- Co-administration of AAV8 and ImmTOR shows first dose benefit of higher and more durable transgene expression, in addition to mitigating the formation of neutralizing antibodies, compared to AAV8 alone
- Data support rapid advancement of Selectas gene therapy pipeline, including lead candidate, MMA-101, for the treatment of methylmalonic acidemia (MMA) in collaboration with AskBio, and ornithine transcarbamylase (OTC) deficiency -
WATERTOWN, Mass., Jan. 06, 2021 (GLOBE NEWSWIRE) -- Selecta Biosciences, Inc. (NASDAQ: SELB, Selecta), a biotechnology company leveraging its clinically validated ImmTOR platform to develop tolerogenic therapies that selectively mitigate unwanted immune responses, today announced preclinical data that validate the ImmTOR platforms potential to enhance the efficacy, safety and durability of adeno-associated viral (AAV) vector gene therapies. In the study, Selecta observed that co-administration of AAV vector and ImmTOR in non-human primates (NHP) enabled higher and more durable transgene expression as well as robust inhibition of anti-AAV8 immunoglobulin G (IgG) and neutralizing antibodies.
The observation that co-administration of AAV vector and ImmTOR leads to higher transgene expression demonstrates the potential for dosing lower levels of AAV gene therapies when combined with ImmTORimproving patient safety and lowering costs. Further, long-term gene therapy data demonstrate that expression of systemic AAV gene therapies may wane over time, a limitation that ImmTOR has the potential to address. Finally, AAV gene therapies cannot currently be re-dosed due to the formation of neutralizing antibodies to the AAV vector. In this study, ImmTOR mitigated the formation of these neutralizing antibodies in NHPs, thereby potentially allowing for redosing, another key unmet need in the gene therapy field.
We are encouraged by the promising data announced today, demonstrating ImmTORs potential to address current limitations in the gene therapy field by both increasing transgene expression levels and durability following the first dose as well as inhibiting the formation of AAV-specific antibodies, said Carsten Brunn, Ph.D., president and chief executive officer of Selecta. Our findings indicate that ImmTOR potentially enables gene therapy administration at a lower initial dose and could allow for incremental gene therapy redosing, firmly supporting ImmTORs ability to enhance the efficacy, safety, and durability of these therapies. Our results, along with previous studies supporting ImmTORs hepatoprotective properties in liver injury models, move us one step closer to transforming the lives of patients and realizing the full potential of gene therapy. We look forward to leveraging these findings in our OTC deficiency and our MMA programs, the latter of which we expect to initiate in the first half of 2021 in collaboration with AskBio.
In the study, researchers evaluated the administration of a single intravenous (IV) infusion of a recombinant adeno-associated serotype eight capsid directing expression of a transgene encoding secreted embryonic alkaline phosphatase (AAV8-SEAP), a widely used reporter gene transgene, either alone or co-administered with ImmTOR inNHP. Five cohorts of NHP each received 2x1012 vector genomes (vg)/kilogram (kg) of AAV8-SEAP either alone (cohort 1) or in combination with a single dose of 6 mg/kg ImmTOR (cohorts 2 and 3) or three-monthly doses of 3 mg/kg ImmTOR (cohorts 4 and 5). Cohort 3 received ImmTOR admixed with AAV8-SEAP prior to infusion. All other cohorts received sequential infusions of ImmTOR followed by AAV8-SEAP on Day 0. Cohorts four and five received additional doses of 3 mg/kg ImmTOR at day 28 and day 56 of the study, with cohort five also receiving additional low doses of AAV8-SEAP (0.2x1012 vg/kg) at day 28 and day 56.
Selecta intends to present these findings at the annual meeting of the American Society of Gene & Cell Therapy (ASGCT) in May.
Key findings include:
ImmTOR holds significant promise and could be revolutionary for the gene therapy field, said Jude Samulski, Ph.D., president and chief scientific officer of Asklepios BioPharmaceutical, Inc. (AskBio). The data announced today suggest the use of ImmTOR in conjunction with gene therapy has the potential to overcome significant challenges in the fieldmaking these therapies safer and more effective at lower doses as well as allowing for repeat dosing. We are proud to partner with Selecta and look forward to advancing our investigational therapy through clinical development for patients with MMA and their families.
