BRISBANE, Calif.--(BUSINESS WIRE)--Sangamo Therapeutics, Inc. (NASDAQ: SGMO), a genomic medicine company, today announced that hemophilia A gene therapy clinical data and hemoglobinopathies ex vivo gene-edited cell therapy data will be featured in poster presentations at the 61st Annual Meeting of the American Society of Hematology (ASH). The ASH abstracts, which were submitted on August 3, 2019, were released online this morning. The conference will take place in Orlando, FL, from December 7-10, 2019.
Gene Therapy
The SB-525 poster will show updated Alta study data including durability of Factor VIII (FVIII) levels, bleeding rate, factor usage, and safety, for all five patients in the high dose cohort of 3e13 vg/kg, with approximately 4 months to 11 months of follow-up after treatment with SB-525.
As of the abstract submission date, four patients in the 3e13 vg/kg cohort achieved FVIII levels within the normal range with no bleeding events reported up to 24 weeks post-administration. These patients did not require FVIII replacement therapy following the initial prophylactic period of up to approximately 3 weeks post-SB-525 administration. The fifth patient in the 3e13 vg/kg cohort had only recently undergone treatment with SB-525 at the time of the abstract submission. As previously reported, one patient had treatment-related serious adverse events (SAEs) of hypotension and fever, which occurred approximately 6 hours after completion of the vector infusion and resolved with treatment within 24 hours, with no loss of FVIII expression. SB-525 is being developed as part of a global collaboration between Sangamo and Pfizer.
The rapid kinetics of Factor VIII expression, durability of response, and the relatively low intra-cohort variability in the context of a complete cessation of bleeding events and elimination of exogenous Factor VIII usage continues to suggest SB-525 is a differentiated hemophilia A gene therapy, said Bettina Cockroft, M.D., M.B.A., Chief Medical Officer of Sangamo, commenting on the published abstract. We are pleased with the progress of the program toward a registrational Phase 3 study led by Pfizer, who announced it has enrolled its first patient in the 6-month Phase 3 lead-in study. We have recently completed the manufacturing technology transfer to Pfizer and initiated the transfer of the IND.
Ex Vivo Gene-Edited Cell Therapy
The ST-400 beta thalassemia poster will show preliminary results from the first three patients enrolled in the Phase 1/2 THALES study. In this study, hematopoietic stem progenitor cells (HSPCs) are apheresed from the patient, edited to knock out the erythroid specific enhancer of the BCL11A gene, and cryopreserved prior to infusion back into the patient following myeloablative conditioning with busulfan. The first three patients all have severe beta thalassemia genotypes: 0/0, homozygous for the severe + IVS-I-5 (G>C) mutation, and 0/+ genotype including the severe IVS-II-654 (C>T) mutation, respectively.
As of the abstract submission date, Patient 1 and Patient 2 had experienced prompt hematopoietic reconstitution. Patient 1 had increasing fetal hemoglobin (HbF) fraction that contributed to a stable total hemoglobin. After being free from packed red blood cell (PRBC) transfusions for 6 weeks, the patient subsequently required intermittent transfusions. Patient 2 had rising HbF levels observed through 90 days post-infusion. For both patients, as of the most recent follow-up reported in the abstract, on-target insertions and deletions (indels) were present in circulating white blood cells. Patient 3 had just completed ST-400 manufacturing at the time of abstract submission. As previously disclosed, Patient 1 experienced an SAE of hypersensitivity during ST-400 infusion considered by the investigator to be related to the product cryoprotectant, DSMO, and which resolved by the end of the infusion. No other SAEs related to ST-400 have been reported and all other AEs have been consistent with myeloablation. No clonal hematopoiesis has been observed. Longer follow-up will be required to assess the clinical significance of these early results. ST-400 is being developed as part of a global collaboration between Sangamo and Sanofi, along with support through a grant from the California Institute for Regenerative Medicine (CIRM).
