Less than three years ago, a group of Canadian scientists got together to brainstorm a better radiopharmaceutical. Radiation has a long history in cancer care, used in imaging to detect the disease as well as in therapeutics that treat it. Radiopharmaceuticals, therapies that deliver a radioactive substance that kills cancer cells, have seen a research resurgence in recent years as big pharmaceutical companies and biotech startups aim to make these therapies more effective against tumors and less toxic to healthy tissue.

The scientists, based in Vancouver, British Columbia, settled upon an idea that they thought could set them apart from the growing radiopharmaceuticals field. They formed a company, secured some initial financing, and then validated their approach in preclinical research. On Thursday, their startup, Abdera Therapeutics, revealed its science along with $142 million in financing behind it.

Abdera, which now splits its operations between Vancouver and Menlo Park, California, came about as a thought exercise, said Adam Judge, one of the co-founders and the startup’s senior vice president of research. Judge’s experience includes senior roles at Genevant Sciences and Tekmira Pharmaceuticals, where his research included building delivery systems for hard-to-deliver drugs. Mike Abrams, another co-founder and a senior advisor to Abdera, has extensive experience in radiopharmaceutical imaging agents. The third co-founder, Lana Janes, was a venture partner at adMare BioInnovations, where Abdera incubated. She is now the startup’s senior vice president, operations and innovation.

The scientists tossed about various ideas for improving radiopharmaceuticals. Wherever the radio-particle goes in the body is where you’re going to see toxicity, Judge said. Ideally, a radiopharmaceutical will deliver as much of the isotope to the tumor as possible, while also clearing out of other tissues to avoid causing toxic effects. Some research efforts are employing small molecules or peptides to target the delivery of a radiopharmaceutical. The problem with both approaches is that the therapy is excreted through the kidneys, which leads to toxic effects there, Judge said. That toxicity problem led the founders to turn to antibodies.

Antibodies avoid the kidneys, and the idea of using an antibody for targeted delivery of a radioisotope has been done successfully. The non-Hodgkin lymphoma radiopharmaceuticals Zevalin, approved in 2002, and Bexxar, approved in 2003, were both made with antibodies from mice. But even though these early antibody-based radiopharmaceuticals avoided the kidneys, they still caused other side effects. Because of their long half-lives, they stayed around for a long time in circulation, causing systemic toxicities, Judge said. Neither Zevalin nor Bexxar was commercially successful and both were eventually discontinued by their manufacturers.

The Abdera scientists still liked the idea of working with antibodies. But rather than using a mouse antibody or repurposing an existing one, Abdera’s founders decided to start from scratch. Abdera’s engineered antibodies behave like a conventional antibody, offering similar targeting capabilities, Judge said. But at half the size and half the molecular weight of a typical antibody, Abdera’s antibodies are better able to penetrate into solid tumors. Furthermore, they don’t stay around in circulation long enough to cause systemic side effects.

“Wherever the antibody goes, the isotope goes,” Judge said. “The antibody drives the clearance.”

The accelerated clearance of the antibody is driven through the liver. This approach is preferred to the kidney because the liver is a large organ that can handle a large radioactive dose and clear the isotope through the gut, Judge said. Also, the liver is more radioresistant than the kidney and it has the capacity to regenerate if needed.

In preclinical testing, Abdera saw good biodistribution into the tumor, as well as adequate and rapid clearance of the therapy from tissues, Judge said. The biodistribution data serve as a positive sign of finding a therapeutic window, the dose range that balances safety and efficacy. The results also show high uptake of therapy by a variety of solid tumors.

Abdera launched in early 2021 backed by 8 million Canadian dollars in seed financing from adMare BioInnovations and AbCellera Biologics, a Vancouver-based antibody developer. In mid-2021, the startup was able to raise its Series A financing, which was led by Versant Ventures and Amplitude Ventures. Other investors in the round include Northview Ventures as well adMare BioInnovations and AbCellera.

Judge said Abdera didn’t announce the $32.5 million Series A round at the time because the startup did not yet have a story to tell. The cash came before the company had shown its technology can work in animal testing. Those data came soon enough. Abdera went “from a thought exercise to in vivo preclinical proof of concept in 10 months,” Judge said.

On the heels of achieving the key preclinical data, the company was able to raise more money. The $110M Series B round is new cash announced Thursday. The latest financing was led by venBio Partners with participation from the earlier investors as well as new ones, including Viking Global Investors, Qiming Venture Partners USA and RTW Investments.

The preclinical data that caught investor interest showed Abdera was able to hit five cancer targets. The startup is disclosing just one of them: Delta-like ligand 3, or DLL3. This protein is expressed in a variety of solid tumor types while also being rarely found on healthy cells. Abdera’s lead program, ABD-147, is being developed for treating small cell lung cancer.

Radiopharmaceuticals are seeing stronger research interest as two new Novartis therapies gain traction in the market, said Abdera President & CEO Lori Lyons-Williams, a former executive at neuroscience drug startup Neumora. In 2018, the FDA approved Novartis’s Lutathera as a treatment for certain gut cancers. Last year, the FDA approved Pluvicto, a bladder cancer radiopharmaceutical that Novartis added via its $2.1 billion acquisition of Endocyte.

“The medical community has been more willing to adopt them,” she said. “I think that’s a reason why there’s been a renaissance in radiopharmaceuticals.”

Novartis is looking to expand its radiopharmaceutical scope beyond Lutathera and Pluvicto. Last month, the pharma giant paid $50 million up front to start a partnership focused on developing new radiopharmaceuticals based on the peptide technology of Bicycle Therapeutics. Among the advantages touted by the Cambridge, U.K.-based biotech is kidney excretion—it avoids liver toxicity.

Bayer entered the radiopharmaceutical field with 2021 acquisitions of Noria Therapeutics and PSMA Therapeutics. Other radiopharmaceutical companies in the space include Aktis Oncology, a startup with financial backing from Novartis and Bristol Myers Squibb; Mariana Oncology, a startup that emerged from stealth in 2021 as Curie Therapeutics; and RayzeBio, a company that like Abdera, counts Versant Ventures as an investor. Venture capital firms usually don’t bet against their own portfolio companies. In Abdera’s funding announcement, Joel Drewry, principal at Versant, said his firm believes “Abdera’s approach represents a new wave of innovation in this space to address important cancer targets that may be intractable to other approaches.”

Lyons-Williams joined Abdera last May when the company had nine employees. Current headcount is 30. Lyons-Williams expects to add 15 more by the end of this year as Abdera works toward an investigational new drug application filing for ABD-147 in 2024.

The targets for Abdera’s four other programs remain undisclosed. Lyons-Williams said some are targets that have clinical validation but have yet to lead to successful therapies with other drug modalities due to toxicity. In other cases, the target is one that few drug hunters are pursuing. She added that once Abdera is able to show clinical validation of its technology, the company may be able to go after novel cancer targets as well.

Photo by Abdera Therapeutics