S3.E7. 更好，更快，更進一步 Better, faster, further

 

開發和製造新藥的過程既複雜又昂貴，科學家探索並選擇他們認為最為相關的疾病結構，然後設計和測試所有可能結果與所選結構的相互作用。最後，他們安排患者進行研究並評估他們的結果。整個過程可能需要花數年時間，耗資數十億歐元，損耗率極高。數位化轉型將如其座右銘所說，徹底改變這些過程讓它更好、更快、更進一步。下列這三項例子說明了百靈佳殷格翰一直以來不斷研究、不斷變化的創新理念。

 

人工智慧軟體，虛擬分子模型和開放式創新理念目前正悄悄的滲入百靈佳殷格翰的研究實驗室中。我們的目標是開發更好的藥物，在擁有精準數據的基礎上，百靈佳殷格翰的科學家們可以在一開始就瞄準更高的目標，並且能夠對照全球研究的所有相關數據來對某種疾病的結構做出更確切的假設。智慧軟體促使研究過程可能達到一定的精確度，電腦在幾秒鐘內從實驗、外部研究團隊的文章和數據統計平台報告中讀取數以萬計的資訊，分析並找出它們之間的連結性。

數位化過程也有助於百靈佳殷格翰研究人員作業更快速，藥物開發通常需要透過模擬過程來操作，因此花的時間更長。從初步實驗，樣品設計和患者研究到為市場開發出的藥物，需要好幾年的時間。在最壞的情況下，因為救命藥物無法及時用於治療，這可能會使患者喪命。

此外，數位化還使我們的科學家們能透過開放式創新概念更進一步的發展。數位平台促使新的連結和合作，因此內部研究團隊與外部專家之間的交流能越來越多。

「數位技術讓我們研究過程中創造出更多的價值，幫助我們識別相關疾病的結構，去發現有希望的結果，並透過開放式創新概念，發現遠遠超過現今視野的驚喜。我們獲得的時間，質量和知識將使我們全球的患者受益」，負責創新部門的董事會成員Michel Pairet博士解釋道。

 

 

「數位技術正促使我們研究過程中創造出更多的價值。」
DRMICHEL PAIRET. 創新部門的董事總經理

通過合併使其更好
複雜的數據

即時更新

在開發每項藥物之前，研究人員需要確定他們想要解決的最相關疾病結構。為此，百靈佳殷格翰正在測試開發NTC Studio應用程式。NTC代表「New Therapeutic ConceptsL」，即為「新治療概念」。

廣泛的結合並分析來自內部和外部的數據，「與我們研究相關的訊息來自世界各地，這些訊息量每天都在增加」，項目負責人Jan Kriegl博士說。「托NTC Studio的福，研究人員可以接觸許多不同的消息來源，並了解當前最新的研究狀況。」

這個應用程式將內部研究項目的結果，科學出版物和專利內容以及臨床研究數據全部同步收集起來，以研究人員正在使用的術語來分類這些資料，並使研究人員能夠從這個合併資料庫發現尚未被發現的關連。

此外，NTC Studio還提供與在類似項目中工作或以前工作過的研究人員，更多合作的可能性。結合許多研究人員的知識，隨著時間的推移，我們能夠建立寶貴的知識基礎。

 

多虧人工智慧

從機器取出的分子

在智慧型手機螢幕上，一個組合複雜的分子形成了。研究數據像是化學結構顯示在螢幕上，下方也一一的列出了其屬性和數值。科學家現在必須做出決定，是要點擊綠色框框並接受建議還是點擊紅色框框拒絕？如果研究人員接受了人工智慧的建議，他可以繼續研究所顯示的分子結構；如果他拒絕，他將立即收到一個人工智慧給的新建議。ADAM是此人工智慧程式的名稱，目標在使開發藥物的人能更輕鬆。

ADAM這個縮寫代表：「advanced design assistant for molecules」，意思是 「高階分子設計助手」，這是至今為止百靈佳殷格翰研究中最先進的數位工具，不同的數位工具不斷的在幫助研究人員處理複雜的數據。

