'遊戲結束了。只有mRNA可以獨當一面’ - 專家預視未來疫苗

Recently Yahoo Finance on-line reported the following:

'It's game over. It's mRNA or nothing:' Expert on future of vaccines

Anjalee Khemlani·Senior Reporter

Yahoo Finance

Tue., September 7, 2021, 1:05 p.m.

Pfizer (PFE) and its partner BioNTech (BNTX) recently got FDA full approval for the most widely-approved and sought after COVID-19 vaccine in the world, to date.

It signals an important change in how vaccines of the future could look, according to Arnaud Bernaert, formerly head of Global Health and Healthcare at the World Economic Forum.

Bernaert, now head of Health Security Solutions at Swiss-based SICPA, told Yahoo Finance, "I think it's game over. I think it's mRNA or nothing. [Other technology] takes too long."

Pfizer, BioNTech and Moderna (MRNA) are invested in the tech, with announcements of pursuits of combination flu-covid shots as well as other diseases.

The potential for mRNA was recognized early. "mRNA vaccines represent a promising alternative to conventional vaccine approaches because of their high potency, capacity for rapid development and potential for low-cost manufacture and safe administration," according to a 2018 article in Nature.

Bernaert cited these reasons as well. "If success needs to be defined as a function of the agility of a manufacturer to be able to reposition the DNA template for combating the next variant, I don't think the U.S. and Europe will do anything else but buy mRNA vaccines" moving forward, he said.

"They [mRNA] will represent 60% or 70% of the market. The other guys will die," he added.

But the pandemic also arrived after early development hurdles had been overcome for the technology. That included the method of delivery, lipid nanoparticles. And within the timeframe of getting the vaccines authorized, Moderna was first to reduce the storage temperatures needed from ultra-cold to normal freezer temperatures.

Now, the next step to unlocking their potential as a dominant technology will be global manufacturing, Bernaert said.

"I think mRNA is going to be a highly decentralized manufacturing technology," he said.

Deals happening now could be viewed as early efforts. That includes the various manufacturing and fill/finish deals that Pfizer and Moderna have penned in the past year.

Moderna has forged relationships with Catalent (CTLT), Switzerland-based Lonza, Spain-based Rovi, and France-based Recipharm for manufacturing. The company also partnered with Takeda (TAK) in Japan, Magenta in the United Arab Emirates and Tabuk in Saudi Arabia for distribution. It has partnered with Thermo Fisher (TMO), Sanofi (SNY), Baxter BioPharma and Samsung Biologics, in South Korea, for fill/finish. In addition, Moderna is working with Canada to set up a new manufacturing facility for future products. That's all on top of investing in its Massachusetts plant to expand manufacturing.

By comparison, pharma giant Pfizer has largely relied on its own sites in the U.S. and Europe, along with BioNTech's capacity, but recently signed agreements for global efforts. That includes with the Biovac Institute in South Africa and Eurofarma in Brazil for manufacturing. It has also partnered with Sanofi for fill/finish.

But further in the future, Bernaert expects mRNA use will lead to a decrease in the need for large-scale manufacturing footprints, "with 20,000-liter bioreactors a story of the past."

Bernaert pointed to California-based Nutcracker Therapeutics, as an example. The company is working on a smaller instrument that could give doctors access to locally-produced mRNA doses.

Already, mRNA companies have achieved improving stability at warmer temperatures compared to ultra-cold temperatures for the first doses. For now, however, the process is "crude," Bernaert said.

"The cold chain challenges will reduce, I think, over time. There will be lots of investments in better encapsulation mechanism, better lipid nanoparticles. It was very crude in the first place. I mean, let's call a spade a spade. The template itself and the way you grow enzymes, I think it's fairly crude."

He foresees synthetic biology DNA templates on the front end and better encapsulation mechanisms (lipids) on the back end. Brought together, it leads to a much more stable manufacturing process, Bernaert said.

Whatever the future holds, mRNA is set to dominate. "Viral vector technologies are going to become obsolete," Bernaert said.

