Lower than three years in the past, a gaggle of Canadian scientists received collectively to brainstorm a greater radiopharmaceutical. Radiation has an extended historical past in most cancers care, utilized in imaging to detect the illness in addition to in therapeutics that deal with it. Radiopharmaceuticals, therapies that ship a radioactive substance that kills most cancers cells, have seen a analysis resurgence lately as huge pharmaceutical firms and biotech startups purpose to make these therapies more practical in opposition to tumors and fewer poisonous to wholesome tissue.
The scientists, based mostly in Vancouver, British Columbia, settled upon an concept that they thought might set them aside from the rising radiopharmaceuticals area. They shaped an organization, secured some preliminary financing, after which validated their method in preclinical analysis. On Thursday, their startup, Abdera Therapeutics, revealed its science together with behind it.
Abdera, which now splits its operations between Vancouver and Menlo Park, California, happened as a thought train, mentioned Adam Decide, one of many co-founders and the startup’s senior vp of analysis. Decide’s expertise contains senior roles at Genevant Sciences and Tekmira Prescribed drugs, the place his analysis included constructing supply methods for hard-to-deliver medication. Mike Abrams, one other co-founder and a senior advisor to Abdera, has in depth expertise in radiopharmaceutical imaging brokers. The third co-founder, Lana Janes, was a enterprise associate at adMare BioInnovations, the place Abdera incubated. She is now the startup’s senior vp, operations and innovation.
The scientists tossed about varied concepts for bettering radiopharmaceuticals. Wherever the radio-particle goes within the physique is the place you’re going to see toxicity, Decide mentioned. Ideally, a radiopharmaceutical will ship as a lot of the isotope to the tumor as attainable, whereas additionally clearing out of different tissues to keep away from inflicting poisonous results. Some analysis efforts are using small molecules or peptides to focus on the supply of a radiopharmaceutical. The issue with each approaches is that the remedy is excreted via the kidneys, which ends up in poisonous results there, Decide mentioned. That toxicity drawback led the founders to show to antibodies.
Antibodies keep away from the kidneys, and the thought of utilizing an antibody for focused supply of a radioisotope has been executed efficiently. The non-Hodgkin lymphoma radiopharmaceuticals Zevalin, authorized in 2002, and Bexxar, authorized in 2003, have been each made with antibodies from mice. However regardless that these early antibody-based radiopharmaceuticals prevented the kidneys, they nonetheless triggered different negative effects. Due to their lengthy half-lives, they stayed round for a very long time in circulation, inflicting systemic toxicities, Decide mentioned. Neither Zevalin nor Bexxar was commercially profitable and each have been finally discontinued by their producers.
The Abdera scientists nonetheless appreciated the thought of working with antibodies. However reasonably than utilizing a mouse antibody or repurposing an current one, Abdera’s founders determined to start out from scratch. Abdera’s engineered antibodies behave like a standard antibody, providing related concentrating on capabilities, Decide mentioned. However at half the dimensions and half the molecular weight of a typical antibody, Abdera’s antibodies are higher capable of penetrate into stable tumors. Moreover, they don’t keep round in circulation lengthy sufficient to trigger systemic negative effects.
“Wherever the antibody goes, the isotope goes,” Decide mentioned. “The antibody drives the clearance.”
The accelerated clearance of the antibody is pushed via the liver. This method is most popular to the kidney as a result of the liver is a big organ that may deal with a big radioactive dose and clear the isotope via the intestine, Decide mentioned. Additionally, the liver is extra radioresistant than the kidney and it has the capability to regenerate if wanted.
In preclinical testing, Abdera noticed good biodistribution into the tumor, in addition to enough and speedy clearance of the remedy from tissues, Decide mentioned. The biodistribution knowledge function a constructive signal of discovering a therapeutic window, the dose vary that balances security and efficacy. The outcomes additionally present excessive uptake of remedy by a wide range of stable tumors.
Abdera 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 capable of elevate its Sequence A financing, which was led by Versant Ventures and Amplitude Ventures. Different traders within the spherical embrace Northview Ventures as effectively adMare BioInnovations and AbCellera.
Decide mentioned Abdera didn’t announce the $32.5 million Sequence A spherical on the time as a result of the startup didn’t but have a narrative to inform. The money got here earlier than the corporate had proven its expertise can work in animal testing. These knowledge got here quickly sufficient. Abdera went “from a thought train to in vivo preclinical proof of idea in 10 months,” Decide mentioned.
On the heels of attaining the important thing preclinical knowledge, the corporate was capable of elevate more cash. The $110M Sequence B spherical is new money introduced Thursday. The most recent financing was led by venBio Companions with participation from the sooner traders in addition to new ones, together with Viking International Buyers, Qiming Enterprise Companions USA and RTW Investments.
The preclinical knowledge that caught investor curiosity confirmed Abdera was capable of hit 5 most cancers targets. The startup is disclosing simply one among them: . This protein is expressed in a wide range of stable tumor varieties whereas additionally being hardly ever discovered on wholesome cells. Abdera’s lead program, ABD-147, is being developed for treating small cell lung most cancers.
Radiopharmaceuticals are seeing stronger analysis curiosity as two new Novartis therapies achieve traction out there, mentioned Abdera President & CEO Lori Lyons-Williams, a former government at . In 2018, the FDA as a remedy for sure intestine cancers. Final 12 months, the , a bladder most cancers radiopharmaceutical that Novartis added through its .
“The medical neighborhood has been extra prepared to undertake them,” she mentioned. “I believe that’s a purpose why there’s been a renaissance in radiopharmaceuticals.”
Novartis is seeking to broaden its radiopharmaceutical scope past Lutathera and Pluvicto. Final month, the pharma large paid $50 million up entrance to start out a . Among the many benefits touted by the Cambridge, U.Okay.-based biotech is kidney excretion—it avoids liver toxicity.
Bayer entered the radiopharmaceutical area with . Different radiopharmaceutical firms within the house embrace ; ; and , an organization that like Abdera, counts Versant Ventures as an investor. Enterprise capital companies normally don’t wager in opposition to their very own portfolio firms. In Abdera’s funding announcement, Joel Drewry, principal at Versant, mentioned his agency believes “Abdera’s method represents a brand new wave of innovation on this house to handle necessary most cancers targets that could be intractable to different approaches.”
Lyons-Williams joined Abdera final Might when the corporate had 9 workers. Present headcount is 30. Lyons-Williams expects so as to add 15 extra by the top of this 12 months as Abdera works towards an investigational new drug software submitting for ABD-147 in 2024.
The targets for Abdera’s 4 different packages stay undisclosed. Lyons-Williams mentioned some are targets which have medical validation however have but to result in profitable therapies with different drug modalities on account of toxicity. In different instances, the goal is one which few drug hunters are pursuing. She added that when Abdera is ready to present medical validation of its expertise, the corporate could possibly go after novel most cancers targets as effectively.
Photograph by Abdera Therapeutics