PDE4 inhibitor rolipram dynamically regulates the balance between D1-MSNs and D2-MSNs in the DMS to modulate abnormal “Go” behavior associated with alcohol addiction

Article

作者: Zhang, Han-Ting ; Zhao, Wei ; Zong, Fang-Jiao ; Zhao, Shuang ; Chen, Xiao-Fei ; Wang, Zi-Qi

Addiction is a chronic relapsing disorder characterized by compulsive seeking and consumption of drugs, with this abnormal "Go" behavior resulting in significant negative consequences. Research has shown that the dorsal medial striatum (DMS) is associated with the pathophysiological mechanisms of addiction; however, drugs targeting the DMS to achieve therapeutic effects for addiction remain unavailable. Intracellular cAMP signaling, regulated by G protein-coupled receptors (GPCRs), critically modulates the excitability, plasticity and neurotransmission of GABAergic medium spiny neurons (MSNs). In this study we investigated how inhibition of PDE4 modulated cAMP levels with a specific focus on how these changes influenced the dopamine D1 receptor MSNs (D1-MSNs) and D2 receptor MSNs (D2-MSNs) in the DMS, thereby influencing abnormal "Go" behavior. We established alcohol-induced conditioned place preference (CPP) model and two-bottle choice drinking model in mice. PDE4 inhibitor rolipram (0.5 μg) were bilaterally microinjected into the DMS of mice 2 h prior to the combination of alcohol. The activation of D1-MSNs and D2-MSNs in the DMS was assayed using c-Fos immunofluorescence staining. We showed that rolipram microinjection significantly increased cAMP levels in MSNs of the DMS and restored the activation balance between D1-MSNs and D2-MSNs. This rebalancing of MSN activity attenuated abnormal "Go" behaviors including high-drinking behavior. We further identified the ERK signaling downstream of cAMP in D2-MSNs of the DMS, together with the PDE4 subtype PDE4B, as key mediators of the inhibitory effects of PDE4 inhibitors on high-drinking behavior. These results highlight a new strategy emphasizing the pivotal role of PDE4 as a key regulator of cAMP signaling in MSNs, maintaining the dynamic balance between D1-MSNs and D2-MSNs, and further identify D2-MSNs specific PDE4B/cAMP/ERK modulation as a promising target for addiction treatment.

2026-05-28·Polish Archives of Internal Medicine-Polskie Archiwum Medycyny Wewnetrznej

Biologic and targeted synthetic treatment of SAPHO syndrome: systematic literature review.

Review

作者: Wroński, Jakub ; Kudraszewska, Emilia ; Adamska, Agnieszka ; Foryś, Agnieszka ; Urba, Jagoda

INTRODUCTION:

SAPHO syndrome is a rare autoimmune / autoinflammatory disorder with no approved therapies or standardized management guidelines. Biologic and targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) are increasingly used off‑label.

OBJECTIVES:

This review aimed to systematically evaluate the evidence for the efficacy of b/tsDMARDs in SAPHO.

PATIENTS AND METHODS:

A PRISMA‑guided search of PubMed database was conducted through March 31, 2025. Studies of any design reporting outcomes of b/tsDMARDs in patients with SAPHO fulfilling the modified Kahn criteria were included. Exclusion criteria were non‑English language, inaccessible full text, and insufficient treatment details. Data on patient characteristics, drug class, follow‑up duration, and treatment response were extracted. As all the included studies were case reports or case series, the risk of bias was not assessed. Treatment responses were summarized using descriptive statistics.

RESULTS:

Of 1610 screened records, 106 studies comprising 385 instances of b/tsDMARD use met the inclusion criteria; no randomized controlled trials were identified. Tumor necrosis factor inhibitors (TNFis) were used in 203 patients, with complete skeletal and skin responses in 81% and 72%, respectively. The use of Janus kinase inhibitors (JAKis) in 77 patients was associated with complete response rates of 89% (skeletal) and 94% (skin). Other b/tsDMARD classes-including interleukin 17 (IL‑17), IL‑23, IL‑1, and IL‑6 inhibitors, as well as phosphodiesterase‑4 inhibitors-demonstrated variable and generally lower efficacy.

CONCLUSIONS:

Evidence for b/tsDMARD efficacy in SAPHO remains limited to low‑quality, uncontrolled studies with substantial heterogeneity and probable publication bias. TNFis and JAKis are among the most consistently effective therapies reported in the available literature, but high‑quality research, including randomized trials or prospective registries, is urgently needed to inform evidence‑based management.

