<cite id="ffb66"></cite><cite id="ffb66"><track id="ffb66"></track></cite>
      <legend id="ffb66"><li id="ffb66"></li></legend>
      色婷婷久,激情色播,久久久无码专区,亚洲中文字幕av,国产成人A片,av无码免费,精品久久国产,99视频精品3
      網易首頁 > 網易號 > 正文 申請入駐

      對話 | 基金募資超20億歐元,資深投資人眼中的抗衰老熱點 | Bilingual

      0
      分享至

      編者按:去年,荷蘭風險投資機構Forbion通過兩支新基金完成逾20億歐元募資,創下該機構迄今最大規模的融資紀錄。這筆資金預計將用于支持約30家企業,加速創新生物技術公司的成長,為全球患者帶來具有深遠影響的療法。作為Forbion的普通合伙人,Marco Boorsma博士在制定公司生物技術投資戰略方面發揮著關鍵作用。近日,我們與Marco Boorsma博士展開對話,憑借其發現和培育突破性科學成果方面的深厚經驗,他分享了對衰老相關治療創新領域的重大機遇與現實挑戰的獨到見解。

      Boorsma博士在生物醫藥行業擁有超過20年的豐富經驗,兼具深厚的學術背景與廣泛的產業實踐。在其職業歷程中,他曾主導創立VectorY Therapeutics并擔任創始首席執行官,同時成功孵化NorthSea Therapeutics、Oxitope Pharma、Dezima Pharma等多家創新企業。其中,Dezima Pharma被安進(Amgen)以最高15億美元收購。目前,Boorsma博士仍活躍于產業前沿,擔任Calluna Pharma、Orbis Medicines等多家生物技術公司的董事會成員。


      Boorsma博士,祝賀Forbion在去年完成了迄今規模最大的基金募集!回顧過去近一年的進展,是否可以分享一些值得關注的里程碑?

      Marco Boorsma博士:這一路走來,成果豐碩,我們深感自豪。在過去一年中,我們已投資至少10家具有發展潛力的新興企業,穩步落實資金規劃,這與我們在未來兩年至兩年半內通過成長基金和風險基金支持約30家企業的規劃一致。更為充裕的資金使我們及被投企業能夠主導更大規模的融資輪次。如今,超過1億美元的單輪融資已屢見不鮮,而在我的職業生涯早期,2000萬至2500萬美元的融資規模才是常態。通過組織更大規模的聯合融資,我們能為企業提供從資本注入、董事會指導、生產優化、臨床經驗分享,到監管咨詢及運營指導等全方位的建設資源。目前,我們的投資組合已涵蓋超過40家企業。我們有充分的信心,能夠助力企業高效運營。在我們所投資的公司中,多家企業在臨床開發、監管推進以及業務拓展方面不斷達到重大里程碑。

      在投資中,您如何平衡前沿機制研究帶來的高風險和高回報,與在較短周期內推動療法落地的需求?

      Marco Boorsma博士:這對風險投資人和基金管理人而言是個重要的問題。我們始終從基金整體配置的角度出發,在投資布局上進行平衡:一方面支持相對成熟、已有驗證數據的項目;另一方面布局具有高影響力的前沿科學探索。對于風險更高的項目,我們采用與預先約定的轉化里程碑掛鉤的階段性投資機制,并依據臨床前模型有效性、可重復的體內數據、早期安全性及藥代動力學(PK)數據,以及初步臨床數據等因素進行評估。明確的“繼續/終止”決策機制至關重要,一旦項目進展未達預期,我們會果斷停止投入,將資金轉投至更具潛力的企業。此外,我們通過運營支持降低企業在運行和執行層面的風險。

