In vitro fecal microbiota modulation properties of pectin and xyloglucan from hazelnut (Corylus avellana L.) skin, an industrial byproduct, and their incorporation into biscuit formula

Article

作者: Sarıoğlan, İhsan ; Arioglu-Tuncil, Seda ; Tunçil, Yunus E ; Gonzales, Miguel Angel Alvarez ; Lindemann, Stephen R ; Alkay, Zuhal ; Dertli, Enes ; Tunçil, Yunus E. ; Lindemann, Stephen R. ; Esen, Emine

The aim of this study was to extract water-soluble dietary fibers (WSDF_skin), pectin (PEC_skin), and xyloglucan (XG_skin) from hazelnut skin and to determine their impacts on colonic microbiota and metabolic function. WSDF_skin, PEC_skin, and XG_skin were extracted by water, acid, and alkali treatments, respectively. Monosaccharide analysis revealed WSDF_skin and PEC_skin were dominated by uronic acids, while the XG_skin was found to contain xyloglucan- and pectin-associated sugars. In vitro fecal fermentation analysis showed that WSDF_skin, PEC_skin, and XG_skin are fermented to different microbial short-chain fatty acid profiles by identical microbiota. 16S rRNA sequencing demonstrated that PEC_skin promoted Faecalibacterium prausnitzii and Lachnospiraceae related operational taxonomic units (OTUs), which are recognized as beneficial members of the human gut, whereas WSDF_skin and XG_skin stimulated Bacteroides OTUs. Interestingly, increased abundances of F. prausnitzii and Lachnospiraceae OTUs in PEC_skin were higher than those in commercially available pectin. Finally, PEC_skin and XG_skin were tested in a biscuit model and the results showed that either PEC_skin or XG_skin can be incorporated into biscuit formulations without impacting physical, textural, and sensory properties of the final product. Overall, our results demonstrated that hazelnut skin, an industrial byproduct, can be utilized for the production of functional dietary fibers, especially pectin, to improve colonic health.

2024-10-01·International Immunopharmacology

Pectolinarigenin targeting FGFR3 alleviates osteoarthritis progression by regulating the NF-κB/NLRP3 inflammasome pyroptotic pathway

Article

作者: Jiang, Peng ; Zhou, Xiaonan ; Yang, Yue ; Bai, Lunhao

OBJECTIVEOsteoarthritis (OA) is a chronic degenerative disease characterized by cartilage degeneration, involving inflammation, pyroptosis, and degeneration of the extracellular matrix (ECM). Pectolinarigenin (PEC) is a natural flavonoid with antioxidant, anti-inflammatory and anti-tumor properties. This study aims to explore the potential of PEC in ameliorating OA progression and its underlying mechanisms.METHODSChondrocytes were exposed to 10 ng/mL IL-1β to simulate OA-like changes. The effect of PEC on IL-1β-treated chondrocytes was assessed using ELISA, western blot, and immunofluorescence. The mRNA sequencing (mRNA-seq) was employed to explore the possible targets of PEC in delaying OA progression. The OA mouse model was induced through anterior cruciate ligament transection (ACLT) and divided into sham, ACLT, ACLT+5 mg/kg PEC, and ACLT+10 mg/kg PEC groups. Micro-computed tomography and histological analysis were conducted to confirm the beneficial effects of PEC on OA in vivo.RESULTSPEC mitigated chondrocyte pyroptosis, as evidenced by reduced levels of pyroptosis-related proteins. Additionally, PEC attenuated IL-1β-mediated chondrocyte ECM degradation and inflammation. Mechanistically, mRNA-seq showed that FGFR3 was a downstream target of PEC. FGFR3 silencing reversed the beneficial effects of PEC on IL-1β-exposed chondrocytes. PEC exerted anti-pyroptotic, anti-ECM degradative, and anti-inflammatory effects through upregulating FGFR3 to inhibit the NF-κB/NLRP3 pyroptosis-related pathway. Consistently, in vivo experiments demonstrated the chondroprotective effects of PEC in OA mice.CONCLUSIONPEC alleviate OA progression by FGFR3/NF-κB/NLRP3 pathway mediated chondrocyte pyroptosis, ECM degradation and inflammation, suggesting the potential of PEC as a therapeutic agent for OA.

