Industry Updates Volume 14

​From the Known…

• Global impacts to date: 260+ Million confirmed cases, 5.2+ Million confirmed deaths
• Delta variant-driven caseloads increasing again world-wide - some locations back to previous highs
  • This has led to lockdowns and/or severe restrictions in Europe (e.g., Austria, Germany), tightening in the UK, and significant caseload increases and selected restrictions in the U.S. and Canada
  • Three European countries experienced riots over the past two weeks - protestors reacted to the increasing social restrictions and the threat of compulsory vaccine mandates to combat Delta surge
  • U.S. caseload range.: Florida (best) at ~30 cases/100K, Michigan (worst) at ~390 cases/100K (7 day rolling average) - a 13X difference
  • Multiple court challenges ongoing against U.S. vaccine mandates
  • Dr. Scott Gottlieb, former FDA Commissioner, hypothesizes that with waning vaccine immunity levels, the number of “breakthrough’ infections is much larger than what is being reported
• ~8 Billion vaccine shots administered globally; however, 70% of these in 10 countries; 30% in China
  • According to the WHO, for every 100 people in high-income countries, 133 doses of COVD-19 vaccine have been administered, while in low-income countries, 4 doses per 100 people have been administered → Clear indication of ‘Vaccine Nationalism’ at play
• In the U.S., recent CDC analysis suggests that if someone is not vaccinated, they are:
  • 5-6X more likely to get infected with COVID-19, even if previously recently infected 
  • 10X more likely to end up in hospital if infected
  • 11X more likely to die from COVID-19

• Fully-vaccinated people make up less than 1% of COVID-19 deaths in the U.S.

...to the Highly Unknown - Omicron Variant (Breaking News - Refana is Monitoring Carefully)

• We have entered a frequently predicted - and almost inevitable - situation, where a major new, highly differentiated, variant has emerged from countries with much lower vaccination rates → Omicron
• World Health Organization and others have been warning for months that Vaccine Nationalism and hoarding of supplies by the richest nations would ultimately prove counterproductive
• Many large populations, for example in Africa, are still almost completely unvaccinated, and thus remain strong breeding grounds for new strains of COVID-19
• Despite all these prior warnings, Omicron’s emergence seems to have caught the world unprepared
• So far, small numbers of Omicron cases have been detected in multiple countries - including Australia, Belgium, Botswana, Canada, Denmark, Germany, Hong Kong, Israel, Netherlands, UK, and South Africa - suggesting that the variant is already spreading (Note: Current data is quite limited)
• Many countries - including the U.S. - have already banned flights from 8 countries in Southern Africa
  • This may prove futile if Omicron didn't originate there, or has already escaped in sufficient volumes over the past 2-4 weeks before the initial sequencing in South Africa identified this new variant
• Israel and Japan have banned all travel with incoming foreigners
  • Fully-vaccinated returning Israelis - even w/negative PCR tests - will need mandatory quarantining
  • These measures were introduced for two weeks, to give time to assess a more complete risk profile
• The severity of Omicron infection, and its ability to overcome vaccinations, is unknown at this point

• Currently the world is lacking key information about this new variant - other than the highly concerning point that Omicron has 50 mutations, of which 32 are on the Spike Protein
  • This suggest that the Spike Protein-based vaccines’ ability to protect may be further weakened 
  • Both mRNA manufacturer CEOs have publicly reiterated this point this over the past few days, building on Pfizer CEO Alber Bourla’s similar comments from six months ago
  • However, Refana has previously observed that 'WIV-centric’ countries have suffered much less severe Delta surges than 'mRNA-centric’ countries
• Regeneron and Eli Lilly have already reported their COVID-19 therapeutic solutions are less effective vs. the Omicron variant; no updates yet re Omricon’s impact on the Pfizer/Merck/AstraZeneca solutions
  • Meanwhile, Merck’s efficacy levels have been lowered from 50% to 30%, given further testing
• South Africa has protested that it is being unfairly punished for ‘discovering’ this variant
  • For both the Alpha strain, discovered in Britain, and the Gamma strain, discovered in South Africa, there was no evidence that those variants had actually emerged in those countries
  • Rather, they have much better testing and sequencing infrastructures than their neighbors
• The timing of Omricon’s arrival is unhelpful:
  • The recent world-wide unrest and protests to the restrictions, mandates and lockdowns could further amplify if these measures need to be strengthened
• Dr. Scott Gottlieb, former FDA Commissioner, summarized the current Omicron situation well over the past weekend (28 November 2021): https://www.cbsnews.com/news/transcript-dr-scott-gottlieb-on-face-the-nation-november-28-2021​

• Four Omicron impact scenarios are possible →  Scenario likelihoods will not be clear for at least  2-6 weeks (Figure 1)
  • Omicron could prove extremely dangerous and prolong COVID-19 as a Pandemic by 12-18 months, requiring new vaccines, and new campaigns with 2-3 shots each
  • Omicron could also prove either largely irrelevant, or even be somewhat benign

Increasing Infection, Decreasing Deaths?

• While new infection rates from Delta had already climbed dramatically in many countries - and death rates have also climbed - the impacts are not as bad as in previous waves
  • This is evident even in countries with very high vaccination rates, e.g., Ireland, which has experienced high levels of breakthrough infections with Delta
  • Very roughly, it could be said that the death rate has fallen from 2% to <1% of those infected with Delta, compared to the earlier death rates from prior strains
  • This does not mean that Delta is inherently less dangerous
  • Indeed, Delta could be significantly more dangerous on its own, but the combined impact of higher vaccination rates and more effective treatments have helped reduced the death rate by half
• It is important to bear this in mind in analyzing the threats of Omicron
  • If the Omicron variant breaks through the current generation vaccine protection firewalls, overall COVID-19-related death rates could rise again

Industry/Market Responses to Omicron

• Omicron is likely to force the Western market leaders - Pfizer and Moderna - to do what they have been reluctant to do - drop their extraordinarily profitable current products and pursue new vaccine approvals
  • It is arguable from a medical perspective that they should have already introduced specific anti-Delta vaccines, as the efficacy has waned to 46% and 58% respectively
• All manufacturers are already running tests of existing vaccines against Omicron
• Some have begun Omicron-specific booster development, as well as to explore other solutions
• Even though the Regulators could allow smaller human testing e.g. 800 vs 15,000 vaccine recipients, there are always uncontrollable, unknown factors in a clinical trial, which could put current providers’ $30 Billion Covid vaccine business at risk
  • It is unlikely that they will be able to achieve the 94-95% efficacy they reported the first time, as those trials had unusually favorable factors, e.g., U.S. sample only, no new variants, and apparently ‘softer rules’ allowing the exclusion from the calculations of non-symptomatic cases, combined with a political environment wanting a ‘positive’ result
  • Given the disappointment with the rapid declines in vaccine effectiveness, and with the greater COVID-19 knowledge today, there could be greater regulatory scrutiny this time, depending on the frequency/severity impacts
• However, If the more dangerous impact scenario emerges from Omicron, regulators could weigh the cost/benefit tradeoffs of human testing vs. in vitro lab testing of new vaccine formulations - as is currently done annually for the flu - this is speculative, but was also suggested by an mRNA CEO
• On the WIV side:
  • Experts in the UK have stated that because a WIV vaccine has more parts of the virus for the immune system to learn from it could be more ‘variant-proof’ than the others
  • European Union has ordered up to 60 million WIV vaccines from Valneva
  • Sinovac has recently re-engaged with the EMA as to a potential European approval and market entry
• Global investor markets have become rattled and volatile, given the news of the Omicron variant

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