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Phase 1b clinical trial of KM-001 demonstrated favorable safety pro high responder rate of 87% in patients with palmoplantar keratoderma and pachyonychia congenita In vitro and in vivo data of KM-001 and KM-023 demonstrated significant improvements in skin histology and significant reductions in scratching NESS ZIONA, Israel, May 17, 2024 (GLOBE NEWSWIRE) -- Kamari Pharma, a privately-held clinical stage biotechnology company developing first and best-in-class treatments for rare and severe genetic skin diseases, today announced two presentations reporting results for its novel TRPV3 inhibitors, KM-001 (topical) and KM-023 (oral), were given at the 81st Annual Meeting of the Society for Investigative Dermatology (SID) that is taking place May 15-18, 2024 in Dallas, TX, USA. Below are summaries of the presentations: Poster #LB941: “KM-001, a novel TRPV3 inhibitor, demonstrates safety and preliminary efficacy in Phase 1b clinical study for the treatment of palmoplantar keratoderma” presented by Edel O’Toole, M.D., Ph.D. Professor of Molecular Dermatology and Centre Lead of the Centre for Cell Biology and Cutaneous Research, Blizard Institute, Queen Mary University of London and lead investigator in the study. Presented results from twelve-week, Phase 1b open-label studies (UK and Israel) assessing 4g/day of KM-001 1% cream applied to each foot twice daily for the treatment of pachyonychia congenita (PC) and punctate palmoplantar keratoderma type 1 (PPPK1). Eight patients in the UK (7 PC;1 PPPK1) and seven patients in Israel (3 PC;4 PPPK1) completed the treatment period. Safety: No drug-related severe adverse events nor systemic side effects were observed. Minimal treatment emergent adverse events occurred (n=11); all were mild and did not lead to patient discontinuation. Efficacy: Responder rate at the end of treatment was 88% (CI 52.9-97.8%) in UK (n=8) and 86% (CI 48.7-97.4%) in Israel (n=7), as defined by an improvement in at least one of six pre-defined disease parameters. Additionally, 47% of patients improved in at least two parameters with a disease severity reduction trend and pain score measured by VAS was reduced in 60% of PC patients; PPPK1 patients do not have pain as a symptom. Presentation #771: “Novel TRPV3 inhibitors developed for the treatment of palmoplantar keratodermas, demonstrate safety and efficacy in preclinical models” presented by Liora Braiman-Wiksman, Ph.D., Chief Scientific Officer at Kamari. Presented preclinical results for KM-001 and KM-023, Kamari’s specific and highly selective TRPV3 inhibitors designed to address both molecular and local damage to the skin by regulating Ca²⁺ influx into the cell. In 3D skin models of PC and PPPK1, KM-001 and KM-023 normalized proliferation and differentiation markers and enhanced epidermal barrier formation. In in vivo efficacy studies performed in DS-Nh mice, a gain-of-function TRPV3 mutation model, KM-001 showed significant improvement in skin histology vs vehicle (70% vs 30%) and exhibited significant reduction in scratching bouts (80%, p>0.04) and KM-023 showed a significant reduction in keratoderma severity score (p=0.003) and reduced scratching significantly (p<0.001) vs vehicle. Based on these results, Kamari plans to initiate Phase 2 development of KM-001 for the treatment of palmoplantar keratoderma and advance KM-023 into first-in-human studies for the oral treatment of Olmstead syndrome, severe keratoderma and Ichthyosis. The full content of these posters is available in the News page of Kamari's corporate website ( ). About Kamari Pharma Kamari Pharma is a privately-held clinical stage biotechnology company developing first and best in class treatments for rare and severe genetic skin diseases. Kamari’s lead molecules, KM-001 (topical) and KM-023 (oral) are novel, highly specific and selective TRPV3 inhibitors that are initially being developed to treat palmoplantar keratodermas, Olmstead syndrome and Ichthyosis. Kamari’s management team is comprised of industry leaders highly experienced in drug discovery, dermatological pharmaceutical development and rare disease drug development. Contact Information Investors and Media Marcy Nanus Managing Partner Trilon Advisors, LLC mnanus@trilonadvisors.com

