Poxel

Earnings Release • May 28, 2025

New Clinical and Scientific Data on TWYMEEG® to be Presented at the 68th Annual Meeting of the Japan Diabetes Society

LYON, France, May 28, 2025 – POXEL SA (Euronext : POXEL - FR0012432516), a clinical stage biopharmaceutical company developing innovative treatments for chronic serious diseases with metabolic pathophysiology, including metabolic dysfunction-associated steatohepatitis (MASH) and rare metabolic disorders, today announces that new clinical and scientific data on TWYMEEG® will be presented at the 68th Annual Meeting of the Japan Diabetes Society (JDS 2025), taking place from May 29 to 31, 2025, in Okayama, Japan.

A total of 15 presentations 1 , including results from 7 clinical trials, 3 post-hoc analyses 2 and 5 non-clinical studies supported by Sumitomo Pharma, will be delivered by leading Japanese diabete experts. These findings further confirm TWYMEEG®'s efficacy in monotherapy and combination therapies, safety, dual mechanism of action and potential benefits in specific patient populations. Main topics include:

• TWINKLE (TWYMEEG® in diabetic patients with renal impairment: A postmarketing long-term study) study (Phase 4 study): confirmation of TWYMEEG® efficacy and safety in diabetic patients with renal impairment
• FAMILIAR Study: confirmation of TWYMEEG® efficacy and safety in combination with DPP-4 inhibitors
• PARADIME Clamp: confirmation of TWYMEEG® dual mechanism of action in diabetic patients – clinical data showing effects on insulin sensitivity (clamp part) and glucose stimulated insulin secretion (OGTT part)
• PARADIME TIR: confirmation of TWYMEEG® effects on glucose variability
• PET/MRI Study: confirmation of TWYMEEG® effect on glucose excretion in the gut

Thomas Kuhn, Chief Executive Officer of Poxel, stated: "We are proud to see the scientific community's continued interest and the commitment of our partner Sumitomo Pharma to document and promote TWYMEEG®'s attributes and value. These presentations further support the product's clinical and commercial trajectory

² Refers to a statistical analysis specified after a study has been concluded and the data collected

¹ Detailed program included in Appendix

in Japan. They also highlight its value proposition for Japan and other territories and its unique profile across diverse patient subgroups."

About Poxel SA

Poxel is a clinical stage biopharmaceutical company developing innovative treatments for chronic serious diseases with metabolic pathophysiology, including metabolic dysfunction-associated steatohepatitis (MASH) and rare disorders. For the treatment of MASH, PXL065 (deuterium-stabilized Rpioglitazone) 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 now 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.

Contacts - Investor relations / Media

NewCap Aurélie Manavarere, Théo Martin / Arthur Rouillé investors@poxelpharma.com +33 1 44 71 94 94

Appendix

Title	Main Results	Speaker	Institution	Type
A post-marketing clinical trial to evaluate the safety, tolerability, and efficacy of Imeglimin in Japanese type 2 diabetes patients with renal impairment (Twinkle Study results;Phase 4)	Imeglimin was shown to be safe and effective in patients with T2D associated with renal dysfunction with eGFR less than 45 mL/min/1.73 m2	Dr. Babazono	Ishikawa Memorial Association	Clinical
Efficacy and safety of Imeglimin as an add-on treatment in type 2 diabetes patients treated with DPP-4 inhibitors: interim analysis of the FAMILIAR study	Combination therapy of Imeglimin and DPP-4 inhibitors significantly reduced HbA1c at 24 weeks in type 2 diabetes patients with inadequate glycemic control with DPP-4 inhibitor therapy, confirming that Imeglimin may be a new treatment option when combined with a DPP-4 inhibitor regardless of age.	Dr. Kaku	Kawasaki Medical School	Clinical
Comparison of the effects of Imeglimin and metformin on insulin and incretin secretion	Imeglimin enhanced insulin secretion as well as increased not only GLP-1 but also GIP secretion, unlike metformin	Dr. Omori	Kansai Electric Power Hospital	Clinical
Effect of Imeglimin use on Time in Range in type 2 diabetes: A multicenter randomized controlled trial (Paradime-TIR)	Imeglimin alone and in combination with DPPIV inhibitors increased Time in Range by more than 10% without increasing Time Below Range, confirming the efficacy of the product in reducing glycemic variability	Dr. Ueda	Kobe Univ.	Clinical
The effects of Imeglimin and metformin on insulin secretion and sensitivity (Paradime-Clamp; OGTT part)	No differences were observed between Imeglimin and Metformin on glucose lowering effects, and on insulin secretion and insulin sensitivity	Dr. Yamada	Kobe Univ.	Clinical

The effects of Imeglimin and metformin on insulin secretion and sensitivity (Paradime-Clamp; Clamp part)	effects No differences were observed between Imeglimin and Metformin on insulin secretion, insulin sensitivity and their ability to switch energy sources	Dr. Katsura	Kobe Univ.	Clinical
Effects on glucose excretion to gut by using FDG/PET MRI study	Imeglimin improved glucose excretion into the intestinal lumen	Dr. Fukumitsu	Kobe Univ.	Clinical
Post-hoc analysis (Atypical cluster analysis of Imeglimin + Metformin)	The highest A1c reduction of the combination Imeglimin + metformin was observed in obese patients or those with a high baseline HbA1c	Kitayama	SMP	Clinical
Post-hoc analysis: Insulin combination therapy	Combination therapy with Imeglimin and insulin exerted glucose lowering effects independent of obesity type	Hagi, PhD	SMP	Clinical
Post-hoc analysis: Monotherapy	Imeglimin monotherapy exerted glucose lowering effects independent of obesity type	Maruyama	SMP	Clinical
Vascular protection effects of Imeglimin, a mitochondrial function improving drug	Imeglimin showed protective effect against vascular lesions like SGLT2 inhibitors and GLP-1 receptor agonists	Dr. Iwazawa	Juntendo Univ. Shizuoka Hospital	Non clinical
Effect of Imeglimin on diabetic neuropathy in type 1 diabetic rat models	Imeglimin may be effective against diabetic neuropathy as shown in this study in STZ induced diabetic rats,	Dr. Nihei	Aichi Gakuin Univ.	Non clinical
Combined effects of anaerobic exercise and Imeglimin on skeletal muscles	The combination of Resistance Training and Imeglimin may be an effective treatment by improving mitochondrial	Dr. Ishiguro	Niigata Univ.	Non clinical

	function, glucose metabolism and glucose uptake
Effect of Imeglimin on periodontitis associated with type 1 diabetes	Imeglimin may be useful in preventing the worsening of periodontal disease due to type 1 diabetes.	Dr. Kondo	Aichi Gakuin Univ.	Non clinical
Imeglimin effect on intestinal gene expression	Imeglimin induced similar gene expression as metformin in the whole intestinal tissue, but single cell analysis revealed different effects on specific cell types, including intestinal cell clusters and macrophage clusters	Dr. Hozumi	Kobe Univ.	Non clinical