里程碑合作背后：格博生物與分子膠的星辰大海｜專訪盧剛博士丨Bilingual

2026年2月12日，距離農歷春節僅剩五天。一大早，格博生物（GluBio Therapeutics）獲得賽諾菲（Sanofi）3000萬美元的消息傳來。作為格博生物創始人、董事長兼首席執行官，盧剛博士來不及回復手機上一連串的祝賀消息，便趕往機場。忙碌一年后，他終于得以短暫放下工作，趕去與家人團聚。

飛機升空，舷窗下方城市的燈火通明使他感到久違的放松。作為一家初創公司的掌舵人，他習慣了未雨綢繆，也經歷過無數輾轉反側的時刻——創新藥研發“九死一生”的常態，創業路上的艱辛，時刻提醒著他前行的風險。而此刻，歷經數月談判、成功完成這次融資之后，“如釋重負”是他最真切的心境。

與此同時，數千里外的北方草原上，一位40多歲的男性患者正滿懷期待地規劃春節行程。他是一名難治的淋巴瘤患者，因侵襲至眼眶的病灶險些失明。而如今，他已回歸正常生活，只要按期服藥，他幾乎感覺不到疾病的存在。

將他從病痛深淵中拽回的，是一項正在進行的臨床試驗。作為參與者，他有機會用上了格博生物研發管線中的一款在研新藥GLB-002——那是盧剛博士和團隊多年心血的成果之一。

“你能想象嗎？”盧剛博士激動地說，“這款藥目前還在臨床試驗階段，但我們已經在一些患者身上看到了令人鼓舞的藥效反應。看到他們生活上的積極改變，這種成就感，無可比擬。”

這兩個畫面，共同勾勒出格博生物五年來發展的注腳：一邊是科學家和創業者的抉擇與堅守，一邊是臨床上患者生活的悄然改變。而連接它們的，是一家公司、一個行業對“做創新藥”的投入與執著。

“我們的產品數據包足夠扎實”

2021年春天，盧剛博士離開藥企，從“舒適區”走向一條截然不同的道路。

“我要自己支配資源，開發創新藥。”當年3月，他和志同道合的伙伴付利強博士一起創立了格博生物，開啟了一場“冒險”之旅。

公司啟航之初，便聚焦分子膠降解劑的研發。分子膠，是近年來快速發展的新藥研發新方向。盧剛博士將其比作是新藥研發的“星辰大海”。但他與分子膠的緣分，可以追溯至更早。

早在2010年，科學家率先發現了沙利度胺可以與一個E3泛素連接酶CRBN結合，但仍未能完全揭示沙利度胺的作用機制。受好奇心驅動，彼時尚在哈佛大學醫學院從事研究的盧剛博士便開始設計一個利用高通量篩選方式研究蛋白穩定性的平臺。2013年底，盧剛博士作為第一作者在Science期刊發表論文，闡明了度胺類免疫調節藥物來那度胺的分子膠作用機制。該論文與同期發表的另一篇研究論文，首次共同明確了這一機制，被視為分子膠領域的里程碑。

“從那時起，我就堅定認為，分子膠是未來新藥開發最具潛力的方向之一。”

為什么？因為太多疾病靶點常受困于“不可成藥”——要么沒有結合口袋，或者有結合口袋但無法抑制其功能。而分子膠的邏輯完全不同：它不需要強結合，只需要一個微弱、短暫的結合，就能誘導E3連接酶高效標記目標蛋白，引導它們的降解。

“人體內存在600多種E3連接酶，一萬多個蛋白。平均每個E3連接酶都有幾十個天然的底物蛋白。”盧剛博士語帶興奮，“假設未來有一天我們針對多數E3連接酶都能開發出全新的分子膠藥物，那么有多少新底物蛋白可以被分子膠藥物降解？這一領域的想象空間太大了。”