      在研發層面,我們始終著眼于終局:明確從藥物發現到獲批上市的整體路徑,并在項目早期就遵循監管指南要求。具體而言,首先,在早期研究中采用與人類生理相關、可產生量化結果的實驗體系;同時,投入資源開發可銜接臨床前與臨床研究階段的轉化生物標志物,并倡導使用類器官等人源模型。其次,我們高度重視藥物CMC的可交付性,確保藥物能夠以合理成本進行規模化生產。在團隊架構方面,我們從項目啟動階段就組建包含生物學家、轉化醫學專家、監管顧問及生產工藝專家的多學科團隊。此外,項目早期需注重避免研發中的常見誤區:例如過度依賴單一且缺乏轉化價值的傳統動物模型,延用便利但無法有效預測人體反應的檢測方法,或是推遲對臨床終點的討論。需要強調的是,所設定的監管終點必須從一開始就具備明確的臨床意義。


      圖片來源:123RF

      隨著老齡化成為全球化大趨勢,您認為哪些領域最有可能率先產生變革性療法?

      Marco Boorsma博士:許多常見疾病都與衰老相關,例如阿爾茨海默病、代謝性疾病、纖維化疾病以及心血管疾病等。在神經退行性疾病領域,如今我們已能夠更有效地靶向其根本生物學機制進行干預,幾十年來首批治療阿爾茨海默病的新藥已獲批準,但仍有大量挑戰有待攻克。人工智能將推動神經退行性疾病、腎臟疾病及代謝疾病領域加速取得突破。得益于GLP-1類藥物及肥胖相關研究的進展,代謝疾病領域已取得實質性進展并備受矚目,預計不久將迎來重大突破。免疫衰老領域雖已初現曙光,但真正惠及患者尚需時間。總體而言,某些領域的突破已近在眼前,有些尚處于中期發展階段,另一些則雖需更長時間但前景可期。

      我們將持續聚焦于新興生物學機制的探索,盡管過去三年阿爾茨海默病等領域取得了重大進展,但仍有大量工作需要推進。肌萎縮側索硬化(ALS)、帕金森病以及其他中樞神經系統衰老相關疾病領域也面臨著類似局面。作為投資者,我們的目標是確保優秀的科研成果能夠轉化為可行的藥物。更充裕的資金使我們有能力參與更大規模的融資輪次,為企業提供足夠資金支持,助其達到重要臨床里程碑。這一原則不僅適用于衰老領域企業,也適用于我們的整個投資組合。從企業構建角度來看,基于創新生物學機制的藥物開發往往需要更長的研發周期和更多的資金投入。與以往的早期基金相比,如今我們已具備更強大的能力,可為這類需要長期投入的創新項目提供更有力的支持。

      2022年,您曾在藥明康德健康老齡化論壇上分享了關于應對衰老相關疾病的下一代前沿技術的洞見。此后這些前沿領域出現了哪些新進展?當前最具突破性的機遇又在哪里?

      Marco Boorsma博士:這一領域已逐漸分化出兩個相對清晰的方向。一方面,近期轉化項目更聚焦于纖維化、腎臟疾病、代謝紊亂等領域中已獲驗證的疾病特異性生物學機制,以及部分神經系統靶點。另一方面,更早期的機制性衰老生物學研究則側重于免疫重塑、表觀遺傳“時鐘”及全身性代謝調控。在這些復雜疾病領域,具備轉化潛力的生物標志物正不斷積累,能夠更精準指引藥物開發的預測模型也逐漸建立。我們的策略是將企業構建與資本增長相結合,在上述兩大方向的早期階段同步布局。


      圖片來源:123RF

      當前最具突破性的機遇,在于將機制性衰老生物學研究成果轉化為改變疾病進程的療法。實現這一目標,仍需要眾多科研人員、藥物開發團隊以及像我們這樣的投資者共同投入大量工作。例如,研究人員正在探索清除衰老細胞以延長人類健康壽命的方法,研究老年人群的全身代謝狀態,并針對多器官纖維化病變展開攻關。這些領域不僅充滿機遇,也以大膽創新的方式推動著新型療法的誕生。

      隨著老齡化成為全球范圍內的重要議題,您如何看待當前衰老相關研發工作的優勢與不足?Forbion如何確定自身在國際格局中的定位?

