Category Archives: Genetic Therapy

Back in 2017, in the wake of back-to-back setbacks and a reorganization, a struggling little biotech named Endocyte completed a $12 million licensing deal that would ultimately put it on a path toward a $2.1 billion buyout.

As it turned out, Versant Ventures was also eyeing that very same drug out of Germany: PSMA-617, a radioligand therapeutic for castration-resistant prostate cancer.

We actually put a term sheet out on that asset because we just thought the efficacy data were so profound there, managing director Jerel Davis told Endpoints News, referring to a drug that registered a progression-free survival rate of 7.6 months among PSMA-positive patients, with one cohort hitting an overall survival rate of 13.5 months.

After three years of scouting the (small) space for opportunities Versant reckons a fresh start is the way to go. The biotech fledgling, RayzeBio, is debuting today with $45 million in Series A money, with venBio as a co-leader and Samsara BioCapital also chiming in.

With Novartis now claiming two of the most advanced programs in the field both PSMA-617 and FDA-approved Lutathera, from a $3.9 billion acquisition of Advanced Accelerator Applications radiopharmaceuticals has intrigued quite a few biotech observers, noted CEO Ken Song. But securing a steady supply of therapeutic radioisotopes, especially the more potent alpha isotopes, has been a challenge for anyone looking to mount an early-stage effort.

While the targeted delivery approach behind radiopharmaceuticals is similar to antibody-drug conjugates, radioisotopes such as Actinium-225, which RayzeBio is deploying, are many fold more potent, probably 100 or 500 times more potent than cytotoxic payloads in ADCs, Davis added.

What has happened over the last several years is that a multitude of groups in both academia and industry have devised alternate ways to generate Actinium-225 where theyve actually provided data to show that this can be produced and scaled up to sufficient quantities, he said. Thats only come to light over the last year, year and a half.

That opened up a white space that Song, who was looking to take a considerable amount of time off and turned down dozens of other offers as he stepped down from the helm at Metacrine, couldnt pass up.

The founders, led by Nektar vet and former Third Rock entrepreneur Deborah Charych, were intent on creating a purpose-built operation that would go broader and deeper than current players, said Aaron Royston, managing partner of venBio.

Instead of repurposing existing molecules to target cancer antigens, for instance, RayzeBio has partnered up with Japans PeptiDream to discover new peptides against a range of validated solid tumor targets. The peptides will then be radiolabeled with Actinium-225 in-house for preclinical work and by contract manufacturers in clinical studies through commercialization.

Were really asking the peptides to do exactly what peptides do well, Royston said. They can penetrate tumors with their small sizes, are specific to targets, and have relatively short half life properties that people usually dont want in a drug. Yet with radiopharma I think its a perfect application.

In line with a vision to be the first radiopharma platform play, the biotech has put together 7 active programs, with the goal to have at least one development candidate by the second half of 2021. The first clinical trials should happen no more than one year thereafter.

Notably, RayzeBio will be able to use part of its drugs to identify the patients it wants to recruit into trials by taking the same binders but swapping out the therapeutic isotope for an imaging agent. It spells a targeted yet broadly applicable approach that Song believes would attract and accommodate a large number of players.

Someone needs to be part of the early pack, Song said about RayzeBios team, which consists of 10 full timers and about a dozen consultants and advisors. Our goal obviously is to always be ahead of everyone because were getting a head start by focusing on it now. But that is up to us to ensure that we maintain that advantage.

Link:
Novartis bet $6B on the idea now Versant, venBio have $45M to birth a platform play for radiopharmaceuticals - Endpoints News

TORONTO -- Canada has surpassed 20,000 active cases of COVID-19, with more than 2,100 new cases added in the last day. Here's what else you need to know to start your day.

1. U.S. election: U.S. President Donald Trump faces the bleakest October polling numbers of any candidate in the past four presidential elections. CTVNews.ca takes a look at the state of the race 19 days before the U.S. election.

2. Fighting for identity: A First Nations formally declared extinct in Canada could soon have that declaration reversed by the Supreme Court after more than half a century.

