編者按：去年，荷蘭風(fēng)險(xiǎn)投資機(jī)構(gòu)Forbion通過(guò)兩支新基金完成逾20億歐元募資，創(chuàng)下該機(jī)構(gòu)迄今最大規(guī)模的融資紀(jì)錄。這筆資金預(yù)計(jì)將用于支持約30家企業(yè)，加速創(chuàng)新生物技術(shù)公司的成長(zhǎng)，為全球患者帶來(lái)具有深遠(yuǎn)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(shù)投資戰(zhàn)略方面發(fā)揮著關(guān)鍵作用。近日，我們與Marco Boorsma博士展開對(duì)話，憑借其發(fā)現(xiàn)和培育突破性科學(xué)成果方面的深厚經(jīng)驗(yàn)，他分享了對(duì)衰老相關(guān)治療創(chuàng)新領(lǐng)域的重大機(jī)遇與現(xiàn)實(shí)挑戰(zhàn)的獨(dú)到見(jiàn)解。

Boorsma博士在生物醫(yī)藥行業(yè)擁有超過(guò)20年的豐富經(jīng)驗(yàn)，兼具深厚的學(xué)術(shù)背景與廣泛的產(chǎn)業(yè)實(shí)踐。在其職業(yè)歷程中，他曾主導(dǎo)創(chuàng)立VectorY Therapeutics并擔(dān)任創(chuàng)始首席執(zhí)行官，同時(shí)成功孵化NorthSea Therapeutics、Oxitope Pharma、Dezima Pharma等多家創(chuàng)新企業(yè)。其中，Dezima Pharma被安進(jìn)（Amgen）以最高15億美元收購(gòu)。目前，Boorsma博士仍活躍于產(chǎn)業(yè)前沿，擔(dān)任Calluna Pharma、Orbis Medicines等多家生物技術(shù)公司的董事會(huì)成員。

Boorsma博士，祝賀Forbion在去年完成了迄今規(guī)模最大的基金募集！回顧過(guò)去近一年的進(jìn)展，是否可以分享一些值得關(guān)注的里程碑？

Marco Boorsma博士：這一路走來(lái)，成果豐碩，我們深感自豪。在過(guò)去一年中，我們已投資至少10家具有發(fā)展?jié)摿Φ男屡d企業(yè)，穩(wěn)步落實(shí)資金規(guī)劃，這與我們?cè)谖磥?lái)兩年至兩年半內(nèi)通過(guò)成長(zhǎng)基金和風(fēng)險(xiǎn)基金支持約30家企業(yè)的規(guī)劃一致。更為充裕的資金使我們及被投企業(yè)能夠主導(dǎo)更大規(guī)模的融資輪次。如今，超過(guò)1億美元的單輪融資已屢見(jiàn)不鮮，而在我的職業(yè)生涯早期，2000萬(wàn)至2500萬(wàn)美元的融資規(guī)模才是常態(tài)。通過(guò)組織更大規(guī)模的聯(lián)合融資，我們能為企業(yè)提供從資本注入、董事會(huì)指導(dǎo)、生產(chǎn)優(yōu)化、臨床經(jīng)驗(yàn)分享，到監(jiān)管咨詢及運(yùn)營(yíng)指導(dǎo)等全方位的建設(shè)資源。目前，我們的投資組合已涵蓋超過(guò)40家企業(yè)。我們有充分的信心，能夠助力企業(yè)高效運(yùn)營(yíng)。在我們所投資的公司中，多家企業(yè)在臨床開發(fā)、監(jiān)管推進(jìn)以及業(yè)務(wù)拓展方面不斷達(dá)到重大里程碑。

在投資中，您如何平衡前沿機(jī)制研究帶來(lái)的高風(fēng)險(xiǎn)和高回報(bào)，與在較短周期內(nèi)推動(dòng)療法落地的需求？

Marco Boorsma博士：這對(duì)風(fēng)險(xiǎn)投資人和基金管理人而言是個(gè)重要的問(wèn)題。我們始終從基金整體配置的角度出發(fā)，在投資布局上進(jìn)行平衡：一方面支持相對(duì)成熟、已有驗(yàn)證數(shù)據(jù)的項(xiàng)目；另一方面布局具有高影響力的前沿科學(xué)探索。對(duì)于風(fēng)險(xiǎn)更高的項(xiàng)目，我們采用與預(yù)先約定的轉(zhuǎn)化里程碑掛鉤的階段性投資機(jī)制，并依據(jù)臨床前模型有效性、可重復(fù)的體內(nèi)數(shù)據(jù)、早期安全性及藥代動(dòng)力學(xué)（PK）數(shù)據(jù)，以及初步臨床數(shù)據(jù)等因素進(jìn)行評(píng)估。明確的“繼續(xù)/終止”決策機(jī)制至關(guān)重要，一旦項(xiàng)目進(jìn)展未達(dá)預(yù)期，我們會(huì)果斷停止投入，將資金轉(zhuǎn)投至更具潛力的企業(yè)。此外，我們通過(guò)運(yùn)營(yíng)支持降低企業(yè)在運(yùn)行和執(zhí)行層面的風(fēng)險(xiǎn)。

