Category Archives: Gene therapy

A gene therapy for bladder cancer that recently received $400 million in support from the private equity company Blackstone Group helped more than half of treated patients with resistant disease achieve remission.

The therapy, called nadofaragene firadenovec, was discovered by a Finnish-based research institute and first entered clinical study in 2012. The data revealed today at the Society of Urologic Oncology meeting came from a Phase 3 trial that is part of the agent's Biologics License Application now before the FDA.

Licensed by its original owner, FKD Therapies Oy, to Switzerland-based Ferring Pharmaceuticals, nadofaragene firadenovec is now in the hands of the U.S. subsidiary FerGene. That company was created with the Blackstone investment and an additonal $170 million from Ferring. FerGene will commercialize the gene therapy in the U.S., with Ferring holding rights elsewhere.

Nadofaragene firadenovec is an an adenovirus-based gene therapy encoding production of the immunity-stimulating protein interferon alfa-2b. Viral vectors containing the gene are administered by catheter once every three months into the bladder, where they are absorbed into cells in the organ's walls and begin stimulating interferon.

Delivery through a catheter, called intravesical administration, limits systemic exposure to both the viral vectors and to inteferon, said Neal Shore, medical director for the Carolina Urologic Research Center and an investigator in the trial.The side-effects of interferon include flu-like symptoms in patients who inject it for other conditions like multiple sclerosis.

The clinical trial enrolled 157 patients with bladder cancer that has not spread to muscle walls and has stopped responding to treatment with Bacillus Calmette-Gurin vaccine.

Alternative treatments for these patients include chemotherapy or a procedure called "complete cystectomy." This surgery entails complete removal of the bladder, which in men means removal of the prostate and seminal vesicles and in women the uterus, ovaries, fallopian tube and part of the vagina.

"Radical cystectomy is one of the most invasive surgeries we do not just in urology but in all of surgery," Shore said, requiring a lengthy hospital stay and having a high rate of post-procedural complications.

Out of a group of 103 patients with superficial tumors in the bladder wall, just over half were in complete remission at three months, 41% at six months, and 24% at one year. In a group of 48 patients whose cancer had spread to the connective tissue outside the bladder, 73% had no recurrence of serious disease at three months, which fell to 44% at 12 months.

In this type of bladder cancer, the FDA has said a single-arm trial, without a placebo control, using complete remission is sufficient to be considered for approval, and the study does not need to pre-specify a rate that would define success. "The natural history of [disease]is well understood, and the complete response rate is negligible in the absence of therapy," the agency said in guidelines published in February 2018.

One chemotherapy agent, called Valstar (valrubicin), is approved for this patient group. It won FDA approval on a complete response rate of 18%.

In seeking FDA approval, nadofaragene firadenovec is in a race with Merck & Co.'s Keytruda (pembrolizumab) to achieve approval first. That immuno-oncology agent tested Keytruda in a similar population in the Keynote-057 trial, in which it achieved a 39% complete response rate.

Keytruda will be the subject of a meeting of the FDA's Oncologic Drugs Advisory Committee on Dec. 17.

Aside from the remission rates,Shore said nadofaragene firadenovec would differentiate itself from Keytruda in practice because its intravesical delivery means it could be administered by community-based urologists at outpatient clinics.

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Cancer gene therapy backed by Blackstone gets trial win - BioPharma Dive

On the heels of an FDA speedy review for Keytrudas potential use in non-muscle invasive bladder cancer (NMIBC), its close rival, a gene therapy by Ferring Pharmaceuticals spinout FerGene, has posted late-stage data. By the looks of it, the two drugs are up for a fight.

Among patients with high-risk NMIBC superficial disease thats unresponsive to standard-of-care Bacillus Calmette-Gurin (BCG), nadofaragene firadenovec eliminated tumors in 53%, or 55 of 103 patients,at month three in a phase 3 study, FerGene unveiled Thursday at the Society of Urologic Oncology meeting.

By comparison, in Keytrudas own registrational trial on the same target patient population, the Merck & Co. PD-1 completely cleared tumors in 41.2%, or 42 of 102 patients, after three months, according to an update at the European Society for Medical Oncology annual meeting in September.

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The length of time responses lasted appeared similar between the two drugs in their separate studies. For Keytruda, 24 patients (23.5%) continued to show no signs of disease after a year. As for nadofaragene firadenovec, 24.3%, or 25 patients, were still tumor-free at month 12.

In terms of safety, Keytruda recorded Grade 3/4 side effects in12.7% of patients, while FerGene said there were no Grade 4/5 events in its study.

We are pleased with these Phase 3 data results, including the complete response rates and favorable safety profile seen with nadofaragene firadenovec, Nigel Parker, scientific founder of FKD Therapies, said in a statement. The data have also helped FKD'snew drug application earn an FDA priority review.

RELATED:Merck's Keytruda is bound for new bladder cancer territory. But can it hold up against gene therapy?

Ferring recently gained commercial rights to the gene therapy from FKD, and, with $400 million in help from Blackstone Life Sciences, spun it into FerGene. Interestingly, it was Merck that licensed the drugout to FKD in the first place in 2011 in return for an equity stake in the then-newly formed Finnish company.

Priority reviews in hand, the two companies could be looking at FDA approvals soon. The burning question is, how does FerGene plan to price a gene therapy, which belongs to a class of drug thats notoriously costly? In a statement sentto FiercePharma, Ferring said it's too early to discuss pricing, that its top priority is still to get nadofaragene firadenovec approved andinvest into R&Dto study the product in more indications.

Keytruda is meant to be given ata fixed dose every three weeks. Nadofaragene firadenovec, which uses an adenovirus vector to deliver the gene interferon alfa-2b to stimulate an innate immune response to fight cancer, is administered into the bladder every three months.