      Marco Boorsma博士:歐洲擁有生物學研究底蘊深厚的學術中心、優秀的小分子及生物制品化學與生產團隊,以及日益完善的轉化基礎設施和臨床試驗中心。歐洲在推動前沿科學研究方面也取得了顯著進展,例如,在衰老及更廣泛的藥物研發領域,人工智能如今在藥物發現、靶點驗證乃至高效評估商業計劃等方面都發揮著重要作用。

      然而,短板仍然存在。例如,目前仍缺乏標準化且經過驗證的生物標志物,尤其是在衰老研究領域。我們需要與生物學年齡相關的生物標志物來有效開展臨床試驗。此外,一些新型療法需精準遞送到衰老大腦的特定區域,而相關生產能力仍需進一步提升。不僅如此,我們還需要將科研成果成功轉化為藥物研發企業。


      圖片來源:123RF

      Forbion通過廣泛的顧問、科學家、前醫藥高管及學者網絡,為企業提供運營支持。我們在規?;a、臨床開發及CMC、以及主導更大規模的融資輪次方面為企業提供指導,并長期陪伴企業成長,降低執行風險、提高成功率。隨著Forbion規模與業務版圖的擴展(尤其是在波士頓的布局),我們聚焦投資兼具頂尖科研與執行團隊的地區,并在歐洲和北美地區提供本地化運營支持。在適當的情況下,我們會與美國頂尖的基金共同投資,并運用自身在企業建設方面的經驗,幫助歐洲的創新成果降低進入全球市場的風險。更大規模的基金可提升后續投資能力,并加速企業規模擴張。我們還與中國醫藥企業開展合作,在北美與歐洲地區開發高質量項目,并取得良好成效。

      展望未來,您認為十年后健康老齡化的討論會繼續圍繞當今的挑戰,還是會出現全新的議題?

      Marco Boorsma博士:長壽固然可貴,但生命質量才是關鍵。健康老齡化的核心,是在延長壽命的同時保持良好的生活質量。Forbion始終聚焦于以疾病為導向、以患者為中心的治療理念:有效治療疾病自然會延長壽命。因此,我們致力于攻克那些限制壽命并影響生活質量的疾病,確保人們能夠健康地老去。

      我期望當今的許多疾病在十年后能夠被有效治療。盡管由于生活方式和人口老齡化的影響,目前許多重大疾病,如纖維化、神經退行性疾病和代謝性疾病在未來仍將繼續存在,但我認為未來將轉向基于經過驗證的生物學年齡標志物和個體化風險評分的精準健康老齡化模式。針對衰老這一多維問題的聯合治療方案,以及藥物遞送系統的進步將使干預措施更具可及性。人工智能將處于這一變革的核心,加速創新進程并優化臨床試驗設計。盡管核心臨床挑戰仍將存在,但診療工具、監管框架和患者分層將更加精細化。Forbion也將繼續從早期階段到商業化全程支持創新科學的發展。


      Advancing Age-Related Therapies: A Conversation with Dr. Marco Boorsma, General Partner, Forbion

      Editor’s Note:Last year, the Netherlands-based venture capital firm Forbion closed more than €2 billion across two new funds, its largest raise to date. The capital is expected to back roughly 30 portfolio companies, accelerating innovative biotechs and advancing impactful therapies for patients worldwide. Dr. Marco Boorsma, General Partner at Forbion, has been instrumental in shaping the firm’s biotech investment strategy. With deep experience in identifying and nurturing breakthrough science, he shares his perspective on the bold opportunities and the hard realities shaping age-related therapeutic innovation.


      Marco, congratulations on closing your largest fund to date last year. Looking back almost 12 months later, what exciting progress and milestones can you share with us?

