Moderna

Moderna, Inc (/məˈdɜːrnə/ mə-DUR-nə)[8] is an American pharmaceutical and biotechnology company based in Cambridge, Massachusetts. It focuses on drug discovery, drug development, and vaccine technologies based on messenger RNA (mRNA).[9][10] Moderna's technology platform inserts synthetic nucleoside-modified mRNA (modRNA) into human cells using a coating of lipid nanoparticles. This mRNA then reprograms the cells to prompt immune responses. It is a novel technique, abandoned by other manufacturers due to concerns about the toxicity of lipid nanoparticles at high or frequent doses.[11][12]

Moderna, Inc.
FormerlyModeRNA Therapeutics
(2010–2018)
TypePublic
IndustryBiotechnology
FoundedSeptember 2010; 10 years ago (2010-09)
Founders
Headquarters200 Technology Square
Cambridge, Massachusetts, U.S.[3]
Key people
ProductsBiotechnological products[6]
RevenueIncrease US$ 232.65 million (2020)[7]
Negative increase US$−488 million (2020)[7]
Negative increase US$−474 million (2020)[7]
Total assetsIncrease US$ 4.75 billion (2020)[7]
Total equityIncrease US$ 2.759 billion (2020)[7]
Number of employees
830 (2019)[7]
Websitemodernatx.com

In November 2020, it was announced that the Moderna COVID-19 vaccine candidate, mRNA-1273, had shown preliminary evidence of 94% efficacy in preventing COVID-19 disease in a Phase III trial, with only minor flu-like side effects. This led to its submission for emergency use authorization (EUA) in Europe, the United States, and Canada.[13][14] On December 18, 2020, mRNA-1273 was issued an EUA in the United States.[15] On December 23, 2020, it was authorized for use in Canada.[16][17] On January 6, 2021, it was authorized for use in the European Union.[18] On January 8, 2021, mRNA-1273 was authorized for use in the United Kingdom.[19]

HistoryEdit

2010–2016Edit

 
Moderna headquarters in Cambridge, Massachusetts

In 2010, ModeRNA Therapeutics was formed to commercialize the research of stem cell biologist Derrick Rossi. Rossi had developed a method of modifying mRNA by first transfecting it into human cells, then dedifferentiating it into bone marrow stem cells which could then be further differentiated into desired target cell types.[20][21] Rossi approached fellow Harvard University faculty member Tim Springer, who solicited co-investment from Kenneth R. Chien, Bob Langer, and venture capital firm Flagship Ventures.[21][22]

In 2011, the CEO of Flagship Ventures (now Flagship Pioneering), Noubar Afeyan, brought in European pharma sales and operations executive Stéphane Bancel as CEO.[21][11] Afeyan personally owned 19.5% of Moderna and was the largest single shareholder, while his fund, Flagship Pioneering, owned 18%.[23]

In March 2013, Moderna and AstraZeneca signed a five-year exclusive option agreement to discover, develop, and commercialize mRNA for treatments in the therapeutic areas of cardiovascular, metabolic, and renal diseases, and selected targets for cancer.[11][24][25] The agreement included a $240 million upfront payment to Moderna, a payment which was "one of the largest ever initial payments in a pharmaceutical industry licensing deal that does not involve a drug already being tested in clinical trials",[24] and an eight percent share in Moderna.[23] As of May 2020, only one candidate has passed Phase I trials, a treatment for myocardial ischemia, labelled AZD8601.[a][27]

In 2013, Rossi, Chien and their team reported that they were able to improve heart function in mice and enhance their long-term survival with a "redirection of their [stem cell] differentiation toward cardiovascular cell types" in a significant step towards regenerative therapeutics for Moderna.[28][29] In the same year and on the strength of the Nature Biotechnology paper, Moderna received from other investors $110 million.[28]

In January 2014, Moderna and Alexion Pharmaceuticals entered a $125 million deal for orphan diseases in need of therapies. Alexion paid Moderna $100 million for ten product options to develop rare-disease treatments, including for Crigler-Najjar syndrome, using Moderna's mRNA therapeutics platform.[30] By 2016, Bancel told an audience of JPMorgan Chase investors that the work with Alexion would shortly enter human trials. However, by 2017, the program with Alexion had been scrapped as the animal trials showed that Moderna's treatment would never be safe enough for humans.[11][12]

