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Timber Pharmaceuticals, Inc., a LEO Pharma company, today presents preliminary results from the ASCEND trial in a late-breaking session at the 2024 American Academy of Dermatology (AAD) Annual Meeting.1 The results offer a first look at the safety, efficacy and pharmacokinetic (PK) data from 17 adult and adolescent participants (aged 12-64 years) enrolled in the open-label maximum use arm of the phase 3 ASCEND trial.1.

利奥制药公司Timber Pharmaceuticals，Inc.今天在2024年美国皮肤病学会（AAD）年会的后期会议上介绍了ASCEND试验的初步结果。1该结果首次展示了17名成人和青少年参与者（12-64岁）的安全性，有效性和药代动力学（PK）数据参加了第3阶段ASCEND试验的开放标签最大使用部门。

These late-breaker results are part of a wide-ranging data program from LEO Pharma at AAD, with eight abstracts accepted in total for the meeting, showcasing an ongoing commitment to advancing the standard of research in medical dermatology.

这些最新的突破性结果是AAD LEO Pharma的广泛数据计划的一部分，会议共接受了八篇摘要，表明了对提高医学皮肤病研究标准的持续承诺。

ASCEND is a clinical trial of TMB-001, a polyethylene glycol (iPEG™) based investigational topical isotretinoin being developed for the treatment of moderate-to-severe X-linked and autosomal recessive congenital ichthyosis (CI).3 CI is a group of rare genetic keratinization disorders that leads to dry, thickened, and scaling skin.4-7 Currently, no specific treatments are approved by the U.S.

ASCEND是TMB-001的一项临床试验，TMB-001是一种基于聚乙二醇（iPEG™）的研究性局部异维a酸，正在开发用于治疗中度至重度X连锁和常染色体隐性先天性鱼鳞病（CI）。CI是一组罕见的遗传性角化疾病，导致皮肤干燥，增厚和鳞屑。目前，美国尚未批准任何特定的治疗方法。

Food and Drug Administration (FDA) to treat CI.2.

美国食品和药物管理局（FDA）治疗CI。

Patients enrolled in the open-label maximum use arm of the ASCEND trial with 75-90% body surface area involvement and moderate-to-severe disease on the Investigator Global Assessment (IGA) scale (IGA scores ≥3) were included in this analysis.1

纳入ASCEND试验开放标签最大使用组的患者，研究者全球评估（IGA）量表（IGA评分≥3）中75-90%的体表面积受累和中重度疾病被纳入本分析

TMB-001 results showed that, from baseline to Week 12, the mean total Investigator Global Assessment (IGA) composite scaling and fissuring score decreased from 3.2 to 1.6 (p=0.0001). In the same timeframe, 59% of patients achieved a ≥2 point decrease in IGA scores from baseline, while 82% demonstrated a clinically significant (≥1 point) improvement in IGA scores from baseline.1.

TMB-001结果显示，从基线到第12周，平均总研究者全球评估（IGA）综合评分和裂隙评分从3.2降至1.6（p=0.0001）。在同一时间段内，59%的患者IGA评分比基线下降≥2分，而82%的患者表现出IGA评分比基线有临床显着（≥1分）的改善。

No serious adverse events (SAEs) were reported.1 65% of participants experienced at least 1 adverse event (AE), with a total of 35 events.1 The top three treatment-emergent AEs were erythema (N=7), pruritus (N=4), and stinging/pain (N=2).1

没有报告严重不良事件（SAE）。1 65%的参与者经历了至少1次不良事件（AE），共有35次事件。前三位治疗出现的AE是红斑（N=7），瘙痒（N=4）和刺痛/疼痛（N=2）

“The preliminary findings from the ASCEND trial are encouraging and indicate the potential of TMB-001 to provide hope for those living with X-linked and autosomal recessive CI,” said Kreesten Meldgaard Madsen, Chief Development Officer, LEO Pharma. “We know that the management of this disease can be incredibly challenging and, given the limited treatment options available, we remain focused on pushing the development of TMB-001 forward with the goal of helping to address this considerable unmet need.”

