Category Archives: Gene therapy

Researchers at Washington University School of Medicine in St. Louis have demonstrated a new gene therapy that builds strength and muscle mass quickly while preventing obesity even when the recipient is eating a high-fat diet. This isnt some crazy new bodybuilding tool, though, but rather something that could be used as a physical therapy aid for people with muscle-weakening arthritis or those suffering from osteoarthritis-related joint pain.

We know that obesity and joint injury are the primary risk factors for osteoarthritis, Farshid Guilak, professor of orthopedic surgery and director of research at Shriners Hospitals for Children in St. Louis, told Digital Trends. However, in cases of severe obesity or muscle loss, it is extremely difficult if not impossible to lose weight or improve muscle strength through normal exercise and diet. The goal of this study was to show the importance of muscle strength in overriding many of the harmful effects of obesity on the joint.

So far, the gene therapy approach has only been demonstrated in mice. The researchers delivered the gene for a molecule called follistatin to the muscle of eight-week-old mice, via injection. The protein blocks myostatin, a molecule normally responsible for stopping muscle growth. The mice in the experiment gained around twice their normal muscle mass and were able to completely burn off all the extra energy from an unhealthy high-fat diet. This prevented almost all the metabolic complications of obesity, such as systemic inflammation and high blood sugar, while also reducing arthritis and pain significantly.

The researchers worried that the gene therapy could potentially have a negative effect on the mices hearts. However, these fears proved unfounded and heart function in the mice actually improved, along with overall cardiovascular health.

These first studies in mice have shown that the procedure has excellent efficacy and safety, Guilak said. The next steps will be to do longer-term studies in mice and possibly larger animals to ensure safety of this procedure.

Guilak said that, should these steps prove successful, the researchers would consider testing the approach in humans with the initial trials in those with severe, possibly life-threatening diseases of the muscles, such as muscular dystrophy.

A paper describing the work was recently published in the journal Science Advances.

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New gene therapy cuts fat and builds muscle with ease. But theres a catch - Digital Trends

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Approach may lead to new treatment approach for osteoarthritis, obesity

Researchers at Washington University School of Medicine in St. Louis found that gene therapy in mice helped build strength and significant muscle mass quickly, while reducing the severity of osteoarthritis. The gene therapy also prevented obesity, even when the mice were fed a high-fat diet.

Exercise and physical therapy often are recommended to help people who have arthritis. Both can strengthen muscle a benefit that also can reduce joint pain. But building muscle mass and strength can take many months and be difficult in the face of joint pain from osteoarthritis, particularly for older people who are overweight. A new study in mice at Washington University School of Medicine in St. Louis, however, suggests gene therapy one day may help those patients.

The research shows that gene therapy helped build significant muscle mass quickly and reduced the severity of osteoarthritis in the mice, even though they didnt exercise more. The therapy also staved off obesity, even when the mice ate an extremely high-fat diet.

The study is published online May 8 in the journal Science Advances.

Obesity is the most common risk factor for osteoarthritis, said senior investigator Farshid Guilak, PhD, the Mildred B. Simon Research Professor of Orthopaedic Surgery and director of research at Shriners Hospitals for Children St. Louis. Being overweight can hinder a persons ability to exercise and benefit fully from physical therapy. Weve identified here a way to use gene therapy to build muscle quickly. It had a profound effect in the mice and kept their weight in check, suggesting a similar approach may be effective against arthritis, particularly in cases of morbid obesity.

With the papers first author, Ruhang Tang, PhD, a senior scientist in Guilaks laboratory, Guilak and his research team gave 8-week-old mice a single injection each of a virus carrying a gene called follistatin. The gene works to block the activity of a protein in muscle that keeps muscle growth in check. This enabled the mice to gain significant muscle mass without exercising more than usual.

Even without additional exercise, and while continuing to eat a high-fat diet, the muscle mass of these super mice more than doubled, and their strength nearly doubled, too. The mice also had less cartilage damage related to osteoarthritis, lower numbers of inflammatory cells and proteins in their joints, fewer metabolic problems, and healthier hearts and blood vessels than littermates that did not receive the gene therapy. The mice also were significantly less sensitive to pain.

One worry was that some of the muscle growth prompted by the gene therapy might turn out to be harmful. The heart, for example, is a muscle, and a condition called cardiac hypertrophy, in which the hearts walls thicken, is not a good thing. But in these mice, heart function actually improved, as did cardiovascular health in general.

Longer-term studies will be needed to determine the safety of this type of gene therapy. But, if safe, the strategy could be particularly beneficial for patients with conditions such as muscular dystrophy that make it difficult to build new muscle.

In the meantime, Guilak, who also co-directs the Washington University Center for Regenerative Medicine and is a professor of biomedical engineering and of developmental biology, said more traditional methods of muscle strengthening, such as lifting weights or physical therapy, remain the first line of treatment for patients with osteoarthritis.

Something like this could take years to develop, but were excited about its prospects for reducing joint damage related to osteoarthritis, as well as possibly being useful in extreme cases of obesity, he said.

Tang R, Harasymowicz NS, Wu CL, Collins KH, Choi YR, Oswald SJ, Guilak F. Gene therapy for follistatin mitigates systemic metabolic inflammation and post-traumatic arthritis in high-fat diet-induced obesity. Science Advances, published online May 8, 2020.

This work was supported by the Shriners Hospitals for Children, the National Institute of Arthritis and Musculoskeletal and Skin Diseases, the National Institute on Aging and the Office of the Director of the National Institutes of Health (NIH). Grant numbers AR50245, AR48852, AG15768, AR48182, AG 46927, AR073752, OD10707, AR060719, AR057235. Additional funding was provided by the Arthritis Foundation and the Nancy Taylor Foundation for Chronic Diseases.