In February 2016, a Nature editorial criticized Moderna for not publishing any peer-reviewed papers on its technology, unlike most other emerging and established biotech companies, and compared its approach to that of the controversially failed Theranos.[31] In September 2018, Thrillist published an article titled, "Why This Secretive Tech Start-Up Could Be The Next Theranos",[32] criticizing its reputation for secrecy and the absence of scientific validation or independent peer-review of its research, though having the highest valuation of any U.S. private biotech company at more than $5 billion.[11][33] A former Moderna scientist told Stat: "It's a case of the emperor's new clothes. They're running an investment firm, and then hopefully it also develops a drug that's successful."[11]

2018–2020Edit

In 2018, the company rebranded as "Moderna Inc." with the ticker symbol MRNA, and further increased its portfolio of vaccine development.[10] In December 2018, Moderna became the largest biotech initial public offering in history, raising $621 million (27 million shares at $23 per share) on NASDAQ, and implying an overall valuation of $7.5 billion for the entire company.[34][35] The year-end 2019 SEC filings showed that Moderna had accumulated losses of $1.5 billion since inception, with a loss of $514 million in 2019 alone, and had raised $3.2 billion in equity since 2010.[10][23] At the time, Moderna was selling itself as a "Personalized Cancer Vaccines" manufacturer and one journalist remarked on the "Army of Robots" in the new 200,000-square-foot manufacturing plant with "five fluorescently lit clinical clean rooms" they had recently commissioned that was necessary just for the pre-clinical research:[36]

In the first room, large stainless steel machines turn a digital sequence of genetic building blocks called nucleotides into ring-shaped DNA plasmids. In the second, enzymes convert that DNA into strands of mRNA. In room three, the mRNA gets coated in lipid nanoparticles to help it enter cells. The last and most critical room is deep in the middle of the building, in a sealed-off aseptic block. To go there, employees have to don double layers of gowns and gloves, and move slowly so they don't stir up any microbes that might have slipped past air filters and sanitizing scrub-downs. Preventing contamination here is of utmost importance. It's where the mRNA gets deposited into the vials that will take them to their final destination. [The fifth room is] where the company plans to install a handful of refrigerator-sized, custom-designed robots for producing personalized cancer vaccines.

— Megan Molteni for Wired Magazine[36]

In 2018, the President of the company told a journalist of the planned personalised cancer vaccines that "It's not something that is like 'oh, this is the right color for you,' it's actually, 'no, we invented this color for you.'"[36]

Another well-regarded senior scientist who works for Moderna, Melissa Moore, predicted in 2018 that her team "is about to publish a paper showing they can engineer an off-switch into mRNAs, so they only express proteins in the cells Moderna wants them to, like, say, cancer cells".[36]

In March 2020, in a White House meeting between the Trump administration and pharmaceutical executives, Bancel told the president Moderna could have a COVID-19 vaccine ready in a few months.[10] The next day, the FDA approved clinical trials for the Moderna vaccine candidate, with Moderna later receiving investment of $483 million from Operation Warp Speed.[10] Moderna board member, Moncef Slaoui, was appointed head scientist for the Operation Warp Speed project.[10]

The Guardian mentioned CMO Tal Zaks as well as Moore who is "chief scientific officer in charge of the mRNA technology" in a profile about the corporation, which has yet to turn a yearly profit in the decade since its inception. Moderna plans to sell its covax product at US$32 to $37 per shot.[37]

As of December 2020 with all of the effervescence surrounding COVID-19 for which they were developing a vaccine, Moderna was valued at $60 billion.[38]

OverviewEdit

Moderna develops mRNAs that are delivered in lipid nanoparticle, using mRNA with pseudouridine nucleosides. Candidates are designed to have improved folding and translation efficiency via insertional mutagenesis.[39]

