Intermittent Claudication

TAIPEI, May 28, 2024 /PRNewswire/ -- Genovate Biotechnology Co., Ltd. (TPEx: 4130), a Taiwan-based specialty pharmaceutical company, today announced its plans to submit a New Drug Application (NDA) with the United States Food and Drug Administration (US FDA) for PMR, an investigational once daily extended-release form of cilostazol for the treatment of Intermittent Claudication, in the second half of 2025. In the written responses to the pre-NDA meeting package, the FDA confirmed that the clinical studies conducted are sufficient to support the submission of a marketing application under the 505(b)(2) regulatory pathway. The key study in the submission package, GBL23-001 (NCT06167265), is a randomized, fully replicate crossover study designed to evaluate the bioequivalence and within-subject variability between PMR 145 mg once daily and the immediate-release tablet of cilostazol 100 mg twice daily. This study is expected to be completed in mid-2024, and the top-line results have shown that the primary endpoints of the study were achieved, and the decision to submit the application was made following the successful outcome of study GBL23-001. Furthermore, Genovate has been improving the PMR formulation and its manufacturing processes in order to address additional FDA comments. All clinical study and manufacturing data are expected to be included in the final submission package. "We are pleased to share what we believe is an efficient regulatory pathway for PMR with the goal of bringing a new treatment option to the people who suffer from intermittent claudication and recurrence of cerebral infarction, from the US to the globe." said Chia-Chen Chu, General Manager of Genovate. About PMR (Cilostazol Extended-Release Tablets) PMR, a novel extended-release (ER) formulation of cilostazol, was designed to reduce the concentration-dependent side effects associated with immediate-release (IR) tablet form of cilostazol. Cilostazol is currently available in IR tablet form at 50 and 100 mg strengths administered twice daily. The IR formulation of cilostazol, marketed as Pletal® in the US (Pletaal® in Taiwan and other Asian countries), was first available in Japan in 1988 for the treatment of peripheral arterial diseases and the prevention of recurrence of cerebral infarction and later approved by the US FDA in 1999 for the treatment of intermittent claudication (IC). Cilostazol is a specific PDE III inhibitor that can cause reduced platelet aggregation and increased vasodilatation. Cilostazol showed good efficacy in preventing secondary strokes, notably reducing the rates of ischaemic stroke recurrence. Nevertheless, the results from eight placebo-controlled clinical trials indicated that 15.4% of patients withdrawn from cilostazol treatment were as a result of adverse reactions. Headache, palpitations, and diarrhea were the most frequently reported adverse reactions among these patients. These adverse reactions were attributable to the peak concentration of cilostazol. Genovate is developing an ER tablet form of cilostazol, PMR, to be administered once daily aiming to improve adherence and to reduce the side effects associated with the high peak-to-trough variation of the concentration of cilostazol IR. About Intermittent Claudication Peripheral arterial disease (PAD) affects over 200 million people globally and around 8.5 million Americans over the age of 40. PAD occurs as a result of the narrowing or blockade of blood vessels that carry blood from the heart to the legs. The main symptom of PAD observed in approximately 70% of patients is intermittent claudication (IC), a condition that presents as pain and cramping in the lower extremities (thigh, calf, hip and buttock muscles), as a result of limited blood flow. IC is commonly viewed as a signal of substantial atherosclerosis, suggesting a higher likelihood of heart attack or stroke. The symptoms of IC are intermittent, exacerbated when walking or during exercise, and are alleviated with rest, but reoccur when activity resume; as a result, IC can be very debilitating, drastically affecting the quality of life of those affected. In severe cases, IC may require surgical intervention, but in general, it can be treated and managed with a combinational approach including medication, life style changes that modify or eliminate risk factors, and exercise program. Drugs improving blood flow such as anti-clotting agents (aspirin), anti-hypertensives, statins, and phosphodiesterase (PDE) III inhibitors such as cilostazol are currently used to treat IC. About Genovate Biotechnology Co., Ltd. Genovate Biotechnology Co., Ltd. is a Taiwan-based, fully integrated specialty pharmaceutical company focusing on the new drug development in new formulation, new active ingredient, new treatment modality in cardiovascular, autoimmune, neurodegenerative, and liver diseases. Genovate is equipped with PIC/S GMP manufacturing, marketing, and distribution capabilities. Forward-Looking Statements All statements other than statements of historical facts contained in this press release are forward-looking statements, including statements regarding the timing of any regulatory process or ultimate approvals for PMR for the treatment of IC. These forward-looking statements speak only as of the date of this press release and are subject to a number of