Merck does have an upper hand against FerGene. The Big Pharma has been the sole supplier of BCG in the U.S. and several other key markets globally for several years now. So, it could offer BCG and Keytruda as a one-two punch for NMIBC, similar to the wayBayer is billing Nexavar and Stivarga as a part of the same continuumin first- and second-line liver cancer.

RELATED:Merck limits orders for bladder cancer drug as demand outstrips supply

There are other players eyeing the same patient population. Sesen Bio has Vicinium, an antibody-drug conjugate that targets epithelial cell adhesion molecule antigens on the surface of tumor cells to deliver a toxin payload. In its own phase 3 trial dubbed Vista also in high-risk, BCG-unresponsive NMIBC, Vicinium eradicated tumors in 40% of 89 patients at month three, according to an update the company provided in August. However, its response seems to wane over time more quickly than its rivals', as only 17% of patients showed no signs of tumor activity after 12 months.

The Cambridge, Massachusetts-based biotech recently held two meetings with the FDA and confirmed a submission process, including the design for a post-marketing confirmatory trial. It would enroll BCG-refractory patients who, because of supply constraints, haven't received an optimal BCG dose, which the company said represents a broader patientpopulation in light of anongoing shortage.

Sesen now expects to submit a biologics license application under rolling review by year-end with potential approval in 2020.

As for its pricing, during a presentation at the H.C. Wainwright investor conference in September, Sesens president and CEO Thomas Cannell pointed out that PD-1/L1s would cost about $150,000 to $200,000 per patient per year in NMIBC.

Weve done two rounds of market research with payers, and they think thats reasonable, he said. They think at those levels, there will probably be minimal prior authorization or step edits in terms of restricting a treatments use.

Assuming an official launch in 2021, Jefferies analysts, in a Nov. 12 note to clients, pegged $167.5 million for Viciniums U.S. sales in 2024. Before the priority designation, SVB Leerinks Daina Graybosch predicted a Keytruda launch in NMIBC in 2022 and forecastU.S. sales of $250 million in the indication for the Merck PD-1 inhibitor in 2025.

Editor's Note: The story has been updated with a statement from Ferring Pharma.

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Watch out, Keytruda. Ferring's bladder cancer gene therapy rival has new dataand they look competitive - FiercePharma

Bayersinvestigationalgene therapy BAY 2599023 safely and effectively increased the levels ofclotting factor VIII (FVIII) and prevented or lessened bleeding in the first two people with severe hemophilia A treated ina Phase 1/2 clinical trial, preliminary data show.

The ongoing trial (NCT03588299; 2017-000806-39) is enrolling up to 30 eligible adult patients. More information, including recruiting sites in the U.S. and Europe, is availablehere.

These early results will be presented in the poster, First-in-human Gene Therapy Study of AAVhu37 Capsid Vector Technology in Severe Hemophilia A, at the 61st American Society of Hematology (ASH) Annual Meeting & ExpositionrunningDec. 710 in Orlando, Florida.

BAY 2599023 initially by Dimension Therapeutics as DTX201 is being developed by Bayer in collaboration with Ultragenyx Pharmaceuticals. The potential gene therapy aims to promote a sustained production of FVIII and overcome its deficit in hemophilia A patients, reducing or eliminating the need for prophylatic, or preventive, FVIII replacement therapy and the occurrence of bleeding events.

Administered as a single infusion, the therapy uses a modified and harmless version of the adeno-associated virus (AAV), called AAVhu37, to deliver a shorter but functionalcopy of the FVIII gene to liver cells, where clotting factors are produced. This version of the FVIII gene is known as B-domain deleted FVIII gene.

Preclinical studies showed that AAVhu37 effectively delivered the FVIII gene to liver cells, had a favorable distribution, and induced a durable FVIII production.

In addition, preclinical data showed that BAY 2599023 had a good safety profile, and the potential to promote FVIII production to levels considered to be therapeutic over a long period of time.

The ongoing, dose-establishingPhase 1/2 trial (NCT03588299; 2017-000806-39) is evaluating the safety, tolerability and early effectiveness of three ascending doses of BAY 2599023 in adult men with severe hemophilia A who have been previously treated with FVIII products.

It is the first clinical trial to evaluate a gene therapy based on the AAVhu37.

Up to 30 enrolled patients will be given a single intravenous infusion of one of three doses of BAY 2599023. The studys primary goal is to measure safety through reports of adverse events. Secondary goals include measuring FVIII activity and assessing the number of patients who reach more than 5% of FVIII production at six and 12 months after treatment at the different doses.

Data on the first two men treated at BAY 2599023s starting dose (0.5 x 1013 gene copies/kg) will be presented at the meeting. These men had more than 150 days of treatment with FVIII products, no history of FVIII inhibitors, and no detectable immune response against AAVhu37.

No adverse events were reported after more than 15 weeks of safety evaluations (about four months). Blood levels of liver enzymes also remained within a normal range, and either of these patients needed to be treated with corticosteroids.

The first man reached a stable FVIII production of around 5%, and was free of bleeding events or a need for prophylactic treatment for six weeks. The second patient, who had 99 bleeds in the year before receiving the gene therapy, reached a stable FVIII production of around 17%, and has been bleed-free for more than 5.5 months (at the time of data collection).

These preliminary data suggest that BAY 2599023 is safe and effective in promoting the production of FVIII and in reducing or preventing the occurrence of bleeding events and the need for prophylactic treatment, the researchers wrote.

Overall, data generated from this first dose cohort demonstrate that successful translation from pre-clinical to clinical development and proof-of-mechanism for BAY 2599023 was achieved, they concluded.

Marta Figueiredo holds a BSc in Biology and a MSc in Evolutionary and Developmental Biology from the University of Lisbon, Portugal. She is currently finishing her PhD in Biomedical Sciences at the University of Lisbon, where she focused her research on the role of several signalling pathways in thymus and parathyroid glands embryonic development.

