We combine
the tumor-killing
power of radiation
with cancer seeking agents
Higher & Multi-Dose
Regimen Possibilities
Lower impurities allows for the possibility of frequent repeated doses.
Potential Disease Modifying Effects
Repeated doses allows for the accumulation of radiation with the potential to treat the underlying bone cancer disease
Broader Indications
Disease-modifying treatments leads to the potential of treating multiple bone cancer types
The Problem
There are few good options to treat bone cancer!
According to the American Cancer Society, about 400,000 new cases of malignant bone metastasis are diagnosed and around 350,000 people die from bone metastases in the United States each year.
Osteosarcoma and Ewing’s sarcoma are the most common malignancies of bone tissues in children.
The current standard of care is aggressive and suboptimal, and has led to marginal success with significant side effects and poor long-term survival prognosis.
Our Solution
Initial Tecnology: CycloSam®
CycloSam® is a targeted, bone-seeking therapeutic radiopharmaceutical that features a patented, low specific activity form of Samarium-153, a medium energy beta-emitting radioisotope with a short 46-hour half-life, and a superior chelating agent, DOTMP.
CycloSam® selectively targets sites of high bone mineral turnover to deliver a prescribed tumor-killing dose of radiation to the site and reduces off-site migration.
Developed by pioneers in radiopharmaceuticals,
Dr. R. Keith Frank and Dr. Jim Simón
CycloSam® represents a potential change in the treatment paradigm for bone cancer with Samarium-153
from not only managing the signs and symptoms of bone cancer (e.g. pain palliation),
but also treating the underlying bone cancer disease itself.
How it Works
Improved next generation therapeutic over prior FDA-approved pharmaceutical
1
Radioisotope:
Samarium-153
Penetrating tissue up to 3.1 mm, Samarium 153 emits radiation to destroy tumor cells resulting in a clinical response in the tumor, but low enough dose to avoid the occurrence of significant adverse effects in other organs.
Samarium 153 also emits gamma photons that make it possible to take images of the skeleton, locate and characterize the size and nature of tumors, and track biodistribution of the drug.
2
Bone Targeting Agent: DOTMP
CycloSam’s chelating agent, DOTMP, naturally seeks out locations of high bone mineral turnover, typical in tumor growth, and deposits Sm-153 which emits radiation at the tumor site while also limiting the off-target migration to healthy cells seen with other radiopharmaceuticals.
3
CycloSam® Dose
Just-in-time manufacturing model used to deliver patient-specific dose to the treating physician for IV administration within 48 hours of radioisotope irradiation in the nuclear reactor.
CycloSam® Indications
We believe that the ability to safely administer CycloSam® for higher and multiple-dose regimens may expand its clinical utility for therapeutic uses in areas of high unmet medical needs.
CYCLOSAM® CAUSES SIGNIFICANTLY LESS BUILDUP OF LONG-LIVED RADIOANUCLIDIC IMPURITIES THAN PRIOR FDA APPROVED DRUG
Our method of manufacturing Samarium-153, compared to the prior FDA-approved Samarium-153 product, has shown in pharmacopeial limits studies to produce a 30-fold reduction in levels of long-lived radioactive impurities, mainly Europium-154 (8.6 y half-life).
CycloSam’s low impurity profile coupled with its short 46-hour half-life may allow for more frequent and repeated dosing, leading to greater ability to slow or reverse tumor growth.
Precedent for Efficacy - The Vienna Protocol
In August 2011, Dr. Helmut Sinzinger published a study in the Quarterly Journal of Nuclear Medicine and Molecular Imaging, which demonstrated that despite the described limitations of Samarium-153 EDTMP (Quadramet®), it could still be used to effectively treat bone metastasis.
The Vienna Protocol, as it was labeled, was based on a 550 patient study developed by Dr. Sinzinger to deliver therapeutic doses of Quadramet® on a periodic low dose basis balancing hematological toxicity and europium buildup with clinical results.
The specific regimen used very low doses of the predecessor drug (30 mCi) on an outpatient basis. The treatment was administered at three month intervals during the first year, followed by another five treatments at six month intervals, then five therapies at nine month intervals, and then annually indefinitely.
During Dr. Sinzinger’s trials, a wide range of positive clinical responses were seen including arrested tumor growth and even regression of the cancer in the bone. Some patients were treated for over five years exhibiting significant clinical response.
73%
of patients experienced regression
5 Years
Prolonged Survival
Prostate Patient after 5 Treatments
Precedent for Safety - FDA-Cleared Single patient study
EARLY SAFETY SIGNALS AT HIGH DOSAGES
A single high dose (32 mCi/kg) of CycloSam® administered for bone marrow ablation prior to stem cell transplant on terminally ill, 25-year-old male with Osteosarcoma and Myelodysplastic Syndrome.
Outcomes
CycloSam® targeted bone; preferential uptake in tumors
CycloSam® delivered to target
Dose to marrow
Dose proportionate radiation
Cleared major organs within hours
Normal kidney function
ROBUST PATENT ESTATE FOR THE USE OF CYCLOSAM® AS A RADIOPHARMACEUTICAL
The CycloSam® kit is protected by the extensive patent estate that broadly protects DOTMP kit formulations for radioisotopes, potentially allowing for efficient distribution of the product and widespread use. Additionally, the patents cover the use of low-specific activity Samarium-153 allowing for daily supply of the isotope with lower impurities from a broader range of reactors. Lastly, they cover the methods relating to repeat dosing regimens for therapeutic radiopharmaceutical agents, which suggest increased efficacy based on prior research.