2026-04-01·Cancer research communications

Metastasis-Associated Wound Repair Promotes Reciprocal Lung Epithelium Activation and Breast Cancer Metastatic Outgrowth

Article

作者: Christenson, Jessica L. ; Richer, Jennifer K. ; O’Neill, Kathleen I. ; Spoelstra, Nicole S. ; Orlicky, David J. ; Van Bokhoven, Adrie ; Williams, Michelle M. ; Kuo, Li-Wei ; Diamond, Jennifer R. ; Logan, Linda L. ; Wagner, Jennifer A. ; Baker, Nolan T. ; Goodspeed, Andrew ; Staley, Alyse W. ; Crump, Lyndsey S.

Abstract:

When tumor cells colonize distant organs during metastasis, they interact extensively with surrounding cells. These interactions often change the behavior of surrounding cell populations which collectively induce a protumor microenvironment that permits tumor cell outgrowth into overt, clinically detectable metastatic disease. The lung is one of the most common sites of breast cancer metastasis. A chronic wound repair–related phenotype developed within the lung microenvironment during metastatic outgrowth in immunocompetent preclinical mouse models of breast cancer. This phenotype was characterized by an increased number and activation of lung type II alveolar epithelial (AT2) cells surrounding growing metastases. Metastatic outgrowth significantly changed AT2 gene expression, resulting in a modified secretome. AT2-derived secreted factors also promoted triple-negative breast cancer growth. AT2-secreted factors are regulated by the cyclic adenosine monophosphate response element-binding protein (CREB). Targeting CREB signaling with the phosphodiesterase 4 (PDE4) inhibitor roflumilast reduced AT2 breast cancer reciprocal interactions in vitro and metastatic outgrowth in vivo. Finally, AT2 cells adjacent to metastases in lungs from patients with metastatic breast cancer expressed higher PDE4B compared with AT2 cells in normal lungs.

Significance::

Alveolar epithelial cells are the most common cell type in the lung. Our studies demonstrate the potential for targeting metastasis-associated wound repair and lung epithelial cell activation during metastatic outgrowth with FDA-approved PDE4 inhibitors. This strategy may be an effective way to treat and manage progression of established metastatic breast cancer within the lung.

