Category Archives: Genetic Therapy

SAN RAFAEL, Calif., Jan. 10, 2021 /PRNewswire/ --BioMarin Pharmaceutical Inc. (NASDAQ: BMRN) today announced positive topline results from its ongoing global Phase 3 GENEr8-1 study of valoctocogene roxaparvovec, an investigational gene therapy for the treatment of adults with severe hemophilia A. This is the largest global Phase 3 study to date for any gene therapy in any indication, with 134 participants. All participants in the study received a single dose of valoctocogene roxaparvovec and completed a year or more of follow-up.

Data from the GENEr8-1 Phase 3 study with a mean follow-up of 71.6 weeks showed that in the pre-specified primary analysis for Annualized Bleeding Rate (ABR) a single dose of valoctocogene roxaparvovec significantly reduced ABR by 84% from a prospectively collected 4.8 (median 2.8) at baseline to 0.8 (median 0.0) bleeding episodes per year (p-value <0.0001), among a pre-specified group of prior participants in a non-interventional baseline observational study (rollover population; N=112). 80% of participants were bleed-free starting at week five after treatment.

Valoctocogene roxaparvovec also significantly reduced the mean annualized Factor VIII in the rollover population by 99% from 135.9 (median 128.6) to 2.0 (median 0.0) infusions per year (p-value <0.0001).

Table 1: Mean/Median Annualized Bleeding Rate (ABR) and FVIII Infusion Rate in Phase 3 GENEr8-1 Study Rollover Population (N=112) from Week 5 Through Week 52 at Nov. 2020 Cut Off

Phase 3

Rollover Population*

On Factor VIII prophylaxis, beforevaloctocogene roxaparvovec infusion

N=112

Phase 3

Rollover Population*

After valoctocogene roxaparvovecinfusion

N=112

Mean (SD)

Median (IQR)

Mean (SD)

Median (IQR)

Annualized

Bleeding Rate

(bleeding

episodes per

4.8 (6.5)

2.8 (0.0, 7.6)

0.8 (3.0)

0.0 (0.0, 0.0)

Annualized

FVIII Infusion

135.9 (52.0)

128.6 (104.1, 159.9)

2.0 (6.4)

0.0 (0.0, 0.9)

*See study descriptions for patient population information.

At the end of the first year post-infusion with valoctocogene roxaparvovec, participants in the modified intent-to-treat (mITT) population (N=132) had a mean endogenous Factor VIII expression level of 42.9 (SD 45.5, median 23.9) IU/dL, as measured by the chromogenic substrate (CS) assay, supporting the marked clinical benefits observed with abrogation of bleeding episodes and Factor VIII infusion rate. Factor VIII expression declined at a slower rate compared to the Phase 1/2 study, and remained in a range to provide hemostatic efficacy. In a subset of the mITT population that had been dosed at least two years prior to the data cut date (N=17), Factor VIII expression declined from a mean of 42.2(SD 50.9, median 23.9) IU/dL at the end of year one to a mean of 24.4 (SD 29.2, median 14.7) IU/dL at the end of year two with continued hemostatic efficacy demonstrated by a mean ABR of 0.9 (median 0.0) bleeding episodes per year.

Table 2: Factor VIII Activity Levels in 6-Month Intervals

Median Factor

VIII Activity,

IU/dL

Phase 3 Rollover

Population

(N=112)

Mean (SD)

Median

Phase 3 mITT

Subset

Population

(N=17*)

Mean (SD)

Median

Phase 1/2

6e13 vg/kg

Cohort

(N=7)

Mean (SD)

Median

Phase 1/2

4e13 vg/kg

Cohort

(N=6)

Mean (SD)

Median

Week 26

55.1 (57.4)

38.6

43.9 (42.1)

33.8

71.0 (41.6)

61.2

18.0 (8.7)

18.0

Week 52

43.6 (45.3)

24.2

42.2 (50.9)

23.9

63.6 (36.5)

60.3

21.1 (12.3)

23.8

Week 76

27.9 (30.6)

15.8

53.9 (31.2)

50.2

20.6 (15.4)

21.3

Week 104

24.4 (29.2)

14.7

36.4 (26.3)

26.2

12.3 (8.2)

Read the original:
BioMarin Announces Positive Phase 3 Gene Therapy Trial Results in Adults with Severe Hemophilia A; Study Met All Primary and Secondary Efficacy...

ML-powered gene therapy promises to be a ray of hope for patients with rare genetic diseases who cannot be treated using existing drugs and treatments.

FREMONT, CA: A major argument in favor of gene editing is its potential to cut out disease-causing genes. However, while technologies have come a long way, the risk of error remains significant, and safety must be a top priority for gene editing to evolve. AI and Machine learning algorithms are useful in finding where the alteration must be made and how to ensure that the DNA is repaired properly, reducing the potential for errors throughout the process. Similar to diagnosing disease using a genomic basis, AI can find which genes have been impacted by harmful mutations to be targeted in gene therapy. So, here is how AI and machine learning can help gene therapy.

