Ilya Rachman, MD, PhD
I am a physician scientist, who received my MD/PhD from the University of Illinois in 2000. Towards the end of my graduate studies, I became interested in mechanisms of how advanced cancers evade the immune system detection and develop resistance to therapies. After graduating from medical school, I completed Internal Medicine residency at UCLA in 2003 and began my medical practice. Every year since then, I've been expecting some biotech or a pharmaceutical company to develop new types of cancer medications based on the same insights that were so compelling to me as a graduate student. Year after year, despite celebrating new advances, I’ve been left with a feeling that more can be done. Then, in 2011, two of my own friends were diagnosed with metastatic cancer before the age of 50. That was the last straw and it propelled me into action. In 2012, Immix Biopharma was born with a singular mission of developing medicines for advanced metastatic forms of cancer.
At this point, our company has developed two therapies with encouraging data in brain, colorectal, triple-negative breast and ovarian cancer preclinical models. The first compound is on its way into its first-in-human clinical trial in 2017. With additional funding, new anti-cancer therapies based on our promising platform can be transitioned into clinical trials faster, reducing unnecessary delays and giving patients the fighting chance they deserve.
The dream is that no cancer patient ever has to worry about hearing, "your cancer is back" -- a world where, instead of a chronic disease, cancer can become a disease of the past. At Immix, to realize this, we set out to build a combination treatment that induces tumor cell death without toxicity and, simultaneously, inhibits genomic evolvability mechanisms - therein stopping resistance to therapy from developing.
In most cancers, senescence, metabolic perturbation and chemotherapy induce expression of nuclear factor kappa B (NF-κB). The NF-κB–induced cascade of gene expression generates tumors that are resistant to therapies, largely by up-regulating ‘inhibitory of apoptosis proteins’ and promoting tumor proliferation, invasion and metastasis. Induced or constitutive NF-κB overexpression is correlated with resistant phenotypes in breast, colon, pancreas, and other tumors. Chemotherapeutic agents such as doxorubicin (DOX) and others, while aimed at killing cancer cells, also upregulate NF-κB activity in these cells. Therefore, simply delivering more chemotherapy into cancer cells will not arrest cancer growth or induce apoptosis.
To suppress cancer cells’ resistance, NF-κB must be inhibited before chemotherapy administration. Curcumin (CUR) is known to inhibit NF-κB in cancer cells in vitro. Moreover, CUR was given at MD Anderson in oral forms; however, because of its poor water solubility and oral bioavailability, it required high doses to be administered and led to unacceptable gastrointestinal side effects. Immix overcame this solubility problem by enclosing CUR in a water-soluble, nano carrier that can be administered intravenously. By adding DOX to this nano-carrier, Imx-110 is able to induce cancer cell death with just 3% of current chemotherapy doses given today.
This project will test 7 novel therapies with a similar thesis shared above in glioblastoma (GBM) models. The candidate with the best results of the 7 tested in this study will advance to safety testing on its way towards human clinical trials.
Why is this important?
Glioblastoma presents a significant treatment challenge with limited therapeutic options and poor response rates for patients diagnosed. New and better options are badly needed. Our approach takes advantage of the Achilles' heel of glioblastoma in its reliance on high glucose metabolism and its addiction to a protein called NF-kB. By targeting the proteins expressed on the surface of tumor cells, our therapy attempts to trick these tumor cells to take up our drug, delivering the therapeutic payload to the inside and causing tumor cell death, without harming the normal cells around it.
Who will benefit?
Patients with glioblastoma will be the direct beneficiaries of this work as they will have access to the novel type of therapy, that, hopefully, will produce meaningful long-term responses with minimal toxicity.
BudgetTarget Budget: $45,000. Use of funds: $25,000 will be spent on comparing the effectiveness of various versions of this therapeutic against GBM spheroids (3-dimensional cell cultures); $20,000 will be used to test the most effective of those therapies in animal models
Immix GBM results presented at Harvard
Our work demonstrating the proof of concept for this approach to GBM treatment has recently been published in a peer-reviewed journal and was presented at a conference held at Harvard :
Nanomedicine based curcumin and doxorubicin combination treatment of glioblastoma with scFv-targeted micelles: In vitro evaluation on 2D and 3D tumor models. Sarisozen C, Dhokai S, Tsikudo EG, Luther E, Rachman IM, Torchilin VP. Eur J Pharm Biopharm. 2016 Aug 25. pii: S0939-6411(16)30464-7