The Moderna COVID-19 vaccine candidate, mRNA-1273, was shown in a Phase I trial to be immunogenic in a small number of volunteers aged 18–55 years.[40] As of December 2020, no mRNA vaccine had completed Phase III clinical trials or had been licensed for prophylactic use against COVID-19, although the Moderna and Pfizer COVID-19 vaccines had been approved for marketing under emergency use authorizations from the FDA and regulatory agencies in other countries.[41][42]

LeadershipEdit

Since 2011, Moderna has been led by CEO Stéphane Bancel, a French businessman with a pharmaceutical sales and operations background.[11][10] Bancel has been described as having a secretive approach to Moderna, and as being a tough operator.[11][10] Though never having worked with RNA before, Stat noted that Bancel "is listed as a co-inventor on more than 100 of Moderna's early patent applications, unusual for a CEO who is not a PhD scientist".[11] After Noubar Afeyan and Robert Langer, Bancel is the largest individual shareholder in the company.[43]

Stephen Hoge, M.D., is president and a former McKinsey & Company management consultant who joined in 2012; he is the fourth-largest individual shareholder in the company.[43][5]

David Meline is CFO.[5]

BoardEdit

Noubar Afeyan, CEO of Flagship Pioneering, has been the chairman of Moderna's board of directors since 2011.[44] Afeyan who has a Ph.D. in biochemical engineering[45] holds his interest in Moderna through various Flagship Pioneering vehicles. At the 2018 IPO, documents filed stated that Afeyan owned 19.5% of the company, while Flagship owned 18%, thus giving Afeyan control over 37.5% of the company.[23]

In May 2020, Moderna board member Dr. Moncef Slaoui resigned from the company to become Chief Scientist for US's "Operation Warp Speed", a group designed to accelerate the development of a vaccine for the coronavirus. Slaoui continued to hold more than $10 million in stock options in the company in his new role while the federal government invested $483 million in the company to assist in coronavirus vaccine trials. Senator Elizabeth Warren called the holding a conflict of interest and said Slaoui should have divested his options.[46]

COVID-19 vaccineEdit

 
Vials of Moderna COVID-19 vaccine

The Moderna COVID‑19 vaccine, codenamed mRNA-1273, is a COVID‑19 vaccine developed by the United States National Institute of Allergy and Infectious Diseases (NIAID), the Biomedical Advanced Research and Development Authority (BARDA), and Moderna. It is administered by two 0.5 mL doses given by intramuscular injection given four weeks apart.[47]

It is an RNA vaccine composed of nucleoside-modified mRNA (modRNA) encoding a spike protein of SARS-CoV-2, which is encapsulated in lipid nanoparticles. Along with the Pfizer–BioNTech COVID-19 vaccine, it was one of the two RNA vaccines developed and deployed in 2020 against COVID‑19.

On 18 December 2020, mRNA-1273 was issued an Emergency Use Authorization by the United States Food and Drug Administration (FDA).[48][49][50][51] It was first authorized for use in Canada on 23 December 2020,[52] in Israel on 5 January 2021,[53] in the European Union on 6 January 2021,[54][55][56] in the United Kingdom on 8 January 2021,[57][58] and in Singapore on 3 February 2021.[59]

See alsoEdit

NotesEdit

  1. ^ The relative success of AZD8601 is attributed to the fact that Moderna has been able to inject mRNA direct into the heart muscle without needing a drug delivery system. However, only the heart and some skin areas are capable of absorbing "naked mRNA".[26]

