Focused therapies and immunotherapies provide new therapy choices for extra kinds of most cancers, however these medicine are much less useful when tumors produce a number of copies of a gene. This gene amplification contributes to drug resistance. Boundless Bio’s analysis into what drives this phenomenon has yielded new understanding of most cancers biology. The corporate now has $100 million in IPO money to help two packages in early medical improvement and extra in its pipeline.
Boundless Bio late Wednesday priced its providing of 6.25 million shares at $16 every, which was the midpoint of the preliminary $15 to $17 worth vary the San Diego-based firm set final week. These shares will commerce on the Nasdaq beneath the inventory image “BOLD.”
The analysis of Boundless Bio focuses on extrachromosomal DNA, or ecDNA. These circle-shaped models of DNA aren’t current in wholesome cells however they’re discovered floating inside some most cancers cells, the place they’re a main driver of gene amplification, the corporate mentioned in its IPO submitting. The ecDNA permits resistance to a focused remedy by switching amplification to a unique gene that’s not focused by the drug. Amplification of a mutant cancer-driving gene can even spark resistance to therapies focusing on that mutation. However ecDNA-enabled resistance just isn’t restricted to focused therapies. It may additionally allow resistance to chemotherapy, the corporate mentioned within the submitting.
Slightly than focusing on proteins produced by amplified oncogenes the way in which that focused most cancers therapies do, Boundless Bio goals to intrude with a most cancers cell’s potential to make use of ecDNA. Boundless Bio’s proprietary platform expertise, Spyglass, identifies druggable targets which are important to ecDNA formation and performance. The corporate hits these targets with ecDNA-directed therapeutic candidates, or ecDtx for brief. These small molecules work by exploiting mobile vulnerabilities of ecDNA-enabled cancers.
“Accordingly, our ecDTx are designed to preferentially kill ecDNA-bearing most cancers cells, however not wholesome cells with out ecDNA,” Boundless Bio mentioned within the submitting. “They’re engineered to disrupt the underlying mobile equipment that permits ecDNA to perform correctly, equivalent to proteins important for ecDNA replication, transcription, meeting, restore, and segregation.”
Boundless Bio’s lead drug candidate, BBI-355, targets checkpoint kinase 1 (CHK1), an enzyme that manages ecDNA replication and transcription in most cancers cells. There aren’t any FDA-approved CHK1 inhibitors, however Acrivon Therapeutics is in Part 2 testing with a CHK1 and CHK2 inhibitor licensed from Eli Lilly. That drug is run intravenously. Boundless Bio’s CHK1 inhibitor is an oral drug. A Part 1/2 check is underway in sufferers with oncogene-amplified cancers and preliminary proof-of-concept information are anticipated within the second half of this yr. Preclinical information can be offered subsequent week throughout the American Affiliation for Most cancers Analysis annual assembly in San Diego.
A second program, BBI-825, is designed to dam ribonucleotide reductase (RNR), an enzyme that Boundless Bio says is crucial for ecDNA meeting and restore in most cancers cells. Final month, the corporate started a Part 1/2 check of this drug; preliminary information are anticipated within the second half of 2025. A 3rd Boundless Bio program targets a beforehand undrugged kinesin protein that the corporate says is crucial for ecDNA throughout cell division. An investigational new drug utility is predicted within the first half of 2026.
Gene amplification has been noticed in additional than 14% of most cancers sufferers, in keeping with Boundless Bio. The corporate has developed a diagnostic to determine sufferers amenable to therapy with an ecDNA-directed drug. Within the IPO submitting, the corporate mentioned it’s working with an in vitro diagnostic firm to develop this check right into a medical trial assay for the lead program’s medical trial.
Boundless Bio’s method is predicated on the analysis of scientific founder Paul Mischel, who’s now a Stanford College pathology professor. The corporate was based in 2018 by Arch Enterprise Companions and is led by CEO Zach Hornby, a former govt at Ignyta, a most cancers drug developer that was acquired by Roche in 2017. Mischel is chairman of Boundless Bio’s scientific advisory board.
Previous to the IPO, Boundless Bio had raised $252.1 million, in keeping with the submitting. The newest financing was a $100 million Sequence C spherical final Could co-led by Leaps by Bayer and RA Capital Administration. The submitting reveals that Arch is Boundless Bio’s largest shareholder with an 11.2% post-IPO stake, adopted by the ten.6% of the corporate owned by Constancy and the 8.4% owned by RA Capital. Bayer’s post-IPO stake is 6.6%.
As of the tip of 2023, Boundless Bio reported having $120.7 million in money, money equivalents, and short-term investments. The corporate mentioned within the submitting that it plans to use $22 million of the IPO proceeds towards the medical improvement of lead program BBI-355. One other $29 million is budgeted for the event of BBI-825. Boundless Bio plans to spend $24 million on the R&D of different ecDNA-directed drug candidates, together with the development of a 3rd program into human testing. The brand new capital can even help ongoing work on the diagnostic check and the Spyglass platform.
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