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Margarida graduated with a BS in Health Sciences from the University of Lisbon and a MSc in Biotechnology from Instituto Superior Tcnico (IST-UL). She worked as a molecular biologist research associate at a Cambridge UK-based biotech company that discovers and develops therapeutic, fully human monoclonal antibodies.

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First 2 Adults with Severe Hemophilia A Respond Well to Gene Therapy BAY 2599023 in Clinical Trial - Hemophilia News Today

In the summer, a mother in Nashville with a seemingly incurable genetic disorder finally found an end to her suffering -- by editing her genome.

Victoria Gray's recovery from sickle cell disease, which had caused her painful seizures, came in a year of breakthroughs in one of the hottest areas of medical research -- gene therapy.

"I have hoped for a cure since I was about 11," the 34-year-old told AFP in an email.

"Since I received the new cells, I have been able to enjoy more time with my family without worrying about pain or an out-of-the-blue emergency."

Over several weeks, Gray's blood was drawn so doctors could get to the cause of her illness -- stem cells from her bone marrow that were making deformed red blood cells.

The stem cells were sent to a Scottish laboratory, where their DNA was modified using Crispr/Cas9 -- pronounced "Crisper" -- a new tool informally known as molecular "scissors."

The genetically edited cells were transfused back into Gray's veins and bone marrow. A month later, she was producing normal blood cells.

Medics warn that caution is necessary but, theoretically, she has been cured.

"This is one patient. This is early results. We need to see how it works out in other patients," said her doctor, Haydar Frangoul, at the Sarah Cannon Research Institute in Nashville.

"But these results are really exciting."

In Germany, a 19-year-old woman was treated with a similar method for a different blood disease, beta thalassemia. She had previously needed 16 blood transfusions per year.

Nine months later, she is completely free of that burden.

For decades, the DNA of living organisms such as corn and salmon has been modified.

But Crispr, invented in 2012, made gene editing more widely accessible. It is much simpler than preceding technology, cheaper and easy to use in small labs.

The technique has given new impetus to the perennial debate over the wisdom of humanity manipulating life itself.

"It's all developing very quickly," said French geneticist Emmanuelle Charpentier, one of Crispr's inventors and the cofounder of Crispr Therapeutics, the biotech company conducting the clinical trials involving Gray and the German patient.

Crispr is the latest breakthrough in a year of great strides in gene therapy, a medical adventure started three decades ago, when the first TV telethons were raising money for children with muscular dystrophy.

Scientists practising the technique insert a normal gene into cells containing a defective gene.

It does the work the original could not -- such as making normal red blood cells, in Victoria's case, or making tumor-killing super white blood cells for a cancer patient.

Crispr goes even further: instead of adding a gene, the tool edits the genome itself.

After decades of research and clinical trials on a genetic fix to genetic disorders, 2019 saw a historic milestone: approval to bring to market the first gene therapies for a neuromuscular disease in the US and a blood disease in the European Union.

They join several other gene therapies -- bringing the total to eight -- approved in recent years to treat certain cancers and an inherited blindness.

Serge Braun, the scientific director of the French Muscular Dystrophy Association, sees 2019 as a turning point that will lead to a medical revolution.

"Twenty-five, 30 years, that's the time it had to take," he told AFP from Paris.

"It took a generation for gene therapy to become a reality. Now, it's only going to go faster."

Just outside Washington, at the National Institutes of Health (NIH), researchers are also celebrating a "breakthrough period."

"We have hit an inflection point," said Carrie Wolinetz, NIH's associate director for science policy.

These therapies are exorbitantly expensive, however, costing up to $2 million -- meaning patients face grueling negotiations with their insurance companies.

They also involve a complex regimen of procedures that are only available in wealthy countries.

Gray spent months in hospital getting blood drawn, undergoing chemotherapy, having edited stem cells reintroduced via transfusion -- and fighting a general infection.

"You cannot do this in a community hospital close to home," said her doctor.

However, the number of approved gene therapies will increase to about 40 by 2022, according to MIT researchers.

They will mostly target cancers and diseases that affect muscles, the eyes and the nervous system.

Another problem with Crispr is that its relative simplicity has triggered the imaginations of rogue practitioners who don't necessarily share the medical ethics of Western medicine.

Last year in China, scientist He Jiankui triggered an international scandal -- and his excommunication from the scientific community -- when he used Crispr to create what he called the first gene-edited humans.

The biophysicist said he had altered the DNA of human embryos that became twin girls Lulu and Nana.

His goal was to create a mutation that would prevent the girls from contracting HIV, even though there was no specific reason to put them through the process.

"That technology is not safe," said Kiran Musunuru, a genetics professor at the University of Pennsylvania, explaining that the Crispr "scissors" often cut next to the targeted gene, causing unexpected mutations.

"It's very easy to do if you don't care about the consequences," Musunuru added.

Despite the ethical pitfalls, restraint seems mainly to have prevailed so far.

The community is keeping a close eye on Russia, where biologist Denis Rebrikov has said he wants to use Crispr to help deaf parents have children without the disability.

There is also the temptation to genetically edit entire animal species -- malaria-causing mosquitoes in Burkina Faso or mice hosting ticks that carry Lyme disease in the US.

The researchers in charge of those projects are advancing carefully, however, fully aware of the unpredictability of chain reactions on the ecosystem.

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Charpentier doesn't believe in the more dystopian scenarios predicted for gene therapy, including American "biohackers" injecting themselves with Crispr technology bought online.

"Not everyone is a biologist or scientist," she said.

And the possibility of military hijacking to create soldier-killing viruses or bacteria that would ravage enemies' crops?

Charpentier thinks that technology generally tends to be used for the better.

"I'm a bacteriologist -- we've been talking about bioterrorism for years," she said. "Nothing has ever happened."