2024-08-01·International Journal of Biological Macromolecules

Development of biopolymer films loaded with fluconazole and thymol for resistant vaginal candidiasis

Article

作者: Argenta, Débora Fretes ; Parize, Alexandre Luis ; Caon, Thiago ; Saatkamp, Rodrigo Henrique ; Sanches, Mariele Paludetto ; da Rosa Monte Machado, Gabriella ; Conte, Júlia ; Kretzer, Iara Fabrícia

Vulvovaginal candidiasis (VVC) is an opportunistic infection caused by a fungus of the Candida genus, affecting approximately 75 % of women during their lifetime. Fungal resistance cases and adverse effects have been the main challenges of oral therapies. In this study, the topical application of thin films containing fluconazole (FLU) and thymol (THY) was proposed to overcome these problems. Vaginal films based only on chitosan (CH) or combining this biopolymer with pectin (PEC) or hydroxypropylmethylcellulose acetate succinate (HPMCAS) were developed by the solvent casting method. In addition to a higher swelling index, CH/HPMCAS films showed to be more plastic and flexible than systems prepared with CH/PEC or only chitosan. Biopolymers and FLU were found in an amorphous state, contributing to explaining the rapid gel formation after contact with vaginal fluid. High permeability rates of FLU were also found after its immobilization into thin films. The presence of THY in polymer films increased the distribution of FLU in vaginal tissues and resulted in improved anti-Candida activity. A significant activity against the resistant C. glabrata was achieved, reducing the required FLU dose by 50 %. These results suggest that the developed polymer films represent a promising alternative for the treatment of resistant vulvovaginal candidiasis, encouraging further studies in this context.

