S5. E4. 集眾人之力，對抗 COVID-19 COMBINING FORCES TO FIGHT COVID-19

身為研究型生物製藥企業，百靈佳殷格翰責無旁貸，投入全球對抗 COVID-19新冠肺炎的戰役。我們貢獻資源與專業知識，全力支持研究工作，希望盡快找到這種致命傳染病的有效醫療方案。

2020年1月下旬，空中巴士「Kurt Schumacher」從德國軍事機場Cologne-Wahn起飛，開往中國武漢。一種新型的肺部疾病「COVID-19新冠肺炎」正在從這個城市擴散。根據中國政府的命令，武漢幾乎被完全封鎖。德國空軍從這個受病毒侵襲的城市，撤離數百位德國公民（包含疑似有症狀者）回法蘭克福機場。德國衛生部在機場內的一間體育館開設了臨時醫療院所，配有嬰兒床和塑膠隔離帷幕。

一同返程的不只有醫生與護士，還有科學家們，包含來自德國感染研究中心（German Center for Infection Research，以下簡稱DZIF）的研究人員。他們自感染者採集血液樣本，進行檢驗，分離患者的免疫細胞。百靈佳殷格翰長期與DZIF中心維持密切關係，不時提供建議，進行意見交流。科學家們希望能在接下來數月中，研究並開發出對SARS-CoV-2 新型冠狀病毒具有中和作用的抗體。早在去年12月中旬時，研究進入了臨床試驗階段。第I/IIa期臨床研究包含未受與已受SARS-CoV-2病毒感染的個案。

身為研究型生物製藥公司，百靈佳殷格翰自COVID-19新冠肺炎疫情蔓延之初，就已經在許多面向與這個致命的傳染病進行抗爭：

• 為了防止病毒散播，著手研發微小的小分子（very small molecules）

• 舉例來說：檢查用於治療HIV或C型肝炎的物質，是否能幫助COVID-19患者

百靈佳殷格翰積極參與國際發展計畫，例如，由歐盟創新醫藥研究先導計畫（Innovative Medicines Initiative，IMI） 發起、成立的冠狀病毒歐洲加速研發聯盟（Corona Accelerated R&D in Europe，CARE）。百靈佳殷格翰也公開支持比爾暨梅琳達蓋茲基金會（Bill and Melinda Gates Foundation），希望全球各地皆能享有並獲得醫療方案與疫苗的公平機會。

 

全球宣戰：COVID-19 治療加速器

比爾暨梅琳達蓋茲基金會與惠康基金會（Wellcome Trust）聯合，於2020年3月啟動COVID-19 治療加速器（COVID-19 Therapeutics Accelerator）行動計畫。製藥與生物科技公司正與政府、研究單位，以及非政府組織合作，希望儘速抑制COVID-19疫情。百靈佳殷格翰也貢獻自己的專業知識，共享物質資料庫。

燃眉之急—未被滿足之醫療需求

百靈佳殷格翰正在與生物科技領域的夥伴們合作，進行各種嘗試。與DZIF中心合作就是其中一個例子。百靈佳殷格翰子公司ViraTherapeutics常務董事暨跨界研究（Research Beyond Borders）團隊資深顧問Knut Elbers回憶說：「當 Becker教授確認（COVID-19）感染者的第一批抗體後，詢問我是否要一起進行抗體研究時，我們毫不猶豫的加入！」負責DZIF中心新創感染部門的Elbers和Becker，原本就已相識多年。DZIF中心和科隆大學由Florian Klein教授帶領的研究團隊，貢獻他們的專業知識和設備，從感染者的B細胞（B cells）中提取抗體；百靈佳殷格翰負責進一步鑽研抗體表徵，並在實驗中產生有發展性的備選抗體。這個合作案的成員並不是隨機組成的，是因為百靈佳殷格翰被視為研究、研發並生產單科隆抗體以及其它生物製藥的造浪者企業，因而擔負此重責大任。

位於德國比伯拉赫（Biberach）和維也納的歐洲生物製藥研發部門負責人David Wyatt說：「 我們將研發新抗體視為高度優先，希望這些抗體可以強化醫生們的治療方案武器庫。」疫苗可能要花費一些時間，才能讓人體的免疫系統產生適當的反應，中和抗體則是在施藥後可以立即見效。這些中和抗體是免疫分子的一種，可以附著在病毒上，使其喪失能力，即時保護患者。它們與病毒表面結合，就可以阻止病毒侵入人類的健康細胞。Wyatt說：「我們的目標是防止患者病情惡化，或者將這些藥物預防性的投入於高危險社群。」

雖然首批COVID-19疫苗已經獲准使用，抗體依然佔據極其重要的地位。疫苗接種需要時間生效，已接種的個人依然具有傳染力。當病毒進入人體後，免疫系統可能無法即刻發揮足夠的效力抑止病毒。