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A #ReUp of 2019: The year when gene therapy, DNA modifications came of age & saved lives - Economic Times

GERMANTOWN, Md., Dec. 06, 2019 (GLOBE NEWSWIRE) -- Orgenesis Inc. (NASDAQ: ORGS)(Orgenesis or the Company), a leading cell and gene therapy enabling company providing centralized CDMO manufacturing and development services through its subsidiary Masthercell Global, Inc., as well as localized point-of-care(POCare) development and processing centers for therapeutic treatments, today announced a strategic partnership agreement (Partnership) between the HYGEIA Group and the TheracellOrgenesis joint venture (JV). Under the Agreement, the JV will implement Orgenesis POCare cell therapy platform for clinical development and commercialization of cell and gene therapies within HYGEIA Groups network of three hospitals in Greece. As previously announced, Orgenesis and TheraCell Advanced Biotechnology formed a JV to advance Orgenesis POCare platform in Greece, Cyprus, the Balkan region and selected Middle Eastern countries.

The POCare platform is designed to collect, process and supply cells within the patient care setting for various therapeutic treatments. The goal of the platform is to reduce the cost and complexity of supplying cell and gene therapies, as well as elevate quality standards by integrating automated processing units and proprietary technologies.

HYGEIA is the first hospital network in this region to implement Orgenesis POCare cell therapy platform. The Partnership is intended to provide HYGEIA Group with resources to advance clinical development and deliver personalized, advanced therapies across its network for a wide range of diseases in oncology, hematology, orthopedics, nephrology, dermatology and diabetes.

This partnership with the HYGEIA Group further validates the significant value proposition of our POCare platform, as it enables the development and delivery of cell and gene therapies onsite at hospitals. We believe this platform has the potential to transform the cell and gene therapy market, by bringing life-saving therapies to market in a much more time and cost-effective manner, said Vered Caplan, CEO of Orgenesis. Theracell has proven to be an ideal partner with extensive experience and capabilities in autologous cell therapy and regenerative medicine, with operations in Greece and strong relationships throughout the region. We are in active discussions to establish PoCare locations and partnerships with hospitals and healthcare networks in other countries and regions across the world.

Andreas Kartapanis, CEO, HYGEIA Group, commented, HYGEIA Group is honored to work with Theracell and Orgenesis to become the first hospital network in Greece to provide advanced cell and gene therapies for both clinical research and patient treatment utilizing the POCare platform. We believe this Partnership will provide us a strong competitive advantage in this rapidly developing field. More importantly, this Partnership will benefit patients that will now have greater access to these important therapies.

About HYGEIA Group

HYGEIA Group operates three hospitals in Greece, with a total capacity of 1,261 beds, 52 operating rooms, 19 delivery rooms and 10 intensive care units. More than 3,100 employees and approximately 3,900 associate physicians offer their services to the HYGEIA Group, which was founded in 1970 by medical doctors, most of which were professors at the University of Athens and have since been active in providing primary and secondary care services. The following hospitals are also part of the HYGEIA Group: MITERA General, Obstetrics - Gynecology & Pediatrics Hospital and LITO Obstetrics, Gynecology & Surgical Center, licensed for 459 and 100 hospital beds, respectively.

About Theracell

TheraCell is a regenerative biotechnology company with operations in Greece, where its laboratories and primary facilities are located. The Company focuses in the areas of autologous cell therapy and regenerative medicine. TheraCell has extensive experience in the isolation, processing and application of adipose derived stem cells (ADSCs), as well as somatic cells and has developed a patented platform for tissue engineering and cell therapies in the areas of Dermatology, Chondral Defects and Chronic Kidney Injury.

About Orgenesis

Orgenesis is a biopharmaceutical company specializing in the development, manufacturing and processing of technologies and services in the cell and gene therapy industry. The Company operates through two platforms: (i) a point-of-care (POCare) cell therapy platform (PT) and (ii) a Contract Development and Manufacturing Organization (CDMO) platform conducted through its subsidiary, Masthercell Global. Through its PT business, the Companys aim is to further the development of Advanced Therapy Medicinal Products (ATMPs) through collaborations and in-licensing with other pre-clinical and clinical-stage biopharmaceutical companies and research and healthcare institutes to bring such ATMPs to patients. The Company out-licenses these ATMPs through regional partners to whom it also provides regulatory, pre-clinical and training services to support their activity in order to reach patients in a point-of-care hospital setting. Through the Companys CDMO platform, it is focused on providing contract manufacturing and development services for biopharmaceutical companies. Additional information is available at: http://www.orgenesis.com.

Notice Regarding Forward-Looking StatementsThis press release contains forward-looking statements which are made pursuant to the safe harbor provisions of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities and Exchange Act of 1934, as amended. These forward-looking statements involve substantial uncertainties and risks and are based upon our current expectations, estimates and projections and reflect our beliefs and assumptions based upon information available to us at the date of this release. We caution readers that forward-looking statements are predictions based on our current expectations about future events. These forward-looking statements are not guarantees of future performance and are subject to risks, uncertainties and assumptions that are difficult to predict. Our actual results, performance or achievements could differ materially from those expressed or implied by the forward-looking statements as a result of a number of factors, including, but not limited to, the success of our reorganized CDMO operations, the success of our partnership with Great Point Partners, our ability to achieve and maintain overall profitability, the sufficiency of working capital to realize our business plans, the development of our transdifferentiation technology as therapeutic treatment for diabetes which could, if successful, be a cure for Type 1 Diabetes; our technology not functioning as expected; our ability to retain key employees; our ability to satisfy the rigorous regulatory requirements for new procedures; our competitors developing better or cheaper alternatives to our products and the risks and uncertainties discussed under the heading "RISK FACTORS" in Item 1A of our Annual Report on Form 10-K for the fiscal year ended November 30, 2018, and in our other filings with the Securities and Exchange Commission. We undertake no obligation to revise or update any forward-looking statement for any reason.

