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Transitioned from Pre-Clinical to Clinical Stage company in FY 2023 Phase 1/2a trial, designed to assess both healthy volunteers and patients diagnosed with Treatment-Resistant Depression, PTSD or Generalized Anxiety Disorder, progressing through Phase 1 portion Plans to enroll final two out of five cohorts into the single dose portion of the Phase 1 trial within the next month NEW YORK, NY / ACCESSWIRE / April 1, 2024 / Protagenic Therapeutics Inc. (NASDAQ:PTIX), a leader in biopharmaceutical innovation, today provided a corporate update and reported financial results for the fourth quarter and full year 2023. "In 2023, Protagenic Therapeutics achieved a significant milestone as we began enrolling patients for our neuropeptide drug candidate, PT00114," said Dr. Garo Armen, Executive Chairman. "Our primary focus lies in advancing this drug candidate, designed to address the substantial unmet needs across a spectrum of stress-related neuropsychiatric disorders, including Treatment-Resistant Depression, PTSD, Generalized Anxiety Disorder and Addiction withdrawal." 2023 Highlights about PT00114 First Clinical Trial: PT00114, the company's synthetic version of the stress-regulating peptide TCAP, began the single ascending dose (S.A,D,) portion of a Phase 1 clinical trial. Notably, PT00114 has shown excellent tolerability with no adverse safety findings during these ongoing Phase 1 studies. With promising preclinical efficacy in anxiety, depression, PTSD, and addiction models, PT00114 is moving forward in clinical evaluation, representing a key step toward transformative therapies. Safety Validation: Building on the low dose safety validation announced February 13th, as announced on March 27th, PT00114 has now demonstrated safety at a medium dose of 500 micrograms administered subcutaneously in the third of five planned cohorts of subjects in the single dose portion of the Phase I trial. No adverse reactions were observed among subjects, consistent with the two lower dose cohorts (125 micrograms and 250 micrograms), with no reported injection site reactions or tolerability issues in the week following dosing. Based on preclinical pharmacology, PT00114 is expected to be administered once weekly via subcutaneous injection. Clinical Protocol Progress: This marks progress in the ongoing Phase 1/2a trial, designed to assess both healthy volunteers and patients diagnosed with Treatment-Resistant Depression, PTSD, or Generalized Anxiety Disorder. The company plans to enroll the final two cohorts into the single dose portion of the Phase 1 trial within the next month. Comprehensive Approach: In addition to monitoring disease status, the trial incorporates biomarker assessments, including circulating cortisol levels, to measure initial treatment response. Dr. Maurizio Fava, Psychiatrist-in-Chief at Massachusetts General Hospital, serves as the Principal Investigator in Protagenic's Phase 1/2a clinical trial with a basket design. Strategic Collaboration: Axiom Real-Time Metrics, a CRO/Data Analytics firm, manages the clinical program. Fourth Quarter and Full Year 2023 Financial Results Our financial results reflect an increase in research & development spending to pursue our primary objective of developing and commercializing PT00114 during FY 2023, particularly during the fourth quarter. In the fourth quarter of 2023, we spent $1.0 million on R&D, an increase of 301% over our $258,000 R&D spend in the fourth quarter of 2022. This significant increase in R&D expenditures was entirely due to the clinical trial that is now in progress for PT00114, which commenced just as Q4 was starting. Our G&A spend for the fourth quarter of 2023 was just $201,000, down 50% from our G&A spend in the comparable quarter a year ago. Our net loss for Q4 was $1.2 million, compared to a net loss of $656,000 in the year-ago quarter. For the full year 2023, we spent $3.3 million on R&D, up 109% from the $1.6 million we spent on R&D for the full year 2022. Our full-year G&A of $1.2 million was, similar to the quarter, down almost 40% from the amount spent in the year-ago period. For full year net income, we lost $4.5 million, which is 27% more loss than we had in 2022, driven primarily by our higher R&D spend because of our clinical trial activities. For cash, we ended the year with $4.1 million in cash and cash equivalents, down from the $8.0 million we had as of Dec 31, 2022. We believe that our current cash reserves are sufficient to fund all of our Phase I clinical