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Ratnaveer precision a newly headed steel company (12-06-2024)
They claim to be family of ratnamani steel & tubes
Multi-Disciplinary Reading – Book Reviews (12-06-2024)
Genentech, Sally Smith Hughes, 2013 - The book follows the birth of Genentech and consequently the birth of Biotech itself and follows its people, the tech, regulations and economics of recombinant DNA tech and how it transformed the landscape of medicine which was until then dominated by small molecules. Wanting to understand GLP-1s in depth while investing in Shaily got me into this book, among others
My notes -
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Genentech was founded by Herbert Boyer (professor of microbiology) and Robert Swanson (Unemployed VC). Its name a play on Genetic Engineering Technology and its goal to apply recombinant DNA tech to make insulin, growth hormone and other drugs
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Balancing freewheeling academic culture (profs and research guys from universities), federal guidelines from recombinant DNA tech (there was lot of fear of Frankenstein, like we are fearing AI now) and need to make profit - balancing science, tech, legal, political, economical was Swanson’s job
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Within 3 yrs of its founding in successive years, Genentech cloned and expressed Insulin, the growth hormone and human interferon and got listed and raised $38m within 4 yrs of founding in 1980 - listing pop from $35 to $89 (largest listing gain for its time) - ushered in Biotech industry as we know it today there on
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Recombinant DNA tech - discovered in ‘73 and modern biotech was born. It entails joining of different pieces of DNA and cloning it in a bacteria and expressing the DNA as a protein or RNA with the bacteria acting as a factory (This is what peptide manufacturing through fermentation is. Today’s GLP-1 drugs are made this way)
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Restriction enzymes (naturally occurring) - these cut DNA at specific sequences and were a crucial piece in recombinant DNA tech (Boyer’s fascination with this led to the tech)
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Plasmids (circular double-stranded DNA fragments) in bacteria carried the antibiotic resistance genes and helped pass these genes horizontally to other bacteria. This is how antibiotic resistance spreads in bacterial population. The same is used to transfer the recombinant DNA transferred to the plasmids to spread it to the population
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EcoRI (restriction enzyme) cuts DNA in a staggered fashion that makes its ends cohesive (like two zippers cut staggered aligned together can have a runner run through them). This was a crucial piece of recombinant DNA tech
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The very first experiment involved cloning recombinant plasmids containing frog DNA in E.coli - it didn’t matter to the bacteria that the DNA came from an animals several levels higher in the evolutionary tree
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Once the recombinant DNA tech was published in Science, a moratorium was imposed on the tech until a conference was convened to consider the risks and develop guidelines (not unlike the call for regulating AI - but this time no such has happened)
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In the 1970s the popular approach to recombinant DNA tech was “wait and watch”. Practical applications being 5-10 yrs away, there was no rush to get started
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Swanson and Boyer were both naive and with their naivete and inability to foresee all problems in advance, they boosted each other over the bar
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Insulin in the 70s was extracted from pigs and cows and was an essential staple of medical practice. People had allergic reactions to it. Since insulin’s amino acids were well known (only 50 of them, so it was small as well) and there was good demand ($100m in sales then), it was ideal candidate for first target of recombinant DNA tech
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Genentech’s business model was to license the engineered bacteria (after sequencing, splicing, cloning) to established pharma firms for manufacturing, trials, filing and marketing
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Kleiner and Perkins, a VC firm known to Swanson agreed to invest $100k in the venture (it would be the first of billions that would be needed to be raised later)
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Chemical DNA synthesis - laboratory construction of artificial genes and DNA fragments from chemicals off the shelf (can be then used for some or all fragments in recombinant DNA tech). It behaved just like natural DNA and was biologically functional (somatostatin with 14 amino acids was the first one to be synthesised this way)
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Companies like Eli Lilly tied up with various academic institutions for the tech for recombinant insulin (something that gave them strong headstart that they maintain to this date). Lilly also tied up with Genentech for human insulin - supporting the effort at $50k/month
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Insulin’s 51 amino acids were present in 2 chains, called A and B chains which meant the scientists had to synthesise two separate DNA sequences. The DNA for insulin was completely synthesised in the lab within 6 months. This gave Genentech a huge advantage since they did not have to comply with expensive regulations governing human genetic material (highest level of biological containment)
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Lilly signed a licensing agreement with Genentech for $500k for worldwide marketing of human insulin alongside 6% royalty for using the tech in human insulin alone (Lilly violated this to make growth hormone and paid $150m fine to Genentech later)
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Molecular biology, nucleic acid chemistry, protein chemistry were Genentech’s divisions, each quite diverse in talent
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Cetus, Genentech, Biogen, Genex and Bethesda Research labs were all founded in the 70s and attracted lot of capital from VCs and other corporates (like Lubrizol, Monsanto) though none had yet made a penny of profit. Post Genentech’s listing, Amgen, Chiron, Calgene, Molecular Genetics, Integrated Genetics were created in the early 80s
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Human growth hormone was extracted from pituitary glands of dead bodies so was very scarce and expensive (Kabi was leading supplier). Kabi signed up with Genentech like Lilly. For a price of $1m Genentech was to engineer bacteria to produce human growth hormone (HGH)
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HGH is larger than insulin at 191 amino acids. Chemical synthesis of DNA for these would take inordinate amount of time. The approach was to partly synthesise (24 amino acids) and partly use human DNA and splice them together to form a hybrid gene
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The bacteria was producing 200,000 molecules of HGH per bacterium with Genentech’s hybrid gene. The HGH was biologically active and identical to the natural hormone.
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Protein chemists, process engineers and fermentation experts help with purifying the peptides synthesised by the bacteria before it is usable in clinical trials
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NIH had a 10 litre limit for batch size for fermentation of peptides. To overcome this and to meet demand, Genentech worked with Kabi on continuous cycles with max of 10L
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Humulin, the Genentech-Lilly recombinant insulin was the first recombinant pharmaceutical to be approved by FDA, followed by Genentech-Kabi Protropin (HGH). Within 2 decades Protropin reached $2b in sales (Genentech became profitable barely 3 yrs into operation)
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Genentech partnered with Hoffman-La Roche for Interferon, Monsanto for Animal growth hormone, Merieuz for Hep-B vaccine and self-funded thymosin after their success with insulin and HGH
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Biomania - investment in industrial biology totalled $150m in 1979. Deregulation helped ease of doing business in biotech field as there was no adverse impact on human health or natural environment. The scope for Interferon in cancer treatment helped Genentech’s IPO valuations
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Interferon types - fibroblast, leukocyte and immune interferon - none of the structures of amino acids were known. Roche had several cell lines which would provide the invaluable m-RNA to Genentech. First two were cloned within 2 weeks and Genentech could produce them 600L facilities (Deregulation helped inc. capacity). They could produce as much in a week as was produced in a year prior (Interferon products had $2b in sales in 2005)
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Diamond v Chakrabarty case - whether living organisms were patentable or not. Chakrabarty, working for GE had constructed a bacteria that could degrade crude oil. Once he won the case, Genentech’s case became stronger because its the engineered bacteria that’s patentable product. (court ruled in favour since it was not natural bacteria but something created by Chakrabarty) - a significant role in biotech
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Today Hoffmann-La Roche owns Genentech (60% in 1990 and 40% in 2009 for $47b)
This is a great book for understanding peptides and recombinant DNA tech irrespective of your aptitude since it makes it very easy to understand. You will also get a reasonable idea into businesses that work on Monoclonal antibodies as well since those are large proteins composed of amino acids too but specifically for antibodies but the tech is very similar. So understanding businesses like Biocon or other companies that work on biosimilars becomes a lot easier when you understand the basics of the industry from a book like this. 10/10
Corporate Fraud/Misdemeanor – Public Domain – Global lessons (12-06-2024)
Hope you got the reply with factual evidence . Of Promoter offloading stake consistently.
You asked to care for cheking , but how have you overlooked that, incase u checked and were in false assumption sir?
Buy Unlisted Shares (12-06-2024)
Part of the problem is with the spread charged by these platforms. Specifically for Vikram Solar the price was 195/- but was available on platforms for 230/- around March time. A very close friend who works in the group mentioned at the time that some people are selling unlisted shares at 195/-. He also advised to stay away for what ever reasons.
Anyone please give insights on Gujarat Toolroom Ltd company, what is the case for it? should I buy now or just gamble 3000 INR on it? (12-06-2024)
anyone please give insights on Gujarat Toolroom Ltd company, what is the case for it? should I buy now or just gamble 3000 INR on it?
Screener link: Gujarat Toolroom Ltd share price | About Guj. Toolroom | Key Insights - Screener
NPST – Technology Provider for UPI Tech (12-06-2024)
The company is in a fast moving tech market. To keep being relevant even the incumbents need to be on their toes and work hard to develop new products/offerings. Company spoke about this in last call.
Last year itself company added 2 new products and got some orders on them (Bharat Bill Payment & Online Dispute Resolution) to the 2 major existing product basked (i.e., TSP, API rail for payment aggregators)
Company also gave hint about working on 2 different new products. i.e, Payer solution and offline payment model and spoke of one of them giving some topline in FY25 itself.
Company is handling some crazy incremental volumes. Which often means, company has to constantly think of implement further scalability of it’s systems. Risk & fraud monitoring & compliances also become very very important as the UPI acceptability has grown. Then company has to make investment into AI/ML to see how they can fit into this ecosystem.
Company also has to hire top talents/product leaders who can manage these new lines of products from end to end and deliver to market. It also hired top HR & marketing talent last year to make the transition from being promoter led to more of an institution. Inspite of the scorching growth of around 130% cagr of last 3 years, it is still guiding for 75-100% growth for this year and working on future products.
So, i guess, we could give them some slack in understanding why the money is required. All of the above require money.
Clean Science and Technology Limited (CSTL) – A clean and green future ahead (12-06-2024)
Hello,
In the below tracker, I have started tracking important company goals for Clean Science.These goals are referred to as ‘monitorables’ in the tracker.I will update this document regularly to reflect the current status of these goals.
Here’s a snapshot of what the tracker includes:
- Company Ticker: For identifying the company
- Monitorable Description: Description of the goal or metric being tracked
- Date of Announcement: When the monitorable was announced
- Deadline: Target date for achieving the monitorable
- Status: Current progress (e.g., Not Fulfilled, Pending)
- Verification Link: A link to see where I got the information about the goal.
I hope this information makes it easier to observe how well companies are progressing towards their stated goals.
Screenshot of the tracker below:
Full tracker attached below:
Tracking Company Monitorables-3.xlsx (122.3 KB)
Welspun India – most vertically integrated textile co (12-06-2024)
Hi,
are you guys still holding this stock? It seems to be stuck
@luckbychance ranvir