项与 PEC Direct 相关的新闻（医药）

2024-10-03

·poxelpharma

Poxel Reports Financial Results for Full Year 2023 and Provides Corporate Update

Agreement with OrbiMed to monetize a portion of TWYMEEG® Royalties for USD 50 million in the form of bonds issuance In return OrbiMed to obtain the royalties received by Poxel from sales by Sumitomo Pharma of TWYMEEG® in Japan for a total amount of USD 100 million Proceeds from the OrbiMed’s bonds issuance will be used to reduce the Company's debt towards IPF Partners and the PGE1 banks and to support its strategic plan in rare diseases, while pursuing partnership discussions for its products Following the non-dilutive financing agreement with OrbiMed, cash runway extension until end of 2025, including the full residual drawdown of the equity-linked financing facility put in place with IRIS The management team will host webinars today; October 3, 2024, at: 6:00 pm CEST, Paris time (12:00 pm ET) in French and 1:15 pm ET, New York time (7:15 pm CEST) in English. A presentation will be available on Poxel's website in the Investor section. To register for the webinar in French: https://app.livestorm.co/newcap-1/poxel-presentation-des-resultats-financiers-pour-lannee-2023?type=detailed To register for the webinar in English: https://app.livestorm.co/newcap-1/poxel-presentation-of-financial-results-for-full-year-2023?type=detailed LYON, France--(BUSINESS WIRE)-- Regulatory News: POXEL SA (Euronext: POXEL - FR0012432516), a clinical stage biopharmaceutical company developing innovative treatments for serious chronic diseases with metabolic pathophysiology, including non-alcoholic steatohepatitis (MASH2) and rare metabolic disorders, today announced its results for the year ended December 31, 2023, and provided a corporate update. “With the royalty monetization agreement concluded with OrbiMed, we are now focused on the plans for each of our products. First, as we recovered the rights for countries, other than Japan, covered under the agreement with Sumitomo Pharma, we have already engaged in partnering discussions to develop and market Imeglimin in China, the world's second-largest type 2 diabetes market, and other regions where Imeglimin can potentially be quickly developed and approved. We are also looking forward to the results of the discussions by Sumitomo Pharma with the regulatory authorities in Japan on revising TWYMEEG® package insert for type 2 diabetic patients with renal impairment, anticipated in FY 20243. For PXL770 and PXL065, we aim to finalize discussions with several potential partners before deciding on our investment decisions and development strategies,” stated Thomas Kuhn, Chief Executive Officer of Poxel. TWYMEEG® (Imeglimin) For the quarter ended June 2024, TWYMEEG® gross sales in Japan increased by 62% to JPY 1.7 billion (EUR 10.1 million)4 over the prior quarter sales of JPY 1.1 billion (EUR 6.6 million)5 as reported by Sumitomo Pharma. For its FY 20243, Sumitomo Pharma forecasts6 gross sales for TWYMEEG® of JPY 11.3 billion (EUR 69.1 million)2 which would represent a 150% increase over FY 2023 TWYMEEG® gross sales. During Sumitomo Pharma FY 20243, Poxel expects TWYMEEG® net sales in Japan to reach at least JPY 5 billion (EUR 31.3 million)4 entitling Poxel to receive 10% royalties on all TWYMEEG® net sales and a sales-based payment of JPY 500 million (EUR 3.1 million)4. Based on this FY 2024 forecast, TWYMEEG® net sales could also reach JPY 10 billion (EUR 62.6 million)4 entitling Poxel to receive 12% royalties on all TWYMEEG® net sales and a second sales-based payment of JPY 1 billion (EUR 6.3 million)4. Based on the recent royalty monetization agreement with OrbiMed, these proceeds for FY2024 will go the reimbursement of the bonds issuance. Beyond 2024, Poxel expects to receive escalating double-digit royalties as well as additional sales-based payments upon achievement of contractually based sales thresholds. As announced on August 7, 2024, topline results obtained from the post-marketing clinical study, TWINKLE (TWYMEEG® in diabetic patients with renal impairment: A post-marketing long-term study) conducted by Sumitomo Pharma in Japanese type 2 diabetic patients with renal impairment confirmed TWYMEEG®’s safety and tolerability profile, which is consistent with prior clinical studies in the general type 2 diabetes population. Based on these results, Sumitomo Pharma is planning to conduct discussions with the regulatory authorities in Japan during its FY 20243, on revising TWYMEEG® package insert for patients with renal impairment with eGFR (estimated glomerular filtration rate) less than 45 ml/min/1.73m2. In parallel of the non-dilutive financing agreement with OrbiMed, Poxel recovered the Imeglimin rights for Asian countries other than Japan7 from Sumitomo Pharma8. The Company has already initiated