项与 PDE4 inhibitors(Hainan University) 相关的新闻（医药）

2026-07-03

·ChinChemLett

【CCL文章Twitter关注超三万】海南大学黄玲/徐从军/熊婉迪/黄仪有：海洋真菌来源的二苯并呋喃类PDE4抑制剂用于阿尔茨海默病治疗。

成果简介近日，海南大学黄玲/徐从军/熊婉迪/黄仪有团队在《Chinese Chemical Letters》上发表了题为“Discovery of a novel PDE4 inhibitor with dibenzofuran moiety from marine fungal metabolites for Alzheimer's disease therapy”的研究论文（DOI：10.1016/j.cclet.2026.113012）。本研究通过对海洋真菌来源的二苯并呋喃类次生代谢物的系统活性筛选与结构优化，发现了一系列新型PDE4抑制剂，并在APP/PS1 AD模型小鼠中开展了药效评价与机制探索。研究思路本研究基于前期建立的计算机虚拟筛选方法，从自主构建的海洋天然产物库中，筛选获得先导化合物HX02，其具有一定的PDE4抑制活性（半数抑制浓度IC₅₀ = 719.0 nmol/L），但其水溶性和代谢稳定性不佳。本研究以HX02为先导化合物，采用结构简化和电子等排策略，对其进行逐步结构优化，最终获得了优选化合物HXB-6j。该化合物表现出更优的类药性质，PDE4抑制活性增强（IC₅₀ = 32.6 nmol/L）、水溶性改善（32.3 μg/mL）且具有良好的药代动力学特征（生物利用度F = 44.67%）。在APP/PS1小鼠模型中，HXB-6j可显著增强其记忆与认知能力。此外，HXB-6j通过激活CREB通路增强了体内突触功能，并缓解包括Aβ沉积和神经元损伤在内的AD相关病理改变。上述结果表明，HXB-6j是一个极具前景的AD候选治疗药物。该研究可为海洋来源的活性先导的发现及开发提供研究思路。论文标题截图 Twitter关注超三万图文导读图1. 海洋来源二苯并呋喃类PDE4抑制剂的发现本研究发现了海洋真菌来源的次级代谢产物HX02，具有一定的PDE4抑制活性（IC₅₀ = 719.0 nM），但水溶性差（< 0.1 μg/mL）且代谢稳定性不佳（HLM T₁/₂ = 30 min）。通过合理药物设计，对HX02进行结构简化与优化，获得了优选化合物HXB-6j。该化合物具有强效PDE4抑制活性（IC₅₀ = 32.60 nM），且其水溶性（32.3 μg/mL）和代谢稳定性（HLM T₁/₂ = 302 min）均得到改善，并在体内显著增强记忆与认知功能。图2. 化合物HXB-6j在体外通过CREB-BDNF轴发挥神经保护作用。 PDE4作为水解cAMP和cGMP的酶，会限制PKA诱导的CREB磷酸化，而该轴是调控BDNF表达及炎症反应的重要通路。免疫荧光显示，经化合物HXB-6j处理后，细胞核内磷酸化CREB（p-CREB）的活化水平升高（图 2A、B）。同时，HXB-6j处理还提高了SY5Y细胞中BDNF水平，并降低诱导型一氧化氮合酶（iNOS)水平（图 2C-F），表明化合物HXB-6j通过PKA-p-CREB-BDNF通路发挥神经保护作用。图3. 化合物HXB-6j可改善APP/PS1小鼠的记忆损伤与认知障碍。在旷场实验中，与野生型（WT）组相比，APP/PS1模型小鼠警觉性降低，表现为中央区活动时间增加和站立次数增多。给予化合物HXB-6j（5 mg/kg和15 mg/kg）后，APP/PS1小鼠警觉性明显提高，中央区活动时间和站立次数均减少（图3A、B）。在新物体识别测试中，15 mg/kg HXB-6j和1 mg/kg多奈哌齐处理的APP/PS1小鼠辨别指数升高（图3C）。在海马依赖的Morris水迷宫任务中，HXB-6j对训练和测试期间的游泳速度无影响（图3D）。航行轨迹的详细分析显示，15 mg/kg HXB-6j和1 mg/kg多奈哌齐处理的APP/PS1小鼠采取了策略性寻路方式，边缘绕行路径较少（图3E）。此外，15 mg/kg HXB-6j和1 mg/kg多奈哌齐处理的APP/PS1小鼠还表现出更短的潜伏期和更长的目标象限停留时间（图3F、G）。图4 化合物 HXB-6j 在体内表现出良好的安全性。 H&E染色结果显示，各组海马CA1、CA3和DG区的体细胞均未受损（图4A），且各区神经元数量在组间无明显差异（图4B-D）。综上所述，化合物HXB-6j在体内安全性良好，对海马神经元损伤极小。图5. 化合物HXB-6j对APP/PS1小鼠脑内磷酸化CREB与BDNF表达的影响。为进一步评估化合物HXB-6j在APP/PS1小鼠体内对PDE4的抑制活性，我们检测了海马与前额叶皮层中p-CREB的免疫荧光。结果显示，15 mg/kg HXB-6j处理组小鼠CA1、CA3及前额叶皮层（PFC）区域的p-CREB水平升高，而1 mg/kg多奈哌齐组仍维持在低水平（图5A、B）。随后通过BDNF免疫荧光评估其神经保护作用，发现HXB-6j能在一定程度上恢复APP/PS1小鼠海马和前额叶皮层的BDNF水平（图5C、D）。这些结果表明，HXB-6j能够在体内抑制PDE4活性，从而有效提升p-CREB水平并发挥神经保护作用，与前述体外细胞实验结果一致。图6. 化合物HXB-6j对APP/PS1小鼠Aβ沉积与神经炎症的逆转作用。在APP/PS1小鼠海马和前额叶皮层中，HXB-6j与多奈哌齐处理均降低了6E10和4G8信号，但硫黄素S信号未变（图6A、B）。神经炎症作为AD另一突出病理表型，深度参与其发病机制。海马和前额叶皮层白细胞介素-6（IL-6）免疫荧光显示，HXB-6j处理通过下调IL-6水平减轻了APP/PS1小鼠的神经炎症（图6C、D）。