Chediak-Higashi Syndrome

SANTA MONICA, Calif., Aug. 22, 2022 (GLOBE NEWSWIRE) -- Opiant Pharmaceuticals, Inc. (Opiant) (NASDAQ: OPNT) today announced that the United States Patent and Trademark Office (USPTO) has issued a Notice of Allowance for Opiant’s pipeline candidate OPNT004 (drinabant) for the treatment of cannabinoid hyperemesis syndrome (CHS), a condition among cannabis users that leads to repeated and severe bouts of vomiting. A Notice of Allowance is issued after the USPTO decides that a patent can be granted from an application. "This patent allowance is welcome news, and a testament to our commitment of bringing innovative science to the treatment of addictions and drug overdose,” said Roger Crystal, M.D., President and Chief Executive Officer of Opiant. “With the consumption of cannabis increasing, due in large part to the legalization of its recreational use, we are developing OPNT004 in anticipation that emergency departments may receive more and more cases of side effects related to chronic or heavy use.1 Drinabant is being developed as an injection, which is ideal for these patients, who have frequent bouts of intractable nausea and vomiting that are generally unresponsive to traditional anti-emetics.” The USPTO issued a Notice of Allowance for U.S. Patent Application 16/904,359, entitled “Compositions and methods for treating cannabinoid hyperemesis syndrome with a cannabinoid receptor antagonist” for OPNT004. This patent covers OPNT004 as a method of treatment for CHS using drinabant administered as a parenteral formulation. Opiant expects this patent to issue within the next few months and expire no earlier than 2040. About OPNT004 OPNT004 (drinabant) is a high affinity, CB-1 antagonist for the treatment of excessive cannabinoid use. Cannabinoids are compounds found in the cannabis plant or made synthetically, that bind to cannabinoid receptors found in the central nervous system, gastrointestinal tract and immune system. With support from the National Center for Advancing Translational Sciences (NCATS), Opiant is developing a formulation for the parenteral administration of OPNT004 for the potential treatment of cannabinoid-related toxicities, which include cannabinoid hyperemesis syndrome (CHS) and acute cannabinoid overdose (ACO), a condition when excessive tetrahydrocannabinol (THC) can cause anxiety, paranoia, visual and auditory hallucinations, and nausea. There are currently no FDA approved therapeutics for either CHS or ACO. Opiant expects to initiate Phase I studies for OPNT004 in 2023. Opiant is developing drinabant under a license from Sanofi-Aventis. About cannabis hyperemesis syndrome (CHS) Cannabinoid hyperemesis syndrome (CHS) is a syndrome of cyclic vomiting associated with cannabis use. While the onset of symptoms is sudden, CHS occurs in people who use cannabis regularly, and has been linked to long term cannabis use. People with CHS experience reoccurring episodes of nausea, vomiting, dehydration, and abdominal pain, which can result in frequent visits to the emergency department. The condition is generally unresponsive to traditional anti-emetics, which are medications used to prevent or treat nausea and vomiting. However, CHS can lead to health complications if left untreated. Only a small portion of people who regularly use cannabis develop CHS. Because CHS was first described in the medical literature less than 20 years ago, many people may have it and either not report it or are misdiagnosed. One analysis found that CHS was responsible for up to 6% of patients who visited the emergency room for vomiting.2 About Opiant Pharmaceuticals, Inc. Opiant Pharmaceuticals, Inc., the company that developed NARCAN® Nasal Spray, is building a leading franchise of new medicines to combat addictions and drug overdose. For more information visit: www.opiant.com.