Washington University School of Medicines 1,500 faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Childrens hospitals. The School of Medicine is a leader in medical research, teaching and patient care, ranking among the top 10 medical schools in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Childrens hospitals, the School of Medicine is linked to BJC HealthCare.

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Gene therapy in mice builds muscle, reduces fat Washington University School of Medicine in St. Louis - Washington University School of Medicine in...

PHILADELPHIA, May 07, 2020 (GLOBE NEWSWIRE) -- Passage Bio, Inc. (NASDAQ: PASG), a genetic medicines company focused on developing transformative therapies for rare, monogenic central nervous system (CNS) disorders and the Gene Therapy Program (GTP) at the University of Pennsylvania (UPenn) today announced the expansion of their collaboration agreement to include an additional five programs and extending Passage Bios period to exercise new programs for an additional three years (through 2025). Additionally, Passage Bio will fund discovery research at GTP and will receive exclusive rights, subject to certain limitations, to technologies resulting from the discovery program for Passage Bio products developed with GTP, such as novel capsids, toxicity reduction technologies and delivery and formulation improvements.

Our collaboration with the GTP gives us access not only to the best discovery, technology, and research available but also to pioneering expertise in the field of gene therapy, including pre-clinical development and manufacturing experience that will help guide our programs as we move into clinical development, said Bruce Goldsmith, Ph.D., president and chief executive officer of Passage Bio. Expanding this collaboration provides us with the opportunity to not only deepen our pipeline but also strengthen our own expertise and capabilities as we strive to develop transformative gene therapies for patients. We are tremendously proud of the progress we have accomplished to date through this partnership and look forward to continuing this momentum in the years to come.

This expansion builds upon the original collaboration, which successfully established a strong partnership between Passage and GTP. Under the expanded agreement, Passage will pay $5 million annually to Penn to fund research across numerous technology applications for gene therapy. In addition to five additional program options and an extension of the relationship through 2025, Passage will receive exclusive rights, subject to certain limitations, to IP arising from this research and related indications that are applicable to the products it develops with GTP.

The partnership between GTP and Passage Bio continues to be extremely strong and productive as we collaborate to bring our gene therapy products to patients. We are extremely excited to expand the reach of our CNS products and discovery research through this continued collaboration, said James Wilson, M.D., Ph.D. director of the Gene Therapy Program at the University of Pennsylvania and chief scientific advisor of Passage Bio. As a co-founder of the company, I am also deeply committed to the growth and success of Passage. I believe that the expansion of this strong collaboration further establishes Passage Bios leadership in gene therapy and I look forward to continuing to work with our dedicated teams to reach these shared goals of helping patients with rare, monogenic CNS disorders.

About Passage Bio Passage Bio is a genetic medicines company focused on developing transformative therapies for rare, monogenic central nervous system disorders with limited or no approved treatment options. The company is based in Philadelphia, PA and has a research, collaboration and license agreement with the University of Pennsylvania and its Gene Therapy Program (GTP). The GTP conducts discovery and IND-enabling preclinical work and Passage Bio conducts all clinical development, regulatory strategy and commercialization activities under the agreement. The company has a development portfolio of six product candidates, with the option to license eleven more, with lead programs in GM1 gangliosidosis, frontotemporal dementia and Krabbe disease.

Forward Looking StatementThis press release contains forward-looking statements within the meaning of, and made pursuant to the safe harbor provisions of, the Private Securities Litigation Reform Act of 1995, including, but not limited to: our expectations about our collaborators and partners ability to execute key initiatives and the benefits and obligations associated with our arrangements with our collaborators and partners; and the ability of our lead product candidates to treat the underlying causes of their respective target monogenic CNS disorders. These forward-looking statements may be accompanied by such words as aim, anticipate, believe, could, estimate, expect, forecast, goal, intend, may, might, plan, potential, possible, will, would, and other words and terms of similar meaning. These statements involve risks and uncertainties that could cause actual results to differ materially from those reflected in such statements, including: our ability to develop, obtain regulatory approval for and commercialize our product candidates; the timing and results of preclinical studies and clinical trials; the risk that positive results in a preclinical study or clinical trial may not be replicated in subsequent trials or success in early stage clinical trials may not be predictive of results in later stage clinical trials; risks associated with clinical trials, including our ability to adequately manage clinical activities, unexpected concerns that may arise from additional data or analysis obtained during clinical trials, regulatory authorities may require additional information or further studies, or may fail to approve or may delay approval of our drug candidates; the occurrence of adverse safety events; failure to protect and enforce our intellectual property, and other proprietary rights; failure to successfully execute or realize the anticipated benefits of our strategic and growth initiatives; risks relating to technology failures or breaches; our dependence on collaborators and other third parties for the development of product candidates and other aspects of our business, which are outside of our full control; risks associated with current and potential delays, work stoppages, or supply chain disruptions caused by the coronavirus pandemic; risks associated with current and potential future healthcare reforms; risks relating to attracting and retaining key personnel; failure to comply with legal and regulatory requirements; risks relating to access to capital and credit markets; and the other risks and uncertainties that are described in the Risk Factors section in documents the company files from time to time with theSecurities and Exchange Commission(SEC), and other reports as filed with theSEC. Passage Bio undertakes no obligation to publicly update any forward-looking statement, whether written or oral, that may be made from time to time, whether as a result of new information, future developments or otherwise.

