Targeted therapies and immunotherapies offer new treatment options for more types of cancer, but these drugs are less helpful when tumors produce multiple copies of a gene. This gene amplification contributes to drug resistance. Boundless Bio’s research into what drives this phenomenon has yielded new understanding of cancer biology. The company now has $100 million in IPO cash to support two programs in early clinical development and more in its pipeline.
Boundless Bio late Wednesday priced its offering of 6.25 million shares at $16 each, which was the midpoint of the preliminary $15 to $17 price range the San Diego-based company set last week. Those shares will trade on the Nasdaq under the stock symbol “BOLD.”
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The research of Boundless Bio focuses on extrachromosomal DNA, or ecDNA. These circle-shaped units of DNA aren’t present in healthy cells but they are found floating inside some cancer cells, where they are a primary driver of gene amplification, the company said in its IPO filing. The ecDNA enables resistance to a targeted therapy by switching amplification to a different gene that’s not targeted by the drug. Amplification of a mutant cancer-driving gene can also spark resistance to therapies targeting that mutation. But ecDNA-enabled resistance is not limited to targeted therapies. It can also enable resistance to chemotherapy, the company said in the filing.
Rather than targeting proteins produced by amplified oncogenes the way that targeted cancer therapies do, Boundless Bio aims to interfere with a cancer cell’s ability to use ecDNA. Boundless Bio’s proprietary platform technology, Spyglass, identifies druggable targets that are essential to ecDNA formation and function. The company hits those targets with ecDNA-directed therapeutic candidates, or ecDtx for short. These small molecules work by exploiting cellular vulnerabilities of ecDNA-enabled cancers.
“Accordingly, our ecDTx are designed to preferentially kill ecDNA-bearing cancer cells, but not healthy cells without ecDNA,” Boundless Bio said in the filing. “They are engineered to disrupt the underlying cellular machinery that enables ecDNA to function properly, such as proteins essential for ecDNA replication, transcription, assembly, repair, and segregation.”
Boundless Bio’s lead drug candidate, BBI-355, targets checkpoint kinase 1 (CHK1), an enzyme that manages ecDNA replication and transcription in cancer cells. There are no FDA-approved CHK1 inhibitors, but Acrivon Therapeutics is in Phase 2 testing with a CHK1 and CHK2 inhibitor licensed from Eli Lilly. That drug is administered intravenously. Boundless Bio’s CHK1 inhibitor is an oral drug. A Phase 1/2 test is underway in patients with oncogene-amplified cancers and preliminary proof-of-concept data are expected in the second half of this year. Preclinical data will be presented next week during the American Association for Cancer Research annual meeting in San Diego.
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A second program, BBI-825, is designed to block ribonucleotide reductase (RNR), an enzyme that Boundless Bio says is essential for ecDNA assembly and repair in cancer cells. Last month, the company began a Phase 1/2 test of this drug; preliminary data are expected in the second half of 2025. A third Boundless Bio program targets a previously undrugged kinesin protein that the company says is essential for ecDNA during cell division. An investigational new drug application is expected in the first half of 2026.
Gene amplification has been observed in more than 14% of cancer patients, according to Boundless Bio. The company has developed a diagnostic to identify patients amenable to treatment with an ecDNA-directed drug. In the IPO filing, the company said it is working with an in vitro diagnostic company to develop this test into a clinical trial assay for the lead program’s clinical trial.
Boundless Bio’s approach is based on the research of scientific founder Paul Mischel, who is now a Stanford University pathology professor. The company was founded in 2018 by Arch Venture Partners and is led by CEO Zach Hornby, a former executive at Ignyta, a cancer drug developer that was acquired by Roche in 2017. Mischel is chairman of Boundless Bio’s scientific advisory board.
Prior to the IPO, Boundless Bio had raised $252.1 million, according to the filing. The most recent financing was a $100 million Series C round last May co-led by Leaps by Bayer and RA Capital Management. The filing shows that Arch is Boundless Bio’s largest shareholder with an 11.2% post-IPO stake, followed by the 10.6% of the company owned by Fidelity and the 8.4% owned by RA Capital. Bayer’s post-IPO stake is 6.6%.
As of the end of 2023, Boundless Bio reported having $120.7 million in cash, cash equivalents, and short-term investments. The company said in the filing that it plans to apply $22 million of the IPO proceeds toward the clinical development of lead program BBI-355. Another $29 million is budgeted for the development of BBI-825. Boundless Bio plans to spend $24 million on the R&D of other ecDNA-directed drug candidates, including the advancement of a third program into human testing. The new capital will also support ongoing work on the diagnostic test and the Spyglass platform.
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