A2 Biotherapeutics

Overview

A2 Biotherapeutics is a clinical-stage biotechnology company founded in 2018 and based in Agoura Hills, California. The company specializes in developing innovative, precision-targeted cell therapies for the treatment of solid tumors. Key aspects of A2 Biotherapeutics include:

Technology Platform

At the core of A2 Bio's approach is the proprietary Tmod™ platform, a modular and flexible system that enables the creation of diverse cancer therapy candidates. This platform utilizes a combination of activator and blocker receptors to precisely target tumor cells while sparing normal cells. The blocker technology acts as a self-actuated safety switch, leveraging irreversible genetic losses specific to tumor cells to protect normal tissues.

Pipeline

A2 Bio has a robust pipeline featuring one clinical and three pre-clinical programs targeting various solid tumors. The two lead programs are:

1. A2B530: A CAR-T cell therapy targeting tumors that express carcinoembryonic antigen (CEA) but lack the HLA-A*02 antigen. It is being studied in the EVEREST-1 clinical trial for patients with non-small cell lung cancer (NSCLC), colorectal cancer (CRC), and pancreatic cancer (PANC).
2. A2B694: A CAR-T cell therapy targeting tumors that express mesothelin (MSLN) but lack the HLA-A*02 antigen. It is intended for a clinical trial studying patients with NSCLC, CRC, PANC, ovarian cancer (OVCA), and mesothelioma. In addition to these autologous programs, A2 Bio is also developing allogeneic candidates.

Clinical Trials

The company is conducting seamless phase 1/2 clinical studies, including EVEREST-1 and EVEREST-2. Patient enrollment is facilitated through the BASECAMP-1 prescreening study, which utilizes AI-enabled precision diagnostics.

Funding

A2 Biotherapeutics recently closed an $80 million Series C financing round to support its clinical development programs and advance its pipeline of CAR-T cell therapies based on the Tmod™ platform.

Leadership

The company is led by a highly experienced executive team with proven track records in the discovery, development, manufacturing, and commercialization of oncology therapeutics across multiple modalities, including cell therapy. A2 Biotherapeutics stands at the forefront of developing precision cell therapies aimed at addressing significant unmet needs in the treatment of solid tumors, with a strong focus on safety, efficacy, and personalized medicine.

Leadership Team

A2 Biotherapeutics' leadership team comprises experienced executives with extensive backgrounds in the biopharmaceutical industry. Key members include:

James Robinson

• Chief Executive Officer and Member of the Board of Directors
• Appointed effective April 1, 2024
• Over 30 years of experience in the industry
• Previously served as President and CEO of Urovant Sciences, President and COO of Paragon Biosciences, and President and COO of Alkermes plc
• Spent over 12 years at Astellas Pharma, where he was President of the Americas

Alexander Kamb, Ph.D.

• Founder, Chief Scientific Officer, and Member of the Board of Directors
• Founded A2 Biotherapeutics to advance cell therapy for disease treatment
• Decades of experience, including roles at Amgen as senior vice president and head of discovery research
• Previously led the oncology research group at Novartis
• Founder of Arcaris and former employee at Myriad Genetics

David Goeddel, Ph.D.

• Chairman of the Board of Directors
• Oversees the company's strategic direction

David Lucas

• Chief Operating Officer
• Responsible for operational aspects of the company

Former Leadership

• Scott Foraker: Served as the first CEO of A2 Biotherapeutics, leading the company from early discovery through the dosing of its first clinical candidate (no longer in the CEO role as of April 2024) The leadership team at A2 Biotherapeutics is characterized by their deep experience in biotechnology, oncology, and cell therapy, positioning the company to advance its innovative therapeutic platforms.

