Ruxolitinib Phosphate

Trillions of bacteria, fungi and viruses live within our bodies, making up our microbiome. Scientists have been studying the role these microorganisms play in our health, and in recent years, the focus has shifted to oncology. Specifically, could mitigate complications of cancer treatments and potentially improve the bodys response to certain cancer treatments leading to improved survival?MaaT Pharma is at the forefront of innovation in this field, striving to achieve the first-ever approval of a microbiome-driven immunomodulator in oncology.In 2022, the biotech company launched a Phase 3 clinical trial, in Europe, in patients with acute graft versus host disease (aGvHD), and topline results are anticipated as early as January 2025. If approved, the drug candidateMaaT013could offer a new treatment option to patients with steroid refractory and ruxolitinib refractory or intolerant aGvHD.Herv AffagardPermission granted by MaaT PharmaWe have decided to focus on oncology patients because that's where we believe the most unmet medical need and potential for microbiome-based therapies exists, says Herv Affagard, CEO and co-founder of MaaT Pharma. What were doing is modulating the immunity of the patient in oncology to improve survival.We sat down with Affagard to talk about the potential of microbiome therapeutics for oncology patients, and his vision for the future.The microbiome is increasingly recognized as crucial for health and disease. Can you explain how it's relevant for oncology, and why MaaT Pharma is focused on this area?Affagard: We know that 25% of the worlds population shows an alteration of its microbiome, and there can be different reasons for that. In oncology, cancer patients are receiving harsh treatments, such as chemotherapy, antibiotics and stem cell transplantation, that can alter the microbiome to the point that sometimes the microbiome becomes unstable or ineffective, resulting in dysbiosis. When that happens, the immune system loses its counterpart which can trigger hyperinflammation in the body. These changes are often more significant in cancer than we see in other diseases, so the potential in oncology is very clear.At MaaT Pharma, we want to restore the balance between the microbiome and the immune system. We are on the verge of demonstrating, potentially for the first time, that a microbiome-based therapy could improve overall survival in patients with acute Graft-versus-Host Disease. Everything that has been done before, especially in infectious disease, is only dealing with symptoms and complications, but here we are dealing with a hard end point: survival.That's fascinating. So, how does MaaT Pharma leverage the gut microbiome to potentially treat cancer?Affagard: We approach the potential to treat cancer in two ways. One, we accompany anti-cancer treatments as a partner to optimize the treatment. In that situation, were aiming to create a drug which is a phenotype that will make the patient respond to the treatment, such as immune checkpoint inhibitors. Also, were aiming to directly treat certain diseases, such as aGvHD, by replacing the microbiome with a very specific microbiome that may be able to reduce inflammation.What makes your approach different from others who are exploring these kinds of therapies?Affagard: There are different modalities to trick the microbiome. For example, you could have something simple, like a probiotic or a prebiotic to promote certain bacteria, which can be effective when dysbiosis is mild. But with aGvHD patients were dealing with an emergencyhalf of them die after just 28 days, to give you an idea. So, we want to repair everything as fast as possible. Thats why were dealing with a full reset of the microbiome, and what sets MaaT Pharma apart from others in this space is the fact that we are restoring the entire ecosystem. Weve developed a high-density drug using pooling technology, which allows us to pool donor-derived microbiota donations to create a standardized product with highly rich and diverse microbial content that will be impactful for the maximum number of patients. We are the only company in the world with an investigational new drug authorized to use this pooling technology in clinical trials in the U.S.Your lead candidate, MaaT013, has shown promise in clinical trials. What can you tell us about its progress?Affagard: Through the Early Access Program for MaaT013, weve treated more than 200 patients with aGvHD, including different subsets of these patients. One subset, for example, resembles the patients that we are treating in our Phase 3 clinical trial, and we see a significant overall survival benefit in this subset. Historical data showed that one-year survival rates for aGvHD patients receiving third-line treatments have been dismal, with only 15% surviving at 12 months. In contrast, our latest results presented at ASH 2024 highlight an impressive 49% overall survival at one year for similar patients population treated with MaaT013tripling the historical survival rate (from literature). Its very promising and were encouraged by what were seeing, which underscores MaaT013s potential to address a significant unmet need for patients with aGvHD.Weve also initiated the first treatment at City of Hope in the U.S. of a patient with aGvHD under the US Food and Drug Administration (FDA) Single Patient Expanded Access. How do these therapies have the potential to impact patients lives, especially those who are undergoing cancer treatments?Affagard: The feedback were receiving from physicians evaluating MaaT013 in patients through clinical trials is that its safe. You see, HSCT is a treatment often used in leukemia and other blood cancers. However, it comes with its own challenges, such as GvHDa complication where the donor cells attack the recipient's body. When this happens, immunosuppressants are usually the drug used. And immunosuppressants, at a certain point in time, create complications as the patient risks developing infections because the immune system is down. But you don't see that with our microbiome-based therapy, which has a direct impact on quality of life for the patients. In addition, our treatment is not a chronic treatment. You receive three doses, and when it works, it works very well. And if it doesn't work, it doesn't work, but you do not have to be under treatment for six months, which would be the case for immunosuppressants.Looking