OncoSense® : Solving the Cancer Problem Using Nanotechnology

B-Aegis was formed on October 05, 2017, for solving the most complex problems in healthcare sectors, especially in oncology, using simple yet futuristic & effective solutions. The Startup was found by a group of clinicians, academicians and young entrepreneurs coming from distinctive fields like dental medicine, oncology, molecular biology, nanotechnology etc. B-Aegis is combining nanotechnology, chemistry, life sciences and material sciences to produce the next generation of products.

B-Aegis bagged many awards &recognition in both India and Abroad. The company have filled multiple intellectual property rights. The startup received 15 lakh funding from Mangalore Refinery and Petrochemicals Limited on 05/01/2019, 7 lakh prototyping grant from Kerala Startup Mission on 18/05/2019, 1.5 lakh initial exploration grant from IIT Mandi on 29/11/2019. We were shortlisted for many prestigious innovation events like XPOMET© Medicinale 2019 in Berlin and represented India in many international events like Oiweek X, 2nd edition of Franco-Indian Knowledge summit etc.

Cancer is a leading cause of death worldwide, accounting for an estimated 9.6 million deaths in 2018. In India, in 2018 over 1.3 million new cancer patients were registered and 0.90 million people died of cancer. India has less than 250 dedicated cancer-care centres and nearly 40% of these are in eight metropolitan cities. As a result, more than 80% of India’s cancer cases are detected at an advanced stage and more than 70% of patients with cancer die of the disease in India, compared to about 30% in the US. Cancer mortality can be reduced if cases are detected and treated early. For many types of carcinomas, an early diagnosis is still elusive, even in developed countries. For example, Non-small cell lung cancer doesn't have a proven early-stage diagnosis solution. Currently used low-dose CT method fails to diagnose most cases at early stages, has a very low sensitivity and specificity and carries a high carcinogenic risk of ionizing radiation. There are many other types of cancers and their metastatic forms for which we have no proven early diagnostic solutions, like pancreatic cancer, ovarian cancer, cancers of the brain and spinal cord, carcinoma of unknown primary origin etc. MRI is a widely recognized method for assessing many lesions like isolated axillary lymph node metastases and suspected occult primary breast carcinoma (after negative mammography and sonography findings) and MRI with contrast dye is the best way to see the brain and spinal cord tumours, but even MRI can also fail in detecting tumours under 8mm.

OncoSense^® is a revolutionary next-generation MRI Contrast Media containing superparamagnetic iron oxide nanoparticles conjugated with a patent-pending tumour targeting peptide, which can be used for screening and early diagnosis of carcinomas. OncoSense^® is highly sensitive towards very early stage adenocarcinomas and squamous cell carcinomas. OncoSense^® makes MRI systems to see the tumours even under the size of 5mm (T1a) in our preclinical animal trials. It can also target almost all types of epithelial origin solid tumours at later stages (above the size of 8mm). OncoSense^® is most sensitive to the changes in molecular information rather than anatomic changes, which helps in the early detection of hidden/occult micrometastasis. It uses triple targeting technology (T3)™ including receptor targeting & endocytosis along with Endothelial Leakiness Effect and Enhanced Permeability and Retention Effect (EPR). Being an iron oxide-based agent, OncoSense^® can easily cross the blood-brain barrier more effectively than any other MRI contrast agent available currently in the market. OncoSense^®, with its extreme sensitivity and good specificity, aims to identify individuals with a higher risk of having a carcinoma or precancerous lesions who have not developed any symptoms and refer them promptly for a confirmation test and follow on treatment. The time it takes to complete diagnostic tests will also be reduced. For example, the time it takes to complete diagnostic tests for colorectal cancer will be reduced from an average of 13 days using standard multimodal diagnostics to an average of 5 days using OncoSense^® MRI contrast media. For Non-Small Cell Lung Cancer, the time will be reduced from 19 days to 6 days. For the diagnosis of brain tumours in children, the time will be reduced from an average of 60 days to 16 days!

Completion of PK/PD and ADME-Tox Studies in Mice and Rabbits in a GLP certified laboratory: Time Frame - 4 months

• Xenograft models using immunocompromised NSG mice will be used to study in-vivo efficacy of OncoSense^® nanoparticles via tail vein injection. MR Image will be taken at magnetic field strengths of 0.35 Tesla (T), 1.0 T, 3.0 T, 5 T and 7 T.

• Balb/c and NOD.CB17-Prkdc mice will be used for PK/PD, ADME and Toxicity studies.

• New Zealand White Rabbits will be used for DMPK studies.

• Both Acute toxicity and Repeated-dose toxicity will be extensively studied in the three animal models.

• All the animal studies will be done in a GLP certified facility like the CSIR-IITR, approved by NGCMA, Government of India.

All intravenous medicines at a certain dose produce side effects. Doctors need to know what that dosage amount is and the potential side effects that may occur - regardless of the effectiveness of the compound. OncoSense^® may also produce some side effects starting from a certain dose, as it contains the active ingredient in the form of a biologically active peptide. To assess the side effects if any, doctors use the Guidelines of the National Cancer Institute for classification (Common Criteria for Adverse Events, CTCAE). Using these guidelines, a dose is obtained, which consequently may not be exceeded during the following usages. The phase 3 trial will be randomized. This means that patients are put into a treatment group, called trial arms, by chance. Randomization is needed to make sure that the people in all trial arms are alike. This lets scientists know that the results of the clinical trial are due to the usage of OncoSense and not differences between the groups.

• To compare the efficacy of the OncoSense^® with the standard contrast-enhanced MRI.

• To determine the pharmacokinetic profile of OncoSense^® and selected metabolites in patients with Adenocarcinomas & Squamous cell carcinomas.

In the OncoSense Phase 3 study the following side effects will be monitored:

• Condition of the immune system measured by counting immune cells in the blood

• Oxygen supply measured by counting red blood cells in the blood

• Nausea measured by observing and questioning the patient

• Liver toxicity measured via laboratory analysis of blood counts

• Cardiotoxicity measured by pulse analysis and electrocardiogram

• Balance, motor skills and reflexes measured by sensory tests and questioning

• Tumour targeting capability compared to the standard MRI contrast agent.

• Sensitivity & specificity compared to the standard MRI contrast agent.