risks, uncertainties and assumptions, including the risks and uncertainties associated with the projected timeline of our NDA submission, whether FDA will agree with our interpretation of the data or the adequacy of data to support an NDA, the FDA's review of our NDA, market conditions, as well as risks and uncertainties inherent in Genovate's business. The events and circumstances reflected in the company's forward-looking statements may not be achieved or occur and actual results could differ materially from those projected in the forward-looking statements. Except as required by applicable law, the company does not plan to publicly update or revise any forward-looking statements contained herein, whether as a result of any new information, future events, changed circumstances or otherwise. SOURCE Genovate Biotech

While semaglutide has already enjoyed ample popularity, “I do believe that these results really move the needle,” Novo Nordisk's executive medical director Michael Radin, M.D., said. While it’s hard to overstate the success Novo Nordisk’s GLP-1 franchise has already achieved, the company’s latest deep dive into semaglutide data in chronic kidney disease (CKD) could help set a new standard for “holistic” care for many diabetes patients, the company’s executive medical director, Michael Radin, M.D., told Fierce Pharma. Early Friday, Novo shared full results from the FLOW trial assessing the ability of once-weekly semaglutide 1.0 mg to help combat major kidney outcomes such as kidney failure, loss of kidney function and death from kidney or cardiovascular causes in people with Type 2 diabetes and CKD. Of note in the latest data drop, semaglutide helped slash the risk of major cardiovascular events by 18% and reduced the risk of all-cause mortality by 20%. Further, the rate of kidney function decline over time was “significantly slower” with semaglutide versus placebo, as tracked by estimated glomerular filtration rate—a common measure of kidney function—Radin said. Novo presented its detailed look at the FLOW results at the 61st meeting of the European Renal Association. The data were also published Friday in The New England Journal of Medicine. The full results come after Novo shared headline data in March that found semaglutide reduced the risk of kidney disease progression and kidney and cardiovascular death by 24%. Back in October, the company halted its FLOW trial early thanks to a positive efficacy signal. While semaglutide has already enjoyed ample popularity and uptake, “I do believe that these results really move the needle,” Radin said. “In other words, Type 2 diabetes doesn’t exist in a vacuum: These patients often have concomitant cardiovascular disease, they have chronic kidney disease, and there’s a move in the medical community to be able to treat these patients holistically,” he explained. CKD affects more than 800 million people worldwide, according to Novo Nordisk. Some 40% of patients with Type 2 diabetes also have CKD, many of whom will eventually require dialysis, Radin noted. Those patients are also more likely to die of cardiovascular death. In Radin’s eyes, the FLOW data make "semaglutide stand out uniquely amongst the options that are available for patients with type 2 diabetes and chronic kidney disease.” The medical director pointed to other pillars of care for CKD, including Bayer’s Kerendia (finerenone), RAS inhibitors and SGLT2 inhibitors, which each come with shortcomings. Kerendia and RAS drugs can't help with glycemic control, Radin said, whereas SGLT2 inhibitors’ glycemic efficacy wanes as kidney function worsens. Safety results in FLOW were on par with semaglutide’s known profile in other clinical trials, Radin said. The Novo exec noted that “significantly fewer” patients in the trial’s semaglutide group experienced a serious adverse event versus the control arm. However, more patients on semaglutide discontinued therapy compared to placebo, driven by gastrointestinal disorders, which is consistent with the GLP-1 class as a whole, Radin noted. Back in March, when Novo unveiled its headline data in CKD, the company said it would file for regulatory approvals in the U.S. and Europe this year to expand semaglutide’s label. While Radin was unable to provide an update on that front, he confirmed that Novo is sticking by its plan to seek updated approvals in kidney disease by the end of 2024. Elsewhere, Novo is far from done with its semaglutide development journey. The company currently has a functional trial underway in patients with Type 2 diabetes who have peripheral arterial disease with symptomatic claudication, which is set to read out at the end of the year, Radin said. In terms of liver health, Novo is also assessing semaglutide’s potential ability to help with fibrosis in patients with fatty liver disease and steatohepatitis in a phase 3 trial. The company is testing oral semaglutide for its ability to help people with early Alzheimer’s disease as well. Novo currently has two trials underway in that space—evoke and evoke+—which are assessing semaglutide in diabetes and non-diabetes Alzheimer’s populations.  Semaglutide is currently approved in its injectable form as Ozempic for Type 2 diabetes and as Wegovy in obesity. Both medicines also boast nods for cardiovascular risk reduction. There's also an oral form of the drug called Rybelsus for diabetes.