每個工具都知道：百靈佳殷格翰所有當前研究與歷史研究項目中的相關分子和數據資料。在幾秒鐘內，數位工具告知科學家百靈佳殷格翰研究項目中的分子變化資訊，這使該工具的用戶不需要每次都進行人工搜索。ADAM使用無數目前和以前研究項目的新訊息和數據，來不斷更新電腦程式算法。使用這項專有技術可提高藥物研究的效率，因此，ADAM將人與機器之間的合作提升到一個全新的水平。

「人體內的生物機能與過程非常複雜」，百靈佳殷格翰研究部的Matthias Zentgraf博士強調。「但藥物研究過程中，也經常有反復的問題出現。多虧了數位工具，我們將能夠在不久的將來更有效率的工作。ADAM已經展現了這項優勢。」

 

Discovering and developing new medicines is complex and expensive. Scientists explore and select what they think are the most relevant disease mechanisms, then design and test promising candidate molecules that interact with the selected mechanism. Finally, they organise patient studies and evaluate their results. All of that may take years and cost billions of euros with high attrition rates. The digital transformation will revolutionise these processes in line with the motto – better, faster, further. Three examples illustrate the changing nature of research at Boehringer Ingelheim.

 

A rtificial intelligence-supported software, virtual molecular models and open innovation are currently finding their way into Boehringer Ingelheim’s research laboratories. The goal is to develop better medicines. On the basis of highly precise data, scientists at Boehringer Ingelheim can aim higher right from the start: with an exact hypothesis on a certain disease mechanism that takes into account all relevant data from global research results. A smart software makes this kind of precision possible. Computers read the ever-growing flood of data from experiments, external research teams’ articles and the values reported in statistics portals in a matter of seconds, evaluate them and reveal links.

Digital processes also help Boehringer Ingelheim researchers to be faster, since drug development often takes too long using analogue processes. Several years can elapse from an idea via initial experiments, prototypes and patient studies to a medicine that is ready for the market. In the worst-case scenario, that may cost human lives since life-saving drugs will not be available in time for treatments.

In addition, digitalisation also takes our scientists further: through open innovation. Digital platforms make new connections and collaborations possible. The borders between internal research teams and external experts are increasingly porous.

“Digital technologies are boosting value creation in our research processes. They help us to identify relevant disease mechanisms, to discover promising molecules and to explore the unexpected far beyond current horizons – through open innovation. The time, quality and knowledge we gain thereby will above all benefit our patients worldwide,” explains Dr Michel Pairet, Member of the Board of Managing Directors with responsibility for the Innovation Unit.

 

“Digital technologies are boosting value creation in our research processes.”

DR MICHEL PAIRET Member of the Board of Managing Directors  with responsibility for the Innovation Unit

 

BETTER THROUGH MERGING COMPLEX DATA

Instantly up­to­date

Before starting a drug discovery project, researchers need to identify the most relevant disease mechanisms they want to address. For this, Boehringer Ingelheim is developing the NTC Studio application in a pilot project. The acronym stands for “New Therapeutic Concepts” NTC merges, that is to say combines and analyses, data from the widest range of internal and external sources. “The volume of information that is relevant for our research comes from all over the world and increases every day,” says the project leader, Dr Jan Kriegl. “Thanks to NTC Studio, researchers have access to many different sources and are always up-to-date with the current state of research.”

The application links results from internal research projects, content from scientific publications and patents, and clinical study data. The programme scours this information for terms which researchers are seeking, groups them and enables the researchers to detect unknown  connections from this merged perspective.

In addition, NTC Studio provides the possibility of effective  collaboration with researchers who are working, or have worked, on similar projects. Combining the internal know-how of many individual researchers makes it possible over time to build up a valuable fundament of knowledge.

 

FASTER THANKS TO ARTIFICIAL INTELLIGENCE

Molecules from a machine

A strand of molecules with many branches develops on a smartphone screen. Chemical structures appear, with properties and values listed below – this is research data. The scientist must now decide: should he click on the green box and accept the suggestion? Or click on the red box and reject it? If the researcher accepts the suggestion, he can continue to work on the molecule displayed. If he rejects it, he will instantly receive a new suggestion, generated by means of artificial intelligence. ADAM is the name of this application, which is intended to make life easier for those who develop medicines.

The abbreviation stands for “advanced  design assistant for molecules” and denotes the most  advanced digital assistant to date within research at Boehringer Ingelheim. Different digital assistants have been helping researchers in processing complex data for some time now.