For further information, please contact:

Investors:Sarah McCabeStern Investor Relations, Inc.212-362-1200sarah.mccabe@sternir.com

Media:Emily MaxwellHDMZ312-506-5220emily.maxwell@hdmz.com

Financial Disclosure: The University of Pennsylvania and Dr. James Wilson are both co-founders of Passage Bio and hold equity interests in the company. Dr. Wilson is also the chief scientific advisor of the Company. Penn and GTP are the recipients of significant sponsored research support from the Company under research programs directed by Dr. Wilson. Penn has licensed or optioned numerous technologies to Passage Bio under an existing license and these ongoing sponsored research activities, and both Penn and Dr. Wilson stand to receive additional financial gains in the future under these licensing arrangements.

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Passage Bio Announces Expansion of Gene Therapy Collaboration with University of Pennsylvania - GlobeNewswire

All three patients in Cohort 3 now confirmed responders

All three complete responders in the study remain clinically and metabolically stable after longer-term follow-up

Ultragenyx to host ASGCT recap investor conference call Friday, May 15 at8:30 a.m. Eastern Time

NOVATO, Calif., May 13, 2020 (GLOBE NEWSWIRE) -- Ultragenyx Pharmaceutical Inc. (NASDAQ: RARE), a biopharmaceutical company focused on the development and commercialization of novel products for rare and ultra-rare diseases, today announced positive longer-term safety and efficacy data from the first three cohorts of the ongoing Phase 1/2 study of DTX301, an investigational adeno-associated virus (AAV) gene therapy for the treatment of ornithine transcarbamylase (OTC) deficiency. Six of nine patients in the study have responded to the gene therapy (three female, three male), including all three patients in Cohort 3 who are now confirmed responders. The three previously disclosed complete responders, who have discontinued all ammonia scavengers and liberalized their diet, remain clinically and metabolically stable after longer-term follow-up. Data from the Phase 1/2 study were presented today at the American Society of Gene & Cell Therapy (ASGCT) virtual 2020 Annual Meeting.

We are seeing durable and clinically meaningful responses to DTX301. We are extremely encouraged that the patients who have stopped alternate pathway medications and liberalized dietary restrictions continue to do very well over these longer periods of time, saidEric Crombez, M.D., Chief Medical Officer of the Ultragenyx Gene Therapy development unit. The recent data also reinforces the higher response rate seen with the Cohort 3 dose of 1x10^13 GC/kg. All three patients in Cohort 3 have responded to DTX301 and the treating physician of one of these patients reported that this is the best she has been health wise. This dose has been selected for the Phase 3 study, which is currently expected to initiate in the first half of 2021.

Cohort 3 Updated Data: All three patients at 1x1013 GC/kg dose now confirmed responders

Patient 9 (newly confirmed responder, male):Patient 9 showed a 188 percent increase in rate of ureagenesis, from 25 percent of normal at baseline to 73 percent of normal at Week 24. He now has shown two significantly increased ureagenesis measures and is confirmed as a responder. His ammonia levels have remained in the normal range since treatment. He has not yet discontinued alternate pathway medications or liberalized his diet.

Patient 8 (previously disclosed responder, female): As previously disclosed, Patient 8 has experienced a significant and sustained reduction in her elevated baseline ammonia levels. This patient has now increased protein intake and has discontinued one of her two ammonia scavenger medications. She continues to do well clinically and the plan is to begin to taper her second alternate pathway medication once she is able to return to clinic post COVID-19 restrictions.

Patient 7 (previously disclosed complete responder, female): As previously disclosed, Patient 7 demonstrated a meaningful change in rate of ureagenesis and has maintained normal ammonia levels since treatment. She continues to be clinically and metabolically stable after liberalizing diet and discontinuing ammonia scavenger medications.

Cohorts 1 and 2 Long-term Data Show Sustained Efficacy The two complete responders in Cohorts 1 and 2 (Patients 1 and 4) have shown ongoing durable responses for 2 years and 1.5 years, respectively. Their ureagenesis rates remain above 100% of normal. Both patients have discontinued alternate pathway medications and liberalized restricted protein diets for more than one year, and remain stable with ammonia levels maintained in the normal range. They remain in excellent clinical condition with no significant adverse events, hospitalizations, or other events related to OTC deficiency. The third responder from the earlier cohorts (Patient 6) continues to do well, and is currently tapering her medications and liberalizing her diet. Her increase in ureagenesis and normalization of ammonia have been maintained.

Safety SummaryAs of the data cutoff date, there have been no infusion-related adverse events and no treatment-related serious adverse events reported in the study. All adverse events have been Grade 1 or 2. As previously reported, six patients experienced mild, clinically asymptomatic elevations in ALT levels, similar to what has been observed in other programs using AAV-based gene therapy. All six of these patients have responded to reactive tapering courses of steroids, and all patients remain clinically stable.

Prophylactic Steroid Cohort PlannedA fourth cohort of three patients at the Cohort 3 dose (1.0 10^13 GC/kg) is planned, using prophylactic steroids. Dosing in this cohort is currently on hold due to the COVID-19 pandemic, but data are still expected in the second half of 2020, barring further delays related to clinical site closures due to COVID-19.

Phase 3 Study Planning UnderwayUltragenyx is currently planning the Phase 3 study of DTX301 in parallel to conducting the prophylactic steroid cohort. The Company intends to hold an end of Phase 2 meeting with the U.S. Food and Drug Administration (FDA) in the second half of 2020, based on data from the first three cohorts of the Phase 1/2 study. The use of prophylactic steroids in the Phase 3 study is anticipated, and will be confirmed by the Phase 1/2 fourth cohort data once available. For the Phase 3 study, ammonia is expected to be a primary endpoint based on direct FDA feedback to date. The Phase 3 study is currently expected to begin enrollment in the first half of 2021, barring any significant delays due to COVID-19.

