I have opened a long position with Ocugen (OCGN) as I am very bullish in this company now that they’ve partnered with Bharat Biotech. I believe this ticker has great potential to reach $30+ (as a conservative estimate) once it receives US FDA EUA approval which I suspect will be given in March 2021. Phase 1 and Phase 2 trials have gone very well producing encouraging results, therefore, I believe phase 3 trials will follow a similar suit.
Price Targets… $15, $25, $30+
I believe the stock is undervalued at the moment and has room for good entry points.
Week commencing Feb 8th 2021 $15
Phase 3 trials if all is well $25
If FDA EUA approval $30+
Day traders have a lot of opportunities to flip a few dollars in this stock, and…
Investors have a great opportunity to get a handsome return on their investment in the next 6 to 8 weeks, from the current price of $8.61.
I believe there is a lot of upside for both Day Traders and Investors.
Why? I’ve given some basic DD below. There are other catalysts that go in Ocugen’s and Bharat Biotech’s favour such as Fphizer pulling out of India, Covaxin can treat the new trains on COVID, other vaccine companies cannot produce enough vaccines that are needed etc… But I’ve not talked about them in this post.
The deal Ocugen has with Bharat Biotech will bring much need COVID vaccines to the US. Ocugen history of developing drugs at this point doesn’t really influence my decision as Ocugen is not the developer of Covaxin. Bharat Biotech history of developing drugs is what is important. How successful are Bharat Biotech? Well, I’ve listed below Bharat Biotech key achievements and the company is very impressive.
Ocugen will take Bharat Biotech developments and distribute Covaxin in the US. The only importance is that Ocugen is a company that specialises in drug manufacturing. Why is this important? Because if Bharat Biotech partnered with a non-drug manufacturing company then I’d be concerned.
About Ocugen in Regards to Covaxin
Ocugen, Inc. is a biopharmaceutical company focused on discovering, developing and commercializing transformative therapies to treat blindness diseases. Our breakthrough modifier gene therapy platform has the potential to treat multiple retinal diseases with one drug – “one to many”.
Ocugen and Bharat Biotech Announce Execution of Definitive Agreement for the Commercialization of COVAXIN™ in the US Market.

• A definitive Agreement provides details of the previously announced intent to co-develop COVAXIN™ for the US market
• Ocugen and Bharat Biotech to share US commercialization profits
• Ocugen to receive an initial supply of COVAXIN™ doses from Bharat Biotech upon authorization from US regulatory authorities while it ramps up manufacturing in the US
• COVAXIN™ received EUA (Emergency Use Authorization) in India in January and is currently in a fully enrolled Phase 3 clinical trial involving 25,800 patients
• COVAXIN™ (whole-virion inactivated COVID-19 vaccine candidate) effectively neutralizes UK variant of SARS-Cov-2 reducing the possibility of mutant virus escapeD

Some people say… Just because Covaxin has EUA in India that doesn’t automatically mean it’ll get FDA EUA approval in the US. It will need to produce the necessary data to get FDA EUA approval in the US. However, Bharat Biotech are following the FDA guidelines, therefore, if the data is good from phase 3 trials, the FDA will grant EUA in the US.
People are betting on Covaxin does get FDA EUA approval. However, if it does get approval this stock will be worth a lot more than $8. If Covaxin gets FDA EUA in the US surely this stock is worth $30+ and that’s a conservative estimate.
You're right about this stock running from 0.29c to $8.62 is crazy, however, with what has been announced since mid-December, the current price falls in line with what is expected.
Dec 22nd 2020 - Ocugen announced that they will be partnering up with Bharat Biotech to product Covaxin COVID 19 vaccine to the US. The stock ran up from 0.29c to $3.05. That is a fair price for a company with this LOI agreement in place.
https://ir.ocugen.com/news-releases/news-release-details/ocugen-and-bharat-biotech-co-develop-covaxintm-whole-virion
Dec 22nd 2020 - Ocugen Inc. Announces Plan to Adjourn Annual Meeting of Stockholders, Modify Proposal Regarding Increase in Number of Authorized Shares. Clearly, they know what they have planned and are looking to go down a different route to splitting the shares and not giving an offering.
https://ir.ocugen.com/news-releases/news-release-details/ocugen-inc-announces-plan-adjourn-annual-meeting-stockholders
Dec 23rd 2020 - Ocugen announced that they’ve established a Vaccine Scientific Advisory Board. This board consists of some very experienced people.
https://ir.ocugen.com/news-releases/news-release-details/ocugen-establishes-vaccine-scientific-advisory-board
The two above things alone make Ocugen a solid $4+ stock. They got a partnership with a great Indian drugs manufacture and they clearly have been working on this project for some time to be able to put together this advisory board.
Jan 8th 2021 - Ocugen Inc. to Present at CTIC, HC Wainwright and Noble Capital Investor Conferences. This further supports Ocugen’s announcement on Dec 22nd 2020 regarding stockholders meeting. They are looking at alternative means for funding.
https://ir.ocugen.com/news-releases/news-release-details/ocugen-inc-present-ctic-hc-wainwright-and-noble-capital-investor
Jan 8th 2021 - Ocugen Inc. Regains Compliance with Nasdaq Bid Price Rule. This, in itself, adds value to the stock. It allows the company to be stable on the exchange and allows investors to gain confidence in the company’s future. This has to be worth at least a $1 increase in stock value. So now we’re at $5+ evaluation.
https://ir.ocugen.com/news-releases/news-release-details/ocugen-inc-regains-compliance-nasdaq-bid-price-rule
Jan 12th 2021 - Ocugen Inc. Announces the Cancellation of Stockholder Meeting Previously Adjourned. This again supports funding is being or has been raised in alternative means and there will be no offering. With no offering, people can have confidence in this stock maintaining its value and the company not needing to raise money from the public. This strengthens the current value and can add value to the $5+price target. $6+, now?
https://ir.ocugen.com/news-releases/news-release-details/ocugen-inc-announces-cancellation-stockholder-meeting-previously
Feb 2nd 2021 - Ocugen and Bharat Biotech Announce Execution of Definitive Agreement for the Commercialization of COVAXIN™ in the US Market.
This gives us investors a clearer picture of what we can expect Ocugen to get in return on this business venture. “Ocugen retaining 45% of the profits”. Not revenue, PROFITS. This says to me that Bharat Biotech and Ocugen will fundraise together to pay for the development of Covaxin in the US and when they sell the product, costs will be deducted and the remaining money (profits) will be split with Ocugen receiving 45%. This tells me that the risk to Ocugen is very little and the upside is good. This should raise the price target from $5 or $6 to $10.
https://ir.ocugen.com/news-releases/news-release-details/ocugen-and-bharat-biotech-announce-execution-definitive
About Bharat Biotech
We seek to address the health care needs of the 5.8 billion people in the emerging markets by driving innovation and being a frontrunner in research and development of new vaccines and bio-therapeutics.
Bharat Biotech was formed in 1996 and today, Bharat Biotech has over 160 patents. As a leading biotechnology company, we seamlessly straddle the worlds of product research and manufacturing to create effective vaccines and therapeutics for patients around the world.

1. 1996 - Dr. Krishna M. Ella & Mrs. Suchitra Ella start Bharat Biotech in Genome Valley, Hyderabad, India—the first company to set up operations in the biotechnology park.
2. 1998 - Dr. A.P.J Abdul Kalam launches Revac-B+®—world’s first Cesium Chloride free Hepatitis B vaccine created by Bharat.
3. 1999 - Expands capacity to make 100 million doses of Revac-B+® annually to become the largest manufacturers of Hepatitis B vaccines in the world.
4. 2001 - Chandrababu Naidu, then Chief Minister of Andhra Pradesh launches BIOGIT®—India’s first probiotic yeast and Bharat Biotech’s first bio-therapeutic product.
5. 2002 - Becomes the first Indian company to receive two grants from the Bill & Melinda Gates Foundation through Program for Appropriate Technology in Health (PATH) to develop new vaccines against Malaria and Rotavirus.
6. 2003 - Bharat Biotech felicitates Dr. John B. Robbins—the father of polysaccharide vaccines for his tremendous contribution to the world of vaccines.
7. 2004 - Bharat Biotech pioneers REGEN-D®—India’s first recombinant human epidermal growth factors for Degree I & Degree II burns, skin grafts, and diabetic foot ulcers. Simultaneously launches its 2nd bio-therapeutic product, ZELECT®.
8. 2005 - Announces a manufacturing and marketing agreement with Cambridge-based Acambis, plc., for developing the Japanese Encephalitis vaccine—a neglected disease.
9. 2006 - Dr Julie Gerberding, Director, Centre for Disease Control and Prevention (CDC) launches the chromatographically purified vero cell rabies vaccine, INDIRAB® (then Rabirix®).
10. 2007 - Launches BioHib®—India’s first indigenously developed and manufactured Haemophilus Influenza Type B (Hib) vaccine.
11. 2008 - Dr. Manmohan Singh, then Prime Minister of India, presents FICCI Award to Bharat Biotech by the Federation of Indian Chambers of Commerce and Industry for “Excellence in Science, Technology and Technological Innovation”.
12. 2009 - Senior General Mr. Than Shwe, Chairman, State Peace & Development Council, Union of Myanmar launches Comvac 5 PFS® (Pre-filled syringes)—Pentavalent Combination vaccine—Bharat Biotech’s best-selling product.
13. 2010 - Launches HNVAC® – India’s first cell culture-based H1N1 (Human Inactivated Influenza A virus) Swine flu Vaccine.
14. 2011 - Bill Gates, co-chair of the Bill & Melinda Gates Foundation and Chairman of Microsoft, meets Dr. Krishna Ella, CMD of Bharat Biotech, regarding the development of Rotavac—Bharat Biotech’s affordable diarrheal vaccine.
15. 2012 - Bharat Biotech & University of Maryland collaboratively receive USD 4 Million ‘Strategic Translation Award’ from the Wellcome Trust for clinical development of a new life-saving conjugate vaccine for Invasive Non-Typhoidal Salmonella (iNTS).
16. 2013 - Launches Typbar TCV®—the world’s 1st clinically proven conjugate Typhoid vaccine.
17. 2014 - Launches JENVAC®—a safe and highly effective vaccine that protects against all the known strains of Japanese encephalitis.
18. 2015 - ROTAVAC—rotavirus vaccine was launched by Shri. Narendra Modi, Prime Minister of India. It becomes the first vaccine under the “Make-in-India’ initiative.
19. 2016 - Bharat Biotech becomes the first company in the world to file a global patent for Zika vaccine.
20. 2017 - TYPBAR-TCV demonstrates 87% efficacy in the world’s first Typhoid Human Challenge study carried out at Oxford University.
21. 2018 - WHO prequalifies TYPBAR-TCV and ROTAVAC vaccines.
22. 2019 -
    
23. Bharat Biotech has acquired Chiron Behring from GSK in March 2019 to become largest rabies shot, producer.
    
24. Rotavac 5D was launched by Hon’ble Vice President M. Venkaiah Naidu in New Delhi.
    
25. Chirorab, earlier marketed under the trade name Rabipur®, was launched on November 13th, 2019.
    
26. Bharat Biotech hits the landmark figure of 100 million doses supply of Rotavac.
    
27. 2021 - Covaxin…https://www.bharatbiotech.com/covaxin.html
    

WARNING: It is up to you to judge the accuracy and veracity of the below before trading. I take no responsibility for the accuracy of the information in this thread.

Your Pre Market Brief for Wednesday December 9th 2020

Back because I'm having problems finding value plays in this inflated market and need a few good ideas. Will continue until I get exhausted.
You can subscribe to the daily 4:00 AM Pre Market Brief on The Twitter Link Here . Alerts in the tweets will direct you to the daily 4:00 AM Pre Market Brief in this sub.
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Published 3:41 AM EST / Updated as of 4:00 AM EST
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Stock Futures:

• Pre-Market Trading

Wednesday 12/08/2020 News and Markets Recap:

• News and Market Recap

Friday August 28th 2020 Economic Calendar (All times are Eastern)

• 12:00 PM MBA Mortgage Applications
• 12:00 PM MBA 30-Year Mortgage Rate 04/DEC
• 03:00 PM Wholesale Inventories MoM OCT
• 03:00 PM JOLTs Job Openings OCT
• 03:30 PM EIA Distillate Stocks Change 04/DEC
• 03:30 PM EIA Cushing Crude Oil Stocks Change 04/DEC
• 03:30 PM EIA Crude Oil Stocks Change 04/DEC
• 03:30 PM EIA Gasoline Stocks Change 04/DEC
• 03:30 PM EIA Refinery Crude Runs Change 04/DEC
• 03:30 PM EIA Heating Oil Stocks Change 04/DEC
• 03:30 PM EIA Distillate Fuel Production Change 04/DEC
• 03:30 PM EIA Gasoline Production Change 04/DEC
• 03:30 PM EIA Crude Oil Imports Change 04/DEC

Overnight News Heading into Wednesday December 9th 2020
(News Yet to be Traded 8:00 PM - 4:00 AM EST)
^{It is up to you to judge the accuracy and veracity of the below before trading. I take no responsibility for the accuracy of the information in this thread.}