Elbers解釋：「病毒依然可能在人群中散播，無法產生免疫反應的人，依然容易感染COVID-19。我們需要各種工具對抗COVID-19。也因此，我們的抗體研究可能成為重要關鍵。」

百靈佳殷格翰除了與DZIF中心合作，也是COVID-19 新冠肺炎治療加速器（COVID-19 Therapeutics Accelerator）計畫的一份子，致力於研發病毒中和抗體。加速器計畫是由39間公共研究機構和製藥公司聯盟組成，聯盟成員一起努力，盡全力加速推動COVID-19治療方案，以防止冠狀病毒帶來的威脅。身為計畫聯盟的一員，百靈佳殷格翰與數間生物科技公司、政府、非政府組織、多邊公司等單位分享研究成果。

 

時間軸

 

一種物質，多種功效？

百靈佳殷格翰一直在檢視既有產品臨床研究的每一個臨床／臨床前試驗步驟與物質。纖維蛋白溶酶原激活物 （plasminogen activator） Actilyse^® 栓體舒，在全球許多國家皆獲准用於治療患者中風之腦部血栓溶解。因為具備預防重症COVID-19患者器官衰竭功效，因此成為治療COVID-19的備選藥物。

「科學界正在迅速的發展，我們在各方面都必須認真、竭盡全力。」Knut Elbers 說。他也相信，與合作夥伴的關係非常重要。人類只有透過合作，方能打贏這場戰爭。

 

對抗COVID-19的現行及備選方案

 

於維也納進行的新SARS-CoV-2 新型冠狀病毒試驗

維也納生物中心的研究人員正在檢驗RT-LAMP，確認每次都能取得類似成果。RT-LAMP試驗也比PCR試驗經濟實惠。PCR試驗是將病毒傳染物質複製到DNA片段中，重複多次同樣步驟；RT-LAMP試驗則只需恆溫器或恆溫為63℃的水即可，且能在30分鐘後取得成果。目前RT-LAMP已使用PCR試驗分析儀進行測試，並在特定地區醫院開始進行試驗駐點計畫。

維也納分子病理學研究所（Research Institute of Molecular Pathology，IMP）由百靈佳殷格翰贊助，集結來自40個國家／地區的200位研究人員，持續地推動研究工作。

「科學家們致力於迅速研發有效的VOCID-19醫療方案，我們不只要幫助患者，也同時減輕全球醫療系統的壓力。」

Michel Pairet博士

百靈佳殷格翰董事會—創新部門

 

 

 

COMBINING FORCES TO FIGHT COVID-19

As a research-driven biopharmaceutical company, Boehringer Ingelheim is participating in the global fight against COVID-19. The company is contributing its resources and its expertise in support of the research efforts, in order to identify effective treatments for this deadly infectious disease as quickly as possible.

 

It is late January 2020. The Airbus “Kurt Schumacher” takes off from the military airport Cologne-Wahn, Germany. It is bound for Wuhan in eastern China. A novel lung disease, COVID-19, is spreading in this metropolis. The city is almost completely sealed off by order of the Chinese authorities. The German air force is repatriating hundreds of Germans – including infected individuals – from this hot spot to Frankfurt Airport. In a gym on the airport site, the German Minis- try of Health has set up a temporary infirmary equipped with cots and plastic partition walls.

It is not just doctors and nurses who are awaiting the returnees but also scientists, including those from the German Center for Infection Research (DZIF) and the University Hospital of Cologne. They take blood samples from the infected persons, examine these samples, and isolate these patients’ immune cells. Boehringer Ingelheim has long maintained a close relationship with the DZIF and is asked for its advice. By working together, the scientists hope to discover and develop antibodies over the next few months that have a neutralizing effect on the SARS-CoV-2 virus. In mid-December, their research entered the clinical testing phase; the Phase 1/2a studies include both SARS-CoV-2-uninfected and SARS-CoV-2-infected individuals.

As a research-driven biopharmaceutical company, Boehringer Ingelheim has been fighting against the deadly infectious disease on several different fronts since the start of the COVID-19 pandemic:

∙ The family-owned company is working on the development of very small molecules, with the aim of preventing viruses from spreading.

∙ Substances that have already been used to treat HIV or hepatitis C, for instance, are being examined in terms of whether they offer any benefits for COVID-19 patients.

Boehringer Ingelheim is also actively engaged in international development initiatives such as the COVID-19 Therapeutics Accelerator and the Corona Accelerated R&D in Europe (CARE) consortium established by the Innovative Medicines Initiative (IMI). The company also supports the communiqué initiated by the Bill & Melinda Gates Foundation in support of equal global access to therapies and vaccines, since the scientists will only be able to stop the pandemic if global access to new solutions is guaranteed.