ReferencesEdit

  1. ^ "What we know about Moderna's COVID-19 vaccine candidate—and what we don't". PBS News Hour. November 16, 2020. Archived from the original on December 4, 2020. Noubar Afeyan is a co-founder and chairman of Moderna ...
  2. ^ "Moderna chairman: We don't need deep-freeze conditions for vaccine". CNN. November 16, 2020. Archived from the original on December 4, 2020. Retrieved December 4, 2020.
  3. ^ "Key Facts". Moderna. Retrieved May 19, 2020.
  4. ^ Alspach, Kyle (May 22, 2013). "Moderna CEO Bancel joins Flagship Ventures as senior partner". Boston Business Journal (Blog). American City Business Journals. Archived from the original on January 31, 2014. Retrieved March 12, 2020.
  5. ^ a b c "Executive Committee & Leadership". Archived from the original on November 16, 2020. Retrieved August 13, 2020.
  6. ^ "Christmas comes early as first Moderna vaccines arrive in Canada". Global News. December 24, 2020. Retrieved December 25, 2020.
  7. ^ a b c d e f "Moderna Reports Third Quarter 2020 Financial Results". Moderna. October 29, 2020. Retrieved December 19, 2020.
  8. ^ Moderna (October 23, 2019). mRNA-3704 and Methylmalonic Acidemia (Video). YouTube. Retrieved January 19, 2021.
  9. ^ Catherine Shaffer (December 6, 2013). "Moderna Makes Entrance with $40M Round for mRNA Work". BioWorld. Archived from the original on November 16, 2020. Retrieved December 11, 2013.
  10. ^ a b c d e f g h Elizabeth Cohen (November 30, 2020). "Moderna applies for FDA authorization for its Covid-19 vaccine". CNN. Retrieved December 4, 2020.
  11. ^ a b c d e f g h i Garade, Damien (September 13, 2016). "Ego, ambition, and turmoil: Inside one of biotech's most secretive startups". Stat. Archived from the original on November 16, 2020. Retrieved May 18, 2020.
  12. ^ a b Garde, Damien (January 10, 2017). "Lavishly funded Moderna hits safety problems in bold bid to revolutionize medicine". Stat. Archived from the original on November 16, 2020. Retrieved May 19, 2020.
  13. ^ Ludwig Burger (December 1, 2020). "COVID-19 vaccine sprint as Pfizer-BioNTech, Moderna seek emergency EU approval". Reuters. Retrieved December 4, 2020.
  14. ^ Hannah Kuchler (November 30, 2020). "Canada could be among the first to clear Moderna's COVID-19 vaccine for use". The Financial Post. Retrieved December 4, 2020.
  15. ^ "Statement from NIH and BARDA on the FDA Emergency Use Authorization of the Moderna COVID-19 Vaccine". US National Institutes of Health. December 18, 2020. Retrieved December 19, 2020.
  16. ^ "Regulatory Decision Summary—Moderna COVID-19 Vaccine". Health Canada. December 23, 2020. Retrieved December 23, 2020.
  17. ^ "Moderna COVID-19 Vaccine (mRNA-1273 SARS-CoV-2)". COVID-19 vaccines and treatments portal. December 23, 2020. Retrieved December 23, 2020.
  18. ^ Strauss, Marine (January 6, 2021). "UPDATE 1-European Commission gives final approval to Moderna vaccine". Reuters. Retrieved January 10, 2021.
  19. ^ releases, 8:30am to 5pm For real-time updates including the latest press; Statements, News; https://www.twitter.com/mhragovuk, see our Twitter channel at. "Moderna vaccine becomes third COVID-19 vaccine approved by UK regulator". GOV.UK. Retrieved January 10, 2021.
  20. ^ Erin Kutz (October 4, 2010). "ModeRNA, Stealth Startup Backed By Flagship, Unveils New Way to Make Stem Cells". Xconomy. Archived from the original on February 8, 2017. Retrieved February 7, 2017.
  21. ^ a b c Gregory Huang (December 6, 2012). "Moderna, $40M in Tow, Hopes to Reinvent Biotech with "Make Your Own Drug"". Xconomy. Archived from the original on November 22, 2018. Retrieved June 21, 2013.
  22. ^ Catherine Elton (March 2013). "The NEXT Next Big Thing". Boston Magazine. Archived from the original on November 16, 2020. Retrieved December 11, 2013.