• JKS JinkoSolar Announces Proposed At-The-Market Offering of up to US$100,000,000 of ADSs
• SNY Sanofi, Kiadis Satisfy Competition Condition Regarding Tender Offer
• PSTI Pluristem Announces DMC Recommendation Following Interim Analysis of its Phase III CLI Study
• LPCN ($1.68) Lipocine Announces Tentative Approval of TLANDO™
• LPCN Lipocine Announces Deletion of Unauthorized Changes to Company's Website
• CE Mitsubishi Gas Chemical Company and Celanese Corporation Sign MOU to Restructure Korea Engineering Plastics JV
• BDX New Clinical Trial Data Demonstrates BD Libertas™ Wearable Injector as a Drug Delivery System
• RHHBY MRNA Roche joins Moderna to include antibody test in COVID-19 vaccine trial
• STMP Metapack Announces TDC 2021 to Take Place Virtually in February
• AMYT Amryt Group Receives Marketing Authorisation Approval for Lojuxta® in Brazil
• TGA ($0.88) TransGlobe Energy Corporation Announces DirectoPDMR Shareholdings
• ASX ($5.66) ASE Technology Holding Co., Ltd. Announces Monthly Net Revenues
• AVYA Batelco Sees Growth In Avaya OneCloud Business
• NTRS Standard Chartered and Northern Trust Partner to Launch Zodia, a Cryptocurrency Custodian for Institutional Investors
• SRNE Sorrento Receives Licensure From the State of California for Clinical Testing Laboratory Allowing for Clinical Sample Testing
• AAPL Apple Gets $200 Bull Case Target From Wedbush On Strongest Product Cycle Since 2014
• KURA Kura Oncology Announces Pricing of $300 Million Public Offering of Common Stock
• SBTX $999,999.00 of shares acquired by Presidio Management Group Xii, L.l.c. (10% Owner), reported in a new form 4 filed with the SEC
• STRO Sutro Biopharma Announces Pricing of $126.0 Million Public Offering
• ATRA Atara Biotherapeutics Announces Pricing of $175.0 Million Public Offering
• ATOS Atossa Therapeutics Announces Pricing of $20.0 Million Underwritten Public Offering
• HOOK HOOKIPA Pharma Announces Pricing of Public Offering of Common Stock and Preferred Stock (Note: Offering was proposed after market close. The offering was announced at 10:00 pm)
• LMT reported 8+ new insider trades (Selling) to the SEC slightly before 8:00pm
• HUBG reported 4 new insider trades (sold) to the SEC after market close
• IGMS IGM Announces Pricing of Upsized $200 million Public Offering
• AY Atlantica Sustainable launches share offering
• BRP Group, Inc. Announces Pricing of Its Public Offering of Common Stock of $29.50 per share (Earlier news below in the offering section)

End of Day and After Hours News Heading into Wednesday December 9th 2020
(News Traded 4:00 PM - 8:00 PM EST)
^{It is up to you to judge the accuracy and veracity of the below before trading. I take no responsibility for the accuracy of the information in this thread.}

• MSFT Microsoft Says Key Xbox Game ‘Halo Infinite’ Coming in Fall
• PRPH ($9.08) ProPhase Labs Expands COVID-19 Testing Capacity with New 25,000 Square Feet Testing Facility in Garden City, New York
• AAPL New Orders of Apple’s AirPods Max Won’t Arrive for Christmas
• GME GameStop Stock Sinks After Third-Quarter Sales Tumble
• VIAV ($13.75) Viko Optics Technical enters licensing agreement with VIAVI for 3D sensing filters
• AT ($2.04) Atlantic Power Corporation Provides Update on Calstock Power Purchase Agreement and Cadillac Insurance Settlement
• GSM ($1.78) U.S. Silicon Metal Producers Welcome Duties on Unfairly-Traded Silicon Metal Imports from Bosnia and Herzegovina, Iceland
• BRF ($4.52) 5-Brazil's BRF shares soar after bold 10-year plan
• RARE GeneTx and Ultragenyx Announce Presentation of Phase 1/2 Data on Investigational GTX-102 in Patients with Angelman Syndrome
• BAX OMCL Baxter seeks to buy Omnicell for $5B-plus - Reuters
• WTI W and T Offshore Provides Operational Update and Increases Production Guidance for the Fourth Quarter of 2020
• WAT Waters Collaborates with Dr. Sunghwan Kim of Kyungpook National University to Advance Precision Analysis of Complex Chemical Compounds
• CHWY Chewy Stock Dips Even After Earnings Beat Expectations
• BA U.K. to Drop Tariffs on U.S. Goods in Airbus-Boeing Dispute
• ZGNX Form 8-K: Entry into a Material Definitive Agreement.On December 3, 2020,, Zogenix, entered into a Collaboration, Option and License Agreement with Tevard Biosciences for the research, developmet
• CMBM Cambium Networks announces litigation settlement
• FDX FedEx Shares Pierce $300 Level For First Time Ever
• FEYE FireEye Stock Falls After ‘State-Sponsored’ Cyber Attack
• UBER Uber sells flying taxi Elevate business to Joby Avionics and makes $75M investment
• UBER Uber offloads troubled self-driving unit to startup Aurora
• CR Crane Elects New Director
• SHO Sunstone Hotel Investors Announces The Sale Of The 502-Room Renaissance Los Angeles Airport For $91.5 Million
• MFAC Form 8-K: Notice of Delisting or Failure to Satisfy a Continued Listing Rule or Standard; Transfer of Listing. On December 8, 2020, Megalith Financial Acquisition Corp. where the Company has bee
• MFAC Megalith Financial Acquisition Corp. Transfers Listing to NYSE American
• PFE U.S. FDA Accepts for Priority Review the Biologics License Application for Pfizer’s Investigational 20-valent Pneumococcal Conjugate Vaccine for Adults 18 Years of Age and Older
• MUX ($1.03) McEwen says production resumes at San José mine
• QS QuantumScape ‘Hitting a Home Run’ in Battery Technology
• PRCP ($6.97) Perceptron Shareholders Approve Merger Agreement with Atlas Copco
• RWLK ($1.23) ReWalk Robotics Announces Closing of $8.0 Million Private Placement Priced At-the-Market
• SALT Scorpio Bulkers sells Ultramax vessel
• MDP MongoDB reports Q3 beats, upside Q4 and full-year forecasts
• EFX Equifax Announces SVP of Product, Data & Analytics for Consumer Business
• AVAV AeroVironment Acquires ground robotic solutions provider, Telerob
• GWRE Guidewire Software EPS beats by $0.22, beats on revenue
• ASMB ($6.20) Assembly Biosciences pulls the plug on microbiome program
• MA Mastercard Board of Directors Announces Quarterly Dividend and $6 Billion Share Repurchase Program
• TUFN Tufin to Present at Barclays Global Technology, Media and Telecommunications Conference
• ENR Energizer Holdings, Inc. Announces Conditional Full Redemption of 7.750% Senior Notes Due 2027
• CRIS ($6.55) Curis Announces Proposed Public Offering of Common Stock
• AZN Oxford-AstraZeneca COVID-19 vaccine 'safe and effective,' but questions remain for elderly - Lancet
• VVNT Vivint Smart Home Announces Redemption of Public Warrants
• TTCF Tattooed Chef Newest Innovation Features Plant-Based Meat Alternatives
• CUBE CubeSmart Announces 3.0% Increase in Quarterly Common Dividend
• PLDI PDL Announces Timeline for Voluntarily Delisting from Nasdaq
• BRX Brixmor Property Group Announces Fourth Quarter 2020 Earnings Release And Teleconference Dates
• ILMN Illumina and Harvard Pilgrim Health Care Expand Access to Whole-Genome Sequencing for Genetic Disease Testing
• FBHS Fortune Brands Increases Quarterly Dividend for 8th Consecutive Year
• RCKT Rocket Pharmaceuticals Announces Positive Gene Expression, Clinical Biomarker and Preliminary Functional Data from Phase 1 Trial of RP-A501 for the Treatment of Danon Disease
• TAK Takeda’s Pipeline Has Potential to Contribute Significantly to Revenue Growth Over Next Decade
• ALBOAlbireo submits U.S. and European applications for odevixibat in liver disease

Possible Dip Buying Opportunities in the near future (Other suggestions appreciated):
Suggested Dip Trading Strategy

• AOUT: Posturing before earnings on the 15th
• PFSW: Dipping as a result of low volume trading weeks after earnings, nearing support
• TOL: Poor guidance and headwinds in the real estate market (Reliable company though)
• LEN: Dipping as a result of TOLL's guidance. Posturing for earnings on the 16th
• SPWH: Dropping as analysts expect a decrease in revenue earned next year.
• ITB: Real estate expected to cool off in the winter before popping again in the Spring
• LMT: Typical post dividend dip (Update: Be careful, just announced 8 insider sells at 8:01 PM)
• CRM: Dipping because investors assess they paid too much for the Slack purchase
• KMX: Been trading sideways for nearly 6 months. Earnings on 12/22

Offering News:

• UBER Uber Announces Pricing of $1.0 Billion Convertible Senior Notes Offering
• YCBD cbdMD Announces Pricing of $15 Million 8.0% Series A Cumulative Convertible Preferred Stock Offering
• PCF High Income Securities Fund Announces Non-Transferable Rights Offering
• HD Form SC TO-T/A (tender offer statement by third party) filed with the SEC
• HDS Form SC TO-T/A (tender offer statement by third party) filed with the SEC
• TSLA Elon Musk Shrugs at Tesla’s $5 Billion Stock Issuance
• OMF OneMain Holdings, Inc. Announces Pricing of Upsized $850 Million Aggregate Principal Amount of Senior Notes due 2030
• OXY Occidental Announces Upsize of Previously Announced Cash Tender Offers and Consent Solicitations for Certain of its Senior Notes
• HOOK HOOKIPA Pharma proposes public offering of common and preferred stock
• BRP Group Announces Proposed Public Offering of Common Stock
• TALO ($10.51) Talos Energy Announces Public Offering Of Common Stock
• ICHR Ichor readies 3.5M shares public offering
• DCTH Delcath System proposes public offering
• NVO Novo Nordisk Completes Acquisition of Emisphere Technologies for $1.35 Billion
• RUSH Rush Enterprises Adopts $100 Million Stock Repurchase Program and Announces Holiday Employee Gift
• WSFS WSFS Financial Announces Closing of Senior Notes Offering
• CVM CEL-SCI Announces Bought Deal Offering

Upcoming Earnings:

• Earnings Calendar
• Earnings Calendar II

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Subscribe to This Brief and the daily 4:00 AM Pre Market Brief on The Twitter Link Here . Alerts in the tweets will direct you to the daily brief in this sub
WARNING: It is up to you to judge the accuracy and veracity of the above before trading. I take no responsibility for the accuracy of the information in this thread.

Intro What is $ATNM and why do I like it? According to it's about page, Actinium Pharmaceuticals is "... a clinical-stage biopharmaceutical company developing ARC’s or Antibody Radiation-Conjugates, which combine the targeting ability of antibodies with the cell killing ability of radiation. " They're currently in a pivotal Phase 3 trial for their new drug Iomab-B that condition's elders with relapsed or refractory acute myeloid leukemia for life saving bone marrow transplants. I think Actinium has a product with promise and it's at a reasonable price for a long-term speculative play.
Disclaimer This is not financial advice. I'm just a random guy on the internet. Always do your own due diligence.
The Product with Potential What separates $ATNM from other pharmaceutical companies is their cancer-targeting technology. They call it their Antibody Warhead Enabling (AWE) platform because they "exploit the use of highly selective targeted biological agents such as monoclonal antibodies that can seek out and bind cancer antigens found on the tumor cell surface." Which basically means they modify antibodies with the ability to deliver tumor destroying radiation (the "warhead") directly to the cancer cells. This is in contrast to general chemotherapy that irradiates healthy cells in the process of irradiating cancer cells. The ability to specifically target cancer cells opens the door to life saving treatments for elders who can't endure traditional chemotherapy.
If that sounds too good to be true, then check out the data collected from their ongoing trials. With only 75% enrollment to their Phase 3 trials in December 2020, Yahoo Finance reported on positive results with patients already enrolled. The article goes into detail about the trials, stating "100% (49/49) of patients receiving a therapeutic dose of Iomab-B in SIERRA have successfully proceeded to Bone Marrow Transplant (BMT) compared to 16% (9/56) of patients in the control arm who received physician's choice of salvage therapies... Of the 84% (47/56) of patients that did not achieve complete remission on the control arm, 64% (30/47) of patients crossed over to receive Iomab-B with 100% (30/30) of those patients successfully proceeding to BMT." They provide a helpful chart to help visualize this.
Remember, Iomab-B isn't the cure for cancer, it's the means of conditioning elders to be able to receive bone marrow transplants. It's the bone marrow transplants that save lives, and using Iomab-B significantly increases survivorship. Their page on Iomab-B shows increased survival rates from ~10% in year one to 30% survival in year one and 0% survival in year two to 19% survival in year two. Additionally, Iomab-B lets patients receive bone marrow transplants 12 days after therapy compared to 42 days with chemotherapy according to the chart they provide.
I'm not a doctor, but an increased survival rate of ~20% for year one and two independently seems significant considering the current survival rates. In my opinion, the results from the study point to a new, more accessible cancer therapy that looks prime to be approved by the FDA at the end of Phase 3.
The Company When buying stocks, it's important to remember that you're buying portions of a company in hopes that they can use your cash to generate more profits for you later down the line. The ability for a company to do that is hinged on a few factors, the first factor being the company management. $ATNM provides us with a page of their executive team which includes all of the people who make the company run. The CEO Sandesh Seth seems capable of the position with 25+ years in investment banking, equity research, and most importantly, the pharma industry (to include working for Pfizer [who's currently rolling out Covid vaccines]). He even has several patents related to radiopharmaceuticals. Of course, the doctors on staff at $ATNM are equally as important to take into consideration when developing new drugs. The Scientific Advisory Board (for Iomab-B) is made up of experts in their field from Cancer Centers all over the country; It's worth viewing their extensive credentials.
Another important factor in determining a company's value is their financial statements. I've had some struggle with valuing $ATNM because their financial statements are not like the ones I'm accustomed to reading. Meaning, I don't have much experience knowing if a clinical-trial pharmaceutical company's financials are good or not, but I did my best with what I know. For starters, I looked into the company's ability to pay back its debt, because a company with large, unexplainable debts is a red flag for me. In the case of $ATNM, I noticed that their Quick and Current Ratio were very good (at 1.74 and 1.89 respectively). This means that they have enough assets to pay off well over 100% of the short-term debt they owe. Having learned this, I looked into their assets and liabilities to discover that their current assets, which are mostly in cash and short-term investments, have been steadily draining at a rate of ~$5million annually. This is due to high operating expenses that are mostly in the research and development of their new drugs. I assume that they will simply leverage their low debt to borrow capital if needed. Additionally, although net income and earnings per share are negative, they've been increasing year over year from 2018 and 2015 respectively. I think EPS is going to be positive in the short term if it continues its trend. I used stockrow.com to get financials.
The Valuation So what's $ATNM worth? How much money can you make? Yahoo Finance estimates that $ATNM will hit a price target of $38.74 in one year with a low of $25 and high of $65. I take it with a grain of salt. All I know is that I think the cancer treatment they're developing is outstanding enough to separate it from other treatments already available for AML. The data from their research has earned my confidence in the treatment and I think buying and holding $ATNM long will be rewarding. This is speculative though, so I would only put in money you can afford to lose.
I hope this was helpful!