Investor contact for Orgenesis:David WaldmanCrescendo Communications, LLCTel: 212-671-1021Orgs@crescendo-ir.com

Media contact for Orgenesis:Image Box CommunicationsNeil Hunter / Michelle BoxallTel +44 20 8943 4685neil@imageboxpr.co.uk/michelle@imageboxpr.co.uk

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Orgenesis and Theracell to Launch Point of Care Cell and Gene Therapy Centers within HYGEIA Group's Hospital Network in Greece - GlobeNewswire

The geneticist whose work helped map the human genome, the first step in the quest to manipulate what is essentially the software of human life, says reversing the aging process in humans may be less than 20 years away. George Church takes Scott Pelley into his Harvard Medical School lab to see his latest work for a 60 Minutes report to be broadcast Sunday, December 8, at 7:30 p.m. ET and 7 p.m. PT on CBS.Thanks to Church and others whose work decoded DNA, called the building blocks of life, the day when humans will no longer be prone to viruses or genetic diseases is coming. But one of the next breakthroughs could be reversing the basic process of age itself. "Age reversal is something that's been proven about eight different ways on animals," says Church. He tells Pelley that in mice, tissue damage has been repaired, reaction times sped up and cognition improved.

Knowing the specific functions of genes in a creature's DNA allows scientists to edit or add genes to the sequence and change outcomes. A paper just published by Church and several other scientists shows how added multiple genes in mice improved heart and kidney function and levels of blood sugar. "The gene function is going down [with age] and so we're boosting it back up by putting in extra copies of the gene," he explains, saying that this is gene therapy.The next step toward replicating this science in humans is to achieve the same results in a clinical trial using dogs that he is conducting now. The process could be perfected in humans in less than 20 years says Church. "That veterinary product might be a couple years away. And then that takes another 10 years to get through the human clinical trials."Church's lab at Harvard is working on about a hundred cutting-edge projects. They are currently experimenting with growing mini-organs from patients' own cells, to help test the effectiveness of medicine. And they are also aiming to turn these organoids, as they are called, into organs available for transplant. Another project is a start-up to make full-scale pig organs safe for human transplant. Church and his team also want to program human DNA to prevent people from hosting viruses, which could offer the cure for the common cold. Church's lab has also received much attention for its project to create a modern version of the extinct woolly mammoth, a process known as de-extinction.Church acknowledges the controversial nature of such experimenting, but says it's already being done. He understands the world may not be ready for some of the implications of this technology. "The more powerful or the more rapidly moving the technology, the more cautious we need to be, the bigger the conversation involving lots of different disciplines, religion, ethics, government, art to see what its unintended consequences might be."

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Leading geneticist George Church says reversing the aging process in humans could be 20 years away - 60 Minutes - CBS News

Sarepeta Therapeutics and StrideBio will collaborate to advance novel gene therapies for four genetic neurological disorders, including Rett syndrome, the companies have announced.

Under the agreement, StrideBio, which specializes in viral-based delivery systems for gene therapy, will conduct initial research, development, and manufacturing for the first four gene targets in these neurological disorders: MECP2 (Rett syndrome), SCN1A (Dravet syndrome), UBE3A (Angelman syndrome), and NPC1 (Niemann-Pick).

The main goal of the early development stage is to obtain investigational new drug approvals from the U.S. Food and Drug Administration, which are mandatory to start clinical trials.

In turn, Sarepta, a company focusing on precision genetic medicine, expands its gene therapy pipeline by gaining exclusive licenses on the selected targets. It also gains the possibility to extend licensing to four additional targets (for a total of eight) in neuromuscular and central nervous system diseases.

StrideBio owns aplatform to create adeno-associated viral (AAV) vectors, a class of modified viruses that are used to deliver gene therapy. They are engineered to be harmless (non-infectious) and work to deliver functioning genes directly into specific cells and tissues.

One of the current challenges in gene therapy is that some people carry a natural immunity against AAVs, in the form of neutralizing antibodies that react against these vectors and prevent gene therapies from working. In addition, immune reactions against AAVs can also become toxic for patients. This limits the number of patients who can benefit from AAV-based gene therapies, as carriers of neutralizing antibodies are excluded from gene therapy trials and treatments.

StrideBios platform addresses this problem by creating novel AAV capsids, or protein shells, that enclose the genetic material to be delivered and are able to escape pre-existing neutralizing antibodies.

As such, the platform holds promise for gene therapies to be used in a greater number of patients, the company says.

These new capsids can also be engineered to improve specific delivery of gene therapy to tissues of interest in a particular condition.

Sarepta and StrideBio plan to address re-dosing challenges as well in patients who have received some sort of AAV-based gene therapy.

With our partnership with StrideBio, Sarepta continues to build on its leadership position in gene therapies to treat rare diseases. We are excited to work with StrideBio and access its innovative AAV platform for next-generation capsids, Doug Ingram, Sareptas president and CEO, said in a press release.

Our partnership with StrideBio expands our research portfolio by up to eight new targets and ensures that we gain access to new technology and targets while not distracting Sarepta from its near-term priorities, he added.

Sapan Shah, PhD, StrideBios CEO, said: This partnership will provide significant resources and expertise to enable StrideBios continued rapid expansion of our research and manufacturing platform, as well as accelerate the development of AAV gene therapies for multiple rare disease targets.

We are looking forward to working together with Sarepta to bring novel treatments to patients as quickly as possible, he added.

Sarepta will pay StrideBio $48 million as upfront payment, in addition to future payments for development, regulatory, and commercial milestones for the four programs. StrideBio will also receive royalties on potential worldwide sales.

If the collaboration is expanded to the four additional targets, Sarepta will pay up to $42.5 million along with future milestone payments.

Ana is a molecular biologist with a passion for discovery and communication. As a science writer she looks for connecting the public, in particular patient and healthcare communities, with clear and quality information about the latest medical advances. Ana holds a PhD in Biomedical Sciences from the University of Lisbon, Portugal, where she specialized in genetics, molecular biology, and infectious diseases.