  23. ^ a b c d Terry, Mark (November 29, 2018). "Can Moderna Live up to the Hype? mRNA Company Increases IPO Goal to $600 Million". BioSpace. Archived from the original on November 16, 2020. Retrieved May 19, 2020. The filings with the U.S. Securities and Exchange Commission (SEC) not only updated the proposed IPO but disclosed the size of the company's largest investors' stakes. Noubar B. Afeyan, company chairman, holds 19.5 percent, or 58,882,696 shares. Flagship Pioneering holds 18 percent of Moderna shares
  24. ^ a b Andrew Pollack (March 21, 2013). "AstraZeneca Makes a Bet on an Untested Technique". The New York Times. Archived from the original on November 16, 2020. Retrieved December 11, 2013.
  25. ^ Robert Weisman (March 21, 2013). "Moderna in line for $240m licensing deal". The Boston Globe. Archived from the original on November 16, 2020. Retrieved December 11, 2013.
  26. ^ "Moderna's gamble: what's behind biotech's biggest-ever IPO?". Pharmaceutical Technology. February 21, 2019. Archived from the original on November 16, 2020. Retrieved May 20, 2020.
  27. ^ "Our Pipeline". Moderna. Archived from the original on November 16, 2020. Retrieved May 19, 2020.
  28. ^ a b Timmerman, Luke (November 20, 2013). "Moderna Vacuums Up Another $110M to Make Messenger RNA Drugs". Xconomy, Inc.
  29. ^ Zangi, Lior; Lui, Kathy O.; von Gise, Alexander; Ma, Qing; Ebina, Wataru; Ptaszek, Leon M.; Später, Daniela; Xu, Huansheng; Tabebordbar, Mohammadsharif; Gorbatov, Rostic; Sena, Brena; Nahrendorf, Matthias; Briscoe, David M.; Li, Ronald A.; Wagers, Amy J.; Rossi, Derrick J.; Pu, William T.; Chien, Kenneth R. (2013). "Modified mRNA directs the fate of heart progenitor cells and induces vascular regeneration after myocardial infarction". Nature Biotechnology. 31 (10): 898–907. doi:10.1038/nbt.2682. PMC 4058317. PMID 24013197.
  30. ^ Chris Reidy (January 13, 2014). "Alexion, Moderna announce agreement to develop messenger RNA therapeutics". The Boston Globe. Archived from the original on November 16, 2020. Retrieved March 18, 2020.
  31. ^ "Research not fit to print". Nature. 34 (115). February 5, 2016. Archived from the original on November 16, 2020. Retrieved May 19, 2020.
  32. ^ McGauley, Joe (September 23, 2018). "Why This Secretive Tech Start-Up Could Be The Next Theranos". Thrillist. Retrieved May 18, 2020.
  33. ^ Crow, David (September 6, 2017). "Secretive Moderna yet to convince on $5bn valuation". Financial Times. Archived from the original on July 1, 2020. Retrieved May 18, 2020.
  34. ^ Mukherjee, Sy (December 8, 2018). "Moderna Had the Biggest Biotech IPO Ever. Here's What That Says About the Industry's Future". Fortune. Archived from the original on November 16, 2020. Retrieved May 18, 2020.
  35. ^ Ramsey, Lydia (December 7, 2018). "Moderna just priced the biggest IPO in biotech history, valuing the startup at $7.5 billion". Business Insider. Archived from the original on November 16, 2020. Retrieved May 18, 2020.
  36. ^ a b c d MOLTENI, Megan (July 25, 2018). "Making Personalized Cancer Vaccines Takes an Army—of Robots". Condé Nast. Wired Magazine.
  37. ^ Kollewe, Julia (November 16, 2020). "Covid vaccine: who is behind the Moderna breakthrough?". Guardian News & Media Limited.
  38. ^ "Moderna stock price and market value". Yahoo Finance. December 4, 2020. Retrieved December 4, 2020.
  39. ^ Servick, Kelly (February 1, 2017). "This mysterious $2 billion biotech is revealing the secrets behind its new drugs and vaccines". Science. doi:10.1126/science.aal0686. Archived from the original on November 16, 2020. Retrieved May 17, 2018.
