Eltrombopag Diolamine

Graphite entered into a license and option agreement with an undisclosed third party in August Matthew Porteus, M.D., Ph.D., is trying to write another chapter for his sickle cell disease project. Three years after Graphite Bio launched to build on his work, Porteus has struck a deal to save the floundering project and advance deeper into the clinic under a new biotech. Porteus studied the use of CRISPR to correct the mutation that drives sickle cell at his Stanford University lab. The studies led to Graphite, which listed Porteus as a scientific founder when it emerged with a $45 million series A round in 2020. Graphite’s story quickly took a dark turn, with the biotech seeing a serious adverse event in the first patient it dosed and halting development of the candidate weeks later. Those events marked the beginning of the end for Graphite, which went from raising a $238 million IPO to entering into a reverse merger in less than 30 months. But Porteus has given the sickle cell program a chance of outliving the biotech that first tried to bring it to market. The Stanford professor has co-founded a new biotech, Kamau Therapeutics, to emerge from the ashes of Graphite. Kamau “received an option to acquire all genome editing assets” through a “strategic transaction with Graphite.” The newly minted biotech plans to study the sickle cell asset, nulabeglogene autogedtemcel (nula-cel), that Graphite walked away from in the wake of the adverse event. Investigators have now tracked the patient who received nula-cel for one year. Ahead of the release of the one-year data Monday, Kamau shared a look at six-month results, identifying “lower-than-expected cell survival rate, necessitating platelet and red blood cell transfusions due to low platelet counts” as a problem and fingering eltrombopag as the cause of the adverse event. Eltrombopag is used to treat low platelets in the blood and was not initially part of the trial protocol.  The findings have informed a focus on manufacturing. Kamau is working with an outsourcing partner to increase cell yield and improve overall cell health. The goal is to establish a more robust manufacturing framework. Graphite entered into a license and option agreement with an undisclosed third party in August. Under the terms of the deal, the third party secured an option on nula-cel and related assets and gave Graphite a 20% stake in its business. The option was contingent on the timely achievement of “a financing milestone” by the third party. Graphite’s last update described a tweak it made to the agreement in September. Meanwhile, what's left of Graphite folded into vision-loss biotech LENZ Therapeutics in November. 

Clinical data on lead program, nula-cel, demonstrating curative outcome in first treated patient with sickle cell disease (SCD) to be presented at the 2023 Annual ASH Meeting Kamau aims to enroll additional patients with SCD in the Phase 1/2 clinical trial within the next 18 months Improved manufacturing processes; Contract Development and Manufacturing Organization agreement signed, technology transfer initiated SAN FRANCISCO--(BUSINESS WIRE)-- Kamau Therapeutics ("Kamau" or "the Company"), a clinical-stage gene correction company, announced today its emergence from stealth, following a strategic transaction with Graphite Bio (“Graphite”). Under the terms of the agreement, Kamau received an option to acquire all genome editing assets, including a platform technology that integrates precision DNA repair, using homology directed repair (HDR) and CRISPR/Cas9. The HDR platform technology, developed by gene-editing pioneers Drs. Matthew Porteus and Maria Grazia Roncarolo at Stanford, received U.S. Food and Drug Administration (FDA) clearance for the Investigational New Drug (IND) application of nulabeglogene autogedtemcel (nula-cel). This technology now forms the basis for Kamau's lead program, nula-cel, previously developed by Graphite. The newly established company will retain control of all intellectual property (IP) related to HDR-based CRISPR gene correction as well as the IND application. Nula-cel is an investigational, potentially first-in-class hematopoietic stem-cell therapy engineered to restore normal adult hemoglobin (HgbA) by precisely correcting the mutation that causes sickle hemoglobin (HgbS), which may provide a cure for patients with this life-threatening genetic disease. The therapy has established proof of concept in the first patient treated for sickle cell disease (SCD). The data will be presented during a poster session (Abstract #5000) on Monday, December 11, at the 2023 Annual Meeting of the American Society of Hematology (ASH). Redefining Genetic Disease Treatment Kamau's HDR gene correction technology holds immense promise in enhancing human health outcomes through curative cell therapies. The versatile and robust platform corrects disease-causing DNA mutations, offering unmatched precision, template-based gene correction, and minimal off-target effects with the capacity to replenish the bloodstream with healthy red blood cells. Kamau co-founders Dr. Porteus, previously a scientific co-founder of CRISPR Therapeutics and academic co-founder of Graphite Bio, and Dr. Roncarolo, will also serve as the company’s scientific leadership to expand the use of the platform HDR technology in addressable genetic diseases beyond SCD. Jane Gorgan, Ph.D., previously the chief scientific officer at Graphite, and Jerry Cacia, previously the chief technical officer at Graphite, will serve as strategic advisors to Kamau. Dr. Porteus commented, “Our HDR technology brings to life the concept of genome editing. Kamau's approach surpasses first-generation technologies, which often introduce new errors in the genome. Instead, our technology can correct, add, replace, and rearrange disease-causing genes with functional or new