Our Lead Program - MUL001

 

MUL001 is a genetically engineered, live-attenuated strain of Salmonella Typhimurium designed to selectively colonize tumors. The strain incorporates two key mutations:

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• purI deletion (adenine auxotrophy): Restricts bacterial growth to the nutrient-rich, necrotic tumor microenvironment.

• msbB deletion (modified lipid A): Reduces the risk of potential toxicity by lowering TNF-α induction.

 

In animal models, once inside the tumor, MUL001 triggers tumor cell death through direct cytotoxicity, anti-angiogenesis, and immune activation. MUL001 reprograms tumor-associated macrophages from an immunosuppressive (M2) to a tumoricidal (M1) phenotype, increases cytotoxic T-cell infiltration, and decreases regulatory T-cells. It is generally understood that human NF2-SWN tumors have an immunosuppressive tumor microenvironment that MUL001 converts to an immunogenic (or pro-inflammatory) environment, thus generating systemic anti-tumor immunity.

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​​MUL001's first indication is NF2-related schwannomatosis​

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​​​​​MUL001 is based on pioneering research conducted at Harvard University and Massachusetts General Hospital (MGH), as well as extensive clinical and scientific experience with attenuated Salmonella Typhimurium in humans. Mulberry holds an exclusive license from the Massachusetts General Hospital (MGH), enabling us to advance this innovative technology for clinical use in slow-growing tumors such as NF2-SWN.

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Foundational animal studies at MGH established the potential of engineered bacteria to selectively target and modulate the tumor microenvironment in animal models of NF2-SWN. These studies, together with the available systemic (intravenous) and intratumoral clinical safety data on the same attenuated Salmonella Typhimurium strain, provide robust proof-of-concept evidence to proceed with the development of MUL001 in NF2-SWN.

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Important: MUL001 is investigational. It has not been approved by the FDA or other regulators. Clinical studies are needed to test safety and potential benefits. Safety and efficacy have not been established. Results from preclinical models and related clinical experience may not anticipate outcomes in NF2-SWN. Future clinical trials will evaluate outcomes in patients.

 

How MUL001 Works

 

MUL001 attacks tumors through multiple, complementary mechanisms:

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• Direct tumor cell killing and immunogenic cell death: MUL001 selectively destroys tumor cells and triggers the release of signals that alert and activate the immune system.​

• Anti-angiogenic effects: MUL001 disrupts the tumor’s blood supply, starving the tumor of nutrients and slowing its growth.

• Macrophage polarization: MUL001 reprograms tumor-associated macrophages from an immunosuppressive (M2) state to a pro-inflammatory, tumor-fighting (M1-like) state. This is particularly important for a macrophage-rich tumor such as a schwannomas.

• Activation of cytotoxic T cells and immune memory: MUL001 stimulates the body’s cytotoxic T cells to attack tumor cells and helps develop immune memory, enabling the immune system to recognize and respond to tumor tissue elsewhere in the body.

 

Together, these effects aim to shrink treated tumors and stimulate a targeted immune response that can recognize and attack tumor tissue throughout the body.​

 

Bacteria-Mediated Immunotherapy is Effective in Treating Slow-Growing Tumors

 

For more than four decades, intravesical BCG (a live, attenuated bacterium) has been a standard-of-care immunotherapy for non–muscle-invasive bladder cancer (NMIBC), a typically slow-growing tumor. The success of BCG demonstrates that locally delivered live bacteria can safely and effectively control tumor growth.​​

Schwannomas, which develop in NF2-SWN disease, are typically genetically stable, slow-growing, and highly vascularized tumors with hypoxic regions - an environment that is ideal for bacterial colonization.

 

MUL001: First-in-Class Therapy Advancing Toward Clinical Trials in NF2

 

All IND-enabling non-clinical studies for MUL001 are complete, and we have engaged with the FDA to align our clinical development plan. The upcoming clinical study is designed to evaluate safety, pharmacokinetics/pharmacodynamics (PK/PD), and tumor response.

 

Key elements of the clinical program:

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• Design: Dose-escalation study in patients with Neurofibromatosis type 2-related schwannomatosis.

• Primary endpoints: Safety and tolerability, with PK/PD characterization.

• Efficacy assessment: Objective changes in tumor volume, consistent with regulatory precedents for NF-associated tumor trials.

• Manufacturing: The GMP manufacturing process for MUL001 has been established, and clinical-grade material has been manufactured.

• Timeline: The first clinical trial is planned to begin in 2026.

• Administration: Image-guided intratumoral injection of MUL001.

 

Final study design is subject to regulatory feedback and protocol approval.

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Expanding Beyond NF2-SWN: Potential in Additional Indications

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In addition to our lead program in NF2-SWN, we will evaluate the potential of our platform in several other conditions that share key biological features - such as slow tumor growth, a vascular or hypoxic microenvironment, and accessibility for image-guided delivery. These follow-on indications include:

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• Neurofibromatosis type 1 (NF1) - associated nerve sheath tumors (termed neurofibromas)

• Schwannomatosis (also known as non-NF2-related schwannomatosis)

• Meningioma (the most common brain tumor in the general population, which also develops in individuals with NF2-SWN)

 

Preclinical research has shown encouraging signals in models of NF1- associated nerve sheath tumors and meningioma, supporting further investigation. The selection and timing of future programs will be guided by patient need, scientific rationale, and regulatory clarity - ensuring that we prioritize indications where our platform can deliver the greatest impact.