Cav2.2

Pharmacodynamic Results from the CAN-001 Phase 1b Study of PP-01, an Investigational Product, intended to Mitigate Cannabis Withdrawal Syndrome PHOENIXVILLE, Pa., Nov. 18, 2024 /PRNewswire/ -- PleoPharma, Inc., a privately held company focused on cannabis-related health issues, announced today, the presentation of data from their Phase 1b Pharmacokinetic and Pharmacodynamic study of Cannabis Withdrawal Syndrome ("CWS") in participants with Cannabis Use Disorder ("CUD") at the annual meeting of the American Academy of Addiction Psychiatry (AAAP) in Naples, Fla. "We are pleased to present our proof-of-concept study that evaluated the safety and effectiveness of PP-01, a novel, dual-mechanism investigational agent containing tapering and titrating doses of nabilone and gabapentin in mitigating cannabis withdrawal symptoms in participants with moderate to severe CUD. We are excited to be developing PP-01 with the goal of being the first FDA approved product to help people suffering from CWS, a rapidly growing patient population in need of treatment. We are currently preparing for PP-01 to enter Phase 3", stated Shelli Graham, PhD, Senior Vice-President of Medical/Clinical Research. Participants in the CAN-001 Study reported using an average of 3.5 ± 2.2 grams/day of cannabis with a mean age of first use 14 years (range 6 to 22). By DSM-5 criteria, 64% had severe CUD and 36% had moderate CUD. Compared to placebo, PP-01 administered once daily significantly reduced mean CWS ratings beginning 4 hours post first dose of PP-01 (first measured timepoint). This effect was sustained through Day 5 (P values < 0.0009; all timepoints). Participants experienced fewer cravings, better sleep and were also less bothered by their withdrawal symptoms when treated with PP-01 than with placebo (P values < 0.007; all timepoints). PP-01 was well tolerated. There were no serious adverse events, and all adverse events in the PP-01 group were mild in severity. About cannabis withdrawal/cannabis use disorder The US Government reported that in 2023 (samhsa.gov), ~19.2 million Americans had CUD with 1.64 million people receiving treatment (~500k inpatient, ~1.1 million outpatient). The number of individuals who received treatment for cannabis related health problems has grown by an average of 28% annually from 2018 to 2023. People with CUD commonly experience significant withdrawal symptoms, known as CWS, that can make it extremely difficult to reduce or discontinue cannabis. There are currently no FDA approved medications for the treatment of CWS or CUD. About PleoPharma, Inc. PleoPharma, Inc. is a clinical stage development company in the neuropsych and addiction space with a lead asset, PP-01, that is being developed as the first FDA approved treatment of CWS in people with CUD. The PleoPharma team includes a world class management team and board of directors who have produced multiple high value exits, >50 worldwide product approvals, and 100+ INDs. For more information on PleoPharma, please visit or email Dawn Halkuff, head of Investor Relations at [email protected]. This release includes 'forward-looking statements' regarding the operations of PleoPharma, Inc., actual results may differ from its expectations, estimates, and projections and, consequently, you should not rely on these forward-looking statements as predictions of future events. All statements other than statements of historical facts contained herein are forward-looking statements that reflect the current beliefs and expectations of management of PleoPharma. These forward-looking statements involve significant risks and uncertainties that could cause the actual results to differ materially from those discussed in the forward-looking statements. PleoPharma does not undertake or accept any obligation or undertaking to release any updates or revisions to any forward-looking statements to reflect any change in its expectations or any change in events, conditions or circumstances on which any such statement is based. SOURCE PleoPharma, Inc WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

Company also provides updates on its Phase 2 RECONNOITER Study in Raynaud's Phenomenon and Systemic Sclerosis and other corporate activities BOSTON, Sept. 9, 2024 /PRNewswire/ -- Aisa Pharma, Inc. a private, clinical-stage biopharmaceutical company announced that the U.S. Food and Drug Administration (FDA) has granted orphan drug designation to AISA-021(cilnidipine), a fourth-generation calcium channel antagonist. Aisa is developing AISA-021 for the treatment of Systemic Sclerosis (SSc), a rare disease, which impacts approximately 175,000 Americans and has the highest mortality rate of any autoimmune disease. Continue Reading "To our knowledge, this is the first time the FDA has granted orphan drug designation to a calcium channel antagonist for an autoimmune illness," said Andrew Sternlicht, MD, CEO and Founder of Aisa Pharma. "We hope this designation will accelerate our development program for