BBOT Announces Publication in Cancer Discovery Highlighting Preclinical Data Demonstrating BBO-11818 is a Potent and Selective panKRAS Inhibitor

Rhea-AI Summary

BridgeBio Oncology Therapeutics (Nasdaq: BBOT) announced publication in Cancer Discovery of preclinical data for BBO-11818, a non‑covalent, orally bioavailable panKRAS inhibitor that binds KRAS in both ON and OFF states and shows activity across KRASG12D, G12V, and G12C mutants.

Key facts: >500‑fold selectivity for KRAS over other RAS isoforms, robust monotherapy tumor inhibition in preclinical models across colorectal, pancreatic, and lung cancers, and a confirmed partial response (56% tumor reduction) in the ongoing Phase 1 KONQUER‑101 trial. Additional clinical data and an internal combination with BBO‑10203 are expected later in 2026.

Positive

• Publication in Cancer Discovery indicates peer‑reviewed preclinical validation
• >500‑fold selectivity for KRAS over HRAS/NRAS reported in preclinical assays
• Activity across multiple KRAS mutants (G12D, G12V, G12C) in vitro and in vivo
• Confirmed Phase 1 partial response with 56% tumor reduction in PDAC patient
• Planned internal combination study with BBO‑10203 expected later in 2026

Negative

• Clinical evidence remains limited to early Phase 1 data; broader efficacy and safety not yet established
• Additional clinical readouts are pending in the second half of 2026, creating short‑term data risk
• Preclinical potency and selectivity do not guarantee clinical success or regulatory approval

Key Figures

Tumor reduction: 56% tumor reduction Objective response rate: 65% ORR (11/17) 6-month PFS: 66% 6-month PFS +5 more

8 metrics

Tumor reduction 56% tumor reduction Confirmed partial response in PDAC patient in BBO-11818 Phase 1 KONQUER-101

Objective response rate 65% ORR (11/17) BBO-8520 monotherapy in KRASG12C NSCLC (data cutoff Nov 15, 2025)

6-month PFS 66% 6-month PFS BBO-8520 monotherapy in KRASG12C NSCLC

Selectivity over other RAS >500-fold selectivity BBO-11818 selectivity for KRAS over other RAS isoforms in preclinical data

Dose level 500 mg QD Selected expansion dose for BBO-10203 in earlier data

Shares registered 63,054,549 shares Common Stock registered for resale under 424B3 prospectus supplement

Shares outstanding 80,032,823 shares Shares outstanding as of March 2, 2026 in Form 10-K

Year-end cash $425.5 million Cash, cash equivalents and marketable securities at end of 2025 (8-K)

Market Reality Check

Price: $9.92 Vol: Volume 141,539 is below t...

low vol

$9.92 Last Close

Volume Volume 141,539 is below the 20-day average of 299,339 (relative volume 0.47x), suggesting a subdued pre-news session. low

Technical Shares at $9.92 are trading below the 200-day MA of $11.45, after a -2.75% move in the prior session.

Peers on Argus

Within Biotechnology, several peers showed notable declines pre-news: AVXL -4.5%...

1 Up

Within Biotechnology, several peers showed notable declines pre-news: AVXL -4.5%, GERN -2.74%, IMNM -4.82%, IVA -2.42%, PRAX -2.88%. Momentum scanners only flagged GERN with an +8.80% upside move at one point, indicating mixed, stock-specific activity rather than a uniform sector rotation.

Historical Context

5 past events · Latest: Feb 12 (Neutral)

Pattern 5 events

Date	Event	Sentiment	Move	Catalyst
Feb 12	Conference participation	Neutral	-1.5%	Management participation in two investor healthcare conferences with webcast access.
Feb 11	Inducement grants	Neutral	-5.2%	Stock-option inducement awards to new hires under 2025 Inducement Plan.
Jan 13	Inducement grant	Neutral	+4.6%	Inducement stock options for a December 2025 hire under Inducement Plan.
Jan 07	Clinical data update	Positive	+4.4%	Preliminary Phase 1 safety and antitumor data across three RAS/PI3Kα programs.
Dec 16	Conference presentation	Neutral	-3.5%	Planned presentation at the 44th Annual J.P. Morgan Healthcare Conference.