discussions to develop and market Imeglimin in China, the world's second largest type 2 diabetes market. Royalty monetization agreement based on TWYMEEG® sales with OrbiMed, and concurrent debt restructuring with IPF Partners and PGE banks9 Under the terms of the agreement, Poxel received a gross upfront payment of USD 50 million from the OrbiMed funds in exchange for an issuance of its bonds in the same aggregate amount. From such proceeds, a deposit of USD 7.5 million has been made by the Company into a deposit account, from which USD 1.25 million will be withdrawn quarterly and paid in partial repayment of the bonds issued to OrbiMed, until net sales of TWYMEEG® reach JPY 5 billion (USD 31.3 million4), at which point OrbiMed will begin to receive sales-based payments and royalties (anticipated in early 2025, based on the expected achievement of this sales threshold by the end of 20243). The residual amount of the deposit will then be available to the Company, in addition to the USD 42.5 million deposit received upon signature of the agreement. For the bonds issued by Poxel, the OrbiMed funds will receive (i) royalties payable by Sumitomo Pharma on net sales of TWYMEEG® in Japan, net of Poxel's obligation to Merck Serono, (ii) sales-based payments due by Sumitomo Pharma in connection with the commercialization of TWYMEEG® in Japan, and (iii) a portion of the cash flows received by the Company, in the event of partnership for the development and commercialization of Imeglimin in Asian countries other than Japan7. The agreement will expire, and the bonds deemed repaid once OrbiMed receives a capped return equivalent to 2 times its investment, i.e. USD 100 million, plus specified expenses, if any. Upon such repayment, Poxel will regain full rights to TWYMEEG® royalties in Japan and to any sales-based commercial payments and will use the majority of these proceeds to repay the outstanding amount owed to IPF Partners. Part of the bonds issuance amount from this transaction was used to reduce significantly the Company's debt towards IPF Partners and the PGE banks: EUR 23.7 million for partial repayment of IPF debt, reducing it to EUR 12.3 million; and EUR 2.8 million for partial repayment of the debt to the banks that granted the PGE Loan, reducing it to EUR 3 million. Consequently, the Company amended its agreements respectively with IPF Partners and the banks that granted a PGE loan for the repayment of the outstanding principal of each of these debts. Financial Statements for Full Year 2023 (IFRS Standards) Income statement *Net of R&D tax credit. The audit procedures are ongoing. Poxel reported revenues of EUR 2.0 million for the year ended December 31, 2023, as compared to EUR 0.674 thousand during the corresponding period in 2022. Revenues for 2023 mostly reflects the JPY 313 million (EUR 2.0 million) of royalty revenue from Sumitomo Pharma, which represents 8% of TWYMEEG® net sales in Japan. Cost of sales amounted to EUR 1.980 million, corresponding to the 8% royalties on net sales of Imeglimin in Japan due to Merck Serono, as part of the Merck Serono license agreement. R&D expenses totaled EUR 3.8 million in 2023, as compared to EUR 12.4 million in 2022. The 2023 decrease primarily reflects the end, in 2022, of the positive Phase 2 DESTINY study evaluating PXL065 in MASH. R&D costs are net of the R&D Tax Credit (CIR) and other subsidies that resulted in income of EUR 0.6 million in 2023, as compared to EUR 1.5 million in 2022. As presented in the Company’s half-yearly financial results 2023, the amount of amortization and depreciation of intangible assets includes exclusively the impairment of PXL065 for EUR 16.6 million. This impairment translates the Company's need to obtain additional financing to pursue its development plan in MASH or ALD, its current market capitalization and the macroeconomic context in which it operates. However, the Company considers that the potential of PXL065 in its targeted indications remains unchanged and very promising. General and administrative expenses totaled EUR 8.4 million in 2023, as compared to EUR 9.4 million in 2022. The financial loss amounted to EUR 6.3 million in 2023, as compared to a loss of EUR 9.5 million in 2022. It primarily reflects the interests attached to the Company indebtedness. The net result for the financial period ending December 31, 2023, was a net loss of EUR 35.1 million, as compared to a net loss of EUR 31.4 million in 2022. Cash Following the non-dilutive financing agreement with OrbiMed, and according to Poxel's current forecasts, including in particular: The Company’s cash position estimated, as of August 31st, 2024, at EUR 2,9 million the net upfront of USD 42.5 million (EUR 38,1 million4) from the monetization of royalties from TWYMEEG® sales; the partial redemption of the IPF Partners bond loan and the PGE loans for a total amount of EUR 26,5 million the advisory fees linked to the transaction the full residual drawdown of the equity-linked financing facility put in place with IRIS10;and the anticipated business plan including strict control of its operating expenses; the Company expects that its resources will be sufficient to finance its operations and capital expenditures until the end of 2025. 