CD11a

DSMB approval to proceed to second cohort of REGALS trial (T Regulatory Cells for ALS). Ongoing Phase 1/1b study evaluating safety and efficacy of CK0803 (Neurotrophic T regulatory cells) HOUSTON, Feb. 19, 2024 /PRNewswire/ -- Cellenkos® today announced encouraging safety data from its innovative CK0803 neurotrophic T regulatory (Treg) cell therapy, being developed to help treat individuals with Amyotrophic Lateral Sclerosis (ALS). The company can now begin treating the second group of patients in the trial (clinicaltrials.gov: NCT05695521) The company was given the green light to move ahead following a review of safety data by the Data Safety Monitoring Board (DSMB). The DSMB found none of the participants experienced any serious adverse events or dangerous side effects from the therapy. "We are very excited and encouraged by this development," says Tara Sadeghi, Chief Operating Officer of Cellenkos. "This recommendation from the DSMB is an important step in bringing this potential disease modifying therapy to the patients and takes us closer to our ultimate goal of curing ALS." CK0803 is a neurotrophic, allogeneic, umbilical cord blood-derived T regulatory (Treg) cell therapy that preferentially homes towards inflamed microglia, developed by using Cellenkos' proprietary CRANE® technology, to generate disease-specific products. The completion of cohort 1 dosing allows for the continued enrollment on the Phase 1 Safety Run-in Study, to be followed by a Phase 1b Randomized, Double Blind, Placebo Control Trial of CK0803 in patients with ALS. The treatment will include four weekly infusions followed by five monthly infusions. Regulatory T Cells for Amyotrophic Lateral Sclerosis (REGALS) is a multicenter study including Columbia University, New York; Michael E. DeBakey VA Medical Center, Houston and Baylor College of Medicine, Houston. The primary objective of this study is to establish safety and tolerability of multiple doses of CK0803 in ALS patients. This study will also provide preliminary efficacy data of CK0803 in ALS using the primary endpoint of combined assessment of function and survival (CAFS) that ranks patients' clinical outcomes based on survival time and change in the ALS Functional Rating Scale-Revised (ALSFRS-R) score, and secondary endpoint of longitudinal measurement of neurofilament light chain levels in serum and cerebrospinal fluid (CSF). About Amyotrophic Lateral Sclerosis (ALS) According to the National Institute of Neurological Disorders and Stroke, amyotrophic lateral sclerosis (ALS) is a group of rare neurological diseases that mainly involve the nerve cells (neurons) responsible for controlling voluntary muscle movement. In ALS, both the upper motor neurons and the lower motor neurons degenerate or die and stop sending messages to the muscles. Unable to function, the muscles gradually weaken and waste away (atrophy). Eventually, the brain loses its ability to initiate and control voluntary movements. The disease is progressive, meaning the symptoms get worse over time. Majority of ALS cases (90 percent or more) are considered sporadic. This means the disease seems to occur at random with no clearly associated risk factors and no family history of the disease. In a small (approximately 10%) of cases, ALS is caused by a mutation in a known ALS-associated gene. Most people with ALS eventually die from respiratory failure, usually within 3 to 5 years from when the symptoms first appear. However, about 10 percent of people with ALS survive for 10 or more years. Currently, there is no cure for ALS and no effective treatment to halt or reverse the progression of the disease. About CK0803 CK0803 is a novel allogeneic cell therapy product consisting of T regulatory cells, with a high cell surface expression of CD11a, that leverage CXCR3/CXCL10 axis to engage with the inflamed microglia. CK0803 is derived from clinical-grade umbilical cord blood units and manufactured using Cellenkos' proprietary CRANE® process. There is no requirement for HLA or ABO matching of CK0803 to the recipient. Multiple doses of CK0803 can be manufactured from a single umbilical cord blood unit, where the final cryopreserved product is readily available for use, at the point of care, which makes it an ideal therapy that can be infused intravenously, in the outpatient setting. About Cellenkos®, Inc. Cellenkos is a clinical-stage biotechnology company located in Houston, Texas, USA, dedicated to the development and commercialization of the allogeneic, "off-the-shelf" cell-based products for the treatment of rare inflammatory diseases and autoimmune disorders. Cellenkos' T regulatory cells (Tregs) are derived from umbilical cord blood and as such are naïve, bonafide suppressor cells that do not require HLA or ABO matching and resolve inflammation through multiple direct and indirect mechanisms. Cellenkos' proprietary CRANE® process allows for tailoring of Tregs to become disease specific. Cellenkos' current clinical portfolio includes CK0801 (bone marrow failure); CK0802 (COVID ARDS); CK0803 (ALS) and CK0804 (myelofibrosis). For more information, please visit . Contact: Stacy Minor [email protected] SOURCE Cellenkos, Inc.

First cohort of REGALS (T Regulatory Cells for ALS) has been completed. Ongoing Phase 1/1b study evaluating safety and efficacy of CK0803 (Neurotrophic T regulatory cells). HOUSTON, Jan. 19, 2024 /PRNewswire/ -- Michael E. DeBakey VA Medical Center announces opening of a new clinical trial using CK0803- off-the-shelf, allogeneic T regulatory cells that have been modified to target neuroinflammation to treat the fatal neurodegenerative disease – Amyotrophic Lateral Sclerosis (ALS). Continue Reading ALS Clinical Coordinator Richel Aliboso, NP, Principal Investigator Dr. James Orengo and Study Coordinator Michelle Espiritu are thrilled to enroll Houston VA Veterans into this groundbreaking clinical trial. "We are very excited to open this first-in-class, best-in-class, cell therapy aimed to resolve neuroinflammation which fuels the ALS disease process. We believe that this novel approach of calming the inflamed microglia in the brain and spinal cord holds the promise for halting this relentlessly progressing disease", said Dr. James Orengo, principal investigator at the Michael E. DeBakey VA Medical Center and Assistant Professor of Neurology at Baylor College of Medicine. "Specifically, we are thrilled that our veterans will get the opportunity to receive such a cutting edge therapeutic that could be life altering. The incidence of ALS is elevated in Veterans and novel therapies are desperately needed. We are proud to be the first and only VA hospital in the nation to be part of this multi-center study". Please click here for the VA announcement. ALS is a rare, rapidly progressing and fatal neurodegenerative disorder that affects approximately 55,000 people globally. People with ALS experience muscle weakness, loss of movement, and difficulty breathing and swallowing, resulting in a severely declining quality of life and eventually death. The incidence of ALS has been rising in the veteran population and is a large unmet need. More than 16% of patients with ALS are veterans1. There are many health issues that veterans are at increased risk of, including ALS2. Veterans are twice as likely to be diagnosed with ALS than people who haven't served in the military3. "There is an urgent need for novel treatments for all forms of ALS, a devastating disease that affects far too many patients and their families. We made a conscious decision to make this novel cell therapy available to the veterans and remain committed to provide our continued support to those who have served our country," said Tara Sadeghi, Cellenkos' chief operating officer. "Leveraging our experience in consistently developing and manufacturing, robust, T regulatory cell therapies that are targeted towards disease specific mechanism of action and our intimate connection to the ALS patient community, Cellenkos made the decision to advance CK0803 to the clinic and, ultimately, to the market because we believe we are uniquely positioned to make it available to patients living with ALS." The first cohort of phase 1/ 1b CK0803 trial has been completed and is currently open for enrollment at Columbia University, New York, NY, led by PI, Dr Neil Shneider, M.D., Ph.D., director of Columbia University's Eleanor and Lou Gehrig ALS Center. About Amyotrophic Lateral Sclerosis (ALS) According to the National Institute of Neurological Disorders and Stroke, amyotrophic lateral sclerosis (ALS) is a group of rare neurological diseases that mainly involve the nerve cells (neurons) responsible for controlling voluntary muscle movement. In ALS, both the upper motor neurons and the lower motor neurons degenerate or die and stop sending messages to the muscles. Unable to function, the muscles gradually weaken and waste away (atrophy). Eventually, the brain loses its ability to initiate and control voluntary movements. The disease is progressive, meaning the symptoms get worse over time. The majority of ALS cases (90 percent or more) are considered sporadic. This means the disease seems to occur at random with no clearly associated risk factors and no family history of the disease. In a small (approximately 10%) of cases, ALS is caused by a mutation in a known ALS-associated gene. Most people with ALS eventually die from respiratory failure, usually within 3 to 5 years from when the symptoms first appear. However, about 10 percent of people with ALS survive for 10 or more years. Currently, there is no cure for ALS and no effective treatment to halt or reverse the progression of the disease. About CK0803 CK0803 is a novel allogenic cell therapy product consisting of T regulatory cells, with a high cell surface expression of CD11a, that leverage CXCR3/CXCL10 axis. CK0803 is derived from clinical-grade umbilical cord blood units and manufactured using Cellenkos' proprietary CRANE® process. There is no requirement for HLA or ABO matching of CK0803 to the recipient. Multiple doses of CK0803 can be manufactured from a single umbilical cord blood unit, where the final cryopreserved product is readily available for use, at the point of care, which makes it an ideal therapy that can be infused intravenously, in the outpatient setting. About Cellenkos®, Inc. Cellenkos is a clinical-stage biotechnology company located in Houston, Texas, USA, dedicated to the development and commercialization of the allogeneic, "off-the-shelf" cell-based products for the treatment of rare inflammatory diseases and autoimmune disorders. Cellenkos' T regulatory cells (Tregs) are derived from umbilical cord blood and as such are naïve, bonafide suppressor cells that do not require HLA or ABO matching and resolve inflammation through multiple direct and indirect mechanisms. Cellenkos' proprietary CRANE® process allows for tailoring of Tregs to become disease specific. Cellenkos' current clinical portfolio includes CK0801 (bone marrow failure); CK0802 (COVID ARDS); CK0803 (ALS) and CK0804 (myelofibrosis). For more information, please visit . Contact: Stacy Minor [email protected]. SOURCE Cellenkos, Inc.

First report to show link between GDF-15 and LFA-1/ICAM-1 cell adhesion axis in cancer, resulting in impaired infiltration of T cells into the tumor microenvironment. Neutralizing GDF-15 reverses inhibitory effects and re-sensitizes tumors to anti-PD-1 treatment achieving commensurate survival benefit of anti-GDF-15-anti-PD-1 combination therapy in vivo. Data highlight GDF-15 as central factor of innate resistance to PD-1 treatment in solid tumor patients. Preclinical and existing clinical data underline the potential of neutralizing GDF-15 in combination with PD-1 inhibition as a novel treatment strategy for solid tumor patients. MUNICH--(BUSINESS WIRE)-- CatalYm today announced the publication of preclinical data in Nature Communications under the title “Tumor-derived GDF-15 blocks LFA-1 dependent T cell recruitment and suppresses responses to anti-PD-1 treatment”. The study reveals a central role of GDF-15 in the resistance of tumors to current immunotherapy. These findings further highlight the therapeutic significance of CatalYm’s proprietary anti-GDF-15 antibody candidate, visugromab, currently in advanced Phase 2 clinical studies. This press release features multimedia. View the full release here: Action of GDF-15 as illustrated by CatalYm, all rights reserved. (Graphic: Business Wire) This foundational research, which was performed together with founder Jörg Wischhusen and collaborators, is the first to describe a mechanistic link between tumor-produced Growth Differentiation Factor-15 (GDF-15) and the LFA-1/ICAM-1 cell adhesion axis. The interaction between LFA-1/ICAM-1 is a critical step in the infiltration of T cells into the tumor microenvironment. This is essential for the extravasation of T cells from the blood vessels into the surrounding tissue. GDF-15 is primarily known for its function in feto-maternal tolerance, an immunosuppressive mechanism that protects the fetus from the mother’s immune system. The researchers demonstrated that GDF-15 blocks LFA-1-dependent T cell recruitment into the tumor microenvironment, a prerequisite for responses to anti-PD-1/-L1 treatment but also other immunotherapeutic strategies. Conversely, the blockade of GDF-15 with antibodies like the anti-GDF-15 antibody visugromab improved T cell infiltration into tumors. Combined with a PD-1 inhibitor, it increased tumor clearance and survival with a synergistic effect. In line with these findings, serum analysis of melanoma patients showed that response to anti-PD-1 negatively correlates with GDF-15 serum levels. Therefore, GDF-15 serum levels may be a predictive biomarker for the response to anti-PD-1 therapy and overall survival in these patients. These findings further underscore the immunosuppressive role of GDF-15 in the tumor and contribute to the growing body of data supporting GDF-15-neutralizing therapy as a promising approach for hard-to-treat tumors resistant or refractory to anti-PD-1/-L1 