Conference Call and Webcast InformationUltragenyx will host a conference call on Friday, May 15, 2020, at 8:30 a.m. ET/ 5:30 a.m. PT during which Emil D. Kakkis, M.D., Ph.D., the company's Chief Executive Officer and President, will discuss the new data from the DTX301 and DTX401 studies presented at ASGCT. The live and replayed webcast of the call and slides will be available through the companys website at http://ir.ultragenyx.com/events.cfm. To participate in the live call by phone, dial (855) 797-6910 (USA) or (262) 912-6260 (international) and enter the passcode 2366186. The replay of the call will be available for one year.

About the OTC Phase 1/2 Study (DTX301)The Phase 1/2 dose-escalation study evaluates the change in the rate of ureagenesis, ammonia levels, neurocognitive assessment, biomarkers, and safety of DTX301 in adult patients with OTC deficiency. Three patients have been dosed in each of three dose cohorts of 2.0 10^12 GC/kg (Cohort 1), 6.0 10^12 GC/kg (Cohort 2), and 1.0 10^13 GC/kg (Cohort 3). Patients in the first three cohorts received steroids to reactively manage ALT elevations. In the fourth cohort, three patients will receive a 1.0 10^13 GC/kg dose and will all receive a prophylactic tapering course of steroids.

About OTC DeficiencyOTC deficiency, the most common urea cycle disorder, is caused by a genetic defect in a liver enzyme responsible for detoxification of ammonia. Individuals with OTC deficiency can build up excessive levels of ammonia in their blood, potentially resulting in acute and chronic neurological deficits and other toxicities. It is estimated that more than 10,000 people are affected by OTC deficiency worldwide, of whom approximately 80 percent are classified as late-onset and represent a clinical spectrum of disease severity. In the late-onset form of the disease, elevated ammonia can lead to significant medical issues for patients. Neonatal onset disease occurs only in males, presents as severe disease, and can be fatal at an early age. Approved therapies, which must be taken multiple times a day for the patient's entire life, do not eliminate the risk of future metabolic crises. Currently, the only curative approach is liver transplantation.

About DTX301DTX301 is an investigational AAV type 8 gene therapy designed to deliver stable expression and activity of OTC following a single intravenous infusion. It has been shown in preclinical studies to normalize levels of urinary orotic acid, a marker of ammonia metabolism. DTX301 was granted Orphan Drug Designation in both the United States and Europe.

About UltragenyxUltragenyx is a biopharmaceutical company committed to bringing to patients novel products for the treatment of serious rare and ultra-rare genetic diseases. The company has built a diverse portfolio of approved therapies and product candidates aimed at addressing diseases with high unmet medical need and clear biology for treatment, for which there are typically no approved therapies treating the underlying disease.

The company is led by a management team experienced in the development and commercialization of rare disease therapeutics. Ultragenyxs strategy is predicated upon time- and cost-efficient drug development, with the goal of delivering safe and effective therapies to patients with the utmost urgency.

For more information on Ultragenyx, please visit the companys website at http://www.ultragenyx.com.

Forward-Looking StatementsExcept for the historical information contained herein, the matters set forth in this press release, including statements related to Ultragenyx's expectations and projections regarding its future operating results and financial performance, anticipated cost or expense reductions, the timing, progress and plans for its clinical programs and clinical studies, future regulatory interactions, and the components and timing of regulatory submissions are forward-looking statements within the meaning of the "safe harbor" provisions of the Private Securities Litigation Reform Act of 1995. Such forward-looking statements involve substantial risks and uncertainties that could cause our clinical development programs, collaboration with third parties, future results, performance or achievements to differ significantly from those expressed or implied by the forward-looking statements. Such risks and uncertainties include, among others, the effects from the COVID-19 pandemic on the companys clinical trial activities, business and operating results, smaller than anticipated market opportunities for the companys products and product candidates, manufacturing risks, the uncertainties inherent in the clinical drug development process, including the potential for substantial delays and the risk that earlier study results may not be predictive of future study results, the lack of predictability in the regulatory approval process, the timing of regulatory filings and approvals (including whether such approvals can be obtained), and other matters that could affect sufficiency of existing cash, cash equivalents and short-term investments to fund operations, the companys future operating results and financial performance, the timing of clinical trial activities and reporting results from same, and the availability or commercial potential of Ultragenyxs products and drug candidates. Ultragenyx undertakes no obligation to update or revise any forward-looking statements. For a further description of the risks and uncertainties that could cause actual results to differ from those expressed in these forward-looking statements, as well as risks relating to the business of Ultragenyx in general, see Ultragenyx's Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission on May 7, 2020, and its subsequent periodic reports filed with the Securities and Exchange Commission.

Contact Ultragenyx Pharmaceutical Inc.Investors & MediaDanielle Keatley415-475-6876

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Ultragenyx Announces Positive Longer-term Results from First Three Cohorts of Phase 1/2 Study of DTX301 Gene Therapy in Ornithine Transcarbamylase...

PHILADELPHIA, May 12, 2020 (GLOBE NEWSWIRE) -- Passage Bio, Inc. (NASDAQ: PASG), a genetic medicines company focused on developing transformative therapies for rare, monogenic central nervous system disorders, today announced the presentation of preclinical data for its Krabbe disease program. This data was presented today in an virtual oral presentation at the American Society of Gene and Cell Therapy (ASGCT) 23rd Annual Meeting by Juliette Hordeaux, D.V.M., Ph.D., senior director of translational research at the University of Pennsylvanias Gene Therapy Program.

