FABP4

--FX-909 is highly potent and selective for the PPARG transcription factor, and demonstrates tumor eradication in preclinical animal models of urothelial cancer at low oral doses-- --Therapeutic efficacy of FX-909 assessed through gene expression profiling of normal skin tissue, potentially offers a less invasive surrogate biospecimen collection method compared to a traditional tumor biopsy-- CAMBRIDGE, Mass., April 17, 2023 /PRNewswire/ -- Flare Therapeutics, a biotechnology company targeting transcription factors to discover precision medicines for cancer and other diseases, today highlighted the first preclinical data from its lead compound FX-909, a novel, small molecule peroxisome proliferator-activated receptor gamma (PPARG) inhibitor to potentially treat patients with advanced urothelial cancer (UC), in an oral presentation and poster format at the AACR Annual Meeting being held in Orlando, FL from April 14-19, 2023. "These initial findings suggest that FX-909 could become a backbone therapy for patient populations harboring the luminal subtype of UC, much like ER therapies in the luminal subtype of breast cancer," said Rob Sims, Ph.D., Chief Scientific Officer and Co-founder of Flare. "We are eager to continue advancing FX-909, which will be further evaluated in a Phase 1 trial that will begin later in the year. This will be a milestone moment for Flare, as we are the first company slated to enter the clinic with a small molecule inhibitor targeting the PPARG transcription factor for advanced UC." Flare is building a pipeline of potentially first-in-class therapies against genetically validated transcription factor targets, initially focused on cancer. Although challenging to drug, elusive transcription factors remain high-value targets across numerous disease categories, most notably oncology. Treatments that target cell lineage have become mainstay therapies in breast and prostate cancer, through the successful inhibition of the estrogen receptor (ER) and androgen receptor (AR) transcription factors. Similar to ER and AR, PPARG drives luminal cell identity and accounts for two thirds of all advanced UC, highlighting its potential as a therapeutic target. The oral presentation, titled, "Discovery of FX-909, a first-in-class inverse agonist of the peroxisome proliferator-activated receptor gamma (PPARG) lineage transcription factor, to potentially treat patients with the luminal subtype of advanced urothelial cancer (UC)," shows that administration of FX-909 elicited durable tumor regressions in animal models of UC. The projected human starting dose of 50 mg/kg is also anticipated to be pharmacologically active. Additional key takeaways are as follows: FX-909 is a highly selective and potent covalent small molecule inhibitor of PPARG (cellular EC50, 1 nM), showing >2000-fold selectivity for PPARG over PPARA/PPARD (related transcription factors) – acting through a mechanism that promotes a repressive conformation of PPARG. FX-909 inhibited cell growth in UC cell lines with activated PPARG signaling but had no effect on cell lines without activated PPARG. FX-909 administered orally twice a day caused tumor regression in PPARG-amplified and RXRA-mutant UC xenograft models at 1 mg/kg doses, and tumor eradication at 3 mg/kg doses. FX-909 demonstrated predictable, on-target and reversible pharmacology in normal tissues at supra-pharmacologic doses, mimicking PPARG loss-of-function mutations with notable remodeling in adipose tissue and the normal urothelium. The poster presentation titled, "Development of a surrogate tissue pharmacodynamic (PD) assay for potential clinical use with FX-909, a novel inhibitor of the urothelial luminal lineage transcription factor peroxisome proliferator-activated receptor gamma (PPARG)," outlines the FX-909-dose dependent expression of PPARG target genes as markers of PD response in tumor, adipose and skin tissue from mouse xenograft, and normal rat and normal human skin preclinical models. "Based on our observation of the consistent correlation of PPARG target gene expression patterns in tumor and normal tissues, we have elected to develop a normal skin PD biomarker assay to support early assessment of FX-909 biological activity in our Phase 1 study," said Michaela Bowden, Ph.D., Chief Development Officer of Flare. "These findings reinforce the importance of uncovering valuable translational insights and applying them to further guide our drug development process, potentially enabling us to reduce the burden of repeated, invasive tumor biopsy collections for patients with late-stage cancer by offering surrogate skin biopsies as a viable alternative." Additional key takeaways are as follows: In a rat pharmacology study, 30% of all genes that responded to FX-909 treatment in skin displayed a similar dose-dependent response profile in fat. PPARG target genes including FABP4/Fabp4, AGT/Agt, IVT/Ivd and ARG1/Arg1 are repressed across different species and/or tissues, exemplified by dose-dependent suppression of FABP4/Fabp4 (a target gene for PPARG) and showing a strong correlation (r=0.98, p value=0.003) between tumor and skin tissues. Skin explant models bridge the interspecies translational gap for studying FX-909-mediated effects, where preliminary evidence shows on-target