Diagnostic & Therapeutic Center of Athens Hygeia SA

VANCOUVER, BC, June 24, 2024 /PRNewswire/ - The first patient has entered the Phase II/III trial of ST-02, Sustained Therapeutic's innovative cancer medication targeting Upper Tract Urethral Carcinoma (UTUC). A rare form of cancer, UTUC affects over 7,000 individuals annually across North America. UTUC is a cancer of the inside lining of the kidney (the "collecting system" – where urine starts to drain after it is made by the kidney) and the ureter (the tube that carries urine from the kidney to the bladder). Its location in the upper collecting system makes it challenging to access and completely remove with traditional laser resection. "This is a major step forward in the treatment of UTUC," says Dr. Peter Black, lead investigator of the clinical trial and a Senior Research Scientist with the Vancouver Prostate Centre. "Currently we have limited treatment options for this uncommon and challenging cancer, and this approach may allow better disease control without having to remove a kidney." The first patient in the clinical trial has been enrolled at the Vancouver Prostate Centre, and it is anticipated that 5 other sites will take part in the study. The company plans on enrolling approximately 75 patients in the combined Phase II/III trial and believes that ST-02 may be designated an orphan drug. Orphan drug designation can qualify the company for incentives such as tax credits, exemption from user fees, and seven years of market exclusivity after approval. Sustained Therapeutics' ST-02 product for UTUC is a sustained release formulation that enables direct delivery of chemotherapy to the site of the carcinoma via a catheter. Using the company's proprietary platform technology, the medication releases slowly over about 24 hours exactly where the cancer is located, coating the tissue and delivering chemotherapy at higher concentrations and for longer than the current standard of care. The company believes that this direct sustained delivery may be more effective and result in fewer side effects than other forms of chemotherapy that are a current standard of care. "ST-02 is Sustained Therapeutic's second product to reach Phase II trials, and demonstrates our potential to develop multiple products using our novel drug delivery platforms. As such, it is a very important development in our portfolio," says Dr. Martin Gleave, Founder and Chief Medical Office of Sustained Therapeutics and Distinguished Professor in the UBC Department of Urologic Sciences and Director of the Vancouver Prostate Centre (VPC). "This new therapeutic, designed specifically for UTUC, could address and important unmet need for patients. It's an exciting time to be a part of this work." About Sustained Therapeutics: Sustained Therapeutics is a clinical-stage company utilizing its advanced clinical and research expertise to develop its novel sustained-release drug delivery platform. Its first product, ST-01, is a non-opioid locally injected sustained-release therapeutics primarily for the treatment of pain and currently is in two Phase II trials. A spin-off from the University of British Columbia and the Vancouver Prostate Centre, has the potential to enable sustained release treatments for multiple other products, including in cancer and inflammatory diseases. sustainedtherapeutics.com Notice Regarding Forward-Looking Statements: This news release contains forward-looking statements within the meaning of the U.S. Private Securities Litigation Reform Act of 1995 and forward-looking information within the meaning of applicable Canadian securities laws (collectively, "forward-looking statements"), including statements regarding the results of the Phase I trial, the objectives and potential results of the Phase II trial, and the potential benefits of the Company's therapeutics. Statements in this document regarding future expectations, beliefs, or plans constitute forward-looking statements that involve risks and uncertainties, which may cause actual results to differ materially from the statements made. Without limiting the foregoing, the words "seeks", "believes", "plans", and "indicates" are intended to identify forward-looking statements. You are cautioned that such statements are subject to a multitude of risks and uncertainties that could cause actual results, future circumstances, or events to differ materially from those projected in the forward-looking statements. These risks include, but are not limited to: those associated with the success of research and development programs, the ability to raise additional funding, and the need to obtain regulatory approval. Forward-looking statements are developed based on assumptions about such risks, uncertainties and other factors, including, but not limited to: research and development plans proceeding substantially as envisioned, safety of product, and availability of financing on reasonable terms. Forward-looking statements are made as of the date hereof, and the Company disclaims any intention and has no obligation or responsibility, except as required by law, to update or revise any forward-looking statements, whether as a result of new information, future events, or otherwise. SOURCE Sustained Therapeutics