2023 Universal Registration Document The Company will make its 2023 Universal Registration Document in French available to the public and file it with the Autorité des marchés financiers no later than October 11, 2024. A translation in English will be available later on the Company’s website. Planned Presentations and Participation at the Following Upcoming Events: H.C. Wainwright 8th Annual MASH Virtual Conference, October 7, 2024 (virtual) Thomas Kuhn, CEO, will be available for one-on-one meetings. Bio Europe, November 4 – 6th 24 (in-person) Tejdeep Bawa, Head of Business Development, will be available for one-on-one in-person meetings. Next Financial Press Releases: 2024 Third Quarter Financial Update, on November 6, 2024 2024 First Half Results, on December 9, 2024 About Poxel SA Poxel is a clinical stage biopharmaceutical company developing innovative treatments for chronic serious diseases with metabolic pathophysiology, including non-alcoholic steatohepatitis (NASH) and rare disorders. For the treatment of NASH, PXL065 (deuterium-stabilized R-pioglitazone) met its primary endpoint in a streamlined Phase 2 trial (DESTINY-1). In rare diseases, development of PXL770, a first-in-class direct adenosine monophosphate-activated protein kinase (AMPK) activator, is focused on the treatment of adrenoleukodystrophy (ALD) and autosomal dominant polycystic kidney disease (ADPKD). TWYMEEG® (Imeglimin), Poxel’s first-in-class product that targets mitochondrial dysfunction, is marketed for the treatment of type 2 diabetes in Japan by Sumitomo Pharma and Poxel expects to receive royalties and sales-based payments. Poxel has a strategic partnership with Sumitomo Pharma for Imeglimin in Japan. Listed on Euronext Paris, Poxel is headquartered in Lyon, France, and has subsidiaries in Boston, MA, and Tokyo, Japan. For more information, please visit: www.poxelpharma.com 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. The Company does not endorse or is not otherwise responsible for the content of external hyperlinks referred to in this press release. Glossary You will find below a list of words and/or expressions that are used in this press release or in Poxel’s communication, with the aim to bring clarification and transparency: Sumitomo Pharma fiscal year runs from April to March. As an example, Fiscal Year 2023 is April 1, 2023, through March 31, 2024. TWYMEEG® royalties: As per the Sumitomo Pharma’s agreement, Poxel is entitled to receive royalties from the sales of TWYMEEG® (Imeglimin) in Japan TWYMEEG® royalties are calculated on net sales, while Sumitomo Pharma communicates only TWYMEEG® gross sales. Poxel entitled to receive escalating royalties of 8-18% on TWYMEEG® net sales from Sumitomo Pharma. Positive net royalties: refers to royalties Poxel receives from TWYMEEG® net sales after paying Merck Serono the first 8%, once Poxel starts to receive 10% royalties upon TWYMEEG® net sales exceeding JPY 5 billion in a fiscal year. 1 State-guaranteed loan in response to the health crisis in 2020 2 Metabolic dysfunction-associated steatohepatitis also called NASH. 3 Sumitomo Pharma fiscal year 2024 ends March 31, 2025 4 Converted at the exchange rate on October 2, 2024 5 Converted at the exchange rate on March 31, 2024 6 As per Sumitomo Pharma FY2024 forecast published on May 14, 2024 7 China, South Korea, Taiwan, Indonesia, Vietnam, Thailand, Malaysia, The Philippines, Singapore, Republic of the Union of Myanmar, Kingdom of Cambodia and Lao People's Democratic Republic. 8 In accordance with the Sumitomo Pharma license agreement, Poxel is entitled to receive escalating royalties of 8 - 18% on net sales of TWYMEEG 9 For more information: https://www.poxelpharma.com/en_us/investors/news-events/press-releases/detail/269/poxel-announces-agreement-with-orbimed-to-monetize-a 10 Since March 31, 2023, 14 additional tranches have been drawn down for a total of EUR 7.3 million. 6 tranches are currently secured for a total of EUR 3 million. and an additional amount of 1.2 million euros could be drawn down by the Company depending on the liquidity and exposure conditions under the contract.. View source version on businesswire.com: https://www.businesswire.com/news/home/20241003313137/en/ Investor relations / Media NewCap Nicolas Fossiez, Aurélie Manavarere / Arthur Rouillé investor@poxelpharma.com +33 1 44 71 94 94 Source: Poxel Released October 3, 2024