基于十余年分子膠研發經驗的積累，盧剛博士帶領團隊迅速布局，建立了自己專有的核心技術平臺——Glue Degrader Discovery（GDD?），并打造出一套完整的一體化研發體系，涵蓋靶點識別與驗證、多維蛋白降解篩選、AI驅動的分子膠理性設計，以及多樣化專有化合物庫等。

在分享分子膠發現與開發的關鍵思路時，他分享了兩個關鍵詞：一是“站在巨人的肩上”；二是“理性設計”。盧剛博士指出，得益于CRBN E3連接酶結構的高度可塑性，該領域的靶點并不難找——目前根據公開信息獲知的可降解蛋白就有成百上千個，但難點在于如何選擇可成藥靶點、如何理性設計對應的分子膠，以及如何優化分子的成藥性。

正因如此，團隊在過去多年積累的“know-how”，成為其最大優勢。盧剛博士擁有超過10年靶向蛋白降解領域的藥物研發經驗，加之創始團隊豐富的產業積淀，為產品的精準設計和開發奠定了堅實基礎，也進一步提升和強化了“理性設計”的實施能力和效率。

據介紹，格博生物從創立之初啟動的近十個研發項目，覆蓋腫瘤、自免和遺傳性疾病等多個治療領域，至今幾乎無一停滯，全部在穩步推進中。盧剛博士表示：“從靶點選擇到藥物分子設計，只有完全確定一款產品能夠潛在地為患者帶來更大獲益、值得往前推進，團隊才會下定決心立項。”

此次獲得賽諾菲青睞的GLB-005和GLB-007，是兩款靶向轉錄因子WIZ的在研分子膠項目。它們有希望在鐮狀細胞病領域為患者帶來突破性的治療選擇。

合作消息公布后，盧剛博士收到了來自全球多家媒體的采訪邀約。面對外界的關注與好奇，他的回答坦率而篤定：“我們的產品數據包足夠扎實。”

他進一步解釋，盡管市場上還有其他鐮狀細胞病在研管線，也有其他公司已經研發出靶向WIZ的分子膠在研管線，但格博生物憑借其分子選擇性、安全性等關鍵指標上的潛力贏得了信任。

“我們打動賽諾菲研發團隊的，是高質量的產品與扎實的研發數據。”盧剛博士表示，“從當前數據來看，這兩款產品具備真正的“best-in-class”潛力，有望解決尚未被滿足的臨床需求。”

致敬合作，眾行致遠

“這是天時、地利、人和的一次完美契合。”盧剛博士對這次合作這樣總結。

他表示，有了這筆新的資金注入，格博生物未來大約3年無需擔心現金流問題了。按照規劃，公司將在2026年啟動多項2期臨床研究，以及提交多個新的IND申報。

更關鍵的是，有了賽諾菲這樣的國際性合作伙伴的加持，這些在研藥物有望加速研發，以更快的速度釋放臨床潛力，真正走向全球病患。

這正是合作推動創新的生動寫照。從業多年，盧剛博士與投資機構、臨床機構、CXO乃至法務團隊均有深度合作。每一次碰撞，他都能感受到靈感的火花。合作也使格博生物能夠更加專注于自己最擅長的事——回歸科學本身。

尤其是五年的創業歷程，讓他更加堅信：找到專業且彼此契合的合作伙伴，至關重要。

采訪中，他還提到了公司創立五年來貫穿始終的一家合作伙伴——藥明康德。

“我們幾乎所有外部的化學合成都是在藥明康德做的。”盧剛博士說。早在國際藥企工作時，他就和藥明康德的化學團隊有過合作。創業之初，他和團隊幾乎沒有猶豫，一致決定把化學方面的工作交給了這個熟悉的伙伴。

他回憶起2022年與藥明康德子公司合全藥業攜手共渡難關的一段經歷。彼時受疫情影響，他一度擔心某個早期項目進度可能延誤。但藥明康德團隊最終如期且高質量地完成了兩個IND項目的需求交付。“那個時候大家都很困難，但我們的項目進度絲毫沒有間斷，我們真的非常感動。”