Despite being a radical treatment methodology, gene therapy's success lies in ensuring the therapeutic gene is particularly targeted to the right cells and the right tissue. If poorly executed, gene therapy could encourage harmful mutations in the DNA, resulting in health problems for the patient. In addition to cell targeting, other hurdles facing gene therapists include inadvertently integrating the gene into germline cells and accurately assessing the body's natural immune responses to viral vectors that carry the gene-modifying DNA payloads.

A key remedy to address all of the above challenges is genome sequencing. This technique breaks down and sequences DNA components to better understand their function within the overall genetic code. However, analyzing this wealth of information through legacy statistical techniques can be slow, resource-intensive, and daunting. This is where Machine Learning systems are proving to be valuable. ML provides a learning opportunity from statistical data and performing actions based on the learnings. By using ML, the analysis of complex data can be achieved in a faster and effective way.

ML accelerates the analysis of sequenced data and also predicts the genetic alterations associated with a particular disease. This helps mitigate the time and effort needed in the process of developing precision medicine. Algorithms are developed based on patterns identified in large data sets, translating to human models to understand their effect.

See Also:

Top Artificial Intelligence Solution Companies

Top Artificial Intelligence Consulting/Service Companies

The rest is here:
How AI and ML Transforms Gene Therapy - Healthcare Tech Outlook

- 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

See original here:
Selecta Biosciences Announces Data in Non-Human Primates, Further Validating Multiple Potential Benefits of the ImmTORTM Platform in Gene Therapy -...

Companies looking to bring machine learning into drug discovery are a dime a dozen, but Boston-based Valo Health believes its proprietary platform could give it a leg up in identifying candidates for a range of therapeutic areas. Now, investors are placing a big down payment to see if Valo is right.

Valo Health, which aims to merge AI with human data to formulate cancer therapeutics and beyond, has closed a $190 million Series B financing round. Valo said the financing will expedite several new therapeutic programs using the companys novel drug development platform.

Valo has keyed in on technology dubbed the Opal Computational Platform that integrates human data and artificial intelligence and machine learning to accelerate the drug discovery and development process. This has allowed the company to identify previously unsuspected associations between genetic markers and disease, and identify the specific changes in gene activity.

Valo thus far has focused on oncological, neurodegenerative and cardiovascular diseases with an initial focus on oncology, neurodegenerative, and cardiovascular diseases. In a release, Valo highlighted four cancer genes the company hopes to target in its current portfolio: NAMPT, which is associated with solid tumors and hematological cancers; PARP1, a key protein involved in DNA repair and programmed cell death; USP28, a gene tied to c-myc driven cancers; and HDAC3.

The $190 million comes in the form of preferred equity capital and raises Valos total raised to over $285 million.Financing was led by The Public Sector Pension Investment Board, Valo said in the release. Joining the financing round are all of Valos existing major investors, including Flagship Pioneering, and several new investors including Invus Public Equities, HBM Healthcare Investments, Atinum Investment, and Mirae Asset Capital.

The proceeds from the Series B, Valo said, will support the continued discovery and development of therapeutic programs and will further expand the Opal platform and working capital.

Go here to see the original:
Looking to blend AI and human data, Valo Health scores new financing to test drug discovery platform in oncology, beyond - Endpoints News

SAN FRANCISCO, Jan. 11, 2021 (GLOBE NEWSWIRE) -- Vineti, developer of the leading digital platform of record for personalized therapeutics, today announced a new suite of flexibility features for its Personalized Therapy Management (PTM) solution. These new PTM capabilities deliver unprecedented real-time process controls for advanced therapy manufacturers and Healthcare Providers, ultimately providing better care for patients.

Advanced therapies, such as CAR-T cell therapies, are produced via the most complex supply chain in the history of medicine, with rigorous regulatory requirements every step of the way. Manufacturing batches are typically small often just one single patient-specific product per batch and rely on highly variable manufacturing processes driven by multiple stakeholders scattered across different geographies and facilities. Orchestrating the production, transport, and patient delivery of each batch requires a high degree of flexibility, so that manufacturers can make adjustments and troubleshoot challenges in real time. Keeping each patient product moving quickly, safely, and compliantly demands digital solutions.

As the leader in advanced therapy supply chain orchestration technology, Vineti knows first-hand what types of support these transformative therapies require. Vinetis new set of PTM flexibility features solves critical supply chain workflow challenges that could otherwise hinder advanced therapies and keep some patients including those facing cancer or rare genetic disorders from receiving the personalized treatments they need.

We know what it takes to deliver advanced therapies at scale, and our PTM platform is making that happen through continuous updates and improvements, said Vineti CEO and Co-founder Amy DuRoss. This new set of flexibility-related features is just one of many ways well be expanding our platform, enabling standards and industrial scale for advanced therapies, and helping to provide better patient care throughout the year ahead.

