Title: Product Development Sr. Program Manager
Description
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Sangamo Therapeutics, Inc. (Nasdaq: SGMO) is the world’s leading developer of customized DNA-binding proteins for targeted gene regulation and genome engineering. We are applying this technology in diverse therapeutic areas including HIV / AIDS, hemophilia, Huntington's disease, hemoglobinopathies, and lysosomal storage diseases. Sangamo also has active programs and collaborations in a variety of other areas including crop engineering, gene-edited stem cells, and the development of humanized donor animals for xenotransplantation.
The Product Development function at Sangamo leads product strategy and execution from IND through clinical development and approval. The senior Project Manager in Product Development will be a highly-organized and versatile team player responsible for supporting two or more core teams and alliance management. The Project Manager supports the core team and core team leader in all aspects of product development (strategic, operational, and technical), from the time of IND filing to product launch. The Project Manager is focused on leading the operational aspects of the program and the team like program strategy and planning; timelines; budgets, meeting agendas, facilitation, minutes, and action-item follow-up) while also supporting and influencing the team in making complex cross-functional decisions.
The primary responsibility will be to provide project management expertise and support to cross-functional core teams and core team leader, ensuring that project priorities and plans are developed and executed in accordance with corporate goals. This position will eventually lead to core team leadership roles.
RESPONSIBILITIES
EDUCATION
A Bachelor of Science required. PhD in a scientific discipline, MBA or other advanced degree, highly preferred. Certification or professional training in project management is a plus.
SKILLS / EXPERIENCE
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Monday, July 24, 2017
Xenotransplantation !
Sangamo job opening describes areas of interest to include Xenotransplantation.
Tuesday, July 11, 2017
uniQure Presents New Clinical Data in Hemophilia B Patients Demonstrating Therapeutic Efficacy of AAV5 Gene Therapy in the Presence of Pre-Existing Neutralizing Antibodies
-- Findings Further Support Expanding the Eligibility of AAV5 Gene Therapies to Nearly All Patients with Hemophilia B --
LEXINGTON, Mass. and AMSTERDAM, the Netherlands, July 11, 2017 (GLOBE NEWSWIRE) -- uniQure N.V. (NASDAQ:QURE), a leading gene therapy company advancing transformative therapies for patients with severe medical needs, today presented new clinical data demonstrating that the presence of pre-existing anti-AAV5 neutralizing antibodies (NABs) does not predict the potential efficacy of AAV5-mediated gene transfer in patients with hemophilia B. Clinically meaningful factor IX (FIX) activity levels from the ongoing Phase I-II trial of AMT-060 were observed at NAB titers up to 1:341, determined as corresponding up to the 90th percentile of a healthy control population. NABs were quantified in the blood sera of these patients using a highly sensitive assay. These clinical data were presented today in a poster presentation at the 26th Biennial Congress of the International Society on Thrombosis and Hemostasis (ISTH), taking place this week in Berlin, Germany.
The presence of pre-existing NABs to adeno-associated virus (AAV) vectors has long posed a critical challenge for the clinical application of gene therapies, as patients who currently screen positive for NABs are generally excluded from treatment. Researchers from uniQure recently presented data in non-human primates suggesting that AAV5 could successfully mediate gene transfer in the presence of NABs at levels as high as 1:1031.
In a poster presentation at the ISTH meeting, a re-analysis was described of pre-gene transfer screening samples from the 10 patients who have been treated in the ongoing Phase I/II trial of AMT-060 for hemophilia B. The patients had tested negative for pre-existing anti-AAV5 NAbs using a green fluorescent protein-based (GFP) assay before receiving treatment. These samples were later re-assessed using a highly sensitive luciferase-based (LUC) NAB assay. Anti-AAV5 NABs were detected retrospectively in three patients who had been treated with the low dose (5x1012 gc/kg) of AMT-060. However, all three patients presented increases in FIX expression and, especially, the patient with the highest NAB level (titer 1:341) had the highest FIX-activity (steady-state FIX 6.8% of normal; latest FIX measurement 10.7% of normal) among all five patients treated in the low-dose cohort. None of the three patients who tested positive for NAB titers, experienced over time elevations in liver enzymes post gene transfer, FIX activity loss, or clinically relevant T-cell responses to the capsid.