treatment. "Our publication is the first to demonstrate the effect of tumor-derived GDF-15 on the LFA-1/ICAM-1 axis. As this axis orchestrates cell-cell-interactions that are essential for immune-mediated tumor control, GDF-15 likely contributes to immune escape across many different tumors and therapies,” said Prof. Dr. Jörg Wischhusen, Co-Founder of CatalYm and Professor at the Julius-Maximilians-University Würzburg, who is the senior author of the publication. “Unraveling the details of the underlying biologic pathways is crucial to develop effective therapeutic approaches that can reverse tumor-mediated immunosuppression resulting in drug resistance, one of the major challenges in cancer medicine. We are committed to rapidly advancing our Phase 2 evaluation of visugromab on our mission to expand the treatment horizon for current and future immunotherapies,” added Dr. Christine Schuberth-Wagner, Chief Scientific Officer at CatalYm. The published data adds further valuable mechanistic understanding to the clinical findings from CalaYm’s GDFather (GDF-15 Antibody-mediaTed Human Effector Cell Relocation) trials with visugromab in combination with the anti-PD-1 inhibitor nivolumab in patients with advanced solid tumors. The Phase 1 (NCT04725474) study results announced in September 2022 showed an excellent safety and tolerability pro well as significant clinical benefit in last-line tumor patients that were anti-PD-1/-L1 relapsed or refractory. Interim data from the Phase 2 (NCT04725474) trial recently presented at ASCO continue to demonstrate a very good safety and tolerability pro promising early responses in major cancer indications, including non-small cell lung cancer (NSCLC), bladder cancer and hepatocellular carcinoma (HCC). Mature data readouts for efficacy and safety data of the core Phase 2a program as well as main biomarker-correlations are expected to become available by late 2023. About the GDFATHER-2 Trials The GDFATHER-2a trial (GDF-15 Antibody-mediaTed Human Effector Cell Relocation Phase 2) (NCT04725474) is an ongoing Phase 2a trial with several cohorts investigating the effect of visugromab (CTL-002) as monotherapy and/or in combination with a PD-1 checkpoint inhibitor in patients in various advanced-stage, relapse/refractory solid tumor types and a biomarker-selected cohort. The study can enroll > 200 patients in Simon-2-stage designs and a biomarker-evaluation directed cohort to confirm certain response rates and potential biomarker-based responder patient selection. About Visugromab (CTL-002) Visugromab is a humanized monoclonal antibody that neutralizes the tumor-derived Growth Differentiation Factor-15 (GDF-15). GDF-15 is an essential player in feto-maternal tolerance, a powerful mechanism that cancer cells hijack to create an immunosuppressive environment to evade destruction. By neutralizing GDF-15, visugromab reverses the immunosuppressive effects that block an efficient anti-tumor immune response in the tumor microenvironment and the draining lymph nodes. Visugromab drives an activated and differentiated immune cell infiltration into the solid tumor as well as enables priming of T cells and enhances the tumor-killing effects of T cells and NK cells. GDF-15 is currently investigated in an ongoing Phase 2 program that includes confirmatory studies in multiple solid tumor indications and the analysis of a predictive response biomarker to better identify the patients benefiting from this new class of immunotherapy. About CatalYm CatalYm is pioneering a novel immuno-oncology therapy that safely overcomes GDF-15-mediated immunosuppression in the tumor microenvironment. Our lead product, visugromab, a first-in-class GDF-15 neutralizing antibody, has demonstrated potent and durable anti-tumor efficacy with multiple, long-lasting objective responses in combination with anti-PD-1 treatment in phase 1/2 studies in advanced cancer patients. CatalYm is focused on maximizing visugromab’s potential as a new class of cancer immunotherapy with a clinically distinct pro a range of solid tumor indications. View source version on businesswire.com: Contacts CatalYm GmbH Dr. Phil L’Huilier, CEO info@catalym.com Media Inquiries Trophic Communications Dr. Alison Opalko Phone: +49 151 54041130 catalym@trophic.eu Source: CatalYm Smart Multimedia Gallery Photo Action of GDF-15 as illustrated by CatalYm, all rights reserved. (Graphic: Business Wire) Logo View this news release and multimedia online at: