Khabib shares his thoughts on getting older and remaining grounded 🙏🏽⏳
"I'm 37. Maybe tomorrow is my last day, you never know. But getting older, just like everybody else, I don't like it. But this is what Allah gave us. We have to deal with this, and we have to understand. This is a very good reminder to be just a regular human, to come down to earth, and this is a good feeling."
(via: za.Khabiba)
12-year-old Brayden Baldwin has faced off with cancer twice.
But nothing will stop him from chasing his dream: becoming a goaltender for the Philadelphia Flyers.
Growing up in Toronto & going to Leafs games, I don’t think I ever witnessed the absolute born & bred crazy that is Oilers’ fans.
Just a special bunch & definitely the best atmosphere of any of the rinks I have been to across Canada & the US.
💙🧡🤍
Steve Kerr on his biggest concern about America Today
“When I finished college almost forty years ago, if you went to school and got a degree, you could get a job and you could buy a house. Now that's out of reach for most people between student debt and home prices and the economy slanted toward the very, very top one per cent. We don't really have a middle class, and we don't have what used to represent the American Dream, which was: you can do better than your parents. We're going backward on all that. Our family is lucky. I'm in a position where my family can live well. But there are millions of people out there, young people who are looking at the horizon and saying, "I did everything I was told I needed to do, and I can't buy a house, and I can't chase my dream." Think about what that means for the stability of communities and cities and a whole country.”
(Via @NewYorker h/t @warriorsworld )
$ABCL It seems to me like AbCellera is seeking to be a Zero to One company in GPCR targeting antibodies:
GPCRs are one of the most validated classes of drug targets in medicine, with about 1/3 of all FDA-approved drugs targeting GPCRs. Yet virtually none of them are antibodies.
"GPCRs are among the most valuable drug targets in medicine, but their tiny exposed surface, fragile membrane-dependent structure, similarity across species (triggering immune tolerance), and incompatibility with conventional screening methods have made them nearly impossible to drug with antibodies."
At the same time, AbCellera is betting half of their in-house molecules and initiated programs on GPCR targeting antibodies, showing very high confidence in their capabilities.
In this article, we take a look at the different bottlenecks that have historically stopped GPCR targeting antibody drugs from being developed and the different ways AbCellera is approaching it.
As discussed in AbCellera's “Engine”: How It Works & Why It Matters, it is the end-to-end integration of many technologies that defines the moat. This proves to be true once again:
The Tetrahymena, Trianni mice, two-stage enrichment, single-cell functional screening capabilities, counter-screening for specificity, and RepSeq all serve their own purposes that are critical. It is the seamless integration of them together that makes this work, along with the rest of the technologies in the broader platform.
That being said, the one part that stands out to me specifically for GPCR targeting is the Tetrahymena platform, thanks to their acquisition of Tetragenetics in 2021:
Basically, one of the biggest obstacles with developing antibodies that target GPCRs is obtaining a GPCR protein to immunize animals and invoke a natural immune response from to obtain the desired antibodies. There's various reasons for this discussed in the article, but to summarize it: GPCRs lose their shape when removed from a cell membrane, mammalian cells can't produce enough of them without dying, and the immune system suppresses its response against them because they look too similar to the animal's own proteins.
AbCellera's method of using Tetrahymena to express the GPCR on its surface at high density solves this problem.
While alternatives exist, it looks like they deliver lower antigen density and weaker immune responses compared to the Tetrahymena's ability to "overexpress full-length GPCRs at high density without toxicity". Without that edge, you struggle to produce enough GPCR protein to generate a strong immune response. Without a strong immune response to generate antibodies, nothing else matters. Because of this, I believe AbCellera's acquisition of Tetragenetics in 2021 was absolutely brilliant. From what I understand, no other company appears to have a direct equivalent to the Tetrahymena-based system for producing cells with high-density native GPCR expression on their surface, aimed at antibody discovery. And even if a competitor does exist or comes along in this regard, they'd still need all the other links in the chain (Trianni mice, single-cell functional screening, two-stage enrichment, RepSeq, etc), some of which AbCellera's management refers to as "best-in-world" or close to. That's a moat.
The application of RepSeq here also really stands out to me:
"The S-1 explicitly states that using natural antibody variants from the repertoire to design optimized candidates is "particularly powerful for high-value membrane protein targets such as GPCRs and ion channels (which cannot be optimized by conventional display-based methods).""
When AbCellera finds a functional GPCR antibody but it has a problem, they can search the RepSeq data for naturally evolved relatives of that antibody rather than trying to optimize it through display methods that can't work with GPCRs because the protein falls apart outside a membrane (another significant bottleneck solved). The combination of the functional single cell data with the ocean of RepSeq data essentially unlocks lineage mapping of the entire immune response. This is powerful.
After going through all of this, it now makes perfect sense to me why AbCellera seems to be so confident in their GPCR targeting capabilities.
When I look at the different technologies AbCellera has integrated to overcome bottlenecks and target GPCRs, and consider how it's only a piece of the broader ecosystem of technologies they've integrated together across the entire antibody discovery platform, I can't help but to believe this company is special.
The next 6-12 months will be very telling... Phase 1/2 readouts on ABCL635, a GPCR targeting antibody therapy, should be sometime in Q3 of this year.
(Pictured below: Tetrahymena thermophile)
Be Reid Wiseman
He’s a hardworking single father of two girls whose wife passed from cancer 6 years ago, and his daughters supported his becoming one of the farthest-travelled human beings in history as Artemis II mission commander
This man is a great example for fathers
Jeremy Hansen of the Canadian Space Agency (CSA) is a mission specialist, meaning he has trained for all roles to jump into action wherever needed, like Koch. Artemis II is his first spaceflight, and he is the first Canadian to fly to the Moon. https://t.co/9ABDQfD4P2
Hind Rajabs words on a mobile phone as Israel was murdering her.
‘“I’m not talking because every time I talk blood comes out of my mouth & makes my clothes dirty and I don’t want my mom to have to clean it.”