The data presented today showcase the promising potential of pairing CSF administration with high potency vectors to achieve robust, scalable effects utilizing cross-correction on central and peripheral nerve function, said James Wilson, M.D., Ph.D., director of the Gene Therapy Program at the University of Pennsylvania and chief scientific advisor of Passage Bio. The marked improvements on critical markers of disease such as myelination and neuroinflammation as well as, and perhaps more importantly, phenotypic improvements in function and ultimately prolonged survival suggest that ICM gene therapy may be incredibly efficacious for rare CNS indications such as Krabbe disease.

We are extremely excited about this data for our Krabbe program. We believe it demonstrates the potential of the AAVhu68 GALC therapeutic PBKR03 as a life-altering therapy for patients with infantile Krabbe disease, and we look forward to advancing this program into the clinic, said Bruce Goldsmith, Ph.D., president and chief executive officer of Passage Bio. These findings suggest that PBKR03 may be able to normalize GAL-C activity and restore myelination and nerve function in both the brain and key peripheral tissues that would have otherwise resulted in neurodegeneration and eventual death. We believe these data strongly support the continued development of PBKR03 and look forward to continuing to build and evaluate our preclinical models as we prepare for our IND submission in the second half of this year.

In the Twitcher mouse model of Krabbe, CSF delivery of AAVhu68 encoding GALC showed substantial increases in GALC enzyme activity, improved myelination of peripheral nerves, improved neuromotor function and increased survival. In the naturally occurring Krabbe canine model, a single ICM injection of AAVhu68 encoding GALC showed normalization of GALC activity, reduction of CSF psychosine levels, normalization of peripheral nerve conduction velocity, improvement in brain myelination, reduction in brain inflammation, phenotypic correction and increased survival. Treatments in both the mouse and canine models were shown to be well-tolerated with no observed toxicities.

Presentation details

Presentation title: Evaluating the Efficacy and Safety of Cerebrospinal Fluid-Delivered Gene Therapy for Krabbe Disease in Murine and Canine ModelsPresentation date and time: Tuesday, May 12, 2020 4:30pm - 4:45pm ETPresenter: Juliette Hordeaux, D.V.M., Ph.D., University of PennsylvaniaSession title: AAV Gene Delivery for CNS DisordersSession date and time: Tuesday, May 12, 2020 3:45pm - 5:30pm ETAbstract number: 95

About Krabbe DiseaseKrabbe disease is a rare and often life-threatening lysosomal storage disease caused by mutations in the GALC gene, which encodes galactosylceramidase, an enzyme that breaks down galactosylceramide and psychosine. Without adequate levels of galactosylceramidase, psychosine accumulates, causing widespread death of myelin-producing cells and progressive damage to nerves in both the brain and peripheral tissues. The early infantile form of the disease is the most severe and common, typically manifesting before six months of age and accounting for 60% to 70% of diagnoses. In these patients, the disease course is highly predictable and rapidly progresses to include loss of acquired milestones, staring episodes, apnea, peripheral neuropathy, severe weakness, unresponsiveness to stimuli, seizures, blindness, deafness and eventual death by two years of age. Late infantile patients, defined by onset between seven to twelve months of age, present similar symptoms and a median survival of approximately five years from onset of symptoms. There are currently no disease-modifying therapies for Krabbe disease, and we believe incidence may be 2.6 in 100,00 births, which is higher than reported due to lack of adequate screening at birth.

About PBKR03PBKR03 is an AAV-delivered gene therapy encoding GALC currently in late preclinical development for the treatment of infantile Krabbe disease, in which patients have a mutations in the gene that codes for galactosylceramidase (GAL-C). Low GAL-C activity results in accumulation of psychosine which is toxic to the myelin producing oligodendrocytes of the CNS and Schwann cells in the periphery, resulting in damage to both the central and peripheral nervous systems. PBKR03 utilizes a next-generation proprietary AAVhu68 capsid to deliver, through intra-cisterna magna administration, a functional GALC gene. In preclinical models, PBKR03 has shown meaningful transduction of both the central and peripheral nervous system, with restoration of myelination in the brain and peripheral nerves. PBKR03 thus has the potential to treat both the central nervous system and peripheral nerve manifestations observed in Krabbe disease patients. We expect to submit an IND for PBKR03 in the second half of 2020 and to initiate a Phase 1/2 trial in the first half of 2021.

About Passage Bio Passage Bio is a genetic medicines company focused on developing transformative therapies for rare, monogenic central nervous system disorders with limited or no approved treatment options. The company is based in Philadelphia, PA and has a research, collaboration and license agreement with the University of Pennsylvania and its Gene Therapy Program (GTP). The GTP conducts discovery and IND-enabling preclinical work and Passage Bio conducts all clinical development, regulatory strategy and commercialization activities under the agreement. The company has a development portfolio of six product candidates, with the option to license eleven more, with lead programs in GM1 gangliosidosis, frontotemporal dementia and Krabbe disease.

