Technology
Pioneering a new approach to safer immune stimulation.
Improving Immunotherapy Across Indications
Our pipeline centers on two first-in-class small molecules, Alintegimod and 7HP935, for a risk-diversified range of oncology and hematology indications.
Over $34 million in grants awarded by NIH institutions* and CPRIT
*National Institute of Allergy and Infectious Diseases, National Heart, Lung, and Blood Institute, National Cancer Institute
Alintegimod
First-in-class dual LFA-1 and VLA-4 agonists to augment solid tumor immunity with a fast-track designation.
Problem
Overcoming Resistance to Immune Checkpoint Inhibitors
Immune checkpoint inhibitors (ICIs) like anti-PD-1 and aCTLA-4 antibodies have revolutionized cancer treatment by harnessing the immune system to fight tumors. However, many solid tumors remain resistant to these therapies, especially immunologically ‘cold’ tumors that fail to elicit strong immune responses to current cancer therapeutics. These 'cold' tumors have low levels or no immune cells in the tumor microenvironment (i.e., low T-cell infiltration). Without the body's immune cells to rally a sustained defense, certain traditional immuno-oncology therapies (e.g., anti-PD-1s) allow tumors to proliferate unchecked. The challenge lies in enhancing the cancer immunity cycle, particularly T cell recruitment, activation, and their ability to target tumor cells effectively. Overcoming anti-PD-1 resistance is critical to improving outcomes for patients with these difficult-to-treat cancers.
Alintegimod
A New Hope for Patients with Advanced Solid Tumors
Alintegimod (formerly 7HP349) is a groundbreaking, orally delivered small molecule designed to address anti-PD-1 resistance by selectively activating the integrins LFA-1 and VLA-4. These immune cell adhesion molecules are essential for multiple steps in the cancer immunity cycle:
Leukocyte Trafficking: Directing neutrophils and antigen-presenting cells to the tumor site.
Antigen Presentation and T Cell Activation: Enhancing communication between T cells and antigen-presenting cells in lymph nodes and expanding tumor-specific T cells.
Trafficking of Activated T Cells: Ensuring activated cells reach the tumor.
Stabilization of Killing Synapse: Strengthening the connection between T cells and tumor cells for effective killing.
By improving adhesion at each step, Alintegimod enhances the efficacy of immune checkpoint inhibitors in tackling anti-PD-1/PD-L1-resistant solid tumors.
The Evidence
Preclinical and Clinical Success
Alintegimod has demonstrated both single-agent activity and synergy with multiple checkpoint blockade therapies in multiple preclinical mouse models. Building on this success, 7 Hills Pharma completed a Phase I clinical trial in 2021, which showed:
Monotherapy Safety: Confirming Alintegimod is well-tolerated.
Oral Bioavailability: Establishing effective delivery through an oral route.
Defined Phase II Dose Range: Laying the groundwork for future clinical trials.
These results validate Alintegimod’s potential to enhance anti-tumor immune responses and overcome resistance in previously unresponsive tumor types.
The Future
Advancing Alintegimod in Clinical Trials
Supported by over $17 million in nondilutive state and federal grant awards, 7 Hills Pharma is advancing a Phase Ib/IIa clinical trial. This study explores Alintegimod in combination with sequential dual checkpoint blockade therapies to treat patients with anti-PD-1-resistant solid tumors.
By addressing key limitations in cancer immunotherapy, Alintegimod has the potential to transform the treatment landscape for patients with limited options, offering hope for improved outcomes against resistant cancers.
Clinical Trial | Enrolling Now
Alintegimod, A New Hope for Patients with Advanced Solid Tumors
The 7HP-111 Phase Ib/IIa clinical trial (ADD NCT number/link here) is testing Alintegimod, a first-in-class integrin agonist, in combination with dual checkpoint inhibitors (anti-PD-1 and anti-CTLA-4) to treat advanced solid tumors, including those resistant to anti-PD-1 therapy.
Trial Highlights
Goals: Assess safety, tolerability, and preliminary efficacy.
Therapeutic Focus: Patients with advanced solid tumors, including anti-PD-1-resistant cases.
Innovative Approach: Enhances immune response by improving T cell activation and tumor targeting.
Alintegimod offers a promising solution for patients with limited options, redefining treatment possibilities in cancer immunotherapy.
7HP935
First-in-class VLA-4 agonist to augment stem cell engraftment.
The Problem
Challenges in Hematopoietic Stem Cell Transplantation (HSCT)
Hematopoietic stem cell transplantation (HSCT) is a critical treatment for hematological malignancies and genetic disorders. HSCT involves replacement of a patient's damaged or diseased blood-forming cells with healthy hematopoietic stem cells from a living donor. While HSCT offers curative potential, several barriers limit its success:
Graft Failure: Up to 10% of transplant patients experience graft failure, leaving them at significant risk of death without an immediate replacement graft after undergoing myeloablation.
Racial Disparities: Patients from ethnic minority groups often struggle to find matched donors, creating inequities in access to life-saving transplants.
Recovery Risks and Costs: Prolonged recovery times increase the risk of complications and drive up healthcare costs.
CRISPR Therapy Limitations: CRISPR-based treatments for genetic disorders require efficient HSCT to safely implant gene-edited cells, but current CRISPR methods often result in prolonged time to engraftment, increasing the risk of deadly infections during patient recovery.
These challenges highlight the urgent need for innovative solutions to improve outcomes, reduce costs, and make stem cell therapy accessible to all patients.
The Solution
7HP935 – A Breakthrough in Stem Cell Engraftment
7HP935 is a first-in-class small molecule that selectively activates the integrin VLA-4, a key cell adhesion molecule crucial for the homing and engraftment of hematopoietic stem cells into the bone marrow niche. Its innovative approach potentially offers transformative benefits:
Faster Engraftment: Accelerates the timeline from HSCT to successful stem cell engraftment, reducing the risk of complications during recovery.
Improved Success Rates: Lower risk of deadly infections and other complications during transplant recovery.
Cost Reduction: Faster engraftment may reduce patient time in hospital, cutting overall treatment costs and improving the efficiency of healthcare delivery.
Addressing Inequities
Increasing Access for All Patients
One of the most pressing issues in the transplant field is the lack of matched donors for ethnic minority patients. By combining 7HP935 with umbilical cord blood transplants—which are more readily available and require less stringent matching—this approach offers a safer, more effective, and accessible therapy. It provides a potentially curative option for patients who otherwise face limited or no alternatives, addressing critical disparities in access to care.
Supporting CRISPR-Based Therapies for Genetic Disorders
CRISPR-based therapies represent a revolutionary approach to treating genetic disorders of the bone marrow. However, their success depends on safe and efficient stem cell engraftment. 7HP935 aligns perfectly with this need, enhancing the homing and integration of gene-edited stem cells into the bone marrow. By doing so, it offers potential CRISPR partners a durable competitive advantage, enabling better outcomes, improved scalability, and profitability in the genetic therapy marketplace.
The Future of HSCT with 7HP935
With its ability to accelerate engraftment, improve success rates, and reduce costs, 7HP935 is poised to redefine the HSCT landscape. By addressing key challenges like graft failure, racial disparities, and the limitations of CRISPR-based therapies, 7HP935 offers a comprehensive solution that could transform outcomes for patients with hematological malignancies and genetic disorders alike.