      Marco Boorsma:It has been a ride, and we are very proud.In the last 12 months, we've invested in at least 10 new promising companies, putting meaningful capital to work. This aligns with our plan to finance about 30 companies from the growth and venture funds over the next two to two and a half years.Larger pools of capital help us and the companies to lead larger financing rounds. Today, $100 million-plus financing rounds are not unheard of. When I was younger, rounds of $20-25 million were the standard. We can now syndicate larger rounds and provide more company-building resources, including capital, board support, manufacturing, clinical experience, regulatory advice, and operational guidance. With a current portfolio of over 40 companies, we believe we can help run companies effectively. On the portfolio front, we continue to see great milestone cadence across companies advancing through clinical and regulatory paths, along with significant business development activities. We have celebrated several major exits from prior funds, which underpins investor confidence.

      How do you balance investing in high-risk, high-reward mechanisms with the need to deliver tangible therapies in the near term?

      Marco Boorsma:That's a great question for a venture capital investor and fund manager. We operate from a fund perspective, balancing investments in advanced, validated opportunities with bold, high-impact science. To manage higher-risk investments, we use stage-gated funding tied to pre-agreed translational milestones, based on preclinical models, reproducible in vivo signals, early safety PK, and early clinical data.Strong go/no-go decisions are crucial. If something doesn’t work, we cut it and focus our capital on more promising companies. Operational support helps de-risk operations and execution.

      From an R&D perspective, we focus on the endgame. Where does this program need to go from discovery to approval, following regulatory guidelines early on.Funnel experiments to human-relevant, quantitative readouts early. Invest in translational biomarkers that link preclinical and clinical stages, ideally using human-derived assays like organoids. Prioritize CMC deliverability. Ensure the drug can be produced at scale and at the right cost. Assemble cross-functional teams from the start, including biologists, translational medicine experts, regulatory advisors, and manufacturing expertise. Early priorities include over-reliance on a single legacy animal model that’s not translational, sticking to convenient but non-predictive assays, and deferring endpoint discussions.Regulatory endpoints must align with clinical meaningfulness early on.


      Source:123RF

      As aging becomes a megatrend, which areas do you think are closest to yielding transformative therapies?

      Marco Boorsma:Many common diseases are related to aging, such as Alzheimer’s, metabolic and fibrotic diseases, and cardiovascular diseases.Neurodegenerative diseases now target underlying disease biology more effectively, with the first drugs for Alzheimer’s approved in decades. But there's still much to do. AI will enable faster strides in neurodegenerative diseases, kidney, and metabolic diseases. With significant advancements and interest in metabolic diseases, thanks to GLPs and obesity-related research, big strides are expected soon.Immune aging shows early promise but will take longer to benefit patients. So, some areas are around the corner, others mid-term, and some further out but exciting.

      For us, we continue to look into new biology because for diseases like Alzheimer’s, despite great strides in the past three years, there's still a lot to do. The same goes for ALS, Parkinson’s, and other aging diseases of the central nervous system.As investors, we need to ensure that great science results in viable drugs.Larger funds enable us to join bigger rounds and give companies the financial runway to reach meaningful clinical milestones. This applies not only to aging companies but across our portfolio.In company building, novel biology requires longer development times and more capital.Now, we can fund these endeavors much better than historically with our earlier funds.

      In 2022, you spoke on our Healthy Aging Forum, sharing your insights on the next frontiers in tackling age-related disorders. How have those frontiers evolved since, and where is the boldest opportunity now?

      Marco Boorsma:The field has evolved in two distinctive branches. Near-term translational programs target more validated disease-specific biology in diseases like fibrosis, kidney disease, metabolic disorders, and some neuro targets. Meanwhile, earlier mechanistic aging biology approaches focus on immune remodeling, epigenetic clocks, and systemic metabolism.These complex diseases are steadily accumulating translationally relevant biomarkers and better models to predict where to go in drug development.Our playbook combines company building and growth capital, operating across both branches at the earliest stages.


