Could one small herd of cows slow or prevent the event of type 1 diabetes in lots of 1000’s of individuals worldwide? A biotech startup named SAb Biotherapeutics is betting that it may. Scientists from the firm have genetically engineered cows to provide human antibodies which were demonstrated to guard against the autoimmune attack that defines type 1 diabetes. These antibodies may be extracted — with little or no harm to the cow — and administered to individuals with newly diagnosed type 1.
The primary human trials of the therapy, which is currently named SAB-142, are starting right away. SAb’s leaders expect that the antibody infusion will provide protected and sturdy protection to participants’ capability to secrete insulin. They consider that SAB-142 could deliver lifelong advantages to individuals with newly diagnosed type 1 diabetes — and possibly even prevent its development in the primary place.
The therapy, if it ever sees the sunshine of day, is years away. But investors are betting big on its potential: SAb recently secured $67 million in financing from a constellation of enterprise capital firms, including the JDRF T1D Fund.
It Starts With Rabbits
The story of this futuristic bovine medicine actually starts with rabbits. For many years, doctors have used rabbit antithymocyte globulin (ATG) as an antirejection medication for organ transplants. Rabbit ATG powerfully blocks the immune system attacks that result in acute organ rejection. Naturally, researchers have explored its potential to inhibit autoimmune attacks, too.
“That exact same motion can be used to stop an autoimmune response, which is precisely what type 1 diabetes is,” says Eddie Sullivan, the president and CEO of SAb Biotherapeutics. And it really works: “ATG has been utilized in multiple clinical trials and has shown a few of one of the best efficacy data in stopping the progression of type 1 diabetes.”
A 2019 experiment, for instance, showed that a low quantity of ATG, delivered in two doses over two days, helped preserve beta cell function and reduced A1C levels for not less than two years in individuals with newly diagnosed type 1 diabetes. In essence, the drug infusion strengthened and prolonged the honeymoon phase.
Despite the extremely promising results, ATG has never been developed as a industrial therapy for type 1 diabetes. Sullivan speculates that it have to be due to ATG’s uncomfortable side effects, which may be considerable.
“The issue is, if you happen to give humans an animal antibody, like a rabbit antibody, there’s an immune response called serum sickness that may be quite severe,” says Sullivan. “The patient may even create antibodies to attack the drug itself, which is a foreign protein.”
Rabbit ATG’s uncomfortable side effects are well definitely worth the risk within the case of a life-saving organ transplant. But for an individual with new-onset type 1 diabetes, who can treat their condition without the necessity for drastic measures, the chance will not be worthwhile.
But what if doctors had a source of human ATG, which must be much less more likely to provoke bad auto-immune reactions?
Enter the Genetically Engineered Cows
It seems like science fiction. In South Dakota, there’s a herd of cloned cows which were genetically engineered to grow medicine for humans. SAb’s cows are transgenic: Their cells contain human DNA which is designed to “turn off the cow antibody genes and produce fully human antibodies.”
“We are able to immunize these animals to specific targets, equivalent to autoimmune diseases,” says Sullivan. And their first goal is type 1 diabetes. They create human ATG.
The cows, SAb Executive Chairman Sam Reich insists, are treated “like royalty.”
“They’re on a fantastic farm that might resemble a dairy farm. They will go inside and outdoors, and their pens are each heated and air-conditioned.” These cows are useful — every one can produce enough medicine to treat several thousand people.
About thrice per 30 days, each cow “donates” blood. “These cows donate plasma as an alternative of milk, but they’re handled the identical way,” says Reich. “We’re not doing anything to those cows that humans don’t voluntarily do to themselves.”
Because each cow is so productive, Reich said, SAb won’t ever require a big herd. At launch, as few as 15 cows would supply good enough human ATG for the corporate’s demand projections. Even when every human on earth with new-onset type 1 diabetes received SAB-142 — about half one million people are diagnosed with type 1 diabetes worldwide in a 12 months — SAb would still require only a small dairy’s price of cows.