引进/卖出临床结果临床2期财报

2024-08-07

·Business Wire

Sumitomo Pharma and Poxel Announce Topline Results from Post-Marketing Clinical Study on TWYMEEG® for the Treatment of Type 2 Diabetes in Japan

OSAKA, Japan & LYON, France--( BUSINESS WIRE )--Regulatory News: Sumitomo Pharma Co., Ltd. (Head Office: Osaka, Japan; Representative Director, President and CEO: Toru Kimura) and POXEL SA (Euronext : POXEL - FR0012432516), a clinical stage biopharmaceutical company developing innovative treatments for chronic serious diseases with metabolic pathophysiology, including non-alcoholic steatohepatitis (NASH) and rare metabolic disorders, announced today topline results obtained from a post-marketing clinical study, TWINKLE ( TW YMEEG ® in d i abetic patients with re n al impairment: A post-mar k eting l ong-t e rm study) (“ the Study ”), in Japanese type 2 diabetic patients with renal impairment for TWYMEEG ® Tablets 500 mg (generic name: imeglimin hydrochloride, “ the Drug ”) being sold in Japan, based on the Risk Management Plan. The Study was an open-label, uncontrolled, long-term study in 60 Japanese type 2 diabetic patients with renal impairment, who had no experience of type 2 diabetes treatment other than diet and exercise therapy or insufficient glycemic management in monotherapy with a hypoglycemic agent excluding insulin formulation. The Drug was administered at 500 mg twice-daily to patients with moderate and severe renal impairment, characterized by an estimated glomerular filtration rate (eGFR) between 15 mL/min/1.73 m 2 or higher to less than 45 mL/min/1.73 m 2 , or at 500 mg once-daily to patients with end-stage renal disease, characterized by an eGFR less than 15 mL/min/1.73m 2 , in monotherapy or in combination therapy with a hypoglycemic agent excluding insulin formulation, to evaluate safety and tolerability when administered orally for 52 weeks. The Drug was observed to be safe and well tolerated in Japanese type 2 diabetic patients with renal impairment and no significant differences were found in the incidence of adverse events, their types and severities in this study from previous clinical studies. Specifically, most of the adverse events were mild or moderate in severity. The incidence of serious adverse events was 16.7% (10 of 60 subjects) and causality with the Drug could be ruled out in all cases. Incidence of adverse events leading to study treatment discontinuation was also limited (4 of 60 subjects). At present, administration of the Drug is not recommended for patients with renal impairment with eGFR less than 45 mL/min/1.73m 2 . Based on the results of the Study, Sumitomo Pharma is planning to conduct discussions with the regulatory authorities in Japan, on revising the package insert in fiscal 2024 1 for patients with renal impairment with eGFR less than 45 mL/min/1.73m 2 . About TWYMEEG ® TWYMEEG ® is the first agent in a class of tetrahydrotriazine-containing molecules. It is thought that the Drug shows a glucose lowering effect by both a pancreatic action that promotes glucose concentration-dependent insulin secretion and an extra-pancreatic action that improves glucose metabolism in the liver and skeletal muscle (suppression of gluconeogenesis and improvement of glucose uptake), through acting on mitochondria. The Drug has the potential to prevent endothelial and diastolic dysfunction, which could provide protective effects on micro- and macrovascular defects induced by diabetes. It may also have protective effects on pancreatic β cell survival and function. Owing to its unique mechanism of action, the Drug is widely used for glucose lowering in the treatment of type 2 diabetes, either as monotherapy or as an add-on to other therapies for this purpose. In October 2017, Sumitomo Pharma concluded a development and commercialization partnership agreement for Japan, Chinese mainland, Taiwan, Korea and nine Southeast Asian countries with Poxel SA (Head Office: Lyon, France; CEO: Thomas Kuhn) and started selling the Drug in Japan in September 2021. About Sumitomo Pharma Co., Ltd. Sumitomo Pharma Group defines its Mission as "To broadly contribute to society through value creation based on innovative research and development activities for the betterment of healthcare and fuller lives of people worldwide." By pouring all our efforts into the research and development, the Group aims to provide innovative and valuable pharmaceutical and healthcare solutions to people in Japan and around the world in order to realize its Mission. The Group will remain committed to research and development with the aim of continually discovering excellent pharmaceuticals, regenerative medicine/cell therapy, non-pharmaceutical products, and others with a focus on the Psychiatry & Neurology and Oncology as priority disease areas. For more detail, please visit our website. ( https://www.sumitomo-pharma.com ) About Poxel SA Poxel is a clinical stage biopharmaceutical company developing innovative treatments for chronic serious diseases with metabolic pathophysiology , including non-alcoholic steatohepatitis (NASH) and rare disorders. For the treatment of NASH, PXL065 (deuterium-stabilized R -pioglitazone) met its primary endpoint in a streamlined Phase 2 trial (DESTINY-1). In rare diseases, development of PXL770 , a first-in-class direct adenosine monophosphate-activated protein kinase (AMPK) activator, is focused on the treatment of adrenoleukodystrophy (ALD) and autosomal dominant polycystic kidney disease (ADPKD). TWYMEEG ® (Imeglimin), Poxel’s first-in-class product that targets mitochondrial dysfunction, is marketed for the treatment of type 2 diabetes in Japan by Sumitomo Pharma and Poxel expects to receive royalties and sales-based payments. Poxel has a strategic partnership with Sumitomo Pharma for Imeglimin in Japan, China, and eleven other Asian countries. Listed on Euronext Paris, Poxel is headquartered in Lyon, France, and has subsidiaries in Boston, MA, and Tokyo, Japan. For more information, please visit: www.poxelpharma.com 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. The Company does not endorse or is not otherwise responsible for the content of external hyperlinks referred to in this press release. 1 Sumitomo Pharma fiscal year 2024 ends March 31, 2025.