      Source:123RF

      The boldest opportunity now lies in translating mechanistic aging biology into disease-modifying medicines.There's still a lot of work to be done, involving many researchers, developers, and funders like us. For example, researchers are exploring ways to eliminate senescent cells to increase the human healthspan, examining the systemic metabolic state of aging people, and targeting fibrotic conditions in various organs. These areas are rich in opportunity and bold in their approach to finding novel treatments.

      As aging becomes a global priority, how do you perceive the current strengths and gaps in aging-related R&D? How does Forbion think about positioning itself within this international landscape?

      Marco Boorsma:Here in Europe, we have deep biology expertise at academic centers, excellent small molecule and biologics chemistry, manufacturing groups, and growing translational infrastructure and clinical sites. Europe is also making great strides in developing interesting science. For example, in aging and broader drug development, AI now plays a significant role in drug discovery, target validation, and even assessing business plans efficiently.

      However, gaps remain,such as the lack of standardized validated biomarkers, especially in aging.We need biomarkers related to biological age to execute clinical trials efficiently.Certain new treatments are needed to reach specific parts of the aging brain, and manufacturing capacity for these treatments needs to be developed further. Also,we need to translate the science into drug development companies.

      Forbion contributes operationally by helping companies with an extended network of advisors, scientists, ex-pharma executives, and academics. We guide companies on scaling, clinical, and CMC, leading larger financing rounds, and being there for the long term to reduce execution risk and increase the probability of success. With our growing company and footprint, notably our Boston presence, we invest where the best science and execution teams are, providing local operating support in Europe and North America. We co-invest with leading US funds when appropriate and leverage our company-building DNA to de-risk European innovation for global markets. Larger funds enable greater follow-on capacity and faster scaling. We’ve also collaborated with Chinese pharma companies, developing high-quality programs in North America and Europe, which has been fruitful.

      Looking at the future, 10 years from now, will the conversation around healthy aging still revolve around today's challenges, or do you foresee entirely new issues emerging?

      Marco Boorsma:Longevity is great, but quality of life is key.Healthy aging is about extending lifespan while maintaining good quality of life.Forbion's focus remains on disease-focused, patient-focused treatments.Treating diseases effectively will naturally extend lifespan.We invest in addressing diseases that limit lifespan and impact quality of life, ensuring that people age healthily.

      I wish today's diseases could be treatable in 10 years. Many current priorities like fibrosis, neurodegenerative diseases, and metabolic diseases will still be there due to lifestyle factors and an aging population.But I expect a shift towards precision healthy aging, based on validated biomarkers of biological age, and individualized risk scores.Combination treatments addressing aging as a multi-axis problem and advancements in delivery systems will make interventions more accessible.AI will centralize this evolution, speeding up innovation and refining clinical trial designs.The core clinical problems remain, but tools, regulatory frameworks, and patient stratification will be more sophisticated. Forbion will continue to support innovative science from early stages to commercialization.

      參考資料:

      [1] A Trailblazer in Neuroscience and Biotech Leadership. Retrieved JNovember 4, 2025, from https://www.targetals.org/2025/03/28/a-trailblazer-in-neuroscience-and-biotech-leadership/

      免責聲明:本文僅作信息交流之目的,文中觀點不代表藥明康德立場,亦不代表藥明康德支持或反對文中觀點。本文也不是治療方案推薦。如需獲得治療方案指導,請前往正規醫院就診。

      版權說明:歡迎個人轉發至朋友圈,謝絕媒體或機構未經授權以任何形式轉載至其他平臺。轉載授權請在「藥明康德」微信公眾號回復“轉載”,獲取轉載須知。

      特別聲明:以上內容(如有圖片或視頻亦包括在內)為自媒體平臺“網易號”用戶上傳并發布,本平臺僅提供信息存儲服務。

      Notice: The content above (including the pictures and videos if any) is uploaded and posted by a user of NetEase Hao, which is a social media platform and only provides information storage services.

