Streptozocin

Sana Biotechnology is launching a clinical trial of its hypoimmune platform in humans through a Swedish university and expects to have data sometime in 2024. Sana Biotechnology’s genetically engineered pancreatic islet cells controlled glucose levels for six months in a diabetic primate without requiring insulin or immunosuppression, according to new preclinical data published online Feb. 13. The development is a step toward treating Type 1 diabetes without injectable insulin.  In an article in the journal Cell Stem Cell, scientists from Sana reported that they had transplanted a primate version of the company’s islet cells—which are hypoimmune, meaning they have been genetically altered to avoid provoking an immune response—into a long-tailed macaque with Type 1 diabetes. “The results of this preclinical study are remarkable, and if they translate into the clinic, we have the potential to profoundly change the way that type 1 diabetes is addressed, potentially eliminating the need for insulin injections or immunosuppression,” Sana’s head of hypoimmune platform Sonja Schrepfer, M.D., Ph.D., said in a press release. The research is proof-of-concept for the company's hypoimmune platform, which will ultimately be paired with engineered islet cells grown from induced pluripotent stem cells, or iPSCs.  Type 1 diabetes is an autoimmune condition that typically begins in childhood, though it can develop at any age. The disease is believed to arise from the immune system attacking the insulin-producing beta islet cells in the pancreas. To control their blood glucose levels, patients must take external insulin injections in some form—be it an insulin pump or shots multiple times a day—for the rest of their lives.  Sana’s product for Type 1 diabetes, SC451, aims to replace a patient’s lost islet cells with genetically engineered ones that are derived from donors or grown from iPSCs. In the new study, they engineered islet cells taken from a macaque of a different species that had a markedly different genetic immune profile from the recipient—a way to show that the engineered therapy could work despite a high “immunological bar,” as Sana put it in the company's press release.   Prior to the therapy, the recipient monkey was receiving two units of insulin per day to keep its blood sugar controlled. After the engineered islet cells were administered, the monkey was weaned off insulin at a rate of about half a unit every three days until it was completely discontinued. The monkey was followed for the next six months, over the course of which it didn’t receive any immunosuppressive therapy to prevent its immune system from rejecting the donor cells.  The animal had “tightly controlled” blood sugar levels for the full six-month period without any insulin injections, and its levels of C-reactive protein—an inflammatory marker that has been shown to rise in organ transplant recipients at risk of graft rejection—remained stable as well. The monkey didn’t experience any behavioral or physical changes besides some mild weight gain, the researchers noted. Furthermore, analysis of T cells, natural killer cells, macrophages and antibodies showed no signs that the animal’s immune system was flaring up in response to the transplant.  “These data demonstrate that our hypoimmune engineering completely circumvents allograft rejection, does not build immune memory, and thus achieves markedly better protection than systemic immunosuppression, and it is associated with no observed side effects,” the researchers wrote in the paper. “This successful NHP study provides proof of concept for an upcoming clinical trial using allogeneic, HIP-edited primary islets in patients with type 1 diabetes.” There are some limitations to the study. First, the researchers in this case induced destruction of the recipient monkey’s beta islet cells using a drug called streptozotocin. This is different from the autoimmune mechanisms that cause the disease in humans; however, previous positive results in mouse models of diabetes caused by autoimmunity suggest that it still works the same way, regardless of how the damage is caused. Second, there was no control animal in the study that received unedited islet cells due to evidence that they would be rejected, the researchers noted.  Still, the evidence is enough to show that the concept is safe to test in humans. Sana is launching a clinical proof-of-concept study on the hypoimmune platform paired with donor-derived islet cells, UP421, through a Swedish university and expects to have data sometime this year, according to a Jan. 4 corporate presentation from the company.

AUSTIN, TX / ACCESSWIRE / April 19, 2023 / On their own, cancer or diabetes can be debilitating and deadly. The two are common diseases with tremendous impact on health worldwide. To make matters worse, epidemiologic evidence suggests that people with diabetes - especially Type 2 diabetes - are at significantly higher risk for many forms of cancer. The two pose a significant health problem and threat globally. In oncology, Genprex, Inc.(NASDAQ: GNPX) is initially focused on lung cancer. Annually, there are more than 2 million new cases of lung cancer worldwide with an average five-year survival rate of 18.6%. Over 537 million people worldwide suffer from diabetes with annual global mortality of about 6.7 million. Gene Therapy To The Rescue? Genprex Inc., a clinical-stage gene therapy company, is focused on developing for these patients with serious medical conditions and unmet need new and better treatment options that are life-changing. Founded in 2009 and headquartered in Austin, Texas, the company has been at the forefront of gene therapy research, focusing on harnessing the power of cutting-edge technologies to improve the lives of those affected by debilitating conditions. Driven by a deep commitment to scientific excellence and patient-centricity, Genprex reports that its mission is to revolutionize the treatment landscape by developing innovative gene therapies that have the potential to transform the lives of patients who have limited treatment options. Innovative Pipeline Genprex's oncology program utilizes the company's proprietary, non-viral ONCOPREX® Nanoparticle Delivery System, which it believes is the first systemic gene therapy delivery platform used for cancer in humans. ONCOPREX® encapsulates