临床结果临床2期上市批准细胞疗法

2024-07-15

·Business Wire

Poxel Provides an Update on Its Financial Position for the Second Quarter and First Half of 2024 and Announces the Rescheduling of Its Annual General Meeting

LYON, France--( BUSINESS WIRE )--Regulatory News: POXEL SA (Euronext : POXEL - FR0012432516), a clinical stage biopharmaceutical company developing innovative treatments for chronic serious diseases with metabolic pathophysiology, including non-alcoholic steatohepatitis (NASH) and rare metabolic disorders, today publishes its cash position, provides an update on its financial situation for the second quarter and first half of 2024, ending June 30, 2024, reviews its activities on June 30, 2024 and announces the rescheduling of its Annual General Meeting 2024, in view of the postponement of the closing of its social and consolidated financial statements for the year ended December 31, 2023. Thomas Kuhn, Chief Executive Officer of Poxel , stated: “ TWYMEEG ® 's commercialization in Japan continues to gain momentum, supported by many scientific papers and articles in Japanese journals, some of which were or will be presented at international scientific congresses. In parallel with the expected finalization of our exclusive financing discussions based on the monetization of royalties from TWYMEEG ® sales in Japan, the additional protection granted to TWYMEEG ® until 2036 potentially represents a further opportunity for the product”. TWYMEEG ® (Imeglimin) Clinical development, intellectual property and scientific publications The Long-Term, 52-week, Open-label, Phase 4 Study conducted by Sumitomo Pharma of Imeglimin in Japanese Type 2 Diabetic Patients with Renal Impairment is currently ongoing in Japan to strengthen TWYMEEG ® profile in this key subpopulation. Top line results are expected soon. On May 29, 2024, the Japanese Patent Office approved the remaining two PTE applications, granting Poxel an extension to patents n°5542066 and n°5758010, protecting Imeglimin’s synthesis process. Several scientific presentations on TWYMEEG’s ® innovative mechanism of action and potential additional benefits, in addition to its anti-diabetic activity were shared at the 67 th Annual Meeting of the Japanese Diabetes Society (JDS), held in Tokyo, Japan, from May 17 to 19, 2024, and at the 84 th Scientific Sessions of the American Diabetes Association in Orlando, Florida. New preclinical and clinical data will be presented at the 60 th Annual Congress of the European Association for the Study of Diabetes (EASD). Cash and cash equivalents in the second quarter and first half of 2024 As of June 30, 2024, total cash and cash equivalents amounted to EUR 2.8 million (USD 3 million 1 ), compared with EUR 2.3 million (USD 2.6 million 2 ) as of December 31, 2023 (unaudited data). Net financial debt (excluding IFRS16 impacts and derivative debts) amounted to EUR 46.6 million as of June 30, 2024, compared with EUR 45.6 million as of December 31, 2023 (unaudited data). EUR (thousands) Q2 2024 Q4 2023 Cash 2,812 2,341 Cash equivalents - - Cash and cash equivalents 2,812 2,341 Unaudited data. Finalization of exclusive discussions with a leading investor to monetize royalties from sales of TWYMEEG ® (Imeglimin) in Japan and cash runway With the priority objective of relaunching its R&D activities and executing its strategic plan in rare diseases, the Company has focused in recent months on securing additional financing, in particular non-dilutive solutions. In this context, the Company is currently finalizing exclusive negotiations with a leading investor to monetize royalties from TWYMEEG ® (Imeglimin) sales in Japan. In addition, the Company is in advanced discussions – in some cases on an exclusive basis – with several potential partners for each of its three products: Imeglimin, for several countries not covered by its agreement with Sumitomo Pharma, PXL065 and PXL770. Based on: its cash position on June 30, 2024, tranches already drawn 3 or fully available as of the date of this press release under the equity-linked financing facility with IRIS, no research and development expenses, and a strict control of operating expenses, Poxel expects that its resources, including funds available to it, will be sufficient to maintain its operations and capital expenditure until completion of the current process to monetize