AISA-021, which is designed to provide a once-daily, well-tolerated, and economical treatment that we hope can improve the lives of patients with SSc. We are actively seeking a development partner and investors to support bringing this much-needed treatment to patients." AISA Pharma receives FDA orphan drug designation for their new drug treatment for Systemic Sclerosis Post this Under the FDA's Orphan Drug Act, orphan drug status provides incentives, including tax credits, grants and waiver of certain administrative fees for clinical trials, and seven years of market exclusivity following drug approval. To be granted the orphan drug designation, FDA concludes that it is medically plausible that the treatment may improve the disease. Aisa submitted information from the ongoing Phase 2 study demonstrating improvement on several endpoints versus placebo, including SSc symptoms of overall disease severity, disease-related pain, gastrointestinal dysfunction, skin ulcers, disability, and breathing symptoms, as well as Raynaud's symptoms. In a preliminary review by an independent data safety committee, the ongoing study of 60 patients demonstrated a much lower incidence and severity of side effects as well as improved efficacy for preventing Raynaud's attacks, when compared to published reviews of current therapies. Aisa also provided the following corporate updates: A Pre-IND meeting with the FDA for AISA-021 in the treatment of Systemic Sclerosis and Secondary Raynaud's Phenomenon is scheduled for September 2024. The initial drug screening performed by the NIH as part of the Preclinical Pain Screening Platform to evaluate the suitability of AISA-021 as a non-opioid analgesic, demonstrated no abuse liability or addictive potential for the drug. Additional results are pending. Two abstracts on AISA-021 will be presented at the ACR Convergence Scientific Meeting in Washington DC on 11/16/2024: AISA 021, a Novel Calcium Channel Antagonist in Development for Raynaud's & Systemic Sclerosis, Has Activity at Sodium Channel Targets for Pain Relief and Treats Scleroderma Pain Better Than Current Calcium Channel Blockers in a Phase 2A StudyPreliminary Results from the RECONNOITER Trial, a Phase 2 Study of AISA 021 in the Treatment of Secondary Raynaud's, Primarily Due to Systemic Sclerosis About AISA-021: AISA-021 is a form of cilnidipine, a fourth-generation calcium channel blocker (CCB), distinguished from other dihydropyridine CCBs by its increased selectivity for the N-type calcium channel. Cilnidipine is approved in certain Asian countries and widely used to treat hypertension there, but was never approved in the US, Canada, EU and UK. Cilnidipine causes vasodilation and further improves function in the heart, kidney and vasculature. In robust studies of hypertension treatment, cilnidipine is better tolerated with a wider therapeutic window than other approved CCBs, which are used off-label for Raynaud's. Unlike other approved CCBs, AISA-021 may also have a role in treating pain. About Systemic Sclerosis and Raynaud's Phenomenon in Systemic Sclerosis: Systemic Sclerosis (SSc) is the most fatal of autoimmune illnesses and affects approximately 175,000 patients in the United States. Approximately half of patients die of the disease within 12 years from initial diagnosis and 95% of SSc patients experience Raynaud's symptoms, which they describe as their most debilitating symptom. Raynaud's Phenomenon is characterized by decreased blood flow which can cause severe pain and tingling in the hands and fingers. Cardiac, renal and vascular disease, which have been shown to improve in patients treated for hypertension, contribute to morbidity and mortality in patients with SSc. No drug has been approved anywhere in the world for the treatment of Raynaud's. About Aisa Pharma Inc. Aisa is a private biopharmaceutical company in Boston, MA, founded in 2019. For additional information: [email protected]; SOURCE Aisa Pharma

Researchers studied the effects of their compound, CBD3063, in multiple models of acute and chronic pain. A small molecule alleviates four different types of acute and chronic pain in rodents, so far with none of the side effects associated with widely prescribed non-opioid painkiller gabapentin. In an article published Nov. 13 in Proceedings of the National Academy of Sciences, researchers from New York University described how they discovered their compound, dubbed CBD3063, and tested it in models of injury- and chemotherapy-induced neuropathy, trigeminal nerve pain and inflammatory pain. They hope to eventually take it to the clinic. “The compound can be given [via] multiple routes, it works in different species—mice and rats—and in males and females,” senior author Rajesh Khanna, Ph.D., who is also working on a gene therapy for chronic pain, told Fierce Biotech Research in an interview. “No toxicity has been seen, and it works across an array of pain conditions. That’s really the crux of this paper.” CBD3063, gabapentin and pregabalin all ultimately