regulation of genes involved in known PPARG-mediated processes. About Urothelial Cancer Bladder cancer is the third most common cancer in men in the United States alone. Each year, there are more than 83,000 new cases diagnosed among men and women, and about 25% of those cases are classified as muscle-invasive UC. This disease has high rates of recurrence and the five-year survival rate is approximately 15% in metastatic cases. The transcription factor peroxisome proliferator-activated receptor gamma (PPARG) is associated with the luminal lineage subtype reflecting approximately 65% of all advanced UC cases. Recurrent genetic alterations in PPARG, including focal amplification, missense mutations, and fusions, as well as hotspot mutations in its binding partner, retinoid X receptor alpha (RXRA) are characteristic of this molecular subtype. About Flare Therapeutics Flare Therapeutics is a biotechnology company changing the paradigm in drugging transcription factors with an initial focus in precision oncology. Flare's proprietary engine is founded on the identification of novel druggable pockets, or 'switch sites', within transcription factor complexes that solve for where to drug and how to tune gene expression to discover small molecule precision medicines for cancer and other diseases. The team has rapidly advanced an emerging pipeline of assets and plans to advance its lead precision oncology program, FX-909, a small molecule inhibitor targeting PPARG into the clinic in 2023 in individuals with locally advanced or metastatic urothelial cancer. For more information, please visit . SOURCE Flare Therapeutics

Enrollment of Phase 2a CAReS Study Expected to Commence Near Year-End $19.5 Million in Cash and Investments as of September 30, 2022 SOLANA BEACH, Calif., Nov. 08, 2022 (GLOBE NEWSWIRE) -- Artelo Biosciences Inc. (Nasdaq: ARTL), a clinical-stage pharmaceutical company focused on modulating lipid-signaling pathways to develop treatments for people living with cancer, pain, and neurological conditions, today reported financial and operating results for the three months ended September 30, 2022 and provided a business update. “Based on ART27.13’s favorable safety pro date, the Phase 1b Cancer Appetite Recovery Study (CAReS) evaluating ART27.13 for the treatment of cancer-related anorexia and weight loss was expanded to include a fourth, higher dose cohort earlier this year. This final cohort is nearly fully enrolled. Once clinical results are evaluated, we expect to commence enrollment of our Phase 2a clinical trial near year-end,” stated Gregory D. Gorgas, President and Chief Executive Officer of Artelo Biosciences. “With over $19.5 million in cash and investments as of September 30, 2022, we expect to fund operations through the first half of 2024 and, thus, support the achievement of key clinical and preclinical milestones,” added Mr. Gorgas. Other Business Highlights Promising Non-clinical Data for Multiple Potential Uses from Artelo’s Fatty Acid Binding Protein 5(FABP5) Platform At the International Cannabinoid Research Society’s annual meeting in Galway, Ireland, June 26-30, 2022, Artelo shared data from multiple non-clinical animal research studies with ART26.12, its lead FABP5 inhibitor, indicating that chronic, oral administration was effective at preventing and treating both oxalplatin- and paclitaxel-induced pain sensitivity without any sedating effects. These findings support further development of ART26.12 in neuropathies, including neuropathy associated with chemotherapy, which represents a significant unmet need for which there are no approved treatments in the US, UK, or Europe. With regulatory enabling research well underway, Artelo anticipates filing an Investigational New Drug application with the FDA late next year. In addition to the research with ART26.12, Artelo reported positive non-clinical results from one of its other novel FABP5 inhibitors, which suggests that the inhibition of FABP5 can be a promising neurobiological approach for the development of anxiety-inhibiting pharmacotherapies. Data from this research are expected to be shared at the Society for Neuroscience annual meeting in San Diego November 12-16, 2022 by Steven Laviolette, PhD whose research was conducted at the University of Western Ontario, Canada. Financial Results Ended September 30, 2022 Operating expenses for the three months ended September 30, 2022, were $2.4 million compared to $2.2 million for the same period in 2021. The increase in operating expenses for the three months ended September 30, 2022, was primarily related to increases in payroll and in subcontractor expenditures relating to the CAReS trial. Net loss was approximately $2.3 million, or $0.82 per basic and diluted common share, for the three months ended September 30, 2022, compared to a net loss of $2.2 million, or $1.37 per basic and diluted common share, for the three months ended September 30, 2021. As of September 30, 2022, the Company had approximately $19.5 million in cash and investments, compared to $25.6 million as of December 31, 2021. About ART27.13 ART27.13 is a highly potent, peripherally restricted synthetic, dual G-Protein Coupled Receptor agonist believed to target the cannabinoid receptors CB1 and CB2, which has the potential