Document


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



a991_selectainvestorpres
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