No person has ever tried redosing rabbit ATG in individuals with type 1 diabetes, perhaps because the chance of uncomfortable side effects is believed to extend after exposure. Serum sickness is considerably more common even in individuals who have previously kept rabbits as pets, in line with an academic survey.
Human ATG, nonetheless, could potentially be redosed repeatedly, in line with Alexandra Kropotova, SAb’s chief medical officer:
“Every year redosing could keep the beta cells shielded from the autoimmune response.”
While SAB-142 is not going to cure diabetes or confer insulin independence, it could help patients preserve some endogenous insulin production for years. And if it may be redosed repeatedly, there’s no telling how long the effect might last.
We all know that a sturdy honeymoon phase “is related to reduced prevalence of long-term complications.” Even a small amount of natural insulin production is strongly associated with higher health outcomes; in a study of Joslin gold medalists, some were found to have measurable natural insulin production even 50 years after diagnosis with type 1, suggesting that residual insulin production could also be a key to longevity. And lucky patients with higher levels of beta cell activity also enjoy improved blood sugar control and reduced risk of hypoglycemia, presumably resulting in each higher health and better quality of life.
Many drugs have been evaluated to increase the honeymoon period; the newest news is that the buzzy blockbuster semaglutide (Ozempic) may have the option to cut back insulin requirements, in line with On a regular basis Health. But up to now, no drug has been approved by the U.S. Food and Drug Administration (FDA) to slow the progression of type 1 diabetes after diagnosis.
“Only 30 percent of individuals with type 1 diabetes maintain an A1C below 7.0 percent,” says Kropotova. “We’re failing 70 percent of patients, despite the provision of very advanced technologies.”
SAB-142 has many hurdles to pass before it is prepared for FDA approval. The phase 1 study starting now will mostly evaluate the drug’s safety in a reasonably small number of individuals. Results could also be complete by the tip of 2024. If all goes well, phase 2 would enroll volunteers soon after; those results wouldn’t be ready until the tip of 2026. If SBA-142 has proved to be protected and effective after those two major tests, SAb will embark on a number of phase 3 trials, the longest and largest experiments required by the FDA. Within the best-case scenario, assuming that the therapy has the terrific results that its backers consider it’s going to, SBA-142 could also be ready for FDA approval in six or seven years.
Though the vast majority of medical therapies don’t survive all the multiphase clinical trial process, Reich is confident that SAB-142 is “uniquely positioned, because we already know that it really works. Rabbit ATG has already proved itself, and our therapy is mechanistically equivalent.”
Could SAB-142 Prevent T1D within the First Place?
While SAb is currently focused on extending the honeymoon period for individuals with newly diagnosed type 1 diabetes, the firm also plans to see if its experimental therapy can delay or prevent the event of full-blown T1D in individuals with a really high risk of developing the condition.
There is precisely one medication currently approved to do that: the recently approved teplizumab (Tzield). When given to patients known to hold the antibodies that cause type 1 diabetes, Tzield delays the onset of symptoms by a median of nearly three years.
Kropotova calls Tzield “a trailblazer and a big, life-changing drug.” But she believes that SAB-142 may very well be even more practical than Tzield, since it is a polyclonal versus monoclonal treatment.
“Monoclonal antibodies [like Tzield] by definition only affect one specific cell lineage. But other broken pathways should not being corrected. And the pathogenic cells are still alive, still lively, and still attacking and destroying the beta cells.”
“Using a polyclonal approach, we achieve two goals. Primary, we bind to several cell subsets that take part in autoimmune destruction. Number two, this platform allows a much higher probability of a better proportion of patients who will reply to the drug.”
We may know more soon about ATG’s potential on this patient population. Type 1 Diabetes TrialNet — a frontrunner in diabetes antibody testing — is spearheading the STOP-T1D trial, which can test rabbit ATG in volunteers with stage 2 type 1 diabetes.