechnology Products
Review and Research, FDA
When the Immune System
Thwarts Lifesaving Drugs
Patients often produce antibodies to the very
treatments keeping them alive, sometimes to
disastrous effect…
January 2018 Edition
Mitigating Unwanted Immunogenicity via Selecta’s
SVP-Rapamycin Technology Platform
5
Spleen
Preventing ADAs
Inducing a tolerogenic
response to a biologic
drug (antigen)
Implementing
the message
Sending precise
instructions
Targeting
immune cells
• By dosing the “free biologic”
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)
Naïve T cell
B cell
Helper T cell
Dendritic cell
Regulatory
T cell
Potential to enable new therapies and improve efficacy/safety of existing biologics
SVP-Rapamycin Biologic drug
Kishimoto et al., Improving the efficacy and safety of biologic drugs with tolerogenic nanoparticles, Nature Nanotechnology, Aug. 2016
Leveraging Nanoparticles to Target and Deliver
Instructions to the Immune System
6
I.V. Injection
(6hr post-injection)
Spleen harvested 24 hr after I.V.
Injection of fluorescent NPs
SVP
Macrophages
Dendritic cells
B cells
SVP Antigen
Spleen
SEL-212 for Chronic
Severe Gout
SEL-212: Advancing a Potential New Treatment Option
for Chronic Severe Gout Patients
8
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
Immunogenicity Barrier
• Uricases are highly effective in breaking down uric acid deposits, but are foreign to the human immune system, causing
immunogenicity in nearly all patients that can negate efficacy and present safety risks
Clear Clinical Path
• Serum uric acid level reduction – a robust FDA/EMA primary endpoint for approval – 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
Today’s Unmet Needs in Chronic Severe Gout
• Monthly dosing (vs. biweekly for today’s approved uricase therapy)
• Ability to complete full therapy cycles
- Persistent reduction in Serum Uric Acid levels (SUA)
- Elimination of tophi
• Gout flare reduction
• Avoidance of “off-label” and global immunosuppressive therapies
9
We believe SEL-212 has the potential to address these unmet needs and holds billion-dollar potential
Phase 1b Single Dose Patient Cohorts
10
IMVACS 2016 Presentation. Clinicaltrials.gov NCT02648269
S
er
um
U
ric
A
ci
d
(m
g/
dL
)
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 0
0
2
4
6
8
1 0
0
2
4
6
8
1 0
0
2
4
6
8
1 0
0
2
4
6
8
1 0
N = 5
N = 5
N = 10
N = 5
N = 5
= Pegsiticase; = SVP-Rapamycin
Days
S
in
gl
e
D
os
e
0%
70%
100%
100%
20%
% Patient SUA <
6mg/dL at Day 30
0 7 14 21 30
Phase 2 Trial Overview
11
Enrollment Criteria
Primary/Secondary
Endpoints
Design
Dosing
Stopping Rules
As of March 9th
• Patients with symptomatic gout and SUA levels >6 mg/dL
• Safety, tolerability and pharmacokinetics of multiple doses of SEL-212
• Reduction of SUA levels
• Reduction of ADA levels
• Multiple ascending dose cohorts
• Control cohorts: pegsiticase alone every 28 days for up to five doses
• Three combination doses of SEL-212 every 28 days followed by
2 doses of pegsiticase alone
• In February began dosing cohorts that will receive five monthly combination doses of SEL-212 every
28 days
• Dosing stopped upon loss of SUA control at Day 21 after each dose
• 111 patients dosed at 15 active clinical sites in the USA
12
Unaudited data as of October 23, 2017 | Clinicaltrials.gov NCT02959918
Progressing SEL-212 into Phase 3
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
N ~ 125
Phase 1
Dose Finding
Pegsiticase
(N= 22)
SVP-Rapamycin
(N= 63)
6 Monthly Combination Injections of SEL-212
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
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
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
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
