9 is NOT enough!

AUTHOR: David Oarr

In June, I traveled to Washington D.C. where I joined more than 700 pancreatic cancer patients and advocates on the Hill.  We met with congressmen and senators, and we collectively proclaimed that a 9 percent  five-year-survival rate is NOT GOOD ENOUGH. In between events and running from one congressional office to another, I talked with a few patients and family members about CytImmune’s technology, and how CytImmune hopes to  improve the current 9% survival rate by introducing a therapy that has shown to have up to a 95% tumor response rate.
I wanted to follow-up on those conversations by:

  • Sharing an overview of CytImmune’s anti-tumor technology with a specific emphasis on pancreatic cancer; and
  • Asking for the support of the pancreatic cancer community to get CytImmune’s technology out of the lab and into the hands of patients and doctors. Support is easy. Read this post. Tell a friend about us on Twitter or Facebook and sign our petition of patient support. It makes a big difference to potential investors and partners if we can show that you know and care about our technology.

**Note: If you are already familiar with our technology, feel free to jump to the pancreatic cancer specific section below to read the science most applicable to you.

CytImmune’s Clinical Approach

The Clinical Problem:
Pancreatic cancer tumors have high internal fluid pressure (IFP).  High IFP pushes cancer therapies toward the periphery of the tumor and away from cancer cells growing in the tumor’s interior. This limits the effectiveness of radiation therapy, chemotherapy and even immunotherapy.  It’s a primary reason why tumors shrink after treatment, but then quickly grow back to their original size when treatment is stopped.

The Root(s) of the Problem:
Like all cancers, pancreatic tumors require new blood vessels to grow. These blood vessels are healthy but malformed.  In normal blood vessels, epithelial cells (see pink cells in diagram below) are tightly connected (see healthy blood vessel wall in diagram below). In tumor blood vessels, many blood vessel epithelial cells have gaps between them (see arrows in diagram below). These gaps allow fluid and small blood components to flow into tumors. The amount of material flowing in is greater than the amount of material flowing out. This creates a high fluid pressure environment inside all primary and metastatic pancreatic cancer tumors.

Read More: Releasing Pressure in Tumors: What Do We Know So Far and Where Do We Go from Here? A Review

PDAC and PNET

The majority of pancreatic cancer tumors have the added complication of being extremely dense. Inside Pancreatic Ductal Adeno Carinoma (PDAC) tumors are an unusually high number of non-cancer cells and structural flotsam such as collagen and hyaluronan that make it difficult for cancer killing therapies to reach the cancer cells they are trying to kill. Additionally, there are several techniques that these tumors use to evade the immune system.

Pancreatic Neuro Endocrine Tumors (PNETs) are a less common form of pancreatic cancer, making up less than 5% of pancreatic cancers. While the five year survival rate is better for these patients, more than two thirds will experience metastatic disease. Many individuals who have PNET tumors, and their family members, feel that there is little being done to support new research and treatment for these tumors.

CytImmune’s technology has the potential to help both PDAC and PNET patients.

CytImmune’s Nanotechnology Destroys PDAC and PNET tumors from the inside:
CytImmune has developed a nanomedicine, Aurimune™, that destroys solid tumor blood vessels in primary and secondary solid tumors — including PNET and PDAC tumors. Unlike therapies that slow new blood vessel growth over time, such as VEGF inhibitors like Avastin, CytImmune’s nanomedicine catastrophically collapses the tumor’s vasculature (blood vessel network) in a matter of hours or less.

Unlike most systemically administered therapies, our nanotechnology targets tumors, but leaves healthy surrounding tissues and vital organs unharmed. Aurimune enters tumors through the gaps in tumor blood vessels and attacks the tumor micro-environment from the inside. Since non-tumor blood vessels lack gaps, Aurimune does not enter healthy patient tissues.

We have successfully completed a Phase I clinical trial, which demonstrated no significant adverse events and no dose limiting toxicity. We are raising funds to begin Phase II clinical trials for both PDAC and PNET patients.

Read More: Phase I and Pharmacokinetic Studies of CYT-6091, a Novel PEGylated Colloidal Gold-rhTNF Nanomedicine

A special note for PDAC Patients: While AurImmune does not directly deal with the challenges presented by the dense PDAC tumor micro-environment, we know our nanotechnology can penetrate these tumors and destroy the network of blood vessels supporting cells in the tumor’s interior. Even PDAC cancer cells need working blood vessels to survive! We currently have multiple preclinical studies ongoing with the National Cancer Institute and Rutgers Cancer Institute of New Jersey University to determine the ideal conditions for our Phase II clinical trial.

CytImmune’s Tumor Destroying Nanotechnology

CYT-6091, our first-generation nanomedicine, carries an immune/inflammatory molecule, Tumor Necrosis Factor alpha (TNF).  TNF is the most potent of a class of molecules called vascular disruption agents (VDAs). CYT-6091 is injected into a vein and travels safely through the body. When it reaches a primary or secondary tumor, CYT-6091 passes through the gaps between blood vessel epithelial cells. The TNF on CYT-6091 very quickly binds a receptor known as the  “death receptor”, which is present in a high concentration on all tumor blood vessel epithelial cells. Binding of TNF to the death receptor results in a rapid collapse and destruction of the blood vessels nourishing the tumor’s interior.