Data shows deep repression of HBV both in primary cells and ‘gold standard’ humanized mouse model Therapeutic targets a single "master controller" sequence to silence all forms of the virus Approach offers a path to functional cure for HBV DURHAM, N.C. & SEATTLE--(BUSINESS WIRE)-- Leading epigenome editing company Tune Therapeutics presented data in support of its chronic Hepatitis B Virus (HBV) program, demonstrating the ability to durably silence essential mechanisms of viral replication and persistence across a range of model systems. TUNE-401 represents a fundamentally new approach to HBV treatment, in that it utilizes Tune’s precision genetic tuning platform, TEMPO, to inactivate viral DNA integrated into host chromosomes, while simultaneously silencing the extra-chromosomal, cccDNA “viral factories” necessary for sustained HBV infection. Importantly, the TEMPO platform does this via epigenetic processes, and without cutting, damaging, or altering genomic DNA sequences in any way. The ability to suppress the virus in both contexts – both within and outside the host genome – is an established prerequisite for control of the virus in chronic HBV patients, and this new epigenetic silencing approach offers a pathway toward a functional cure for HBV as a standalone therapy. The Tune HBV data, shared for the first time at the 2023 HepDART hepatology conference, showed: near-complete repression of viral DNA in primary human hepatocytes and cell lines in vitro, with ongoing durability now beyond 550 days, and more than 275 cell doublings similarly high levels of repression in successfully epi-edited cells in vivo, using chimeric, true-infection mouse models highly specific targeting and methylation by TUNE-401 for both integrated virus and cccDNA – with little or no expression change in non-targeted genes Moreover, these results were achieved via a single target sequence, common to all viral contexts and locations within the cell, and highly conserved across HBV genotypes. “We used TEMPO to screen for epigenetic repression targets that are active in cccDNA, and also in integrated HBV DNA,” explained Principal Scientist Brian Cosgrove, who presented the data at HepDART. “Through the richness of these data sets, we found multiple repression candidates that worked well in both contexts. The most compelling targets went on to yield near-complete repression of viral DNA in primary human hepatocytes, when corrected for per-cell delivery efficiency limits.” In validating this target in vivo, Tune took care to select a comprehensive and informative HBV infection model featuring humanized FRG mice. “We know from clinical research,” said Cosgrove, “that less than 5 percent of chronic HBV patients achieve full viral clearance and cure. Many who do, however, show epigenetic inactivation of the cccDNA. And while a variety of in vivo models exist for HBV infection, very few allow for the effective study of HBV regulation in its natural, extrachromosomal (cccDNA) context. The chimeric FRG mouse model does just that.” Chimeric FRG mice are created via the ablation and replacement of mouse liver cells with transplanted, human hepatocytes – effectively “humanizing” the liver. As such, they represent the gold standard for assessing the dose and efficacy for liver-directed therapeutics ahead of human clinical trials. When tested in this model system, TUNE-401 showed high repression in delivered cells. Though no large animal model is available for HBV, Tune has demonstrated durable, liver-directed epi-editing of non-human primates (NHPs) using a surrogate target (PCSK9) and the same, essential mode of action – targeted DNA methylation. “Based on the breadth of our preclinical data, we have every reason to believe that this novel therapeutic strategy will translate,” says Derek Jantz, Chief Scientific Officer at Tune Therapeutics. “We sincerely hope that this will revitalize the field and lead to the standalone functional cure that HBV patients have been waiting for.” Tune expects its HBV program to enter the clinic by the end of 2024, under the guidance of leading international clinical investigator Dr. Edward Gane. About Tune Therapeutics Armed with its powerful and innovative genetic tuning platform (TEMPO), Tune Therapeutics aims to bring gene, cell, and regenerative therapies into a new era of human medicine – expanding their range of application to common, chronic and age-related diseases that are straining healthcare systems and limiting human healthspan on a global scale. Tune is currently hiring for additional members to join the team. For more information, please visit . About TUNE-401 TUNE-401 is a first-in-class investigational product candidate for the treatment of Hepatitis B (HBV) infection. TUNE-401 utilizes Tune’s TEMPO platform to epigenetically silence viral HBV DNA in host chromosomes, while simultaneously silencing the extra-chromosomal, cccDNA “viral factories” necessary for sustained HBV infection. Lipid nanoparticle technology for TUNE-401 has been provided by Acuitas Therapeutics Inc.