  40. ^ Jackson, Lisa A.; Anderson, Evan J.; Rouphael, Nadine G.; Roberts, Paul C.; Makhene, Mamodikoe; Coler, Rhea N.; McCullough, Michele P.; Chappell, James D.; Denison, Mark R.; Stevens, Laura J.; Pruijssers, Andrea J. (July 14, 2020). "An mRNA Vaccine against SARS-CoV-2—Preliminary Report". New England Journal of Medicine. 383 (20): 1920–1931. doi:10.1056/NEJMoa2022483. ISSN 0028-4793. PMC 7377258. PMID 32663912. At the 100-microgram dose, the one Moderna is advancing into larger trials, all fifteen patients experienced side effects, including fatigue, chills, headache, muscle pain, and pain at the site of injection. All side effects were considered mild or moderate. A higher, 250-microgram dose led to more serious reactions and has been set aside.
  41. ^ Singh, Jerome Amir; Upshur, Ross E G (2020). "The granting of emergency use designation to COVID-19 candidate vaccines: implications for COVID-19 vaccine trials". The Lancet Infectious Diseases. doi:10.1016/s1473-3099(20)30923-3. ISSN 1473-3099. PMC 7832518. PMID 33306980.
  42. ^ Safura Abdool Karim (December 18, 2020). "Emergency use authorization of Covid-19 vaccines could hinder global access to them". STAT. Retrieved December 27, 2020.
  43. ^ a b Wink, Ben (May 18, 2020). "Here are the 5 multimillionaire scientists and executives getting the richest off Moderna's spike to record highs". Business Insider. Archived from the original on November 16, 2020. Retrieved May 19, 2020.
  44. ^ "Moderna's Board of Directors". Moderna. Archived from the original on November 16, 2020. Retrieved May 19, 2020.
  45. ^ "One Of Biotech's Biggest Investors Says The Industry Must Be 'Unreasonable'". www.wbur.org. Archived from the original on November 16, 2020. Retrieved July 15, 2020.
  46. ^ Corcoran, Kieran (May 16, 2020). "The ex-pharma exec leading Trump's COVID-19 vaccine program has $10 million in stock options for a company getting federal funding". Business Insider. Archived from the original on November 16, 2020. Retrieved May 18, 2020.
  47. ^ "Moderna COVID-19 Vaccine". Dosing & Administration. Infectious Diseases Society of America. January 4, 2021. Retrieved January 5, 2021.
  48. ^ "FDA Takes Additional Action in Fight Against COVID-19 By Issuing Emergency Use Authorization for Second COVID-19 Vaccine". U.S. Food and Drug Administration (FDA) (Press release). Retrieved December 18, 2020.
  49. ^ "Statement from NIH and BARDA on the FDA Emergency Use Authorization of the Moderna COVID-19 Vaccine". US National Institutes of Health. December 18, 2020. Retrieved December 19, 2020.
  50. ^ Oliver SE, Gargano JW, Marin M, Wallace M, Curran KG, Chamberland M, et al. (December 2020). "The Advisory Committee on Immunization Practices' Interim Recommendation for Use of Moderna COVID-19 Vaccine – United States, December 2020" (PDF). MMWR. Morbidity and Mortality Weekly Report. 69 (5152): 1653–56. doi:10.15585/mmwr.mm695152e1. PMID 33382675. S2CID 229945697.
  51. ^ Lovelace Jr B (December 19, 2020). "FDA approves second Covid vaccine for emergency use as it clears Moderna's for U.S. distribution". CNBC. Retrieved December 19, 2020.
  52. ^ "Moderna COVID-19 Vaccine (mRNA-1273 SARS-CoV-2)". COVID-19 vaccines and treatments portal. December 23, 2020. Retrieved December 23, 2020.
  53. ^ "Israel authorises use of Moderna's COVID-19 vaccine". Yahoo! News. Retrieved March 28, 2021.
  54. ^ "COVID-19 Vaccine Moderna EPAR". European Medicines Agency (EMA). Retrieved January 20, 2021.
  55. ^ "COVID-19 Vaccine Moderna". Union Register of medicinal products. Retrieved January 14, 2021.
  56. ^ "European Commission authorises second safe and effective vaccine against COVID-19". European Commission (Press release). Retrieved January 6, 2021.
  57. ^ "Moderna vaccine becomes third COVID-19 vaccine approved by UK regulator". U.K. Government. January 8, 2021. Retrieved January 8, 2021.
  58. ^ "Regulatory approval of COVID-19 Vaccine Moderna". U.K. Government. April 1, 2021. Retrieved April 5, 2021.
  59. ^ "Singapore becomes first in Asia to approve Moderna's COVID-19 vaccine". Reuters. February 3, 2021. Retrieved March 28, 2021.

External linksEdit