Abdera Comes Out Of Stealth With Radiopharmaceutical-Specialized Antibody Approach
Executive Summary
The company has sought to develop antibodies purpose-built for delivering radiotherapy rather than repurposing existing antibodies for that purpose, as some other players have done.
Abdera Therapeutics Inc.’s approach for breaking into what it estimates is a $30bn market for radiopharmaceuticals centers around developing antibodies specifically designed to carry radioisotopes to a tumor, by which it hopes to avoid some of the pitfalls that previous efforts have fallen into.
The company came out of stealth mode with the 20 April announcement that it has raised $142m in combined series A and series B venture capital, which will fund the development of programs using its ROVEr antibody engineering platform technology. The company raised $32m in a series A round in 2021, while still in stealth, followed by a new $110m series B round.
“There’s a lot happening in radiopharmaceuticals right now,” CEO Lori Lyons-Williams told Scrip. “There’s been a lot of acquisitions, there have been recent launches, and the market is expected to be about $30bn in the next decade or so.”
Novartis AG, for example, has successfully brought two radioligand therapies to market recently, with demand for Pluvicto (lutetium Lu 177 vipivotide tetraxetan) in prostate cancer outpacing supply. (Also see "Radioligands Advance Radiotherapy Premise With Greater Precision" - In Vivo, 11 Aug, 2022.)
Abdera’s lead program is ABD-147, a DLL3-targeting therapy that is in late investigational new drug (IND) application-enabling studies as a candidate for small cell lung cancer, and the company plans to file its IND in 2024. There are four additional programs in preclinical development with undisclosed targets, though Lyons-Williams said the company is focusing on solid tumors. She added that Abdera’s pipeline programs do not include PSMA or somatostatin as targets, as many other radiopharmaceutical developers’ pipelines do.
Versant Ventures and Amplitude Ventures led the series A round, with Northview Ventures and founding partners of Abdera, adMare BioInnovations and AbCellera participating. VenBio Partners led the series B round, with existing investors participating along with new investors such as Viking Global Investors, Qiming Venture Partners USA and RTW Investments.
Antibodies Purpose-Built For Radiotherapy
While a large number of antibody-drug conjugates (ADCs) have already hit the market, radioisotopes conjugated to antibodies have been further behind in development. Abdera’s co-founder and senior vice president for research, Adam Judge, said the company has sought to succeed where others have failed by developing its antibodies in-house rather than attempting – as others have – to conjugate radioisotopes to existing antibodies.
“I think what sort of distinguishes us from companies that have gone before us in this space is that we set out to build the antibody as sort of purpose-built for the radiotherapy, so making sure we engineered into the antibody the basic requirements in terms of its pharmacokinetics and distribution in the body,” he told Scrip. “A lot of the work before us has been trying to use antibodies that have been developed for other purposes and then attaching an isotope to it and hoping that it will work better.”
He said the design enables Abdera to choose from a variety of radioisotopes, whether therapeutic isotopes such as Lutetium-177 or Actinium-225, or an imaging isotope such as Indium-111.
Another reason for taking an antibody approach is that while other approaches have involved leveraging small molecules or peptides, those tend to be metabolized in the kidney, which is radiosensitive, thus making toxicity a limiting factor and narrowing the potential therapeutic index, Lyons-Williams said. By contrast, antibodies are larger and thus aren’t metabolized in the kidney.
Judge added that Abdera is using a “small-format” antibody of about half the molecular weight of other antibodies.
“We think that offers some potential advantages in terms of tissue penetration and penetration deep into solid tumors,” he said.
Mixed Results For Radioisotope Conjugates To Date
Various biopharma firms have sought to employ the approach of conjugating radioisotopes to monoclonal antibodies.
Actinium Pharmaceuticals, Inc. has said it plans to file for US Food and Drug Administration approval of its radiotherapy-drug conjugate, Iomab-B, in acute myeloid leukemia in the second half of 2023, following positive results in late 2022 from its Phase III trial. (Also see "Actinium Seeks to Disrupt As Radioligand Candidate Succeeds In Pivotal Pre-Transplant AML Trial" - Scrip, 31 Oct, 2022.)
Others have not been so successful, however, such as Nordic Nanovector ASA, whose Betalutin (177Lu lilotomab satetraxetan) was in development for follicular lymphoma. The program was discontinued following a negative interim analysis. (Also see "Nordic Nanovector To Restructure After Discontinuing Lymphoma Trial" - Scrip, 7 Jul, 2022.)