Oncology

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

HighField’s drug development reflects a diverse strategy for alerting the body’s immune system to the cancers hiding in plain sight, as well as attacking 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.

On one level, we design our lipids to maximize their inherent targeting properties towards rapidly growing tissue, like cancer tissue. On another level, we enhance the targeting by attaching antibodies to the lipids to form an Antibody Drug Complex (LipoADCplex™). The programs each use uniquely designed lipid structures to infiltrate the tumor microenvironment and strike specific molecular targets that expose solid tumors to different effects.

Our immunoliposomes offer greater payload capacity and flexibility than other targeted therapeutics such as existing antibody-drug conjugates (ADCs). This allows for greater safety while also improving the therapeutic effect, resulting in a larger therapeutic window.

We have developed even more advanced lipid systems to interact with multiple cell types of the tumor microenvironment in order to facilitate and sustain immunotherapy against cancer.

Technology

HighField’s Oncology 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

TL01+TL02
+R848

HFK2
Cancer

TL01
conjugated liposome

Lipid-based Antibody Drug Complex Platform - K1

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

Our LipoADCplex platform offers greater payload capacity and flexibility than other targeted therapeutics such as antibody-drug conjugates (ADCs). This allows for greater safety while also improving the therapeutic effect, resulting in a larger therapeutic window.

Kl is the most advanced LipoADCplex under development in our pipeline. It contains the antibody lipid TL01, which is directed to HER2. The encapsulated drug payload is doxorubicin. In animal models, K1 has higher anti-tumor activities than the leading drugs, such as T-DM1 and DS-8201a. Importantly, K1 had no associated chemo-resistance effect that is found in these other drugs.

In Phase I clinical studies, K1 has also been shown to be safe at doxorubicin dose level of 30mg/m2. The first patient treated has achieved PFS of over 6 months.

TRAFsome™ T cell Engager - HF50

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 TRAFsome. HF50 also carries a payload of Resiquimod, a small molecule compound that modulates T cell response toward cancer cells.

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 tumors.

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.

Immune Modulator - K16

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.