Read More: Exposing the tumor microenvironment: how gold nanoparticles enhance and refine drug delivery

After exposure to CYT-6091, many cancer cells in the tumor’s interior die, but that’s not the greatest benefit of CYT-6091. The altered tumor microenvironment with lower pressure provides anti-cancer agents access to the cancer cells they are designed to destroy. These anti-cancer agents may be administered independently, or they can be attached to CytImmune’s nanotechnology using our second-generation nanoparticles.

Attaching cancer-killing-agents to nanoparticles eliminates toxicity and dramatically increases anti-cancer effectiveness (Publication pending, 2017). We believe CYT-6091 and other Aurimune platform nanomedicines could be useful for many stages of pancreatic cancer treatment, especially metastasized cancer.

Research Relevant to Pancreatic Cancer Patients

We tested CYT-6091 + Paclitaxel (Taxol), the active ingredient in Abraxane®, a common pancreatic cancer chemotherapy, in a genetically engineered pancreatic cancer mouse model (GEMM). We used a GEMM because the tumor blood vessel structure more closely approximates what we find in human solid tumors. These particular mice developed PNET tumors. In these experiments, when CYT-6091 was given before chemotherapy, we observed a 6-fold increase in paclitaxel inside tumors.

Moreover, in our second generation nanomedicine, CYT-21000, when we attached paclitaxel to our nanotechnology and delivered it systemically to tumors, not only did more of the drug end up inside the tumor, but the side effects were nearly eliminated. And the clinical outcomes improved dramatically. I can’t release the data from this just yet, but once it’s published, I will update this post with more data and a link to the source. (Publication pending, 2017).

David Kingston of VA Tech assisted with the development of CYT-21000. In a 2016 interview, he notes: “In early lab tests in treating mouse melanoma, a 2.5-milligram dose of paclitaxel delivered on Kingston’s gold nanoparticles vehicle was essentially as effective as a dose of 40 milligrams of paclitaxel by itself.”

Additionally, we have performed a procedure using an MRI machine to detect whether CYT-6091  destroys PNET/PDAC tumor blood vessels. Dye was injected into tumor-bearing mice and we watched to see if the dye would leak out of the tumor. Normally, it would not. After administration of CYT-6091, the MRI demonstrated a massive vascular (blood vessel) leak, which is evidence that tumor blood vessels had been destroyed. (note: the x axis below is minutes; data from PNET GEMMS)

In PDAC mice, the vascular leak was smaller (~half), but still present. This was expected as PDAC tumors have far fewer functional blood vessels than PNET tumors.

Our Phase 1 clinical trial (29 advanced stage IV cancer patients)  included a pre-surgery stage IV PDAC patient.  As part of the trial protocol, we collected multiple biopsies from each patient’s primary tumor and surrounding healthy tissue. We found a high concentration of our nanoparticle inside this patients primary tumor, suggesting CYT-6091 is able to penetrate the dense PDAC tumor environment.

Read More: Phase I and Pharmacokinetic Studies of CYT-6091, a Novel PEGylated Colloidal Gold-rhTNF Nanomedicine

What’s Next?

We are working with the National Cancer Institute, Montefiore Cancer Center, Rutger Cancer and other academic researchers to demonstrate Aurimune’s effectiveness.

Pre-Clinical Next Steps

  1. We are currently conducting multiple pre-clinical studies in a genetically engineered PDAC mouse model to determine which chemotherapeutic agents are optimal for use with CYT-6091 in treating PDAC tumors. Preliminary data will be available in the early fall.
  2. We  are working with the NCI to test CYT-6091 in combination with a popular immunotherapy. This study should be completed in the early fall, with data availability dependent on publication timing.
  3. We are working with academic and industry partners to plan and execute a series of experiments to demonstrate the effectiveness of radiation therapy in combination with CYT-6091 in a mouse pancreatic tumor model. We are currently seeking funding to complete this study.

Clinical Next Steps

  1. We are  raising funds for a Phase II clinical trial in pancreatic cancer patients. The FDA has already approved our protocol for a short dosing study followed by a multi-center clinical trial. We are hoping this trial could begin early in 2018.

What can you do?

  • First, I encourage patients and advocates to ask questions. It’s hard to cover of all the details in a blog post. You may enter questions in the comments section of this post, or reach out to us on Twitter, @CytImmune. If you have chats and want an expert to participate, we are happy to supply someone.
  • Keep advocating for more pancreatic cancer research funds. Like other small biotechs, we rely on the NIH and NCI. We’ve invested millions in our technology, but our story sits inside a much larger research narrative that is born out of the great work done at governmental and academic institutions.
  • Keep advocating for pancreatic cancer patients. Let us know how we can help. We will march along side you, add our voices and perspective where appropriate, and listen to your suggestions. We are a company, but we are also a collection of people who are passionate about improving cancer care.
  • If you want to keep up to date on how our research is progressing, follow us on Twitter or check this blog periodically.
  • If you want to help us, please sign our petition of patient support. It really does help when we can tell potential investors and partners that patients and advocates care about what we’re doing.

 

**Since CYT-6091 is a clinical stage product, we are unable to provide treatment outside of a clinical trial.

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