SANTA MONICA, Calif., Aug. 22, 2022 (GLOBE NEWSWIRE) -- Opiant Pharmaceuticals, Inc. (Opiant) (NASDAQ: OPNT) today announced that the United States Patent and Trademark Office (USPTO) has issued a Notice of Allowance for Opiant’s pipeline candidate OPNT004 (drinabant) for the treatment of cannabinoid hyperemesis syndrome (CHS), a condition among cannabis users that leads to repeated and severe bouts of vomiting. A Notice of Allowance is issued after the USPTO decides that a patent can be granted from an application. "This patent allowance is welcome news, and a testament to our commitment of bringing innovative science to the treatment of addictions and drug overdose,” said Roger Crystal, M.D., President and Chief Executive Officer of Opiant. “With the consumption of cannabis increasing, due in large part to the legalization of its recreational use, we are developing OPNT004 in anticipation that emergency departments may receive more and more cases of side effects related to chronic or heavy use.1 Drinabant is being developed as an injection, which is ideal for these patients, who have frequent bouts of intractable nausea and vomiting that are generally unresponsive to traditional anti-emetics.” The USPTO issued a Notice of Allowance for U.S. Patent Application 16/904,359, entitled “Compositions and methods for treating cannabinoid hyperemesis syndrome with a cannabinoid receptor antagonist” for OPNT004. This patent covers OPNT004 as a method of treatment for CHS using drinabant administered as a parenteral formulation. Opiant expects this patent to issue within the next few months and expire no earlier than 2040. About OPNT004 OPNT004 (drinabant) is a high affinity, CB-1 antagonist for the treatment of excessive cannabinoid use. Cannabinoids are compounds found in the cannabis plant or made synthetically, that bind to cannabinoid receptors found in the central nervous system, gastrointestinal tract and immune system. With support from the National Center for Advancing Translational Sciences (NCATS), Opiant is developing a formulation for the parenteral administration of OPNT004 for the potential treatment of cannabinoid-related toxicities, which include cannabinoid hyperemesis syndrome (CHS) and acute cannabinoid overdose (ACO), a condition when excessive tetrahydrocannabinol (THC) can cause anxiety, paranoia, visual and auditory hallucinations, and nausea. There are currently no FDA approved therapeutics for either CHS or ACO. Opiant expects to initiate Phase I studies for OPNT004 in 2023. Opiant is developing drinabant under a license from Sanofi-Aventis. About cannabis hyperemesis syndrome (CHS) Cannabinoid hyperemesis syndrome (CHS) is a syndrome of cyclic vomiting associated with cannabis use. While the onset of symptoms is sudden, CHS occurs in people who use cannabis regularly, and has been linked to long term cannabis use. People with CHS experience reoccurring episodes of nausea, vomiting, dehydration, and abdominal pain, which can result in frequent visits to the emergency department. The condition is generally unresponsive to traditional anti-emetics, which are medications used to prevent or treat nausea and vomiting. However, CHS can lead to health complications if left untreated. Only a small portion of people who regularly use cannabis develop CHS. Because CHS was first described in the medical literature less than 20 years ago, many people may have it and either not report it or are misdiagnosed. One analysis found that CHS was responsible for up to 6% of patients who visited the emergency room for vomiting.2 About Opiant Pharmaceuticals, Inc. Opiant Pharmaceuticals, Inc., the company that developed NARCAN® Nasal Spray, is building a leading franchise of new medicines to combat addictions and drug overdose. For more information visit: . Forward-Looking Statements This press release contains forward-looking statements. These statements relate to future events or our future financial performance and involve known and unknown risks, uncertainties and other factors that may cause our actual results, levels of activity, performance, or achievements to be materially different from any future results, levels of activity, performance or achievements expressed, implied or inferred by these forward-looking statements, and among other things, the completion of the development of OPNT004. In some cases, you can identify forward-looking statements by terminology such as "may," "will," "should," "could," "would," "expects," "plans," "intends," "anticipates," "believes," "estimates," "predicts," "projects," "potential," or "continue" or the negative of such terms and other comparable terminology. These statements are only predictions based on our current expectations and projections about future events. You should not place undue reliance on these statements. Actual events or results may differ materially. In evaluating these statements, you should specifically consider various factors. Additional factors that could materially affect actual results can be found in our Form 10-K for the year ended December 31, 2021, and our Form 10-Q for the quarter ended June 30, 2022, filed with the Securities and Exchange Commission on March 4, 2022, and August 11, 2022, respectively, including under the caption titled "Risk Factors." These and other factors may cause our actual results to differ materially from any forward-looking statement. We undertake no obligation to update any of the forward-looking statements after the date of this press release to conform those statements to reflect the occurrence of unanticipated events, except as required by applicable law. For Media and Investor Inquiries: Ben Atkins, Opiant (310) 598-5410 batkins@opiant.com The United Nations World Drug Report 2022; Press Release: Simonetto DA, Oxentenko AS, Herman ML, Szostek JH. Cannabinoid hyperemesis: a case series of 98 patients. Mayo Clin Proc. 2012 Feb;87(2):114-9. doi: 10.1016/j.mayocp.2011.10.005. PMID: 22305024; PMCID: PMC3538402.