The first three patients enrolled in the THALES study all have severe beta thalassemia genotypes that result in almost no endogenous beta globin production. The increases in fetal hemoglobin and presence of on-target indels in circulating blood cells suggests successful editing using zinc finger nucleases. The results are preliminary and will require additional patients and longer-term follow-up to assess their clinical significance, said Adrian Woolfson, BM., B.Ch., Ph.D., Head of Research and Development. It is important to note that myeloablative hematopoietic stem cell transplantation reboots the hematopoietic system, and that sufficient time is required for the stem cells to fully repopulate the marrow and for new blood cells to form. In other myeloablative conditioning studies in a similar patient population, full manifestation of the effects of gene modification in the red blood cell compartment has taken as long as 12 months or more to become evident.
Sanofis in vitro sickle cell disease poster details a similar approach to ST-400, using mobilized HSPCs from normal donors and SCD patients and utilizing the same zinc finger nuclease for gene editing, delivered as transient non-viral RNA, and designed to disrupt the erythroid specific enhancer of the BCL11A gene, which represses the expression of the gamma globin genes, thereby switching off HbF synthesis. Results from ex vivo studies demonstrated enriched biallelic editing, increased HbF, and reduced sickling in erythroid cells derived from non-treated sickle cell disease patients. Sanofi has initiated a Phase 1/2 trial evaluating BIVV003, an ex vivo gene-edited cell therapy using ZFN gene editing technology to modify autologous hematopoietic stem cells using fetal hemoglobin to produce functional red blood cells with higher BhF content that are resistant to sickling in patients with severe sickle cell disease. Recruitment is ongoing.
About the Alta study
The Phase 1/2 Alta study is an open-label, dose-ranging clinical trial designed to assess the safety and tolerability of SB-525 gene therapy in patients with severe hemophilia A. SB-525 was administered to 11 patients in 4 cohorts of 2 patients each across 4 ascending doses (9e11 vg/kg, 2e12 vg/kg, 1e13vg/kg and 3e13vg/kg) with expansion of the highest dose cohort by 3 additional patients. The U.S. Food and Drug Administration (FDA) 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.
About the THALES study
The Phase 1/2 THALES study is a single-arm, multi-site study to assess the safety, tolerability, and efficacy of ST-400 autologous hematopoietic stem cell transplant in 6 patients with transfusion-dependent beta thalassemia (TDT). ST-400 is manufactured by ex vivo gene editing of a patient's own (autologous) hematopoietic stem cells using non-viral delivery of zinc finger nuclease technology. The THALES study inclusion criteria include all patients with TDT (0/0 or non- 0/0) who have received at least 8 packed red blood cell transfusions per year for the two years before enrollment in the study. The FDA has granted Orphan Drug status to ST-400.
About Sangamo Therapeutics
Sangamo Therapeutics, Inc. is focused on translating ground-breaking science into genomic medicines with the potential to transform patients' lives using gene therapy, ex vivo gene-edited cell therapy, in vivo genome editing, and gene regulation. For more information about Sangamo, visit http://www.sangamo.com.
Forward-Looking Statements
This press release contains forward-looking statements regarding Sangamo's current expectations. These forward-looking statements include, without limitation, statements regarding the Company's ability to develop and commercialize product candidates to address genetic diseases with the Company's proprietary technologies, as well as the timing of commencement of clinical programs and the anticipated benefits therefrom. These statements are not guarantees of future performance and are subject to certain risks, uncertainties and assumptions that are difficult to predict. Factors that could cause actual results to differ include, but are not limited to, the outcomes of clinical trials, the uncertain regulatory approval process, uncertainties related to the execution of clinical trials, Sangamo's reliance on partners and other third-parties to meet their clinical and manufacturing obligations, and the ability to maintain strategic partnerships. Further, there can be no assurance that the necessary regulatory approvals will be obtained 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.