ahead, what are your predictions for the microbiome therapy space over the next five years?Affagard: I believe there will be more and more applications leveraging the microbiome in oncology, especially coming from small companies. Academic research has been very important since 2010, and now were at a point where there's a lot of innovation. I believe that the field of inflammatory bowel disease, neurodegenerative disease and oncology will be the next big things in microbiome therapies.What are the next goals for MaaT Pharma?Affagard: Our primary focus is to deliver the topline results for the Phase 3 trial in January 2025, because it will be the cornerstone of everything else in our pipeline. We believe a success in aGvHD will open the doors to many other therapeutic areas. Looking ahead, we have other programs in blood cancers but also in solid tumors and neurodegenerative disease where we are generating proof of concept data. But first, we need to demonstrate that by modulating the microbiome you can modulate the immune system and potentially cure diseases. That will be absolutely fantastic. '

- Safety profile established and encouraging efficacy signals demonstrated by reductions in spleen volume and symptom burden scores - Data underscore the vast potential of allogeneic, non-HLA matched, T regulatory cell therapy program in addressing diseases driven by dysregulated inflammation Dec. 10, 2024 -- Cellenkos, Inc., a clinical-stage biotechnology company focused on developing allogeneic, off-the-shelf, T regulatory (Treg) cell therapies for inflammatory diseases of high unmet needs and autoimmune disorders, presented new Phase 1b results highlighting the safety and efficacy of CK0804 for patients with myelofibrosis who did not respond to standard of care during the 66th Annual Meeting & Exposition of the American Society of Hematology (ASH), taking place in San Diego, CA, held from December 7 – 10, 2024. “There is a significant need for new therapeutic options for patients living with myelofibrosis who have suboptimal responses to approved JAK inhibitors,” said Simrit Parmar, MD, Founder of Cellenkos. “CK0804 is a CXCR4-enriched Treg cell therapy product candidate engineered to home to the bone marrow and offers a differentiated approach to address dysregulated inflammatory pathways driving this debilitating disease. We are greatly encouraged by the safety profile and early signs of efficacy observed in this patient cohort and look forward to continuing our evaluation of the clinical potential of CK0804 in our planned expansion cohort.” Title: A Phase 1b, Open-Label Study of Add-on Therapy with CK0804 in Participants with Myelofibrosis and Suboptimal Response to Ruxolitinib Abstract Number: 999 Oral Session: 634. Myeloproliferative Syndromes: Clinical and Epidemiological: Advancing MPN Care: Innovative Therapies and Clinical Breakthroughs in Myelofibrosis Date and Time: Monday, December 9, 2024. 5:00 p.m. PST Treatment Regimen: Six CXCR4-enriched Treg infusions (106 cells/infusion) were administrated every four weeks in the outpatient setting and were well tolerated (n=9) Conditioning: No lymphodepletion was administered. No HLA matching was performed. All CK0804 Tregs were cryopreserved and thawed and infused by the bedside. Spleen Volume Reduction: Four out of six evaluable patients showed spleen volume reduction when measured by MRI Transfusion Requirements: Two patients experienced a reduced need for monthly transfusions at the end of the study period Symptom Improvement: All treated patients reported overall improvement in symptom burden, including diminished fatigue and early satiety Biomarker Analysis: A reduction in levels of TGFβ, a pro-inflammatory cytokine, was observed and correlated with overall clinical response Systemic Inflammation: Additional analyses of multiple plasma inflammatory cytokines suggest a promising decline in systemic inflammation Following these encouraging results, Cellenkos is advancing this Phase 1 study with the addition of an expansion cohort to evaluate a modified CK0804 dosing regimen to account for the high level of inflammation observed in myelofibrosis patients with suboptimal responses to ruxolitinib. This expansion cohort is now enrolling patients. Cellenkos’ allogeneic, off-the-shelf, Treg therapies hold potential to treat a broad range of inflammatory and autoimmune conditions where long-term immune modulation is anticipated to durably modify the course of disease. In addition to CK0804, Cellenkos’ CK0801 candidate for aplastic anemia has shown promising efficacy, including transfusion independence in treated patients. Myelofibrosis is a rare, chronic, and progressive blood cancer that causes scar tissue to form in the bone marrow, disrupting the production of normal blood cells. Patients with myelofibrosis often experience debilitating symptoms such as fatigue, spleen enlargement, and night sweats. Approximately 16,000 to 18,500 people in the U.S. are living with myelofibrosis, and those who fail to respond adequately to current treatments including ruxolitinib, face limited options and a poor prognosis. Inflammation is a key driver for disease pathogenesis and progression in myelofibrosis. CK0804 is an investigational, allogeneic, off-the-shelf Treg cell therapy that leverages the CXCR4/CXCL12 axis to suppress inflammatory cytokines implicated in myelofibrosis pathogenesis. CXCR4 enriched Tregs home faster to bone marrow compared to unmanipulated Tregs. Derived from clinical-grade umbilical cord blood and manufactured using Cellenkos' proprietary CRANE® process, CK0804 does not require HLA matching, making it an ideal therapeutic option for patients in need of prompt intervention. The therapy is administered intravenously and can be infused in an outpatient setting. Cellenkos is a clinical-stage biotechnology company based in Houston, Texas, focused on developing off-the-shelf Treg cell therapies for rare inflammatory diseases and autoimmune disorders. Cellenkos' Treg therapies, derived from umbilical cord blood, are designed to provide powerful anti-inflammatory effects and long-lasting immune modulation without the need for donor matching. The company is committed to advancing the development of these promising therapies to improve the lives of patients with rare and underserved conditions. The content above comes from the network. if any infringement, please contact us to modify.