PyschoMarket Recap - Monday, September 14, 2020
Stocks rose Monday as investors eyes newly announced mergers & acquisitions, positive vaccine news, and a lowering coronavirus infection rate in hotspot states. Tech shares appear to be recovering, opening the day high before paring gains to finish mostly even. The major indexes all closed green, the SPY finished up 1.3%, the QQQ was up 1.7% and the DIA up 1.2%
Today it was announced Oracle (ORCL) made a deal with TikTok parent company ByteDance to become the company’s “trusted technology provider.” The new deal between TikTok and Oracle comes after Microsoft Corporation (MSFT) said Sunday that ByteDance had rejected its buyout offer. National Security Concerns: On Monday, U.S. Treasury Secretary Steven Mnuchin said he will be reviewing the proposed deal between ByteDance and Oracle this week. “I will just say from our standpoint, we’ll need to make sure that the code is, one, secure, Americans’ data is secure, that the phones are secure and we’ll be looking to have discussions with Oracle over the next few days with our technical teams,” Mnuchin said.
Elsewhere, NVIDIA (NVDA) announced it was purchasing Arm, semiconductor and software design company from SoftBank Group for $40 billion, the largest ever M&A in the semiconductor industry. Jensen Huang, the CEO of NVIDIA, said “ Uniting NVIDIA’s AI computing capabilities with the vast ecosystem of Arm’s CPU, we can advance computing from the cloud, smartphones, PCs, self-driving cars and robotics, to edge IoT, and expand AI computing to every corner of the globe.
Gilead (GILD) announced it was acquiring biotech company Immunomedics (IMMU) for $21 billion. Immunomedics developed Trodelvy, an antibody-drug conjugate used to treat triple-negative breast cancer. Trodelvy received FDA approval in April and recorded $20 million in sales in its first two months on the market. Shares of GILD were up 2.22% and IMMU finished 97% up.
AstraZeneca (AZN) announced over the weekend that its late-stage Covid-19 vaccine trials with the University of Oxford resumed after safety concerns over a suspected adverse reaction from a participant made the company pause trials temporarily last week. Shares rose 0.52% today.
Andrew Cuomo reported today, “Of the 63,358 tests reported yesterday, 583 were positive (0.92% of total). Total hospitalizations are at 464. Sadly, there were 4 COVID fatalities yesterday.” The numbers in New York have been steadily decreasing, according to a chart accompanying the statement.
Highlights

• DraftKings (DKNG) says it entered into a multi-year agreement with ESPN to become a co-exclusive sportsbook link-out provider and exclusive daily fantasy sports provider of the media giant. DKNG finished the day 17.27% up.
• Nikola (NKLA), recently published their response to the fraud allegations being levied at the company and its founder, Trevor Milton. Furthermore, today the SEC announced to open an investigation on the allegations.
• NFL Media and DISH Network (DISH) have reached an agreement on a new multi-year contract for NFL Network and NFL RedZone.
• Snowflake (SNOW) lifts IPO price to $100-110 range. IPO date expected Wednesday. Keep a close eye out!
• Overstock (OSTK) coverage initiated by Needham & Company Llc. $96 at BUY (implies a 20% upside). up 16% for the day
• Penn International Gaming (PENN) reiterated by Goldman Sachs $66 BUY
• Micron Technology (MU) upgraded by Goldman Sachs (GS) $58 NEUTRAL to BUY.
• Apple (AAPL) reiterated by Oppenheimer at BUY $125
• Adobe (ADBE) Target Raised by Morgan Stanley (MS) $450 to $560 OVERWEIGHT
• Gamestop (GME) up 13% today after missing earnings last week.

What is Sesen Bio & what do they do?

• They are a late-stage company developing fusion protein medicines. Their fusion protein approach tethers a tumor-targeting antibody fragment to a protein cytotoxic payload to form a single protein molecule designed to selectively and broadly kill cancer cells while minimizing toxicity to healthy cells and to activate the body’s innate immune response system.
• In other words, they work to make a better treatment, one that kills cancer effectively in a way that does not harm normal healthy cells the same way traditional chemotherapy does.
• Their key product is Vicinium for both:
  • Head and neck cancer
  • Cancer of the bladder

What is Vicinium?

• Vicinium, also known as VB4-845, is an antibody-drug conjugate (ADC), developed for the treatment of high-grade non-muscle invasive bladder cancer (NMIBC). Vicinium is comprised of a recombinant fusion protein that targets epithelial cell adhesion molecule (EpCAM) antigens on the surface of tumor cells to deliver a potent protein payload, Pseudomonas Exotoxin A (ETA). EpCAM has been shown to be overexpressed in NMIBC cells with minimal to no EpCAM expression observed on normal bladder cells.
• The current standard/traditional form of treatment for bladder cancer at the moment is bacillus Calmette-Guérin (BCG) During phase 1 & 2 of clinical trials, Vicinium is proving to be more successful than the current standard form of treatment for Bladder Cancer. I will provide evidence for said statement soon.

** How successful is the current standard form of treatment(BCG) and how successful is Vicinium proving to be so far compared to BCG?**

• According to this medical publication found on the government US National Library of Medicine website, it states that the current standard form of treatment which is "BCG", has upto 40% of people fail the treatment.
• According to another medical publication posted on the same gov website, [the article states that Nearly three-fourths of patients](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3773281) diagnosed with high-risk bladder cancer will recur, progress, or die within ten years of their diagnosis.
• according to the preliminary findings of phase 3 of Vicinium trials, it goes to show that at the end of the 12month study:
  • 40% of participants showed complete response rate to Vicinium
  • 71% were recurrence free
  • Overall survival rate at 12 months for those participating in the study is 98% (this just shows that currently on Vicinium, at the 12month mark, survival rate is at 98%. At the two year mark it could be the same or much lower, that statistic is unknown as of right now)
• Here are links on what i have mentioned regarding phase 3 preliminary results
  • Link 1
  • Link 2
  • Link 3
  • Link 4

Significant Vicinium Press releases

• In August 2018, SESN received Fast Track designation from the FDA for Vicinium for the treatment of high-risk NMIBC
• In May 2019, SESN met with the FDA for a Type C meeting for CMC and reached agreement with the FDA on the analytical comparability plan to be used to assess comparability between the drug supply used in clinical trials and the potential commercial drug supply to be produced by Fujifilm.
• In June 2019, SESN met with the FDA for a Type B Pre-BLA meeting regarding the approval pathway for Vicinium for the treatment of patients with high-risk, BCG-unresponsive NMIBC. At the meeting, we reached alignment with the FDA on an accelerated approval pathway for Vicinium along with Rolling Review
• In November 2019, SESN met with the FDA for a Type C meeting to discuss the details of a post-marketing confirmatory trial for Vicinium for the treatment of high-risk NMIBC.
• On December 4, 2019, SESN met with the FDA for a Type B pre-BLA meeting for CMC. At that meeting, we reached agreement with the FDA on the final content for Module 3 of the BLA.
• On December 6, 2019, SESN initiated their BLA submission for Vicinium to the FDA under Rolling Review The submission consisted of Modules 1, 2, 4 and 5, with information amendments to be submitted to these modules throughout 2020. They anticipate completing Module 3 to finalize the BLA submission in the second half of 2020 (Q2).

Recent Financials (Q1 of 2020)

• Their estimated EPS for the quarter according to the NASDAQ website was at -0.1 but they beat expectations and reported an EPS of 0.31
• Net income was $41.6 million, or $0.31 per basic share and $0.31 per diluted share, for the three months ended March 31, 2020, compared to a net loss of $6.5 million, or $0.08 per basic and diluted share, for the same period in 2019
• As stated in their most recent SEC Filings: "Based on our current operating plan, we anticipate having sufficient cash to fund our operations into 2021".

Manufacturing of Vicinium

• In October 2018, SESN entered into a Master Bioprocessing Services Agreement with Fujifilm for the manufacturing process and technology transfer of Vicinium drug substance production.
• In April 2019, the first full, commercial-scale cGMP run was completed at Fujifilm and all quality acceptance criteria were met. This supports Fujifilm’s ability to produce the bulk drug substance form of Vicinium for commercial purposes if we receive regulatory approval to market Vicinium for the treatment of high-risk NMIBC. Link
• In February 2020, manufacturing of the pre-process performance qualification batch was completed at Fujifilm Full quality release testing of the drug substance has been completed and all quality acceptance criteria were met. In addition, the bulk drug substance from the Fujifilm pre-PPQ batch has been used to manufacture the first drug product PPQ batch by Baxter Oncology GmbH. Full quality release testing of the first drug product process performance qualification batch is currently underway.

Target Price & Forecasts

• CNN money sets a median target price of $3, a low of $2.25 and a high estimate of $5
• TipRanks sets a median target price at $3.63, a low of $2.25 and a high of $5
• NASDAQ website sets a median target price of $3 and a high of $5

Risks involved

• as requested, I will be providing a risks portion to my DDs
• As stated in their recent SEC FIlings:
  • "On March 2, 2020, we received written notice (the “Notice”) from The Nasdaq Stock Market, LLC (“Nasdaq”) indicating that we are not in compliance with the $1.00 minimum bid price requirement for continued listing on The Nasdaq Global Market, as set forth in Nasdaq Listing Rule 5450(a)(1). In accordance with Nasdaq Listing Rule 5810(c)(3)(A), we had a period of 180 calendar days, or until August 31, 2020, to regain compliance with the minimum bid price requirement. To regain compliance, the closing bid price of our common stock must meet or exceed $1.00 per share for a minimum of ten consecutive business days during this 180-day period." Link for this
• Sesen Bio Received an extension and they have until November 12 2020 to reach compliance, if they do not they run the risk of delisting and would have to reapply to be listed on the Nasdaq market. If they do not come to compliance by then, they will "consider implementing available options to regain compliance with the minimum bid price requirement under the Nasdaq Listing Rules, including effecting a reverse stock split."

** Final thoughts and comments**

• I believe that they will be approved by the FDA in the foreseeable future. Especially with the fact that they have been granted a fast track designation to approval of vicinium.
• Not only that, but during their first quarter market research, data shows that Uruologists prefer Vicinium over Keytruda and traditional treatments. As stated by SESEN bio on their website: " The research revealed that, when prescribing a branded agent, Urologists would prescribe Vicinium to 83% of their patients compared to 17% for Keytruda" Link
• I have personally invested 100 shares of SESN at the price of .78
• I firmly believe they will reach to their low estimated price target due to all the science behind their work and the fact that they are currently debt free and have enough funds to last them through 2021.
• As i always tell everyone, dont blindly buy stocks without doing your own research. I highly recommend that you do your own DD alongside reading all the material and links i have provided.
• I do this so you, the reader, can have the best knowledge/information on a stock so you can , make a well informed decision before purchasing a stock.
• Always remember, do not go all in on any stock, if you do, thats on you. Always purchase any stocks youre interested in with what you are comfortable spending
• I hope this DD can help you make a well informed decision to either purchase or stay away from.
• EDIT: I FORGOT TO MENTION THIS: Another reason why I believe in this stock & their flagship product is because there currently is a shortage of BCG. This shortage, alongside the fact Vicinium is expected to be approved sooner due to their fast track designation & successful manufacturing with partner Fujifilm, is why I truly do believe in this stock.
  • Here are links regarding the shortage: Link 1 Link 2 Link 3 Link 4

Hope you guys enjoyed this DD and i hope it has helped you guys with making any decisions/answered questions regarding SESN.
Take care guys! :)

