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|Item 7.01|| |
Regulation FD Disclosure.
On November 8, 2021, Selecta Biosciences, Inc. (the “Company”) posted a slide presentation in the “Investors & Media” portion of its website at www.selectabio.com containing top-line data for the Phase 1 clinical trial evaluating the potential of the ImmTOR platform in mitigating the formation of neutralizing antibodies against adeno-associated viral serotype 8 (AAV8) vectors used in gene therapies. A copy of the slide presentation is furnished as Exhibit 99.1 to this Current Report.
The information contained in Item 7.01 of this Current Report (including Exhibit 99.1 attached hereto) shall not be deemed “filed” for purposes of Section 18 of 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 or the Exchange Act, except as expressly provided by specific reference in such a filing. The Company undertakes no obligation to update, supplement or amend the materials attached hereto as Exhibit 99.1.
|Item 8.01|| |
On November 8, 2021, the Company announced top-line data from the Phase 1 clinical trial evaluating the potential of the ImmTOR platform in mitigating the formation of neutralizing antibodies against adeno-associated viral serotype 8 (AAV8) vectors used in gene therapies. Top-line results include:
AAV8 empty capsids elicited peak median anti-AAV8 neutralizing antibody (NAb) titers of 1:6875.
Median day 30 titers of neutralizing anti-AAV8 antibodies were 1:25 and 1:5 in the 0.15 mg/kg and 0.3 mg/kg ImmTOR cohorts, respectively.
Median day 30 titers of neutralizing anti-AAV8 antibodies were 50-fold and 250-fold lower in the 0.15 mg/kg and 0.3 mg/kg ImmTOR cohorts respectively compared to the median of control subjects dosed with AAV8 empty capsid alone.
At 30 days 6 of 6 or 100% of subjects that received 0.3 mg/kg of ImmTOR exhibited an anti-AAV8 neutralizing antibody titer of 1:25 or less. 4 of 6 or 67% of subjects at this dose had a titer of 1:5 or less.
At 30 days 6 of 9 or 67% of subjects that received 0.15 mg/kg of ImmTOR exhibited an anti-AAV8 neutralizing antibody titer of 1:25 or less. 2 of 9 or 22% of subjects at this dose had a titer of 1:5 or less.
1 of 8 or 12.5% of subjects that received AAV8 empty capsid alone had a neutralizing antibody titer of 1:25 or less at 30 days and no subjects (0/8) had a titer of 1:5 or less.
At 90 days 2 of 6 subjects in the 0.3 mg/kg cohort were observed to have sustained control of neutralizing antibodies with titers of 1:25 or less.
Consistent with preclinical data, the Company observed that the single dose ImmTOR cohorts saw delayed formation of neutralizing antibodies eventually reaching similar median levels of neutralizing antibodies to the control group by day 90.
No serious adverse events were reported. The most common treatment-related adverse events included stomatitis and rash.
Any statements in this Current Report on Form 8-K about the future expectations, plans and prospects of the Company, including without limitation, statements regarding the proprietary technology platform of the Company, and the proprietary platform of its partners, the programs and disease indication targets anticipated under this collaboration, the anticipated timing or the outcome of ongoing and planned clinical trials, studies and data readouts, the Company’s ability to conduct those clinical trials and studies, the timing or making of any regulatory filings, the ability of the Company and its partners where applicable to develop gene therapy products using ImmTOR, the novelty of treatment paradigms that the Company is able to develop, whether the observations made in non-human primate and mouse study subjects will translate to studies performed with human beings, the potential of any therapies developed by the Company to fulfill unmet medical needs, the Company’s plan to apply its ImmTOR technology platform to a range of biologics for rare and orphan genetic diseases, the ability to re-dose patients and the potential of ImmTOR to allow for re-dosing, the potential to safely re-dose AAV, the ability to restore transgene expression, the potential of the ImmTOR technology platform generally and the Company’s ability to grow its strategic partnerships, 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 proof of concept trials, including the uncertain outcomes, the availability and timing of data from ongoing and future clinical trials and the results of such trials, whether preliminary or topline 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 ability to predict results of studies performed on human beings based on results of studies performed on non-human primates and mice, the unproven approach of the Company’s ImmTOR technology, the Company’s partners’ ability to re-engineer or develop any protein therapeutics, 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, licenses or contractual relationships, 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, the Company’s recurring losses from operations and negative cash flows from operations, substantial fluctuation in the price of its common stock, and other important factors discussed in the “Risk Factors” section of the Company’s most recent Annual Report on Form 10-K and Quarterly Report on Form 10-Q, and in other filings that the Company makes with the Securities and Exchange Commission. In addition, any forward-looking statements included in this Current Report 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 intention to update any forward-looking statements included in this Current Report.
