PXL-770

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.

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.