3. Internet freedom: Canada is considered one of the top countries in the world when it comes to internet freedom, even as overall digital freedom is experiencing a dramatic erosion globally as a result of the COVID-19 pandemic, according to a new report.

4. 'Dramatic changes': Research out of Ontario's York University suggests more and more lakes are not freezing over during the winter months, which can harm the local ecosystem and make it hard for people to enjoy two winter pastimes: ice fishing and skating.

5. Moving the goalpost: Trying to guess when the COVID-19 pandemic will end has felt a bit like trying to follow a bouncing ball, but experts say the constantly shifting timeline carries a psychological benefit.

One more thing

'I never saw stars': For the first time, a targeted gene replacement therapy has been approved in Canada, bringing hope to thousands of people struggling with a genetic condition in which their sight slowly degrades.

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5 things to know on CTVNews.ca for Thursday, October 15, 2020: US election, internet freedom, gene therapy - CTV News

PHILADELPHIA, PA, Oct. 13, 2020 (GLOBE NEWSWIRE) -- PHILADELPHIA, PA, October 13, 2020 Spirovant Sciences, a gene therapy company developing treatments and cures for genetic lung diseases including cystic fibrosis, todayannounced that its CEO, Joan Lau, PhD, has been selected to receive the Ernst & Young LLP (EY US) Entrepreneur of The Year 2020 Award in Greater Philadelphia by an independent panel of judges. The Entrepreneur of The Year Awards program is one of the preeminent competitive awards for entrepreneurs and leaders of high-growth companies. The award recognizes those entrepreneurial leaders who are excelling in overcoming adversity; financial performance; societal impact and commitment to building a values-based company; innovation; and talent management.

Spirovant Sciences has experienced significant growth under Laus strategic leadership and vision for the company, including being acquired twice in 2019. The company also continues to progress its pipeline, with its lead candidate, SPIRO-2101, recently receiving FDA Orphan Drug and Rare Pediatric Disease designations for the treatment of cystic fibrosis.

I thank the EY Entrepreneur of The Year Award judges and Ernst & Young for this incredible honor, said Lau. I also owe a debt of gratitude to our incredible Spirovant team. Together, we are achieving some amazing company successes in advancing our gene therapy programs. I am honored to represent this team, the incredible Greater Philadelphia entrepreneurial community, and the broader gene therapy and biotech industries.

About EY Entrepreneur of the Year

Entrepreneur of The Year is the worlds most prestigious business awards program for unstoppable entrepreneurs. These visionary leaders deliver innovation, growth and prosperity that transform our world. The program engages entrepreneurs with insights and experiences that foster growth. It connects them with their peers to strengthen entrepreneurship around the world. Entrepreneur of The Year is the first and only truly global awards program of its kind. It celebrates entrepreneurs through regional and national awards programs in more than 145 cities in over 60 countries. Winners go on to compete for the EY World Entrepreneur of The Year title. Founded and produced by Ernst & Young LLP, the Entrepreneur of The Year Awards are nationally sponsored by SAP America and the Kauffman Foundation. In Greater Philadelphia, sponsors also include PNC Bank, DFIN, SolomonEdwards Group, Ballard Spahr LLP, Morgan, Lewis & Bockius LLP, Murray Devine & Company and Pepper Troutman LLP.

About Spirovant Sciences, Inc.Spirovant is a gene therapy company focused on changing the course of cystic fibrosis and other genetic lung diseases. The company's current investigational gene therapy technologies are designed to overcome the historical barriers that have prevented effective genetic treatments for cystic fibrosis. Spirovant is advancing programs for cystic fibrosis with both AAV and lentivirus vectors. Spirovant is a wholly owned subsidiary of Sumitovant Biopharma Ltd., which is itself a wholly owned subsidiary of Sumitomo Dainippon Pharma Co., Ltd. Spirovant is located inPhiladelphia, PA.More information is available athttps://www.spirovant.com/.

About Sumitovant BiopharmaLtd.Sumitovant is a global biopharmaceutical company with offices inNew York CityandLondon. Sumitovant is a wholly owned subsidiary of Sumitomo Dainippon Pharma Co., Ltd. Sumitovant is the majority shareholder of Myovant and Urovant, and wholly owns Enzyvant, Spirovant andAltavant. Sumitovant'spipeline is comprised of early- through late-stage investigational medicines across a range of disease areas targeting high unmet need. For further information about Sumitovant please visithttps://www.sumitovant.com/.