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
1 0 3
1 0 4
1 0 5
#
♦
*
+
#114-0004
111-0004
103-0018
104-1014
106-1039
105-0001
114-0007
104-0019
104-0024
104-0020
114-0009
S
er
um
U
ric
A
ci
d
(m
g/
dL
) A
nti-U
ricase A
ntibody Titer
Cohort 7:
0.2 mg/kg Pegsiticase + 0.1 mg/kg SVP-Rapamycin
13* #♦
Patient
Unaudited data reported as of October 23, 2017 | Clinicaltrials.gov NCT02959918
Pegsiticase AlonePegsiticase + SVP-Rapamycin
Day
0.1 mg/kg
0.2 mg/kg
Discontinuation due to infusion reaction Withdrawal of consent SAE; infusion reaction Stopping rules met+
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
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
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
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
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
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
14
104-0018
110-0015
103-0020
104-0017
106-0054
106-0045
107-0008
103-0019
111-0008
104-0023
106-0065
106-0064
*
#
#
#
#
*
ϴ
ϴ
Cohort 8:
0.4 mg/kg Pegsiticase + 0.1 mg/kg SVP-Rapamycin
Unaudited data reported as of October 23, 2017 | Clinicaltrials.gov NCT02959918
Patient
S
er
um
U
ric
A
ci
d
(m
g/
dL
) A
nti-U
ricase A
ntibody Titer
0.1 mg/kg
0.4 mg/kg
Pegsiticase AlonePegsiticase + SVP-Rapamycin
Day
SAE; not study drug related SAE; infusion reaction Stopping rules metϴ * #
Ways to Increase Efficacy Seen in Mid-Dose Cohorts
15
Unaudited data reported as of October 23, 2017 | Clinicaltrials.gov NCT02959918
0
50
100
0 28 56 84 112 140
% of Patients With
SUA <6 mg/dL
0.1 mg/kg
0.2 or 0.4 mg/kg
Mid-Dose Cohorts
(Cohorts 7 & 8**)
Number of Patients with SUA <6 mg/dl.
70%
Pegsiticase + SVP-Rapamycin Pegsiticase Alone
%
P
ts
S
UA
<
6
m
g/
dl
.
Days
0.2 or 0.4 mg/kg
Days
Potential to increase
to 0.15 mg/kg and
combo for 5 doses
= Pegsiticase
= SVP-Rapamycin
0
50
100
0 28 56 84 112 140
% of Patients With
SUA <6 mg/dL
70%
Pegsiticase + SVP-Rapamycin
%
P
ts
S
UA
<
6
m
g/
dl
.
All Combination Dose Cohort
Illustrative
Number of Patients with SUA <6 mg/dl.
1 1 2 3 4 5
0
2 0
4 0
6 0
16
• Data indicate SEL-212 lowers flares initially and over time during treatment
• Urate lowering therapies typically increase the incidence of flares at the beginning of therapy
Unaudited data as of October 23, 2017 | Clinicaltrials.gov NCT02959918
%
o
f P
at
ie
nt
s
w
/F
la
re
Pegsiticase
Alone
% of Patients Experiencing Flares by Month
SEL-212
Month
50%
24%
16%
3%
11%
5%
Low Frequency of Gout Flares Observed
with SEL-212 Treatment
SEL-212 Generally Well Tolerated at Clinically
Active Doses
17
• SEL-212 has been generally well tolerated at clinically active doses following >300
administrations
• Fifteen SAEs reported in the 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 a higher dose cohort
- None occurred after treatment period 2
• All SAEs were successfully treated without further issues
Unaudited data as of March 22, 2017 | Clinicaltrials.gov NCT02959918
SEL-212 Expected to Enter Phase 3 in 2018
18
• SEL-212 (SVP-Rapamycin + pegsiticase) designed to be the first non-immunogenic uricase
treatment for chronic severe gout
• Phase 2 trial ongoing:
- SEL-212 has been demonstrated to be clinically active and generally well tolerated
- Cohorts receiving 0.125 and 0.15 mg/kg doses of SVP-Rapamycin ongoing; plan to report initial
data for these cohorts at PANLAR on April 10th
- In February initiated enrollment of patients expected to receive five monthly doses of SVP-
Rapamycin in combination with pegsiticase. The patients will be receiving SVP-Rapamycin doses
ranging from 0.1mg/kg-0.15mg/kg in combination with 0.2mg/kg of pegsiticase. Plan to present
data from these patients at a medical meeting in Q3 2018.