ones. In our lead program, nula-cel, the technology transforms the sickle cell gene into a non-pathogenic one, addressing the root cause of the illness at the genomic level. This results in a significant reduction of pathogenic sickle hemoglobin and the production of non-pathogenic adult hemoglobin. Kamau aims to achieve the gold standard in genome engineering: directly correcting mutations that cause diseases, and we are making strides toward this ambitious goal.” One Year Follow-up on the First Patient Treated with Nula-Cel At the 2023 ASH Annual Meeting, Dr. David Shyr, Clinical Assistant Professor in Pediatric Stem Cell Transplantation from Stanford Medicine, will present a poster detailing outcomes of the first patient treated with investigational nula-cel during a Phase 1/2 clinical trial. The abstract is available here, and the poster with one-year data will be available on the Kamau website on December 11. Key highlights from the six-month follow up include the following: Prior to joining the trial, the patient experienced six painful blood vessel blockages known as vaso-occlusive crises and had been hospitalized four times each year for the past two years. The patient underwent meticulous procedures to harvest and store CD34+ cells, with treatment initiated in August 2022 post-chemotherapy. While early stages showed promise, subsequent tests revealed a lower-than-expected cell survival rate, necessitating platelet and red blood cell transfusions due to low platelet counts. The introduction of eltrombopag, not initially part of the trial protocol, temporarily posed a significant adverse event but did not interrupt the trial. Upon gradual discontinuation of eltrombopag, the patient's blood counts improved, alongside positive changes in other markers. Blood tests indicated a favorable impact of nula-cel treatment on reducing sickle hemoglobin and increasing healthier types (HgbA and HgbF). Dr. Shyr explained, “Current sickle cell treatments focus on managing acute symptoms such as pain crises and avoiding severe complications like stroke, without curing the patients. Bone marrow transplant has been the only curative option, but carries significant risks for transplant related complications, some of which can be life threatening. Kamau's gene-editing technology can offer a potential cure using the patient's cells. Further study of nula-cel is eagerly anticipated.” Dr. Roncarolo added, “Nula-cel represents a groundbreaking approach to target the underlying mutation in sickle cell disease. These proof of concept data offer important insights and hope to those grappling with this debilitating disease. We look forward to treating additional patients in the clinical trial with the goal of curing this disease.” ASH Poster Presentation Details Title: One Year Follow-up on the First Patient Treated with Nula-Cel: An Autologous CRISPR/Cas9 Gene Corrected CD34+ Cell Product to Treat Sickle Cell Disease Abstract #: 5000 Session: 801. Gene Therapies: Poster III Hematology Disease Topics & Pathways: Biological therapies, Sickle Cell Disease, Hemoglobinopathies, Gene Therapy, Diseases, Therapies Presenter: David Shyr, MD, Stanford Medicine Advancing Manufacturing Capabilities with Strategic Agreement Kamau has reached a significant milestone in its commitment to advancing its manufacturing processes. The company recently entered into a Contract Development and Manufacturing Organization (CDMO) agreement, marking a strategic move toward enhanced capabilities. Through this collaboration, Kamau is actively initiating technology transfer and is focused on elevating the HDR technology, increasing cell yield, and improving overall cell health. These advancements aim to optimize production efficiency, ensuring a more robust and sustainable manufacturing framework. About Sickle Cell Disease Sickle Cell Disease (SCD) is a common genetic condition affecting over 500,000 people worldwide every year. In the U.S., more than 100,000 individuals have SCD, and around 20% of them have a severe form of the disease. SCD occurs when a gene called HBB undergoes a specific change, which changes one substance in its genetic code to another. This genetic alteration leads to the creation of a variant known as HbS. The irregular shape of red blood cells resulting from this mutation causes serious health issues, including anemia, blockages in blood flow, severe pain, an increased risk of stroke, damage to multiple organs, and ultimately a shorter lifespan, representing a significant medical need. About Kamau Therapeutics Kamau Therapeutics is a clinical-stage, gene correction company dedicated to transforming the lives of patients with devastating genetic diseases through best-in-class, curative stem-cell therapies. Kamau stands apart through the unique capabilities of its next-generation gene correction platform that directly corrects genetic mutations with unprecedented precision: removing the pathologic mutation and replacing it with the healthy version. The company’s platform technology is based on the pioneering research of company co-founder Dr. Matthew Porteus, MD, PhD, and offers broad potential for transforming human health. Kamau’s lead clinical program, nulabeglogene autogedtemcel (nula-cel), previously developed by Graphite Bio, is the only hematopoietic stem-cell based therapy in clinical development for sickle cell disease (SCD) that precisely corrects the mutation in the beta-globin gene found in the sickled hemoglobin (HgbS) of SCD patients, restoring patient’s stem cells to normal adult hemoglobin (HgbA). Kamau plans to enroll additional patients with SCD in the Phase 1/2 clinical trial of nula-cel, for which it has received both fast track and orphan drug designations from the U.S. Food and Drug Administration (FDA). For more information, please visit and follow the company’s progress on our LinkedIn page.