Researchers on a deep-sea expedition have found PCB in sediment samples from the more than 8,000-meter-deep Atacama Trench in the Pacific Ocean. PCB has been banned in most countries since the 1970s, but that doesn't mean it no longer exists. Now, deep-sea researchers report that they have found PCB at the bottom of the Atacama Trench in the Pacific Ocean. During their expedition to the deep-sea trench, the research team retrieved sediment cores and analyzed them for PCB occurrences at five different locations in the trench. All the samples of surface sediment analyzed contained PCB. The study, led by Professor Anna Sobek from the Department of Environmental Science at Stockholm University and Professor Ronnie N. Glud, director of the Danish Center for Hadal Research at the University of Southern Denmark, has been published in the scientific journal Nature Communications. PCB is short for Poly-Chlorinated Biphenyls, which covers 209 different substances. They were introduced in the 1930s and have been used primarily in building materials and technical components, but are now banned in most countries and classified as a highly persistent environmental toxin. PCB can be carcinogenic and cause reproductive harm. Although the world's production of PCBs dropped significantly in the 1970s, the substances still pose an environmental threat. In 2018 researchers reported, for example, that half of the world's killer whale populations were weakened by PCB. Another study has found that scavenging amphipods in the deep sea contained large amounts of PCBs. "It is thought-provoking that we find traces of human activity at the bottom of a deep-sea trench; a place that most people probably perceive as distant and isolated from our society," says Professor Ronnie N. Glud, who has participated in more than 10 expeditions to deep-sea trenches around the world. These expeditions have helped to dispel the myth that deep-sea trenches are unaffected by what happens on the surface and have provided insight into the surprisingly rich, active, and varied life at the greatest depths of the ocean. The studies have also shown that deep-sea trenches accumulate large amounts of organic material, contributing to the oceans' ability to absorb carbon released into the atmosphere through fossil fuel burning. However, not only organic material accumulates in deep-sea trenches, which are also called hadal trenches. For example, the Danish Center for Hadal Research reported in 2021 that mercury also accumulates in the trenches' sediments, and in 2022, a similar announcement was made about black carbon, which is particles that are mainly formed by the combustion of fossil fuels. The concentration of PCBs in samples from the Atacama Trench is not alarmingly high, according to Ronnie N. Glud. He points out that much higher concentrations have been found in places like the Baltic Sea, North Sea, and Tokyo Bay. Concentrations 300-1500 times higher have been measured in the Baltic Sea. "These are places with a lot of human activity, so one would expect that. The Atacama samples do not show very high concentrations but considering that they were retrieved from the bottom of a deep-sea trench, they are relatively high. A priori no one would expect to find pollutants in such a place," says Ronnie N. Glud. PCBs are hydrophobic, meaning they are not very soluble in water. Instead, they bind to organic material that sinks to the bottom. "The Atacama trench is located in an area with relatively high production of plankton in surface waters. When the plankton dies, it sinks to the bottom of the ocean," explains Anna Sobek. In addition, large amounts of material are transported down the steep slopes and deposit in the deepest areas. Some of the organic material that reaches the bottom of the Atacama trench is eventually decomposed by microorganisms, and as a result, PCBs accumulate in sediment. PCBs are persistent compounds that are slowly redeposited over time, which is why increasing concentrations can be found in inaccessible areas such as the hadal trenches, even though they were largely banned worldwide in the 1970s. "Unlike coastal areas where PCB concentrations are typically higher in deeper sediment layers deposited 50 years ago, PCB concentrations in hadal sediments are highest in the upper sediment layers, indicating that PCBs have only recently reached the deeper trenches and that concentrations have not yet peaked: We may see higher concentrations in a few years," says Ronnie N. Glud. The deep-sea trenches are home to many different microorganisms and animals that have adapted to the extreme living conditions. Perhaps they are also home to organisms that can metabolize the pollutants that are deposited there. That is one of the focus points of Danish Center for Hadal Research and for this research, the center holds a solid stock of frozen sediment samples collected from expeditions to different deep-sea trenches in 2021 and 2022. "We are interested in finding out if PCBs are also present in other deep-sea trenches or if they are unique to the Atacama trench. We also want to investigate the bacteria that live down there and learn more about their function," says Ronnie N. Glud. The deep-sea trenches are located in the hadal zone of the ocean, which lies at depths of 6-11 km. There are about 27 deep-sea trenches, also called hadal trenches, named after the Greek god Hades, who ruled the underworld.

