Ginkgo Announces New Advisory Board!

 January 8, 2024

Today we’re thrilled to announce the formation of our new Biopharma Advisory Board!

This council of experts from across the biopharmaceutical industry will provide critical insight into the development of Ginkgo’s core platform service offerings across target discovery, drug discovery, optimization, and manufacturing. The group, which will conduct regular meetings at Ginkgo and with its partners, includes (in alphabetical order) —

How many of these CEO's have signed deals with Ginkgo Bioworks to provide Ginkgo with revenue rather than Ginkgo providing the CEO's with income? 

“We try never to forget that medicine is for the people. It is not for the profits.”

– George Merck

I would like to focus on one of the members of the new committee. Previously I have talked about one of the new members of Ginkgos Advisory Board.

• John Maraganore, PhD, served as the founding Chief Executive Officer and a Director of Alnylam from 2002 to 2021. Under his leadership, Alnylam helped lead the interventional RNA revolution by launching the first RNAi therapeutic medicine, ONPATTRO®, in 2018, followed by four more RNAi therapeutics through mid-2022. Dr. Maraganore was the chair of the Biotechnology Innovation Organization (BIO) from 2017 to 2019 and is an active mentor to leaders across the biotechnology industry. John is the principal of JMM Innovation, and also serves as a Venture Partner for Arch Ventures and Atlas Ventures, an executive partner for RTW Investments, a senior advisor for Blackstone Life Sciences, and as an advisor for M28.

A quick search of ONPATTRO: 

Wikipedia

Onpattro is a medication used for the treatment of polyneuropathy in peop[le with hereditary transthyretin-mediated amyloidosis, a fatal rare disease that is estimated to affect 50,000 people worldwide.

The per-patient cost is between US $451,430 and $677,145, depending on the number of vials needed. As of 2020, there were 1050 people globally receiving parisian, generating $65.5M in net revenues. 

The FDA

Alnylams Pharmaceuticals push for parisian to be expanded to a much larger pool of patients...

In a briefing document released ahead of the Sept. 13 meeting of the FDA's Cardiovascular and Renal Drugs Advisory Committee, the agency called into question the efficacy of the drug in treating that pool of patients.

Remember, medicine is for the people, not the profits. 

Patisiran was already approved by the FDA in 2018 for the treatment of hereditary ATTR amyloidosis polyneuropathy, which made it the first-ever RNA interference therapeutic approved by the regulator.

Nevertheless, vutrisan - sold under the brand name Amvuttra - still represents the company's most lucrative product. In its second-quarter 2023 financial update, net revenues for the drug were $132 million, versus $91 million for Onpattro. In the fourth quarter Onprattro sales were down to $79M.

For the full-year 2023 net product revenues of $1.24B were reported. The revenues come from sales of its four marketed products Onpattro, Amvuttra, Givlaari and Oxlumo.

Onpattro: $355M

Ambuttra: $558M

4060 patients worldwide were receiving commercial Onpattro and Amvuttra as of year-end 2023.

Givlaari: $219M

Oxlumo: $110M

650 patients were receiving Givlaari as of year-end 2023

430 patients were receiving Oxlumo as of year-end 2023

So roughly 5140 patients are generating $1.24B. 

Yahoo Finance

In October 2023, Alnylam experienced a massive setback after the FDA issued a Complete Response Letter (CRL) in response to the company's supplemental new drug application (sNDA) for the label expansion of Onpattro to treat the cardiomyopathy of transtheyretin-mediated (ATTR) amyloidosis. 

However, following this development, the company shifted its focus to the phase III HELIOS-B label-expanding study of Amvuttra in the treatment of cardiomyopathy of ATTR amyloidosis. 

CCS

John Maraganore has long struggled to get dubious RNAi drug products on the market. From the perspective of the market, he has succeeded. But then again, so did the Covid vaccine. Safety and efficacy can be dealt with best under emergency conditions. John Maraganore has succeeded. He is a hard working man. Long listed here as a Cargo Cult Scientist he has created over $25B in market capitalization. 

Alas, only 5,140 patients are receiving treatment. Those patients are already very sick people. They get results only a professional statistician working in the Cargo Cults can detect. We have to wonder what it is like for the patients receiving the RNAi drug product. Do they feel a difference? Are they less sick?

In the Cargo Cults the natives still look to the skies. They believe what they are doing will one day provide results. Ginkgo Bioworks has said that John Maraganore has produced results and he will now advise them on how they too can see the massive returns on their investments. Although the expertise of John Maraganore was in RNAi drugs, he seems to have now moved on to biotechnology capital. He is an investment strategist. He advises on money. Ginkgo does not do RNAi drugs. Nonetheless, they have found an ally. A man who knows that medicine can make great profits even if the people don't need them. 

Book List

 1.  Betyrayers of the Truth - William Broad and Nicholas Wade

The lures of careerism and big money, the pressures of huge research factories, the repeated failure of supposedly fail-safe mechanisms of scientific inquiry to detect and correct fraud - Betrayers of the Truth is about how science really works and why scientists are tempted to cheat. 

2.  On Bullshit - Harry G Frankfurt

Most people are rather confident of their ability to recognize bullshit and to avoid being taken in by it. So the phenomenon has not aroused much deliberate concern. We have no clear understanding of what bullshit is, why there is so much of it, or what functions it serves. And we lack a conscientiously developed appreciation of what it means to us. In other words, as Harry Frankfurt writes, "we have no theory."

3.  Innumeracy - John Allen Paulos

Mathematical Illiteracy and It's Consequences. Innumeracy - the mathematical counterpart of illiteracy- is a disease that has ravaged our technological society.

4.  A Drunkards Walk - Leonard Mlodinow

How Randomness Rules Our Lives. 

5. Predictably Irrational - Dan Ariely

Challenging assumptions about making decisions based on rational thought. No amount of education can reliably prevent us from making mistakes. We can be, because of our biases, the easiest person for us to fool. 

A healthy dose of skepticism is necessary when looking at information. Be it the modern day media to science to technology, we all must have the ability to separate the truth from everything else. Our bias is our biggest enemy. We will prefer certain truths over others. 

Wax On Wax Off

It is assumed, in science, that a true genius comes along once and a while. All of the people in between are just stewards of the collective knowledge given to us by the geniuses. They teach the new generation about the work. As Richard Feynman pointed out in Cargo Cult Science. "That is the idea that we all hope you have learned in studying science in school—we never explicitly say what this is, but just hope that you catch on by all the examples of scientific investigation." In the process of learning the thing that was discovered long ago we hope to learn how to think as well. 

What is "what this is"? It is not the fruits of the labor that matter most in science. It is the scientific method that we learn, teach and practice (as scientists) that matters. The journals Cell, Science and Nature all insist that the fruits of the labor defines the level of genius of the scientist. They do not seem to value the labor of thought, experimental design, execution and proper conclusions as much. This leads to the individual scientists focusing on their narrative more than their methodology. 

The Cargo Cult Scientist believes that the method is what matters. The scientific politician focuses on the fruit. Think of it like Ginkgo Bioworks laboratory produced meat. Technologists can produce meat-like substances. They cannot produce the biologically produced meat that evolved over billions of years. Would you prefer cutting into a steak or scooping up the pooding produced by a biotech company?

Think of that disgusting meat the same as the miracle molecules we put into peoples bodies. We find individual proteins the are part of a complex system. We manufacture them because that is within the complicated paradigm of our understanding. Then we take the final product and use it in our simple understanding.

Indeed Ginkgo Bioworks seeks to replace your companies research team. BIOLOGY BY DESIGN! I suppose, unlike nature, Ginkgo will design biology to do what you want it to do. The problem is in the understanding of the scientific method. We don't design biology. We seek to understand it. 

As always, we return to the problem of Simple-Complicated-Complex. Ginkgo Bioworks programs cells to "make everything from food to materials to therapeutics". Programming a cell is complicated. So the biotech or biopharma company hires Ginkgo rather than hiring a research staff. They get the cell line they want. They have the product that comes from a bio-engineered cell. Now what? 

I ran into this problem at every biotech company. One example was producing a library of peptides that could be screened to find that one magical peptide that would deliver RNA to specific cell targets. RNA interference won two scientists the Nobel Prize in 2006. It was all the rage in knocking out gene products in biotechnology. But it didn't work in most situations. Why? It was assumed that the laboratory staff were doing something wrong. When this square peg couldn't be hammered through the round hole people began looking for a peptide or protein to deliver the RNA to the cell target. The narrative was in place. The project failed. We were all let go. The project was turned over to a prestigious professor at a European University. He too produced nothing to support the narrative. The narrative was simply changed. The science was working! Occasional reports were put out via company press releases that the scientist was making progress.

The project was most likely doomed from the start. Yet if, in an alternative universe, we had been allowed to fail we could have learned. Had we been given years of exhaustive research we may have made some valuable discoveries in our failures. We would have advanced our knowledge in the process/methodology. Instead we all went on to the next attempt to maintain employment in biotechnology. Most of us failed to do so. 

The future of Ginkgo Bioworks is no different. They are pursuing the idea that understanding complicated biotechnologies will lead to the kind of discoveries that make science work. There is a disconnect there. Like Mr. Myagi in the Karate Kid taught, wax on, wax off. Why? It was a Hollywood creation based in dubious reality but the concept is real. In science, the method is the thing. Learn how to conduct research and the results will teach you new things. Unfortunately, in business, there is not enough time to wax on and wax off until the time comes to apply the knowledge. People in offices who mostly attend meetings need data. They need charts and claims of near future riches. Ginkgo promises you they can help. In time you will end up with a few fish but no understanding of how to fish.