Pattern Detected

Recent history shows stronger positive reactions to clinical data updates, while routine corporate items like conferences and inducement grants have often coincided with mild or negative moves.

Recent Company History

Over the last several months, BBOT’s newsflow has alternated between pipeline progress and corporate housekeeping. Clinical data on its three RAS/PI3Kα programs on Jan 7, 2026 was followed by a positive move, highlighting investor focus on efficacy signals such as BBO-11818’s 56% tumor reduction in PDAC. By contrast, conference participation and inducement option grants in Dec 2025–Feb 2026 were met with modest to negative reactions. Today’s preclinical and early clinical update on BBO-11818 extends this sequence of RAS-pathway–focused milestones.

Market Pulse Summary

This announcement highlights expanded preclinical and early clinical evidence that BBO-11818 is a po...

Analysis

This announcement highlights expanded preclinical and early clinical evidence that BBO-11818 is a potent, selective panKRAS inhibitor with activity across KRAS mutants, including a confirmed PDAC partial response showing a 56% tumor reduction. It builds on prior multi-program updates from Jan 7, 2026 and detailed risk disclosures in recent SEC filings. Investors may focus on upcoming Phase 1 readouts in the second half of 2026 and how BBOT deploys its $425.5 million year-end cash to advance combinations with BBO-10203.

Key Terms

krasg12c, immune checkpoint inhibitors, phase 1, partial response

4 terms

krasg12c medical

"including KRASG12D, KRASG12V, and KRASG12C, with high selectivity for KRAS"

KRAS G12C is a specific genetic change in the KRAS gene where one building block of the gene is swapped, causing a protein to stay stuck in an “on” position that drives some cancers to grow. It matters to investors because medicines that specifically block this faulty protein can change treatment choices, patient outcomes, and revenue prospects for drug developers—similar to fixing a stuck switch that controls a machine’s behavior.

immune checkpoint inhibitors medical

"demonstrated strong combination potential with immune checkpoint inhibitors, anti-EGFR antibodies"

Drugs that release the immune system’s natural “brakes,” allowing immune cells to recognize and attack cancer cells; imagine taking the safety off a guard dog so it can chase intruders. They matter to investors because they can become high-value treatments with large sales potential, but their commercial success depends on clinical trial results, regulatory approval, competition and side-effect management, which all affect a company’s valuation.

phase 1 medical

"BBO-11818 is currently being evaluated in the Phase 1 KONQUER-101 trial"

Phase 1 is the first stage of testing a new drug or medical treatment in people, focused primarily on safety, how the body handles the product, and finding a tolerated dose. Think of it as a short, tightly controlled experiment with a small group to check for dangerous side effects before wider testing; for investors it is an early milestone that reduces some uncertainty but still carries high risk and potential for both big value changes and setbacks.

partial response medical

"including a confirmed partial response in a patient with pancreatic ductal adenocarcinoma"

A partial response is a clinical outcome where a treatment produces a clear, measurable improvement in a disease — for example a substantial shrinkage of a tumor or reduction in symptom measures — but does not eliminate the disease entirely. For investors it signals meaningful efficacy that can support regulatory progress, further trials, or commercial potential, like seeing a product gain market traction even though it hasn’t achieved a complete cure.

AI-generated analysis. Not financial advice.

BBO-11818 is a selective, orally bioavailable non-covalent inhibitor that targets KRAS in both the ON and OFF states, has high selectivity over HRAS and NRAS, and displays strong activity in KRAS mutant preclinical models, including KRAS^G12D and KRAS^G12V

BBO-11818 showed significant tumor growth inhibition across multiple tumor types in preclinical models and demonstrated enhanced efficacy in combination with other anti-tumor agents, including BBO-10203, BBOT’s selective RAS:PI3Kα breaker

Preliminary clinical data from the BBO-11818 Phase 1 KONQUER-101 trial showed encouraging anti-tumor activities and differentiated safety, with additional data expected in the second half of 2026; internal combination with BBO-10203 is anticipated to open later in 2026

SOUTH SAN FRANCISCO, Calif., March 06, 2026 (GLOBE NEWSWIRE) -- BridgeBio Oncology Therapeutics, Inc. (“BBOT”) (Nasdaq: BBOT), a clinical-stage biopharmaceutical company focused on RAS-pathway malignancies, today announced the publication of preclinical data describing the discovery and characterization of BBO-11818, a panKRAS inhibitor targeting KRAS in both the ON and OFF states, with significant therapeutic potential for patients with KRAS mutant cancers. The publication, titled “Discovery of BBO-11818, a Potent and Selective Non-covalent Inhibitor of (ON) and (OFF) KRAS with Activity Against Multiple Oncogenic Mutants” was published in the peer-reviewed journal Cancer Discovery, a journal of the American Association for Cancer Research’s (AACR).