More here:
- About the Gene Therapy Review - November 8th, 2009 [November 8th, 2009]
- Contribute an Article - November 8th, 2009 [November 8th, 2009]
- EBSCO Publishing Deal - November 8th, 2009 [November 8th, 2009]
- Advertising Opportunities - November 8th, 2009 [November 8th, 2009]
- Instructions for Authors - November 8th, 2009 [November 8th, 2009]
- Isis Collaboration With Ortho-McNeil Inc for Metabolic Diseases - November 8th, 2009 [November 8th, 2009]
- Dystrophin Gene Transfer safe in Duchenne muscular dystrophy - November 8th, 2009 [November 8th, 2009]
- Researchers Identify Gene for Rare Form of Spinal Muscular Atrophy - November 8th, 2009 [November 8th, 2009]
- Fatal brain cancer tamed by New gene therapy - November 8th, 2009 [November 8th, 2009]
- Gene therapy effective in fighting obesity in mice - November 8th, 2009 [November 8th, 2009]
- Genzyme gene therapy for people with peripheral artery disease failed in a clinical trial to help them regain some mobility - November 8th, 2009 [November 8th, 2009]
- Gene Therapy May Stall Inherited Emphysema - December 31st, 2009 [December 31st, 2009]
- Gene Therapy and Stem Cells Save Limb - December 31st, 2009 [December 31st, 2009]
- TNVitamins.com – $10 Off Of $50 order - May 7th, 2011 [May 7th, 2011]
- 15% Off Any PetAlive Order - May 7th, 2011 [May 7th, 2011]
- At PetAlive – $10 off order of $50 or more - May 7th, 2011 [May 7th, 2011]
- Native Remedies coupon – 5% Off Any Order - May 7th, 2011 [May 7th, 2011]
- Native Remedies – Save $5 coupon - May 7th, 2011 [May 7th, 2011]
- Welcome to the Gene Therapy Review - May 15th, 2011 [May 15th, 2011]
- Editorial Board - May 15th, 2011 [May 15th, 2011]
- Gene Therapy Job Board - May 15th, 2011 [May 15th, 2011]
- Corporate Membership - May 22nd, 2011 [May 22nd, 2011]
- Native Remedies coupon – 25% Off Any Order - May 29th, 2011 [May 29th, 2011]
- What is Gene Therapy? - June 19th, 2011 [June 19th, 2011]
- Research and Markets: Recent Advances in Cancer Research and Therapy - Increased Research on one of the Major Causes ... - April 25th, 2012 [April 25th, 2012]
- Gene Therapy part 2 - Video - April 30th, 2012 [April 30th, 2012]
- Gene therapy reverses Parkinson's symptoms: study - Video - April 30th, 2012 [April 30th, 2012]
- CBS This Morning - Gene therapy reverses Parkinson's symptoms: study - Video - April 30th, 2012 [April 30th, 2012]
- Engineering adenoviruses for gene therapy - Video - April 30th, 2012 [April 30th, 2012]
- What is Gene Therapy (The General Explains) - Video - April 30th, 2012 [April 30th, 2012]
- What is Gene Therapy - Animation - Video - April 30th, 2012 [April 30th, 2012]
- Microbiology Gene Therapy - Video - April 30th, 2012 [April 30th, 2012]
- Gene Therapy in Detail - Video - April 30th, 2012 [April 30th, 2012]
- Breakthrough in Haemophilia treatment - Video - April 30th, 2012 [April 30th, 2012]
- Virology Seminar - Gene Therapy - April 30th, 2012 [April 30th, 2012]
- Gene Therapy Video - Video - April 30th, 2012 [April 30th, 2012]
- Study: Gene Therapy for HIV Safe, But Effectiveness Still Unclear - May 4th, 2012 [May 4th, 2012]
- Gene Therapy Safe in Decade-Long HIV Study That May Widen Use - May 4th, 2012 [May 4th, 2012]
- Gene therapy for HIV safe, but effectiveness still unclear - May 4th, 2012 [May 4th, 2012]
- A Step Forward For Gene Therapy To Treat HIV - May 4th, 2012 [May 4th, 2012]
- A Media Event on Clinical Developments in Gene and Cell Therapy - May 4th, 2012 [May 4th, 2012]
- Families of SMA Awards New Funding to Advance a CNS Delivered Gene Therapy for Spinal Muscular Atrophy - May 4th, 2012 [May 4th, 2012]
- AIDS gene therapy safe -- is it a "cure"? - May 4th, 2012 [May 4th, 2012]
- Generational Achievements in Gene and Cell Therapy Honored at ASGCT 15th Annual Meeting - May 5th, 2012 [May 5th, 2012]