royalties from sales of TWYMEEG ® (Imeglimin) in Japan. Rescheduling of the Annual General Meeting 2024 In view of this transaction, which is key for the Company to continue its operations, and which will be taken into consideration for the closing of its social and consolidated financial statements for the year ending December 31, 2023, Poxel announces that it requested and received confirmation from the Lyon Commercial Court of the rescheduling of its Annual General Meeting, which must be held before December 31, 2024. Once its social and consolidated financial statements are approved, Poxel will inform the market and its shareholders of its new financial calendar for 2024, including the new date of the General meeting, as soon as possible. Upcoming presentation and participation of the Company in an event 3 rd H.C. Wainwright Kidney Conference, July 15, 2024: A virtual presentation of the Company is scheduled at 4 pm CEST - French time (10 am ET, New York time) and will focus on PXL770, a novel direct activator of adenosine monophosphate-activated protein kinase (AMPK), for the treatment of autosomal dominant polycystic kidney disease (ADPKD). Thomas Kuhn, Chief Executive Officer, will be available for one-to-one interviews on the same day. About Poxel SA Poxel is a clinical stage biopharmaceutical company developing innovative treatments for chronic serious diseases with metabolic pathophysiology , including non-alcoholic steatohepatitis (NASH) and rare disorders. For the treatment of NASH, PXL065 (deuterium-stabilized R -pioglitazone) met its primary endpoint in a streamlined Phase 2 trial (DESTINY-1). In rare diseases, development of PXL770 , a first-in-class direct adenosine monophosphate-activated protein kinase (AMPK) activator, is focused on the treatment of adrenoleukodystrophy (ALD) and autosomal dominant polycystic kidney disease (ADPKD). TWYMEEG ® (Imeglimin), Poxel’s first-in-class product that targets mitochondrial dysfunction, is marketed for the treatment of type 2 diabetes in Japan by Sumitomo Pharma and Poxel expects to receive royalties and sales-based payments. Poxel has a strategic partnership with Sumitomo Pharma for Imeglimin in Japan, China, and eleven other Asian countries. Listed on Euronext Paris, Poxel is headquartered in Lyon, France, and has subsidiaries in Boston, MA, and Tokyo, Japan. For more information, please visit: www.poxelpharma.com 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. There can be no assurance that the Company will complete any of the foregoing transactions or that it will do so on a timely basis. The Company does not endorse or is not otherwise responsible for the content of external hyperlinks referred to in this press release. Glossary You will find below a list of words and/or expressions that are used in this press release or in Poxel’s communication, with the aim to bring clarification and transparency: Sumitomo Pharma fiscal year runs from April to March. As an example, Fiscal Year 2023 runs from April 1, 2023, through March 31, 2024. TWYMEEG ® royalties: As per the Sumitomo Pharma’s agreement, Poxel is entitled to receive royalties from the sales of TWYMEEG ® (Imeglimin) in Japan Sumitomo Pharma communicates gross sales of TWYMEEG ® , while TWYMEEG ® royalties are calculated on net sales. Net sales represent the amount of gross sales to which are deducted potential rebates, allowances, and costs such as prepaid freight, postage, shipping, customs duties and insurance charges. Poxel is entitled to receive escalating royalties of 8-18% on TWYMEEG ® net sales from Sumitomo Pharma. Positive net royalties : as part of the Merck Serono licensing agreement, Poxel will pay Merck Serono a fixed 8% royalty based on the net sales of TWYMEEG ® , independent of the level of sales. All royalties that Poxel receives from TWYMEEG ® net sales above that 8% level are considered as positive net royalties. Net royalties will therefore be positive for Poxel when TWYMEEG ® net sales exceed JPY 5 billion in a fiscal year and royalties reach 10% and above. __________________________________ 1 Converted at the exchange rate on June 30, 2024 2 Converted at the exchange rate on December 31, 2023 3 Since March 31, 2023, 11 additional tranches have been drawn for a total amount of EUR 5.8 million.

临床2期上市批准引进/卖出

100 项与 PEC Direct 相关的药物交易

登录后查看更多信息