Scientists discovered the potential of the animals\u2019 antibodies to thwart diseases.<\/b>
\nOne llama is sprawled on the grass with its neck craned, basking in a patch of sunshine. Another stands on a dirt hill, ears flattened defiantly. A third rushes to greet visitors with a friendly nuzzle.
This isn\u2019t a petting zoo. The furry beasts are in Belgium for work.
Scientists have discovered the potential of the animals\u2019 antibodies to thwart multiple diseases, and now drug developers are collectively plowing billions of dollars into a field that may yield a fresh generation of life-changing medicines. The targets include some hard-to-treat conditions like cancer, nerve pain and a chronic skin ailment.
The llamas are a vital part of the experiment. In between dust baths and grazing, they get injections to trigger the production of their precious antibodies. The animals are some of the few to produce the tiny proteins, dubbed nanobodies, which scientists praise as easy to produce, manipulate and engineer.
\u201cThey have this Lego-like nature that you can just snap them together any way you want to, which is really unique,\u201d says Mark Lappe, the chief executive of U.S. biotech Inhibrx Biosciences Inc. \u201cIf you try to do that with regular antibodies, it\u2019s wildly complex.\u201d
The field is burgeoning, albeit quietly for now. A Sanofi drug for a rare autoimmune blood disorder was the first medicine developed using llama antibodies to hit the market. AstraZeneca Plc recently released results for an experimental medicine to treat another autoimmune dysfunction that could be a potential blockbuster. And U.S. pharma giant Eli Lilly & Co. has partnered with Belgian biotech firm Confo Therapeutics to gain rights to a product exploring a new approach to pain management.
\u201cI do think nanobodies will be a mainstay of many portfolios going forward,\u201d says Michael Quigley, Sanofi\u2019s chief scientific officer. \u201cSanofi from our perspective is leading the field.\u201d
Inhibrx, for its part, is working on a therapeutic that can induce the death of some tumor cells while sparing healthy tissue \u2014 a progress over some existing cancer regimens. The shares more than doubled after a study showed patients with a rare type of bone cancer and no treatment options lived longer on the experimental drug without the disease progressing. The treatment is undergoing tests for several types of tumors.
The immune system of all mammals produces antibodies to thwart viral and bacterial attacks. Those made by llamas and other members of the camelid family can squeeze into tighter spots and better penetrate tissue than human ones, because they\u2019re smaller and simpler. Some have been reported to cross the blood-brain barrier, eliciting hope for neurological diseases.
For the llamas, it\u2019s not necessarily a bad job. They get injected with an antigen a couple of times and some weeks later, when their immune system has reacted, a vial of blood gets drawn that contains antibodies scientists will then tweak in the lab.
When they get older, they might go on to a second career in wildfire prevention or as livestock guardians. Some will get adopted, while others will simply retire.
\u201cWe have a llama pension plan,\u201d Cedric Ververken, the chief executive officer of closely held Confo, said in an interview. \u201cOnce we\u2019ve immunized them and have generated the antibodies, we want to make sure that the llama still has a happy life.\u201d
A look behind the scenes confirms the animals at one large farm in Belgium live freely on a big, partly wooded terrain divided into multiple enclosures, each with a shed.
The llamas live in herds with one dominant member. They are social animals and their mobile ears betray their state of mind, much like horses\u2019: ears slanted forward, they\u2019re curious, ears flattened back, they\u2019re alert and somewhat suspicious. Unlike horses, they can kick sideways. One testy female, Jane, is known to spit at her carer if her daily serving of hay and pellets isn\u2019t delivered fast enough.
The exact location of the farms is often kept secret, though the use of llamas in medical research is regulated.
The beasts also play a big role when it comes to branding. Inhibrx has a picture of the furry creatures in a brochure about its clinical pipeline. The investor presentation of Swiss company MoonLake Immunotherapeutics includes friendly-looking cartoon animals. Dutch-incorporated biotech Argenx SE, which deals with another type of llama antibody, also shows cartoon images on its website, including one wearing a beret to denote some of the animals they use live in the south of France.
\u201cPeople love the llama,\u201d Tim Van Hauwermeiren, Argenx\u2019s chief executive officer, said in an interview. \u201cThey want to know all about the llama. Retail investors want a stuffed llama when they go home.\u201d
Much of the nanobody activity is rooted in or near Belgium because the Free University of Brussels is where the antibodies were first discovered. The original findings related to dromedaries, but researchers soon found that other types of camels, llamas and alpacas shared the same properties, as did sharks.
The university, a large block of mismatched buildings on the outskirts of Brussels, has given birth to a number of the field\u2019s first biotechs along with the Flemish Institute for Biotechnology. One example is Ablynx NV, which Sanofi bought in 2018 for \u20ac3.9 billion ($4.6 billion) after outbidding Novo Nordisk A\/S. Lilly\u2019s partner Confo is another.
The Brussels campus still houses work on nanobodies \u2014 a term trademarked by Ablynx. VIB Nanobody VHH Core, which engineers these camelid antibodies for pharma and biotech clients, works out of a set of barracks in a leafy corner of the campus. The group focuses mostly on treatments and diagnostics for cancer and inflammatory diseases, but it\u2019s also investigating nanobodies for other applications, including a new type of contraceptive for the Gates Foundation.
\u201cEverywhere you have a target an antibody can bind to, you can have a nanobody application,\u201d says Steve Schoonooghe, one of VIB\u2019s scientists. \u201cGive us a target on a cancer cell and we can make a nanobody against it.\u201d One goal, like at Inhibrx, is to tackle tumors while avoiding the damage wrought by chemotherapy.
For now, the nanobody world has yet to prove it can deliver a blockbuster. Sanofi\u2019s Cablivi drug was a trailblazer, but after about seven years on the market for a blood-clotting disorder it has only garnered sales of \u20ac202 million in the first three quarters of last year. The French drugmaker has stopped research on five experimental nanobody drugs in recent years, although it\u2019s still working on others. Two in particular are undergoing tests for ailments including asthma, diabetes and inflammatory bowel disease.
The field has endured setbacks as well. MoonLake\u2019s market value crashed in September after a study of its experimental skin treatment prompted analysts to conclude it was no better than a rival medicine.
\u201cIt\u2019s important to remember the overarching arc of drug discovery and development, and the maturation of any given platform, which takes time,\u201d says Quigley, Sanofi\u2019s chief scientific officer.
A big hit could help turbo-charge things, and AstraZeneca\u2019s experimental rare-disease drug gefurulimab is billed as having that potential. The medicine could become a blockbuster in 2031 and is one of four nanobody medicines the UK drugmaker is developing.
\u201cFrom my perspective, nanobodies represent a very important new tool in our toolkit,\u201d said Seng Cheng, head of research and product development at Alexion, Astra\u2019s rare-disease business. \u201cWe still haven\u2019t tapped all the potential of what it can offer.\u201d
The need to work with actual llamas could soon be made obsolete by artificial intelligence, but for now the animals still serve a purpose.
Inhibrx\u2019s Lappe estimates the California-based biotech has immunized more than one hundred llamas located in rural San Diego County. Like some others, they lease the animals instead of owning them because \u201cwe\u2019re drug developers \u2014 we\u2019re not really farmers.\u201d<\/p>\n