 

A GLOBAL ENDEAVOR: THE COVID-19 THERAPEUTICS ACCELERATOR

Together with the Wellcome Trust and Mastercard, the Bill & Melinda Gates Foundation established the COVID-19 Therapeutics Accelerator in March 2020. Pharmaceutical and life science companies are cooperating with governments, research institutions, and non-governmental organizations in order to curb the COVID-19 pandemic. Boehringer Ingelheim is contributing its expertise and has made its substance data- base available.

 

An Acute Unmet Medical Need

In all of its endeavors, Boehringer Ingelheim is working with partners throughout the life science community. Its cooperation with the DZIF is one such example of this. “When Professor Becker asked me after the identification of first antibodies of infected patients whether we would like to jointly pursue antibody research, we didn’t hesitate to come on board,” recalls Knut Elbers, Managing Director of Boehringer Ingelheim’s subsidiary ViraTherapeutics and Senior Advisor to the research initiative Research Beyond Borders. Elbers and Becker, who coordinates the DZIF’s Newly Emerging Infections department, have known each another for many years now. While the DZIF and a team of researchers led by Prof. Dr. Florian Klein of the University of Cologne contributed their expertise and equipment in order to extract anti- bodies from the B cells of infected patients, Boehringer Ingelheim was responsible for further characterization of these antibodies and for the production of promising candidates in the laboratory. That is no coincidence, since Boehringer Ingelheim is considered a leading company in the research, development, and production of monoclonal antibodies and other biological medicines.

“We are advancing these new antibodies with high priority, hoping they can contribute to a broader therapeutic armamentarium for physicians,” says David Wyatt, Group Head of Biotherapeutics Discovery Europe in Biberach and Vienna.

Unlike a vaccine, which takes time until the body’s immune system has produced an appropriate response, neutralizing antibodies are effective immediately once administered. These neutralizing antibodies are immune molecules that attach themselves to viruses and incapacitate them, thus providing immediate protection. They bind to the surface of the virus and prevent it from entering a person’s healthy cells. “Our goal is that patients will be prevented from developing more severe disease, or that these medicines can be used in a preventative setting for high-risk individuals,” says Wyatt.

Although first COVID-19 vaccines have been approved, antibodies are expected to remain important, as it will take time to vaccinate everyone. And while vaccination has a prophylactic effect and prevents an outbreak of the illness, it seems likely that vaccinated individuals can nonetheless pass on the virus. This is because the immune system is most likely not efficient enough to stop the virus from multiplying at the point where it enters the body.

“The virus may thus still be able to spread in the population and people who are unable to develop a protective immune response may remain susceptible to falling ill with COVID-19,” Elbers explains. “We require a broad range of tools to tackle COVID-19. Our antibody re- search is potentially an important contribution to this.” 

Boehringer Ingelheim is researching and developing virus-neutralizing antibodies not just in collaboration with the DZIF, but also as part of the CARE (Corona Accelerated R&D in Europe) consortium. This consortium consists of 37 public research institutions and pharmaceutical companies. Together, its members intend to accelerate the development of COVID-19 therapies and thus to prevent future coronavirus threats. As a member of the consortium, Boehringer Ingelheim is sharing its research findings with life science companies as well as governments, non-governmental organizations, multilateral institutions, and others.

 

A Known Substance with a New Function?

Boehringer Ingelheim has also been searching through its products as well as its clinical and preclinical pipeline for substances. The tissue-specific plasminogen activator ACTILYSE^® is approved for the use after a stroke to dissolve blood clots in the brain in many countries worldwide. It might be a potential candidate for the treatment of COVID-19 as it may prevent organ failure in seriously ill COVID-19 patients.

“The scientific community is making good progress and we are contributing as best as we can at all levels,” remarks Knut Elbers in summary of Boehringer Ingelheim’s efforts. Cooperation with partners is crucial, according to Elbers. Humanity will only be able to win that fight by working together.

 

CURRENT AND POTENTIAL FUTURE OPTIONS TO FIGHT COVID-19

 

NEW SARS-COV-2 TEST FROM VIENNA

Researchers at the Vienna Bio-Center are achieving results with their RT-LAMP Tests that are similarly specific and significantly less expensive than standard PCR tests. With the PCR test, the viral genetic material is first copied into DNA and then duplicated many times. With the RT-LAMP Test, however, an incubator or a simple water bath with a constant temperature of 63 degrees Celsius suffices. A positive result is already available after 30 minutes. Tests of RT-LAMP with PCR standard analysis have already been performed, and pilot projects for hospitals in selected regions have started.

Research is being carried out by the Research Institute for Molecular Pathology (IMP). It employs 200 researchers from 40 countries, and is funded by Boehringer Ingelheim.

“Our scientists are com- mitted to rapidly finding effective treatments to fight COVID-19.

By doing so, we are not only helping patients, but also relieving pressure on healthcare systems around the world.”

Dr. Michel Pairet

Member of the Board of Managing Directors Innovation