Selecta Biosciences Announces Top Line Data from the Phase I SEL-399 AAV Empty Capsid Study, Highlighting Potential Benefits of ImmTOR™ in Gene Therapy
- At day 30, of subjects in the 0.3mg/kg ImmTOR cohort, 100% showed NAb titers of ≤ 1:25, and 67% showed NAb titers of ≤ 1:5 -
- With co-administration of AAV8 empty capsids and ImmTOR,
- Based on these data
“We believe these data demonstrate ImmTOR’s potential to address one of the biggest current limitations in gene therapy, the inability to re-dose life-saving gene therapies due to the formation of neutralizing antibodies against AAV capsids,” said
In the Phase I study, researchers evaluated the administration of a single intravenous (IV) dose of a AAV8 empty capsid containing no DNA with and without a single dose of ImmTOR. Healthy subjects (n=23) were enrolled in a randomized 3:1 ratio of AAV8 dose of 2e12 vector genomes (vg)/kilogram (kg) alone (n=8) or in combination with either 0.15 mg/kg (n=9) or 0.3 mg/kg (n=6) of ImmTOR. The primary endpoints evaluated were safety and neutralizing anti-AAV8 antibody titers.
Key findings include:
- No Serious Adverse Events were reported. All treatment-related adverse events were expected for ImmTOR, readily monitorable, and transient.
- AAV8 empty capsids elicited a strong immune response with 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 titer of control subjects dosed with AAV8 empty capsid alone
- At 30 days, of subjects who received 0.3 mg/kg of ImmTOR, 6 of 6, or 100%, exhibited an anti-AAV8 neutralizing antibody titer of 1:25 or less, and 4 of 6 or 67% had a titer of 1:5 or less
- At 30 days, of subjects that received 0.15 mg/kg of ImmTOR, 6 of 9, or 67%, exhibited an anti-AAV8 neutralizing antibody titer of 1:25 or less, and 2 of 9, or 22% had a titer of 1:5 or less
- By comparison, of subjects that received AAV8 empty capsid alone, only 1 of 8, or 12.5%, 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, we 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
While most subjects treated with a single dose of ImmTOR showed increases in antibody titers by Day 90, preclinical studies in mice and nonhuman primates indicate that if antibodies can be controlled at Day 30, we can maintain control with additional two monthly doses of ImmTOR.
As of the issuing of this press release, the FDA’s 30-day review period for our IND to conduct a Phase 1/2 clinical trial of our SEL-302 product candidate in pediatric patients with methylmalonic acidemia has expired. However, we have been informed orally by FDA that they are still considering certain aspects of our filing related to chemistry, manufacturing and control, or CMC. We intend to wait for formal clearance from FDA before initiating the proposed Phase 1/2 clinical trial.
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Selecta 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 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 Quarterly Report on Form 10-Q to be filed for the quarter ended
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