在研發(fā)層面，我們始終著眼于終局：明確從藥物發(fā)現(xiàn)到獲批上市的整體路徑，并在項(xiàng)目早期就遵循監(jiān)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(guān)、可產(chǎn)生量化結(jié)果的實(shí)驗(yàn)體系；同時(shí)，投入資源開發(fā)可銜接臨床前與臨床研究階段的轉(zhuǎn)化生物標(biāo)志物，并倡導(dǎo)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(jìn)行規(guī)?；a(chǎn)。在團(tuán)隊(duì)架構(gòu)方面，我們從項(xiàng)目啟動(dòng)階段就組建包含生物學(xué)家、轉(zhuǎn)化醫(yī)學(xué)專家、監(jiān)管顧問(wèn)及生產(chǎn)工藝專家的多學(xué)科團(tuán)隊(duì)。此外，項(xiàng)目早期需注重避免研發(fā)中的常見(jiàn)誤區(qū)：例如過(guò)度依賴單一且缺乏轉(zhuǎn)化價(jià)值的傳統(tǒng)動(dòng)物模型，延用便利但無(wú)法有效預(yù)測(cè)人體反應(yīng)的檢測(cè)方法，或是推遲對(duì)臨床終點(diǎn)的討論。需要強(qiáng)調(diào)的是，所設(shè)定的監(jiān)管終點(diǎn)必須從一開始就具備明確的臨床意義。

圖片來(lái)源：123RF

隨著老齡化成為全球化大趨勢(shì)，您認(rèn)為哪些領(lǐng)域最有可能率先產(chǎn)生變革性療法？

Marco Boorsma博士：許多常見(jiàn)疾病都與衰老相關(guān)，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(jīng)退行性疾病領(lǐng)域，如今我們已能夠更有效地靶向其根本生物學(xué)機(jī)制進(jìn)行干預(yù)，幾十年來(lái)首批治療阿爾茨海默病的新藥已獲批準(zhǔn)，但仍有大量挑戰(zhàn)有待攻克。人工智能將推動(dòng)神經(jīng)退行性疾病、腎臟疾病及代謝疾病領(lǐng)域加速取得突破。得益于GLP-1類藥物及肥胖相關(guān)研究的進(jìn)展，代謝疾病領(lǐng)域已取得實(shí)質(zhì)性進(jìn)展并備受矚目，預(yù)計(jì)不久將迎來(lái)重大突破。免疫衰老領(lǐng)域雖已初現(xiàn)曙光，但真正惠及患者尚需時(shí)間?？傮w而言，某些領(lǐng)域的突破已近在眼前，有些尚處于中期發(fā)展階段，另一些則雖需更長(zhǎng)時(shí)間但前景可期。

我們將持續(xù)聚焦于新興生物學(xué)機(jī)制的探索，盡管過(guò)去三年阿爾茨海默病等領(lǐng)域取得了重大進(jìn)展，但仍有大量工作需要推進(jìn)。肌萎縮側(cè)索硬化（ALS）、帕金森病以及其他中樞神經(jīng)系統(tǒng)衰老相關(guān)疾病領(lǐng)域也面臨著類似局面。作為投資者，我們的目標(biāo)是確保優(yōu)秀的科研成果能夠轉(zhuǎn)化為可行的藥物。更充裕的資金使我們有能力參與更大規(guī)模的融資輪次，為企業(yè)提供足夠資金支持，助其達(dá)到重要臨床里程碑。這一原則不僅適用于衰老領(lǐng)域企業(yè)，也適用于我們的整個(gè)投資組合。從企業(yè)構(gòu)建角度來(lái)看，基于創(chuàng)新生物學(xué)機(jī)制的藥物開發(fā)往往需要更長(zhǎng)的研發(fā)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(qiáng)大的能力，可為這類需要長(zhǎng)期投入的創(chuàng)新項(xiàng)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(guān)于應(yīng)對(duì)衰老相關(guān)疾病的下一代前沿技術(shù)的洞見(jiàn)。此后這些前沿領(lǐng)域出現(xiàn)了哪些新進(jìn)展？當(dāng)前最具突破性的機(jī)遇又在哪里？

Marco Boorsma博士：這一領(lǐng)域已逐漸分化出兩個(gè)相對(duì)清晰的方向。一方面，近期轉(zhuǎn)化項(xiàng)目更聚焦于纖維化、腎臟疾病、代謝紊亂等領(lǐng)域中已獲驗(yàn)證的疾病特異性生物學(xué)機(jī)制，以及部分神經(jīng)系統(tǒng)靶點(diǎn)。另一方面，更早期的機(jī)制性衰老生物學(xué)研究則側(cè)重于免疫重塑、表觀遺傳“時(shí)鐘”及全身性代謝調(diào)控。在這些復(fù)雜疾病領(lǐng)域，具備轉(zhuǎn)化潛力的生物標(biāo)志物正不斷積累，能夠更精準(zhǔn)指引藥物開發(fā)的預(yù)測(cè)模型也逐漸建立。我們的策略是將企業(yè)構(gòu)建與資本增長(zhǎng)相結(jié)合，在上述兩大方向的早期階段同步布局。

