Pipeline

HighField is developing lipid-based systems offering pioneering therapeutic approaches

HighField Development Pipeline

Product
Indication

API

Preclinical Development

Clinical Studies

PK/PD

CMC

TOX

IND

Ph 1a

Ph 1b/2

HF1K16
IO

ATRA

HF158K1
IO/Her2 low

TL01+
doxorubicin

HF50
IO/Her2 low

TL02+R848

HFG1
Diabetes

mRNA based GLB-1R

What's Ahead for HighField

Product
Indication

API

Progress

PCC

PK/PD

CMC

IND

HFK2
Cancer

TL01
conjugated liposome

HFG2
Auto-immune

TL02
conjugated
LNP

HFG3
Metabolic
Disease

siRNA

Our therapies represent unique approaches for targeting specific molecular elements of the tumor microenvironment

The company’s drug development reflects a diverse strategy for alerting the body’s immune system to the cancers hiding in plain sight, as well as attack the tumor directly. The most advanced programs each use uniquely designed lipid structures to infiltrate the tumor microenvironment and strike specific molecular targets that expose solid tumors to different effects.

In Phase 1 clinical trials, our ATRA-encapsulated immune modulating liposome has shown encouraging results in treating brain tumors

K16 combines a lipid bilayer structure and all-trans retinoic acid (ATRA). In high concentrations, ATRA can induce immature immune cells (MDSCs) to become mature, active immune cells (dendritic cells). ,

MDSCs have an immune suppressive activity, so converting them to mature active immune cells generates an anticancer effect. Moreover, cancer patients tend to accumulate MDSCs beyond what is found in healthy people and also accumulate them in the tumors themselves. This is a particularly insidious suppression of the immune systems of cancer patients that when reversed can have a profound effect on tumors.

As ATRA is a metabolite of vitamin A, this lipid system has demonstrated a high degree of safety in human trials. In the initial human trial data, this lipid system has also shown a strong signal of single-agent efficacy in cancer, particularly in brain tumors .

Beyond this, given its strong safety profile and unique mechanism against tumors, K16 is a prime candidate for combination with other cancer therapeutics.

This drug-encapsulated immunoliposome represents a new generation of targeted cancer therapy

K1 is a lipid bilayer system with targeting antibodies directed to HER2. HER2 is an antigen expressed on cells, but tends to be overexpressed on many tumors. K1 also carries a drug payload of doxorubicin which is a known anticancer agent.

By optimizing these components to each other and to cancer tissue, the resulting lipid system has shown an ability to effectively target, bind and deliver to HER2+, HER2 low and even triple negative tumors in relevant animal models without adverse interactions with healthy tissue. Effectively targeting HER2 low tumors has only been achieved by one drug to date.

Given the animal model experience, K1 has been approved for human trials and is in clinical development for patients with advanced refractory HER2 low and HER2+ solid tumors. These include breast, bladder, pancreatic, ovarian, stomach, colon, prostate, lung, uterine and cervix cancers.

This lipid system can be compared to current antibody-drug conjugate immunotherapy. However, K1 offers efficacy with a lower toxicity drug payload and a higher payload to antibody ratio resulting in a much safer and more effective design.

Directing T cells towards cancer cells and enhancing anticancer activity with an immune modulator

HF50 is a lipid bilayer system with two different antibodies attached. The first is directed to immune T cells, while the second antibody is directed to HER2 expressing tumors. This system is called T cell Redirecting Antibody Fragment-anchored Liposomes, or TRAFsomes. HF50 also carries a payload of Resiquimod, a small molecule compound that modulates T cell response toward cancer cells.

The use of a lipid bilayer in this system has another effect. Unlike tumor cells, T cells do not internalize the lipids when they attach to the T cell membrane. The lipids stay attached on the outside of the T cell and provide a coating that includes the HER2 targeting antibodies. This effectively results in a T cell that has HER2 antibodies attached to its outer cell membrane.

By optimizing these components to each other and to HER2 expressing tumors, relevant animal model data show this to be effective against HER+ tumors. Moreover, this is the first systemic use of Resiquimod, and data show that stimulating the immune T cells in this manner greatly enhances the anti-tumor activity.

This lipid system can be compared to a bispecific antibody but exceeds it in many aspects. Bispecifics have very limited antibody conjugation schemes. An optimal ratio of the components cannot be achieved. This limits the therapeutic window and their efficacies in solid tumor.

HF50 as an enhanced CAR T is a more apt comparison. The goal of CAR T is to produce T cells expressing anti-tumor antibodies on their outer membrane. HF50 achieves this goal without the complex and expensive processing inherent in CAR T-cell therapies. Moreover, the immunomodulatory payload also plays an important role in enhancing T cell activity.

HF50 is in preclinical development.

An LNP-mRNA complex for very long term expression of GLP-1R agonist

HFG1 is an LNP-mRNA complex that provides expression of a GLP-1R agonist, for weight loss and treating diabetes. HFG1 is presently in IND enabling studies for a U.S. IND filing scheduled for 3Q2024.

The components of HFG1’s LNP complex were selected to provide prolonged expression of the GLP-1R agonist without observable immune response. HFG1 requires fewer injections than existing GLP-1 products while providing steady-state agonist activity.

Diabetic monkeys treated with HFG1 show weight loss and significant A1C reduction over an extended period. After an initial activity peak at dosing, a steady state of GLP-1R activity and A1C control were observed for at least 60 days. This translates into therapeutic activity of about 4-5 months in humans for a single injection. No behavior changes or toxicities were observed other than an initial loss of appetite at the time of injection.