Each assistant knows the relevant molecules and data points from all of Boehringer Ingelheim’s current research projects and also has access to historical project data. Within a few seconds, the assistants inform scientists about what is known about a molecule variant at Boehringer Ingelheim, without users having to search for it every time. ADAM constantly updates its algorithms with new  information and data from countless current and previous company projects. Use of this know-how raises efficiency in pharmaceutical research. ADAM thereby takes the interaction between man and machine to a completely new level.

“The biological processes in the human body are highly complex,” stresses Dr Matthias Zentgraf, of Boehringer Ingelheim’s Research Department. “But there are also frequently recurring questions in drug research. Thanks to digital assistants, we will be able to work much more efficiently here in the near future. ADAM already offers a foretaste of it.”

 

從她的角度你看到了什麼 SEE WHAT I SEE：THROUGH OTHERS’EYES

 

 

百靈佳殷格翰的研究人員在全球研發新藥，其版圖跨越國界與不同的大陸。通過遠端應用程式「XpertEye」，美國研究人員可以藉由智慧眼鏡，向德國實驗室的同事展示他正在做什麼，同樣的，德國的實驗室也能如此。這個應用程式能支持遠端合作，例如修復設備或數據分析，它的優勢是顯而易見的，例如，研究項目中的問題可以通過電子通訊解決，團隊不需要飛往世界的另一端。這不僅更具有發展性，還可以節省時間和成本。

Researchers at Boehringer Ingelheim are working on new medicines worldwide, across national frontiers and continents. With the remote app “XpertEye”, a researcher in the USA wearing smartglasses can show colleagues in a laboratory in Germany what he is working on, and vice versa. The app enables remote collaboration of an activity – such as repairing equipment, or data analysis. The advantages are obvious: instead of having to travel to the other side of the world to see colleagues, issues in research projects can be resolved by means of electronic communication. Not only is this more sustainable, it also saves time and cost. 

進一步透過開放式創新的方法

由我們設計，由您開啟

 

百靈佳殷格翰創新平台「opnMe.com」的推出，旨在促進藥物研究合作領域，擴展到公司以外的範圍。例如，快遞員可能會送包裹到北美一所大學，包裹內是一些小管子，管子裡裝有百靈佳殷格翰研究組織、一些非常具有價值的分子，這些分子都是百靈佳殷格翰內部開發的高品質化合物和專利產品。美國科學家透過opnMe.com平台，訂購了這些免費的產品，在這個平台上，該公司提供了30種分子化合物，這些分子化合物在數位化時代來臨以前都被嚴格控管著。

在opnMe平台上，所有科學家只需點擊幾個按鍵，就可以在平台上訂購符合他們研究所需的分子。在世界各地，他們可以在一周內免費收到，可以開始自己的實驗，不必擔心侵犯專利的問題。在過去的幾個月，已有超過1,700種化合物被運往29個不同的國家─因此，外部研究人員也成為公司內部藥物研究的一份子。

「opnMe能使我們學習到有關疾病生物學、令人興奮的新事物，同時提高我們在藥物開發方面的科學聲譽和卓越性」，百靈佳殷格翰的藥物化學家和opnMe負責人Florian Montel博士說。「他們還向科學界證明，百靈佳殷格翰在加速新藥發現的研究領域中是採取開放、誠實和公平的態度。」

OpnMe.com還提供與外界聯合研究項目的機會：對於他們研究有興趣的科學家，可以報名參加並提交具有獨特和新穎的研究假設，最具潛力的提案將與百靈佳殷格翰內的科學家一起進行研究。到目前為止，有三種分子已經在opnMe上公開，而百靈佳殷格翰一共收到275份申請文件。「我們從這些申請文件中選擇了最好的一些，並將這些分子提供給研究人員來做進一步研究。因此，我們已經開始了七項新的合作」，負責opnMe.com全球研究人員關係的Markus Koester博士解釋說。

目前正在進行心臟代謝疾病、傳染病和呼吸道疾病領域的合作項目。另一個令人興奮的研究項目即將很快地推出，這將為製藥公司史上首次提供肺特異性腺相關病毒（AAV），來測試治療新遺傳性的呼吸系統疾病。「這將支持我們在AAV的基因療法科學中領導的雄心」，Koester補充表示。

