IO+ is a better way to deliver combination cancer therapies.
The IO+ Platform
Built around engineered gold nanoparticles, our IO+ platform includes stealth and targeting components, and is designed to allow novel and already approved cancer therapies to be delivered in combination in a safer, more effective way.
We differentiate ourselves from other nanotherapies through the inclusion of TNF alpha on all IO+ products. TNF remodels the tumor microenvironment enabling our nanoparticles and other co-delivered therapies to rapidly penetrate and accumulate inside the tumor. By treating solid tumors with immune modulating cytokines in previously impossible-to-dose combinations , we are able to remodel the tumor environment, activate an immune response, and kill cancer cells in hard to reach regions of the tumor.
Two Types of Combination Therapies: Two Better Approaches
IO+ Improves Standard of Care
Standard of care cancer therapies can be given in combination with CYT-6091 or other IO+ therapeutics. Delivering multiple therapies in combination is a common approach to treating many cancers. Cytimmune’s first generation therapeutics including CYT-6091 are designed to attack the tumor in multiple ways while also enhancing the performance of other co-administered therapies.
Remodeling the tumor environment for treatment success
Our animal model data show that when common cancer therapies such as paclitaxel or doxorubicin are administered immediately following CYT-6091, the intra-tumoral concentration of these drugs increases by 500-700%. Pairing CYT-6091 with existing therapies significantly improves response rates.
IO + Platform Delivery
Nearly any cancer therapy can be delivered on the IO+ platform.
Our data show that tadrgeting cancer therapies to tumor tissues using IO+ results in:
· More drug reaching and concentrating inside the tumor
· Fewer or no dose-limiting toxicities
· Increased clinical efficacy.
The IO+ platform allows multiple cancer therapies to be delivered systemically in the same “package,” and is capable of delivering nearly any combination of cancer therapies including complex biologics, antibodies, small molecule chemotherapies, precision medicines, and even genetic material.
TNF alpha is a catalyst for IO+ success
Tumor Necrosis Factor alpha (TNF) is a cytokine secreted by Natural Killer cells and other immune system cells in response to disease. At clinically relevant doses, it has many anti-tumor functions.
It rapidly destroys tumor blood vessels, eliminates high fluid pressure inside tumors, and disrupts tumor organization. This enables our IO+ therapeutic particles as well any additional therapy given after an IO+ therapy to penetrate deeper and stay longer inside the tumor. It is a powerful Death Ligand — meaning it can induce many types of cancer cells to undergo a self-killing process known as apoptosis.
Finally, TNF alpha is a potent immune system activator and is known to activate killer T-Cells (CD8+), which are critical to generating an anti-tumor immune response.
Systemic delivery of a clinically relevant dose of TNF has been limited due to toxicities. IO+ makes systemic delivery possible. Our first clinical trial delivered 4x the previous maximum tolerated dose (MTD) of TNF alpha with no dose limiting toxicities.
IO+ Therapeutics Attack Tumors in Three Ways
Activating Immune Cells
IO+ therapeutics activate key elements of the immune system. High-dose TNF alpha drives an increase in cytotoxic “killer” T-cells within the tumor. Other IO therapies delivered on the construct have demonstrated the potential to down-regulate immune suppression inside the tumor and activate key immune system components such as Macrophages, NK cells, and APCs.
Remodeling the TME
All IO+ therapies radically alter the conditions inside the tumor. Changes effected include destruction of blood vessels that feed the tumor; elimination of high intra-tumoral fluid pressure, which is known to significantly limit the efficacy of many therapies; and disruption of organization within the tumor interior.
Killing Cancer Cells
IO+ therapeutics indirectly and directly attack and kill cancer cells by:
Induction of apoptosis through death domain receptors;
Delivering cytotoxic therapies directly to cancer cells;
Starving cancer and supporting cells by cutting off blood flow;
Activating the immune system inside the tumor.
Engineering IO+ Therapeutics
First Generation IO+ Therapeutics
Designed to deliver a high dose of a single therapeutic, this IO+ construct was created to be used in combination with existing standards of care. Special stabilizers (not shown) are used to strengthen the binding of each component to the gold particle.
CYT-6091 (shown left)
Our lead therapeutic CYT-6091 has a 27nm gold core and carries 100 copies of the anti-cancer agent TNF alpha. In a phase 1 clinical trial, Cytimmune demonstrated the ability to deliver 4x the MTD of TNF alpha with no DLTs and an AUC 32x that of native TNF alpha delivered at the MTD.
Second Generation IO+ Therapeutics
All IO+ therapeutics have a gold core, PEG thiol, bond stabilizing agents, and TNF alpha.
Additional anti-cancer agents including hydrophobic and hydrophilic small molecule therapies, biologics, genetic material, and other immunotherapies may be attached through patented or trade secret bind-and-release chemistries. Therapeutics may be permanently tethered to the particle or released once inside the tumor with independently tailored kinetics.
An additional hydrophobic layer may be introduced around the core of the particle to stabilize certain small molecule drugs in route to the tumor.
Our Flexible Platform Enables Multiple Combination Therapies
IO Combinations
A diverse array of immune activating therapeutics are approved and in development. Creating combinations of these therapies improves anti-cancer activity and reduces the dangers of off-target autoimmune issues that currently occur in a high percentage of patients.
Enhanced Therapeutics
The IO+ platform has demonstrated ability to localize drugs to the tumor and reduce side effects. Whereas numerous other small molecule drugs that target cancer cells are known to be effective but highly toxic, or effective but limited by poor accumulation inside the tumor.
Pharma Rescue
Many promising anti-cancer therapeutics are similar to TNF alpha. They may have clear clinical benefit, but are too toxic or not targeted enough to be given at clinically relevant doses. Therapeutic delivery using the IO+ platform can solve these challenges.