“藥明康德在很多地方都太給力了，尤其是一體化平臺，質量靠譜、效率很高。另外，藥明康德能為我們提供更多的想法，我們之間經常能碰撞出許多火花。”

圖片來源：123RF

在分子膠等蛋白降解領域，藥明康德的布局足夠早，積累了豐富的經驗。

有一次，一個小分子因合成難度大，給工藝開發和分析帶來極大挑戰。但憑借藥明康德平臺所提供的偶聯、結晶技術等全面能力，雙方共同努力最終克服了挑戰，保障項目按期完成。

古語說：“積力之所舉，則無不勝也；眾智之所為，則無不成也。”一個人的執念，一群人的堅守，一個行業的協作，最終匯聚成改變患者命運的力量。

走向未來的星辰大海

山海不遠，行則將至。

回顧創業初期的五年，盧剛博士將其定義為“階段性的勝利”。

但對于分子膠的未來，他的想象遠不止于此。“隨著分子文庫設計的多樣性，以及AIDD在理性設計中的深度應用，未來幾乎所有與疾病相關的蛋白，都有可能通過分子膠來實現降解。這個領域的邊界，正在被不斷拓寬。”

談及格博生物的前景，盧剛博士理性中透著確信的從容：“我們想做的是真正的創新藥，我們有想法，有對新藥研發的深刻理解，我們有‘know-how’，更有成功的經驗。如果有足夠的資源支撐，我們只會做得更好。”

創業之路從不平坦，但他從未后悔。“人生有能有幾回搏？博一下、拼一下！哪怕失敗，大不了從頭再來。”在他看來，人生短暫，真正值得在意的，不是世俗意義上的成功，而是“當你退休時回望數十年職業生涯，能清晰地看到——你真的做成了什么。”

這份信念，已經得到印證。正如開頭提到的那位患者，盡管格博生物的在研產品尚在臨床開發階段，未來仍存不確定性，卻已經為一些臨床患者帶來了積極的改變。

“當你看到那種改變時，就會覺得一切努力都有了意義——你真的幫助到了一些病人，開始滿足那些未被滿足的臨床需求。”他頓了頓，“那種時刻，真的非常鼓舞人心。”

Behind the Partnership: Dr. Gang Lu and the Vast Frontier of Molecular Glues

On February 12, 2026, news arrived early in the morning: GluBio Therapeutics had secured a $30 million strategic equity investment from Sanofi. As the Founder, Chairman, and CEO of GluBio, Dr. Gang Lu barely had time to acknowledge the flurry of congratulatory messages on his phone before heading to the airport. After a busy year, he was finally able to briefly set aside his work and rush to reunite with his family.

As the plane ascended, the bright city lights sprawling beneath his window offered a rare moment of relaxation. As the leader of a startup, he was accustomed to planning ahead and had endured countless sleepless nights—the reality of innovative drug R&D, the challenges of the entrepreneurial journey—constant reminders of the risks ahead. At this moment, however, after months of negotiations and successfully securing this financing, he felt profound relief.

Meanwhile, a patient in his 40s was eagerly planning his vacation itinerary. He had once suffered from refractory follicular lymphoma, with metastases to his eye socket that nearly caused blindness. Now, life had returned to normal: as long as he took his medication on schedule, he could barely feel the presence of the disease.

What pulled him from the throes of illness was an ongoing clinical trial. As a participant, he gained access to an investigational new drug GLB-002 from GluBio—one of the key achievements resulting from years of dedicated work by Dr. Lu and his team.

"Can you imagine?" Dr. Lu exclaimed excitedly. "Although this drug is still in the clinical trial phase, we have already observed encouraging preliminary responses in some patients. Seeing the positive changes in their lives—there's no comparable sense of achievement."

These two scenes together are hallmarks of GluBio's five-year journey:on one side, the choices and perseverance of a scientist and entrepreneur; on the other, the quiet transformation in patients' lives.Connecting them is a company's and an industry's commitment and dedication to "developing innovative medicines."

"Our Product Data Package is Solid and Compelling"

In the spring of 2021, Dr. Lu left a US biotech company, stepping out of his comfort zone and onto a distinctly different path.