      相關推薦
      熱點推薦
      34 萬周薪已談妥?曼聯冬窗急轉彎,放棄塞門約瞄準大魚

      34 萬周薪已談妥?曼聯冬窗急轉彎,放棄塞門約瞄準大魚

      瀾歸序
      2025-12-26 02:00:00
      鐘麗緹亮相芭莎之夜,胸大腚圓胖到不敢認,一大把年紀還玩性感

      鐘麗緹亮相芭莎之夜,胸大腚圓胖到不敢認,一大把年紀還玩性感

      黃小仙的搞笑視頻
      2025-12-24 11:46:44
      我家水費每月四萬,關掉閘門后,物業發來消息:今天整棟樓停水

      我家水費每月四萬,關掉閘門后,物業發來消息:今天整棟樓停水

      船長與船1
      2025-12-20 10:39:50
      中國拒絕哈薩克斯坦稀土借道,美國算盤落空

      中國拒絕哈薩克斯坦稀土借道,美國算盤落空

      胥言
      2025-12-04 14:58:40
      拜仁為奧利塞標出天價,防止巴黎、曼城、皇馬挖角

      拜仁為奧利塞標出天價,防止巴黎、曼城、皇馬挖角

      星耀國際足壇
      2025-12-25 23:31:30
      中組部:公職人員退休后未經批準經商(包括當律師)的,不再保留黨政機關退休金等待遇

      中組部:公職人員退休后未經批準經商(包括當律師)的,不再保留黨政機關退休金等待遇

      新浪財經
      2025-11-18 12:46:38
      國王大孫女獨美!英王室圣誕禮拜,金發夏洛特公主打假莉莉貝特

      國王大孫女獨美!英王室圣誕禮拜,金發夏洛特公主打假莉莉貝特

      調侃國際觀點
      2025-12-26 00:44:15
      同仁堂集團:持續推動四川健康產品下架、召回涉事產品,責令李聲義辭去四川健康公司總經理職務

      同仁堂集團:持續推動四川健康產品下架、召回涉事產品,責令李聲義辭去四川健康公司總經理職務

      澎湃新聞
      2025-12-25 19:22:29
      妻子與男閨蜜在歐洲玩15天,接到電話立馬回家,卻已于事無補

      妻子與男閨蜜在歐洲玩15天,接到電話立馬回家,卻已于事無補

      紙鳶奇譚
      2025-12-23 10:37:30
      1毫克足以致命!無藥可解!29歲小伙連吃三碗,肝腎衰竭

      1毫克足以致命!無藥可解!29歲小伙連吃三碗,肝腎衰竭

      健身狂人
      2025-11-25 10:34:16
      就在剛剛!昔日總冠軍官宣NBA外援加盟!上賽季場均23分6板4助3斷

      就在剛剛!昔日總冠軍官宣NBA外援加盟!上賽季場均23分6板4助3斷

      老吳說體育
      2025-12-25 17:18:19
      黃維特赦后赴西柏坡,觀后長嘆:蔣介石當敗,我輸得不冤

      黃維特赦后赴西柏坡,觀后長嘆:蔣介石當敗,我輸得不冤

      嘮叨說歷史
      2025-12-25 14:39:05
      剛剛,高中輟學生創辦的 AI 公司,被英偉達花 1400 億「收購」了

      剛剛,高中輟學生創辦的 AI 公司,被英偉達花 1400 億「收購」了

      愛范兒
      2025-12-25 11:43:26
      普京:盡管困難重重,俄羅斯仍在前進

      普京:盡管困難重重,俄羅斯仍在前進

      看看新聞Knews
      2025-12-25 12:53:05
      下月起,你的房貸利率有調整!

      下月起,你的房貸利率有調整!