透過公司的開放政策，百靈佳殷格翰的科學家們可以利用全球科學專家的知識。根據Montel的說法，opnMe.com的功用遠超越了當初藥物開發的目的，它最終將加快為患者開發下一代藥物的時程。

然而，儘管取得了所有進步的技術，但有一件事在未來仍將是不可替代的：不間斷的好奇心，創造力和熱情的天才科學家。

 

FURTHER BY MEANS OF OPEN INNOVATION

Designed by us – unlocked by you

Boehringer Ingelheim’s new open innovation portal “opnMe.com” was launched to enable cooperation in pharmaceutical research far beyond company boundaries. A courier might ring the bell at a university in North America, for instance. Inside the parcel are small tubes carrying some of the most valuable molecules from Boehringer Ingelheim’s research  organisation: high-quality compounds developed in-house and patented. The American scientist has ordered them, free of charge, on the opnMe.com portal: here, the company offers 30 molecules that would probably have been kept strictly under lock and key in predigital times.

On opnMe, however, any scientist can order with only a few clicks molecules that are of interest for their own research. Everywhere in the world, they receive them free of charge within a week and can start their own experiments without having to fear infringements of existing patents. Over the past few months, more than 1,700 compounds were delivered to 29 different countries. External researchers thus become accomplices of the company’s inhouse drug research.“

“opnMe enables us to learn exciting new things about disease biology, at the same time improving our

 scientific reputation and excellence in drug discovery and development,” says Dr Florian Montel, a medicinal chemist and head of opnMe at Boehringer Ingelheim. “They also demonstrate to the scientific community  that Boehringer Ingelheim is open, honest and fair in the field of research accelerating the discovery of new medicines”.

OpnMe.com allows also to commence joint research projects. Scientists interested in accessing them for their  research submit an application with a unique and novel research hypothesis. The proposals with the highest potential will be pursued together with scientists from Boehringer Ingelheim. So far, three of these molecules have been offered on opnMe – and Boehringer Ingelheim has received a total of 275 applications. “We have selected the best projects from these and made the molecules available to researchers. As a result, we have started seven new collaborations,” explains Dr Markus Koester, who is in charge of relations with researchers worldwide via opnMe.com.

Collaborative projects in the field of cardiometabolic diseases, infectious diseases and diseases of the respiratory tract are currently underway. Another exciting call will be launched soon: for the first time a pharmaceutical company will offer a lung-specific adeno-associated virus (AAV) to test new genetic mechanisms for treating respiratory diseases. “This will support our ambition towards scientific leadership in AAV-based gene therapy,” Koester adds.

Through the company opening up, scientists at Boehringer Ingelheim can tap into the knowledge of scientific experts worldwide. According to Montel, opnMe.com goes beyond the frontiers in drug discovery and will eventually accelerate the discovery of next generation medicines for patients in need.

Despite all technological advances, however, one thing will remain irreplaceable in the future: the tireless curiosity, creativity and the genius of enthusiastic scientists.

 

風險與併發症 BRASS：RISKS AND SIDE EFFECTS

當一種藥物上市時，百靈佳殷格翰的醫學科學家就會參與藥物監控，他們收集有關任何可能副作用的數據，進而評估藥物風險。他們很快將擁有一個名為BRASS的數位助手，專家可以將自己的經驗、評估結果以及相關的背景訊息輸入到應用程式中。然後，BRASS可以使用不同的分析方法，自主找出新的發現。此外，BRASS還可以將數據歸納於生物醫學專業的知識背景之中。但是，從安全數據中得出的結論，仍然取決於醫學專家的鑑定。包裝裡的說明書中是否應提及某些風險？是否需要包含使用說明細節？雖然人工智慧在許多領域上支持人類，但它無法取代人類。

 

When a drug is on the market, Boehringer Ingelheim medical scientists attend to pharmacovigilance. They collect data on possible side effects and thus assess risks with medicines.

They will soon be provided with a digital assistant called BRASS. The experts can enter their own experiences and assessments as well as background information into the application. BRASS can then use various analytical methods to independently develop new findings. In addition, BRASS can also place data in the context of biomedical expertise. However, the decision as to which conclusions to draw from the safety data still lies with the medical profession. Should certain risks be mentioned in the package insert? Are the instructions for use to be supplemented? Although artificial intelligence supports humans in many areas, it cannot replace them.