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Jos is a science news writer with a PhD in Neuroscience from Universidade of Porto, in Portugal. He has also studied Biochemistry at Universidade do Porto and was a postdoctoral associate at Weill Cornell Medicine, in New York, and at The University of Western Ontario in London, Ontario, Canada. His work has ranged from the association of central cardiovascular and pain control to the neurobiological basis of hypertension, and the molecular pathways driving Alzheimers disease.

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Rett Among Disorders Targetted for Gene Therapies in Partnership Deal - Rett Syndrome News

The National Academy of Inventors (NAI) has named University of Iowa cystic fibrosis and gene therapy researcher John Engelhardt, PhD, a 2019 Fellow.

Engelhardt, who is professor and head of anatomy and cell biology in the UI Carver College of Medicine and director of the UI Center for Gene Therapy, is recognized for his work in developing gene therapies to treat cystic fibrosis (CF). He will receive the award during an induction ceremony at the Heard Museum in Phoenix, Arizona, on April 10, 2020.

Engelhardts research primarily focuses on the molecular basis of CF, a progressive, inherited disease that causes persistent lung infections and other complications. CF is caused by well-studied mutations in a single gene, and Engelhardt has worked to develop gene therapy and gene editing methods to help treat the condition.

He also develops viral vector systems and animal models to test these methods and ultimately improve gene delivery. The animal models his laboratory has created are used by over 80 CF researchers, and he recently renewed a Research and Resource Center, funded by the National Institutes of Health (NIH), to continue this service to the research community and biotechnology companies that are developing therapies for CF and other lung diseases.

Engelhardt additionally studies airway stem cell niches, or the regulatory mechanisms that control stem cell growth and repair in the lungs, and has developed stem cell therapies for CF.

He currently holds 12 issued US patents, 41 issued foreign patents, and has 23 active patent applications. His patents and applications have been licensed to six companies, including two start-ups and a Fortune 100 company. Engelhardt provides critical tools and assistance to other researchers and companies in the field of CF research, and he is sponsored by the Cystic Fibrosis Foundation.

Engelhardt co-founded the gene therapy company Talee Bio, which was sold and is now Spirovant Sciences. The Philadelphia-based company was recently a part of a $3 billion deal to enhance the development of gene therapies for CF and other genetic diseases. Engelhardt remains on the scientific advisory board for Spirovant Sciences and serves as a key advisor as new therapies are created and tested.

NAI President Paul Sanberg says Engelhardt was selected for induction as he has demonstrated a highly prolific spirit of innovation in creating or facilitating outstanding inventions that have made a tangible impact on the quality of life, economic development, and welfare of society.

The University of Iowa Research Foundation (UIRF) nominated Engelhardt for this award to recognize his impact on creating and broadly commercializing gene therapies and his mentoring of other entrepreneurs on campus.

John has an extensive portfolio of intellectual property for advancing the commercialization of gene therapies, said Marie Kerbeshian, executive director of UIRF and an assistant vice president in the Office of the Vice President for Research. Not only is he a successful entrepreneur, as a UI researcher he is a key supporter of other researchers and other companies as they seek cures for cystic fibrosis.

He is one of 168 distinguished academic inventors across 136 research universities and institutes worldwide to join the academy this year. To date, NAI Fellows hold more than 41,500 issued U.S. patents, and the 2019 class includes six recipients of the U.S. National Medal of Technology & Innovation and U.S. National Medal of Science, four Nobel Laureates, among other honors.

We are very proud to see Dr. Engelhardts innovative and groundbreaking work recognized nationally, said Brooks Jackson, MD, MBA, UI vice president for medical affairs and the Tyrone D. Artz Dean of the UI Carver College of Medicine. He is a pioneer in his field and has set a prime example of how dedication and collaboration can lead to major advances in finding treatments for debilitating diseases.

Engelhardt is the second UI faculty member to join the academy, after UI neurosurgeon Matthew Howard, MD, was named a 2018 fellow for his work in developing brain and spinal cord neuromodulation devices.

Engelhardt joined the UI faculty in 1997 and is the Roy J. Carver Chair in Molecular Medicine and director of the Center for Gene Therapy of Cystic Fibrosis, which has received funding from the NIH continuously over the past 20 years. He earned a doctoral degree in human genetics from Johns Hopkins University and was a post-doctoral fellow at the University of Michigan. He has published 263 articles and book chapters, and has received over $74 million dollars in NIH grant support for his research.

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Engelhardt named 2019 Fellow of the National Academy of Inventors - Iowa Now

Exhilarating. A major advance. A milestone achievement. If one had just tuned into the panel comments on Biogens presentation at CTAD, it would seem that the biotech had an impressive, disease-modifying Alzheimers drug in aducanumab.

But off the stage, reactions to their admittedly complicated dataset and the biotechs explanation for resurrecting a drug that failed its futility analysis were a lot more mixed, with analysts continuing to question whether the evidence is substantial enough to warrant an FDA approval and raising new doubts on the safety side.

In an investor call later in the day, execs noted that they are not planning another study and stood by their intention, publicized in October to much surprise, to submit regulatory filings based on what they have.

We dont file willy nilly, said Al Sandrock, head of R&D. We only go to filing when we believe that there is a benefit-risk argument based on science, based on data. And if you look at our history, we havent done filings right and left without good reason.

Biogen had a theory going into the Clinical Trials on Alzheimers Disease meeting.