"I wanted to control my own resources and develop innovative drugs," he stated. In March of that year, together with his partner, Dr. Liqiang Fu, he founded GluBio, embarking on an "adventurous" journey.

From its inception, the company focused on the research and development of molecular glue degraders. Molecular glues represent a rapidly evolving new frontier in drug discovery. Dr. Lu likens them to a "vast ocean of potential." His own connection with molecular glues, however, dates back even further.

As early as 2010, scientists discovered that thalidomide could bind to an E3 ubiquitin ligase called CRBN. However, the complete mechanism of action of thalidomide and its related analogues remained unveiled. Driven by curiosity, Dr. Lu, then still active in academia at Harvard Medical School, began researching and designing platforms to study protein stability using high-throughput screening methods. In late 2013, as first author, he published a paper in the journal Science explaining the molecular glue mechanism of action of the immunomodulatory drug lenalidomide (a thalidomide analogue). This paper, along with another study published in the same issue, is considered a milestone in the molecular glue field, being the first to clearly define this mechanism for lenalidomide.

"From that point on, I firmly believed that molecular glues represented one of the most promising directions for drug development."

Why? Because too many disease targets are plagued by being "undruggable"—they either lack a binding pocket, or possess one but cannot have their function inhibited.The logic of molecular glues is entirely different: they don't require strong binding. A weak, transient interaction is sufficient to induce the E3 ligase to tag the target protein for degradation.

"The human body has over 600 types of E3 ligases and more than 10,000 proteins. On average, each E3 ligase has dozens of substrate proteins," Dr. Lu explained. "Imagine if, one day in the future, we could develop molecular glue drugs targeting a majority of these E3 ligases. How many distinct proteins could be degraded? The potential of this field is enormous."

Building on over a decade of experience in molecular glue research and development, Dr. Lu led his team to move quickly, establishing their proprietary core technology platform—Glue Degrader Discovery (GDD?). They built a comprehensive, integrated R&D system covering target identification and validation, multi-dimensional protein degradation screening, AI-driven rational design of molecular glues, and diverse proprietary compound libraries.

When sharing key insights into molecular glue discovery and development, he highlighted two concepts:"standing on the shoulders of giants" and "rational design."Dr. Lu pointed out that given the high plasticity of the CRBN E3 ligase, finding targets in the CRBN-based molecular glue field isn't the main challenge—according to the information in the public domain, hundreds or potentially thousands of proteins can be degraded by CRBN-based molecular glue degraders. The real difficulty lies in determining which targets have high druggability, how to rationally design corresponding molecular glues, and how to optimize their drug-like properties.

Precisely because of this, the team's accumulated "know-how" over many years has become their greatest advantage. With Dr. Lu's more than 10 years of experience in targeted protein degradation drug R&D, combined with the founding team's rich industry expertise, they have laid a solid foundation for precise product design and development, further strengthening their practical ability for "rational design."

According to reports, of the nearly 10 R&D projects initiated by GluBio since its founding, spanning multiple disease areas including oncology, autoimmune disorders, and genetic diseases, virtually none have been halted; all are progressing steadily. Dr. Lu stated, "From target selection to drug molecule design, the team only greenlights a project when they are absolutely certain that a product can potentially bring greater benefits to patients and is worth advancing."

The two projects that attracted this recent interest, GLB-005 and GLB-007, are investigational molecular glue candidates targeting the transcription factor WIZ. They show promises in providing breakthrough treatment options for patients with sickle cell disease.

Following the announcement of the partnership with Sanofi, Dr. Lu received interview requests from numerous global media outlets. In response to the external attention and curiosity, his answer was frank and confident: "Our product data package is solid and compelling."

He further explained that although there are other sickle cell disease pipelines in the market, and some have also developed WIZ-targeting investigational molecular glues, GluBio earned trust through its potential in key metrics such as molecular selectivity and safety.