About Sumitomo Dainippon Pharma Co., Ltd.Sumitomo Dainippon Pharma is among the top-ten listed pharmaceutical companies inJapan, operating globally in major pharmaceutical markets, includingJapan, the U.S.,Chinaand the European Union. Sumitomo Dainippon Pharma is based on the merger in 2005 between Dainippon Pharmaceutical Co., Ltd., and Sumitomo Pharmaceuticals Co., Ltd. Today, Sumitomo Dainippon Pharma has more than 6,000 employees worldwide. Additional information about Sumitomo Dainippon Pharma is available through its corporate website athttps://www.ds-pharma.com/.

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Spirovant CEO Joan Lau Selected EY Entrepreneur of The Year in Greater Philadelphia - GlobeNewswire

Last October, the FDA OKd a semi-controversial new antibiotic from Shionogi.

In one of two large studies for the drug, known chemically as cefiderocol and commercially as Fetroja, more patients died in the treatment arm than the control arm. But it had already cleared another randomized controlled trial and the agency determined the benefits at a time of growing drug resistance outweighed the risk.

Now, a year and an expanded approval later, Shionogi has published the full results from both of those studies in a single issue of The Lancet Infectious Disease. And while the papers dont provide any radically new information, they give a final, tempered note on the benefits of a drug that was developed for its new and promising approach to resistant bacteria, but whose late-stage trials left as many questions and answers.

The best interpretation of cefiderocol that can be gleaned from these studies is that it is as good as comparator agents that are frankly suboptimal, University of Maryland School of Medicine professor Emily Heil and Johns Hopkins pediatrics professor Pranita Tamma wrote in a concurrent review.

The results have admittedly tempered some of our initial enthusiasm for cefiderocol, and more data are needed to confidently define its role in the treatment of drug-resistant infections, they added.

Heil and Tamma titled the review Cefiderocol: the Trojan horse has arrived but will Troy fall? Fetroja earned the Grecian moniker because it entered bacteria through the iron transport pathway they rely on to survive, offering a gateway through the cell wall that helps gram-negative bacteria avoid antibiotics and circumventing several of the key methods they use to evolve drug resistance. Unlike other experimental antibiotics, it also was active against a variety of bacteria as opposed to any single one.

Sure enough, in one of the Phase III studies, called APEKS-NP, Fetroja proved just as good at treating patients with hospital-acquired pneumonia as patients who received the antibiotic meropenem. The difference in deaths from any cause at 14 days was 0.8%, far more than close enough to meet the primary endpoint of non-inferiority. Heil and Tamma noted that 70% of patients were in severe condition, and they commended Shionogi for using meropenem, which they deemed a better comparator than what other companies had used.

In the second study, though, known as CREDIBLE-CR, patients with drug-resistant bacteria were randomly assigned to receive Fetroja or the best available therapy. Of these patients, 45% had hospital-acquired pneumonia and 31% had blood-stream infection.

The results met the primary endpoint, a physician-assessed metric known as clinical cure, for both types of infection.

Yet, on mortality, the data were far worse for pneumonia and blood-stream infection than for urinary tract infections. A quarter of pneumonia patients died by day 14 on the treatment, compared with 11% on the control arm. For bloodstream infections, those figures were 22% vs 11%. For complicated UTIs, though, the figures were reversed: 12% mortality in the treatment arm, 42% in the control arm.

Those high mortality rates were primarily driven by one strain of bacteria, called Acinetobacter baumannii. Shionogi attributed the mortality rates in those patients to pre-existing risk factors, echoing investigators who noted little difference in that bacteria in the APEKS study. The reviewers argued, though, that APEKS didnt have enough A baumannii patients to draw a conclusion.

The mortality could mean Fetroja might just be a bad option for that bacteria, the reviewers wrote, but it could also mean that Fetroja just isnt much better than the alternatives.

It adds credence to the idea that cefiderocol is as good as, but no better than, other drugs for most carbapenem-resistant organisms, they said.