“While advances with current KRAS^G12C inhibitors have shown promising clinical efficacy, there are currently no approved targeted therapies for most clinically significant KRAS mutants, including KRAS^G12D and KRAS^G12V,” said Pedro J. Beltran, PhD, Chief Scientific Officer of BBOT. “To address this significant unmet need, we developed BBO-11818 as a potent panKRAS inhibitor with strong binding affinity for KRAS and broad selectivity over HRAS and NRAS, designed to achieve high levels of KRAS inhibition in both the ON and OFF states. BBO-11818 has the potential to be used as a monotherapy treatment, or in combination with standard-of-care therapies, as well as with our RAS:PI3Kα breaker, BBO-10203. These preclinical data underscore the strength of our platform and highlight the promise of BBO-11818 as a foundational therapy that could meaningfully reshape the treatment landscape for KRAS driven tumors.”

The preclinical findings in this publication highlight the key properties BBO-11818 and its potential to address critical limitations associated with other compounds targeting mutant KRAS. Unlike several existing inhibitors that primarily target the inactive GDP-bound state, BBO-11818 potently binds and inhibits KRAS in both its ON and OFF states, as demonstrated through structural analysis, surface plasmon resonance, and functional assays. By targeting the active state of KRAS, BBO-11818 may overcome a critical resistance mechanism observed with current KRAS inhibitors, in which tumors upregulate KRAS expression or activate upstream signaling to sustain pathway activation.

Data demonstrate potent activity against multiple clinically relevant KRAS mutants, including KRAS^G12D, KRAS^G12V, and KRAS^G12C, with high selectivity for KRAS, exhibiting >500-fold selectivity over other RAS isoforms. BBO-11818’s activity across a broad range of KRAS mutants is designed to help prevent the emergence of resistance driven by secondary activating KRAS mutations that can limit the efficacy of allele-specific inhibitors. In addition, its high specificity for KRAS may support improved tolerability and greater potential for combination with other therapeutic agents. Monotherapy studies show robust anti-tumor activity across multiple in vitro and in vivo models of KRAS mutant solid tumors, including colorectal, pancreatic, and lung cancers. BBO-11818 also demonstrated strong combination potential with immune checkpoint inhibitors, anti-EGFR antibodies, and BBO-10203, the company’s RAS:PI3Kα breaker compound.

“The discovery and development of BBO-11818 reflect the exceptional collaboration between the BBOT team and our colleagues at Frederick National Lab,” said Frank McCormick, PhD, FRS, BBOT Board Director, Advisor to the National Cancer Institute’s RAS Initiative at Frederick National Laboratory for Cancer Research, and Professor of Tumor Biology and Cancer Research at UCSF. “We are incredibly proud of what we’ve accomplished together and are hopeful that our collective efforts will ultimately lead to meaningful improvements in patient outcomes.”

BBO-11818 is currently being evaluated in the Phase 1 KONQUER-101 trial (NCT06917079) in subjects with locally advanced unresectable or metastatic KRAS mutant solid tumors. Initial Phase 1 monotherapy data were announced in January 2026, demonstrating encouraging early anti-tumor activity across dose levels and tumor types, including a confirmed partial response in a patient with pancreatic ductal adenocarcinoma (PDAC) with a 56% tumor reduction. The company plans to provide additional data updates in the second half of 2026 and to study the combination of BBO-11818 with BBO-10203 later in 2026.

The discovery and preclinical characterization of BBO-11818 is the result of a collaborative effort between BBOT, the RAS Initiative at Frederick National Laboratory, and Lawrence Livermore National Laboratory.