|Item 9.01|| |
Financial Statements and Exhibits.
|99.1||Slide Presentation of Selecta Biosciences, Inc. dated November 8, 2021|
|104||Cover Page Interactive Data File (embedded within the Inline XBRL document)|
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: November 8, 2021||By:|
|Carsten Brunn, Ph.D.|
|President and Chief Executive Officer|
Exhibit 99.1 SELB AAV8 Empty Capsid plus ImmTOR™ (SEL-399) Human Proof-Of-Concept Study* T op Line Data Report of a Phase 1 Clinical Study in Healthy Volunteers November 8, 2021 * Joint study with AskBio
Safe Harbor / Disclaimer Any statem ents in this presentation about the future expectations, plans and prospects of Selecta Biosciences, Inc. (“the company”), including without lim itation, statem ents regarding the pre-clinical and clinical development of gene therapy product candidates b y the com pany, including with respect to anticipated geographic m arkets, the availability and tim ing of data from any future or planned clinical program , the tim ing and execution of com pany’s plans to sub mit any regulatory filings, the potential m arket opportunity for the com pany’s gene therapy programs, the potential of any com pany gene therapy product candidate to address unm et m edical needs including b ut not lim ited to the ab ility to re-treat gene therapy disease indications or enhance transgene expression, the potential treatment applications and regulatory and clinical development of the com pany’s product candidates utilizing the Im mTOR platform in areas such as enzyme therapy and gene therapy and related tim ing, the potential of the Im m TOR technology platform generally and the com pany’s ab ility to grow its strategic collab orations, upcoming events and presentations, including with respect to the presentation of the SEL-399.101 em pty capsid full data set, and other statem ents containing the words “anticipate,” “b elieve,” “continue,” “could,” “estimate,” “expect,” “hypothesize,” “intend,” “m ay,” “plan,” “potential,” “predict,” “project,” “should,” “target,” “would,” and sim ilar expressions, constitute forward-looking statements within the m eaning of The Private Securities Litigation Reform Act of 1995. Actual results m ay differ m aterially from those indicated b y such forward-looking statements as a result of various im portant factors, including, b ut not lim ited to, the following: the uncertainties inherent in the initiation, com pletion and cost of clinical trials including their uncertain outcomes, the effect of the COVID-19 pandemic on any of the com pany’s planned or ongoing clinical trials, m anufacturing activities, supply chain and operations, the availability and tim ing of data from ongoing and future clinical trials and the results of such trials, whether prelim inary results from a particular clinical trial will b e predictive of the final results of that trial or whether results of early clinical trials will b e indicative of the results of later clinical trials, the unproven approach of the com pany’s Im mTOR technology, undesirable side effects of the com pany’s product candidates, the com pany’s reliance on third parties to m anufacture its product candidates and to conduct its clinical trials as well as the impact of the COVID-19 pandemic on those third parties and their ab ility to continue their operations, the com pany’s inability to m aintain its existing or future collab orations, licenses or contractual relationships and the inability of the com pany’s licensees to m ake up-front and m ilestone paym ents under these collaborations, its inab ility to protect its proprietary technology and intellectual property, m anagement’s ab ility to perform as expected, potential delays in regulatory approvals, the com pany’s b usiness development strategy, the availab ility of funding sufficient for its foreseeab le and unforeseeable operating expenses and capital expenditure requirements, the com pany’s recurring losses from operations and negative cash flows from operations