"These clinical data show that hemophilia B patients presenting with neutralizing antibodies may be considered eligible for AAV5-mediated gene transfer," stated Matthew Kapusta, chief executive officer at uniQure. "This development potentially expands the applicability of AAV5 gene therapies to nearly all hemophilia B patients. We believe these factors contribute to making AAV5 a potential best-in-class vector for delivering gene therapies more effectively and safely to a greater portion of patients in need of treatment."
Friday, July 7, 2017
Biocompare.com Editorial - Gene Editing: Not Just CRISPR
http://www.biocompare.com/Editorial-Articles/339420-Gene-Editing-Not-Just-CRISPR/
The impact of gene editing on biomedical research has been similar in breadth and depth to that of PCR 30 years ago. Readers can find excellent summaries of the principal editing techniques, Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR), transcription activator-like effector nuclease (TALEN), and zinc finger nuclease (ZFN), through any search engine.
ZFN led the surge chronologically, followed by TALEN, then CRISPR. Each succeeding development eclipsed the previous one by virtue of easier use and greater familiarity with gene editing. CRISPR is generally credited with being significantly easier to use, hence its wide adoption among basic researchers.
Yet despite sales of ZFN reagents tailing off to baseline, and TALEN use dropping nearly as precipitously, those methods still hold promise for what is arguably the most value-driven gene editing application of all—therapy. ZFN and TALEN have reputations for being more precise than CRISPR. A recent paper by Schaefer et al., in Nature Methods that described deep sequencing to uncover off-target CRISPR effects, reinforced this belief. The authors noted that “concerns persist regarding secondary mutations in regions not targeted by the single guide RNA...We found an unexpected number of single-nucleotide variants...compared with the widely accepted assumption that CRISPR causes mostly indels at regions homologous to the sgRNA.”
According to Michael Holmes, Ph.D., vice president of research at Sangamo, ZFNs demand a higher level of protein engineering knowledge than CRISPR. “That’s why when researchers think of gene editing they first consider CRISPR, but when you’re thinking therapeutics what’s easiest may not be best.”
In December 2015, FDA approved an Investigational New Drug Application for SB-FIX, Sangamo’s hemophilia B treatment, that inserts a therapeutic gene into the albumin gene locus in liver cells.
Sangamo’s target, the endogenous albumin locus in the liver, is highly expressed. “When we insert a therapeutic transgene into this very powerful promoter we can exploit the liver as a protein production factory, a technique that requires editing a very small number of hepatocytes to produce therapeutic levels of protein,” Holmes says.
Sangamo’s optimized ZFNs provide high specificity with levels of off-target modification below the detection limits of state-of-the-art oligo-capture and deep sequencing assays. “This ability, to obtain editing efficiencies of greater than 80% at the intended on-target site in the genome with no detectable off-targets is where you want to be with therapeutic gene editing,” Holmes adds.
The edits made to the genome by Sangamo’s zinc finger platform are genetically stable, and the process does not appear to affect the inherent stability of the genome in either primary or transformed cells. The reagents act transiently but the traits they confer are permanent, even with rapidly dividing transformed cells—many of which are genomically unstable. “There are of course natural evolutionary forces, which cause cells after many passages to not divide as well or to lose chromosomes over time, which is to be expected” Holmes explains. “But this is neither more nor less likely than in the unedited genome.”
MilliporeSigma recently announced an improvement to CRISPR that makes the editing tool more efficient, flexible, and specific. Proxy-CRISPR, described in a recent Nature Communications paper, will accelerate drug development and gene therapy by accessing “previously unreachable areas of the genome,” according to the company.
Proxy-CRISPR allows greater diversity of DNA targets as might be seen in DNA sequences implicated in disease that often differ among individuals. “To address any possible disease-related mutation, to correct it, or to model it into healthy cells requires an editing technique that can target almost any DNA sequence,” Rook says. “Proxy-CRISPR method opens the door for using many additional CRISPR variants capable of unraveling the significance of genomic differences we can observe through next-generation sequencing.”
Poseida has accumulated multiple gene-editing tools. In addition to NextGEN CRISPR, Poseida employs the piggyBac™ DNA Modification System, XTN™ TALEN site-specific nuclease, and Footprint-Free™ Gene Editing.
“For any given cell type there is not always one superior technology, depending on what you want to do,” says Eric Ostertag, Poseida’s CEO. “CRISPR reagents are easier and faster to design, and slightly cheaper to create than TALEN. But if you’re experienced with TALEN and are making a therapeutic, the cost and design differences amount to a rounding error.”