About BBO-11818
BBO-11818 is a selective, orally bioavailable non-covalent inhibitor that targets KRAS in both the ON and OFF states, has high selectivity over HRAS and NRAS, and displays strong activity in KRAS mutant preclinical models, including KRAS^G12D and KRAS^G12V. In addition, it potently suppresses MAPK signaling and inhibiting cell proliferation in KRAS mutant cell lines. BBO-11818 is currently being evaluated in the Phase 1 KONQUER-101 trial in subjects with locally advanced unresectable or metastatic KRAS mutant solid tumors.

About BBOT
BBOT is a clinical-stage biopharmaceutical company advancing a next-generation pipeline of novel small molecule therapeutics targeting RAS and PI3Kα malignancies. BBOT has the goal of improving outcomes for patients with cancers driven by the two most prevalent oncogenes in human tumors. For more information, please visit www.bbotx.com and follow us on LinkedIn.

Forward-Looking Statements
This press release contains forward-looking statements within the meaning of the U.S. Private Securities Litigation Reform Act of 1995, as amended, and other federal securities laws. Any statements in this press release that are not historical facts may be deemed forward-looking statements,  which generally are accompanied by words such as “believe,” “may,” “will,” “estimate,” “continue,” “anticipate,” “intend,” “expect,” “should,” “would,” “plan,” “predict,” “potential,” “seem,” “seek,” “future,” “outlook” and similar expressions that predict or indicate future events or trends. These statements are based on various assumptions, whether or not identified in this press release, and are the current expectations of BBOT’s management and are not predictions of actual performance. Many actual events and circumstances are beyond the control of BBOT. These forward-looking statements are subject to a number of risks and uncertainties, including changes in domestic and foreign business, market, financial, political, and legal conditions; risks relating to the uncertainty of the projected financial information with respect to BBOT; risks related to the approval of BBOT’s product candidates and the timing of expected regulatory and business milestones, including the progress of enrollment in clinical trials and availability of data from ongoing and planned clinical trials; the impact of competitive products; risks relating to BBOT’s ability to obtain sufficient supply of materials; and those factors discussed in documents BBOT has filed or will file with the U.S. Securities and Exchange Commission.

In addition, forward-looking statements reflect BBOT’s expectations, plans, or forecasts of future events and views as of the date of this press release and are qualified in their entirety by reference to the cautionary statements herein. BBOT anticipates that subsequent events and developments will cause BBOT’s assessments to change. These forward-looking statements should not be relied upon as any guarantee, assurance, prediction or definitive statement of fact or probability or as representing BBOT’s assessments as of any date subsequent to the date of this press release. Neither BBOT, nor any of its affiliates undertake any obligation to update these forward-looking statements, except as required by law.

BBOT Contacts:

Investor Contact:
Heather Armstrong, Head of Investor Relations
BBOT
Heather.Armstrong@bbotx.com

Media Contact:
Jake Robison
Inizio Evoke Comms
Jake.robison@inizioevoke.com

FAQ

What did BBOT announce about BBO-11818 on March 6, 2026 (BBOT)?

BBOT published preclinical data in Cancer Discovery showing BBO‑11818 is a potent panKRAS inhibitor. According to the company, the compound binds KRAS in both ON and OFF states and is active against KRASG12D, G12V, and G12C.

How selective and potent is BBO-11818 according to BBOT (BBOT)?

BBO‑11818 showed high selectivity, with >b500‑fold preference for KRAS over other RAS isoforms. According to the company, assays demonstrated strong binding and functional inhibition across multiple KRAS mutants in preclinical models.

What clinical evidence has BBOT reported for BBO-11818 in 2026 (BBOT)?

Initial Phase 1 KONQUER‑101 results included a confirmed partial response with 56% tumor reduction in PDAC. According to the company, early anti‑tumor activity was observed across dose levels and tumor types.

When will BBOT provide more data on BBO-11818 and combination studies (BBOT)?

BBOT plans additional clinical updates in the second half of 2026 and expects an internal combination with BBO‑10203 later in 2026. According to the company, those timelines guide next‑stage clinical evaluation and combination enrollment.

Does BBOT claim BBO-11818 works against common resistance mechanisms (BBOT)?

BBOT reports BBO‑11818 inhibits KRAS in both ON and OFF states, which may address resistance linked to active‑state signaling. According to the company, this dual‑state binding could limit emergence of secondary KRAS mutations seen with allele‑specific inhibitors.