Chemistry and Mechanism of Action
Chemistry and Mechanism of Action BioMimetix is advancing an entirely new class of small molecules, redox-active metalloporphyrins (MnPs), with potent anti-inflammatory effects. Our MnPs are enzymatic and optimized for redox activity at near diffusion limited rates to provide dual action of tumor killing and protecting healthy tissue. BMX-001 modulates cellular signaling such as by inhibiting of NF-𝛋B and HIF-1𝛂 pathways.
Mechanism of Action: Dual Impact on Tumor Cells and Normal Tissues
In Tumor Cells
- NF-𝛋B supports pro-survival functions
- HIF-1𝛂 supports angiogenesis
- Blocking NF-𝛋B and HIF-1𝛂 by BMX-001, enhances tumor killing, inhibits angiogenesis and reduces long-term tumor proliferation
- This has been demonstrated in animal models (glioblastoma, head and neck, Anal & Rectal) and tumor inhibition confirmed in clinical trial of patients with high-grade glioma
In Normal Cells
- NF-𝛋B is the primary regulator of inflammatory injury following radiation therapy
- HIF-1𝛂 is not expressed under normal conditions
- Blocking NF-𝛋B by BMX-001 markedly reduces inflammatory injury to normal cells by radiation therapy
- Blocking HIF-1𝛂 by BMX-001 has no significant effect on normal cells
- These effects have been seen in preclinical and humans:
- Protects white matter tracks and cognition after brain RT
- Reduces mucositis and xerostomia after HN RT
- Reduces GI/GU incontinence, strictures, and skin inflammation after RT
BMX-001 is lipophilic and optimized for greater systemic availability when subcutaneously injected.
The mechanism supporting BMX-001 + RT as a combination therapy targeting tumor suppression is supported by multiple published preclinical studies:
BMX-001: Addressing an Unmet Medical Need
Significant resistance to therapy is found for many forms of tumor.
Radiation therapy and chemotherapy are limited by multiple side effects.
Efficacy of BMX-001 in both tumor inhibition and protection of normal tissues is backed by preclinical and clinical data.
High-Grade Glioma
Aggressive and malignant tumor with poor prognosis
- Limited treatment options
- The blood brain barrier protects many drugs from reaching the brain (BMX-001 penetrates the BBB)
- Cancer cells mutate and adapt, rendering targeted therapies less effective
Head and Neck Cancer
Complex Anatomy
- Treating cancer in this region while preserving function remains a challenge
- Current SOC (surgery and chemoradiation) causes significant side effects
Anal & Rectal Cancers
Impaired QoL
- Despite advances in treatment, these cancers present several unmet medical needs
Some become resistant to treatment
Chemoradiation therapy causes significant side effects
BMX-001 is a platform solution for cancer treatment
Killing the Cancer
BMX-001 delivered a 6.6 month survival benefit in a large, randomized, controlled trial.
Preclinical studies support tumor inhibition by BMX-001:
- Glioblastoma Multiforme
- Head and Neck cancer
- Anal & rectal cancer
Pharmacokinetics
- BMX-001 is active at a very low dose.
- BMX-001 has been chemically optimized for wide distribution and penetration of blood-brain barrier.
Rigorous HGG Trial Design
Problems with most HGG trials:
- OS was not a primary endpoint,
- > 60% were single-arm,
- relied on historic controls,
- many were single center.
Our Phase 2 HGG trial was designed to avoid these mistakes.
Safety and Protection
BMX-001 has a benign safety profile, with AEs that are minor and manageable.
BMX-001 protects against radiation injury to brain, head and neck tissues, bowel and skin. In HGG patients, cognitive function is preserved.