PTM Label Printing

The new PTM Label Printing solution enables flexible in-process labeling for advanced therapies. Accurate, up-to-date patient and product information, on each and every label, is essential for patient safety. But the in-process nature of the label also has the potential to introduce a great deal of complexity and risk of error. An advanced therapy in-process labeling system requires flexibility, so that advanced therapy manufacturers can control what label content gets printed where and by whom, while maintaining rigorous compliance and quality.

Vinetis new PTM Label Printing solution provides multiple options for label printing, even on a per-site basis, ranging from printing to existing on-site printers or cloud connected printers. The flexibility of the PTM labeling solution enables Vineti to support a wide range of label printing use cases. The system supports a wide variety of label content types and standards, including ISBT-128 and SEC, to provide top-tier compliance and privacy protections.

Order Status Tracking and Rescheduling

The updated PTM Order Status Tracking solution enables an end-to-end view of each patient product journey, while providing even more real-time flexibility and control. A wide range of biopharmaceutical teams supporting an advanced therapy, from manufacturing and supply chain management to market access and commercialization, can use PTMs Order Status Tracking to monitor and respond to key processes for the ordering, collection, manufacturing, transportation, and infusion of each patient product.

Order Status Tracking enables manufacturers to check the progress of each order to see if critical steps are complete, delayed, or on time. The solution also now enables rescheduling, one of the most frequent challenges in advanced therapies. Key steps can now be rescheduled via the Order Status Tracking feature set, and those changes can then be cascaded through the rest of the patient journey to keep all milestones updated and tightly coordinated. The end result is more simplicity and greater control for each patient-specific process.

Additional product information

Learn more about PTM Label Printing.View a short demo of PTM Order Status Tracking and Rescheduling.Learn more about the PTM Platform solution.

About Vinetis PTM PlatformThe Vineti Personalized Therapy Management (PTM) platform is the essential engine for advanced therapy supply chains. This industry-leading, purpose-built cloud service is trusted by biopharma clients worldwide to industrialize and scale advanced therapies, ensuring standards, patient safety, security, compliance, and a seamless customer experience. The PTM platform replaces outdated, costly, disparate, bespoke systems with a single enterprise-grade foundation for scaling personalized therapeutics worldwide. Solving the challenges of medicines most complex supply chain at every stage of clinical development and beyond, PTM accelerates access to advanced therapies and helps biopharmaceutical manufacturers transform patients lives.

About VinetiVineti is the first commercial, configurable cloud-based platform to expand patient access to life-saving cell and gene therapies. Vineti was co-founded by GE and the Mayo Clinic to solve the key challenges that patients, medical providers, biopharmaceutical companies, and regulators face in the delivery and commercialization of individualized therapies. Now a fully independent company, Vineti offers a digital platform of record to integrate logistics, manufacturing, and clinical data for personalized therapies. The Vineti Personalized Therapy Management (PTM) platform aligns and orchestrates the cell and gene therapy process and improves product performance overall. The Vineti platform supports the full continuum of patient-specific therapies, including cancer vaccines and autologous and allogeneic cell therapies. Vineti is currently serving patients, healthcare providers, and researchers in hundreds of leading medical centers and manufacturing centers world-wide, on behalf of a growing number of biopharmaceutical partners. In 2019, the World Economic Forum honored Vineti as a World Economic Forum Technology Pioneer. Vineti is headquartered in San Francisco, California, with offices in Bethesda, Maryland and Yerevan, Armenia. For more information, please visit http://vineti.com.

Media ContactsVinetiStacy Henrypress@vineti.com

Continue reading here:
Introducing new Vineti PTM flexibility features: next-gen label printing and rescheduling innovations deliver critical workflow options that advanced...

Bluebird Bio Inc., a biotech pioneer in the field of gene therapies, plans to split itself in two later this year, spinning off its cancer-drug unit into a new, publicly traded company so it can focus on rare diseases.

Bluebird Chief Executive Nick Leschly will helm the new cancer company and assume a new position as executive chairman of Bluebird. Andrew Obenshain, currently Bluebirds president of severe genetic diseases, will become its chief executive, the company said.

The separation is expected to close in the fourth quarter, the company said.

We built this powerful product engine, and the question is: What is the best way to think about the next five to 10 years? Mr. Leschly said in an interview. We dont believe the past is the best way to head into the future.

The restructuring comes as Bluebird struggles to match its scientific achievements advancing its drug pipeline with commercial success. The Cambridge, Mass., biotech has grappled with painful delays in securing U.S. regulatory approvals and generating revenue from a rare-disease blood drug cleared in Europe.

See the original post:
Bluebird Bio to Spin Off Cancer-Drug Unit - WSJ - The Wall Street Journal