Going forward, Heil and Tamma recommended Fetroja for complicated UTIs and as a salvage option for patients with most other gram-negative, drug-resistant infections. They added it was still unclear how effectively bacteria will learn to resist the new drug.

Cefiderocol will be a valuable soldier in battles against gram-negative resistance, they wrote, but it probably will not win the war.

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Pair of Lancet studies give final word on a promising Shionogi antibiotic that turned out to be 'as good' as the other 'suboptimal' options -...

The University of Manchester, part of the prestigious Russell Group of universities, has announced today a groundbreaking gene therapy partnership to ease the lifelong suffering of people with Hunter syndrome.

The University has agreed to a worldwide license and collaborative research funding agreement with AVROBIO, Inc., a leading clinical-stage gene therapy company with a mission to free people from a lifetime of genetic disease, based in Cambridge, Massachusetts, USA.

The significant partnership agreement is for the clinical development of an investigational lentiviral gene therapy for mucopolysaccharidosis type II (MPS II), or Hunter syndrome, a rare and deadly lysosomal disorder that primarily affects young boys.

Hunter syndrome, which affects an estimated one in 100,000 males worldwide, causes devastating complications throughout the body and brain, including severe cardiac and respiratory dysfunction, skeletal malformations and hearing impairment. Children with severe cases of Hunter syndrome typically show early symptoms in their toddler years and begin to regress developmentally around age six, losing basic motor skills and cognitive function.

The current standard of care is weekly enzyme replacement therapy (ERT), which can delay some complications but does not halt overall progression of the disease and has not been demonstrated to address cognitive issues. Even with ERT, people with Hunter syndrome face life-limiting symptoms and a significantly reduced life span.

The University of Manchester will sponsor the investigator-led Phase 1-2 clinical trial for Hunter syndrome which is expected to begin in 2021. The Hunter syndrome program was developed by Brian Bigger, a professor of cell and gene therapy at The University of Manchester. Professor Bigger has published preclinical data demonstrating that the introduction of the transgene with an optimised, proprietary tag has the ability to correct peripheral disease and normalise brain pathology.

Primary investigators for the clinical trial will be; Professor Robert Wynn, Consultant Paediatric Hematologist at the Royal Manchester Childrens Hospital and Dr. Simon Jones, Consultant Paediatric Physician for inherited metabolic diseases at the Willink Unit, Saint Marys Hospital and the Manchester Centre for Genomic Medicine.

We feel an enormous urgency to bring forward a treatment that may halt this deadly disease in its tracks, before symptoms emerge and before children lose their physical and cognitive skills, said Professor Bigger. We are delighted to be working with AVROBIO on this program. Both of our teams have deep experience running international clinical trials in other lysosomal disorders. AVROBIO also has a leading gene therapy platform, plato, which is designed to optimise the consistency, predictability and efficacy of its gene therapies and to enable efficient scaling for worldwide commercialization. By working together, we believe we can greatly accelerate development of this important program.

The investigational gene therapy, which will be called AVR-RD-05, involves ex vivo transduction of the patients own hematopoietic stem cells with a therapeutic transgene designed to express functional enzyme the patient needs to maintain cellular health, coupled to a proprietary protein tag that is designed to improve stability of the enzyme in the bloodstream and facilitate uptake by tissues from head to toe. When reinfused into the patient, the gene-modified stem cells are expected to engraft in the bone marrow and produce generations of daughter cells, each carrying the transgene. Those daughter cells are then expected to differentiate into macrophages, microglia and other components of the immune system and circulate throughout the body and central nervous system, potentially enabling widespread distribution of functional enzyme.

Geoff MacKay, AVROBIOs president and CEO said: The lentiviral gene therapy approach is well suited to treat a progressive and pervasive disease such as Hunter syndrome, which affects organs throughout the body and severely impairs cognitive function. If we treat children early, before their symptoms arise, we hope to prevent the tragic complications that rob these young children of their futures.