Aging and related diseases are associated with alterations in oxidative status and low-grade inflammation, as well as a decreased endoplasmic reticulum (ER) unfolded protein response (UPR). UPR is a functional mechanism by which cells attempt to protect themselves against ER stress. Researchers analyzed these proteins in peripheral blood mononuclear cells of elderly subjects and used computer simulation to predict the key proteins associated with these biomolecules underlying physiological adaptations to exercise. They collected blood samples about five to six days before and after the training period and analyzed various oxidative stress biomarkers in peripheral blood mononuclear cells. The study takes research one step further in helping to elucidate the benefits of exercise in this population. Aging involves a balance between oxidants and antioxidants, low-grade inflammation and a protein response that occurs at the cellular level, which is responsible for many health disorders. Exercise has been shown to regulate the inflammatory response, balance oxidants such as free radicals that build up in the cells and damage DNA; and ameliorate the process by which cells protect themselves against these stressors. Furthermore, resistance training in older adults is recommended to help maintain muscle, flexibility and balance. Aging and related diseases are associated with alterations in oxidative status and low-grade inflammation, as well as a decreased endoplasmic reticulum (ER) unfolded protein response (UPR). UPR is a functional mechanism by which cells attempt to protect themselves against ER stress, resulting from the accumulation of the unfolded/misfolded proteins. One group of proteins associated with the aging process is the mitochondrial heat shock protein 60 (HSP60), which has been demonstrated to play a protective role in the ability for cells to remain active and healthy. Currently, there is limited research investigating the effects of resistance training in older adults on the expression of HSP60 and Klotho, a gene involved in the aging process in mammals. A new study by researchers at Florida Atlantic University, in collaboration with the University of León in Spain, examined whether an eight-week resistance training program would modulate the oxidative status, the UPR activation and key inflammatory pathways as well as their relationships with HSP60 and Klotho proteins. For the study, researchers analyzed these proteins in peripheral blood mononuclear cells of elderly subjects. In addition, they utilized computer simulation to predict the key proteins associated with these biomolecules underlying physiological adaptations to exercise. They collected blood samples approximately five to six days before and after the training period and just before training intervention in young subjects who were included for basal assessments. Researchers also analyzed various oxidative stress biomarkers in peripheral blood mononuclear cells. Results of the study, published in the journal Antioxidants, demonstrated that the levels of the inflammatory proteins (pIRAK1, TLR4, and TRAF6), as well as different markers of the redox balance (catalase, GSH, LP, NRF2, PC, ROS, SOD1, and SOD2) remained unchanged with training. Importantly, untrained elderly subjects showed a significant reduction in pIRE1/IRE1 ratio when compared to trained elderly subjects. Such a finding was further confirmed by a gene ontology analysis, showing that endoplasmic reticulum stress is a key mechanism modulated by IRE1. Additionally, analysis did not show the training effect on the expression of HSP60 and Klotho or their relationships with other outcome variables. Although elderly male and female subjects were included in the training program, researchers did not find any sex effects in the study. These findings might partially support the modulatory effect of resistance training on the endoplasmic reticulum in the elderly. "Regular physical activity is suggested to be an effective intervention in improving age-related diseases such as osteoporosis, sarcopenia or muscle loss and dynapenia or loss of muscle strength, cardiovascular diseases, and type 2 diabetes," said Chun-Jung "Phil" Huang, Ph.D., co-author and a professor in the Department of Exercise Science and Health Promotion within FAU's Charles E. Schmidt College of Science. "Although the beneficial effects of regular physical exercise to alleviate inflammation and oxidative stress are well-established, the processes of these physiological adaptations with regard to protein folding or UPR remains to be explored. That is why we used a systems biology approach for our study." The resistance training protocol for the study consisted of 16 sessions over eight weeks (two sessions per week), with a minimum of 48 hours between sessions. The participants started with a 10-minute warm-up on a cycle ergometer. Subsequently, eight different resistance exercises (leg press, ankle extension, bench press, leg extension, bicep curl, pec deck, high pulley traction, and dumbbell lateral lift) were performed using the exercise device. For each exercise, participants performed three sets of 12-8-12 repetitions. There was a two-to-three-minute rest between each repetition and a three-minute rest between each exercise. "We know how very important physical activity is for older adults and our study takes research one step further in helping to elucidate the benefits of exercise in this population," said Huang. Study co-authors are senior author Brisamar Estébanez, Ph.D.; Marta Rivera-Viloria; and José A. de Paz, M.D., all with the University of León; José E. Vargas, Ph.D., Universidad Federal do Paraná, Curtiba; and Nishant P. Visavadiay, Ph.D.; and Andy V. Kahmoui, Ph.D., both with FAU's Department of Exercise Science and Health Promotion.