The pipeline of medicines in development for sickle cell disease has shrank, with a trio of drugmakers this week announcing plans to halt further investment in their respective experimental treatments.On Thursday, Intellia Therapeutics, a leading developer of CRISPR gene editing therapies, revealed its partner Novartis had discontinued work on a sickle cell medicine in early human testing. The companies previously collaborated for five years between 2014 and 2019, and the blood disease treatment was one of two that the Swiss pharmaceutical company had taken forward into clinical trials.Intellia will continue its own research on another sickle cell gene therapy, however, that takes a different approach to treating the disease. While the Novartis treatment involves editing a patient stem cells in a laboratory, Intelliasprogram aims to make genetic changes in vivo, or inside the body.We have been focused, really since the outset as we thought about that disease, on doing it in an in vivo setting where one can avoid a bone marrow transplant and the morbidity and occasional mortality that comes with that, Intellia CEO John Leonard said on a conference call with analysts and investors Thursday. That space is wide open and we intend to get there first.The news from Intellia followed separate disclosures Wednesday by SangamoTherapeutics and Graphite Bio that they were stopping the development of sickle cell gene therapies they were respectively advancing.Sangamo, which has been developing a sickle cell treatment that uses a different kind of gene editing known as zinc fingers, said it would complete an ongoing Phase 1/2 study, but make no material investment beyond that.We did not make this decision because of efficacy results or due to any safety concerns, said Sandy Macrae, Sangamos CEO, in an Wednesday earnings call.We have simply decided to redeploy our resources away from the asset and to the companys programs in Fabry disease and renal transplantation.Sangamo regained control of the treatment, known as BIIV003, last year after partner Sanofi handed back rights.Graphites announcement, meanwhile, came alongside layoffs for 50% of the companys workforce and plans to explore strategic alternatives, which usually indicates a sale, merger or other type of business combination. The biotech will seek outside partners for the treatment, called nula-cel and currently being tested in a study called CEDAR.We believe that gene correction is the optimal way to treat sickle cell and many other genetic diseases, said Graphite CEO Josh Leher in a statement. However, after an extensive assessment of the nula-cel program, we made the difficult decision to discontinue nula-cel development based on the time and resources needed to resume the CEDAR study and the evolving treatment landscape for sickle cell disease.Graphite recently paused the CEDAR study after investigators reported that the first treated patient experienced prolonged low blood cell counts requiring transfusions and other medication. Dosing was suspended as a result.All three treatments being discontinued are ex vivo, requiring a laborious process of extracting patients hematopoietic stem cells, genetically editing them and then reinfusingthem back into each patient. Sangamos treatment, as well as the one from Intellia and Novartis, are designed to induce production of a fetal form of the oxygen-carrying protein hemoglobin to address sickle cells genetic cause.Graphites, by comparison, is meant to lower production of sickled hemoglobin and raise levels of functional adult hemoglobin.All three are also well behind two experimental sickle cell treatments from Bluebird bio and partners Vertex Pharmaceuticals and CRISPR Therapeutics. Those companies are in the final stages of preparing applications for Food and Drug Administration approval, potentially setting up regulatory decisions as soon as this year. Clinical trial data shows both could be powerful, potentially even curative, treatments for the blood condition.Other competitors are present too, as sickle cell has become a common target for gene therapy developers, including Editas Medicine and Beam Therapeutics. A recent report from RBC Capital Markets counted another 14 treatments in clinical testing for sickle cell that use other approaches outside of gene replacement or gene editing.The overlapping development pipelines raises the competitive bar for success, and could have played a role in Novartis, Sangamos and Graphites discontinuations. A tough funding environment, meanwhile, has forced many biotechsto decide where to allocate limited resources.In today's environment, we must make difficult choices, said Sangamos Macrae. '