to increase appetite and food intake. Originally developed by AstraZeneca plc, ART27.13 has been in five Phase 1 clinical studies including over 200 subjects where it demonstrated a statistically significant and dose-dependent increase in body weight in healthy subjects. Importantly, the changes in body weight were not associated with fluid retention and the distribution of the drug enables systemic metabolic effects while minimizing central nervous system-mediated toxicity. Artelo is advancing ART27.13 as a supportive care therapy for cancer patients suffering from anorexia and weight loss, where the current annual global market is estimated to be valued in excess of $2 billion. About CAReS The Cancer Appetite Recovery Study (CAReS) is a Phase 1b/2a randomized, placebo-controlled trial of the Company’s lead clinical program, ART27.13, in patients with cancer anorexia and weight loss. Anorexia, or the lack or loss of appetite in cancer patients, may result from the cancer and/or its treatment with radiation or chemotherapy. It is common for patients with cancer to lose weight. Anorexia and the resulting weight loss can affect a patient’s health, often weakening their immune system and causing discomfort and dehydration. A weight loss of more than 5% can predict a poor outcome for cancer patients and a lower response to chemotherapy. The Phase 1b portion of the CAReS study is designed to determine the most effective and safest dose of ART27.13 for dosing in the Phase 2a stage. The Phase 2a portion of the CAReS study is designed to determine estimates of activity of ART27.13 in terms of lean body mass, weight gain, and improvement of anorexia. (ISRCTN registry: ) About ART26.12 Fatty Acid Binding Proteins (FABPs) are a family of intracellular proteins that chaperone lipids including endocannabinoids and fatty acids. Various inhibitors of FABPs may be particularly useful for the treatment of specific cancers, neuropathic and nociceptive pain, and anxiety disorders. ART26.12, Artelo’s lead FABP inhibitor compound, is a selective inhibitor of FABP5. While developing our lead molecule for Chemotherapy-Induced Peripheral Neuropathy, additional compounds from our extensive library of potent and selective inhibitors of FABPs. have been identified for advancement towards regulatory-enabling studies in anxiety, cancer and other areas of high-unmet need where inhibition of FABPs show significant promise. About Artelo Biosciences Artelo Biosciences, Inc. is a clinical-stage pharmaceutical company focused on modulating lipid-signaling pathways to develop treatments for people living with cancer, pain, and neurological conditions. Artelo is advancing a portfolio of broadly applicable product candidates designed to address significant unmet needs in multiple diseases and conditions, including anorexia, cancer, PTSD, pain, and inflammation. Led by proven pharmaceutical executives collaborating with highly respected researchers and technology experts, Artelo applies leading edge scientific, regulatory, and commercial discipline to develop high-impact therapies. More information is available at and Twitter: @ArteloBio. Forward Looking Statements This press release contains certain forward-looking statements within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934 and Private Securities Litigation Reform Act, as amended, including those relating to the Company’s product development, clinical and regulatory timelines, market opportunity, competitive position, possible or assumed future results of operations, business strategies, potential growth opportunities and other statement that are predictive in nature. These forward-looking statements are based on current expectations, estimates, forecasts and projections about the industry and markets in which we operate and management’s current beliefs and assumptions. These statements may be identified by the use of forward-looking expressions, including, but not limited to, “expect,” “anticipate,” “intend,” “plan,” “believe,” “estimate,” “potential,” “predict,” “project,” “should,” “would” and similar expressions and the negatives of those terms. These statements relate to future events or our financial performance and involve known and unknown risks, uncertainties, and other factors which may cause actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements. Such factors include those set forth in the Company’s filings with the Securities and Exchange Commission, including our ability to raise additional capital in the future. Prospective investors are cautioned not to place undue reliance on such forward-looking statements, which speak only as of the date of this press release. The Company undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise, except to the extent required by applicable securities laws. Investor Relations Contact: Crescendo Communications, LLC Tel: 212-671-1020 Email: ARTL@crescendo-ir.com