PyschoMarket Recap - Monday, September 14, 2020
Stocks rose Monday as investors eyes newly announced mergers & acquisitions, positive vaccine news, and a lowering coronavirus infection rate in hotspot states. Tech shares appear to be recovering, opening the day high before paring gains to finish mostly even. The major indexes all closed green, the SPY finished up 1.3%, the QQQ was up 1.7% and the DIA up 1.2%
Today it was announced Oracle (ORCL) made a deal with TikTok parent company ByteDance to become the company’s “trusted technology provider.” The new deal between TikTok and Oracle comes after Microsoft Corporation (MSFT) said Sunday that ByteDance had rejected its buyout offer. National Security Concerns: On Monday, U.S. Treasury Secretary Steven Mnuchin said he will be reviewing the proposed deal between ByteDance and Oracle this week. “I will just say from our standpoint, we’ll need to make sure that the code is, one, secure, Americans’ data is secure, that the phones are secure and we’ll be looking to have discussions with Oracle over the next few days with our technical teams,” Mnuchin said.
Elsewhere, NVIDIA (NVDA) announced it was purchasing Arm, semiconductor and software design company from SoftBank Group for $40 billion, the largest ever M&A in the semiconductor industry. Jensen Huang, the CEO of NVIDIA, said “ Uniting NVIDIA’s AI computing capabilities with the vast ecosystem of Arm’s CPU, we can advance computing from the cloud, smartphones, PCs, self-driving cars and robotics, to edge IoT, and expand AI computing to every corner of the globe.
Gilead (GILD) announced it was acquiring biotech company Immunomedics (IMMU) for $21 billion. Immunomedics developed Trodelvy, an antibody-drug conjugate used to treat triple-negative breast cancer. Trodelvy received FDA approval in April and recorded $20 million in sales in its first two months on the market. Shares of GILD were up 2.22% and IMMU finished 97% up.
AstraZeneca (AZN) announced over the weekend that its late-stage Covid-19 vaccine trials with the University of Oxford resumed after safety concerns over a suspected adverse reaction from a participant made the company pause trials temporarily last week. Shares rose 0.52% today.
Andrew Cuomo reported today, “Of the 63,358 tests reported yesterday, 583 were positive (0.92% of total). Total hospitalizations are at 464. Sadly, there were 4 COVID fatalities yesterday.” The numbers in New York have been steadily decreasing, according to a chart accompanying the statement.
Highlights

• DraftKings (DKNG) says it entered into a multi-year agreement with ESPN to become a co-exclusive sportsbook link-out provider and exclusive daily fantasy sports provider of the media giant. DKNG finished the day 17.27% up.
• Nikola (NKLA), recently published their response to the fraud allegations being levied at the company and its founder, Trevor Milton. Furthermore, today the SEC announced to open an investigation on the allegations.
• NFL Media and DISH Network (DISH) have reached an agreement on a new multi-year contract for NFL Network and NFL RedZone.
• Snowflake (SNOW) lifts IPO price to $100-110 range. IPO date expected Wednesday. Keep a close eye out!
• Overstock (OSTK) coverage initiated by Needham & Company Llc. $96 at BUY (implies a 20% upside). up 16% for the day
• Penn International Gaming (PENN) reiterated by Goldman Sachs $66 BUY
• Micron Technology (MU) upgraded by Goldman Sachs (GS) $58 NEUTRAL to BUY.
• Apple (AAPL) reiterated by Oppenheimer at BUY $125
• Adobe (ADBE) Target Raised by Morgan Stanley (MS) $450 to $560 OVERWEIGHT
• Gamestop (GME) up 13% today after missing earnings last week.

As always fellow autist, enjoy your coffee
Of note for Hotel Names (H, MAR, HLT), NYC officials are reportedly working with hotel officials to potentially convert entire hotels into hospitals for patients without the coronavirus, according to WSJ. Elsewhere, the American Hotel and Lodging Association President and CEO stated “more than half of the hotels across America will close by the end of the month. Whether or not the closure is permanent or temporary. Some of it will be permanent”
Of note for Automakers (GM, F, TSLA), GM and F have been in talks with government officials on how it could support the production of medical equipment to help tackle the coronavirus outbreak. Tesla CEO Musk also announced in a tweet “We will make ventilators if there is a shortage”.

Dow Jones

Pfizer (PFE) announce it has postponed its investor day due to the coronavirus, although a specific date is not mentioned due to uncertainty surrounding the coronavirus. Although it did announce its late stage study of an experimental treatment, abrocitinib, was effective in treating atopic dermatitis in a combination with topical therapies. It also reported positive top line results from its pneumococcal conjugate vaccine in adult patients.
Walmart (WMT) announced US stores will adjust its operating hours to 07:00 to 20:30 to increase cleaning and allow more time for its stock to be stacked.

Nasdaq 100

Align Technology (ALGN) announced as the coronavirus spreads to Europe, Middle East, Africa and Americas, it is expecting a material impact from the virus on its Q120 results.
eBay Inc. (EBAY)– One of its largest shareholders, Starboard Value, announced it has delivered a formal notice to nominate four directors to the company board.
Facebook, Inc. (FB) CEO Zuckerberg dismissed the Washington Post report yesterday that the government is working with tech companies to use location data to tackle the coronavirus.
Marriott Int'l. (MAR) announced it has been implementing cost cutting measures, including shortened work weeks and pay cuts to senior executives. So far, the measures will reduce 2020 corporate general and administrative costs by at least USD 140mln. MAR also expects to eliminate or defer at least one third of its USD 700-800mln spending plans for 2020. It also notes as of March 17th it has drawn down USD 2.5bln of it USD 4.5bln revolving credit facility to support commercial paper maturities. It expects its latest dividend to be the last the conditions get better. Given the mentioned commitments the Co is facing, it has decided to withdraw all aspects of its outlook and assumptions for FY20. Elsewhere, it says there are early signs of improvement in China and the number of closed hotels in the region has fallen to under 30 from 90 previously.
Starbucks Corp. (SBUX) CEO announced on CNBC 95% of its China stores are expected to open by the end of the month, noting the “to go” model is working in both the US and China.
Tesla (TSLA) Fremont Factory in California will reportedly stay open, but at a limited capacity. Reports earlier in the week noted it had been ordered to halt operations temporarily amid the coronavirus pandemic. Elsewhere, the automaker was also upgraded to Equal Weight from Underweight at Morgan Stanley, where analyst Adam Jonas gives a USD 460 PT (Prev. close 361.22), where the analyst notes TSLA has sufficient cash and liquidity available to help against near term disruptions to its production and sales.
T-Mobile (TMUS) announced it is currently financially prepared to close its merger with Sprint (S)
Trip.com (TCOM) Q4 19 (USD): Adj. earnings per ADS 0.28, revenue 1.2bln (+10% Y/Y). Q1 revenue view -45 to 50%.

S & P 500

Abbott Laboratories (ABT) announced the US FDA issued an emergency use authorisation for its coronavirus test.
Accenture plc (ACN) Q2 20 (USD): EPS 1.91 (exp. 1.72), revenue 11.1bln (exp. 11.1bln), new bookings 14.2bln. Q3 revenue view 10.75-11.15bln (exp. 11.74bln). Cut its FY20 EPS view to 7.48-7.70 (exp. 7.84, prev. 7.66-7.84).
Darden Restaurants (DRI) Q3 EPS 1.90 (exp. 1.88), revenue 2.35bln (exp. 2.32bln); Same restaurant sales +2.3%. Withdraws FY20 guidance and announced it has suspended its quarterly dividend amid the coronavirus outbreak.
Diamondback Energy (FANG) announced it has cut activity even further. Due to the reduction in activity It expects to reduce its capital budget for this year by USD 1.2bln to USD 1.5-1.9bln from USD 2.8-3.0bln.
Estee Lauder Cos. (EL) announced it has withdrawing its FY20 guidance.
General Electric (GE) Healthcare CEO issued a statement noting it has increased its manufacturing capacity and output of equipment to help with diagnosis and treatment of patients with coronavirus. Adding it is continuously exploring options to support the increased need of medical equipment.
Harley-Davidson (HOG) announced it is temporarily suspending the majority of its US operations and the majority of its production employees will be on temporary layoff with medical benefits. Elsewhere, Impala Asset Management nominated two candidates to its board of directors.
Intercontinental Exchange (ICE) announced the NYSE will move temporality to fully electronic trading as of Monday the 23rd.
Lennar Corp. (LEN) Q1 20 (USD): EPS 1.27 (exp. 0.84), Revenue 4.5bln (exp. 4.16bln). Deliveries +17% to 10321 homes, Backlog +2% to 17,632. New orders +18% to 12,376 homes.
Marathon Petroleum (MPC) reportedly begun cutting production on Wednesday as demand for motor fuels in the Los Angeles area collapses
Occidental Petroleum (OXY) had its debt rating downgraded to Junk, noting credit challenges ahead following the collapse in energy prices.
TripAdvisor (TRIP) announced it has withdrawn its guidance for FY20 due to the coronavirus.
Twitter, Inc. (TWTR) is reportedly being used by the FDA to stay updated with medical and drug supply issues

Other

Autoliv (ALV) announced the coronavirus outbreak will likely lead to a negative effect on its operations, noting it has drawn down USD 500mln from its USD 1.1bln revolving credit facility to pay existing short-term debt.
Fiat Chrysler (FCAU) announced it has agreed with the UAW to cease production at its plants across North America until the end of March.
Guess (GES) Q4 19: EPS 1.22 (exp. 1.12), revenue 842mln (exp. 851mln; draws down USD 212mln from certain credit facilities and has postponed its decision in relation to a potential quarterly dividend.
Kirkland Lake Gold (KL) announced it has increased its dividend by 100% to USD 0.125/shr.
Qiagen (QGEN) announced it its coronavirus test kit has launched in Europe.
Snap (SNAP) had its PT lowered at Citi to USD 10 from USD 20 to reflect the impact of coronavirus is likely having on its advertising business. The analyst now expects revenue at USD 1.9bln in 2020, down from USD 2.2bln and beneath the street estimate of USD 2.4bln.
Steve Madden (SHOO) announced it has withdrawn its FY20 guidance.
Vail Resorts (MTN) announced its operations across North American properties will be suspended throughout the skiing season due to the coronavirus pandemic.
Williams Sonoma (WSM) Q4 19 (USD): Adj. EPS 2.13 (exp. 2.05), revenue 1.84bln (exp. 1.82bln); temporarily suspending the provision of FY20 guidance.

Additional US Equity Stories

Keurig Dr. Pepper (KDP) announced it has affirms its 2020 forecast of Adj. EPS growth between 13-15% and net sales growth between +3-4%.
Uber (UBER) reportedly expects to have USD 6bln cash on hand by the end of the year, with a USD 2bln revolver.
Airlines (DAL, LUV, AAL) – US Treasury Secretary Mnuchin says they are looking at secured loans for airlines on market terms.
Hotel Operators (HLT, MAR) – Nomura in a research note that HLT and MAR have the ability to survive most economic stresses, adding both have ample cash on hand and within revolvers to deal with the downturn for at least two years, and if needed, it has the sources for liquidity.
Ford (F) has offered new car customers a six-month payment relief, has withdrawn its FY20 guidance, suspended its dividend and notes it will borrow the total unused amounts against two credit lines with USD 13.4bln from its corporate credit facility, and USD 2bln under its supplemental credit facility.
Slack (WORK) announced it added 7000 new paid customers from the beginning of February. Note, previously it added 5000 paid customers per quarter.
Nucor (NUE) Q120 (USD) EPS view 0.95 - 1.00 (Q1 19 EPS was 1.63, Q419 EPS was 0.35/shr)
AbbVie (ABBV) treatment for the coronavirus, Kaletra, did not prove effective in treating the virus, according to a study.
Dish (DISH) announced it is to provide 20 MHZ of AWS-4 and all of its 700 MHz

Context -
The S&P 500 advanced as much as 0.6% on Tuesday on the back of continued strength in the value and cyclical stocks, but broad-based selling in the last hour of trading left the benchmark index down 0.8% snapping a seven-session winning streak. The Nasdaq underperformed with a 1.7% decline.
The late-day selling was attributed to comments from Senate Majority Leader McConnell (R-KY), who told Fox News that White House officials have yet to reconvene with congressional Democrats regarding fiscal relief for households and businesses.
Growth and defensive-oriented stocks saw increased selling that weighed on the S&P 500 information technology (-1.8%), utilities (-2.2%), real estate (-1.9
The financials (+1.3%) and industrials (+0.5%) sectors managed to close higher due to their perceived value.
Notably, U.S. Treasuries and precious metals had sizable pullbacks. The 2-yr yield increased three basis points to 0.16%, while the 10-yr yield increased eight basis points to 0.66% -- this curve-steepening activity was a boon for the financial stocks.
Gold futures fell 4.5% to $1946.90/ozt. The U.S. Dollar Index increased 0.2% to 93.72. WTI crude futures declined 0.7% to $41.66/bbl.
President Trump floated the idea of cutting taxes on capital gains and middle-income families to further stimulate the economy.
Russia jumped ahead key testing stages to approve a COVID-19 vaccine. It appears unlikely that Congress would approve such legislation or that people would seek out the Russian vaccine.
Index Summary -
S&P 500 -0.83%; Nasdaq -1.88%;
DOW -0.34%; Russell 2000 -0.58%
VIX: 24.03 1.9,( +8.59%)
Sector Summary -
The three highest sectors for today were :
Financials +1.16%; Industrials +0.53%; Materials -0.18%;
The three lowest sectors for today were :
Utilities -2.16%; Real Estate -1.92%; Information Technology -1.8%;
Commodities -
Gold - 1927.3,( -0.98%); Crude - 41.58,( -0.07%)
Today’s Option Activity Fast Facts -
CBOE Put/Call Ratio - 0.45
Highest Multiple Over Daily Average - AFL with 43 x the ADV of 1825. There were 39464 calls and 38616 puts.
Ticker with Most Contracts - BAC with 690590 contracts traded today with an AVD of 323255. There were 460137 calls and 230453 puts.
Largest Put / Call Ratio - XLC with a 21.02 P/C ratio. There were 10155 puts and 483 calls.
Largest Call / Put Ratio - ILF with a 156.22 C/P ratio. There were 17497 calls and 112 puts.
\Stocks must be >$6, Highest Multiple must have >1k ADV, Largest ratios must have an option volume >10k*
Recap -
SNAP 21.6 -0.42,( -1.91%)
KRE 41.18 +0.79,(+1.96%)
YELP 23.36 +0.31,(+1.34%)
MT 12.32 +0.04,(+0.33%)
You can find yesterday's post here.
MOMENTUM UNUSUAL OPTION ACTIVITY -
First Momentum Stock Pick -
Ticker : XOM 44.97 +0.46,(+1.03%) Earnings : 2020-10-30
Name : Exxon Mobil Corp.
Industry : Integrated Oil, Sector : Energy Minerals
Special Considerations : ExDiv
Option Information -
Today’s Option Volume: 379352, OptionOI: 1471812
Multiple of ADV: 5, ADV: 72744
Total Calls: 309412, Total Puts: 69940
Calls at Ask: 42.4%, Calls at Bid: 24.2%
Puts at Ask: 27.4%, Puts at Bid: 31.0%
C/P Ratio: 4.4
Notable Strikes :
AUG 14 '20 42.0 C had 11519 VLM and 3969 OI.
AUG 14 '20 43.0 C had 7051 VLM and 2362 OI.
SEP 18 '20 37.5 C had 5115 VLM and 1557 OI.
SEP 18 '20 40.0 C had 9490 VLM and 3189 OI.
OCT 16 '20 35.0 C had 7304 VLM and 2216 OI.
JAN 15 '21 30.0 C had 10400 VLM and 2062 OI.
News :
2020-08-11 19:22 - P97 Networks to Drive Mobile Commerce For ExxonMobil Affiliate Across Its New Zealand Retail Network
SINGAPORE--(BUSINESS WIRE)--P97 Networks, Inc., has been selected by Mobil Oil New Zealand Limited, an affiliate of ExxonMobil Asia Pacific Pte Ltd, to enable mobile payments across its Mobil-branded retail network in New Zealand. ExxonMobil Asia Pacific is the downstream and chemical business hub for the region with over $15 billion of assets under affiliate management. Houston-based P97 Networks is a leader in cloud-based mobile commerce, in-vehicle payments, and frictionless digital marketin
2020-08-11 12:36:01 - Exxon to buy renewable diesel from Global Clean Energy for five years
U.S. oil major Exxon Mobil said on Tuesday it has signed an agreement with Global Clean Energy to buy 2.5 million barrels of renewable diesel per year for five years to help reduce its carbon footprint.
Potential Sympathy Stocks for XOM
CVX, COP, TOT, BP
My Impression :
The Multiple of ADV, Calls at Ask %, and C/P ratio all look good. This stock historical has been a cornerstone as a method to invest oil as well as great dividend. The stock has risen today likely secondary to news of the vaccine in Russia. It does seem that the tide towards Corona Virus has turned and I would expect this stock to perform well mid-term. I’ll likely be investing a portion of my portfolio in this tomorrow.
Second Momentum Stock Pick -
Ticker : RF 11.93 +0.43,(+3.74%) Earnings : 2020-10-20
Name : Regions Financial Corp.
Industry : Major Banks, Sector : Finance
Option Information -
Today’s Option Volume: 66077, OptionOI: 105874
Multiple of ADV: 30, ADV: 2190
Total Calls: 65479, Total Puts: 598
Calls at Ask: 45.4%, Calls at Bid: 43.7%
Puts at Ask: 40.6%, Puts at Bid: 37.4%
C/P Ratio: 109.5
Notable Strikes :
AUG 21 '20 13.0 C had 8413.0 VLM and 0 OI.
SEP 18 '20 13.0 C had 51010 VLM and 0 OI.
News :
No news for today.
Potential Sympathy Stocks for RF
PNFP, TRMK, ONB, WFC
My Impression :
The C/P ratio, MADV, and Calls at Ask % all look bullish. I’ve had a number of banking stocks on here and they have not fared well historically. These stocks are still down considerably from their pre-corona highs. It seems many are betting for a comeback on the banking sector eventually. With this particular stock, the pre-corona highs were around $17. I’ll be following this one closely. The 13C with 51k VLM is very interesting.
CLASSIC UNUSUAL OPTION ACTIVITY -
First Classic UOA Stock Pick -
Ticker : NVAX 149.48 -29.03,( -16.26%), Earnings : 2020-11-04
Name : Novavax, Inc.
Sector : Health Technology, Industry : Biotechnology
Option Information :
2020-08-14 177.5 C - 563 @ 3.50 were traded at 11:09 as a BLOCK Spot Price: 164.09
News :
2020-08-11 12:01:02 - After Mixed Q2 Report, Novavax Analyst Details Possible Coronavirus Vaccine Catalysts
Novavax, Inc. (NASDAQ: NVAX ) released better-than-expected bottom-line results for the second quarter Monday, although revenue trailed estimates. An analyst at H.C. Wainwright said they're focusing on the key milestone events for the company's coronavirus vaccine candidate after the print. The Novavax Analyst: Vernon Bernardino reiterated a Buy rating on Novavax with a $290 price target. The Novavax Thesis: The robust Phase 1 results Novavax reported for its coronavirus vaccine NVX-CoV2373 point to the high likelihood of positive confirmation of efficacy and safety at the "5+50" dose in Phase 2 testing, analyst Bernardino said in a Tuesday note. (See his track record here.) This is a positive late third-quarter … Full story available on Benzinga.com
Potential Sympathy Stocks for NVAX
SRPT, AGEN, EBS, BCRX
Second Classic UOA Stock Pick -
Ticker : SRNE 14.085 -4.735,( -25.16%), Earnings : None
Name : Sorrento Therapeutics, Inc.
Sector : Health Technology, Industry : Biotechnology
Option Information :
2020-08-21 19.0 C - 655 @ 2.10 were traded at 09:56 as a SWEEP Spot Price: 17.38
2020-08-21 20.0 C - 475 @ 2.30 were traded at 11:32 as a SWEEP Spot Price: 18.09
News :
2020-08-11 11:18:54 - Trade Cautiously With Sorrento Therapeutics
Short-term traders may want to nail down profits and be careful in their trading strategy with this name….NVAX
Potential Sympathy Stocks for SRNE
KPTI, EXEL, TRVN, GERN
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Here you can find a full list of tomorrow's events with explanations.
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DISCLAIMER – These are my observations that I have made at the end of each day and trades that I am considering placing or watching. I am not responsible for your financial losses if you follow any of these trades. As always, do your due diligence.
Company Summary : XOM
Exxon Mobil Corp. engages in the exploration, development, and distribution of oil, gas, and petroleum products. It operates through the following segments: Upstream, Downstream and Chemical. The Upstream segment produces crude oil and natural gas. The Downstream segment manufactures and trades petroleum products. The Chemical segment offers petrochemicals. The company was founded by John D. Rockefeller in 1882 and is headquartered in Irving, TX.
Company Summary : RF
Regions Financial Corp. operates as a bank holding company. It provides traditional commercial, retail and mortgage banking services, as well as other financial services in the fields of investment banking, asset management, trust, mutual funds, securities brokerage, insurance and other specialty financing. The company operates through the following segments: Corporate Bank, Consumer Bank, and Wealth Management. The Corporate Bank segment represents the company's commercial banking functions including commercial and industrial, commercial real estate and investor real estate lending. The Consumer Bank segment holds the company's branch network, including consumer banking products and services related to residential first mortgages, home equity lines and loans, small business loans, indirect loans, consumer credit cards and other consumer loans. The Wealth Management segment offers individuals, businesses, governmental institutions and non-profit entities a range of solutions to help protect grow and transfer wealth. Regions Financial was founded in 1971 and is headquartered in Birmingham, AL.
Company Summary : NVAX
Novavax, Inc. is operates as a clinical-stage biotechnology company, which focuses on the discovery, development and commercialization of vaccines to prevent infectious diseases. It produces vaccine candidates to respond to both known and emerging disease threats by using the proprietary recombinant nanoparticle vaccine technology. The firm's vaccine candidates include ResVax and NanoFlu. It also develops immune stimulating saponin-based adjuvants through its wholly owned Swedish subsidiary, Novavax AB. The company was founded in 1987 and is headquartered in Gaithersburg, MD.
Company Summary : SRNE
Sorrento Therapeutics, Inc. engages in the research, development and manufacture of biopharmaceutical products. It focuses on therapies to treat specific stages in the evolution of cancer, from elimination, to equilibrium and escape which include biosimilars, immuno-oncology antibodies, cellular therapy, cell internalizing antibodies, and antibody drug conjugates. The company was founded by Henry H. Ji in 2006 and is headquartered in San Diego, CA.

Every week, I compile the latest peer-reviewed research, preprints, and other news on genetic engineering and synthetic biology. This is the third week, and the response has been positive so far, so I will keep going!
***

Good morning. This week…

The New Yorker’s Raffi Khatchadourian wrote about Jackson Laboratory’s rapid shipments of “designer mice” for SARS-CoV-2 research, NewScientist covered a “radical new theory” on how life began on Earth, and CNN’s Milly Chan wrote a feature on Colorifix’s dyeing of fabrics with synthetic biology.
Meanwhile, the San Francisco Chronicle wrote about how proteins engineered to neutralize SARS-CoV-2 could soon show up in nose sprays, OneZero and Science Friday covered the first genetic edit in a squid, and Sarah Katz wrote a brilliant piece for Discover Magazine explaining why some deaf people oppose a CRISPR cure.
In industry news, Sherlock Biosciences announced a collaboration to launch CRISPR-based tests for SARS-CoV-2 and Mammoth Biosciences inked a deal for Doudna lab’s “miniature” Cas enzyme, CasΦ.

This week in research…

Listening to the Music of a Cell
Eduardo Reck Miranda is a professor of computer music at the University of Plymouth. In his latest paper, he introduces “a system for music composition informed by synthetic biology”, in which music is generated via simulations of various cellular processes, including transcription and protein folding. The study was published in Artificial Life.
E. coli 30875-8#articleInformation)Engineered to Grow Solely on Methanol30875-8#articleInformation) (They must be starving!)
At UCLA, the Liao lab has engineered E. coli to utilize methanol as its sole carbon source. With a paltry doubling time of 8.5 hours, the team began by using “metabolic robustness criteria” to engineer the strain, followed by laboratory evolution, and found that the final organism carefully balanced metabolic flux by tuning gene copy numbers and mutating key enzymes. The work was published in Cell.
Going Deeeep on the SARS-CoV-2 Receptor Binding Domain31003-5) (Open Access)
Researchers at the University of Washington and the Fred Hutchinson Cancer Research Center, in Seattle, have performed a deep-mutational scan on the SARS-CoV-2 receptor binding domain (RBD), the bit that binds to ACE2 on human cells. They created every single amino-acid substitution in the RBD, and show that, while most mutations are deleterious, some mutations enhance affinity for ACE2. The work was published in Cell.
Boosting Photosynthesis in Plants
At the University of Essex, the Raines lab inserted multiple genes, from red algae and cyanobacteria, into Nicotiana tabacum (tobacco) to stimulate both electron transport and Ribulose 1,5-bisphosphate turnover, increasing photosynthesis. The engineered plants also had an increase in above-ground biomass of up to 52% compared to controls. The study was published in Nature Plants. Read the press release.
E. Coli30363-6?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS2451929420303636%3Fshowall%3Dtrue) Gets a 21st Amino Acid30363-6?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS2451929420303636%3Fshowall%3Dtrue) (Open Access)
The Xiao lab at Rice University has engineered E. coli to both synthesize a 21st amino acid (5-hydroxyl-tryptophan, or 5HTP) and then site-specifically incorporate it into proteins. The team then used the engineered cell to “serve as a living indicator for reactive oxygen species”, as stated by Xiao in a Rice press release. The work was published in Chem.

More research…

A three-way combinatorial CRISPR screen for analyzing interactions among druggable targets31005-6) by Zhou, P. et al. in Cell Reports. (Open Access)
Application of CRISPR-Cas12a enhanced fluorescence assay coupled with nucleic acid amplification for the sensitive detection of African swine fever virus by Tao, G. et al. in ACS Synthetic Biology.
A versatile genetic control system in mammalian cells and mice responsive to clinically licensed sodium ferulate by Wang, Y. et al. in Science Advances. (Open Access)
Bacterial mock communities as standards for reproducible cytometric microbiome analysis by Cichocki, N. et al. in Nature Protocols.
Bacterial synthesis of C3-C5 diols via extending amino acid catabolism by Wang, J., et al. in PNAS.
Comprehensive study on Escherichia coli genomic expression: Does position really matter? by Goormans, A.R. et al. in Metabolic Engineering.
CRISPR-Cas13d Induces Efficient mRNA Knockdown in Animal Embryos by Kushawah, G. et al. in Developmental Cell. Read the press release.
De novo rational design of a freestanding, supercharged polypeptide, proton-conducting membrane by Ma, C. et al. in Science Advances. (Open Access)

• Read the press release.

Developing methods to circumvent the conundrum of chromosomal rearrangements occurring in multiplex gene edition [sic] by Borsenberger, V. et al. in ACS Synthetic Biology.
Development of light-responsive protein binding in the monobody non-immunoglobulin scaffold by Carrasco-López, C. et al. in Nature Communications. (Open Access)
Directed evolution of Pseudomonas fluorescens lipase variants with improved thermostability using error-prone PCR by Guan, L. et al. in Frontiers in Bioengineering and Biotechnology.
DNA Scanner: a web application for comparing DNA synthesis feasibility, price, and turnaround time across vendors by Doçi, G. et al. in Synthetic Biology. (Open Access)
Engineering combinatorial and dynamic decoders using synthetic immediate-early genes by Ravindran, P.T. et al. in Communications Biology. (Open Access)
Engineering designer beta cells with a CRISPR-Cas9 conjugation platform by Lim, D. et al. in Nature Communications. (Open Access)
Engineering isoprenoid quinone production in yeast by Kaur, D. et al. in ACS Synthetic Biology.
Engineering of the 2,3-butanediol pathway of Paenibacillus polymyxa DSM 365 by Schilling, C. et al. in Metabolic Engineering. (Open Access)
Engineering regulatory networks for complex phenotypes in E. coli by Liu, R. et al. in Nature Communications. (Open Access)
Evaluating and engineering Saccharomyces cerevisiae promoters for increased amylase expression and bioethanol production from raw starch by Myburgh, M.W., Rose, S.H. and Viljoen-Bloom, M. in FEMS Yeast Research.
Fully biological production of adipic acid analogs from branched catechols by Kruyer, N.S. et al. in Scientific Reports. (Open Access)
Genetically encoded tags for direct synthesis of EM-visible gold nanoparticles in cells by Jiang, Z. et al. in Nature Methods.
Independent component analysis of E. coli's transcriptome reveals the cellular processes that respond to heterologous gene expression by Tan, J. et al. in Metabolic Engineering. (Open Access)
In silico co-factor balance estimation using constraint-based modelling informs metabolic engineering in Escherichia coli by de Arroyo Garcia, L. and Jones, P.R. in PLoS Computational Biology. (Open Access)
Metabolically engineered Caldicellulosiruptor bescii as a platform for producing acetone and hydrogen from lignocellulose by Straub, C.T. et al. in Biotechnology and Bioengineering.
One-pot synthesis of adipic acid from guaiacol in Escherichia coli by Suitor, J.T., Varzandeh, S. and Wallace, S. in ACS Synthetic Biology.
Optogenetic control of protein binding using light-switchable nanobodies by Gil, A.A. et al. in Nature Communications. (Open Access)
Preliminary engineering for in situ in vivo bioprinting: a novel micro bioprinting platform for in situ in vivo bioprinting at a gastric wound site by Zhao, W. and Xu, T. in Biofabrication (Open Access)

• Read the press release.

Regulatory control circuits for stabilizing long-term anabolic product formation in yeast by D’Ambrosio, V. et al. in Metabolic Engineering. (Open Access)
Synthetic cross-phyla gene replacement and evolutionary assimilation of major enzymes by Sandberg, T.E. et al. in Nature Ecology & Evolution.

• Read the press release, written by first author Troy Sandberg.

Synthetic protease-activated class B GPCRs by Willard, F.S. et al. in Biochemical and Biophysical Research Communications.
Unveiling of swainsonine biosynthesis via a multi-branched pathway in fungi by Luo, F. et al. in ACS Chemical Biology.

This week in reviews and commentary…

Cell-free approach for noncanonical amino acids incorporation into polypeptides by Cui, Z., Johnston, W. and Alexandrox, K. in Frontiers in Bioengineering and Biotechnology.
Computer-aided whole-cell design: Taking a holistic approach by integrating synthetic with systems biology by Marucci, L. et al. in Frontiers in Bioengineering and Biotechnology. (Open Access)
Engineering microbial diagnostics and therapeutics with smart control by Amrofell, M.B., Rottinghaus, A.G. and Moon, T.S. in Current Opinion in Biotechnology.
Heterologous biosynthesis as a platform for producing new generation natural products by Park, D., Swayambhu, G. and Pfeifer, B.A. in Current Opinion in Biotechnology.
Synthetic virus-derived nanosystems (SVNs) for delivery and precision docking of large multifunctional DNA circuitry in mammalian cells by Aulicino, F., Capin, J. and Berger, I. in Pharmaceutics. (Open Access)
Use of cell and genome modification technologies to generate improved “off-the-shelf” CAR T and CAR NK cells by Morgan, M.A. et al. in Frontiers in Immunology (Open Access)

This week in preprints…

An ultra-high affinity synthetic nanobody blocks SARS-CoV-2 infection by locking Spike into an inactive conformation by Schoof, M. et al. bioRxiv.

• This preprint was also featured in a STAT News article.

Characterizing and controlling nanoscale self-assembly of suckerin-12 by Hershewe, J.M. et al. bioRxiv.
Coronacept - a potent immunoadhesin against SARS-CoV-2 by Cohen-Dvashi, H. et al. bioRxiv.
dCas9 regulator to neutralize competition in CRISPRi circuits by Huang, H. et al. bioRxiv.
DNA-based nanocarriers to enhance the optoacoustic contrast of tumors in vivo by Joseph, J. et al. bioRxiv.
Dynamic bistable switches enhance robustness and accuracy of cell cycle transitions by Rombouts, J. and Gelens, L. bioRxiv.
Efficacy of Targeting SARS-CoV-2 by CAR-NK Cells by Ma, M.T. et al. bioRxiv.
Elicitation of potent neutralizing antibody responses by designed protein nanoparticle vaccines for SARS-CoV-2 by Walls, A.C. et al. bioRxiv.
Engineered sex distortion in the global agricultural pest Ceratitis capitata by Meccariello, A. et al. bioRxiv.
Rational engineering of Kluyveromyces marxianus to create a chassis for the production of aromatic products by Rajkumar, A.S. and Morrissey, J.P. bioRxiv.
Reproducibility in systems biology modelling by Tiwari, K. et al. bioRxiv.
Single-cell lineage and transcriptome reconstruction of metastatic cancer reveals selection of aggressive hybrid EMT states by Simeonov, K.P. et al. bioRxiv.
Systematic engineering of artificial metalloenzymes for new-to-nature reactions by Vornholt T, et al. bioRxiv.
Thanks for all of the positive feedback so far :D Happy reading.

The detailed study on Meningococcal Infections Vaccine market offers a broad and thorough data based on systematic analysis and interpretation of the market space from a variety of reliable sources and valiant data points. This report sheds lights on a global scale by dividing the space for the industry into various applications, types, and geographical variations.
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The Meningococcal Infections Vaccine industry can be categorized on a global scale across various districts, appropriate distribution and production channels, income generated per capita, general market share and utilized strategy. Here is the complete breakdown for the market,
The Meningococcal Infections Vaccine industry can be segmented into various types based on availability of material and production techniques such as: Meningococcal Conjugate Vaccines, Meningococcal Polysaccharide Vaccine, Serogroup B Meningococcal Vaccine
The Meningococcal Infections Vaccine industry can be segmented into various applications based on product usage such as: Children, Preteens/Teens, Adults
Likewise, the dominant players surrounding the Meningococcal Infections Vaccine industry that control a major market share across all boards are: Sanofi-Pasteur, Beijing Tiantan Biological Products, Shanghai Institute of Biological Products, Wuhan Institute of Biological Products, Lanzhou Institute of Biological Products, Hualan Biological Engineering, Chongqing Zhifei Biological Products, Zhejiang Tianyuan Bio-Pharmaceutical, Walvax Biotechnology, Royal(Wuxi) Bio-Pharmaceutical
Regional Analysis: Asia-Pacific (China, Japan, Korea, India and Southeast Asia), North America (United States, Canada and Mexico), Europe (Germany, France, UK, Russia and Italy), South America (Brazil, Argentina, Columbia), Middle East and Africa (Saudi Arabia, UAE, Egypt, Nigeria and South Africa)
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Report Title: Global Titanium Sponge Market Research Report 2020
The Titanium Sponge Market report gives a broad assessment of the global Titanium Sponge market by categorizing it in terms of Key Players, application, types and regions. The Titanium Sponge market research report gives an overview of Titanium Sponge industries on by analysing various key segments of this market based on the product types, application, end-to-end industries and its scenario.
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Scope of the Titanium Sponge Market Report:
Titanium Sponge is porous, loose metallic titanium with sponge shape. It is the main raw material and intermediate product of making titanium ingot, titanium powder and other titanium products.
Titanium sponge production is limited to Titanium ore resources and Ilmenite, the main Titanium mine production is concentrated in Australia, China, India, South Africa, Brazil, etc. Ilmenite is concentrated in Australia, India, South Africa, etc. Due to the lack of resources, some countries are restricting the Exploitation of Titanium ore, and Ilmenite is the common raw material in Japan and USA.
Market Analysis and Insights: Global Titanium Sponge Market
The global Titanium Sponge market is valued at 2058.1 million USD in 2020 is expected to reach 2451.2 million USD by the end of 2026, growing at a CAGR of 2.5% during 2021-2026.
Global Titanium Sponge Market: Drivers and Restrains
The research report has incorporated the analysis of different factors that augment the market’s growth. It constitutes trends, restraints, and drivers that transform the market in either a positive or negative manner. This section also provides the scope of different segments and applications that can potentially influence the market in the future. The detailed information is based on current trends and historic milestones. This section also provides an analysis of the volume of production about the global market and also about each type from 2015 to 2026. This section mentions the volume of production by region from 2015 to 2026. Pricing analysis is included in the report according to each type from the year 2015 to 2026, manufacturer from 2015 to 2020, region from 2015 to 2020, and global price from 2015 to 2026.
A thorough evaluation of the restrains included in the report portrays the contrast to drivers and gives room for strategic planning. Factors that overshadow the market growth are pivotal as they can be understood to devise different bends for getting hold of the lucrative opportunities that are present in the ever-growing market. Additionally, insights into market expert’s opinions have been taken to understand the market bette
In this study, 2019 has been considered as the base year and 2020 to 2026 as the forecast period to estimate the market size for Titanium Sponge. This report researches the worldwide Titanium Sponge market size (value, capacity, production and consumption) in key regions like United States, Europe, Asia Pacific (China, Japan) and other regions.
Titanium Sponge Market Segment by ProductTypes considering Production, Revenue (Value), Price Trends:

• Ti>99.7
• Ti 99.5~99.7
• Ti 99.3~99.5
• Ti below 99.3

Market Segment by Applications considering Consumption Growth Rate and Market Share:

• Aerospace & Defense
• Chemicals
• Ocean & Ship
• Electric Power
• Other

Major Key Players of Titanium Sponge Market Report:

• AVISMA
• UKTMP
• ZTMK
• Timet
• ATI
• OSAKA Titanium
• Toho Titanium
• Zunyi Titanium
• Pangang Titanium
• Luoyang Shuangrui Wanji Titanium
• Chaoyang Jinda
• Baotai Huashen
• Yunnan Xinli
• Chaoyang Baisheng
• Anshan Hailiang
• Shanxi Zhuofeng

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Further in the Titanium Sponge Market research reports, following points are included along with in-depth study of each point:

• Production Analysis– Production of the Titanium Sponge is analyzed with respect to different regions, types and applications. Here, price analysis of various Titanium Sponge Market key players is also covered.
• Supply and Consumption– In continuation with sales, this section studies supply and consumption for the Titanium Sponge Market. This part also sheds light on the gap between supple and consumption. Import and export figures are also given in this part.
• Key Strategic Developments– The study also includes the key strategic developments of the Titanium Sponge market, comprising R&D, new product launch, M&A, agreements, collaborations, partnerships, joint ventures, Global and regional growth of the leading competitors operating in the market on a global and regional scale.

Titanium Sponge Market Report Includes:

• Industry Trends:Status and Outlook.
• Competitive Landscape: By Manufacturers, Development Trends.
• Product Revenue for Top Players: Market Share, Growth Rate, Current Market Situation Analysis.
• Market Segment: By Types, By Applications, By Regions/ Geography.
• Sales Revenue: Market Share, Growth Rate, Current Market Analysis.

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Table of Contents
1 Study Coverage
2 Executive Summary
3 Breakdown Data by Manufacturers
4 Breakdown Data by Type
5 Breakdown Data by Application
6 North America Titanium Sponge Market by Countries
7 Europe Titanium Sponge Market by Countries
8 Asia Pacific Titanium Sponge Market by Countries
9 Central & South America Titanium Sponge Market by Countries
10 Middle East and Africa Titanium Sponge Market by Countries
11 Company Profiles
12 Future Forecast
13 Market Opportunities, Challenges, Risks and Influences Factors Analysis
14 Value Chain and Sales Channels Analysis and many more
Be sure to follow us on Linkedin at @ 360 Market Updates for more on growth research and the research market.
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• COVID-19 Impact on Surgical Microscopes Market Size 2020 , Share, Trends, Growth, Regional Outlook And Forecast to 2025
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Structure of bacteria

• Introduction:

The agents of human infectious disease bacteria
belong to five major groups of organisms ,and these are fungi, bacteria, protozoa, helminths,and viruses.
Bacteria is present in the prokaryote kingdom.
Depending upon the shape, bacteria are classified into three basic groups, these are cocci, bacilli, spirochetes.
The size of bacteria varies from about 0.2 to 5 μm.
​
https://preview.redd.it/m0gotfqfpl551.jpg?width=1920&format=pjpg&auto=webp&s=9a47dd9a0d17cc6653114c84a1f85d9f83a24b9f
The size of the smallest bacteria (Mycoplasma) and the largest viruses (poxviruses) are almost same.The longest bacteria rods are the size of some yeasts and human RBC.

• Structure of bacteria:

Cell wall of the bacteria:

This the outermost component which is present in all the bacteria (except Mycoplasma species).

The significance of this complex bacterial cell wall are to protect the protoblasts from external noxae, which then help to withstand and to maintain the osmotic pressure gradient between the cell interior and the extracellular environment, to give the cell it's outer form and to facilitate communication with its surrounding.
Some bacteria have surface features external to the cell wall, such as capsule, flagella and pili.
The cell wall is located external to the cytoplasmic membrane and is made up of peptidoglycan.

Cytoplasmic membrane:

The cytoplasmic membrane is present just inside the peptidoglycan layer of the cell wall.It is composed of phospholipid bilayer similar in microscopic appearance to that in eukaryotic cells.

Cytoplasm of bacteria:

When observed through the electron microscope it is seen that the cytoplasm of the bacteria has two distinct areas , these are,

1. An amorphous matrix, in which ribosomes, nutrient granules, metabolites and plasmids are present.
2. An inner, nucleoid region which is composed of DNA.

Ribosomes:

The ribosomes of the bacteria are the place, where protein synthesis takes place, like the eukaryotic cells. But the chemical composition and the size of the bacterial are different from that of eukaryotic ribosomes.
The size of bacterial ribosomes is 70S , and contains 50S and 30S subunits, but the size of the eukaryotic ribosomes are 80S , and it contains 60S and 40S subunits.

Granules:

Nucleoid:

This is the area of the cytoplasm in the bacteria in which DNA is located.The DNA which is present in the prokaryotes ,are circular molecule,and which has a molecular weight of about 2 × 10^9 and also contains about 2000 genes.There is resemblance to the eukaryotic nucleus becuse in the nucleoid nuclear membrane, nucleolus ,mitotic spindle, histone are not present.
There is no introns present in the bacterial DNA.

Plasmids:

Plasmids are extra chromosomal, double-stranded , circular DNA molecules that are capable of replicating independently of the bacterial chromosome.Although plasmids are usually extra chromosomal, they can be integrated into the bacterial chromosome.In both gram positive and gram negative bacteria plasmids occur, and several different types of plasmid can exist in one cell these are
1.Transmissible plasmids

1. Neurotransmissible plasmids.

Transposons:

Transposons are prices of DNA , that move fastly from one site to another either within or between the DNAs of bacteria, plasmids and bacteriophages.They are nicknamed as ''jumping genes'' because of their unusual ability to move.Transposons can code for drug resistance enzymes, toxins or a variety of metabolic enzymes and can either cause mutations in the gene into which they insert or alert the expression of nearby genes.There is four identifiable domains present in the transposons

• Structure out side the cell wall:

Capsule:

It is a gelatinous layer present surrounding the entire bacterium.The capsule is composed of polysaccharide (except in the anthrax bacillus).The capsule is important because of it's four important role
1.It is determinant of virulence of many bacteria since it limits the ability of phagocytes to engulf the bacteria.
2.By using antiserum against the capsular polysaccharides , specific identification of an organisms can be made.
3.In certain vaccines capsular polysaccharides are used as antigens , because of their role in eliciting protective antibodies.
4.In the adherence of bacteria to the human tissues, capsule has an important role, which is an important primary step in causing infections.

Flagella:

Flagella are long, whip-like appendages that help in the movement of bacteria toward nutrient and other attractants,a process which is known as chemotaxis.The long filament, which acts as a propeller,is composed of many subunits of a single protein,flagellin.
Flagellated bacteria have a characteristic number and location of flagella.
Flagella are medially important for two reasons
1.Some species of motile bacteria are common causes of urinary tract infections.
2.Some species of bacteria are identified in the clinical laboratory by the use of specific antibodies against flagellar proteins.

Pili:

Pili are hair like filaments that extend from the cell surface.They are shorter and straighter than flagella,and are made up of pilin.
Pili have two main role:
1.They regulate the attachment of bacteria with the specific receptor present on the human cell surface.
2.A specialized kind of pilus,the sex pilus, forms the attachment between the male and the female bacteria during conjugation.

Glycocalyx(Slime layer) of bacteria:

It is a polysaccharide coating that is secreted by many bacteria. The glycocalyx is an important component of biofilms.
The glycocalyx mediates adherence of certain bacteria.

Bacterial spores:

These highly resistance structures are formed in response to adverse conditions by two genera of medially important gram positive rods: the genus Bacillus and the genus Clostridium.

The Futurology subreddit frequently features highly upvoted posts on cell-based meat, reflecting the media attention and public interest that has followed the industry. There are many introductory resources to how cell-based meat is produced and what its benefits may be, however, there are no comprehensive resources that fully inform those interested in learning more. Below you’ll find the 5th post in a multi-part series that walks through the science driving the innovative technology of cell-based meat. These posts are intended to be educational but lengthy and best understood by those with science backgrounds.
Please check out the previous posts linked below. Each post is also formatted for easier reading here.
Series I: Cell Lines
Series II: Bioprocessing
Series III: Bioengineering 1 and 2
Series IV: Cell culture media 1, 2, and 3
Series V: Final products
Series VI: Impact (environment, human health, food security, animal welfare)
Introduction
Growing cells ex vivo requires the same fundamental inputs as required in vivo: a mixture of a carbon-based energy source, amino acids, salts, vitamins, water, and other components to support cell viability and vitality. This mixture, known as the cell culture medium, is the most important factor in cell culture technology. Although cell culture is routinely performed in academic labs and industrial bioprocesses, creating the biomass required for cell-based meat to achieve mass-market penetration at competitive prices will demand significant reductions in costs, innovations for serum removal, and optimization across a diverse set of species and cell types. An overview of cell culture medium composition and the factors at play to achieve price parity with conventional meat are discussed below.
Common Components of Cell Culture Medium
The first instance of culturing tissues outside of the body came from Sydney Ringer in 1882. By creating a balanced salt solution with similar pH, osmolarity, and salt concentration to that of an animal’s body, Ringer was able to keep various animal tissues alive outside of the body for several days. Subsequent work in the following decades first demonstrated that culturing cells in the presence of blood plasma (i.e. serum) or embryonic extracts assisted in cellular proliferation and viability, allowing tissues to survive for longer periods of time. Over time, researchers identified the importance of glucose, amino acids, glutathione, insulin, and vitamins in the sera being used.¹ Once this was known, scientists aimed at uncovering the additional unknown essential components of serum and other extracts that permitted cell proliferation and viability.
In the 1940s and 50s, working with the first immortalized cell lines such as L cells² and HeLa (discussed in Series I), scientists used iterative approaches to discover that low molecular weight dialyzed fractions of serum containing amino acids were necessary for cell survival. In 1955, Harry Eagle developed a Minimum Essential Medium by testing the amino acid requirements on several different cell lines, discovering that thirteen were indispensable. Eagle’s minimum essential medium additionally consists of glucose, six inorganic salts, eight water-soluble vitamins, and dialyzed serum. Variations on this medium were then derived using a variety of different cell lines as well as trial and error approaches that aimed at replacing serum with chemically defined components. These variations, including Dulbecco’s Minimum Essential Medium (DMEM), Iscove’s Modified DMEM, Ham’s F12, Medium 199, RPMI 1640, Leibovitz’s L-15, and others, still make up the majority of what are referred to as basal cell culture media in use for culturing the variety of cell types used today.^3,4
What makes these formulations essential? Although formulations have been varied and optimized over time, the principal components of basal cell culture media have remained largely unchanged. Importantly, these variations may be cell-type specific, including for the cell types used in cell-based meat (described in Series I). Therefore, rather than discussing optimal conditions for a specific cell line or species, only the general roles of each component of common basal media including glucose, amino acids, inorganic salts, vitamins, and buffers are briefly discussed below.
Glucose
Glucose (specifically D-glucose) is the most common energy input used in cell culture, although some media formulations use galactose or a combination of glucose and its metabolite, pyruvate. Industrially, it is produced enzymatically using amylase enzymes to breakdown starches from maize, potato, wheat, and other crops into constituent sugars used in various downstream products such as industrialized food, fermentation processes, or in this case, culturing of cells. Glucose enters the cell via transporter proteins on the cell surface, using either passive transport down its concentration gradient (more common) or ATP-dependent active transport. Once inside the cell, it serves as a reducing agent against oxidative stress in the form of NADPH generation via the pentose phosphate pathway, as well as a primary source of energy in the form of ATP generation via glycolysis.
In cell culture, glucose is used at concentrations between 5.5 and 55 mM, where the lower end is more common and similar to fasting blood glucose levels in humans. Different cell types will require different amounts of glucose. During periods of rapid cell proliferation and growth, as typically maintained during bioprocessing, glucose metabolism is high and can yield lactic acid even in the presence of sufficient oxygen, leading to pH changes.⁵ Thus, glucose and lactic acid levels are commonly measured and tightly controlled throughout a bioprocess (discussed in Series II).
Amino Acids
Amino acids are necessary to create proteins and other low molecular weight compounds such as nucleotides and small peptides. Amino acids can be split into two groups: essential and non-essential. Non-essential amino acids (NEAAs) can be synthesized de novo by an animal, whereas essential amino acids (EAAs) must be obtained through the diet. Generally speaking, pathways for the de novo synthesis of NEAAs are conserved in vertebrate species.⁶ In humans and many other animals, the EAAs include histidine, isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan, and valine. NEAAs include alanine, arginine, asparagine, aspartate, cysteine, glutamate, glutamine, glycine, proline, serine, taurine, and tyrosine. However, EAA requirements can vary between species. For instance, dogs, cows, and pigs have the same EAA requirements as humans plus arginine, whereas cats and chickens require the same EAA as the former plus taurine and glycine, respectively.
Importantly, what is considered to be “essential” in cell culture is different than what is considered “essential” to a whole organism, as the diversity of cell types that may synthesize certain amino acids in vivo are not present in vitro. For instance, Eagle’s Minimum Essential Medium formulation lists 13 (L-enantiomer) amino acids as being essential across multiple cell lines in vitro: arginine, cysteine, glutamine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan, tyrosine, and valine. As an example, arginine is essential in vitro as its biosynthesis in vivo primarily occurs between epithelial cells in the gut and proximal tubule cells of the kidney. Thus, arginine must be supplied in the absence of these cell types. Media that are particularly nutrient-rich (eg. DMEM/F12 or Medium 199) may contain all amino acids. Alternatively, NEAAs can be supplemented independently.
Industrialized production of amino acids can be obtained through bulk extraction from protein hydrolysates (discussed later), chemical synthesis, or microbial fermentation and purification, with the latter being the most common.⁷ Amino acids enter the cell through a variety of transporter proteins on the cell surface, at rates influenced by the cell’s state and consumption rates due to protein production levels, cell cycle state, and other parameters. Once inside the cell, amino acids serve as substrates for many biosynthetic pathways and optimal concentrations are important for maintaining metabolic equilibrium. The majority of carbon mass in proliferative cells is derived from bulk amino acids rather than glucose or L-glutamine, which are the most rapidly metabolized.⁸
Ultimately, the levels of amino acids required for cell culture are determined not only by their utilization by the growing cells, but also by individual amino acid solubility, stability, and interaction with other medium components such as metal cations, all of which can change once in a complex mixture.⁹ Consideration for all of these variables is highly complex and a full understanding of amino acid behavior, utilization, and optimization in a bioprocess has yet to be accomplished. Given the variety of biosynthetic pathways that involve amino acids, it is likely that amino acid content, concentration, and perfusion rate (when applicable) will need to be optimized for a particular bioprocess across species and cell types for parameters such as growth rates or protein content in the final product. Computational approaches to model specific utilization rates of amino acids and other basal media components are an active area of research¹⁰ (discussed later).
L-glutamine
L-glutamine deserves special consideration as one of the most important amino acids included in cell culture media, as it is readily transported into cells and becomes a major contributor to protein biomass. It is a notable precursor of carbon and nitrogen-containing biomolecules such as the intermediate molecules used in the synthesis of other amino acids and nucleotides¹¹ and it can be added at concentrations 3-40x higher than other amino acids in the medium.¹² During times of high cellular growth and proliferation, the demand for glutamine outpaces its supply, making it de facto an essential amino acid that can be readily metabolized as a replenishing alternative energy source (i.e. anaplerosis). At physiological pH in a cell culture medium solution, L-glutamine is unstable, resulting in its decomposition into pyroglutamate and ammonia, the latter of which is toxic to cells. Ammonia, therefore, is a tightly monitored and regulated metabolite in large scale bioprocesses that involve high densities of cells undergoing rapid growth (discussed in Series II).
In order to avoid some of these disadvantages of L-glutamine, glutamate — which is more stable in solution — can be substituted in when working with cells expressing high levels of glutamine synthetase, an enzyme which enables intracellular conversion of glutamate to glutamine while consuming ammonia in the process. A more common practice involves supplementation with L-glutamine as a stable dipeptide in the form of alanyl-glutamine (i.e. GlutaMAX) or glycyl-glutamine, which enable cells to endogenously cleave the dipeptide for more controlled usage of the amino acids in the dipeptide. There is still much to learn about amino acid metabolism in cell culture. For instance, recent discoveries suggest L-glutamine is entirely dispensable for the culture of pluripotent stem cells.¹³
Inorganic Salts
The inclusion of inorganic salts) is important in establishing and maintaining the osmolarity of the cell with its surrounding cell culture medium solution as well as serving as enzymatic cofactors and important components of receptor and extracellular matrix proteins. These inorganic salts are composed of cations and anions that fully dissociate in solution. The original minimal essential medium solution contained six inorganic salts (calcium chloride, potassium chloride, magnesium sulfate, sodium chloride, sodium phosphate, and sodium bicarbonate), which are based on Earle’s salt solution. Other formulations include additional inorganic salts containing zinc, copper, and iron, which have particular importance for a variety of cellular functions (discussed later).
Although all cells maintain a resting membrane potential, excitable cells such as neurons and skeletal muscle cells are particularly sensitive to changes in ionic concentrations that can readily affect their functionality and viability. Several basal medium formulations have thus been optimized for salt concentrations for neuronal¹⁴ and skeletal muscle cell culture that more accurately recapitulate the interstitial fluids surrounding these cell types. The osmolality or measurement of osmotic pressure within the medium is typically between 260 to 320 mOSM/kg (milliosmoles per kg of solute), although this can vary with cell lines that are particularly robust in varying solute concentrations such as insect cells.¹⁵ Changes in the salt concentration, either abruptly due to medium changing or slowly due to water evaporation, can lead to osmotic shock. Thus, maintenance of osmolarity is an important component of cell culture.
Vitamins
Vitamins are classes of organic compounds that serve as a critical component for the maintenance and growth of cells. Most vitamins are essential in that they need to be obtained directly from the diet or cell culture medium with few exceptions (e.g. vitamin D synthesized by fibroblasts and keratinocytes of the skin or some B vitamins produced in low levels by intestinal microbiota). Vitamins are classified as either fat-soluble or water-soluble and can serve broadly as enzymatic cofactors, antioxidants, and hormones. Vitamins are processed in a variety of ways in vivo following ingestion, often in a complex sequence that ends in absorption into intestinal cells via membrane surface transporters. This complex sequence involved in absorption can be largely avoided in vitro, as hostile environments (e.g. stomach acid) or barriers (e.g. the blood-brain-barrier) are absent.¹⁶ Thus, vitamins are typically included in a medium formulation as a single chemical compound that can be processed and absorbed directly by cells in vitro.
Vitamins can also effectively function as a group of compounds (i.e. vitamers) where each compound can serve the vitamin’s functional role, albeit with varying properties. The natural production of vitamins in microbes and plants has made industrial production of vitamins via microbial fermentation possible, however, improvements in metabolic engineering strategies are needed to increase yields and sustainability in the industry. For these reasons, some vitamins are produced more efficiently via chemical synthesis.¹⁷
Water-soluble vitamins including riboflavin (vitamin B2), nicotinamide (vitamin B3), pantothenic acid (vitamin B5), pyrodoxine and pyridoxal (vitamin B6), biotin (vitamin B7), i-inositol (vitamin B8), folic acid (vitamin B9), cyanocobalamin (vitamin B12), and choline are typically added to and “essential” in cell culture media, sometimes in various modified forms in order to provide stability. Fat-soluble vitamins A, D, E, and K are excluded in basal medium formulations but can be added if necessary when dissolved in an organic solvent. Similar to the different in vivo versus in vitro requirements of amino acids, fat-soluble vitamins play specific roles for certain cell types or bodily functions and are thus only “essential” when culturing a relevant cell type. For instance, a metabolite of vitamin A, retinoic acid, is an important developmental morphogen (discussed in detail later) and may be included as an additive in media to derive spinal motor neuron cells from pluripotent stem cells.¹⁸ Special consideration for stability must be taken when using serum-free medium formulations (discussed later) as the lack of stabilizing serum proteins can lead to rapid degradation via light, heat, oxidation, or pH fluctuations.¹⁹ These properties make it advisable to reconstitute powdered B vitamins immediately before use (discussed later).
Buffering Systems
Buffers are essential to cell culture systems as they serve to maintain pH at a constant level (for mammalian cells, generally 7.4 ± 0.4) despite changes in the composition of acids or bases that would otherwise alter the pH of the cell culture medium. Buffers are mixtures of a weak acid and its conjugate base or a weak base and its conjugate acid, where each mixture serves as a sponge to soak up free protons or hydroxide ions in solution, minimizing their effect on overall pH. Buffer systems in cell culture typically consist of either CO2-bicarbonate systems or buffering agents such as HEPES. As discussed in Series II, a CO2-bicarbonate system can be achieved by exogenous addition of 5-10% gaseous CO2 (often delivered in bioreactor systems via sparging)), which reaches equilibrium in solution with bicarbonate ions, forming a natural buffer system.
pH slowly changes over time due to the respiration of cells and the release of additional CO2, which forms carbonic acid in solution, in addition to the metabolism of glucose and the formation of lactic acid. The resultant decreasing pH changes are counteracted by the inclusion of sodium bicarbonate in the basal medium itself. Importantly, added sodium bicarbonate should be proportional to the atmospheric CO2 being used to maintain equilibrium. For instance, for media containing 1.5 to 2.2 g/L sodium bicarbonate, 5% CO2 is recommended, whereas 10% CO2 is recommended for media containing 3.7 g/L sodium bicarbonate.
HEPES is a zwitterionic buffer that can be used in cell culture systems as a supplemental buffer, especially in the absence of CO2 exposure. As one of Good’s buffers, its high solubility, low toxicity, and membrane impermeability have made it attractive for use in cell culture applications. In the scale-up of highly proliferative stem cell populations, dissolved CO2 due to high metabolism can reach levels that are deleterious for cell growth and nutrient utilization.²¹ Attempts have thus been made to limit dissolved CO2 by culturing cells in the presence of atmospheric CO2 levels with added buffering capacity from HEPES or other Good’s buffers.²² This strategy may be useful for future scale-up efforts in cell-based meat. Consideration for the cost of the buffer must also be weighed, as it may constitute the most expensive component of a basal media formulation at scale.
Preparation
Out of convenience, most academic and lab-scale cell culture is performed using commercially available premade liquid media. However, large volumes necessitate on-site preparation of liquid cell culture media from reconstituted powdered medium ingredients. Powdered medium is more efficiently transported and stored, resulting in cost savings and reduced degradation of fragile ingredients (e.g. B vitamins). Ideally, a powdered medium contains all of the components to be utilized and is created through a process known as micronization, where the average size of crystallized particles in the mix is reduced in order to increase solubility and homogeneity. When ready to use, the powder is typically reconstituted in a dedicated tank using high-quality water prepared by reverse osmosis, deionization, and filtration. The reconstituted medium is then itself sterilized by filtration (e.g. through a 0.22 µm filter), irradiation, or other methods discussed in Series II (e.g. pulsed electric fields). The use of sterilization involving high heat is precluded by some heat-labile ingredients that may be part of the formulation. Other preparation methods for additional ingredients are discussed throughout.
Serum
As previously mentioned, a basal medium formulation is often sufficient to keep cells alive for short periods of time, but in order for them to proliferate efficiently over extended periods of time, a variety of animal sera) (e.g. fetal bovine serum, horse serum, and others) and extracts (e.g. chick embryo extract) have historically been used (notably, on a volumetric basis, serum-free formulations are now more dominant in their usage although FBS is still often included in routine cell culture in academic settings). Serum is a high protein-containing mixture that contains growth and attachment factors, hormones, antioxidants, lipids, and other components (all described later) that mimic a proliferative, fetal-like state. Indeed, most sera used in cell culture are derived from fetal animals, which are rich in the necessary components and contain low immunoglobulin and complement content due to developmentally immature immune systems. As fetal bovine serum (FBS) is the most common sera used in cell culture, it will be used as a reference example throughout this section.
Originally employed in the late 1950s,²⁴ FBS has become a mainstay in biomedical research because it can supplement the growth of virtually all common human, animal, and even insect cell lines. As an added supplement for many cell culture applications in amounts typically 5-20% of total medium volume, FBS — when used — is often the most expensive part of performing cell culture.
FBS is harvested from a fetal calf any time during the last two-thirds of gestation following the discovery of pregnant cows due for slaughter. It has been estimated that up to 8% of cows in the slaughter line may be pregnant, making FBS a byproduct of the meat processing industry.²⁵ It is prepared by the sterile collection of fetal blood followed by coagulation at low temperatures and centrifugation to remove clotting factors and blood cells. The serum supernatant is then filtered and assessed for a variety of quality controls including residual microbial or viral contamination, endotoxin, immunoglobulin content, and total protein, before being bottled and sold commercially, at prices exceeding $1000 USD per liter (at time of writing, July 2019) depending on quality control parameters (some described later), which vary by industry and use-case.
Despite its long history of use, FBS has several well-described issues that have made its replacement a priority in recent years. First, FBS contains hundreds or even thousands of different components and the true composition and amounts of these components are unknown, making it a chemically undefined product. The composition also varies by geographic region where a cow’s diet can vary, by batch within the same geographic region, by seasonality of collection, by the quantity and identity of antibiotics or hormones received by the mother, and by the gestational age of the fetus. Variability can also stem from a single bottled product originating from fetuses of different sexes.²⁶ This variability has led to a growing concern over serum’s contribution to irreproducibility of in vitro experiments within and between labs around the world.²⁷ Rigorous quality control involving testing of serum batches across multiple cell lines or experiments prior to purchasing a specific, well-performing large batch is often performed in industry but can remain burdensome from a labor and economic perspective for smaller academic labs. Thus, the inherent variability and undefined nature of FBS use leads to compounding external costs in quality control testing, experimental irreproducibility or conflicting results, and follow-up research to dissect irreproducible signals.
Second, FBS is a potential source of contamination from multiple organisms, including Mycoplasma, viruses, and bovine spongiform encephalopathy. Mycoplasma are a class of parasitic bacteria that lead to metabolic and gene expression variations for infected cell lines. Mycoplasma are likely the most common cell line contaminant, with recent estimates showing 11% of cell lines being infected, and rates as high as 70% in geographical regions where testing is not routine.²⁸ Although presently FBS is routinely filtered using 0.1 micron systems that should theoretically capture Mycoplasma, suppliers cannot make this guarantee. The common cell line contaminants M. arginini and A. laidlawii, in particular, have been linked in origin to FBS, and ongoing cross-contamination of cell lines has likely propagated this contamination in laboratories since the 1960s and 1970s when FBS batches were routinely positive for these bacteria.²⁹ Additional methods to decontaminate serum from Mycoplasma include gamma irradiation, however, this can also damage growth factors and other proteins in the serum.³⁰ Thus, the use of FBS is responsible for a non-trivial amount of bacterial contamination in cell lines today, leading to compounding problems concerning reproducibility and potential unknown variability stemming from some decontamination practices.
In addition to bacterial contamination, the threat of adventitious viral agents in FBS also persists. Regulations under USDA and the EU mandate the testing and/or treatment (via heat or irradiation) of eight viruses known to be present in FBS from all geographical regions of origin.³¹ Although modern production methods make the risk of contamination in a validated batch low, viral contamination is often still detectable in batches that manufacturer screens claim to be negative.³² Similarly, the threat of FBS containing the causative prion proteins involved in bovine spongiform encephalopathy (i.e. Mad Cow Disease, which manifests in humans as variant Creutzfeldt-Jakob Disease) is persistent and requires additional testing as well as documented traceability for the FBS origin. For instance, countries such as the USA, New Zealand, and Australia have no documented cases of bovine spongiform encephalopathy; thus FBS originating from these countries may be considered ‘safer,’ often commanding significantly higher prices and collectively comprises up to 90% of the serum supply for commercial therapeutics.³³ This fact has also incentivized fraudulent activity in the field, where manufacturers may opt for fake labels from New Zealand in order to solicit higher prices.³⁴ Industry associations have formed in an attempt to mitigate these concerns. Nevertheless, the inherent risk of contamination from FBS poses threats to experimental and bioprocess reproducibility, drives price fluctuations, and can even incentivize bad actors that value profit over safety. Contamination will be discussed further from a food safety perspective in Series V.
Third, there is a limited global supply of FBS and there exists competition for it from profitable, mature industries. For instance, while the vaccine and biologics industries have begun to move to serum-free formulations (discussed later), the rise of cell therapies and stem cell research more generally has ushered in an impending demand that exceeds current availability. Because FBS is a byproduct of a more lucrative product per animal (i.e. meat and dairy) and profits are retained by slaughterhouses rather than farmers, farmers have little incentive to increase cattle herds to meet a future FBS demand.³⁵ It has thus been hypothesized that “peak serum” has been met, with serum availability relatively stagnant and serum demand increasing dramatically as cell therapies begin to be approved.³⁶ The replacement of serum thus may be driven first by limited total availability followed by cost concerns that will spur replacement innovation in the field as non-pharmaceutical players are priced out. In the case of cell-based meat, this cost concern is already prohibitive, making FBS an economic nonstarter as meat products cannot be justified at prices that rival a cell-based therapeutic (currently at a cost of goods of approximately $50,000 and selling price of hundreds of thousands of dollars).
Lastly, the use of FBS carries ethical concerns, making its use inherently misaligned with one of the fundamental benefits of cell-based meat: animal welfare (discussed in Series VI). A single liter of serum requires 1-3 fetuses, with roughly 2 million fetal calves used in serum collection annually, totaling approximately 800,000 liters of FBS produced per year. The collection process involves removal of the fetus from the mother’s womb and aseptic collection of blood by a syringe placed directly into the beating heart as this contains unclotted blood, raising concerns that the fetus could consciously experience the event as painful.³⁷ Thus, the search for serum-free formulations (discussed later) is in alignment with the cell-based meat industry and general animal welfare concerns, manifested by replacement, reduction, or refinement of animal experiments or animal-based products in science.
The next series on cell culture medium will explore the components of serum that have made it a near-universal cell culture supplement and approaches for replacing serum in a cost-effective manner.
About / Disclosure
Elliot Swartz, Ph.D. (e_swartz) is the author and is employed by The Good Food Institute, a 501(c)3 nonprofit using markets and innovation to accelerate the plant-based and cell-based meat sectors.
Feel free to ask anything about the science discussed or how to get more involved in the future of food. Many questions will additionally be addressed in upcoming discussion topic series!