综上，HXB-6j在APP/PS1小鼠中的抗AD作用表明，PDE4抑制剂HXB-6j是治疗AD极具前景的候选化合物。小结本工作通过机器学习驱动的虚拟筛选，发掘了海洋来源的PDE4抑制剂先导化合物HX02。通过结构简化及局部结构修饰的策略，对其类药性进行了优化，最终获得了优选化合物HXB-6j。化合物HXB-6j具有优异的PDE4抑制活性（IC₅₀ = 32.6 nM），较高的水溶性（32.3 μg/mL）以及良好的药代动力学性质（F = 44.67%）。经体内实验证明，腹腔注射HXB-6j能够改善APP/PS1转基因小鼠模型的认知和记忆功能，且表现出良好的安全性。化合物HXB-6j通过促进CREB磷酸化并进一步上调BDNF的表达，从而改善认知功能；同时，还能减少Aβ的沉积，并减轻神经炎症反应。综上，化合物HXB-6j是一种具有良好开发前景的PDE4抑制剂，有望作为AD治疗候选药物进一步开展研究与开发。本研究为PDE4抑制剂的开发提供了新的结构参考，为AD药物的前沿探索提供了新思路。本研究成果得到了国家自然科学基金（Nos. 82560683, 22577021 and 82404601）、海南省优秀人才团队项目(No. HNYT20250004)等基金的支持。通讯作者介绍通讯作者个人简介：黄玲，教授，博士生导师，国家重大人才工程青年项目获得者，现任科学技术发展院副院长、海南全健康国际研究院副院长、海南省全健康研究重点实验室副主任。2011年博士毕业于中山大学药学院，2011年至2021年留校任教，2021年9月引进到海南大学组建“热区海洋创新药物研发团队”，聚焦神经退行性疾病、慢性代谢性肝病和感染性疾病创新药物研发工作，在APSB、J. Med. Chem和Chin. Chem. Lett.等期刊发表SCI论文100余篇，主持国家级、省部级项目等20余项课题，申请中国发明专利30余项，其中1项抗阿尔茨海默病创新药物专利转让给上市公司。担任中国药学会药物化学专业委员会青年委员、中国民族医药学会黎医药分会理事会会副会长、海南省药学会应急与保障专业委员会副主任委员等。《热带生物学报》中英文刊副主编，《药学学报》中英文刊青年编委等。通讯作者个人简介：徐从军，海南大学药学院副教授，博士研究生导师。海南省“拔尖人才”。立足海南当地特色，围绕神经退行性疾病开展海洋来源的小分子创新药物研究（天然来源PDE2/4抑制剂，sEH抑制剂，铁死亡抑制剂），在Acta Pharm. Sin. B., Chin. Chem. Lett., J. Med. Chem., Eur. J. Med. Chem等Top期刊发表SCI论文30余篇，主持国家自然科学基金2项、广东省自然科学基金和海南省自然科学基金等省部级研究项目6项。担任The innovation medicine, Pharmaceutical Science Advances, 中国药物化学杂志青年编委，J. Med. Chem等多个期刊审稿人。通讯作者个人简介：熊婉迪，海南大学药学院副研究员，博士研究生导师。2022年毕业于北京大学获得博士学位。主要研究方向为神经退行性疾病创新药物设计与研发、治疗靶点和药理机制研究。年来以第一作者/通讯作者(含共同)在EMBO J、Signal Transduction and Targeted Therapy、Nature Communications等国际期刊发表多篇文章，申请发明专利2项。主持和参与国家自然科学基金青年，面上和重大研究计划等多项研究项目。通讯作者个人简介：黄仪有，海南大学药学院研究员，博士研究生导师，“靶标结构及新药发现”团队负责人，围绕磷酸二酯酶等重要药物靶点，开展结构生物学与药物化学交叉研究。先后主持国家自然科学基金面上项目/青年基金、海南省自然科学基金优青项目/面上项目等7项基金，并在国内外学术期刊如Proc Natl Acad Sci USA、J Med Chem、Acta Pharm Sin B、Org Lett等发表SCI论文40余篇，含（并列）一作/（共同）通讯论文30余篇，授权发明专利6项。第一作者介绍第一作者个人简介：边泓元，海南大学药学院硕士研究生，2023年于海南大学获得学士学位，研究方向为海南特色来源氰基取代二苯并呋喃类PDE4抑制剂活性优化及抗AD活性研究，硕士期间以负责人身份申请课题立项为海南省高等学校研究生创新科研课题，获优秀研究生称号，以共同第一第三作者发表J. Med. Chem文章一篇，共同第一第一作者发表Chinese Chem Lett文章一篇。第一作者个人简介：张舒婷，海南大学药学院硕士研究生，研究方向为阿尔茨海默症新药研发。以共同第一第二作者发表Chinese Chem Lett文章一篇。第一作者个人简介：黄姝姮，海南大学药学院副教授，博士研究生导师。2022年毕业于重庆大学获得博士学位，并于2022年10月通过高层次人才引进到海南大学药学院工作至今。主要研究领域为计算机辅助药物设计、计算化学和生物信息学等。主要研究方向：1）通过引入人工智能、理论化学和生物信息学等学科技术进行新药设计和筛选；2）采用理论计算模拟等方法揭示生物分子作用机理及与小分子识别机制。先后发表SCI收录论文三十余篇，其中第一/通讯作者十余篇。主持国家自然科学基金等多项省部级以上科研项目。《海南大学学报（自然科学版）》青年编委，担任Acta Pharm. Sin. B, Comput. Struct. Biotechnol. J.等期刊审稿人。文献信息原文链接： https://www.sciencedirect.com/science/article/pii/S1001841726006558 出品｜CCL编辑部供稿｜黄玲、徐从军、熊婉迪、黄仪有审核｜王俊丽审定｜郭焕芳点击“阅读原文”跳转至原文界面