      六安新周報
      2025-12-25 11:31:13
      為干掉越軍狙擊手,一戰士趴水坑40小時,忽見一塊石頭移動一下

      為干掉越軍狙擊手,一戰士趴水坑40小時,忽見一塊石頭移動一下

      云端小院
      2025-12-25 09:12:15
      不接受一國兩制?20萬島內武裝棄械?明確臺灣省最終結局?

      不接受一國兩制?20萬島內武裝棄械?明確臺灣省最終結局?

      文史旺旺旺
      2025-12-24 20:17:22
      靈魂拷問:徐院長與“徐小姐”,究竟是何關系?

      靈魂拷問:徐院長與“徐小姐”,究竟是何關系?

      西門老爹
      2025-12-24 11:50:15
      世上沒有后悔藥!無妻無子、與保姆相伴的何炅,已然走上另一條路

      世上沒有后悔藥!無妻無子、與保姆相伴的何炅,已然走上另一條路

      巧手曉廚娘
      2025-12-24 16:30:32
      保護心臟,朝左睡還是朝右睡好?醫生:若想心臟健康,做好...

      保護心臟,朝左睡還是朝右睡好?醫生:若想心臟健康,做好...

      袁醫生課堂
      2025-12-25 07:34:23
      2025-12-26 06:44:49
      藥明康德 incentive-icons
      藥明康德
      創建賦能平臺,承載醫藥夢想
      8066文章數 17521關注度
      往期回顧 全部

      財經要聞

      新規來了,年化超24%的小貸被即刻叫停

      頭條要聞

      韓國"最毒"財閥千金被捕 韓國人稱"經過她身邊就會死"

      頭條要聞

      韓國"最毒"財閥千金被捕 韓國人稱"經過她身邊就會死"

      體育要聞

      約基奇有多喜歡馬?

      娛樂要聞

      朱孝天把阿信好意當球踢!

      科技要聞

      小米17Ultra發布,徠卡2億像素 ,6999元起

      汽車要聞

      速來!智界在上海西岸準備了年末潮流盛典

      態度原創

      家居
      房產
      本地
      游戲
      公開課

      家居要聞

      經典彌新 品味浪漫居所

      房產要聞

      太猛了!單月新增企業4.1萬家,又一波巨頭涌向海南!

      本地新聞

      這輩子要積多少德,下輩子才能投胎到德國當狗

      逆水寒頂流主播沉迷倩女!三界的魅力藏不住了

      公開課

      李玫瑾:為什么性格比能力更重要?

      無障礙瀏覽 進入關懷版 主站蜘蛛池模板: 国产v综合v亚洲欧美大天堂| jizz在线视频| 精品视频九九| 日本久久久久久久做爰片日本| 成人区人妻精品一熟女| 在线A级毛片无码免费真人| 色悠悠撸视频| 峨眉山市| 久久精品囯产精品亚洲| 免费无码又爽又刺激高潮的视频| 中文字幕在线视频不卡一区二区| 三浦在线| 大香蕉一区| 日韩欧美卡一卡二卡新区| 亚洲丶国产丶欧美一区二区三区| 999福利激情视频| 国产xxx18| 亚洲精品久久久久久一区二区| 国产精品任我爽爆在线播放| 日韩在线视频网| 色哟哟91| 久久久久亚洲精品中文字幕| av天堂永久资源网| 免费无码黄十八禁网站| 亚洲video| 一色屋精品视频在线观看| 国产熟人av一二三区| 亚洲成人视屏| 郸城县| 久久中文字幕无码专区| 99视频精品全部免费 在线| 亚洲最大淫贼网| 26uuu国产日韩综合| 国产爆乳无码av在线播放| 欧美日韩视频综合一区无弹窗 | 亚洲AV一二三| 亚洲综合无码一区二区三区| 全部孕妇毛片丰满孕妇孕交| 婷婷综合缴情亚洲| 欧美阿V| 亚洲日韩国产成网在线观看|