Translation

PFE (輝瑞 ) 及其合作夥伴 BioNTech (BNTX)  最近獲得了 FDA 的全面批准，這是迄今為止世界上最被廣泛批准和最受歡迎的 COVID-19 疫苗。

世界經濟論壇的前全球健康和醫療保健負責人Arnaud Bernaert表示，這標誌著未來疫苗的模樣發生了重大變化。

Bernaert 現在是總部位於瑞士的 SICPA 的Health Security Solutions負責人，他告訴雅虎財經說， “我認為遊戲結束了。我認為只有mRNA可以獨當一面。[其他技術] 需要太長時間。”

輝瑞、BioNTech 和 莫德納 (MRNA) 都投資於這項技術，並宣布尋求出聯合流感病毒疫苗和其他疾病。

mRNA 的潛力很早就被認識到了。《自然》雜誌 2018 年的一篇文章稱, “mRNA 疫苗代表了一種有前途的傳統疫苗方法的替代方案，因為它有高效能, 可以快速發展、有低成本製造和安全管理的潛力” 。

Bernaert 也列舉了這些原因。 他說。“如果成功需要被定義為製造商能夠重新定位 DNA 模板以對抗下一個變體的敏捷性，我認為美國和歐洲除了買 mRNA 疫苗向前邁進之外,不會做任何其他事情”  。

 他補充道,“他們 [mRNA] 將佔市場的 60% 或 70%。其他的都會消失”。

但是，在克服了該技術的早期開發障礙之後，病毒大流行也到來了。障礙包括遞送方法，脂質納米粒子。在獲得批准疫苗的時間範圍內，莫德納(Moderna) 率先將所需的儲存溫度從超低溫降低到正常冷凍溫度。

Bernaert 說，現在，釋放它們作為主導技術的潛力的下一步將是全球製造。

他說,“我認為 mRNA 將成為一種高度分散的製造技術”。

現在進行的交易可以被視為早期的努力。這包括輝瑞和莫德納在過去一年中達成的各種製造和灌裝/完成製成的交易。

莫德納與 Catalent (CTLT)、瑞士的 Lonza、西班牙的 Rovi 和法國的 Recipharm 建立了製造關係。該公司還與日本的武田 (TAK)、阿拉伯聯合酋長國的 Magenta 和沙特阿拉伯的 Tabuk 合作進行分銷。它已與韓國的 Thermo Fisher (TMO)、Sanofi (SNY)、Baxter BioPharma 和 Samsung Biologics 合作進行填充/完成製成。此外，莫德納正在與加拿大合作，為未來的產品建立一個新的製造工廠。這一切都是另外於投資在馬薩諸塞州廠房的擴大製造生產。

相比之下，製藥巨頭輝瑞主要依靠其在美國和歐洲的工廠以及 BioNTech 的產能，但最近也簽署了全球合作協議。其中包括與南非的 Biovac Institute 和巴西的 Eurofarma 合作進行製造。它還與Sanofi合作進行灌裝/完成製成。

但在未來，Bernaert 預計 mRNA 的使用將導致對大規模製造足蹟的需求減少，“20,000 升生物反應器已成為過去。”

Bernaert 以總部位於加利福尼亞的 Nutcracker Therapeutics 為例。該公司正在開發一種更小的儀器，可以讓醫生獲得本地生產的 mRNA 劑量。

與第一批mRNA公司的超低溫劑量相比，該公司已經在更高的溫度下提高了其穩定性。然而Bernaert說，就目前而言，這個過程是 “原始的” 。

“我認為，隨著時間的推移，冷鏈挑戰會減少。會有大量投資放在更好的封裝機制、更好的脂質納米顆粒方面。開始時它非常原始粗。我的意思是，讓我們說真話。在模板本身以及培養酶的方式，我認為它相當原始” 。

他預見了在前面的合成生物學 DNA 模板和在往後更好的封裝機制（脂質）。 Bernaert 說，綜合起來，它會導致更加穩定的製造過程。

Bernaert說, 無論未來如何，mRNA 都將佔據主導地位。 “病毒載體技術將變得過時” 。

       So, according to Bernaert, mRNA is set to dominate while viral vector technologies will become obsolete in the making of vaccines. Let’s wait and see.

Note:

a.       SICPA (acronym for the former name Société Industrielle et Commerciale de Produits Alimentaires, no longer in use) is a Swiss company that provides security inks for currencies and sensitive documents, including identity documents, passports, transport and lottery tickets. The company is also involved in the market for secure traceability of products subject to excise duties, such as alcohol and tobacco stamps, and regulated products, such as halal products. (https://en.wikipedia.org/wiki/SICPA)