An advantage of NextGEN CRISPR is its application to both activated (i.e. dividing) and resting (quiescent) T cells, which confers greater flexibility over editing approaches that work only on activated cells. “The more you manipulate T cells, the greater the likelihood that the end product will exhibit an undesirable phenotype,” Ostertag explains. “Having a stem-like phenotype is critical for product efficacy and durability, which is why we prefer to engineer resting cells.” NextGEN CRISPR works well in resting T cells, whereas TALEN does not.
Wild-type CRISPR uses the Cas9 protein and a guide RNA to cut DNA. The natural ribonucleoprotein is known for high-efficiency cutting of target sequences but “is quite sloppy in the way it causes undesirable off-target mutations,” Ostertag says. Poseida’s NextGEN CRISPR uses nuclease enzymes that are more typical for zinc finger and TALEN in that they require both half-sites to be present at the same time and at the correct location in the genome, thereby resulting in exquisite on-target specificity.
The impact of gene editing on biomedical research has been similar in breadth and depth to that of PCR 30 years ago. Readers can find excellent summaries of the principal editing techniques, Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR), transcription activator-like effector nuclease (TALEN), and zinc finger nuclease (ZFN), through any search engine.
ZFN led the surge chronologically, followed by TALEN, then CRISPR. Each succeeding development eclipsed the previous one by virtue of easier use and greater familiarity with gene editing. CRISPR is generally credited with being significantly easier to use, hence its wide adoption among basic researchers.
Yet despite sales of ZFN reagents tailing off to baseline, and TALEN use dropping nearly as precipitously, those methods still hold promise for what is arguably the most value-driven gene editing application of all—therapy. ZFN and TALEN have reputations for being more precise than CRISPR. A recent paper by Schaefer et al., in Nature Methods that described deep sequencing to uncover off-target CRISPR effects, reinforced this belief. The authors noted that “concerns persist regarding secondary mutations in regions not targeted by the single guide RNA...We found an unexpected number of single-nucleotide variants...compared with the widely accepted assumption that CRISPR causes mostly indels at regions homologous to the sgRNA.”
ZFN and TALEN have reputations for being more precise than CRISPR.
“The simplicity and accessibility of CRISPR to researchers has democratized genome editing and changed the face of disease research to the benefit of scientists and, in fact, the world,” says Martha S. Rook, Ph.D., head of gene editing and novel modalities at MilliporeSigma. “However, mature gene-editing technologies such as ZFN and TALEN remain the methods of choice for critical research where clear intellectual property rights are desirable.”Back to ZFNs?
Where CRISPR relies on a gene-targeting guide RNA to bind a chosen gene sequence, ZFNs have the advantage of being a protein-only construct that may be optimized to increase precision and specificity, particularly for clinical gene editing.According to Michael Holmes, Ph.D., vice president of research at Sangamo, ZFNs demand a higher level of protein engineering knowledge than CRISPR. “That’s why when researchers think of gene editing they first consider CRISPR, but when you’re thinking therapeutics what’s easiest may not be best.”
In December 2015, FDA approved an Investigational New Drug Application for SB-FIX, Sangamo’s hemophilia B treatment, that inserts a therapeutic gene into the albumin gene locus in liver cells.
Sangamo’s target, the endogenous albumin locus in the liver, is highly expressed. “When we insert a therapeutic transgene into this very powerful promoter we can exploit the liver as a protein production factory, a technique that requires editing a very small number of hepatocytes to produce therapeutic levels of protein,” Holmes says.
Sangamo’s optimized ZFNs provide high specificity with levels of off-target modification below the detection limits of state-of-the-art oligo-capture and deep sequencing assays. “This ability, to obtain editing efficiencies of greater than 80% at the intended on-target site in the genome with no detectable off-targets is where you want to be with therapeutic gene editing,” Holmes adds.
The edits made to the genome by Sangamo’s zinc finger platform are genetically stable, and the process does not appear to affect the inherent stability of the genome in either primary or transformed cells. The reagents act transiently but the traits they confer are permanent, even with rapidly dividing transformed cells—many of which are genomically unstable. “There are of course natural evolutionary forces, which cause cells after many passages to not divide as well or to lose chromosomes over time, which is to be expected” Holmes explains. “But this is neither more nor less likely than in the unedited genome.”