The DSMB, based on Phase 3 trial ARES preliminary data, concluded that MaaT013 has a favorable benefit/risk ratio with “high efficacy and low toxicity” in 3rd line aGvHD1. This evaluation confirms previous ones in a similar patient population from the EAP2. Primary endpoint ORR now expected in mid Q4 2024. Good safety pro positive efficacy results with 47% overall survival (OS) at 12 months for all patients with aGvHD (n=111) and 52% for patient subgroup within the EAP with a similar pro those in the ARES trial presented at ASH 2023. Long term follow-up data at EBMT conference 2024. Ongoing recruitment for Phase 2b trial PHOEBUS investigating MaaT033’s impact on OS in allo-HSCT patients. Completion of recruitment in March 2024 for Phase 2a trial PICASSO sponsored by AP-HP3, evaluating MaaT013 in combination with ICI in metastatic melanoma. Results expected end of 2024 or Q1 2025. First positive preclinical data for MaaT034, an AI-generated co-cultured product aimed at improving responses to ICI, presented at SITC conference 2023. New preclinical data at AACR conference 2024. Completion of the largest European cGMP manufacturing facility for Microbiome Ecosystem Therapies with first batches produced. FDA lifted the clinical hold and cleared the IND application for MaaT013 in patients with aGvHD; EMA granted ODD to MaaT033 to improve OS in patients undergoing allo-HSCT. As of December 31, 2023, cash and cash equivalents were €24.3 million, anticipated cash runway now set for end of Q3 2024. Revenues of €2.2 million for 2023, the highest revenues generated from the EAP so far. LYON, France--(BUSINESS WIRE)-- Regulatory News: MaaT Pharma (EURONEXT: MAAT – the “Company”), a clinical-stage biotechnology company and a leader in the development of Microbiome Ecosystem TherapiesTM (MET) dedicated to enhancing survival of patients with cancer, today reported the full-year 2023 annual results and provided a business overview. “As we reflect on the achievements of 2023, I am proud to announce that we have successfully delivered on milestones across our entire pipeline, while being cash conscious. This past year has been pivotal, laying the foundations for the next phase of development for our lead asset MaaT013 with completion of the Phase 3 and readiness for commercialization. We look forward to reaching new milestones in 2024 and anticipate a major inflection point with the publication of the primary endpoint of our Phase 3. By relying on our team and our network of physicians, and continuing to work closely with regulators, we anticipate continuing to create value for our shareholders and make significant progress in bringing new therapeutic options for patients with cancer,” states Hervé Affagard, CEO and co-founder of MaaT Pharma. Pipeline highlights MET-N MaaT013 In hemato-oncology: In April 2023, the U.S. Food and Drug Administration (FDA) lifted the clinical hold and cleared the Investigational New Drug (IND) application for MaaT013 in patients with aGvHD4. The Company has engaged active discussions with prominent US clinicians in the field of stem cell transplantation to explore the most efficient path forward to introduce MaaT013 to patients in the United States. In July 2023, the Company announced that clinical data from its Phase 2 study assessing MaaT013 as a treatment for aGvHD was published in eClinicalMedicine, one of the Lancet Discovery Science suite of journals. In October 2023, the Company announced that the DSMB5 unanimously recommended that the open-label, single arm pivotal Phase 3 ARES clinical trial (NCT04769895), evaluating MaaT013 in aGvHD, continue without modification. The Overall Response Rate (ORR) was superior to pre-defined protocol assumptions. Therefore, the DSMB concluded that the benefit/risk ratio with “high efficacy and low toxicity” was favorable in this patient population. Primary endpoint, gastrointestinal overall response rate (GI-ORR), is now expected mid Q4 2024. In December 2023, the Company presented positive results from the Early Access Program (EAP) in Europe involving 111 patients with aGvHD treated with MaaT013, at the 2023 American Society of Hematology (ASH) Annual Meeting. The GI-ORR was 54% at day 28, positively and significantly impacting overall survival (OS) with 47% OS at 12 months