We believe our deep experience with investigational gene therapies for lysosomal disorders will enable us to efficiently move the program through clinical development in collaboration with Professor Brian Bigger, who has done tremendous work to develop and optimize this investigational gene therapy. Were proud to add this program to our leading lysosomal disorder pipeline and excited about its potential to change the lives of patients and families living with Hunter syndrome.

The University of Manchesters technology transfer office, The University of Manchester Innovation Factory and AVROBIO have negotiated the exclusive, worldwide license to the technology. Under the terms of the license, AVROBIO will pay The University of Manchester an upfront cash payment and additional payments based on the achievement of development and regulatory milestones. The company will pay The University a mid-single digit percentage royalty on annual net sales of licensed products. Additionally, under the collaborative research funding agreement, AVROBIO will cover budgeted clinical trial costs.

Andrew Wilkinson, CEO of the Universitys technology transfer company, The University of Manchester Innovation Factory said: We are delighted that AVROBIO will be working with teams from The University of Manchester and The University of Manchester Foundation Trust to develop a therapy for this debilitating genetic disease. AVROBIOs strategic focus on bringing new personalised gene therapies to the world along with their technical and commercial expertise in this area make them an excellent partner for the investigational Hunter syndrome gene therapy programme.

About Hunter syndrome

Hunter syndrome, also known as mucopolysaccharidosis type II (MPS II), is a lysosomal disorder caused by a mutation in the IDS gene that leads to a deficiency of the lysosomal enzyme iduronate-2-sulfatase (IDS), which is essential for breaking down large sugar molecules called glycosaminoglycans (GAGs, also known as mucopolysaccharides). Without functional IDS, toxic levels of GAGs build up throughout the body and central nervous system, causing a wide range of symptoms including cognitive decline and cardiac and respiratory dysfunction. The current standard of care is weekly enzyme replacement therapy, which may delay some symptoms but does not halt the overall progression of disease and does not cross the blood-brain barrier, an intricate web of protective tissue that selectively prevents macromolecules from entering the brain. Even with treatment, people with Hunter syndrome face life-limiting symptoms and a significantly reduced life span. The disorder affects an estimated 1 in 100,000 males worldwide; about two-thirds of cases have an early, severe progressive form.

About lentiviral gene therapy

Lentiviral vectors are differentiated from other delivery mechanisms because of their large cargo capacity and their ability to integrate the therapeutic gene directly into the patients chromosomes. This integration is designed to maintain the therapeutic genes presence as the patients cells divide, which potentially enables dosing of pediatric patients, whose cells divide rapidly as they grow. Because the therapeutic gene is integrated using the vector into patients own stem cells, patients are not excluded from receiving the investigational therapy due to pre-existing antibodies to the viral vector.

About The University of Manchester

The University of Manchester is a member of the prestigious Russell Group and one of the UKs largest single-site universities.

We have over 40,000 students, 12,000 staff and, with almost 480,000 former students from more than 190 countries, are home to the largest alumni community of any campus-based university in the UK. No fewer than 25 Nobel laureates have either worked or studied here.

We are thetop UK University for graduate employabilityaccording to The Times and Sunday Times Good University Guide; ranked 27th in the world in the QS World University Rankings (2020) and 6th in the UK. Were also listed as 8th in Reuters Top 100: Europe's most innovative universities (2019).

Visit http://www.manchester.ac.uk for further information or https://www.manchester.ac.uk/discover/vision/ for our latest strategic vision.

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University of Manchester announces partnership with AVROBIO for Hunter syndrome gene therapy - PharmiWeb.com

The innovation experts at Cleveland Clinic have peered into their crystal ball and pronounced the most profound medical advancements that will impact the care and treatment of patients in the coming year.

During the closing session of the 2020 Cleveland Clinic Medical Innovation Summit, the 18th year the conference has been held, Cleveland Clinic Innovations shared its annual list of top 10 medical innovations. The breakthrough technologies were selected by a committee of Cleveland Clinic subject matter experts, led by Will Morris, MD, executive medical director, Cleveland Clinic Innovations, and Akhil Saklecha, MD, managing director, Cleveland Clinic Ventures.