Recently Published Findings Support Further Development in Anxiety-Related DisordersSOLANA BEACH, Calif., Aug. 16, 2022 (GLOBE NEWSWIRE) -- Artelo Biosciences, Inc. (Nasdaq: ARTL), a clinical-stage pharmaceutical company focused on modulating lipid-signaling pathways to develop treatments for people living with cancer, pain, and neurological conditions, today announced publication of pre-clinical results indicating a novel fatty acid binding protein 5 (FABP5) inhibitor from the Company’s FABP inhibitor platform reduces anxiety behaviors in an area of the brain known to be important in anxiety and that modulation of the FABP5 system may serve as a promising target for the development of novel anxiolytics. “What was particularly interesting was that we have demonstrated that the CB2 receptor, which is often thought of as the peripheral cannabinoid receptor, is involved in the control of both fear and anxiety and, importantly, is capable of being modulated by FABP5 inhibition for the first time,” said Gregory D. Gorgas. President and Chief Executive Officer of Artelo Biosciences. “This new data further supports the development of our FABP inhibitor platform in anxiety-related disorders such as post-traumatic stress disorder.” “Despite the involvement of endogenous cannabinoid signaling in many psychiatric conditions, including anxiety disorders, the effects of FABPs on the modulation of fear and anxiety have not been thoroughly investigated,” said neuroscience Professor Steven R. Laviolette, Ph.D., one of the lead researchers of the study. “We are encouraged by these findings which indicate inhibiting FABPs represents a promising neurobiological approach for the development of novel anxiety-inhibiting pharmacotherapies.” This research, with one of many of Artelo’s FABP inhibitors, which was led by Taygun C. Uzuneser, Ph.D., and Steven R. Laviolette, Ph.D., both of the University of Western Ontario, London, Ontario, was published in the journal Cerebral Cortex. Another researcher involved in the study was Iwao Ojima, Ph.D., University Distinguished Professor at Stony Brook University and the principal inventor of the multiple FABP inhibitors exclusively licensed to Artelo, including the Company’s lead FABP inhibitor ART26.12 being developed as a potential treatment for Chemotherapy Induced Peripheral Neuropathy. About Artelo’s Platform of FABP InhibitorsFABPs are a family of intracellular proteins that chaperones lipids including endocannabinoids and fatty acids. Inhibitors of FABPs are intended for treatment of cancer, neuropathic and nociceptive pain, and anxiety. Artelo licensed multiple compounds through its collaboration with Stony Brook University. The Company’s lead compound, ART26.12, is a selective inhibitor of FABP5. Artelo’s near-term goal is to develop ART26.12 for the prevention and/or treatment of Chemotherapy Induced Peripheral Neuropathies, for which there are no regulatory approved medicines. While progressing the lead FABP inhibitor in regulatory-enabling studies, additional compound(s) have been identified and selected for advancement in anxiety-related disorders, including Post-Traumatic Stress Disorder. About Artelo BiosciencesArtelo Biosciences, Inc. is a clinical-stage pharmaceutical company focused on modulating lipid-signaling pathways to develop treatments for people living with cancer, pain, and neurological conditions. Artelo is advancing a portfolio of broadly applicable product candidates designed to address significant unmet needs in multiple diseases and conditions, including anorexia, cancer, PTSD, pain, and inflammation. Led by proven pharmaceutical executives collaborating with highly respected researchers and technology experts, Artelo applies leading edge scientific, regulatory, and commercial discipline to develop high-impact therapies. More information is available at www.artelobio.com and Twitter: @ArteloBio. Forward Looking Statements This press release contains certain forward-looking statements within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934 and Private Securities Litigation Reform Act, as amended, including those relating to Artelo’s product development, clinical and regulatory timelines, market opportunity, competitive position, possible or assumed future results of operations, business strategies, potential growth opportunities and other statement that are predictive in nature. These forward-looking statements are based on current expectations, estimates, forecasts and projections about the industry and markets in which we operate and management’s current beliefs and assumptions. These statements may be identified by the use of forward-looking expressions, including, but not limited to, “expect,” “anticipate,” “intend,” “plan,” “believe,” “estimate,” “potential,” “predict,” “project,” “should,” “would” and similar expressions and the negatives of those terms. These statements relate to future events or our financial performance and involve known and unknown risks, uncertainties, and other factors which may cause actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements. Such factors include those set forth in Artelo’s filings with the Securities and Exchange Commission, including our ability to raise additional capital in the future. Prospective investors are cautioned not to place undue reliance on such forward-looking statements, which speak only as of the date of this press release. Artelo undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise, except to the extent required by applicable securities laws. Investor Relations Contact:Crescendo Communications, LLCTel: 212-671-1020Email: ARTL@crescendo-ir.com