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Salmonella typhimurium-based Bacteriotherapy for Orphan Benign Tumors: Neurofibromatosis Type II (NF2)
Phone: (617) 800-3415
Phone: (617) 800-3415
Type: Domestic nonprofit research organization
Neurofibromatosis type 2 (NF2) is a rare genetic disorder that affects about 1 in 25,000 individuals globally.
While usually benign, these tumors result in severe morbidity and mortality in affected individuals. Almost all NF2
patients lose their hearing, and many lose the ability to walk and even to see. NF2 patients’ average age at death
is 36 years, many of whom die in adolescence or early adulthood from their disease. NF2 is an orphan indication
and represents a major unmet medical need, thus supporting an FDA Fast Track designation. NF Bio estimates
the NF2 commercial opportunity to exceed US$1B in annual peak year sales. Success in NF2 treatment will also
lead to testing in other benign and schwannoma-related neoplasms such as NF1.
Operative resection and radiotherapy are the current standards of care. However, these treatments have major
limitations. Resection can lead to a significant sensory loss including deafness, pain, facial paralysis, and motor
dysfunction. Resection also is not always possible due to the risk of nerve or brain stem damage. Radiotherapy
can be contraindicated due to the risk of malignant transformation and typically does not eliminate the
schwannoma. Affected individuals typically have multiple schwannomas with tumors arising throughout life,
further increasing disease-associated suffering and limiting the utility of surgical resection. There is no approved
pharmaceutical therapy and a limited clinical trial pipeline.
NF Bio has developed an NF2 bacteriotherapy that utilizes intra-tumoral (i.t.) injection of attenuated S.
typhimurium, delivered in an image-guided fashion (MRI or ultrasound) by neurosurgeons, otolaryngologists,
pain medicine physicians, or interventional radiologists Use of this bacterial therapy for schwannomas is justified
by the fact that Salmonella thrives in the hypoxic areas of highly vascularized tissues, which is a hallmark of NF2
schwannomas, and its anti-tumor cytotoxic mechanisms do not require tumor cell replication.
NF Bio is the first to develop a bacteria-based therapy for the treatment of NF2. We have demonstrated in animal
models that i.t. injection of attenuated S. typhimurium decreases the volume of the injected tumor through direct
cytotoxic and anti-angiogenic effects; importantly, it also induces a systemic immune response that targets distal
tumors and a memory response that prevents further development of new lesions. This intervention has a lower
risk of neurologic damage than operative resection due to the targeting mechanisms and engineered safety
mechanisms that will be developed in this proposal.
In the proposed Phase I work, NF Bio will develop a next-generation bacterial therapy that enhances direct tumor
killing and induce immune-mediated killing. In future Phase II grant work, we will select a Development Candidate
(DC) based on in vitro and in vivo data, and conduct toxicology and biodistribution studies to enable a US
Investigational New Drug (IND) application.Neurofibromatosis type 2 (NF2) is a rare genetic disorder that results in severe morbidity and mortality
in affected individuals. Our group has developed a novel therapy for NF2 in which intratumoral injection
of attenuated Salmonella typhimurium kills tumor cells directly and stimulates host anti-tumor adaptive
immune responses. The overriding goal of this project is to develop and test the efficacy of genetically
modified versions of S. typhimurium engineered to increase its therapeutic effect as an essential step
for translation to a clinical treatment.
* Information listed above is at the time of submission. *