raise substantial doubt regarding its ab ility to continue as a going concern, sub stantial fluctuation in the price of its com m on stock, and other im portant factors discussed in the “Risk Factors” section of the com pany’s Quarterly Report on Form 10-Q for the quarterly period ended June 30, 2021 filed with the U.S. Securities and Exchange Com m ission (SEC), and in other filings that the com pany m akes with the SEC. In addition, any forward-looking statem ents included in this presentation represent the com pany’s views only as of the date of its pub lication and should not b e relied upon as representing its views as of any sub sequent date. The com pany specifically disclaims any intention to update any forward-looking statements included in this presentation. 2
The Ability to Inhibit The Development of AAV-Specific Antibodies Has The Potential to Enable Re-Dosing of AAV Gene Therapy • Adeno-associated virus (AAV) vectors are the most widely used in-vivo gene therapy vectors • AAV is non-self replicating and over time transgene expression may wane, particularly in growing tissues such as liver in childhood, suggesting that re-dosing of gene therapy may be necessary • Gene therapy with AAV induces a robust immune response in recipients, resulting in high level anti-AAV neutralizing antibodies (NAb) which precludes re-dosing of the gene therapy • Because NAb can reduce the efficiency of gene therapy, treatment with AAV gene therapy is restricted to patients with low levels of pre-existing NAb. For example, Zolgensma NAb titers must be ≤1:50 to be eligible for treatment • In addition to induction of anti-AAV NAb, the immune response to AAV gene therapy may be involved in observed gene therapy associated toxicities such as hepatotoxicity and thrombotic microvascular angiopathy • As a proof-of-concept study, we studied the ability of ImmTOR, an immune tolerizing drug, to inhibit anti-AAV8 NAb formation in healthy volunteers to evaluate the potential of ImmTOR for gene therapy re-dosing 3
AAV Gene Therapy Induces an Immune Response That Precludes Redosing, Inhibits Efficacy, And Causes Adverse Events • Lower efficacy • Prevention of re-dosing • Adverse events • Loss of efficacy 4
Potential for ImmTOR to Enhance AAV Gene Therapy Potential to enable re-dosing of AAV gene therapy • Prevention of AAV antibody production • Potential to re-dose • Inhibition of liver inflammation • Enhanced efficacy • More durable efficacy • Improved safety 5
Long-Term Inhibition of Anti-AAV8 Antibodies With 3 Monthly Doses of ImmTOR in Animals Single And Multiple Dose ImmTOR Data AAV-EC + AAV-EC + 1 Mice AAV8 Empty capsid 2e13 vp/kg Single dose ImmTOR 3 monthly doses ImmTOR 2.0 2.0 1.5 1.5 1.5 1.0 1.0 1.0 0.5 0.5 0.5 0.0 0.0 0.0 Day Day Day BL = baseline AAV-SEAP + AAV-SEAP + Nonhuman AAV8-SEAP 2e12 vg/kg Single dose ImmTOR 3 monthly doses ImmTOR 1.5 1.5 1.5 2 primates 1.0 1.0 1.0 0.5 0.5 0.5 0.0 0.0 0.0 BL 7 14 28 56 84 BL 7 14 28 56 84 BL 7 14 28 56 84 Day Day Day BL = baseline 1 2 ESGCT 2021 Poster P010 / ESGCT 2021 Poster 003 6 BL 7 12 19 27 42 55 70 84 112 140 168 BL 7 12 19 27 42 55 70 84 112 140 168 BL 7 12 19 27 42 55 70 84 112 140 168 Anti-AAV8 IgG (OD ) 450-570 Anti-AAV8 IgG OD 450-570
Study Design 7
SEL-399 Phase 1 Dose-Escalation Study: Objectives and Endpoints § General Objectives § To determine the immune response to AAV8 empty capsids (EMC-101), which contain no DNA payload, in healthy volunteers § To determine whether single escalating doses of ImmTOR can reduce the immune response to AAV8 empty capsids in healthy volunteers 8
SEL-399 Phase 1 Dose-Escalation Study: Subjects and Design § Total healthy volunteers enrolled: 23 (14 males and 9 females) § All subjects with anti-AAV8 NAb titers <1:5 at baseline § Randomized, placebo controlled and double-blind study Drug Infusions 30 45 60 75 90 Study Day 0 15 Placebo* + Empty Capsid (2E12 vp**/kg) n=3 Placebo + Empty Capsid (2E12 vp/kg) n=3 ImmTOR (0.15 mg/kg) + Empty Capsid (2E12 vp/kg) n=9 Placebo + Empty Capsid (2E12 vp/kg) n=2 ImmTOR (0.3 mg/kg) + Empty Capsid (2E12 vp/kg) n=6 Neutralizing antibodies (NAb) measurement * Placebo=saline infusion ** vp=viral particles 9