trial. Profit and Loss Statements For the years ended December 31, 2023 2022 OPERATING AND ADMINISTRATIVE EXPENSES Research and development $ 3,319,867 $ 1,589,239 General and administrative 1,207,107 1,968,549 TOTAL OPERATING AND ADMINISTRATIVE EXPENSES 4,526,974 3,557,788 LOSS FROM OPERATIONS (4,526,974 ) (3,557,788 ) OTHER INCOME Interest income 264,476 185,790 Interest expense (107,682 ) (137,456 ) Realized loss on marketable securities (630,317 ) (46,051 ) TOTAL OTHER INCOME (473,523 ) 2,283 LOSS BEFORE TAX (5,000,497 ) (3,555,505 ) INCOME TAX EXPENSE - - NET LOSS $ (5,000,497 ) $ (3,555,505 ) COMPREHENSIVE LOSS - - Other Comprehensive Loss - net of tax Net unrealized gain (loss) on marketable securities 16,848 (421,738 ) Reclassification of realized losses on debt securities 489,120 - Foreign exchange translation income (loss) 57,393 (6,820 ) TOTAL COMPREHENSIVE LOSS $ (4,437,136 ) $ (3,984,063 ) Net loss per common share - Basic and Diluted $ (1.15 ) $ (0.82 ) Weighted average common shares - Basic and Diluted 4,344,580 4,317,875 Balance Sheet December 31, 2023 December 31, 2022 ASSETS CURRENT ASSETS Cash $ 1,287,893 $ 215,189 Marketable securities 2,768,119 7,763,517 Prepaid expenses 144,025 56,939 TOTAL CURRENT ASSETS 4,200,037 8,035,645 Equipment - net 123,332 1,775 TOTAL ASSETS $ 4,323,369 $ 8,037,420 LIABILITIES AND STOCKHOLDERS' EQUITY CURRENT LIABILITIES Accounts payable and accrued expenses $ 439,757 $ 669,704 Accounts payable and accrued expenses - related party 215,495 105,928 PIK convertible notes payable, net of debt discount - 150,591 PIK convertible notes payable, net of debt discount - related parties - 193,639 TOTAL CURRENT LIABILITIES 655,252 1,119,862 TOTAL LIABILITIES 655,252 1,119,862 STOCKHOLDERS' EQUITY Preferred stock, $0.000001 par value; 20,000,000 shares authorized; none shares issued and outstanding in the following classes: - - Preferred stock; par value $0.000001; 2,000,000 shares authorized; none issued and outstanding - - Series B convertible preferred stock, $0.000001 par value;18,000,000 shares authorized; 0 and 0 shares issued and outstanding at December 31, 2023, and December 31, 2022 - - Preferred stock value - - Common stock, $.0001 par value, 100,000,000 shares authorized, 4,435,132 and 4,321,315 shares issued and outstanding at December 31, 2023, and December 31, 2022 444 434 Additional paid-in-capital 34,559,091 33,371,406 Accumulated deficit (30,777,872 ) (25,777,375 ) Accumulated other comprehensive loss (113,546 ) (676,907 ) TOTAL STOCKHOLDERS' EQUITY 3,668,117 6,917,558 TOTAL LIABILITIES AND STOCKHOLDERS' EQUITY $ 4,323,369 $ 8,037,420 See accompanying notes to the consolidated financial statements in the company's Form 10-K, filed concurrently. Conference Call Date: April 1 , 2024, 4:30 p.m. ET To access dial-in numbers, please register here. Participant link (for all regular participants): Or by phone: 888-506-0062 International: 973-528-0011 Participant Access Code: 628544 Webcast A live webcast and replay of the conference call will be accessible on the company's website at: About Protagenic Therapeutics, Inc.: Protagenic Therapeutics, Inc. (Nasdaq: PTIX) is dedicated to pioneering therapeutics based on neuro-active peptides to alleviate the negative effects of stress and treat stress-related disorders such as anxiety, depression, PTSD, and addiction. For more information, visit . About PT00114: PT00114, a 41-amino-acid residue synthetic peptide, shows promise as a novel treatment for serious neuro-psychiatric conditions, including depression, anxiety, and PTSD. It is a synthetic form of the naturally occurring brain peptide TCAP, which counters the negative biochemical and behavioral effects of stress-induced brain hormones Corticotropin Releasing Factor and Arginine-Vasopressin. Among its benefits is the reduction of excessive circulating levels of cortisol often associated with various stressors. Forward-Looking Statements: This press release contains forward-looking statements concerning Protagenic Therapeutics' product candidates and clinical trial plans. These statements are subject to various risks and uncertainties. Investors are urged to exercise caution and not place undue reliance on these forward-looking statements. Company Contact: Alexander K. Arrow, MD, CFA 
Chief Financial Officer
 Protagenic Therapeutics, Inc. 149 Fifth Ave, Suite 500, New York, NY 10010. Tel: 213-260-4342
 Email: alex.arrow@protagenic.com Investor Relations Contact: Kirin M. Smith, President, PCG Advisory, Inc. 950 Third Avenue, Suite #2700, New York, NY 10022. Tel: 646-823-8656 Email: ksmith@pcgadvisory.com SOURCE: Protagenic Therapeutics, Inc. View the original press release on accesswire.com