- Lewis speaks on gene therapy at Lexington Community Education event - May 7th, 2012 [May 7th, 2012]
- Penn researchers report a gene-therapy success - May 10th, 2012 [May 10th, 2012]
- Gene therapy for hearing loss: Potential and limitations - May 13th, 2012 [May 13th, 2012]
- Gene therapy extends mouse lifespan by 24 pc - May 16th, 2012 [May 16th, 2012]
- Gene therapy dramatically extends mouse lifespan - May 16th, 2012 [May 16th, 2012]
- Gene therapy may extend life: Study - May 16th, 2012 [May 16th, 2012]
- First gene therapy successful against aging-associated decline: Mouse lifespan extended up to 24% with a single ... - May 16th, 2012 [May 16th, 2012]
- Gene Therapy Extends Mouse Lifespan - May 16th, 2012 [May 16th, 2012]
- Gene Therapy for Brain Disease - May 17th, 2012 [May 17th, 2012]
- Children with rare, incurable brain disease improve after gene therapy - May 17th, 2012 [May 17th, 2012]
- FIRST Anti-Aging Gene Therapy (Brainstorm Ep72) - Video - May 23rd, 2012 [May 23rd, 2012]
- Gene therapy can correct forms of severe combined immunodeficiency - May 25th, 2012 [May 25th, 2012]
- RetroSense Therapeutics Completes pre-IND Meeting for RST-001 - May 25th, 2012 [May 25th, 2012]
- Gene therapy can correct forms of severe combined immunodeficiency, study suggests - May 26th, 2012 [May 26th, 2012]
- Alliance for Cancer Gene Therapy celebrates 10 years - May 29th, 2012 [May 29th, 2012]
- Research on gene therapy by Prasad Eye - June 1st, 2012 [June 1st, 2012]
- Baxter Announces Collaboration with Chatham Therapeutics for Factor IX Hemophilia B Gene Therapy Treatment - June 5th, 2012 [June 5th, 2012]
- Transgenomic Launches Breakthrough Blood-Based Cancer Gene Testing Technology at 2012 ASCO Annual Meeting - June 5th, 2012 [June 5th, 2012]
- Baxter Inks Deal with Chatham - June 6th, 2012 [June 6th, 2012]
- PIK3CA Gene Patent for Predicting Response to Targeted Therapy Issued – Exclusively Licensed to Transgenomic - June 11th, 2012 [June 11th, 2012]
- SalutarisMD Announces Positive Case Report of a New Investigational Wet AMD Therapy at ARVO - June 15th, 2012 [June 15th, 2012]
- Research and Markets: Gene Therapy - Global Strategic Business Report - 2012 - June 15th, 2012 [June 15th, 2012]
- New York Law Firm’s MesotheliomaHelp.net Site Publishes Interview with Gene Therapy Author - June 17th, 2012 [June 17th, 2012]
- uniQure Extends Collaboration with Protein Sciences Corporation on Use of its expresSF+® Cell Line for Gene Therapy - June 19th, 2012 [June 19th, 2012]
- Anti-cocaine vaccine described in Human Gene Therapy Journal - June 19th, 2012 [June 19th, 2012]
- bluebird bio Receives U.S. and European Orphan Drug Designation for Novel Gene Therapy to Treat Adrenoleukodystrophy - June 19th, 2012 [June 19th, 2012]
- Close to a cure: Greater Hartford takes on rare Jewish genetic disease - June 19th, 2012 [June 19th, 2012]
- Gene Therapy Helps Treat Children with Rare Brain Disorder - June 20th, 2012 [June 20th, 2012]
- Gold nanoparticles capable of 'unzipping' DNA - June 21st, 2012 [June 21st, 2012]
- ‘Gene-silencing’ drug can halt and reverse deadly brain disorder - June 21st, 2012 [June 21st, 2012]
- uniQure Collaborates with UCSF on GDNF Gene Therapy in Parkinson's Disease - June 22nd, 2012 [June 22nd, 2012]
- Gene-silencing method offers possible therapy for Huntington's disease - June 22nd, 2012 [June 22nd, 2012]
- Gene mutations cause massive brain asymmetry - June 24th, 2012 [June 24th, 2012]
- Research and Markets: Translational Regenerative Medicine - Oncology, CNS and Cardiovascular-Rich Pipeline Features ... - June 25th, 2012 [June 25th, 2012]
- Stress Blocks Gene That Guards Brain Against Depression - June 26th, 2012 [June 26th, 2012]
- Targeted gene therapy enhances treatment for Pompe disease - June 26th, 2012 [June 26th, 2012]