the gene-expressing plasmids using lipid nanoparticles, and the resultant product is administered intravenously, where it is then taken up by tumor cells in which tumor suppressor genes are missing or deficient. Genprex's value proposition lies in its robust and diversified pipeline of gene therapy candidates addressing large underserved patient populations, a strong intellectual property portfolio, and a seasoned management team with extensive experience in biopharmaceutical development and commercialization. The company's pipeline is anchored by its lead product candidate, REQORSA™ Immunogene Therapy (quaratusugene ozeplasmid), an innovative gene therapy that has been shown in pre-clinical testing to be potentially applicable to many types of cancer. Genprex is initially targeting non-small cell lung cancer (NSCLC) patients and small cell lung cancer (SCLC). REQORSA™ works by introducing a tumor suppressor gene (TUSC2) into cancer cells, inhibiting tumor growth and promoting cancer cell death. REQORSA™is being evaluated by Genprex as a treatment for NSCLC in two phase 1/2 clinical trials, with each trial receiving a Fast Track Designation ("FTD") from the U.S. Food and Drug Administration (FDA). One FTD is for use of REQORSA in combination with Merck & Co's Keytruda®, and the other is for use of REQORSA in combination with Astra Zeneca's Tagrisso REQORSA is also being evaluated for SCLC in combination with Genentech's Tecentriq with a trial expected to launch later this year. REQORSA has shown promise in preclinical and clinical studies, demonstrating its potential to improve patient outcomes in combination with other cancer treatments. Genprex sees the potential to use its proprietary gene therapy delivery platform to pursue a number of other cancer indications targeting the delivery of therapeutic genes to tumors as opposed to normal cells. The company's diabetes gene therapy approach comprises a novel infusion process that uses an endoscope and an adeno-associated virus (AAV) vector to deliver Pdx1 and MafA genes to the pancreas. In models of Type 1 diabetes, the genes express proteins that transform alpha cells in the pancreas into functional beta-like cells, which can produce insulin but are distinct enough from beta cells to evade the body's immune system. In Type 2 diabetes, where autoimmunity is not at play, it is believed that exhausted beta cells are rejuvenated and replenished. The company in February announced groundbreaking data from a non-human primate study evaluating its novel gene therapy to treat Type 1 diabetes. Results showed statistically significant decreases in insulin requirements, increases in c-peptide levels and improvements in glucose tolerance compared to baseline. The report was based on results from eight non-human primates (NHPs) with toxin-induced diabetes after streptozocin administration. They received a novel infusion process that used an AAV vector to deliver Pdx1 and MafA genes directly to the pancreas. Big Pharma's Bet On Gene Therapy Big Pharma is rapidly accelerating investment in emerging gene therapies with diabetes being of particular note. Major players, such as Eli Lilly and Company, Sanofi SA, and Novo Nordisk A/S, are advancing novel therapies that may supplant traditional insulin-based therapies. In April 2021, Jaguar Gene Therapy announced the closing of a $139 million Series B investment led by Eli Lilly and Company and Deerfield Management, to support the advancement of a novel gene therapy for type 1 diabetes. In March 2023, Sanofi announced the intention to acquire Provention Bio, and its TZIELD therapy that delays the onset of Type 1 diabetes, in a deal valued at approximately $2.9 billion. In April 2023, Novo Nordisk entered a collaboration with Aspect Biosystems to pursue novel therapeutics for Type 1 diabetes and obesity, in a deal valued at approximately $2.6 billion. Other big players like Amgen Inc., Gilead Sciences Inc., Biogen Inc., and bluebird bio Inc., have also made big bets in gene therapy. Intellectual Property Genprex's intellectual property portfolio - consisting of numerous issued patents and pending patent applications licensed from major academic research institutions - could provide the company with a strong competitive advantage in the gene therapy space. This IP protection covers key aspects of the company's proprietary technologies and product candidates, including methods of gene delivery, therapeutic compositions and manufacturing processes. Experienced Management Team The success of Genprex is driven by its experienced and dedicated management team, which brings decades of combined experience in biopharmaceutical development, commercialization, and business operations. This expertise could ensure that the company is well-positioned to navigate the complex landscape of gene therapy development and deliver on its mission to bring innovative treatments to large populations of patients in need. Genprex Strengthens Diabetes Gene Therapy Program On December 15 last year, the company announced it had entered into an exclusive license agreement with the University of Pittsburgh, granting Genprex a worldwide, exclusive license to certain patent applications and related technology and a worldwide, non-exclusive license to use certain related know-how, all related to modulating autoimmunity in Type 1 diabetes by using gene therapy. The preclinical technology transforms macrophages, enabling them to reduce autoimmune activity in Type 1 diabetes, and could be complementary to the company's existing diabetes technology. Genprex Signs Exclusive License To Additional Diabetes Technology The company also revealed on January 5 that it has entered into another exclusive license agreement with the university, granting Genprex a worldwide, exclusive license to a patent application and related technology and a worldwide, non-exclusive license to use certain related know-how, all related to gene therapy for Type 2 diabetes using the genes of the Pdx1 and MafA transcription factors. The preclinical technology, GPX-003, is believed to work by rejuvenating diminished beta cells to increase insulin expression by introducing transcription factors controlled by an insulin promoter. Featured photo sourced from Shutterstock CONTACT: Genprex investors@genprex.com SOURCE: Genprex View source version on accesswire.com: