Digital ulcer

—Longitudinal Study of a 200+ Real-World Patient Cohort Further Validates CCL24 as a Novel Target for Systemic Sclerosis (SSc), Showing that It is Associated with Disease Severity Across the Fibrotic and Vascular Manifestations of SSc— TEL AVIV, Israel, April 18, 2024 (GLOBE NEWSWIRE) -- Chemomab Therapeutics Ltd. (Nasdaq: CMMB), (Chemomab), a clinical stage biotechnology company developing innovative therapeutics to treat rare fibro-inflammatory diseases with high unmet need, today announced the publication of a new study that further confirms the key role of its novel soluble protein target CCL24 in systemic sclerosis (SSc). The study, “Serum CCL24 as a Biomarker of Fibrotic and Vascular Disease Severity in Systemic Sclerosis,” was published in the current edition of the journal Arthritis Care and Research.1 “This important new longitudinal study in a large cohort of patients with SSc further confirms the extensive body of preclinical evidence we have generated showing that CCL24 is a key driver of the skin, lung and vascular complications in this terrible condition that lacks disease-modifying therapies,” said Adi Mor, PhD, a co-author of the publication and co-founder, CEO and CSO of Chemomab. “These results also reinforce our belief, based on multiple preclinical and patient sample studies, that our novel CCL24-neutralizing antibody CM-101 has substantial potential as a treatment for SSc. Our SSc program is Phase 2-ready with an open US IND, with possible initiation of patient enrollment after the topline readout from our Phase 2 trial in primary sclerosing cholangitis that is expected in the next few months.” The longitudinal study was conducted by prominent SSc researchers at the University of Leeds in the UK and included more than 200 patients. It explored the relationship between serum CCL24 levels and SSc severity and prognosis. One in four patients in a real-life SSc population was found to have a high CCL24 serum concentration, despite standard of care treatment with immunosuppressive therapy. The analysis found that higher CCL24 levels were linked to critical clinical variables associated with the most severe forms of SSc. They include severity of skin fibrosis and calcinosis, presence of interstitial lung disease (ILD), lung microvascular impairment, and a history of digital ulcers and synovitis. Crucially, high serum CCL24 was predictive of lung deterioration and a higher baseline CCL24 level was associated with higher 10-year SSc-related mortality. The association of CCL24 with rapid ILD progression and higher mortality was found to be independent of disease duration and demographic and other factors, highlighting its prognostic value over traditional clinical prognostic indicators. The authors conclude that the findings support the involvement of CCL24 in the pathophysiology of SSc and underscore its potential as a promising therapeutic target for patients with the disease. Professor Francesco Del Galdo , lead author of the new publication and Head of the Raynaud’s and Scleroderma Programme, Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, UK, commented, “This is a crucial addition to the preclinical studies on the role of CCL24 in SSc, supporting the involvement of this profibrotic chemokine in key clinical manifestations of systemic sclerosis. The results provide further evidence that a CCL24-neutralizing antibody such as CM-101 could potentially be a valuable therapy for this devastating disease that has limited treatment options. ” 1 - Serum CCL24 as a biomarker of fibrotic and vascular disease severity in Systemic Sclerosis, Enrico De Lorenzis MD PhD, Adi Mor PhD, Rebecca L. Ross PhD, Stefano Di Donato MD, Revital Aricha PhD, Ilan Vaknin PhD, Francesco Del Galdo MD PhD, Arthritis Care & Research, Forward Looking Statements This press release contains "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act. These forward-looking statements include, among other things, statements regarding the clinical development pathway for CM-101; the expectation that Chemomab will report topline data from the PSC clinical trial by mid-year 2024; the length, duration and impact of the war in Israel on Chemomab’s business and operations; the future operations of Chemomab and its ability to successfully initiate and complete clinical trials and achieve regulatory milestones; the nature, strategy and focus of Chemomab; the development and commercial potential and potential benefits of any product candidates of Chemomab; and that the product candidates have the potential to address high unmet needs of patients with serious fibrosis-related diseases and conditions. Any statements contained in this communication that are not statements of historical fact may be deemed to be forward-looking statements. These forward-looking statements are based upon Chemomab's current expectations. Forward-looking statements involve risks and uncertainties. Because such statements deal with future events and are based on Chemomab's current expectations, they are subject to various risks and uncertainties and actual results, performance or achievements of Chemomab could differ materially from those described in or implied by the statements in this presentation, including those found under the caption "Risk Factors" and elsewhere in Chemomab's filings and reports with the SEC. Chemomab expressly disclaims any obligation or undertaking to release publicly any updates or revisions to any forward-looking statements contained herein to reflect any change in Chemomab's expectations with regard thereto or any change in events, conditions or circumstances on which any such statements are based, except as required by law. About Chemomab Therapeutics Ltd. Chemomab is a clinical stage biotechnology company developing innovative therapeutics for fibro-inflammatory diseases with high unmet need. Based on the unique and pivotal role of CCL24 in promoting fibrosis and inflammation, Chemomab developed CM-101, a monoclonal antibody that neutralizes CCL24 activity. In clinical and preclinical studies, CM-101 appears safe, with the potential to treat multiple severe and life-threatening fibro-inflammatory diseases. Chemomab has reported positive results from three clinical trials of CM-101 in patients, including a Phase 2a liver fibrosis trial in NASH patients and an investigator-initiated study in patients with severe lung injury. A Phase 2 trial in primary sclerosing cholangitis has completed patient enrollment, with topline data expected midyear 2024. Chemomab’s CM-101 program for the treatment of systemic sclerosis is Phase 2-ready with an open U.S. IND. For more information about Chemomab, visit chemomab.com. Contact: Media and Investors: Barbara Lindheim Consulting Vice President, Investor & Public Relations, Strategic Communications Phone: +1 917-355-9234 barbara.lindheim@chemomab.com IR@chemomab.com

EU regulatory approval to administer Adipose-derived mesenchymal Stem Cells (ASCs) in patients with ischemic digital ulcers marks key milestone for partners Toulouse, France, November 16, 2023 - Cell-Easy, a French Contract Development and Manufacturing Organization (CDMO) focused on advanced cell therapies, and the Toulouse University Hospital, today announce that they have obtained IMPD (Investigational Medicinal Product Dossier) approval for a first-in-human clinical trial. This trial will use an allogeneic treatment, developed from an autologous process, for patients with ischemic digital ulcers in systemic sclerosis. The CDMO developed the entire manufacturing process from an initially autologous one where the cell donor was the patient himself. The innovative allogeneic approach uses cells from a single donor to produce therapeutic doses for thousands of patients. This is cost-efficient, and therefore it makes the product more accessible for patients. Cell-Easy has conceived and designed a process for the large-scale manufacturing of ASCs in compliance with the GMP (Good Manufacturing Practice) standards required by regulatory agencies. These ASCs will be used in the A-DUSE clinical trial. Prof. Gregory Pugnet, from the Internal Medicine and Clinical Immunology department, Rangueil Hospital, Toulouse, (France) is the main investigator of the trial, which is sponsored by Toulouse University Hospital. Gaining ANSM/EMA's approval for the A-DUSE clinical trial is a demonstration of the Cell-Easy team’s ability to carry out a cell therapy development program from end to end. Some highlights from the new large-scale manufacturing process of therapeutic doses of allogeneic ASCs: >5,000 doses per tissue donation >4.109 cells per batch x20 cost reduction 26 parameters analyzed per batch The Toulouse University Hospital, through its clinical center of investigation in biotherapy (CIC-BT) structure, stands as a pioneering cell therapy player in Europe. It has 20 years' experience in the field of cell therapy based clinical research. In a bid to kickstart the A-DUSE clinical trial safely and efficiently, Prof. G. Pugnet was looking for a robust industrial partner capable of providing high numbers of clinical grade ASC therapeutic doses. The scientific, technical and regulatory expertise of the French CDMO, and its ability to offer an end-to-end service spanning from patient sample procurement through to IMPD writing, convinced the Toulouse study center. “This project represents another remarkable milestone for Cell-Easy, demonstrating our ability to successfully navigate the entire life cycle of Advanced Therapy Medicinal Products (ATMP) development. Our collaborative work with physicians, supply chain partners, regulators and policymakers has enabled us to effectively address the intricacies of these therapies and establish rigorous quality standards,” said Guillaume Costecalde, president at Cell-Easy. Beyond conventional GMP manufacturing of ASCs, the A-DUSE clinical trial required the selected partner to provide unfailing support in terms of regulatory and scientific matters, as well as medico-economic understanding of the disease. Close collaboration between Cell-Easy, CIC-BT and Prof. G. Pugnet was instrumental in achieving this objective. In less than 20 months, Cell-Easy developed a new production process in ASC along with all the associated analytical tests for robust batch qualification. Within the framework of this partnership, the resources made available by the CDMO have resulted in: Establishment of partnerships with local healthcare centers capable of selecting donors based on medical-biological criteria, of supplying human adipose tissue and of qualifying donations at GMP level, as required by EU/US regulatory agencies Conducting toxicity and tumorogenicity studies in mice, and Co-authoring the IMPD for submission to the local French agency, the ANSM Injection of allogeneic ASC, a promising opportunity for healing digital ulcers Systemic sclerosis is an orphan disease characterized by the development of microangiopathies and progressive fibrosis. Digital Ulcers (DUs) are common in the course of the disease and are an expression of its severity. Not only do DUs cause intense pain and hand disability, but more critically they can lead to infections that can result in gangrene and eventual amputation. With optimal standard of care only 60% of DUs are healed after three months and 46.2% experience recurrence during this period, with 11.2% having a chronic course. To date, no medication has demonstrated a positive effect on the healing of refractory DUs. In this clinical context with no therapeutic alternative, the partnership between Toulouse University Hospital, represented by Prof. G. Pugnet, the CIC-BT, and Cell-Easy, through the A-DUSE Clinical Trial (digital injection of allogeneic ASC), represents a promising opportunity for many patients in the healing of refractory ischemic DUs. Since 2021, French players in biotherapy have been working hard to convert a promising MSC-based therapy concept into reality for patients living with ischemic digital ulcers due to systemic sclerosis. About Grégory Pugnet, coordinating investigator Grégory Pugnet, M.D., PhD., coordinating investigator of the multicentric randomized control clinical trial (ADUSE, NCT04356755, EU CT Number 2023-508432-53-00), is among the few specialists in systemic autoimmune disease; in which he is leading important clinical research activity. He worked for 18 months at the French Reference Center for Systemic Sclerosis in Cochin Hospital (Paris, France). Pugnet is an active member of the GFRS (Groupe Francophone de Recherche sur la Sclérodermie), and a member of the scientific committee of the French Reference Center for Cell Therapy in Autoimmune Diseases (MATHEC network), with the FAI2R network, labeled by the French Ministry of Health in 2017. Grégory also actively participates in CIC-BT, coordinated by Louis Buscail, and has secured funding for three ASC-based cell therapy projects in scleroderma (A-DUSE, A-MUSE) and neuroinflammatory muscular diseases (A-NEMIS) in collaboration with CIC-BT and Cell-Easy. About CIC-BT The Clinical Center of Investigation in BioTherapy (CIC-BT 1436) is an academic organization under the supervision of Toulouse University Hospital (CHUT)/INSERM/University. It was established at the end of 2005 to support researchers and companies developing cell, gene and molecular therapy ATMPs, from the preclinical phases through to the coordination and conduct of phase 1-3 clinical trials. Its structure draws on the expertise of CHUT's research and innovation department for regulatory aspects when CHUT is the study sponsor. Coordinated by Prof. Louis Buscail, CIC-BT has been responsible for numerous projects, funded by a total of six million euros ($6.4M) (CHU promoter), including five national clinical research hospital programs – Programme Hospitalier de Recherche Clinique (PHRC) (2010, 2013, 2014, 2017 and 2022), three inter-regional PHRCs (2013, 2019 and 2022), one Horizon 2020 program, one SudOE program and two associations. CIC-BT also carries out extensive research in cardiovascular and digestive pathologies, in geriatrics and pediatrics, as well as translational research in collaboration with teams involved in regenerative medicine (RESTORE), neurodegenerative diseases (INFINITY), cardiovascular diseases (I2MC) and oncology (CRCT). About Cell-Easy Cell-Easy is a rapidly growing French Contract Development and Manufacturing Organization (CDMO) with a dedicated focus on advanced cell therapies. Established in 2017, Cell-Easy's commitment extends beyond development and manufacturing; it also places a strong emphasis on regulatory and CMC aspects. Cell-Easy offers a comprehensive range of services, from process development and process scale-up through to cGMP manufacturing of next-generation advanced cell therapies. This also includes the development of analytical tests to qualify cell therapies such as ASCs, CAR-T or CAR-NK cells, iPSCs and macrophages. Cell-Easy has demonstrated its ability to support biotech/pharmaceutical companies in advancing their programs up until phase 2, and to partner with top 30 international pharmaceutical multinationals. Thanks to its flexibility and tailored CDMO solutions, Cell-Easy facilitates patient access to these innovative therapies. Media and analysts contact Andrew Lloyd & Associates Saffiyah Khalique - Emilie Chouinard saffiyah@ala.associates / emilie@ala.associates UK: +44 1273 952 481 @ALA_Group

New analysis from long-term study published in Journal of Child and Adolescent Psychopharmacology Reinforces prior data demonstrating AZSTARYS, first and only medicine of its kind, is effective and safe BOSTON , May 22, 2023 /PRNewswire/ -- Corium, LLC, a commercial-stage biopharmaceutical company leading the development and commercialization of novel central nervous system (CNS) therapies, announced that an analysis of a long-term, 12-month, open-label Phase 3 study of children aged 6-12 using its novel attention-deficit hyperactivity disorder (ADHD) medication AZSTARYS (serdexmethylphenidate [SDX] and dexmethylphenidate [d-MPH]) showed no clinically significant impact on weight and height growth rate in pediatric patients. CNS stimulants prescribed for treatment of ADHD have been associated with slowing of height and weight growth in pediatric patients. The study results were published in the peer-reviewed Journal of Child and Adolescent Psychopharmacology (JCAP). "This growth analysis in children, showing no clinically significant impact, addresses important considerations about height and weight growth when prescribing a stimulant such as AZSTARYS," said Ann Childress, M.D., lead author of the study article, president of the Center for Psychiatry and Behavioral Medicine, and lead investigator. "This analysis builds on previous analyses of year-long treatment using SDX/d-MPH that document the medicine delivers safe, well-tolerated, and continued reduction of ADHD symptoms." "This year-long data showing the absence of a clinically significant impact on growth rate for children aged 6-12 adds an important dimension to our understanding of AZSTARYS," said Charles Oh, M.D., Chief Medical Officer of Corium. "This new analysis strengthens the pro AZSTARYS as an important treatment option for safe, effective, and sustained ADHD symptom control that clinicians, parents and patients should consider." AZSTARYS is the first and only medicine indicated for the treatment of ADHD in patients ages 6 years through adulthood that contains SDX, the prodrug of d-MPH, along with immediate-release d-MPH. SDX is a prodrug designed to be pharmacologically inactive until reaching a patient's lower gastrointestinal tract where, by design, it gradually converts to d-MPH throughout the day. This formulation provides rapid control of ADHD symptoms with the immediate-release d-MPH and extended duration of symptom control with the SDX. AZSTARYS is a Schedule II controlled substance, given it contains 30% immediate release d-MPH. The SDX component of AZSTARYS (comprising 70% of the active ingredient) is a Schedule IV controlled substance. Trial Overview This analysis used data from 238 children aged 6 to 12 years enrolled in the year-long, open-label safety study of AZSTARYS (NCT03460652) conducted in the U.S. After dose-optimization, the children received once-daily AZSTARYS doses of 26.1/5.2 milligrams (mg), 39.2/7.8 mg, or 52.3/10.4 mg of SDX/d-MPH. At enrollment, the children averaged (±standard deviation [SD]) 9.1 (±1.9) years in age and 60.9% were male. Their weight ranged from 21.0 to 97.0 kilograms (kg), averaging (±SD) 38.6 (±13.9) kg, with an average (±SD) body-mass index (BMI) of 19.2 (±4.6) kg/m2. They ranged in height from 113.5 to 171.2 centimeters (cm), averaging (±SD) 139.6 (±11.9) cm. Using weight and height measures, the investigators calculated monthly differences for the children during treatment. Using a standard calculation known as a Z-score, they also determined if the children's average weight and height differed from a general population, using 2020 growth chart data of people aged 2 to less than 20 years from the U.S. Centers for Disease Control and Prevention. A change in a Z-score that is greater than 0.5 is considered clinically significant. Expected Weight The children's weight experienced a transient decrease, followed by a slower-than-predicted gain in their first three months of treatment, yet did not significantly differ from the reference population. In the study, the difference between the children's actual weights compared to predicted body weights remained fairly constant until their treatment ended. At 90 treatment days, their average weight of 38.5 kg differed from a predicted weight of 40.2 kg by 1.7 kg. After 360 days of treatment, their weight and predicted weights averaged 41.1 kg and 42.8 kg, respectively, with the same difference as before. The change in their average (±SD) weight Z-score from the study start to 12 months was −0.20 (±0.5) and did not reach the -0.5 threshold for clinical significance. Expected Height Growth The children's height increased steadily during the study. Their increases were less than the reference population but in a range considered not clinically significant. At 90 treatment days, their average height of 140.8 cm differed from a predicted height of 141.4 cm by 0.6 cm. After 360 days of treatment, their height and predicted heights averaged 143.4 cm and 144.8 cm, respectively, a difference of 1.4 cm. The change in their average (±SD) height Z-score from the study start to 12 months was −0.21 (±0.39) and did not reach the -0.5 threshold for clinical significance. About AZSTARYS AZSTARYS, approved for patients ages 6 years through adulthood, is the first and only once-daily treatment for ADHD