• Plan to participate in End-of-Phase 2 meeting in mid-2018
• Plan to enter Phase 3 in 2018
SEL-403 for
Mesothelioma
SEL-403: A Highly Potent Recombinant
Pseudomonas Immunotoxin Targeting Mesothelin
20
Rare and Serious Disease
• Mesothelin expressed in virtually all mesotheliomas (~3,000 annual U.S. diagnoses1) and pancreatic cancers (~50,000); high
percentage of ovarian, lung, breast cancers
• Certain solid tumors are particularly hard to treat and have remained evasive to immunotherapy approaches
Immunogenicity Barrier
• LMB-100 induces inhibitory antibodies upon first dose in almost all patients, limiting dosing to one or two administration cycles;
insufficient to control tumor
• Global immunosuppressants ineffective in preventing ADAs in a vast majority of patients
• SVP allowed 3+ treatment cycles in pre-clinical models, restoring LMB-100 anti-tumor activity
• Initial repeat dose data from ongoing SEL-212 Phase 2 encouraging for this application
Clear Clinical Path
• Both components of SEL-403 (SVP-Rapamycin and LMB-100) have been in the clinic in separate trials
• FDA acceptance of IND for combination treatment announced in January; First patient dosed in March 2018
Ownership
• In-licensed LMB-100 from NCI in April 2017; up to $9.25 million in milestones; low single-digit royalties
• Combination with SVP-Rapamycin now known as SEL-403
1. Beebe-Dimmer et al., Mesothelioma in the United States: a Surveillance, Epidemiology, and End Results (SEER) –
Medicare investigation of treatment patterns and overall survival, Clin Epidemiol., Oct. 2016
Immunotoxin LMB-100
21
• LMB-100: Pseudomonas exotoxin A
linked to antibody Fab targeting
mesothelin
• Technology was licensed to Roche
but later returned to NCI
• Efficacy was limited by
immunogenicity after one or two
cycles in most patients
• Currently in Phase 1 clinical trials
LMB-100 Mesothelin is
overexpressed on
many solid tumors
Ira Pastan, M.D.
Head, Molecular
Biology Section
National Cancer
Institute
• Mesothelioma (>90%)
• Pancreatic cancer (>90%)
• Ovarian cancer (70%)
• Lung cancer (50%)
• Breast cancer (34%)
Clinical Activity of SS1P (LMB-100 Precursor)
in Mesothelioma
22
Day 12 3 months 15 months
Before treatment 1.6 months 8 months
Patient 1
• Widely metastatic
peritoneal
mesothelioma
• Survived 32
months
Patient 2
• Extensive pleural
mesothelioma
• Survival >6 years
(still alive)
S
um
of
ta
rget
le
si
on
s
(c
m
)
Months after treatment
S
um
of
ta
rget
le
si
on
s
(c
m
)
Months after treatment
Science Translational Medicine. 2013 Oct 23;5(208).
While patients receiving ≥4 cycles showed major anti-tumor response, immunogenicity limited treatment to 1 or 2 cycles for most patients
despite use of immunosuppressive therapy
6 Treatment Cycles
4 Treatment Cycles
Preclinical Data Supports the Benefits of
SVP-Rapamycin + LMB-100 Combination Therapy
23
Prevents formation of
anti-drug antibodies
Restores LMB-100’s
anti-tumor response
SVP alone does not
accelerate tumor growth
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
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iz
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(
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m
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0 1 0 2 0 3 0
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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
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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
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A
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A n ti-L M B -1 0 0 A n tib o d y
Proc Natl Acad Sci U S A. 2018 Jan 23;115(4):E733-E742
SEL-403
SEL-403 In Clinical Phase 1 at NCI
24
• Enrolled the first patient of a dose-escalating Phase 1 trial
in March 2018 under a CRADA at NCI (NCT03436732)
• Enrolling up to 18 patients with malignant pleural or
peritoneal mesothelioma who have undergone at least one regimen of chemotherapy
• Patients to receive four treatment cycles of the combination product candidate
• Primary objective: Evaluate the safety and tolerability of the combination therapeutic
candidate in the study population
• Additional measurements: Objective Response Rates and ADA titers
CRADA #3157 with NCI
Proprietary &
Licensed Gene
Therapy Programs
Selecta’s Proprietary Gene Therapy Programs
26
Rare and Serious Disease
