An Innovative Pipeline
Conditionally Activated-Small Molecule Drug Conjugates (CA-SMDCs)TM are designed to co-target cancer
and the tumor immune microenvironment. Our deep pipeline of potential CA-SMDC product candidates
is built on our proprietary and patented IMPACT-2X technology driven by our own bold science and passion to bring new and improved treatment options to patients that suffer from cancer.
IND = Investigatory New Drug; FIM = First-in-Man; NDC = New Drug Candidate; LO = Lead Optimization
STING = Stimulator of Interferon Genes; EGFR = Epithelial Growth Factor Receptor; DDR = DNA Damage Response
MaveriX is leveraging our CA-SMDC platform to develop first-in-class
therapeutics with the potential to effectively and safely treat a broad
range of solid tumors
We believe our CA-SMDC therapeutics have the potential to:
- Improve anti-tumor responses by reducing tumor burden while directing the immune system to attack cancer
- Create or expand the therapeutic window – the balance between
a drug’s effective dose range without causing unacceptable toxicity
- Enhance single-agent activity and enable new therapeutic combinations previously not possible due to toxicities
- Advance new treatment options to patients that suffer from cancer
MVX-484 is a conditionally activated-small molecule drug conjugate (CA-SMDC) bearing a nucleoside
DNA damaging (NUC) payload designed to target the immunomodulatory and immunostimulatory
power of conventional chemotherapeutics.
MVX-484 is systemically stable and inactive in the drug-conjugate form, rapidly
penetrates solid tumors and is activated in the hydroxylase-rich cancer and tumor immune microenvironment.
Translational studies have confirmed homogeneous DNA damage in tumors compared to normal tissues
reflected in broad anti-tumor activity and an excellent safety profile.
The underlying mechanism-of-action is targeted tumor cell killing, targeted immunogenic cell death,
targeted eradication of immune suppressive cell subsets, and stimulation of both innate and adaptive
immune attack on tumors. MVX-484 exhibits good oral bioavailability and will be evaluated
for single-agent activity and combination immunotherapy in phase 1a/1b clinical trials.
MVX-505 is a highly soluble prodrug (pro) form of a conditionally activated-small molecule drug
conjugate (CA-SMDC) bearing an immunogenic nucleoside DNA damaging (NUC) payload.
Plasma pharmacokinetic studies have demonstrated that the solubilized pro-CA-SMDC_NUC is rapidly
and efficiently converted to CA-SMDC_NUC in the systemic circulation.
Prodrug MVX-505 has been successfully formulated for intravenous administration in the clinic
facilitating intravenous administration to patients to optimize dosing regimens
for combination chemotherapy and immunotherapy.
MVX-600 Series (pro-CA-SMDC_NUT)
The MVX-600 series builds on the company expertise in DNA damaging nucleotide (NUT) chemistry
and CA-SMDC therapeutics to address a clear clinical unmet need for the treatment of
metastatic colorectal cancer (mCRC).
The prodrug pro-CA-SMDC_NUT is designed to be systemically stable, rapidly penetrate solid tumors,
to co-target cancer and the tumor immune microenvironment.
The MVX-600 series is activated by a hydroxylase over-expressed to a high frequency in mCRC and a known
target of the immunosuppressive cyclooxygenase-2 (COX-2)/prostaglandin E2 (PGE2) pathways.
The MVX-600 series drug candidate will be evaluated in immunogenically “cold” mCRC
and in combination with immune checkpoint inhibitors.
MVX-700 Series (CA-SMDC_CPT) and MVX-800 Series (CA_SMDC_DCM)
The MVX-700 and MVX-800 series are next generation CA-SMDC therapeutics designed to deliver
high-potency DNA damaging payloads including camptothecin (CPT) and duocarmycin (DCM)
analogues by co-targeting cancer and the tumor immune microenvironment.
These high-potency CA-SMDCs utilize the MaveriX proprietary Pro-XACT ‘molecular mask’ and
extended hydroxylase cleavable linker combinations.
CPT and DCM analogue payloads are commonly utilized in antibody drug conjugates (ADCs)
and CA-SMDC therapeutics are expected to exhibit superior solid tumor penetration,
efficacy, and safety over ADCs.
Discovery Stage CA-SMDC Programs
CA-SMDCs are ideally suited to overcome the limitations of ‘free’ stimulator of interferon genes (STING)
agonists and offer a highly differentiated small molecule targeted approach from other innate immune
modulators that require intra-tumoral administration due to systemic toxicity.
Conjugation of the STING agonist provides protection in the systemic circulation
to minimize off-target effects and expand the therapeutic index.
Discovery stage programs focus on exploiting CA-SMDCs to overcome “off-target” toxicity
and resistance in cancer.