Converting injectable drugs into pills
CEO, chairman and founder: Mir Imran
Based: San Jose, California
The scoop: Tweaking biologic drugs to make them work as pills rather than injections isn’t a new idea: Oral insulin, for example, would be a game-changer for people with Type 1 diabetes who have to inject themselves with the hormone every day. But it’s easier said than done, with researchers over the years trying and failing to design pills with any kind of bioavailability.
Rani Therapeutics is taking a different tack. Instead of changing the drugs themselves, the company changed the nature of the injection. It’s working on a robotic pill, designed to travel through the esophagus and stomach into the small intestine, where the environment triggers the inflation of a small balloon that drives drug-loaded needles into the intestinal wall.
What makes Rani Therapeutics fierce: The company grew out of InCube Labs, the research laboratory CEO Mir Imran set up to address “major clinical needs.” Given Imran’s background in medicine and engineering, InCube’s projects focused mostly on device-based treatments, implantable devices and the like.
“I was not even thinking about doing anything in the oral delivery of biologics,” says Imran. But a passing comment from a pharma executive piqued his interest.
“[The company] had made an investment in a biotech company trying to convert one peptide drug into a pill and they had just shut down. I asked them, 'What was the problem? Why did they fail?'” he says. “They couldn’t get the oral bioavailability of the drug past a fraction of a percent.”
To avoid the pitfalls of his predecessors, Imran dug into his engineering and materials science know-how—as well as his experience in medicine—to design a treatment with the convenience of a pill but the efficacy of an injection.
It took about three years.
The result is a capsule made mostly of ingestible materials, including resorbable, drug-loaded needles that dissolve once they've delivered their payload into the intestinal wall and a (non-ingestible) balloon that inflates to push the needles into the wall of the intestine. It’s an ideal injection site because the intestinal walls don’t have nerve receptors for sharp pains like in the skin, so the patient doesn’t feel the prick.
To bypass the stomach, where biologics are typically broken down and digested before they reach their intended destination, the RaniPill has a coating that is pH sensitive. It keeps the pill safe in the highly acidic stomach environment but dissolves in the small intestine, where the pH is closer to neutral. Once the coating dissolves, the capsule is exposed to moisture in the small intestine, which triggers a reaction that inflates the balloon. This way, the pill doesn’t need “springs, motors, or electronic gadgets” that might not be ingestible and could jack up the price and complexity of the device.
The RaniPill has an optional feature that tracks not just that the patient has taken the pill but that the mechanism has successfully injected the drug. The wireless sensor could be useful in clinical trials, as well as in boosting patient adherence in real life, Imran says.
After testing the pill’s ability to deliver drugs in more than 100 animal studies, Rani wrapped up its first-in-human study in early 2019. The results showed that patients who swallowed a drug-free version of the capsule did not feel it inflating or injecting and did not experience any side effects.
One year later, in January 2020, the company reported success from the first study testing the pill’s ability to deliver octreotide, a hormone used to treat acromegaly and neuroendocrine tumors. The data showed the bioavailability of octreotide had reached more than 70%.
Over the coming year, Rani has three objectives: It will continue testing the RaniPill’s safety and efficacy, improve its manufacturing processes and push forward some partnered programs, as well as its own development efforts.
“This year, we want to scale [manufacturing] up so it can support clinical studies and do some investment in semiautomatic processes,” Imran says. The goal is to eventually fully automate pill production.
“Our third objective is to work with our partners, Takeda and Novartis, taking their models forward, testing them in animal models and supporting those partners,” he says. “We are also in discussions with other partners that we may add. And we have our own internal pipeline of off-patent drugs; we are going to continue to develop those.”
Investors: The company's $53 million round in February 2018 was backed by China’s GeneScience Pharmaceuticals and Shire, along with Bossa Ventures and Cathay Venture. Previous investors include GV, Novartis, AstraZeneca and Ping An Ventures.