LEO Pharma首席开发官Kreesten Meldgaard Madsen说：“ASCEND试验的初步结果令人鼓舞，表明TMB-001有潜力为X连锁和常染色体隐性CI患者提供希望。”“我们知道，这种疾病的管理可能具有难以置信的挑战性，鉴于可用的治疗选择有限，我们仍然专注于推动TMB-001的发展，目标是帮助解决这一巨大的未满足需求。”

The results were taken from participants in the open-label maximal use arm of the ASCEND trial. This arm aimed to analyze the PKs of TMB-001 by determining the level of systemic exposure of isotretinoin and metabolites.1 To do this, the change from baseline of isotretinoin (ISO), 4-oxo-isotretinoin (4-O-ISO), tretinoin (TR), and 4-oxo-tretinoin (4-O-TR) after 14 days of twice-daily application of TMB-001 was assessed.1.

结果来自ASCEND试验开放标签最大使用组的参与者。该组旨在通过确定异维A酸和代谢物的全身暴露水平来分析TMB-001的PKs。为此，评估了每天两次施用TMB-001 14天后，异维A酸（ISO），4-氧代-异维A酸（4-O-ISO），维A酸（TR）和4-氧代-维A酸（4-O-TR）的基线变化。

The data demonstrated low systemic concentrations across all four molecules examined after 14 days of twice-daily application of TMB-001.1 The steady-state mean peak plasma concentrations (ng/mL) in the 17 participants were 4.5 for ISO, 9.0 for 4-O-ISO, and low to not calculable for TR and 4-O-TR.1

数据显示，每天两次施用TMB-001.1 14天后，所有四种分子的全身浓度均较低。17名参与者的稳态平均峰值血浆浓度（ng/mL）为ISO为4.5，4-O-ISO为9.0，TR和4-O-TR.1为低至不可计算

“X-linked and autosomal recessive CI can be incredibly challenging to live with, and in my experience patients are often impacted both psychically and psychologically by a host of symptoms,” said Dr. Christopher Bunick, Lead Author and Associate Professor of Dermatology, Yale School of Medicine. “With no specific treatment currently available, CI patients are currently having to deal with their condition with minimal support.

耶鲁大学医学院皮肤病学首席作者兼副教授克里斯托弗·布尼克博士说：“X连锁和常染色体隐性遗传性CI对患者的生活具有极大的挑战性，根据我的经验，患者经常受到一系列症状的心理和心理影响。”。“由于目前没有具体的治疗方法，CI患者目前必须在最少的支持下处理他们的病情。

I hope that the data and insights presented today can help provide new knowledge and support for this patient community.”

我希望今天提供的数据和见解可以帮助为这个患者社区提供新的知识和支持。”

In January 2024, LEO Pharma finalized the acquisition of Timber Pharmaceuticals, a clinical-stage biopharmaceutical company focused on the development and commercialization of treatments for rare and orphan dermatologic diseases. Upon completion, the Timber Pharmaceuticals lead investigational product candidate, TMB-001, was added to LEO Pharma’s pipeline.

2024年1月，LEO Pharma完成了对Timber Pharmaceuticals的收购，Timber Pharmaceuticals是一家临床阶段的生物制药公司，专注于罕见和孤儿皮肤病治疗的开发和商业化。完成后，Timber Pharmaceuticals首席研究产品候选人TMB-001被添加到LEO Pharma的管道中。

TMB-001 is under investigation and has not been evaluated by any health authority.

TMB-001正在调查中，尚未得到任何卫生部门的评估。

About the ASCEND Trial

关于ASCEND审判

An ongoing, multicenter phase 3 study to evaluate the efficacy and safety of TMB-001 0.05% topical ointment in the treatment of congenital ichthyosis (CI) in subjects (aged ≥6 years) with either the autosomal recessive congenital ichthyosis (ARCI) or X-linked recessive ichthyosis (XLRI) subtypes.3

一项正在进行的多中心3期研究评估TMB-001 0.05%局部软膏治疗常染色体隐性先天性鱼鳞病（ARCI）或X连锁隐性鱼鳞病（XLRI）亚型受试者（年龄≥6岁）先天性鱼鳞病（CI）的疗效和安全性

The clinical trial is divided into two parts. The first is a randomized, double-blind, vehicle-controlled phase III study. Its objective is to ascertain the efficacy of TMB-001 0.05% topical ointment as a treatment for CI compared with vehicle during 12 weeks of treatment.3

临床试验分为两部分。第一项是一项随机，双盲，车辆控制的III期研究。其目的是确定TMB-001 0.05%局部软膏在治疗12周内与载体相比治疗CI的疗效

In the second part of the trial, a subset of preselected centers will recruit subjects in parallel with either the ARCI or XLRI subtypes for enrollment into an Optional Maximal Use arm. The primary objective of this part of the trial is to determine systemic exposure of isotretinoin and metabolites after single or multiple applications of TMB-001 0.005% ointment.