Selecta, in partnership with AskBio, expects to initiate a Phase 1 clinical trial of MMA-101 and ImmTOR for patients with MMA in the first half of 2021, with preliminary data expected by the end of 2021.
About Methylmalonic AcidemiaMethylmalonic Acidemia (MMA) is a rare monogenic disorder in which the body cannot break down certain proteins and fats. This metabolic disease may lead to hyperammonemia and is associated with long-term complications including feeding problems, intellectual disability, chronic kidney disease and inflammation of the pancreas. Symptoms of MMA usually appear in early infancy and vary from mild to life-threatening. Without treatment, this disorder can lead to coma and in some cases death.
About Ornithine Transcarbamylase (OTC) DeficiencyOTC deficiency is an X-linked genetic disorder caused by genetic mutations in the OTC gene, which is critical for proper function of the urea cycle. Individuals with OTC experience accumulation of excessive levels of ammonia in the blood. The most severe form of the disorder presents within the first few days of life and is characterized by an inability to control body temperature and breathing rate, seizures, coma, developmental delays and intellectual disability. Because the disorder is X-linked, males are most often affected by the severe form of the disease. Less severe forms of the disorder are characterized by delirium, erratic behavior, aversion to high protein foods, vomiting and seizures. Most approved therapies are focused on reducing the amount of ammonia in the blood and are not curative. Currently, the only curative approach is liver transplantation at an early age, which can be associated with severe side effects and complications.
AboutSelecta Biosciences, Inc.Selecta Biosciences Inc. (NASDAQ: SELB) is leveraging its clinically validated ImmTOR platform to develop tolerogenic therapies that selectively mitigate unwanted immune responses. With a proven ability to induce tolerance to highly immunogenic proteins, ImmTOR has the potential to amplify the efficacy of biologic therapies, including redosing of life-saving gene therapies, as well as restore the bodys natural self-tolerance in autoimmune diseases. The companys first program aimed at addressing immunogenicity to AAV gene therapies is expected to enter clinical trials in early 2021 in partnership with AskBio for the treatment of methylmalonic acidemia (MMA), a rare metabolic disorder. A wholly-owned program focused on addressing IgA nephropathy driven by ImmTOR and a therapeutic enzyme is also in development among additional product candidates. Selecta recently licensed its Phase 3 clinical product candidate, SEL-212, in chronic refractory gout to Sobi. For more information, please visitwww.selectabio.com.
Selecta Forward-Looking StatementsAny statements in this press release about the future expectations, plans and prospects ofSelecta Biosciences, Inc.(the company), including without limitation, statements regarding the unique proprietary technology platform of the company, and the unique proprietary platform of its partners, the potential of ImmTOR to enable re-dosing of AAV gene therapy, the potential treatment applications of product candidates utilizing the ImmTOR platform in areas such as gene therapy, the ability of the Company and AskBio to develop gene therapy products using ImmTOR and AskBios technology, the novelty of treatment paradigms that the Company is able to develop, whether the observations made in non-human primate study subjects will translate to studies performed with human beings, the potential of any therapies developed by the company and AskBio to fulfill unmet medical needs, the companys plan to apply its ImmTOR technology platform to a range of biologics for rare and orphan genetic diseases, the potential of the companys intellectual property to enable repeat administration in gene therapy product candidates and products, 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 companys 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 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, the unproven approach of the companys ImmTOR technology, potential delays in enrollment of patients, undesirable side effects of the companys product candidates, its reliance on third parties to manufacture its product candidates and to conduct its clinical trials, the companys 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 companys recurring losses from operations and negative cash flows from operations raise substantial doubt regarding its ability to continue as a going concern, substantial fluctuation in the price of its common stock, and other important factors discussed in the Risk Factors section of the companys most recent Quarterly Report on Form 10-Q, and in other filings that the company makes with theSecurities and Exchange Commission. In addition, any forward-looking statements included in this press release represent the companys 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 press release.
For Investors:Bruce MackleLifeSci Advisors, LLC+1-929-469-3859bmackle@lifesciadvisors.com
For Media: Meredith Sosulski, Ph.D.LifeSci Communications, LLC+1-929-469-3851msosulski@lifescicomms.com
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Selecta Biosciences Announces Data in Non-Human Primates, Further Validating Multiple Potential Benefits of the ImmTORTM Platform in Gene Therapy -...
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