for all patients with aGvHD and 52% for a patient subgroup from the EAP with a similar pro those in the ARES trial with GI-ORR of 61% and 58% of complete responses observed at day 28. As a post period event, in March 2024, the Company announced that it will present for the first time extended results that include OS data after 12 months in more aGvHD patients from its EAP that were treated with MaaT013. The data will be shared during an oral presentation at the 50th Annual Meeting of the European Society for Blood and Marrow Transplantation held in Glasgow, UK, from April 14-17, 2024. As a post period event, the Company announces the launch of a retrospective multicenter trial called CHRONOS in Europe. Its objective is to provide the Company efficacy data for 3rd-line therapies for patients not receiving MaaT013 or any Microbiome intervention. This retrospective study does not impact cash projections as funding is already secured. In immuno-oncology: As a post period event, in March 2024, the Company informed on the completion of patient recruitment for the Phase 2a clinical trial (NCT04988841) sponsored by AP-HP and in collaboration with INRAe6 and Institut Gustave Roussy7, evaluating MaaT013, the Company’s lead product candidate, in combination with immune checkpoint inhibitors (ICI), ipilimumab (Yervoy®) and nivolumab (Opdivo®) in ICI naïve patients with metastatic melanoma. Having reached this key recruitment milestone, the first publication will be submitted at the end of 2024 or in the first quarter of 2025. MaaT033 In hemato-oncology: In April 2023, data from the Phase 1b study (CIMON) with MaaT033, previously communicated during the 64th annual ASH meeting, were also presented at the EBMT 2023 conference. In September 2023, the Company announced that the European Medicines Agency (EMA) had granted orphan drug designation (ODD) to MaaT033, which is aimed at improving overall survival in patients undergoing allo-HSCT8. The EMA recognized the significant benefit that MaaT033 could therefore bring to this patient population. The status offers key benefits including market exclusivity, clinical protocol assistance, waivers or reductions in regulatory fees. In November 2023, the Company announced that the first patient was treated in the Phase 2b trial (PHOEBUS) investigating the efficacy of MaaT033 in improving OS at 12 months in patients with blood cancer that are receiving allo-HSCT. The international, multi-center, randomized, double-blind, placebo-control study (NCT05762211), will be conducted in up to 56 clinical investigation sites and is expected to enroll 387 patients. It is, to date, the largest randomized controlled trial assessing a microbiome therapy in oncology. In November 2023, the Company announced that its ongoing Phase 2b trial, PHOEBUS has been selected for funding of 7.4 million EUR as part of the France 2030 Health Innovation plan, in response to the ‘Innovation in Biotherapy and Bioproduction’ call for projects from the ‘Biotherapies and Bioproduction of Innovative Therapies’ acceleration strategy, operated by Bpifrance (project code: METALLO). Post period the first tranche of 1.8 million EUR was received. In neurodegenerative diseases: In September 2023, the Company announced that the first patient was dosed in the IASO Phase 1b pilot study (NCT05889572) in Amyotrophic Lateral Sclerosis (ALS), also known as Lou Gehrig's disease in the U.S. and Charcot's disease in French-speaking countries. As a post period event, in February 2024, the Company announced that the DSMB reviewed safety data in the IASO trial in the first 8 patients with ALS treated with MaaT033. The DSMB recommended that the trial continue without modifications. MET-C MaaT034 In immuno-oncology: In November 2023, the Company had two presentations at the 38th Society for Immunotherapy of Cancer (SITC) Annual Meeting highlighting in vitro results for its new Artificial Intelligence (AI)-generated lead product, MaaT034, designed to improve responses to immunotherapy for patients with solid tumors. MaaT034 is the first member of the MET-C platform. Data presented at SITC 2023 shows that MaaT034 replicates, at large industrial scale, the richness, and diversity of healthy native-based microbiome ecosystems. The first clinical batches are expected to