在试验的第二部分，预选中心的一个子集将招募与ARCI或XLRI亚型平行的受试者，以注册到可选的最大使用组中。这部分试验的主要目的是确定单次或多次应用TMB-001 0.005%软膏后异维A酸和代谢物的全身暴露。

Its primary endpoint is an assessment of individual concentrations of 4-oxo-isotretinoin (4-O-ISO), tretinoin (TR), 4-oxo-tretinoin (4-O-TR) and change from baseline.3.

其主要终点是评估4-氧代-异维甲酸（4-O-ISO），维甲酸（TR），4-氧代-维甲酸（4-O-TR）的个体浓度以及与基线的变化。

About Congenital Ichthyosis

关于先天性鱼鳞病

Congenital ichthyosis (CI) is a group of rare genetic keratinization disorders that can lead to dry, thickened, and scaling skin.4-7

先天性鱼鳞病（CI）是一组罕见的遗传性角化疾病，可导致皮肤干燥，增厚和鳞屑。4-7

Most cases of ichthyosis are inherited, but some types develop in association with genetic syndromes or diseases, such as Hodgkin's Lymphoma.8,9

大多数鱼鳞病病例是遗传性的，但某些类型与遗传综合征或疾病有关，如霍奇金淋巴瘤。8,9

People living with CI may have limited range of motion, chronic itching, an inability to sweat normally, high risk of secondary infections, and impaired eyesight or hearing.4-7

患有CI的人可能活动范围有限，慢性瘙痒，无法正常出汗，继发感染的高风险以及视力或听力受损。4-7

About TMB-001

关于TMB-001

TMB-001, topical isotretinoin in the company’s investigational patented polyethylene glycol (IPEG™) delivery system, is being developed for the treatment of moderate-to-severe subtypes of congenital ichthyosis (CI). During Q4 2021, the positive topline results for its Phase 2b CONTROL Study were announced.

TMB-001是该公司研究性专利聚乙二醇（IPEG™）输送系统中的局部异维A酸，正在开发用于治疗中度至重度先天性鱼鳞病（CI）亚型。在2021年第四季度，宣布了其2b期对照研究的积极结果。

In Q1 2022, TMB-001 received both Breakthrough Therapy Designation and Fast Track Status from the U.S. Food and Drug Administration (FDA). The Phase 3 ASCEND clinical trial was initiated in Q2 2022.

2022年第1季度，TMB-001获得了美国食品和药物管理局（FDA）的突破性治疗指定和快速通道状态。第三阶段ASCEND临床试验于2022年第二季度启动。

About LEO Pharma

关于LEO Pharma

LEO Pharma is a global company dedicated to advancing the standard of care for the benefit of people with skin conditions, their families and society. Founded in 1908 and majority owned by the LEO Foundation, LEO Pharma has devoted decades of research and development to advance the science of dermatology, and today, the company offers a wide range of therapies for all disease severities.

利奥制药（LEO Pharma）是一家全球性公司，致力于提高护理标准，造福皮肤病患者及其家人和社会。LEO Pharma成立于1908年，由LEO基金会拥有多数股权。LEO Pharma致力于数十年的研究和开发，以推动皮肤病学的发展。如今，该公司为所有严重疾病提供了广泛的治疗方法。

LEO Pharma is headquartered in Denmark with a global team of 4,400 people, serving millions of patients across the world. In 2022, the company generated net sales of DKK 10.6 billion.

利奥制药（LEO Pharma）总部位于丹麦，拥有4400人的全球团队，为全球数百万患者提供服务。2022年，公司净销售额106亿丹麦克朗。