SEL-399 Phase 1 Dose- Escalation Study 10
Single Dose ImmTOR Inhibited Formation of Anti-AAV8 NAb at Day 30 100% of subjects dosed with 0.3 mg/kg ImmTOR had NAb titers ≤1:25 at Day 30 67% of subjects dosed with 0.3 mg/kg ImmTOR had NAb titers ≤1:5 at Day 30 Linear Scale Log Scale 10 2000 2000 1000 1500 100 1000 Titer 1:25 10 500 Titer 1:5 1 0 Empty Capsid (n=8) Empty Capsid + 0.15 mg/kg ImmTOR (n=9) Empty Capsid + 0.3 mg/kg ImmTOR (n=6) 11 NAb Titers Log NAb Titers 10
Single Dose ImmTOR Inhibited Formation of Median Anti-AAV8 NAb in a Dose- Dependent Manner at Day 30 1:5 Median NAb titers in subjects dosed with 0.3 mg/kg ImmTOR at Day 30 250-fold lower median NAb titers in subjects dosed with 0.3 mg/kg ImmTOR at Day 30 100000 Median 10000 Titer 1:1250 1000 50-Fold 250-Fold Difference 100 Difference 1:25 10 1:5 1 0 10 20 30 Days Empty Capsid (n=8) Empty Capsid + 0.15 mg/kg ImmTOR (n=9) Empty Capsid + 0.3 mg/kg ImmTOR (n=6) 12 Median Log NAb Titers 10
Subjects Treated With a Single Dose of ImmTOR Developed Delayed NAb Formation by Day 90 Two additional doses of ImmTOR may be required to maintain control beyond Day 30 2 of 6 subjects dosed with 0.3 mg/kg ImmTOR had NAb titers ≤1:25 at Day 90 1 of 6 subjects dosed with 0.3 mg/kg ImmTOR had NAb titers ≤1:5 at Day 90 Day 90 Day 30 Titer 1:25 Titer 1:5 Empty Capsid (n=8) Empty Capsid + 0.15 mg/kg ImmTOR (n=9) Empty Capsid + 0.3 mg/kg ImmTOR (n=6) 13
Empty Capsid Data In-Line With Single Dose ImmTOR NHP Data at Day 90 1 Human Nonhuman Primate Target For Redosing Single dose Single Dose Three Doses 1000000 100000 Titers too high for re-dosing 100000 10000 200+ 10000 Failure 1000 1000 Antibody levels may interfere 50-200 Intermediate with efficient re-dosing** 100 100 Patients eligible for re-dosing* 10 1-50 10 (Zolgensma eligibility: ≤1:50) Target 1 1 AAV8-SEAP AAV8-SEAP * May be dependent on gene therapy dose AAV8-EC + + + ** Ancillary approaches such as IgG protease ImmTOR ImmTOR ImmTOR pre-treatment may be required for re-dosing D0 D0, 28, 56 D0 1 14 ESGCT 2021 Poster 003 Log NAb Titers 10 Log NAb Titers 10
Safety All treatment-related adverse events were expected for ImmTOR, readily monitorable, and transient § There were no Serious Adverse Events (SAEs) § Adverse events related to ImmTOR were expected based on previous clinical trials § Stomatitis (mouth ulcers, redness, or pain) was most common § 3 of 9 subjects in 0.15 mg/kg group and 6 of 6 subjects in 0.3 mg/kg group, all mild to moderate § Average start of stomatitis was on day 11 with an average duration of 8 days § Symptoms were ameliorated with steroid mouth wash § Rash was next most common § 3 of 9 subjects in 0.15 mg/kg group and 3 of 6 subjects in 0.3 mg/kg group, all mild to moderate § Average start of rash was day 12 and resolved after an average of 23 days § No therapy was required § Asymptomatic and transient laboratory AEs in subjects receiving ImmTOR were seen in 2 subjects with mild to moderate thrombocytopenia and 1 subject with grade 3 hypertriglyceridemia 15
Summary and Conclusions § AAV8 empty capsids elicited a strong immune response with peak median anti-AAV8 NAb titers of 1:6875 § ImmTOR inhibited the formation of anti-AAV8 NAb in a dose-dependent manner at Day 30 § After Day 30, 2 of 6 subjects treated with 0.3 mg/kg ImmTOR maintained NAb titers ≤ 1:25, while remaining ImmTOR- treated subjects showed delayed formation of NAb reaching control levels by Day 90 § Animal studies suggest that, if NAb are inhibited at Day 30, administration of two additional monthly doses of ImmTOR may maintain control of NAb beyond 90 days § Safety findings included AEs previously observed with ImmTOR § This promising study in healthy volunteers provides support for the potential use of ImmTOR for the inhibition of neutralizing antibodies to AAV8 in gene therapy clinical trials 17