be produced in 2024 and the first-in-human study is planned for 2025. As a post period event, in March 2024, the Company announced that it will present new in vitro data at the American Association for Cancer Research (AACR) Annual Meeting 2024, taking place on April 5-10 in San Diego, California. Corporate update In February 2023, the Company completed a successful capital increase of approximately €12.7 million with the support of current shareholders. In July 2023, MaaT Pharma joined the Microbiome Therapeutics Innovation Group (MTIG). MTIG is a coalition of companies focused on developing FDA-approved microbiome therapeutics and products to improve medical care, outcomes, and cost-effectiveness. In September 2023, the Company and Skyepharma announced completion of the cGMP manufacturing facility and the transfer of MaaT Pharma’s Production and Development teams to the new site. During 2023 and Q1 2024, MaaT Pharma reinforced its board of directors, executive team, and key functions: Karim Dabbagh as Chairman and Nadia Kamal as Director, both independent. Jonathan Chriqui, as Chief Business Officer and member of the executive management team. Guilhaume Debroas, as Head of Investor Relations. Financial highlights The key financial results for the 2023 full year are as follows: Income Statement In thousands of euros 31 December 2023 31 December 2022 Revenue 2 228 1 430 Cost of Goods Sold (573) (339) Gross Margin 1 655 1 091 Other Income 4 667 4 122 Sales and distribution costs (449) (347) General and administrative costs (4 965) (4 111) Research and development costs (20 851) (14 311) Operating income (expense) (19 943) (13 557) Financial Income 639 45 Financial Expense (413) (201) Net financial income (expense) 226 (156) Income (loss) before income tax (19 717) (13 713) Income tax expense - - Net Income (loss) for the period (19 717) (13 713) Prepared in accordance with international standards, IFRS. Revenues totaled €2.2 million for the year ended December 31, 2023, the highest revenues generated thus far by the Company, which includes compensation invoiced from the Early Access Program in France and for which data was presented at the American Society of Hematology Annual Meeting in December 2023. The gross margin generated by the compassionate access program amounts to €1.7 million. Operating expense amounted to €19.9 million compared with €13.6 million for 2022, an increase of €6.3 million. This increase reflects the growth of research and development costs which have risen from €14.3 million in 2022 to €21.2 million in 2023, representing an overall increase of €6.9 million and consistent with the advancement of clinical and operational activities as detailed in the pipeline highlights’ section above. Other income of €4.7 million includes the R&D tax credit of €3.6 million, an increase of €0.4 million compared with prior year, which amounted to €3.2 million and in line with the growth of research and development activities and eligible expenses. General and administrative expenses amounted to €5.0 million compared with €4.1 million in 2022 reflecting the increase in regulatory advisory costs and expenses to support the early access program. The net loss amounts to €19.7 million for the year ended December 31, 2023, compared with €13.7 million for the year ended December 31, 2022. Average annual employees evolved from 43 in 2022 to 53 in 2023 following the strengthening of the clinical and production and supply chain and to a lesser extent administrative teams. Cash Position As of December 31, 2023, total cash and cash equivalents were €24.3 million, as compared to €31.7 million as of September 30, 2023, and €35.2 million as of December 31, 2022. The net decrease in cash position of €11.0 million between December 31, 2022, and December 31, 2023, is due to the financing of operations for a total of €18.7 million, offset by cash inflows from financing of €8.1 million. Cash inflows from financing reflects the share capital increase in February 2023 of approximately €12.7 million, offset by debt repayments over 2023 €4.2 million. Total financial debt totaled €14.1 million as of December 31, 2023, of which €0.4 million relates to state-backed loans (“PGE”) and €6.1 million of lease liabilities, which includes future contractual