ST-400 ex vivo Gene-Edited Cell Therapy for Beta Thalassemia
We are conducting the Phase 1/2 THALES study, an open-label, single arm clinical trial to evaluate the safety and efficacy ofST-400 in up to six subjects with beta thalassemia.ST-400 is anex vivogene-edited beta thalassemia cell therapy developed in partnership with Sanofi, that involves gene editing of a patient’s own hematopoietic stem progenitor cells usingnon-viral delivery of ZFN technology.
In April 2019, we announced early preliminary data from the first patient treated withST-400 in the THALES study. This patient has the most severe form of transfusion-dependent beta thalassemia (b0/b0) and for the two years prior to treatment in the study, received packed red blood cell, or PRBC, transfusions every other week.
During theST-400 infusion, the patient experienced a serious adverse event, a transient allergic reaction considered related to the cryoprotectant present in the product. Thereafter, the post-transplant clinical course was routine.
The patient demonstrated neutrophil and platelet recovery, within two and four weeks of infusion, respectively, indicating thatST-400 successfully reconstituted hematopoiesis following conditioning. Indels (small insertions or deletions generated at the targeted DNA sequence) have been detected in circulating white blood cells, indicating successful editing of theBCL11A gene and disruption of theBCL11A erythroid specific enhancer, which is intended to upregulate endogenous fetal hemoglobin production in red blood cells.
At seven weeks postST-400 infusion, total hemoglobin levels remained stable (~9 g/dL), and levels of fetal hemoglobin have continued to rise from approximately 1% of total hemoglobin at the time of infusion to 31% as of the most recent measurement.
The patient received several PRBC transfusions for approximately two weeks after theST-400 infusion. During the subsequent five weeks, the most recent data available, no further PRBC transfusions have been required.
We caution that these data regardingST-400 are very early, represent only the first patient dosed, and will require confirmation in additional patients as well as longerfollow-up to draw any clinical conclusion. In addition, these very early data should not be viewed as an indication, belief or guarantee that future dosed patients in the THALES study will achieve similar results or that the early results from the first patient dosed will be maintained. For more information about the risks of early clinical data, including the risk that the very early data from the first patient dosed in the THALES study to date may not be maintained or replicated in that patient or in any other dosed patients, see the risk factor entitled “Success in preclinical studies or early clinical trials may not be indicative of results obtained in later trials. Likewise, preliminary data from clinical trials should be considered carefully and with caution since the final data may be materially different from the preliminary data, particularly as more patient data become available” found in Part I, Item 1A of our Annual Report on Form10-K for the year ended December 31, 2018, filed with the SEC on March 1, 2019.
Enrollment in the THALES study is ongoing. We expect to present longer-termST-400 data in the fourth quarter of 2019, including results from additional patients. Until that time, we are not planning to report additional clinical data from the program.
In vivo Genome Editing Programs
In April 2019, we provided an update on ourin vivo genome editing programs: the ongoing Phase 1/2 clinical trials evaluatingSB-913 (mucopolysaccharidosis type II, or MPS II),SB-318 (MPS I), andSB-FIX (hemophilia B).
We announced that data will continue to accumulate throughout 2019, including in the recently treated expansion cohort patients in the CHAMPIONS study(SB-913), and further updates on all three studies are expected later this year. We expect that no additional patients will be treated at this time with first-generation ZFNs given that clinical benefit has not been demonstrated in analyses conducted to date in ongoing clinical trials and the expected near-term clinical development of second-generation ZFNs.
We are planning a new clinical trial to evaluate second-generation ZFNs forSB-913 to treat MPS II.In vitro preclinical data presented last year showed three potential advantages of second-generation ZFNs for use in the clinic: (1) improvements in efficiency and potency due to structural modifications to the ZFN architecture and expression vector; (2) the ability to function equally well in the patients with a single nucleotide polymorphism, or SNP, in the target locus in the albumin gene (~20% of the population); and (3) improvements in specificity. The clinical trial ofSB-913 using second-generation ZFNs is planned to begin in the second half of 2019. We expect to use data from this study to make a Phase III decision for theSB-913 program in 2020 and to define the next steps for theSB-318 andSB-FIX programs.
