“Want to lose weight? There’s a pill for that.”
“Feeling too anxious? There’s a pill for that.”
“Got irritable bowel syndrome (IBD)? There’s a pill for that.”
There has long been an obsession with the ability to take a pill for any ailment or illness. There’s just something simple and innocuous about a pill, at least compared to being stuck with a syringe or having an IV inserted into a vein. However, not every chemical entity can get to where it needs to go and do what it needs to do by being swallowed in pill or tablet form.
After working at Shire PLC for over a decade, Adi Mohanty was approached by Biora, a biotechnology company looking to reinvent itself. Some side projects caught his eye, and he believed they could solve real challenges and make medicine more personalized and precise. Mohanty said, “When you get sick and say, ‘Can I take a pill for that?’ But a lot of the time, it is an IV, an injection, and you are like, ‘What, there’s no pill?’ Well, we aspire to say, ‘Yes, we have a pill for that.’ We could make practically everything into pill form.”
Chief Executive Officer & Board Member
Biora Therapeutics
Since joining Biora as CEO, Mohanty has pushed the company to build two pill-based systemic and targeted drug delivery platforms—the BioJet and the NaviCap, respectively—with different business approaches.
The systemic platform BioJet, which can convert most large molecules—really any molecule, according to Mohanty—into a pill form, is ripe for partnerships. “Almost every company that’s got approved products has something they are trying to convert,” said Mohanty. “If you just take the top 20 pharma companies, that adds up to approximately 60 plus biologics that need and are looking for ways to convert.”
The targeting technology NaviCap, which in some ways is a little more complex and, according to Mohanty, has been met with some skepticism, has led Biora to work on partnerships and start their own drug pipeline. “The targeting technology is a little difficult for people to see where and how they would use it—they want more proof,” Mohanty explained. “For me, that means moving that further, so that would be our own program that we move forward with and take it through certain clinical steps that give you that next this is a really great way to solve that problem, and yes, you have proof that you can do that.”
Biora has moved forward along Mohanty’s two-pronged approach. Today, they list collaborations for BioJet with AstraZeneca, Ionis, and a couple of undisclosed large pharma partners. NaviCap has moved into clinical trials for delivering therapeutics directly to the site of disease, which could enable safer and more effective treatment of inflammatory bowel disease (IBD).
Swallowing a drug-delivery submarine
In the near-to-intermediate timeline, Moharty believes that the NaviCap’s localization technology is more important because success could mean getting the company beyond the next inflection point. It’s also a bit more nifty.
The NaviCap has a tiny chip on board that processes flashing lights, which activate upon pinching right before swallowing the pill. Sending out light and interpreting the receiving wavelengths provides information as to where the pill is in the anatomy depending on the size and texture of the tissue and differentiates between tissues in the gastrointestinal tract, like the esophagus, stomach, and small intestine. Biora has worked on programming the NaviCap to recognize the colon and drop a payload, and they’ve picked ulcerative colitis as the indication to go after.
“There are like 14 or 15 different drugs approved for ulcerative colitis, and yet, two-thirds of the patients have nothing,” said Mohanty. “All of the drugs that were approved were approved with something in the range of 20–30% response rate. So, there’s almost a therapeutic ceiling. We’re pushing to break that ceiling.” Mohanty believes that a key reason for this ceiling is the tradeoff between drug dose-response and toxicity. But an even more important point, according to Mohanty, is that not enough drugs (in liquid form) can even make it to the colon.
As a proof of concept, Biora is developing BT-600 (formerly PGN-600) as an orally delivered liquid formulation of tofacitinib, which is approved for ulcerative colitis but is dose-limited based on safety concerns. Biora’s preclinical data demonstrates that targeted delivery using BT-600 can lead to reduced drug levels in blood and increased levels in tissue at least 25 times higher along the length of the colon versus the equivalent standard oral dose.
Mohanty said, “The approved label for tofacitinib is 10 mg twice a day or 20 mg a day. They actually tried 15 mg twice a day, or 30 mg a day, and got a much better response. But the FDA said no way. That’s just too much toxicity. So they’re not able to give enough. With BT-600, we got better tissue and plasma numbers with just a 10-mg dose. So we can get five to six times more than what they get with 20 mg a day. We were hoping we could show this, and it looks like it can.”
If Biora moves fast and confirms its preclinical findings in ulcerative colitis patients, it could open the doors to all sorts of partnerships. Biora could move on to something like Humira, the top-selling drug for a decade, bringing in nearly $20 billion annually, until generics came on the market. Humira isn’t interesting just because it’s lucrative; it’s interesting because, according to Mohanty, studies show benefits for targeted drug delivery. “On a technical and therapeutic level, NaviCap gets us excited about solving a real problem,” said Mohanty. “But it’s probably a year or two from significant value for investors.”
Needle-free delivery in a pill
Mohanty thinks that Biora’s most immediate value to an investor is with BioJet, designed for needle-free, liquid jet delivery of large molecules. BioJet, a smaller pill with less tech than NaviCap, works somewhat similarly to the pill Rani Therapeutics developed to move through the stomach, where acids typically break down drugs, and then reach the intestine to deliver the drug via transenteric injection.
“All our IP and technology, nobody is even close,” said Mohanty. “There’s lots of people trying to do systemic delivery and making drugs orally available, and Rani is one of them. The key differences for us are that we can take your formulation, the one you put in the needle, whereas Rani has to be reformulated so they can make crystals, and so when they push it out with their balloon, they push pistols or microneedles into the tissue. We take the liquid and, with pressure, shoot liquid like a jet. That homegrown, fully owned IP for an internal liquid jet injection is what we’re basing our systemic platform on.”
According to Mohanty, Biora has data showing that BioJet makes it past the stomach and to the small intestine, where it can “inject” peptides and anti-sense oligonucleotides. The BioJet uses pH-based chemicals—a concept that precedes Biora—to protect a pill from stomach acidity, which also has an incredibly difficult lining, making it difficult to get the drug through for systemic delivery. After making it through the stomach and into the small intestine, the BioJet senses a pH change, which dissolves a trigger in the pill and engages the pressure release to shoot out the liquid cargo where it goes through the intestinal lining and into the many blood vessels that connect to organs throughout the body.
While BioJet shows 40% bioavailability compared to an IV, Mohanty insists this is a big deal, especially considering that a subcutaneous injection is about 50–60% of an IV in bioavailability. Taking a pill at home instead of injecting yourself or going to a medical center for an IV is an attractive option for many people.
Trying Biora’s smart pills
When I asked if I could see what it was like to swallow one of Biora’s pills, I didn’t get rejected—but I also didn’t get offered to do so. Instead, Mohanty relayed that several employees have swallowed the pill.
“NaviCap is a ‘healthy’ pill, and more than a hundred people have swallowed this in actual clinical trials,” said Mohanty. “We had one person who said, ‘That’s too big.’ The rest were like, ‘Yeah, whatever.’”
So, maybe, after all, there will soon be a pill for that. But will everyone want to swallow a fish oil-sized pill? Probably not. But, all things equal, if I had to choose between stabbing myself with a needle and swallowing a pill, I’d go with the latter every time.