Improving a good idea
Despite its disadvantages CRISPR retains distinct advantages for many applications, Rook explains that CRISPR’s programmable RNA-to-DNA targeting provides the design simplicity that makes CRISPR whole-genome libraries cost-effective and accessible to all researchers off-the-shelf. “Further, the increased cleavage efficiency of CRISPR compared with ZFN and TALENs enhances its application to both whole-genome screens and single target genome-editing projects.”MilliporeSigma recently announced an improvement to CRISPR that makes the editing tool more efficient, flexible, and specific. Proxy-CRISPR, described in a recent Nature Communications paper, will accelerate drug development and gene therapy by accessing “previously unreachable areas of the genome,” according to the company.
Biocompare’s CRISPR Products Search Tool
Find, compare and review CRISPR
products from different suppliers Search
The Proxy-CRISPR method employs two CRISPR binding events for high-efficiency cutting. The first binding event is from a CAS9 that lacks DNA endonuclease (i.e. cutting) activity; the second binding event arises through a CRISPR system that similarly cannot, on its own, cut human DNA. “We discovered that targeting dead Cas9 next to other CRISPR systems can greatly enhance their activity,” Rook says. This strategy mimics what occurs in nature, where many different CRISPR systems bind to different DNA sequences.Find, compare and review CRISPR
products from different suppliers Search
Proxy-CRISPR allows greater diversity of DNA targets as might be seen in DNA sequences implicated in disease that often differ among individuals. “To address any possible disease-related mutation, to correct it, or to model it into healthy cells requires an editing technique that can target almost any DNA sequence,” Rook says. “Proxy-CRISPR method opens the door for using many additional CRISPR variants capable of unraveling the significance of genomic differences we can observe through next-generation sequencing.”
Greater flexibility
Poseida Therapeutics also shows that improving CRISPR technology can overcome off-target effects. The company recently reported preclinical data demonstrating its high-fidelity genome-editing system, NextGEN™ CRISPR, for producing allogeneic “universal donor” chimeric antigen receptor T-cells (CAR-T), an important platform for cancer immunotherapy.Poseida has accumulated multiple gene-editing tools. In addition to NextGEN CRISPR, Poseida employs the piggyBac™ DNA Modification System, XTN™ TALEN site-specific nuclease, and Footprint-Free™ Gene Editing.
“For any given cell type there is not always one superior technology, depending on what you want to do,” says Eric Ostertag, Poseida’s CEO. “CRISPR reagents are easier and faster to design, and slightly cheaper to create than TALEN. But if you’re experienced with TALEN and are making a therapeutic, the cost and design differences amount to a rounding error.”
An advantage of NextGEN CRISPR is its application to both activated (i.e. dividing) and resting (quiescent) T cells, which confers greater flexibility over editing approaches that work only on activated cells. “The more you manipulate T cells, the greater the likelihood that the end product will exhibit an undesirable phenotype,” Ostertag explains. “Having a stem-like phenotype is critical for product efficacy and durability, which is why we prefer to engineer resting cells.” NextGEN CRISPR works well in resting T cells, whereas TALEN does not.
Wild-type CRISPR uses the Cas9 protein and a guide RNA to cut DNA. The natural ribonucleoprotein is known for high-efficiency cutting of target sequences but “is quite sloppy in the way it causes undesirable off-target mutations,” Ostertag says. Poseida’s NextGEN CRISPR uses nuclease enzymes that are more typical for zinc finger and TALEN in that they require both half-sites to be present at the same time and at the correct location in the genome, thereby resulting in exquisite on-target specificity.
Thursday, July 6, 2017
Shire Submits IND for Gene Therapy Treatment of Hemophilia A
Shire submits investigational New Drug Application to FDA for Gene Therapy candidate SHP654 for treatment of Hemophilia A
“Shire is leveraging decades of scientific leadership in hemophilia to advance research in gene therapy for this community,” said Paul Monahan, M.D., Senior Medical Director, Gene Therapy, Shire. “Drawing from our rich heritage, Shire is well equipped to sustainably support the development of gene therapies that aim to advance current standards of care and minimize the burden of this disease. SHP654 uses a proprietary technology platform designed to produce sustained levels of factor similar to the natural mechanisms of the body. Our goal with gene therapy for hemophilia is to uphold the highest standards for safety and efficacy.”