symptoms containing SDX, the prodrug of d-MPH. SDX is designed specifically to be pharmacologically inactive until reaching a patient's lower gastrointestinal tract, where, by design, the prodrug gradually converts to d-MPH throughout the day. This formulation provides control of ADHD symptoms both rapidly with the immediate-release d-MPH and for an extended duration with SDX. Once-daily AZSTARYS is available in the U.S. in three SDX/d-MPH dose strengths of 26.1/5.2 mg, 39.2/7.8 mg, and 52.3/10.4 mg. Indication and Important Safety Information for AZSTARYS (serdexmethylphenidate and dexmethylphenidate) INDICATION AZSTARYS is a central nervous system (CNS) stimulant indicated for the treatment of Attention Deficit Hyperactivity Disorder (ADHD) in patients aged 6 years and older. IMPORTANT SAFETY INFORMATION WARNING: ABUSE AND DEPENDENCE CNS stimulants, including AZSTARYS, other methylphenidate-containing products, and amphetamines, have a high potential for abuse and dependence. Assess the risk of abuse prior to prescribing, and monitor for signs of abuse and dependence while on therapy. CONTRAINDICATIONS Known hypersensitivity to serdexmethylphenidate, methylphenidate, or other product components. Bronchospasm, rash, and pruritus have occurred with AZSTARYS. Hypersensitivity reactions such as angioedema and anaphylactic reactions have occurred with other methylphenidate products. Concomitant treatment with a monoamine oxidase inhibitor (MAOI) or use of an MAOI within the preceding 14 days, because of the risk of hypertensive crisis. WARNINGS AND PRECAUTIONS Sudden death has been reported in association with CNS stimulant treatment at recommended doses in pediatric patients with structural cardiac abnormalities or other serious heart problems. In adults, sudden death, stroke, and myocardial infarction have been reported at recommended doses. Avoid use in patients with known structural cardiac abnormalities, cardiomyopathy, serious heart arrhythmias, coronary artery disease, or other serious heart problems. CNS stimulants cause an increase in blood pressure and heart rate. Monitor all patients for hypertension and tachycardia. Exacerbation of Pre-existing Psychosis: May exacerbate symptoms of behavior disturbance and thought disorder in patients with a pre-existing psychotic disorder. Induction of a Manic Episode in Patients with Bipolar Disorder: May induce a mixed/manic episode in patients with bipolar disorder. Prior to initiating treatment, screen for risk factors for developing a manic episode (e.g., comorbid or history of depressive symptoms, or a family history of suicide, bipolar disorder, or depression). New Psychotic or Manic Symptoms: At recommended doses, may cause psychotic or manic symptoms (e.g., hallucinations, delusional thinking, or mania) in patients without a history of psychotic illness or mania. Discontinue if symptoms occur. Cases of painful and prolonged penile erections and priapism have been reported with methylphenidate products. Immediate medical attention should be sought if signs or symptoms of prolonged penile erections or priapism are observed. CNS stimulants, including AZSTARYS, are associated with peripheral vasculopathy, including Raynaud's phenomenon. Signs and symptoms are usually intermittent and mild; very rare sequelae include digital ulceration and/or soft tissue breakdown. Carefully observe patients during treatment for digital changes. Further evaluation may be required, including referral. CNS stimulants have been associated with weight loss and slowing of growth rate in pediatric patients. Monitor height and weight at appropriate intervals in pediatric patients. Treatment may need to be interrupted in children not growing or gaining weight as expected. ADVERSE REACTIONS Based on accumulated data from other methylphenidate products, the most common (>5 percent and twice the rate of placebo) adverse reactions are appetite decreased, insomnia, nausea, vomiting, dyspepsia, abdominal pain, weight decreased, anxiety, dizziness, irritability, affect lability, tachycardia, and blood pressure increased. DRUG INTERACTIONS Adjust dosage of antihypertensive drug as needed. Monitor blood pressure. Avoid use of AZSTARYS on the day of surgery if halogenated anesthetics will be used. For additional safety information, click here for Prescribing Information and Medication Guide, including BOXED WARNING. You are encouraged to report negative side effects of prescription drugs to the FDA. Visit or call 1-800-FDA-1088. About Corium Corium, LLC, is a commercial-stage biopharmaceutical company that is leading the development and commercialization of CNS therapies that provide physicians with innovative treatment options for patients, their families, and their caregivers. Corium is commercializing two FDA approved products, ADLARITY and AZSTARYS. For further information, please visit . References 1Childress AC, Cutler AJ, Patel M, Oh C. Analysis of Growth Velocity in Children With Attention-Deficit/Hyperactivity Disorder Treated for up to 12 Months With Serdexmethylphenidate/dexmethylphenidate. J Child Adolesc Psychopharmacol. 2023. Ahead of print . Contact: Corium, LLC Gartmanpr@gmail.com 202-413-4226