Solt DB

We're giving students 👉 FREE lifetime access 👈 to Solt DB Invest, the investment research subscription for biotech stocks that funds our mission as a public benefit company. That's a $9,000 value at our current annual subscription rate. Two steps to earn it: 1️⃣ Be a student. 2️⃣ Help annotate 250 new entries to the Solt DB Biotech Company Database (mostly from our unpublished datasets). That's it. As a Database Builder, you'll keep free lifetime access to Solt DB Invest -- even after you graduate and become a super successful nerd. 🤓 This is a great way to learn about the structure of the bioeconomy directly from our founder Maxx Chatsko. You'll also learn about investing "the right way" at the start of your career, when compound interest is the most powerful. Send us an email or DM with your LinkedIn profile to become verified. Full details and a FAQ can be found on our website: https://lnkd.in/d5U6zhtq

Biotech funding crunch got you down? Don't worry, Illumina already figured this out. So, why have no other living technology companies replicated Illumina's success? Instead of waiting for interest rate cuts (which likely won't fall very much due to deficits and demographics), any business, investor, and entrepreneur can choose to prioritize operating efficiency. It's a lost art in company formation. Like it or not, accept it or not, the expansion bias has ended. It won't return. Your business must adapt to survive. https://lnkd.in/e-Qd4wdW

Humira is no longer the world's bestselling drug annually, but it's still the all-time sales leader (until Keytruda takes the crown). How it got there is an interesting case study in how drug developers price their products, the incentives within the complex U.S. healthcare system, and how drug developers are increasingly bolder and more aggressive navigating a lack of price regulation. It's common to hear Americans pay higher prices than international patients for the same drug products because, well, that's the price to pay for innovation. But that's actually a relatively new phenomenon. International sales of Humira outpaced U.S. revenue as recently as 2013. This narrative also doesn't match the financial data. From 2014 to 2023, if Americans paid the same prices as international patients for Humira, then they would've saved over $100 billion. In that decade span, AbbVie spent: ➡ $61.2 billion on R&D ➡ $63.3 billion on dividend payments ➡ $33.7 billion on stock buybacks ... ➡ $7.4 billion in U.S. income taxes (tax rate of ~14%) The U.S. corporate tax rate from 2014 to 2017 was 35%, before dropping to 21%. AbbVie paid an effective U.S. tax rate of 14% in the period above. Interactive data visualization: https://lnkd.in/emj6XrNS

As part of our ongoing commitment to support living technology in Pittsburgh, Solt DB is excited to provide travel grants for our friends at Nucleate Pittsburgh. Travel grants will help support team members attending the 2024 Nucleate Alumni Summit in the Bay Area this August 27th to 29th. The finch got a nice write up in this week's Nucleate Bio newsletter, too.

Today, Recursion announced the completion of BioHive-2, its wholly owned supercomputer for AI-powered drug discovery. The machine is 4x as powerful as its predecessor and would rank 35th on the global TOP500 list. We wrote about efforts to use advanced computational tools in biology last year, including Recursion and BioHive-1, Relay Therapeutics and its Dynamo technology platform, as well scientists at Berkeley Lab and the Pittsburgh Supercomputing Center. Our deep dive: https://lnkd.in/eUcU2462 Press release: https://lnkd.in/gW4A9Xgk

Some tough news out of Ginkgo Bioworks, Inc. The synthetic biology CRO announced plans for layoffs (aiming to reduce labor expenses >25%) and to reduce the lab footprint by up to 60%. These moves suck upfront, but are intended to right-size the unwieldy cost structure. Operations alone have been burning $843,000 per day since the beginning of 2023. Importantly, this lays the groundwork for business model evolution. The focus on downstream value sounded great, but it was unlikely to enable a sustainable business. In drug development, Ginkgo provides discovery-stage help. Most downstream value comes from sales milestones, which are 10+ years away from the company's last touch point (and throughout the industry many sales milestones are never realized). A better path forward likely leans into a heavier services model. Downstream value should only be sprinkled into select contracts strategically. Reorienting around services would allow Ginkgo to focus on providing great work and data while capturing value upfront. It'll be easier to track and improve KPIs around the "work" work -- the labor part, the time part, the efficiency of experiments, etc. There's a tough road and more difficult decisions ahead, but this is an important first step to becoming a more sustainable business. For example, there's a stock split coming soon (a recent article from Solt DB): https://lnkd.in/eMyRTKgy Press release announcing Q1 2024 decisions: https://lnkd.in/eHHd_n2B

One quarter through the "century of biology," we're great at building startups deemed successful by the vanity metrics of success, but terrible at building commercially successful businesses. Why does the storytelling and perception of synthetic biology companies often deviate from the realities of the underlying businesses? https://lnkd.in/e_FGGRY6

Whether Ginkgo Bioworks the business succeeds will be determined by execution over time. As for Ginkgo Bioworks the stock, the outlook is pretty bleak. Those company's rosy pre-SPAC projections allowed it to snag a $14.9 billion valuation at the time of its public debut and $1.51 billion in cash. But the short-term tradeoffs made to juice the valuation are now leading to longer-term problems for shareholders. A reverse stock split is needed in 2024, but it can lead to other challenges. https://lnkd.in/eDjWv9Ut

Verve Therapeutics recently stumbled in the HEART-1 study when a patient treated with the lowest dose developed two serious side effects. A next-generation asset should address one adverse event. The phase 1 clinical trial was evaluating VERVE-101, a CRISPR base editor targeting liver expression of the PCSK9 gene, to treat high levels of LDL cholesterol. The initial indication is an inherited disease called heterozygous familial hypercholesterolemia (HeFH), which is characterized by abnormally high LDL-C levels regardless of diet. Much larger patient populations could be targeted in future studies. A patient developed an increase of liver enzymes and a sudden reduction in blood platelets (thrombocytopenia), both deemed Grade 3 adverse events. ➡ The first was almost certainly caused by the lipid nanoparticle (LNP) used to encapsulate the CRISPR base editing payload. ➡ The second was likely caused by the sudden inhibition of PCSK9, which will be trickier to avoid but should be a manageable side effect. Verve Therapeutics is now prioritizing a next-generation asset, VERVE-102, that uses a refined LNP delivery vehicle. Importantly, it uses GalNAc ligands to transport the drug payload to different receptors on the surface of liver cells, which should significantly reduce the risk of elevated liver enzymes. There are at least six FDA-approved genetic medicines that utilize GalNAc targeting ligands, although none coupled to a LNP.

There could soon be a blood test available to screen for colon cancer. Well, another one. But it might struggle to earn reimbursement. Sensitivity and specificity are important metrics for any diagnostic test. However, colorectal cancer (CRC) – "colon cancer" – is unique in that screening tests must also perform well on a third metric: the ability to detect precancerous lesions. This often-overlooked metric is crucial for a diagnostic test to be commercially competitive. It could also be what trips up Shield from Guardant Health in securing favorable Medicare reimbursement. Shield has an overall sensitivity of 83% and specificity of 90%, but it has the lowest detection of precancerous lesions in the competitive landscape at just 13%. Read this week's article: https://lnkd.in/esYwnUHD