Pitt-Hopkins Syndrome

Study site selection and finalization of clinical trial agreement final step toward initiation of RVL-001 proof-of-concept clinical studies early next year BOSTON, Oct. 24, 2024 /PRNewswire/ -- Unravel Biosciences, Inc., ("Unravel"), an AI-enabled therapeutics company established to advance drugs for complex diseases, and the clinical research unit of the PECET of the University of Antioquia, certified in Good Clinical Practices by the Colombian Health Regulatory Authority ("INVIMA") and located in in Medellín, Colombia, today announced the finalization of a clinical trial agreement enabling PECET to be the designated study site for Unravel's RVL-001 proof of concept clinical trials for Rett syndrome (RTT) and Pitt Hopkins syndrome (PTHS). Unravel's proprietary BioNAV™ drug discovery platform identified RVL-001 as a potentially promising therapeutic drug for Rett Syndrome and PTHS. Building on previously announced initiatives by Unravel to initiate a proof-of-concept clinical trials of RVL-001 in Colombia for RTT as well as a collaboration by the Pitt Hopkins Research Foundation (PTHF) to conduct an extension study of RVL-001 in PTHS, today's agreement with PECET in Colombia formally establishes the clinical infrastructure for Unravel to rapidly evaluate BioNAV™ identified drugs in patients. "We are excited to collaborate with the highly skilled PECET team to accelerate therapeutics development for rare disease patients," said Richard Novak, Ph.D., Unravel Co-Founder and CEO. "By conducting multiple clinical trials in parallel at a single clinical trial site enables faster and less costly drug development to support more patients with unmet needs." RTT and PTHS are both rare neurogenetic disorders starting in early childhood that lead to debilitating cognitive, motor and autonomic disability. Despite one approved treatment for RTT, there remains a significant unmet need for novel treatments having meaningful efficacy and acceptable safety and tolerability. There are no known treatments for PTHS. In addition to Unravel's RVL-001 program for RTT and PTHS, the company has also initiated development work on RVL-002, a first-in-class novel molecule for Rett syndrome. Initiation of patient dosing for the RVL-001 trial in RTT and extension trial in PTHS are both anticipated in early 2025, with study startup activities including clinical trial material manufacturing and patient recruitment initiated earlier this year as previously announced. "We are pleased to be the designated clinical trial center for Unravel, it is a great challenge that we will take on with great enthusiasm to contribute to the search for solutions for this type of disease," said Iván Darío Vélez, Professor Emeritus of the University of Antioquia and founder of PECET. "PECET has extensive expertise conducting clinical studies with international biopharma sponsors including US to support worldwide registration and approval and we look forward to supporting Unravel in their development efforts". About Unravel Biosciences Unravel Biosciences revolutionizes drug development, uncovering disease-modifying targets from patient data powered by AI systems biology computation, rapid in vivo screening, and clinical validation of discovered targets with unprecedented efficiency. Unravel leverages its proprietary BioNAV™ foundational model of human health combining target and drug discovery, preclinical screening and patient stratification to find treatments for complex diseases. Unravel's platform has led to four clinical programs. Unravel's platform developed RVL001, a novel formulation to treat neurodevelopmental disorders, RVL002, a first-in-class new small molecule targeting mitochondrial metabolism, and RVL027, a molecule targeting a novel mechanism to treat dystonias. The rareSHIFT™ program provides platform access to foundation and biotech partners to accelerate and clinically derisk therapeutics using existing drugs as a key stepping stone to validating novel targets and mechanisms in real patient populations. and SOURCE Unravel Biosciences, Inc. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

Primary endpoint met with high rates of clinical cure at day 12 Very low rates of recurrence observed with CRS3123 CRS3123 was generally safe and well tolerated NIAID exercises $4.5 million option to fund phase 2 supporting studies BOULDER, CO, USA I September 05, 2024 I Crestone, Inc. (“Crestone”) today announced positive topline results from the Phase 2 clinical trial evaluating CRS3123 in patients with Clostridioides difficile infection (CDI). CRS3123 is a novel drug candidate that has demonstrated narrow spectrum and minimal disruption of normal gut microbiota in preclinical and Phase 1 studies. Among the 43 patients in the primary intent-to-treat (ITT) analysis population, clinical cure rates at the day 12 test-of-cure visit were comparable in all three treatment groups, including 28/29 (97%) in patients receiving one of two dosages of CRS3123 versus 13/14 (93%) in those receiving vancomycin. There were no clinical failures at the day 12 time point; the results in two patients were indeterminate. Importantly, rates of CDI recurrence were considerably lower in those patients who received CRS3123. For example, at day 40 recurrence rates were 4% for CRS3123 versus 23% for vancomycin. CRS3123 was well tolerated, with no serious treatment-emergent adverse events. Crestone plans to present the results from the Phase 2 trial at an upcoming medical conference. CDI is the most common hospital-acquired infection in the U.S. and is now even more prevalent in the community, including in younger patients. In the U.S. there are almost half a million infections each year and approximately 30,000 deaths. Dr. Thomas Louie of University of Calgary, Canada, principal investigator for this study, stated: “Treatment of C. difficile infection remains in urgent need of agents that spare normal gut microbes, so they can reconstitute the microbiome and prevent further recurrences of CDI. The findings of this study support CRS3123 as such a candidate for further development.” Epidemiology analysis and toxin testing for this study were performed at the University of Leeds. Dr. Mark Wilcox, Professor at Leeds Teaching Hospitals and University of Leeds and Lead on CDI for UK Health Security Agency, stated: “It is now abundantly clear that curbing C. difficile while preserving healthy intestinal flora is what we want in a CDI therapeutic. The outcome of this phase 2 study further reinforces that goal.” “We are very pleased with these results,” said Dr. Jon Bruss, Acting Chief Medical Officer to Crestone. “This was a challenging study to execute given pandemic disruptions to healthcare. We want to sincerely thank all the patients, families, clinicians and collaborators who contributed to the generation of these important data.” The company also announced that, based upon the results of this study, the National Institute of Allergy and Infectious Diseases (NIAID) has exercised its option under an existing agreement with Crestone to provide $4.5 million in new funding for microbiome analyses, manufacturing process optimization and other phase 2 supporting studies. This project has been funded with federal funds from NIAID, National Institutes of Health, Department of Health and Human Services, under Contract No. 75N93019C00056. “We very much appreciate NIAID’s scientific input and the more than $28 million in funding for phase 2 development of CRS3123,” said Urs Ochsner, PhD, co-Founder, Vice President of R&D and CEO at Crestone. “With these topline data and further data to come in the next few months, we look forward to discussions with the FDA and prospective development partners and investors about accelerating into pivotal CDI studies with CRS3123,” said Dr. Ochsner. About the Phase 2 Clinical Trial of CRS3123 The Phase 2, randomized, double-blind, comparator-controlled, multicenter study evaluated safety and efficacy of two dosages of CRS3123 (200 mg and 400 mg) administered twice-daily compared with vancomycin 125 mg administered four times daily in 43 adults diagnosed with a primary episode or first recurrence of CDI. The duration of treatment for all study treatment arms was 10 days. Patients with clinically documented, toxin-positive CDI were enrolled at sites in the U.S. and Canada. The primary endpoint was defined as the rate of clinical cure at day 12 in the ITT population. Secondary and exploratory endpoints included rates of recurrence and global cure, time to resolution of diarrhea and the effect of CRS3123 on commensal bacteria in the gut. About C. difficile Infection CDI has been identified by the Centers for Disease Control and Prevention (CDC) as an “urgent” threat. CDI is an infection of the gut with symptoms of painful diarrhea, associated mental anguish and sometimes toxic megacolon or death. Currently, most patients are treated with suboptimal, broad-spectrum antibiotics that prevent healthy gut microbiota from recovering, contributing to CDI recurrence rates of 20-40%. Once CDI recurs, it is more likely to recur again and again even after further treatment with existing therapeutics, leading to substantially increased morbidity and mortality. 30-day CDI mortality rates ranging from 6% to 11% have been reported by CDC and multiple other sources. Among Medicare beneficiaries over 65 with a first CDI episode, mortality from all causes within 12 months was between 35% and 45%. An effective therapy that treats CDI while preventing recurrent CDI continues to be urgently needed. About CRS3123 CRS3123 is a small molecule that selectively inhibits one form of the bacterial methionyl-tRNA synthetase, which is the mechanistic basis of its narrow spectrum. This target is not present in human cells, nor in other important bacterial species that are part of the normal microbiota of the gut. As a protein synthesis inhibitor, CRS3123 blocks not only C. difficile growth, but also toxin production and spore formation. In Phase 1 trials in healthy subjects and in this Phase 2 trial in CDI patients, CRS3123 achieved high intestinal concentrations, low systemic exposure and was generally safe and well tolerated. The FDA has granted QIDP and Fast Track designations to CRS3123 for the treatment of CDI. About Crestone, Inc. Boulder, Colorado-based Crestone, Inc. is a clinical stage biopharmaceutical company focused on inventing and developing novel mechanism of action, small molecule antimicrobial drugs. Its pipeline includes CRS3123 in clinical development to treat CDI and under investigation to treat symptoms of autism spectrum disorder, symptoms of Pitt Hopkins Syndrome (a rare genetic disease), prevention of graft versus host disease (GvHD) and other indications. The pipeline also includes CRS0540 to treat resistant Gram-positive infections such as methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE), and other programs directed at nontuberculous mycobacterial (NTM) disease and other bacterial and viral diseases. The company has been funded primarily through multiple research and development grants and contracts worth more than $50 million, including two ongoing NIAID contracts for CRS3123 and CRS0540, respectively. The company is owned by its scientific founders and staff and currently retains worldwide, royalty-free rights to both programs. SOURCE: Crestone

Pitt Hopkins Research Foundation to fund proof of concept clinical trial in Colombia to assess the efficacy of vorinostat (RVL-001) in patients with Pitt Hopkins Syndrome (PTHS) BOSTON, June 11, 2024 /PRNewswire/ -- Unravel Biosciences, Inc., ("Unravel"), an AI-enabled therapeutics company established to advance drugs for complex diseases, and the Pitt Hopkins Research Foundation (the "Foundation") today announced a collaboration to conduct a proof of concept clinical trial of vorinostat (RVL-001) in patients with Pitt Hopkins Syndrome (PTHS). Under the terms of the collaboration, the Foundation will fund the clinical trial conducted by Unravel at its study site in Colombia and Unravel will retain rights for further development and commercialization. Unravel's proprietary BioNAV™ drug discovery platform identified RVL-001 as a potentially promising therapeutic drug for PTHS. Building on a previously announced initiative by Unravel to initiate a proof-of-concept clinical trial of RVL-001 in Colombia for Rett Syndrome, the PTHS study will leverage the clinical study infrastructure in Colombia set up by Unravel for rapid evaluation of BioNAV™ identified drugs in patients. "I am pleased to announce this important collaboration with the Pitt Hopkins Research Foundation," said Richard Novak, Ph.D., Unravel Co-Founder and CEO. "A key part of our mission is to rapidly advance promising drugs into clinical testing in multiple orphan disorders, and our partnership with the Foundation will allow us to evaluate the benefit of RVL-001 in this high unmet need patient group." PTHS is a rare genetic disorder of males and females affecting the TCF4 gene in chromosome 18. PTHS is considered an Autism Spectrum Disorder and is characterized by developmental delay, severe cognitive impairment, recurrent seizures/epilepsy, breathing disorders, gastrointestinal issues, lack of speech, and distinctive facial features. There are no known treatments for PTHS. While the overall prevalence of PTHS is not fully known, estimates currently range from 1 in 34,000 to 1 in 300,000 individuals. "In the short time we've been working with Unravel, they've proven that they work with the urgency necessary to develop treatments for our patient population," said Audrey Davidow Lapidus, President of the Pitt Hopkins Research Foundation. "Unravel has put together this trial in record time and we are so grateful- and hopeful.". About Unravel Biosciences Unravel Biosciences is the first rapid prototyping therapeutics company, integrating AI systems biology computation with rapid in vivo screening and clinical validation of discovered targets with unprecedented efficiency. Unravel leverages its proprietary BioNAV™ platform combining target and drug discovery, preclinical screening and patient stratification to find treatments for complex diseases. Unravel's platform has led to four clinical trials starting in 2024. Unravel's platform developed RVL002, a first-in-class new small molecule targeting mitochondrial metabolism, and RVL027, a molecule targeting a novel mechanism to treat dystonias. The rareSHIFT™ program provides platform access to foundation and biotech partners to accelerate and clinically derisk therapeutics. and About Pitt Hopkins Research Foundation The mission of the Pitt Hopkins Research Foundation (PHRF) is to support research dedicated to finding a treatment, and an eventual cure for Pitt Hopkins Syndrome and other similar disorders. The PHRF is also dedicated to supporting the Pitt Hopkins community with resource recommendations, parental support and the latest medical information. For more information, go to