圖片來(lái)源：123RF

當(dāng)前最具突破性的機(jī)遇，在于將機(jī)制性衰老生物學(xué)研究成果轉(zhuǎn)化為改變疾病進(jìn)程的療法。實(shí)現(xiàn)這一目標(biāo)，仍需要眾多科研人員、藥物開發(fā)團(tuán)隊(duì)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(xì)胞以延長(zhǎng)人類健康壽命的方法，研究老年人群的全身代謝狀態(tài)，并針對(duì)多器官纖維化病變展開攻關(guān)。這些領(lǐng)域不僅充滿機(jī)遇，也以大膽創(chuàng)新的方式推動(dòng)著新型療法的誕生。

隨著老齡化成為全球范圍內(nèi)的重要議題，您如何看待當(dāng)前衰老相關(guān)研發(fā)工作的優(yōu)勢(shì)與不足？Forbion如何確定自身在國(guó)際格局中的定位？

Marco Boorsma博士：歐洲擁有生物學(xué)研究底蘊(yùn)深厚的學(xué)術(shù)中心、優(yōu)秀的小分子及生物制品化學(xué)與生產(chǎn)團(tuán)隊(duì)，以及日益完善的轉(zhuǎn)化基礎(chǔ)設(shè)施和臨床試驗(yàn)中心。歐洲在推動(dòng)前沿科學(xué)研究方面也取得了顯著進(jìn)展，例如，在衰老及更廣泛的藥物研發(fā)領(lǐng)域，人工智能如今在藥物發(fā)現(xiàn)、靶點(diǎn)驗(yàn)證乃至高效評(píng)估商業(yè)計(jì)劃等方面都發(fā)揮著重要作用。

然而，短板仍然存在。例如，目前仍缺乏標(biāo)準(zhǔn)化且經(jīng)過(guò)驗(yàn)證的生物標(biāo)志物，尤其是在衰老研究領(lǐng)域。我們需要與生物學(xué)年齡相關(guān)的生物標(biāo)志物來(lái)有效開展臨床試驗(yàn)。此外，一些新型療法需精準(zhǔn)遞送到衰老大腦的特定區(qū)域，而相關(guān)生產(chǎn)能力仍需進(jìn)一步提升。不僅如此，我們還需要將科研成果成功轉(zhuǎn)化為藥物研發(fā)企業(yè)。

圖片來(lái)源：123RF

Forbion通過(guò)廣泛的顧問(wèn)、科學(xué)家、前醫(yī)藥高管及學(xué)者網(wǎng)絡(luò)，為企業(yè)提供運(yùn)營(yíng)支持。我們?cè)谝?guī)?；a(chǎn)、臨床開發(fā)及CMC、以及主導(dǎo)更大規(guī)模的融資輪次方面為企業(yè)提供指導(dǎo)，并長(zhǎng)期陪伴企業(yè)成長(zhǎng)，降低執(zhí)行風(fēng)險(xiǎn)、提高成功率。隨著Forbion規(guī)模與業(yè)務(wù)版圖的擴(kuò)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(zhí)行團(tuán)隊(duì)的地區(qū)，并在歐洲和北美地區(qū)提供本地化運(yùn)營(yíng)支持。在適當(dāng)?shù)那闆r下，我們會(huì)與美國(guó)頂尖的基金共同投資，并運(yùn)用自身在企業(yè)建設(shè)方面的經(jīng)驗(yàn)，幫助歐洲的創(chuàng)新成果降低進(jìn)入全球市場(chǎng)的風(fēng)險(xiǎn)。更大規(guī)模的基金可提升后續(xù)投資能力，并加速企業(yè)規(guī)模擴(kuò)張。我們還與中國(guó)醫(yī)藥企業(yè)開展合作，在北美與歐洲地區(qū)開發(fā)高質(zhì)量項(xiàng)目，并取得良好成效。

展望未來(lái)，您認(rèn)為十年后健康老齡化的討論會(huì)繼續(xù)圍繞當(dāng)今的挑戰(zhàn)，還是會(huì)出現(xiàn)全新的議題？

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

我期望當(dāng)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(jīng)退行性疾病和代謝性疾病在未來(lái)仍將繼續(xù)存在，但我認(rèn)為未來(lái)將轉(zhuǎn)向基于經(jīng)過(guò)驗(yàn)證的生物學(xué)年齡標(biāo)志物和個(gè)體化風(fēng)險(xiǎn)評(píng)分的精準(zhǔn)健康老齡化模式。針對(duì)衰老這一多維問(wèn)題的聯(lián)合治療方案，以及藥物遞送系統(tǒng)的進(jìn)步將使干預(yù)措施更具可及性。人工智能將處于這一變革的核心，加速創(chuàng)新進(jìn)程并優(yōu)化臨床試驗(yàn)設(shè)計(jì)。盡管核心臨床挑戰(zhàn)仍將存在，但診療工具、監(jiān)管框架和患者分層將更加精細(xì)化。Forbion也將繼續(xù)從早期階段到商業(yè)化全程支持創(chuàng)新科學(xué)的發(fā)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/

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