exert their effects through their interactions with a calcium channel called Cav2.2 on pain-sensing neurons, but they do so via different mechanisms. Where gabapentin acts on the outside of the channel, CBD3063 alters it from the inside by stopping a protein called CRMP2 from binding to it. Decoupling the two keeps calcium from entering the channel, which ultimately leads to less neurotransmitter release—and pain reduction. Khanna’s lab first discovered the peptide that would become the basis for CBD3063 back in 2011. Since then, the team has worked on formulating it into a small molecule, figuring out that they could take the number of necessary amino acids down from 15 to just two and pairing those with a protein taken from the HIV virus to help it get into cells. As part of the new study, they worked with the University of Pittsburgh to run a large screen of 27 million existing drug compounds to see whether any had the same composition. The results led them to CBD3063. After a barrage of cell studies to show that the compound did indeed inhibit CRMP2 and was highly selective for Cav2.2—an important consideration, as drugs for arrhythmias and hypertension target similar channels—the researchers tested it in double-blinded experiments on a mouse model of nerve injury, assessing it head-to-head with gabapentin. They found that mice who received the compound were less debilitated by pain than untreated mice. On top of that, CBD3063 worked at a fraction of gabapentin’s effective dose.  “We were getting the same amount of relief [with 1 to 10 milligrams per kilogram of CBD3063] that the clinically available compound gabapentin was producing at 30 milligrams per kilogram,” Khanna said. “That’s very important, because now we are comparing it to a clinical benchmark.” The researchers then conducted experiments on rodents that had nerve damage caused by treatment with paclitaxel, a chemotherapy drug. After giving four doses of paclitaxel over eight days, the researchers waited for the animals to develop nerve damage and an aversion to cold, another common symptom experienced by people who undergo chemotherapy. When the animals developed symptoms two or three weeks later, the team gave them single doses of CBD3063. “We saw a beautiful reversal of both nerve pain and cold aversion,” Khanna said. Next, the researchers looked at how well the drug could control orofacial pain. Until this set of experiments, the scientists had been giving the drug through the animals’ abdomens via what’s known as intraperitoneal delivery. This time, they tried giving it intranasally, thinking that a nasal spray formulation would be ideal for this kind of scenario. “It also bypasses the blood-brain barrier, and it goes right into the regions it needs to,” Khanna said. Once again, the drug worked: It relieved pain consistent with the expected half-life of the compound in such a formulation, he said, which is a little more than three hours. His team then moved to their final models. An assessment of whether CBD3063 could relieve chronic pain from inflammatory conditions like arthritis showed that single injections of the drug into mice with paw inflammation relieved their pain for at least four hours afterward. And an experiment on rats with a chronic nerve injury showed that they didn’t develop tolerance to the drug even with multiple injections over a two-week period. But the researchers weren’t done yet: They wanted to be sure that CBD3063 didn’t block out unrelated types of pain or replicate gabapentin’s side effects, which include memory loss, mood changes, lethargy and more. Experiments on uninjured mice showed that the drug had no effect on types of pain that were unrelated to the type of neuropathy it was designed to treat. Meanwhile, gabapentin seemed to make mice less responsive to important acute pain signals. As for side effects, the scientists found that abdominal injections of CBD3063 had no impact on rodents’ memory or cognition—unlike gabapentin, which dramatically diminished their ability to recognize objects. Their compound also had no effects on the animals’ cardiovascular function, which case studies suggest may be impacted by gabapentin. “This demonstrates that CBD3063 preserves that adaptive role of pain without causing any kind of neurological side effects,” Khanna said. “That’s really the benefit.” There’s still a long road to the clinic. The researchers will need to do many more experiments to understand the drug’s long-term effects as well as whether tolerance eventually arises. And while CBD3063 has never been used for pain relief, it is not technically a new compound. Thus, Khanna’s team will need to substantially transform and optimize it before they can patent it, then will need to partner with a pharmaceutical company to take it into development, he said. “I don’t want to provide any false hope, because the path to humans is three to five years away at the very least,” Khanna said. “In order to get there, there’s a huge journey ahead.”