• Two rare inborn error of metabolism: Methylmalonic Acidemia (MMA) and Ornithine Transcarbamylase (OTC) Deficiency
• Onset in early infancy; significantly reduces life expectancy
Immunogenicity Barrier
• Infants require treatment prior to metabolic crisis to avoid CNS effects; retreatment likely needed as patients grow
• Repeat systemic gene therapy dosing currently not possible due to neutralizing antibodies to viral capsid
• Cellular immune responses to the liver are an additional potential barrier
Clear Clinical Path
• Lead gene therapy program is SEL-302 for MMA
• Clinical endpoints include: Methylmalonyl-CoA mutase and MMA levels
• Expect to file IND in 2019
Ownership
• Two proprietary gene therapies utilizing Anc80 and AAV + SVP-Rapamycin (SEL-302 & SEL-313)
Benefits of ADA Mitigation in Gene Therapy
27
Inhibiting Liver
Inflammation from First Dose
Allowing for Repeat Dosing
And Dose Titration
CD8 T cell Liver Infiltrates
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
Anti-AAV8 Antibody Titer
Serum Factor IX Expression
Preclinical data generated in mice in collaboration with Dr. Federico Mingozzi, Genethon
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)
S V P E m p ty N P
0
5
1 0
1 5
2 0 **
A
LT
a
ct
iv
ity
(
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U
/m
L)
0 2 0 4 0 6 0
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D a y s
A
n
ti
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8
T
it
e
r
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40000
80000
120000
160000
200000
34 41 54
H
um
an
F
IX
(n
g/
m
l)
Days
SVP-Rapamycin
Empty NP
Demonstration of the Role of Regulatory T Cells
28
Day 0 19 20 21 32
0 1 28
Effect can be Transferred to a Recipient T Reg Depletion Negates Effect
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
a
n
ti
-A
A
V
8
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g
G
(
µ
g
/m
L
)
E m p ty N P S V P
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1 0
1 5
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* * *
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
+ +
++- -
- -
Preclinical data generated in mice in collaboration with Dr. Federico Mingozzi, Genethon
Anc80/synMUT Proof of Concept
in Mouse Model of MMA at ASGCT 2017
29
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
(
µ
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
0
5
10
15
20
25
30
35
Weight Gain in 12 days (%)
Anc80 or AAV8 Retro Orbital
injection
Reducing MMA Levels With
Anc80 and AAV8
Increasing Weight Gain
Following Treatment
P
er
ce
nt
w
ei
gh
t g
ai
n
Preventing Anti-Anc80
Antibodies via SVP-Rapamycin
Preclinical data generated in mice in collaboration with Dr. Charles Venditti, NIH, and Dr. Luk Vandenberghe, Mass Eye & Ear
Anti-Anc80 Antibodies
** (P = 0.036)
NS (P = 0.44)
(N=3) (N=3) (N=3)
Anc80 AAV8 No Tx
A
n
ti
-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 (µg )
0
Spark Therapeutics License Agreement
30
• December 2016 agreement provides Spark Therapeutics with
exclusive worldwide rights to Selecta's SVP technology for up
to five gene therapy targets
• Among the largest gene therapy and SMID-cap to SMID-cap
biotech deals announced to date
• Initial focus on combination of SVP with Spark’s Hemophilia A gene therapy
• Received $30 million of initial cash payments and investments in Selecta equity
• Subject to the terms of the license agreement, Spark also agreed to pay to Selecta:
- 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
Pipeline
31
Indication Preclinical Phase 1 Phase 2 Phase 3
Proprietary ADA Mitigation Programs
Chronic Severe Gout
SEL-212
Mesothelioma & Pancreatic Cancer
SEL-403
Methylmalonic Acidemia (MMA)
SEL-302
Ornithine Transcarbamylase Deficiency (OTC)
SEL-313
ADA Mitigation Program License
Hemophilia A
Financial Overview
32
For the Year Ended
(In thousands, except share and per share data)
December 31, 2017 December 31, 2016
Grant & Collaboration Revenue $207 $8,083
Research & Development Expenses 45,165 29,702
General & Administrative Expenses 18,826 13,051
Net Loss Attributable to Common Stockholders $(65,321) $(40,776)
Net Loss Per Basic & Diluted Share $(3.20) $(3.89)
Wtd. Avg. Common Shares Outstanding – Basic & Diluted 20,425,050 10,493,939
As of
(In thousands)
December 31, 2017 December 31, 2016
Cash, Cash Equivalents, Marketable Securities, Restricted Cash $96,967 $84,535
Cash runway into mid-2019
Thank You