Post-hoc analysis from Phase 1b/2a study in pulmonary sarcoidosis presented at the European Respiratory Society (ERS) International Congress 2023. 7.7% of patients in the 3.0 and 5.0 mg/kg efzofitimod group relapsed following steroid taper, compared to 54.4% in the placebo and efzofitimod 1.0 mg/kg group (p=0.017). Rate of change for forced vital capacity (FVC) was significantly improved for the 3.0 and 5.0 mg/kg efzofitimod group compared to placebo and the efzofitimod 1.0 mg/kg group (p=0.035). SAN DIEGO, Sept. 11, 2023 (GLOBE NEWSWIRE) -- aTyr Pharma, Inc. (Nasdaq: LIFE) (aTyr or the Company), a clinical stage biotechnology company engaged in the discovery and development of first-in-class medicines from its proprietary tRNA synthetase platform, today announced the results of a post-hoc analysis of data from its Phase 1b/2a study of efzofitimod in patients with pulmonary sarcoidosis. The analysis was presented in a poster at the European Respiratory Society (ERS) International Congress 2023, which is taking place September 9 – 13, 2023, in Milan, Italy. The poster is available on the Company’s website. “This new data from a post-hoc analysis, which pools efzofitimod 3.0 and 5.0 mg/kg and placebo and efzofitimod 1.0 mg/kg doses from the Phase 1b/2a study of efzofitimod in patients with pulmonary sarcoidosis, is yet another indicator of the robust efficacy demonstrated in this study,” said Sanjay S. Shukla, M.D., M.S., President and CEO of aTyr. “The statistically significant difference in the relapse rate following steroid taper seen in the two highest efzofitimod dose groups, combined with significantly improved FVC and quality of life measures, suggests that efzofitimod has the potential to be the first steroid-sparing and disease-modifying treatment for sarcoidosis.” “Oral corticosteroids remain the mainstay of treatment for patients with pulmonary sarcoidosis, although long-term treatment often comes with severe side effects and toxicity. Steroid tapers in these patients are challenging, as symptoms and FVC can worsen when steroid dose is reduced,” said Robert P. Baughman, M.D., Professor of Medicine at the University of Cincinnati Medical Center. “This analysis demonstrating a relapse rate limited to 7.7% for the efzofitimod therapeutic group is exciting, as we would normally expect to see a relapse rate as high as approximately 50% over the course of 6 months, which is what was observed in the subtherapeutic group, and the difference may even be more evident in a longer study. This is one of the few studies to demonstrate a steroid sparing effect of a drug associated with a significant improvement in patient outcome. A treatment such as efzofitimod that can reduce steroid burden is greatly needed.” Therapeutic Doses of Efzofitimod Significantly Improve Multiple Pulmonary Sarcoidosis Efficacy Measures The poster presents findings from a pooled, post-hoc analysis of data from a Phase 1b/2a randomized, double-blind, placebo-controlled, multiple ascending dose (1.0, 3.0 and 5.0 mg/kg) 24-week study of efzofitimod in patients with pulmonary sarcoidosis receiving oral corticosteroid (OCS) dose ≥ 10.0 mg/day. Patients were randomized 1:2 (placebo:efzofitimod) and underwent a forced steroid taper in the first 8 weeks of the study. Dose dependent improvements in steroid burden, FVC and patient reported outcomes (PRO) were noted, though the study was not powered for efficacy. In this pooled analysis, the 3.0 mg/kg (N=8) and 5.0 mg/kg (N=9) efzofitimod arms were considered therapeutic, and pooled. The placebo (N=12) and 1.0 mg/kg (N=8) efzofitimod arm, which was considered subtherapeutic, were pooled. Time to relapse for steroid use (defined as dose of OCS increased after OCS taper to 5.0 mg or less of prednisone or equivalent for at least five consecutive days), rate of change for FVC and proportion of patients with changes that are multiples of the minimally clinically important difference (MCID) in PRO (Kings Sarcoidosis Questionnaire-Lung, or KSQ-L) were compared. Additionally, a responder endpoint was proposed (defined as reduction in OCS from baseline without worsening in FVC or PRO) and an analysis was performed. Key findings include: 7.7% of patients in the therapeutic group relapsed for steroid use compared to 54.4% of patients in the placebo/subtherapeutic group (p=0.017);The rate of change for FVC was significantly improved for the therapeutic group compared to the placebo/subtherapeutic group (p=0.035);52.9% of patients in the therapeutic group showed an increase ≥12 for KSQ-L (3 times MCID) compared with 15.0% in the placebo/subtherapeutic group (p=0.032); and64.7% of patients in the therapeutic group achieved response compared to 20.0% in the placebo/subtherapeutic group (p=0.008). aTyr is currently conducting EFZO-FIT™, a global Phase 3 randomized, double-blind, placebo-controlled 52-week