payments due to Skyepharma for the use of the manufacturing facility completed in 2023. Based on the development plans and corresponding cash needs, the Company believes it has sufficient cash to finance operations to the end of Q3.2024 extending the cash runway by three months compared to prior communications as a result of a voluntary slowdown in headcount growth, optimization of its manufacturing plan and prioritizing expenses to support on the roll out of the Phase 2b trial PHOEBUS in France and Germany (approved countries) and finalizing recruitment into the Phase 3 ARES trial in Europe. The Company has active discussions ongoing to finance operations beyond the end of Q3.2024 and remains confident in extending its cash runway. Note: This press release contains financial data approved by the Board of Directors on March 27, 2024, based on the financial statements for the year ended December 31, 2023. The audit is in progress at the date of this communication. Upcoming financial communication* May 14, 2024: Publication of revenues for Q1 2024 May 28, 2024: Annual General Shareholders Meeting September 19, 2024: Publication of half year financial results H1 November 5, 2024: Publication of revenues for Q3 2024 *Indicative calendar that may be subject to change. Upcoming investor conferences participation April 15-17, 2024 – Kempen Life Sciences Conference, Amsterdam June 11-12, 2024 – Portzamparc Mid & Small Caps 2024 Conference June 25-27, 2024 – Stifel European Healthcare Summit Lyon Upcoming scientific conference participation April 5-10, 2024 - American Association for Cancer Research (AACR) Annual Meeting 2024, San Diego April 14-17, 2024 – 50th Annual meeting of the European Bone Marrow Transplant (EBMT), Glasgow The Company’s universal registration document, which includes the annual financial report, will be available on MaaT Pharma’s website on 02/04/2024: --- About MaaT Pharma MaaT Pharma, a clinical stage biotechnology company, has established a complete approach to restoring patient-microbiome symbiosis in oncology. Committed to treating cancer and graft-versus-host disease (GvHD), a serious complication of allogeneic stem cell transplantation, MaaT Pharma has launched, in March 2022, an open-label, single arm Phase 3 clinical trial in patients with acute GvHD, following the achievement of its proof of concept in a Phase 2 trial. Its powerful discovery and analysis platform, gutPrint®, enables the identification of novel disease targets, evaluation of drug candidates, and identification of biomarkers for microbiome-related conditions. The company’s Microbiome Ecosystem Therapies are produced through a standardized cGMP manufacturing and quality control process to safely deliver the full diversity of the microbiome, in liquid and oral formulations. MaaT Pharma benefits from the commitment of world-leading scientists and established relationships with regulators to support the integration of the use of microbiome therapies in clinical practice. MaaT Pharma is listed on Euronext Paris (ticker: MAAT). Forward-looking Statements All statements other than statements of historical fact included in this press release about future events are subject to (i) change without notice and (ii) factors beyond the Company’s control. These statements may include, without limitation, any statements preceded by, followed by or including words such as “target,” “believe,” “expect,” “aim,” “intend,” “may,” “anticipate,” “estimate,” “plan,” “project,” “will,” “can have,” “likely,” “should,” “would,” “could” and other words and terms of similar meaning or the negative thereof. Forward-looking statements are subject to inherent risks and uncertainties beyond the Company’s control that could cause the Company’s actual results or performance to be materially different from the expected results or performance expressed or implied by such forward-looking statements. 1 acute Graft versus Host Disease 2 Early Access Program 3 Assistance Publique - Hôpitaux de Paris is the leading university hospital center in Europe 4 acute Graft Versus Host disease 5 DSMB = Data Safety Monitoring Board 6 National Research Institute for Agriculture, Food and the Environment 7 Leading Cancer Centre in Europe 8 Allo-HSCT : Allogeneic hematopoietic stem cell transplantation