"What impressed the Sanofi team was our high-quality products and solid R&D data," Dr. Lu said. "These products possess genuine 'best-in-class' potential, and are expected to address unmet clinical needs."

A Tribute to Collaboration: Together We Go Far

"This was a perfect convergence of timing, opportunity, and synergy," Dr. Lu summarized regarding the partnership.

He noted that with this new capital injection, GluBio’s cash flow is secure for approximately the next three years. According to their plan, the company will initiate several Phase 2 clinical studies and submit several new INDs in 2026.

More critically, with the backing of an international partner like Sanofi, these investigational drugs can potentially advance through R&D more rapidly, unlocking their clinical potential faster to reach broader populations of patients in need.

This vividly illustrates how collaboration drives innovation. Throughout his years in the industry, Dr. Lu has engaged in deep collaborations with investment institutions, clinical organizations, CXOs, and legal teams. Each interaction sparks new ideas. Collaboration also allows GluBio to focus more sharply on what it does best—returning to the science itself.

His five-year entrepreneurial journey, in particular, has reinforced his belief that finding professional and compatible partners is crucial.

During the interview, he also mentioned a collaborative partner that has been with the company throughout its five-year history—WuXi AppTec.

"We do all of our external chemical synthesis with WuXi AppTec," Dr. Lu said. He had collaborated with WuXi AppTec's chemistry teams during his time at an international pharma company. When starting his own venture, he and his team decided without hesitation to entrust the chemistry work to this familiar partner.

He recalled a challenging period in 2022. Amidst the pandemic's disruptions, he worried that progress on an early-stage project might be delayed. However, working closely with WuXi STA, a subsidiary of WuXi AppTec, the team ultimately fulfilled the requirements for two IND projects on time and with high quality.

"It was a difficult time for everyone, yet our project timelines remained uninterrupted. We were truly touched."

Image source：123RF

"WuXi AppTec has been incredibly supportive in many ways, especially with their integrated platform—the quality is reliable, and the efficiency is high. Furthermore, they often bring additional ideas to the table, leading to many productive brainstorming sessions." This was particularly true in areas like molecular glues and protein degradation, where WuXi AppTec's early investments have resulted in a wealth of accumulated experience.

On one occasion, a small molecule with numerous chiral centers posed significant challenges for process development and analysis. However, by leveraging WuXi AppTec's conjugation technologies, crystallization expertise and other advanced technologies, the joint efforts of both teams ultimately overcame the challenge.

An ancient saying goes, "When collective strength is leveraged, nothing is insurmountable; when collective wisdom is employed, nothing is unachievable." The passion of one person, the persistence of a team, and the collaboration of an industry ultimately converge into the power to change patients' destinies.

Towards the Vast Ocean of Opportunity Ahead

Looking back on the initial five years of the startup, Dr. Lu defines them as a "phased victory."

But his vision for the future of molecular glues extends far beyond this. "With the increasing diversity of molecular library design and the deep application of digital technology platforms in rational design, potentially all disease-related proteins could someday be degraded using molecular glues. The boundaries of this field are constantly being pushed outward."

Discussing GluBio's prospects, Dr. Lu spoke with a calm conviction rooted in reason: "What we aim to do is create truly innovative medicines. We have the ideas, a deep understanding of drug R&D, the 'know-how,' and a track record of success. With sufficient resources, we can only do even better."

The entrepreneurial path is never smooth, but he harbors no regrets. "How many chances does one get in life to truly go for it? Take the plunge, give it your all! Even if you fail, you can always pick yourself up and start again." In his view, life is short, and what truly matters is not worldly success, but being able to "look back on a decades-long career upon retirement and clearly see—what you truly accomplished."

This belief has already found validation. Just like the patient mentioned at the beginning. Although GluBio's investigational product is still in clinical development and the future holds uncertainties, it has already made a meaningful difference in the lives of some patients.

"When you see changes like that, you feel that all the effort was worthwhile—you are truly helping some patients, beginning to meet those unmet clinical needs,"he paused for a moment. "Moments like that are incredibly inspiring."

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