Forward-Looking StatementsThis press release contains forward-looking statements within the meaning of, and made pursuant to the safe harbor provisions of, the Private Securities Litigation Reform Act of 1995, including, but not limited to: our expectations about timing and execution of anticipated milestones, including our planned IND submissions, initiation of clinical trials and the availability of clinical data from such trials; our expectations about our collaborators and partners ability to execute key initiatives; and the ability of our lead product candidates to treat the underlying causes of their respective target monogenic CNS disorders. These forward-looking statements may be accompanied by such words as aim, anticipate, believe, could, estimate, expect, forecast, goal, intend, may, might, plan, potential, possible, will, would, and other words and terms of similar meaning. These statements involve risks and uncertainties that could cause actual results to differ materially from those reflected in such statements, including: our ability to develop, obtain regulatory approval for and commercialize our product candidates; the timing and results of preclinical studies and clinical trials; the risk that positive results in a preclinical study or clinical trial may not be replicated in subsequent trials or success in early stage clinical trials may not be predictive of results in later stage clinical trials; risks associated with clinical trials, including our ability to adequately manage clinical activities, unexpected concerns that may arise from additional data or analysis obtained during clinical trials, regulatory authorities may require additional information or further studies, or may fail to approve or may delay approval of our drug candidates; the occurrence of adverse safety events; failure to protect and enforce our intellectual property, and other proprietary rights; failure to successfully execute or realize the anticipated benefits of our strategic and growth initiatives; risks relating to technology failures or breaches; our dependence on collaborators and other third parties for the development of product candidates and other aspects of our business, which are outside of our full control; risks associated with current and potential delays, work stoppages, or supply chain disruptions caused by the coronavirus pandemic; risks associated with current and potential future healthcare reforms; risks relating to attracting and retaining key personnel; failure to comply with legal and regulatory requirements; risks relating to access to capital and credit markets; and the other risks and uncertainties that are described in the Risk Factors section in documents the company files from time to time with theSecurities and Exchange Commission(SEC), and other reports as filed with theSEC. Passage Bio undertakes no obligation to publicly update any forward-looking statement, whether written or oral, that may be made from time to time, whether as a result of new information, future developments or otherwise.

For further information, please contact:

Investors:Sarah McCabeStern Investor Relations, Inc.212-362-1200sarah.mccabe@sternir.com

Media:Emily MaxwellHDMZ312-506-5220emily.maxwell@hdmz.com

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Passage Bio Announces Presentation of Data from Animal Models of Krabbe Disease at the American Society of Gene & Cell Therapy (ASGCT) 23rd Annual...

Hours after Gilead announced that an NIH trial testing their antiviral drug remdesivir in Covid-19 patients had succeeded, NIAID director Anthony Fauci sat on a couch in the Oval Office and gave the world the top-line readout.

The drug induced a 31% improvement on the primary endpoint of time to recovery: 11 days in the drug arm compared to 15 days in the placebo arm, he said, adding that patients taking the drug appeared less likely to die, with an 8% mortality rate in the drug arm compared to 11% in patients given the placebo.

The mortality data were not yet statistically significant, he cautioned but were trending in the right direction. Fauci, surrounded by President Trump, Vice President Mike Pence and several other advisors, said the news was a very optimistic sign in the hunt for treatments to fight the virus.

Although a 31% improvement doesnt seem like a knockout 100%, it is a very important proof of concept, he said. Because what it has proven, is that a drug has blocked this virus.

Fauci said more details would come and that the study would be submitted to a peer-reviewed journal. Trump, who deferred to Fauci in giving the readout, echoed Faucis commentary.

Its a beginning, that means you build on it, Trump said. But its a very positive event.

Shortly after the briefing, the New York Times reported that the FDA was preparing to issue an emergency use authorization for the drugs use in Covid-19. In an email to Endpoints News, the FDA did not confirm or deny the Times report, but a spokesperson said the agency has been engaged in sustained and ongoing discussions with Gilead Sciences regarding making remdesivir available to patients as quickly as possible, as appropriate.

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BioMarin broadens its gene therapy horizons with a new R&D alliance in rare cardio cases - Endpoints News

SAN RAFAEL, Calif., May 3, 2020 /PRNewswire/ -- BioMarin Pharmaceutical Inc. (Nasdaq: BMRN) today announced that the company has entered into a preclinical collaboration and license agreement with DiNAQOR AG (DiNAQOR), a gene therapy platform company, to develop novel gene therapies to treat rare genetic cardiomyopathies. DiNAQOR will receive an undisclosed upfront payment and is eligible to receive development, regulatory and commercial milestones on product sales in addition to tiered royalties on worldwide sales. The company did not disclose financial terms. BioMarin management reiterated its 2020 GAAP net income guidance of $20 to $80 million, inclusive of this collaboration.

The license initially covers DiNAQOR's lead program, DiNA-001 for MYBPC3 hypertrophic cardiomyopathy (HCM). Additionally, the companies will collaborate on several of DiNAQOR's other pipeline programs, and BioMarin has the option to extend the license to include these additional programs on similar terms. Reflecting the long-term commitment to the collaboration, BioMarin is simultaneously investing in DiNAQOR.

"With this agreement, BioMarin is continuing to apply its gene therapy know-how and manufacturing expertise in new areas like cardiology," said Jean-Jacques Bienaim, Chairman and Chief Executive Officer at BioMarin. "This collaboration extends our global leadership position in gene therapy and boosts our potential to transform the lives of patients worldwide with rare genetic cardiomyopathies."

"We are thrilled to collaborate with the researchers at DiNAQOR to conduct this pioneering work on the development of gene therapies for inherited cardiomyophathies," said Lon Cardon, Chief Scientific Strategy Officer and Senior Vice President at BioMarin. "We believe there is tremendous potential in combining our experience in gene therapy research and development with DiNAQOR's in-depth knowledge of genetic heart diseases."