临床结果临床研究

2026-04-02

·allsci.com

Alto discontinues transdermal PDE4 inhibitor after Phase II failure in schizophrenia-linked cognitive impairment

Alto Neuroscience (NYSE: ANRO) reported that ALTO-101 did not meet its primary EEG or cognitive endpoints versus placebo in a Phase II proof-of-concept study in cognitive impairment associated with schizophrenia (CIAS), prompting the company to discontinue independent development of the asset and redirect resources toward its lead program, ALTO-207, in treatment-resistant depression. The Phase II trial (NCT06502964) was assessing ALTO-101 — a transdermal PDE4 inhibitor formulation — in adults with CIAS, enrolling 83 participants across the primary analysis set. ALTO-101 produced a near-significant effect on theta inter-trial coherence (theta-ITC), an EEG measure correlated with cognitive performance, in the full analysis set (n=83; Cohen’s d=0.34, p=0.052). In a pre-specified subgroup of more cognitively impaired patients (n=59), the effect on theta-ITC reached nominal significance (d=0.44, p=0.03). The company also noted that theta-ITC improved from day 5 to day 10 of the trial, raising the possibility that a longer treatment duration could yield larger effects, though the primary endpoints were not met and these observations remain exploratory. Tolerability was notable in one respect: nausea and vomiting rates were in line with placebo, a finding the company attributes to the pharmacokinetic profile of the transdermal formulation — a class-specific barrier that has historically constrained PDE4 inhibitor development. High rates of application site skin reactions were observed in both active and placebo arms, suggesting a formulation effect rather than a drug-specific signal. ALTO-101 belongs to the PDE4 inhibitor class, which has long been associated with pro-cognitive effects in preclinical models but has faced tolerability limitations that have restricted clinical utility. The transdermal delivery approach was designed to circumvent the gastrointestinal side effects that have limited oral PDE4 inhibitors. The near-miss on theta-ITC — a measure that the company describes as correlated with cognitive performance across datasets — suggests some pharmacodynamic engagement, but the gap between that signal and statistical significance on primary endpoints is the critical interpretive question. Cross-trial comparisons are limited, but Biogen’s AMPA receptor potentiator BIIB104, a separate CIAS-targeted program that completed Phase II, but also failed to produce sufficient efficacy in this indication. Alto has separately developed a modified-release oral formulation of ALTO-101 with an improved pharmacokinetic and tolerability profile relative to the immediate-release version. The company intends to explore partnering opportunities for this formulation, which is covered by a pending patent application, and believes it may have utility across multiple therapeutic areas beyond CIAS. Within the same press release, Alto indicated that development of ALTO-207 remains on track to begin a Phase IIb study for treatment-resistant depression (TRD) later this year, and is now the company’s top priority. ALTO-207 is a fixed-dose combination of pramipexole, a dopamine D3/D2 agonist, and ondansetron, a 5-HT3 antagonist, designed to enable rapid titration to higher pramipexole doses by suppressing the dose-limiting nausea and vomiting that have historically prevented patients from reaching therapeutically relevant exposures. The planned Phase IIb trial is a randomized, double-blind, placebo-controlled study in approximately 178 adults with TRD who have experienced two to five prior treatment failures, evaluating ALTO-207 as adjunctive therapy. The mechanistic rationale draws on the PAX-D study, published in The Lancet Psychiatry and conducted by the University of Oxford, which reported a Cohen’s d=0.87 effect size for pramipexole versus placebo at 12 weeks in depression — a figure the company characterizes as substantially larger than those seen with currently approved TRD treatments. Alto’s own Phase IIa trial of ALTO-207 met primary and secondary endpoints, and a 2025 FDA meeting is described as having positioned the company to advance toward Phase III and a potential NDA submission. The TRD landscape ALTO-207 is entering contains one truly TRD-specific intranasal therapy — esketamine (Spravato), approved in 2019 and expanded to monotherapy in January 2025 — alongside oral atypical antipsychotic augmenters such as aripiprazole, brexpiprazole, and quetiapine that carry adjunctive MDD labels rather than TRD-specific indications. Olanzapine/fluoxetine (Symbyax) holds a TRD-specific oral label but is associated with metabolic burden. The dopamine D3-preferring agonism of pramipexole is mechanistically distinct from all currently approved options, and the fixed-dose combination strategy with ondansetron addresses the primary tolerability barrier that has previously prevented pramipexole from reaching therapeutic doses in this population. Cross-trial comparisons are limited by differences in patient populations, prior treatment histories, and endpoint definitions, and the PAX-D effect size for pramipexole alone does not directly predict what ALTO-207 will produce in a rigorously controlled registrational-track study. Your email address will not be published. Required fields are marked * Comment * Name * Email * Website