study to evaluate the efficacy and safety of 3.0 mg/kg and 5.0 mg/kg of efzofitimod in 264 patients with pulmonary sarcoidosis. The trial design incorporates a forced steroid taper. The primary endpoint of the study is steroid reduction. Secondary endpoints include measures of lung function and sarcoidosis symptoms. About Efzofitimod Efzofitimod is a first-in-class biologic immunomodulator in clinical development for the treatment of interstitial lung disease (ILD), a group of immune-mediated disorders that can cause inflammation and fibrosis, or scarring, of the lungs. Efzofitimod is a tRNA synthetase derived therapy that selectively modulates activated myeloid cells through neuropilin-2 to resolve inflammation without immune suppression and potentially prevent the progression of fibrosis. aTyr is currently investigating efzofitimod in the global Phase 3 EFZO-FIT™ study in patients with pulmonary sarcoidosis, a major form of ILD, and in the Phase 2 EFZO-CONNECT™ study in patients with systemic sclerosis (SSc, or scleroderma)-related ILD. These forms of ILD have limited therapeutic options and there is a need for safer and more effective, disease-modifying treatments that improve outcomes. About aTyr aTyr is a clinical stage biotechnology company leveraging evolutionary intelligence to translate tRNA synthetase biology into new therapies for fibrosis and inflammation. tRNA synthetases are ancient, essential proteins that have evolved novel domains that regulate diverse pathways extracellularly in humans. aTyr’s discovery platform is focused on unlocking hidden therapeutic intervention points by uncovering signaling pathways driven by its proprietary library of domains derived from all 20 tRNA synthetases. aTyr’s lead therapeutic candidate is efzofitimod, a first-in-class biologic immunomodulator in clinical development for the treatment of interstitial lung disease, a group of immune-mediated disorders that can cause inflammation and progressive fibrosis, or scarring, of the lungs. For more information, please visit www.atyrpharma.com. Forward-Looking Statements This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Forward-looking statements are usually identified by the use of words such as “believes,” “can,” “expects,” “intends,” “may,” “plans,” “potential,” “will,” and variations of such words or similar expressions. We intend these forward-looking statements to be covered by such safe harbor provisions for forward-looking statements and are making this statement for purposes of complying with those safe harbor provisions. These forward-looking statements include, among others, statements regarding the potential of efzofitimod to provide a differentiated approach to resolving inflammation and preventing the progression of fibrosis to be the first steroid sparing and disease-modifying treatment for sarcoidosis and to reduce steroid burden and significantly improve multiple pulmonary sarcoidosis efficacy measures, and the potential applications of efzofitimod. These forward-looking statements also reflect our current views about our plans, intentions, expectations, strategies and prospects, which are based on the information currently available to us and on assumptions we have made. Although we believe that our plans, intentions, expectations, strategies and prospects, as reflected in or suggested by these forward-looking statements, are reasonable, we can give no assurance that the plans, intentions, expectations, strategies or prospects will be attained or achieved. All forward-looking statements are based on estimates and assumptions by our management that, although we believe to be reasonable, are inherently uncertain. Furthermore, actual results may differ materially from those described in these forward-looking statements and will be affected by a variety of risks and factors that are beyond our control including, without limitation, uncertainty regarding geopolitical and macroeconomic events, risks associated with the discovery, development and regulation of efzofitimod, the risk that we or our partners may cease or delay preclinical or clinical development activities for efzofitimod for a variety of reasons (including difficulties or delays in patient enrollment in planned clinical trials), the possibility that existing collaborations could be terminated early, and the risk that we may not be able to raise the additional funding required for our business and product development plans, as well as those risks set forth in our most recent Annual Report on Form 10-K, Quarterly Report on Form 10-Q and in our subsequent SEC filings. Except as required by law, we assume no obligation to update publicly any forward-looking statements, whether as a result of new information, future events or otherwise. Contact: Ashlee Dunston Director, Investor Relations and Public Affairs adunston@atyrpharma.com