Call Scheduled for Monday, April 1st, 2024, at 4:30 pm ET NEW YORK, NY / ACCESSWIRE / March 25, 2024 / Protagenic Therapeutics, Inc. (NASDAQ:PTIX), a biopharmaceutical innovator, announced that the Company plans to hold its first investor earnings call to discuss the results contained in its FY 2023 Form 10K, which it plans to day, and its outlook for FY 2024. The Company plans to hold its earnings call, open to the public, at 4:30 pm ET on Monday, April 1st, to discuss the results of its Q4 and FY 2023, which it plans to publish in its Form 10K to be filed with the SEC that day. On the call, management also plans to discuss the company's outlook for FY 2024, including expectations for additional data readouts from the ongoing PT00114 clinical trial. Participants in the discussion about the outlook for the trial will be Robert B. Stein, MD, PhD, Chief Medical Officer, and Andrew Slee, PhD, Chief Operating Officer, as well as Garo H. Armen, PhD, Executive Chairman. The log-in link is: . For those wishing to participate by phone only, dial: Toll Free: 888-506-0062 International: 973-528-0011 Participant Access Code: 628544 About Protagenic Therapeutics, Inc.: Protagenic Therapeutics, Inc. (Nasdaq: PTIX) is committed to pioneering neuro-active peptides into therapeutics to mitigate stress-related disorders. For more information, visit . About PT00114: PT00114, a 41-amino-acid residue synthetic peptide, holds promise as a novel treatment for serious neuro-psychiatric conditions, including depression, anxiety, and PTSD. It is a synthetic form of the naturally-occurring brain peptide TCAP, which acts to counter the negative biochemical and behavioral effects of the stress-induced brain hormones Corticotropin Releasing Factor and Arginine-Vasopressin. Among the beneficial effects of PT00114 is the reduction of excessive circulating levels of cortisol that often are part of the response to various stressors. Forward-Looking Statements: This press release contains forward-looking statements concerning Protagenic Therapeutics' product candidates and clinical trial plans. These statements are subject to various risks and uncertainties. Investors are urged to exercise caution and not place undue reliance on these forward-looking statements. Company Contact: Alexander K. Arrow, MD, CFA Chief Financial Officer Protagenic Therapeutics, Inc. 149 Fifth Ave, Suite 500, New York, NY 10010. Tel: 213-260-4342 Email: alex.arrow@protagenic.com Investor Relations Contact: Kirin M. Smith, President, PCG Advisory, Inc. 950 Third Avenue, Suite #2700, New York, NY 10022. Tel: 646-823-8656 Email: ksmith@pcgadvisory.com SOURCE: Protagenic Therapeutics, Inc. View the original press release on accesswire.com

New research suggests affron® saffron effectively normalized HPA-axis dysregulation, enhancing adaptation to stressful experiences MADRID, Jan. 24, 2024 /PRNewswire/ -- A new in vitro study sheds light to the stress relief effect of saffron (Crocus sativus L). The research highlights the ability of affron®, a standardized extract of saffron developed by Pharmactive Biotech Products to enhance resilience to occasional stress. Continue Reading Pharmactive’s Saffron Extract improves Resilience to Occasional Stress The new study, led by Chae-Young Kim PhD, and published November 2023 in the journal Nutrients, focuses on affron's role in regulating the hypothalamic–pituitary–adrenal (HPA axis). Results demonstrated significant improvements following repeated oral administration of the extract in stress model animal subjects. The stress signal The HPA axis is a vital brain signaling system involved in orchestrating responses to stress. It functions to assure survival in life-threatening situations, and its activation provides the energy for a "fight or flight" response. However, persistent activation of the HPA axis due to prolonged stress results in persistently elevated levels of the steroidal hormone glucocorticoids (cortisol in humans), which can have detrimental effects on overall health. The study involved 40 Wistar rats divided into four groups. Three groups were subjected to a series of standardised stress tests during the 4-week trial. Two of the groups were administered daily oral doses of affron at levels corresponding to 100mg/kg and 200mg/kg, respectively. The third group was subjected to stress without receiving affron, and the fourth group received no