Platform

Rationally Designed to Maximize Patient Benefit

We’re overcoming the limitations of current RAS-targeted approaches, aiming to realize the full promise of KRAS and PI3K inhibition.

Program & Indication

Pre-Clinical Phase 1 Phase 2 Phase 3

BBO-8520

- Phase 1

A direct inhibitor targeting the “ON” and “OFF” states of KRAS. We are currently enrolling the ONKORAS-101 trial for patients with KRAS^G12C mutant non-small cell lung cancer (NSCLC).

ONKORAS-101 is an open-label, multi-center Phase 1a/1b study designed to evaluate the safety, tolerability, preliminary antitumor activity, and pharmacokinetics of BBO-8520 as a single agent and in combination with pembrolizumab in patients with KRAS^G12C mutant NSCLC.

BBO-10203

- Phase 1

A RAS:PI3Kα breaker designed to inhibit PI3Kα/AKT signaling in tumors while critically avoiding hyperglycemia. We are currently enrolling the BREAKER-101 trial for patients with locally advanced or metastatic HER2-positive breast cancer, HR-positive/HER2-negative breast cancer, KRAS mutant advanced colorectal cancer, and KRAS mutant advanced non-small cell lung cancer.

BBO-11818

- Pre-Clinical

A pan-KRAS inhibitor targeting its “ON” and “OFF” states with high potency against both G12D and G12V mutants. We are currently enrolling the KONQUER-101 trial for patients with locally advanced unresectable or metastatic KRAS mutant solid tumors.

Expanded Access Policy

Pre-approval Access

BBOT is passionate about developing advanced therapies and delivering transformative medicines to treat patients who suffer from advanced cancers. BBOT provides access to our investigational therapies through enrollment in our ongoing clinical trials. For ongoing clinical trials on BBOT’s investigational therapies currently in development, please visit https://clinicaltrials.gov.

BBOT also recognizes the importance of utilizing the applicable regulatory and legal pathways for providing access to our investigational therapies when patients with life-threatening diseases have exhausted all available treatment options and are not eligible for clinical trials. At certain point when efficacy and safety profile of specific molecule is reasonably established to allow BBOT for risk/benefit assessment, BBOT may be able to provide patients access to its investigational medicines outside of a clinical trial if certain conditions are met.

The use of investigational medicines outside of a clinical trial is known under various terms such as Pre-approval Access, Expanded Access, or Named Patient Programs (also widely referred to as compassionate use). Requests for access to investigational products under these circumstances must be made by treating physicians directly to BBOT. Upon receipt of an unsolicited request by a prescribing healthcare professional, when permitted by local regulations, BBOT may consider access requests from treating physicians for patients with no viable therapeutic alternatives.

Why RAS?

RAS mutations drive more than 30% of all human cancers, including the most deadly types, by effecting aberrant RAS signaling that results in uncontrolled tumor growth.

In 2021, the FDA approved the first therapeutic targeting the KRAS^G12C mutation; a huge breakthrough for non-small cell lung cancer (NSCLC) patients. KRAS mutations appear in approximately 30% of NSCLC cases, 40% of colorectal cancer (CRC) cases, and 90% of pancreatic ductal adenocarcinomas (PDAC) cases.

However, current direct KRAS-targeted approaches exclusively target the “OFF” state of the protein, which has no biological function. These agents “lock” the mutant KRAS in the “OFF” state, limiting the amount of active “ON” KRAS^G12C available to signal. However, this approach has limitations, such as incomplete target inhibition. More importantly, the adaptive resistance that can arise through multiple cellular mechanisms increases the population of the oncogenic “ON” state. These adaptive mechanisms result in short duration of response and limited clinical benefit for patients.

Our approach to rational drug design is informed by RAS cancer biology, and is key to advancing new RAS-targeted approaches that could significantly improve patient outcomes.

What’s RAS?

The RAS gene family encodes proteins crucial in controlling cell proliferation, differentiation, and survival, which can lead to cancer. 

KRAS is a member of the RAS gene family and is one of the most commonly mutated genes in human solid tumors. A specific mutation in the KRAS gene, KRAS^G12C, results in a constantly active (“ON”) K-Ras protein that continuously activates downstream pathways, such as MAPK/ERK and PI3K/AKT, leading to uncontrolled cell growth and cancer progression. The “ON” form was once considered “undruggable,” but we now understand that targeting the “ON” state is possible and represents a clinically meaningful target that is distinct from the “OFF” state.

We aim to overcome the limitations of existing therapies by pursuing multiple approaches with drugs that target both the “ON” and “OFF” forms, including KRAS^G12C and pan-KRAS inhibitors.

Why PI3Kα?

The importance of PI3Kα in cancer has been demonstrated by first generation PI3Kα kinase inhibitors that provide clinical benefit to breast cancer patients. However, these agents are severely constrained by on-target toxicities that limit their effectiveness.

New research is elucidating how RAS activates the PI3Kα pathway, showing that it plays an important role in tumorigenesis but a limited role in normal physiology. This important dichotomy sets the stage for a new therapeutic approach: the potential to block the interaction between KRAS and PI3Kα and deliver more effective cancer therapies, providing physicians and patients with additional therapeutic options to expand treatment possibilities.

We are developing a therapeutic designed to break the cancer-causing interaction between RAS and PI3Kα that does not harm healthy cells, bypasses glucose metabolism signaling, and avoids hyperglycemia.