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UPDATED: Astellas snags a gene therapy upstart with $3B buyout bid inspiring forecasts of more M&A ahead - Endpoints News

BRISBANE, Calif. & NEW YORK--(BUSINESS WIRE)--Sangamo Therapeutics, Inc. (Nasdaq: SGMO), a genomic medicine company, and Pfizer, Inc. (NYSE: PFE), today announced updated follow-up results from the Phase 1/2 Alta study evaluating investigational SB-525 gene therapy in patients with severe hemophilia A. The data showed that SB-525 was generally well tolerated and demonstrated sustained increased Factor VIII (FVIII) levels following treatment with SB-525 through to 44 weeks, the extent of follow-up for the longest treated patient in the 3e13 vg/kg dose cohort. Data from 11 patients treated with SB-525 will be featured in a poster presentation today, December 7, 2019, at the 61st Annual Meeting of the American Society of Hematology (ASH) in Orlando, FL. The SB-525 ASH poster, which includes the full set of data, is available on Sangamos website in the Investors and Media section under Events and Presentations.

I am pleased that all five patients in the high dose (3e13 vg/kg) cohort rapidly achieved normal levels of Factor VIII, and that Factor VIII levels have been stable and durable in the normal range for the first two patients up to 44 and 37 weeks following treatment respectively, with no bleeding events or factor usage up to a follow up of 44 weeks in the longest treated patient, said Barbara Konkle, M.D., Bloodworks Northwest, Professor of Medicine at University of Washington and a Principal Investigator of the Alta study. It is important to continue to follow these patients to determine whether these results are sustained in the longer term as the combination of a favorable safety profile coupled with sustained expression at a level that prevents bleeding and allows normal activity will be the hallmark of a successful gene therapy for hemophilia A.

Alta study data presented at ASH included 11 patients treated across four ascending dose cohorts: 9e11 vg/kg (2 patients), 2e12 vg/kg (2 patients), 1e13 vg/kg (2 patients) and 3e13 vg/kg (5 patients). The data cutoff date was October 17, 2019.

An analysis of plasma FVIII antigen was assessed by ELISA and demonstrated antigen concentrations consistent with the FVIII activity measured by the chromogenic assay. Dose dependent increases in FVIII activity over baseline were observed across the dose cohorts. The lower-dose cohorts indicate durable FVIII activity with up to 52 weeks of follow-up.

In the 3e13 vg/kg dose cohort, patients achieved normal range FVIII activity within 5-7 weeks of treatment with SB-525. The first two patients treated in this cohort (Patients 7 and 8) have achieved stable FVIII levels, demonstrating durability in the normal range through 44 and 37 weeks, respectively, as measured by the chromogenic assay. The two patients most recently treated in this cohort (Patients 10 and 11), with 22 and 12 weeks of follow-up, respectively, demonstrated a similar pattern of FVIII expression. The FVIII expression pattern observed in Patient 9 differed from that of other patients in the cohort. Seven weeks following treatment, Patient 9 achieved normal range FVIII levels. Beginning at week 13, FVIII levels in that patient fluctuated in a range below normal, but still well above the level needed to prevent spontaneous bleeding. At week 18, FVIII levels in Patient 9 began to increase, and as of the latest measurement at week 24, continued to rise. No patient in the 3e13 vg/kg dose cohort has experienced bleeding events up to 44 weeks of follow-up, and no patient in this dose cohort required factor replacement following initial use of prophylactic factor.

SB-525 was generally well tolerated across all dose cohorts. The treatment-related adverse events include: alanine aminotransferase (ALT) elevation (36.4%, n=4), pyrexia (27.3%, n=3), increased aspartate aminotransferase (18.2%, n=2), tachycardia (18.2% n=2), fatigue (9.1%, n=1), hypotension (9.1%, n=1) and myalgia (9.1%, n=1). Treatment-related serious adverse events (SAEs) of hypotension (grade 3) and fever (grade two) occurred in one patient in the 3e13 vg/kg cohort six hours following dosing with SB-525 that fully resolved within 24 hours. No similar events were reported in the other patients dosed in that cohort. No patients treated with SB-525 experienced an ALT elevation associated with loss of Factor VIII expression. In the 3e13 vg/kg dose cohort, four patients experienced transient low grade ALT elevations (>1.5 x baseline) that were managed with a tapering course of oral steroids. The study does not use corticosteroids prophylactically, initiating them only in the event of an ALT elevation that is greater than 1.5x baseline.

The updated results from the Alta study suggest that SB-525 may represent a differentiated gene therapy for patients with severe hemophilia A, said Bettina Cockroft, M.D., Chief Medical Officer of Sangamo. The results continue to suggest that if sustained over a longer duration, SB-525 has the potential to be a predictable, reliable, and safe treatment that may bring clinical benefits to patients with severe hemophilia A.

Sangamo has completed the manufacturing technology transfer and initiated the transfer of the Investigational New Drug (IND) Application to Pfizer, which is expected to be completed in the first quarter 2020. Pfizer is enrolling patients in the Phase 3 lead-in study, the data from which is expected to provide a baseline for patients who are subsequently enrolled into the Phase 3 study (ClinicalTrials.gov Identifier: NCT03587116).

We are pleased with the progress that we have made in progressing SB-525 gene therapy toward a Phase 3 registrational study, including enrolling the first patient in the 6-month lead-in study. We expect to dose the first patient in the Phase 3 registrational study in 2020, said Seng Cheng, Senior Vice President and Chief Scientific Officer of Pfizers Rare Diseases Research Unit. We continue to believe that if the observed safety and efficacy results are sustained, this gene therapy has the potential to transform the treatment paradigm of severe hemophilia A.

About the Alta study

The Phase 1/2 Alta study is an open-label, dose-ranging, multicenter clinical trial designed to assess the safety and tolerability of SB-525 in patients with severe hemophilia A. The mean age of the 11 patients assessed is 30 years (range 18-47 years). All 11 patients are male. The U.S. Food and Drug Administration has granted Orphan Drug, Fast Track, and regenerative medicine advanced therapy (RMAT) designations to SB-525, which also received Orphan Medicinal Product designation from the European Medicines Agency. SB-525 is being developed as part of a global collaboration between Sangamo and Pfizer.