DiNAQOR was founded and is led by several leading pharmaceutical and biotechnology executives and academics with deep cardiology and gene therapy expertise. The company's holistic approach to gene therapy is focused on gene therapies for the heart that deliver a medical solution that can safely deliver gene therapies to the heart muscle, ensure transduction of the cardiac cells, and limit the exposure of the therapy to other organs.

"BioMarin is a global leader in rare disease research, development and commercialization, and their commitment to DiNA-001 is a powerful validation of DiNAQOR's gene therapy platform," said Dr. Johannes Holzmeister, Co-Founder, Chairman and CEO at DiNAQOR. "We believe our platform has many potential applications and this milestone agreement will enable us to invest in expanding our genetic medicine pipeline."

"Momentum for gene therapies continues to build, and BioMarin has demonstrated tremendous scientific, clinical, and manufacturing leadership and expertise in the space," said Thomas Voit, M.D., Ph.D., Co-Founder and Chief Scientific Officer at DiNAQOR and Director of the Biomedical Research Centre at the Great Ormond Street Hospital and the UCL Institute of Child Health, University College London. "We are looking forward to combining our strengths to expand the promise of gene therapy treatments by targeting the heart muscle to treat rare genetic cardiomyopathies."

About HCM and MYPBC3

Hypertrophic cardiomyopathy (HCM) is one of the most common genetic heart diseases, with about 500,000 patients diagnosed with HCM worldwide. Up to 60% of HCM cases have a genetic origin, and it is estimated that 40% of those have mutations in MYBPC3, the gene that encodes cardiac myosin-binding protein C (MyBP-C).

HCM affects the heart muscle, causing the muscle to enlarge. HCM patients have an increased risk of developing heart failure and life-threatening arrhythmias. There are no approved pharmacological treatment options available that address the underlying disease biology of HCM and invasive surgery or heart transplantation may be the only options available for patients with advanced disease.

About BioMarin

BioMarin is a global biotechnology company that develops and commercializes innovative therapies for serious and life-threatening rare genetic diseases. The Company's portfolio consists of six commercialized products and multiple clinical and pre-clinical product candidates. For additional information, please visit http://www.biomarin.com. Information on BioMarin's website is not incorporated by reference into this press release.

About DiNAQOR

Founded in 2019, DiNAQOR AG is a global gene therapy platform company focused on advancing novel solutions for patients suffering from heart disease. The company's lead preclinical program, DiNA-001 is focused on the treatment of MYBPC3-linked cardiomyopathy. DiNAQOR is headquartered in Pfffikon, Switzerland, with additional presence in London, England and Boston, Massachusetts (US). For more information visit http://www.dinaqor.com.

Forward Looking Statement

This press release contains forward-looking statements about the business prospects of BioMarin Pharmaceutical Inc., including, without limitation, statements about: BioMarin's expectations regarding the announced collaboration, the prospects for the lead and follow on pipeline products and it's 2020 GAAP profitability. These forward-looking statements are predictions and involve risks and uncertainties such that actual results may differ materially from these statements. These risks and uncertainties include, among others: results and timing of current and planned preclinical studies and clinical trials; the content and timing of decisions by the U.S. Food and Drug Administration, the European Commission and other regulatory authorities concerning the programs; the ability to manufacture the product candidates, BioMarin's revenue for 2020, especially with the possible impact of COVID-19, and those other risks detailed from time to time under the caption "Risk Factors" and elsewhere in BioMarin's Securities and Exchange Commission (SEC) filings, including BioMarin's Quarterly Report on Form 10-Q for the quarter ended March 31, 2020, and future filings and reports by BioMarin. BioMarin undertakes no duty or obligation to update any forward-looking statements contained in this press release as a result of new information, future events or changes in its expectations.

BioMarin is a registered trademark of BioMarin Pharmaceutical Inc.

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SOURCE BioMarin Pharmaceutical Inc.

Company Codes: NASDAQ-NMS:BMRN

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BioMarin Extends Gene Therapy Leadership with DiNAQOR in a Preclinical Collaboration and License Agreement to Develop Gene Therapies for Rare Genetic...

The Medical Research Council (MRC) and independent medical research charity LifeArc are streaming 16 million into establishing a network of gene therapy innovation hubs.

The centres will offer clinical grade viral vectors as well as translational and regulatory guidance to support academic-led patient trials of new gene therapies.

Operating as 'centrally coordinated facilities', the hubs aim to address challenges faced by academics as they seek to advance novel gene therapy research into early stage clinical trials, such as a shortage of viral vector production capacity and a complex and evolving translational pathway for gene therapies.

LifeArc and the MRC said they will create the network by providing UK-based research organisations with grants for up to five years, to support the costs associated with expanding or repurposing existing viral vector production centres.

The selected centres, or hubs, will also have access to LifeArcs translation advice and support.

We hope that through this unique collaboration with the MRC, LifeArc can offer its funding and expertise in technology transfer and translational science to support the progression of promising gene therapies, said Dr Melanie Lee, the charity's chief executive. Translation of advanced therapies will be a core focus of LifeArcs future strategy for delivering significant new patient benefits.

MRC executive chair Professor Fiona Watt added: Through this partnership, we aim to support clinical development of the most exciting gene therapy projects from the UKs world-leading academic researchers. This investment will streamline and accelerate progress towards a new generation of genetic medicines for patients.

Read more:
LifeArc, MRC create 16m fund to set up gene therapy hubs - PharmaTimes

The team that developed Zolgensma is back for round two. A group of former AveXis executives and investors unveiled a new gene therapy company, and theyre wasting no time. With 15 programs, $30 million in seed funding and an unrivaled partnership with UT Southwestern Medical Center, Taysha Gene Therapies plans to be in the clinic by the end of the year.