Using a mouse model, researchers from Japan uncover the key role of neutrophil extracellular traps in the contact hypersensitivity response. Contact hypersensitivity (CHS), commonly known as contact dermatitis, is an itchy rash that develops when certain substances come in direct contact with the skin. Usually, it is the result of an allergic reaction and can make patients feel uncomfortable. Common substances such as perfumes, household chemicals, and accessories can trigger itchy rashes from contact dermatitis. Although common, the underlying physiological mechanisms that trigger CHS remain elusive. Recently, a research team from Fujita Health University School of Medicine, Japan, has been able to shed light on the precise molecular mechanisms that trigger CHS. The group had previously shown that genetic mutations in the interleukin (IL)36RN gene, which is responsible for the synthesis of the protein interleukin-36 receptor antagonist (or IL-36Ra), may result in enhanced CHS. They also observed that the mutations led to the increased formation of neutrophil extracellular traps (NETs), which are mesh-like structures of DNA and proteins released by neutrophils to capture pathogens.However, the immunological pathophysiology of NETs in CHS remained unclear. On two previous occasions, the research team successfully established links between IL-36Ra and psoriatic lesions as well as between IL-36Ra and wound healing. The same team has now been able to dive in deep to further explore the underlying mechanisms. Their study was recently published in Scientific Reports (published on Aug 4, 2022) and shows that NETs could be a potential therapeutic target for CHS. The lead author, Dr. Yurie Hasegawa, a graduate student at the Fujita Health University School of Medicine, along with co-authors Dr. Yohei Iwata and Prof. Kazumitsu Sugiura, together demonstrated that NETs play a prominent role in the CHS response in the presence of a high number of inflammatory cells like CD4+ and CD8+ T-cells. "NETs may also exacerbate immune reactions in CHS. Therefore, the inhibition of NET formation may be a new therapeutic strategy in contact dermatitis," explains Dr. Hasegawa about the rationale of their study. To test their hypothesis, the team evaluated NET formation in Il36rn-/- mutant mice as well as wild-type mice under the influence of CHS-responsive CD4+ and CD8+ T cells. They first tested the effects of Cl-amidine on the CHS response in the mutant and wild-type mice and found that the number of infiltrating inflammatory cells and area of NETs decreased in both mice types. Histopathology and cell assays confirmed that the mutant mice had considerably more macrophages and CD4+ and CD8+ T cells than the wild-type mice. Moreover, they demonstrated elevated levels of inflammatory cytokines like IL-1, CXCL1, CXCL2, IL-17A, tumor necrosis factor-α, and IL-36. Interestingly, there were striking differences in IFN-γ and CXCL1 levels between Cl-amidine-treated mutant mice and untreated wild-type mice, but not in the levels of inflammatory cytokines. They next used the immunofluorescence staining to show that the mutant mice had more NETs in their ear tissues than the wild-type mice. However, treating mice with Cl-amidine -- an inhibitor that suppresses the formation of NETs -- resulted in a decreased CHS response, suggesting that NETs could be a potential therapeutic target for CHS. Thrilled by their findings, the team is looking forward to further exploring the connections between NET formation and CHS treatment. Dr. Hasegawa explains, "Our study is the first to suggest the involvement of NETs in the immune responses in CHS. All our findings collectively indicate that the blockade of NET formation by Cl-amidine may be a potential treatment approach for allergic contact dermatitis." Let's hope that their discovery facilitates the development of novel therapeutics for the safe and effective treatment of contact dermatitis.