About SB-525 Gene Therapy

SB-525 comprises a recombinant adeno-associated virus serotype 6 vector (AAV6) encoding the complementary deoxyribonucleic acid for B domain deleted human FVIII. The SB-525 vector cassette was designed to optimize both the vector manufacturing yield and liver-specific FVIII protein expression. The SB-525 transcriptional cassette incorporates multi-factorial modifications to the liver-specific promoter module, FVIII transgene, synthetic polyadenylation signal and vector backbone sequence.

About Sangamo Therapeutics

Sangamo Therapeutics is committed to translating ground-breaking science into genomic medicines with the potential to transform patients lives using gene therapy, ex vivo gene-edited cell therapy, and in vivo genome editing and gene regulation. For more information about Sangamo, visit http://www.sangamo.com.

Pfizer Inc: Working together for a healthier world

At Pfizer, we apply science and our global resources to bring therapies to people that extend and significantly improve their lives. We strive to set the standard for quality, safety and value in the discovery, development and manufacture of health care products, including innovative medicines and vaccines. Every day, Pfizer colleagues work across developed and emerging markets to advance wellness, prevention, treatments and cures that challenge the most feared diseases of our time. Consistent with our responsibility as one of the world's premier innovative biopharmaceutical companies, we collaborate with health care providers, governments and local communities to support and expand access to reliable, affordable health care around the world. For more than 150 years, we have worked to make a difference for all who rely on us. We routinely post information that may be important to investors on our website at http://www.pfizer.com. In addition, to learn more, please visit us on http://www.pfizer.com and follow us on Twitter at @Pfizer and @Pfizer_News, LinkedIn, YouTube and like us on Facebook at Facebook.com/Pfizer.

Sangamo Forward Looking Statements

This press release contains forward-looking statements regarding Sangamo's current expectations. These forward-looking statements include, without limitation, statements relating to the investigational hemophilia A gene therapy, SB-525, including its potential therapeutic benefits; the potential long-term durability of SB-525 gene therapy; SB-525 having the potential to be a predictable and reliable treatment that may bring clinical benefit to patients with hemophilia A and to potentially represent a transformative treatment paradigm; plans to advance SB-525 into a potential registrational study; the potential benefits of the RMAT and Orphan medicine designation for SB-525; and other statements that are not historical fact. These statements are not guarantees of future performance and are subject to risks and assumptions that are difficult to predict. Factors that could cause actual results to differ include, but are not limited to, risks and uncertainties related to: the research and development process; additional data, including the risk that the data reported from the Alta to date may not be indicative of the final results from the Alta study or that such final results may not validate and support the safety and efficacy of SB-525; the completion of the Alta study; the possibility of unfavorable new clinical data from the Alta study and further analyses of existing clinical data from the study that may material change clinical outcomes; the risk that clinical trial data are subject to differing interpretations and assessments by regulatory authorities; whether regulatory authorities will be satisfied with the design of and results from the clincal studies relating to SB-525, any potential registrational studies or any other clinical studies of SB-525; whether Sangamo will be able to maintain or receive the benefits associated with RMAT, Orphan Drug, Fast Track and Orphan Medicinal Product designations for SB-525; Sangamo's reliance on Pfizer and other third-parties to meet their clinical and manufacturing obligations; Sangamos ability to maintain strategic partnerships; and the potential for technological developments by Sangamo's competitors that will obviate Sangamo's gene therapy technology. Further, there can be no assurance that the necessary regulatory approvals will be obtained for SB-525 or that Sangamo and its partners will be able to develop commercially viable product candidates. Actual results may differ from those projected in forward-looking statements due to risks and uncertainties that exist in Sangamo's operations and business environments. These risks and uncertainties are described more fully in Sangamo's Annual Report on Form 10-K for the year ended December 31, 2018 as filed with the Securities and Exchange Commission and Sangamo's most recent Quarterly Report on Form 10-Q. Forward-looking statements contained in this announcement are made as of this date, and Sangamo undertakes no duty to update such information except as required under applicable law.

Pfizer Disclosure Notice: The information contained in this release is as of December 7, 2019. Pfizer assumes no obligation to update forward-looking statements contained in this release as the result of new information or future events or developments.

This release contains forward-looking information about an investigational hemophilia A agent, SB-525, including its potential benefits, that involves substantial risks and uncertainties that could cause actual results to differ materially from those expressed or implied by such statements. Risks and uncertainties include, among other things, the uncertainties inherent in research and development, including the ability to meet anticipated clinical endpoints, commencement and/or completion dates for our clinical trials, regulatory submission dates, regulatory approval dates and/or launch dates, as well as the possibility of unfavorable new clinical data and further analyses of existing clinical data; risks associated with interim data; the risk that clinical trial data are subject to differing interpretations and assessments by regulatory authorities; whether regulatory authorities will be satisfied with the design of and results from our clinical studies; whether and when drug applications for any potential indications for SB-525 may be filed in any jurisdictions; whether and when regulatory authorities in any jurisdictions may approve any such applications, which will depend on myriad factors, including making a determination as to whether the product's benefits outweigh its known risks and determination of the product's efficacy and, if approved, whether SB-525 will be commercially successful; decisions by regulatory authorities impacting labeling, manufacturing processes, safety and/or other matters that could affect the availability or commercial potential of SB-525; and competitive developments.

A further description of risks and uncertainties can be found in Pfizer's Annual Report on Form 10-K for the fiscal year ended December 31, 2018 and in its subsequent reports on Form 10-Q, including in the sections thereof captioned "Risk Factors" and "Forward-Looking Information and Factors That May Affect Future Results", as well as in its subsequent reports on Form 8-K, all of which are filed with the U.S. Securities and Exchange Commission and available at http://www.sec.gov and http://www.pfizer.com.

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Sangamo and Pfizer Announce Updated Phase 1/2 Results Showing Sustained Increased Factor VIII Activity Through 44 Weeks Following SB-525 Gene Therapy...