Shire’s gene therapy program for hemophilia A uses a recombinant adeno-associated virus serotype 8 (rAAV8) vector, which selectively targets the liver.1,2 It involves the delivery of a functional copy of FVIII to the body’s liver to enable its own production of FVIII, rather than relying on a factor-based treatment.1 SHP654 uses the rAAV8 vector to deliver a codon-optimized, B-domain deleted FVIII (BDD-FVIII) specifically to a patient’s liver, where FVIII would then be produced and used to manage bleeds.1 The FVIII expression is further controlled in patients by incorporating the liver-specific transthyretin (TTR) promoter/enhancer.1
The IND filing for SHP654 was based on the results of pre-clinical and phase 1 studies demonstrating the potential utility of this candidate, including the following that will be presented at the International Society on Thrombosis and Haemostasis (ISTH) 26th Biennial Congress in Berlin, Germany, from July 8 – 13, 2017:
About SHP654
Shire is developing SHP654 (BAX 888), which includes technology acquired from Chatham Therapeutics, LLC, a spin-out of Asklepios Biopharmaceutical, Inc. SHP654 is an investigational factor VIII (FVIII) gene therapy intended to treat hemophilia A using a recombinant adeno-associated virus serotype 8 (rAAV8) vector to deliver a codon-optimized, B-domain deleted FVIII (BDD-FVIII) specifically to a patient’s liver, where FVIII would then be produced and used to manage bleeds.1,2
About Hemophilia A
Hemophilia A, the most common type of hemophilia, is a rare bleeding disorder that causes longer-than-normal bleeding due to lack of clotting factor VIII in the blood.6 The severity of hemophilia A is determined by the amount of factor in the blood, with more severity associated with lower amounts of factor.7 More than half of patients with hemophilia A have the severe form of the condition.7 Approximately 25-30% of individuals with severe hemophilia A develop inhibitors.8 Inhibitors are a serious medical problem that can occur when a person with hemophilia has an immune response to treatment with clotting factor concentrates.9 Hemophilia primarily affects males, with an incidence of one in 5,000 male births.7,10
References
SHP654 aims to deliver sustained protection against bleeds for patients with hemophilia A
Lexington, Mass. – July 6, 2017 – Shire plc (LSE: SHP, NASDAQ: SHPG), the leading biotechnology company focused on serving people with rare diseases, today announced the submission of an investigational new drug (IND) application to the U.S. Food and Drug Administration (FDA) for SHP654, also designated as BAX 888, an investigational factor VIII (FVIII) gene therapy for the treatment of hemophilia A. SHP654 aims to protect hemophilia A patients against bleeds through the delivery of a long-term, constant level of factor expression.1 The IND filing for SHP654 represents the latest step forward for Shire’s gene therapy program, which shows promise for both hemophilia A and B populations.“Shire is leveraging decades of scientific leadership in hemophilia to advance research in gene therapy for this community,” said Paul Monahan, M.D., Senior Medical Director, Gene Therapy, Shire. “Drawing from our rich heritage, Shire is well equipped to sustainably support the development of gene therapies that aim to advance current standards of care and minimize the burden of this disease. SHP654 uses a proprietary technology platform designed to produce sustained levels of factor similar to the natural mechanisms of the body. Our goal with gene therapy for hemophilia is to uphold the highest standards for safety and efficacy.”
Shire’s gene therapy program for hemophilia A uses a recombinant adeno-associated virus serotype 8 (rAAV8) vector, which selectively targets the liver.1,2 It involves the delivery of a functional copy of FVIII to the body’s liver to enable its own production of FVIII, rather than relying on a factor-based treatment.1 SHP654 uses the rAAV8 vector to deliver a codon-optimized, B-domain deleted FVIII (BDD-FVIII) specifically to a patient’s liver, where FVIII would then be produced and used to manage bleeds.1 The FVIII expression is further controlled in patients by incorporating the liver-specific transthyretin (TTR) promoter/enhancer.1
The IND filing for SHP654 was based on the results of pre-clinical and phase 1 studies demonstrating the potential utility of this candidate, including the following that will be presented at the International Society on Thrombosis and Haemostasis (ISTH) 26th Biennial Congress in Berlin, Germany, from July 8 – 13, 2017:
- Development of SHP654, a highly efficient AAV8-based BDD-FVIII gene therapy vector for treatment of hemophilia A. Session Title: Gene Therapy for Hemophilia: Clinical. Oral # OC 13.6.10th July, 17:45-19:00 CEST; Hall B1
- Integration site analysis in mice demonstrates excellent biosafety profile of a recombinant (r) FVIII adeno-associated virus (AAV8) gene therapy product. Session Title: Poster Session. Poster # PB 1094. 11th July, 12:00-13:15 CEST; Exhibition Hall 4.23
- Dose response and long-term expression of a human FVIII gene therapy construct in hemophilia A mice. Session Title: Poster Session. Poster # PB 1101. 11th July, 12:00-13:15 CEST; Exhibition Hall 4.22
- Nonclinical safety evaluation of a human FVIII gene therapy construct in mice. Session Title: Poster Session. Poster # PB 1099. 11th July, 12:00-13:15 CEST; Exhibition Hall 4.24
About SHP654
Shire is developing SHP654 (BAX 888), which includes technology acquired from Chatham Therapeutics, LLC, a spin-out of Asklepios Biopharmaceutical, Inc. SHP654 is an investigational factor VIII (FVIII) gene therapy intended to treat hemophilia A using a recombinant adeno-associated virus serotype 8 (rAAV8) vector to deliver a codon-optimized, B-domain deleted FVIII (BDD-FVIII) specifically to a patient’s liver, where FVIII would then be produced and used to manage bleeds.1,2
About Hemophilia A
Hemophilia A, the most common type of hemophilia, is a rare bleeding disorder that causes longer-than-normal bleeding due to lack of clotting factor VIII in the blood.6 The severity of hemophilia A is determined by the amount of factor in the blood, with more severity associated with lower amounts of factor.7 More than half of patients with hemophilia A have the severe form of the condition.7 Approximately 25-30% of individuals with severe hemophilia A develop inhibitors.8 Inhibitors are a serious medical problem that can occur when a person with hemophilia has an immune response to treatment with clotting factor concentrates.9 Hemophilia primarily affects males, with an incidence of one in 5,000 male births.7,10
References
- Falkner et al. “Development of SHP654 a highly efficient AAV8-based BDD-FVIII gene therapy vector for treatment of hemophilia A.” International Society on Thrombosis and Haemostasis Congress. Berlin, Germany July 8-13, 2017. Available at: http://onlinelibrary.wiley.com/doi/10.1111/rth2.2017.1.issue-S1/issuetoc
- Hoellriegl et al. “Dose response and long-term expression of a human FVIII gene therapy construct in hemophilia A mice.” International Society on Thrombosis and Haemostasis Congress. Berlin, Germany July 8-13, 2017. Available at: http://onlinelibrary.wiley.com/doi/10.1111/rth2.2017.1.issue-S1/issuetoc
- Hoellriegl et al. “Integration site analysis in mice demonstrates excellent biosafety profile of a recombinant ® FVIII adeno-associated virus (AAV8) gene therapy product.” International Society on Thrombosis and Haemostasis Congress. Berlin, Germany July 8-13, 2017. Available at: http://onlinelibrary.wiley.com/doi/10.1111/rth2.2017.1.issue-S1/issuetoc
- Hoellriegl et al. “Nonclinical safety evaluation of a human FVIII gene therapy construct in mice.” International Society on Thrombosis and Haemostasis Congress. Berlin, Germany July 8-13, 2017. Available at: http://onlinelibrary.wiley.com/doi/10.1111/rth2.2017.1.issue-S1/issuetoc
- U.S Food and Drug Administration. “Investigational New Drug (IND) or Device Exemption (IDE) Process (CBER).” U.S Food and Drug Administration website. https://www.fda.gov/biologicsbloodvaccines/developmentapprovalprocess/investigationalnewdrugindordeviceexemptionideprocess/default.htm. Accessed June 28, 2017.
- World Federation of Hemophilia. “What is hemophilia?” World Federation of Hemophilia website. http://www.wfh.org/en/page.aspx?pid=646. Accessed June 23, 2017.
- National Hemophilia Foundation. “Hemophilia A.” National Hemophilia Foundation website. https://www.hemophilia.org/Bleeding-Disorders/Types-of-Bleeding-Disorders/Hemophilia-A. Accessed June 23, 2017.
- World Federation of Hemophilia. “Who is at risk of developing inhibitors?” World Federation of Hemophilia website. http://www.wfh.org/en/page.aspx?pid=653. Accessed June 23, 2017.
- World Federation of Hemophilia. “What are inhibitors?” World Federation of Hemophilia website. http://www.wfh.org/en/page.aspx?pid=651. Accessed June 23, 2017.
- Centers for Disease Control and Prevention. “Hemophilia.” Centers for Disease Control and Prevention website. http://www.cdc.gov/ncbddd/hemophilia/facts.html. Accessed June 29, 2017.
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