Its working on adeno-associated vector (AAV) gene therapies for monogenic diseasesthat is, diseases caused by a defect in a single geneof the central nervous system. Tayshas lead program targets GM2 gangliosidosis, a very rare disorder that progressively destroys nerve cells in the brain and spinal cord, but the companys portfolio includes conditions that are more prevalent.

The company plans to start clinical trials for three more programs by the end of 2021: treatments for Rett syndrome, a neurodevelopmental disorder; SURF1 deficiency, the most frequent cause of Leigh syndrome; and a SLC6A1 genetic epilepsy, which is similar to Dravet syndrome, Taysha CEO and co-founder R. A. Session II told FierceBiotech.

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And thats not allTaysha has the option to pick up four more prospects from UT Southwestern.

The reason why we can tackle 15 programs with the option to four additional programs is were able to focus on what we do best and were able to allow our collaborators to focus on what they do best, Session said.

Under their partnership, UT Southwestern is working on discovery and preclinical work all the way through IND-enabling studies. It has its own GMP viral manufacturing site to support that work, as well as clinical development, which Taysha will pick up. The company will also take care of regulatory strategy, commercial manufacturing and commercialization. Its a skill set that Tayshas management team honed at AveXis as itdeveloped the gene therapy that eventually became Novartis spinal muscular atrophy treatment Zolgensma.

We essentially flew the plane and built it at the same time when we were developing AveXis We have people with the experience of being able to develop, manufacture and commercialize a gene therapy program and were marrying that with a best-in-class academic research institution, Session said.

RELATED: FDA lets Novartis off the hook in Zolgensma data manipulation

Dividing the labor creates this engine for innovation that allows the partners to advance many programs in parallel, Session added. With about 50 people in its gene therapy unit, UT Southwestern can develop a capsidthe protein shell of a virusfor treatment delivery or get a candidate into animal models much more quickly than a biotech going it alone, he said. The same goes for late-stage development and commercialization on Tayshas side.

For its initial programs, Taysha is focusing on AAV gene therapies because the team knows they work.

AAV9 is the best way we have to treat monogenic CNS disease. If its not broke, dont fix it, Session said. We know how to effectively dose AAV9; we know its safe, effective and efficient. And we know its scalable. These are problems we had to solve at our previous company.

But, moving forward, Taysha and UT Southwestern are working on new technologies, including an AAV delivery platform that would allow for the redosing of gene therapies as well as an AAV capsid platform aimed at improving target delivery.

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Taysha Gene Therapies hits the ground running with $30M, 15 programs - FierceBiotech

The Paris-based BrainVectis, a biotech developing gene therapies for Huntingtons disease and Alzheimers disease, has been acquired by the US clinical-stage gene therapy company AskBio.

AskBios gene therapy experience and manufacturing capacity will help to accelerate BrainVectis lead candidate for Huntingtons into phase I testing. In return, AskBio gets to expand its list of target indications.

AskBio recognized the scientific merit of the work at BrainVectis as an opportunity to strengthen our central nervous system clinical pipeline, Robin Fastenau, VP of Communications for AskBio, told me. No financial details about the acquisition were disclosed.

BrainVectis lead candidate focuses on increasing the expression of a protein called CYP46A1. This enzyme is key for turning excess cholesterol into a derivative that can be cleared from the brain into the blood. It is also reduced in Huntingtons and Alzheimers patients, allowing toxic levels of cholesterol to build up in the brain. By increasing the levels of this enzyme, BrainVectis aims to restore normal cholesterol metabolism and improve the clinical outcome.

So far, BrainVectis lead gene therapy candidate has shown proof-of-concept in animal models of Huntingtons. It also received orphan drug designation from the European Commission last year.

According to Nathalie Cartier-Lacave, CEO and Founder of BrainVectis, AskBio offers a strong cell-line manufacturing process. In particular, it can manufacture a range of viral vectors, including BrainVectis vector of choice: the adeno-associated virus.

This powerful adeno-associated virus technology and Askbios expertise in clinical applications will allow us to rapidly go to clinical application in patients, Cartier-Lacave told me.

There are currently no approved treatments able to slow down the progress of Huntingtons and Alzheimers. Combined with aging populations in developed countries, these debilitating diseases are creating a healthcare challenge. Many companies are trying and sometimes failing to develop drugs able to stop the progression of Alzheimers, for example, as such a drug could make a huge impact on society.

According to Cartier-Lacave, Huntingtons disease is the first target for the company going forward. The disease is caused by a mutation in a gene called HTT that is important for the function of nerve cells. Its a very severe disease for which we think the treatment may not only decrease the toxic mutated protein, but also preserve neurons from death, she added.

Gene therapies are becoming ever more popular in the biotech industry for their potential to tackle previously incurable conditions. BrainVectis is one of several companies aiming gene therapies at the brain; another is the French company Lysogene. However, there are major challenges with developing gene therapies for the brain, for example, getting the therapy past the blood-brain barrier and into the brain tissue.

AskBio might be up to the challenge, as it has taken several gene therapies to the clinic. Its proprietary treatment for the neuromuscular indication Pompe disease is currently in phase I/II, and it has licensed its technology to several big pharmaceutical companies. Those currently in clinical development include treatments for Duchenne muscular dystrophy (Pfizer), hemophilia (Takeda), and spinal muscular atrophy (AveXis), which was approved by the FDA last year, and is awaiting marketing approval by the EMA.

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AskBio Takes Over French Gene Therapy Company to Treat Alzheimers and... - Labiotech.eu