1. Gene Therapy for Hemoglobinopathies

Experimental gene therapy gives new hope to those suffering from hemoglobinopathies, genetic disorders responsible for sickle cell disease and thalassemia. Through treatment, those with these conditions have the potential ability to make functional hemoglobin molecules, reduce the presence of sickled blood cells or ineffective red blood cells in thalassemia, and prevent associated complications.

2. Novel Drug for Primary-Progressive Multiple SclerosisA new, U.S. Food and Drug Administration (FDA)-approved therapeutic monoclonal antibody with a novel target is the first and only multiple sclerosis (MS) treatment for 15% of primary-progressive patients, who experience gradual onset and steady progression of signs and symptoms. In those with MS, the immune system attacks the fatty protective myelin sheath that covers the nerve fibers, causing communication problems between the brain and the rest of the body that can result in permanent damage or deterioration and eventual death.

3. Smartphone-Connected Pacemaker Devices

Remote monitoring of implantable pacemakers and defibrillators traditionally occurs through a bedside console that transmits data to the physician. Yet many patients don't understand how it functions, and adherence to remote monitoring has been suboptimal. New Bluetooth-enabled pacemaker devices used in conjunction with a mobile app, offer a convenient new method to transmit data, while also providing patients greater insight into their health status.

4. New Medication for Cystic Fibrosis

A new combination drug, approved by the FDA in October 2019, provides relief for patients with the most common cystic fibrosis gene mutation (F508 del), estimated to represent 90% of individuals living with the disease. Medications developed prior to last year had only been effective in a subset of people with certain mutations.

5. Universal Hepatitis C Treatment

A new, approved fixed-dose combination medication has vastly improved hepatitis C treatment. More than 90% effective for hepatitis C genotypes one through six, the therapy represents an effective option for a wider scope of patients. With no vaccine for the hepatitis C virus, patients have been limited to medication, but many treatments were accompanied by adverse side effects or only effective for certain genotypes of the disease.

6. Bubble CPAP for Increased Lung Function in Premature Babies

Newborns with infant respiratory distress syndrome now have access to a safer method of ventilation though b-CPAP, a non-invasive ventilation strategy. Unlike mechanical ventilation, which administers a surfactant that can cause lasting lung injury, b-CPAP maintains lung volumes during exhalation through oscillating, rather than constant pressure, minimizes physical trauma, and stimulates lung growth when administered over a prolonged period.

7. Increased Access to Telemedicine through Novel Practice and Policy Changes

While telehealth technologies and initiatives have been around for years, COVID-19 forced them into the spotlight and stimulated widespread adoption. "Since March, state and federal regulators have moved quickly to reduce telehealth adoption barriers, understanding that these tools can speed access to care while protecting healthcare workers and community members," according to Cleveland Clinic. "These measures opened the floodgates for telehealth, allowing for new programs and the expansion of existing networks."

8. Vacuum-Induced Uterine Tamponade Device for Postpartum Hemorrhage

A low-tech solution is now part of the arsenal to fight postpartum hemorrhage (PPH). Vacuum-induced uterine tamponade uses negative pressure created inside the uterus to collapse the bleeding cavity, causing the muscle to close off the hemorrhaging vessels. The device represents another minimally invasive tool that is potentially translatable to developing countries with minimal resources.

9. Prostate Cancer PARP Inhibitors

Previously known for their success in treating womens cancers, two PARP inhibitors, which block proteins that help repair damaged tumor DNA in people with BRCA1 and BRCA2 gene mutations, were approved for prostate cancer treatment in May. These pharmacological agents have been demonstrated to delay the progression of prostate cancer in men with refractory cancer and DNA repair pathway mutations.

10. Immunologics for Migraine Prophylaxis

New medications were developed in 2018 help head off migraine pain by blocking activity of the calcitonin gene-related peptide (CGRP) molecule, which spikes during these headaches. In 2020 this FDA-approved class of medication became the first actively prescribed therapeutic for preventative treatment of migraines, which affect an estimated 12% of the U.S. adult population.

More information about the these innovations, including videos and year-by-year comparisons is available on the website.

Mandy Roth is the innovations editor at HealthLeaders.

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Cleveland Clinic Names Top 10 Medical Innovations; Sickle Cell Therapy Tops the List - HealthLeaders Media