临床2期临床结果上市批准

2026-02-02

·FierceBiotech

China\'s Newsoara pens $135M deal for remaining rights to vTv\'s inflammation drug

Newsoara CEO Benny Li touted HPP737 as “highly differentiated oral PDE4 inhibitor with the potential to address unmet needs in inflammation-mediated disease.”\n Having already secured regional rights to vTv Therapeutics’ inflammation drug, China’s Newsoara is fronting $20 million to take ownership of the clinical-stage asset across the rest of the world.The therapy in question is HPP737, a phosphodiesterase type 4 (PDE4) inhibitor that vTv has taken into phase 1 development to treat psoriasis. Newsoara originally secured the rights for the drug in China and various other Pacific Rim countries in 2018 for an undisclosed price.Targeting PDE4 drives anti-inflammatory and antifibrotic effects and has been put to good use with Arcutis’ psoriasis cream Zoryve and Amgen’s oral psoriasis drug Otezla.According to vTv Therapeutics, the preclinical and clinical data for HPP737 suggest the oral drug “may be able to expand the therapeutic use for [the PDE4] target, which has been limited by the side effects of currently available PDE4 inhibitors,” such as nausea, vomiting and diarrhea.Now, Newsoara is willing to hand over $20 million for the global rights to HPP737. The new deal means North Carolina-based vTv could also be in line for up to $50 million in development milestones, $65 million in sales milestones and tiered royalties on sales should Newsoara manage to get HPP737 to market.“Over the last several years, vTv and Newsoara have enjoyed a productive and collaborative relationship, and this exciting expansion of the relationship will help accelerate the clinical development of our highly differentiated and potential best-in-class PDE4 inhibitor HPP737,” vTv’s chief business officer Rich Nelson said in the release. The company’s CEO, Paul Sekhri, said vTv “remain[s] opportunistic in exploring potential collaborations” for its in-house pipeline while it continues to push to get its lead candidate, the Type 1 diabetes drug cadisegliatin, through phase 3 development. The FDA placed a hold on a trial of the liver-selective glucokinase activator in 2024, but the hold was lifted last year.In this morning\'s release, Newsoara CEO Benny Li touted HPP737 as a “highly differentiated oral PDE4 inhibitor with the potential to address unmet needs in inflammation-mediated disease.”“With this expanded license, we plan to leverage our development and commercialization capabilities to advance HPP737’s progress and, if approved, bring it to patients worldwide,” Li added.There was a continued buzz of activity in the PDE4 inhibitor space last year, especially around respiratory conditions. This included the approval of Boehringer Ingelheim’s idiopathic pulmonary fibrosis (IPF) drug Jascayd as well as Merck & Co.’s $10 billion acquisition of Verona Pharma for its approved PDE3 and PED4 inhibitor Ohtuvayre for chronic obstructive pulmonary disorder (COPD).GSK secured its own PED3/4 inhibitor for COPD as part of a $12 billion biobucks, 12-asset deal with Hengrui Pharma, while Transpire Bio licensed an inhaled PDE4 inhibitor for IPF from China’s Intragrand Pharma.

$China\'s Newsoara pens $135M deal for remaining rights to vTv\'s inflammation drug$