interventions at all as a control. Several stress-related parameters were evaluated, including hypothalamic gene expression and stress hormone levels. The two groups of affron treated rats showed marked decreases in the presence of arginine vasopressin and Corticotropin Releasing Factors (CRF) within the hypothalamus. These hormones play a pivotal role in triggering the release of other stress-related hormones, including adrenocorticotropic hormone (ACTH) from the pituitary gland, which in turn signals the adrenal glands to release cortisol (corticotropin in rodents). Serum concentration of these secondary hormones increased at first and then diminished by the third week, with a more pronounced reduction noted in the higher dose group. The high dose group also experienced a significant reduction in glucocorticoid receptor (GR) expression, reflecting a properly functioning negative feedback mechanism for orchestrating daily rhythms, managing stress responses, and facilitating adaptation to changing conditions. This effect avoids the known glucocorticoid receptor resistance that occurs due to the continuous release of glucocorticoids. The ability to mitigate this resistance through reduced GR expression demonstrates the body's effectiveness in managing stress. Saffron lightens the stress load "Chronic or excessive activation of the HPA axis and prolonged elevation of these hormones can contribute to the maladaptative response called allostatic overload—a state of cumulative strain wherein the body and mind get overwhelmed by constant anxiety or challenges, but don't have the time to recover," explains Inés Morán, PhD, Scientific Studies Manager at Pharmactive. "Beyond the mental overload, it can contribute to various health problems, such as metabolic diseases, and accelerate long-term wear and tear on the body's systems." Further examination of the affron treated rats showed they maintained high levels of Brain-Derived Neurotrophic Factor (BDNF) in the hypothalamus tissue, a protein that promotes brain plasticity, and eases the adaptation in response to life experiences by ensuring the growth, survival, and maintenance of nerve cells. The rats were also subject to a Sucrose Preference Test in which the three groups subjected to stress were observed to lose interest in sugar. Supplement with affron revived interest in sugar. "This outcome is significant, because extreme cases of anxiety or depression, can produce symptoms of anhedonia, which is a lack of interest and motivation for anything, including food," adds Morán. The renewed interest in sugar is evidence of a behavioural improvement due to the rebalanced levels of physiological regulators tested in the affron-treated groups. Current global challenges, such as political instabilities, pandemics, and economic upheavals, have brought the multifaceted impact of stress to the forefront. Simultaneously, the consumer demand for "better-for-you" solutions is fueling deeper exploration of botanicals and other natural agents for relief. Saffron is a distinguished botanical with a rich history of medicinal use. A series of studies previously confirmed the efficacy of affron across diverse populations (including adolescents) in alleviating stress, tension, and mood disturbances while enhancing mental well-being. "Despite the growing body of research on saffron's anti-stress properties, which includes six published studies of our proprietary, highly concentrated saffron extract, few studies have specifically investigated its role in normalizing the regulation of the HPA axis, a crucial system for stress modulation in the body," asserts Carlos Rodríguez, Communication Manager for Pharmactive. "Through ongoing research, we are unearthing more about saffron's benefits on cognitive well-being, and its mechanisms of action. We are realizing these extend beyond influencing serotonin expression but actually demonstrates a potential to boost resilience to occasional stress and prevent its detrimental impact on overall mental and physical health." About Pharmactive Pharmactive Biotech Products, SLU, is a Madrid-based pioneering biotechnology company that develops, and manufactures differentiated natural ingredients supported by science, such as damiana extract, pure saffron extract, and aged black garlic. The company's mission is to make a daily positive and significant impact on people's health and well-being through premium botanical ingredients backed by scientific studies and approved by ethics committees. Photo - SOURCE Pharmactive Biotech Products, S.L.