History

A2 Biotherapeutics, a biotechnology company focused on developing innovative cell therapies for cancer, has a rich history marked by significant milestones:

Founding and Initial Funding

• Founded in 2018 by veteran biotechnology leaders with experience from companies like Amgen and Kite Pharma
• Emerged from stealth mode in November 2019 with a $57 million Series A financing round
• Backed by investors including The Column Group, Vida Ventures, Samsara BioCapital, and Nextech Invest

Technology Development

• Developed the proprietary Tmod™ platform, designed to selectively target and destroy tumor cells while sparing healthy cells
• Utilizes the HuTARG™ technology, licensed from Innovative Targeting Solutions, to identify and engineer precise binders derived from antibodies and T-cell receptors

Leadership and Team

• Led by a management team with over 90 years of combined experience in cell therapy and biotechnology
• Key members included Scott Foraker (former President and CEO) and Agi Hamburger, Ph.D. (Chief Operating Officer)

Pipeline and Development

• Established a robust pipeline with multiple programs focusing on solid tumors
• Advanced programs through collaborations and planned innovations in manufacturing
• Launched an autologous cell manufacturing facility
• Highlighted progress in CAR T-cell clinical programs at various scientific meetings

Funding and Growth

• Raised a total of $190.5 million across various funding rounds, including a Series C round
• Expanded capabilities with support from additional investors such as Euclidean Capital

Current Status

• Headquartered in Agoura Hills, California
• Operates as a fully integrated discovery, development, and manufacturing organization A2 Biotherapeutics continues to grow and innovate in the field of cell therapy, leveraging its unique technologies and experienced leadership to address unmet needs in cancer treatment.

Products & Solutions

A2 Biotherapeutics is at the forefront of developing innovative cell therapies for solid tumor cancers, with a primary focus on CAR-T cell therapies. Their product pipeline is built on the foundation of their proprietary Tmod™ platform.

Tmod™ Platform

The Tmod™ platform is a modular and flexible system designed to create precise and personalized T cell therapies. Its key feature is a dual-receptor design:

• Activator: Targets tumor-specific antigens to identify and attack cancer cells.
• Blocker: Binds to antigens on normal cells, preventing unintended damage and acting as a safety switch to protect healthy tissue.

Clinical Programs

A2 Biotherapeutics has several programs in various stages of development:

1. A2B530
   • Targets tumors expressing carcinoembryonic antigen (CEA) but lacking the HLA-A*02 antigen.
   • Currently being evaluated in the EVEREST-1 clinical trial for recurrent, unresectable, locally advanced, or metastatic non-small cell lung cancer (NSCLC), colorectal cancer (CRC), and pancreatic cancer.
   • Received the US FDA's orphan drug designation for colorectal cancer treatment.
2. A2B694
   • Targets tumors expressing mesothelin (MSLN) but lacking the HLA-A*02 antigen.
   • To be evaluated in the EVEREST-2 clinical trial for NSCLC, CRC, pancreatic cancer, ovarian cancer, and mesothelioma.
3. Allogeneic Program
   • A third CAR-T program with an undisclosed target, focusing on allogeneic (off-the-shelf) therapies using donor cells.
   • Aims to overcome scalability and manufacturing challenges associated with autologous CAR-T therapies.

Technology and Manufacturing

• The Tmod™ platform leverages irreversible genetic losses specific to tumor cells, allowing for highly specific targeting and potentially safer treatment doses.
• Compatible with both autologous and allogeneic immune cell therapies.
• In-house cGMP manufacturing capabilities for both autologous and allogeneic cell products.
• Utilizes AI-driven pre-screening studies, such as BASECAMP-1, to efficiently identify eligible patients for clinical trials. A2 Biotherapeutics' approach to CAR-T cell therapies aims to overcome the challenges of targeting solid tumors by selectively distinguishing between tumor and normal cells, potentially offering a safer and more effective treatment option for cancer patients.

Core Technology

A2 Biotherapeutics' core technology revolves around their proprietary Tmod™ platform, designed to enhance the precision and safety of T cell therapies, particularly for treating solid tumors.

Key Components of Tmod™ Platform

1. Dual-Receptor Design
   • Utilizes a system consisting of an activator and a blocker.
   • Activator: Targets specific antigens on tumor cells, triggering their destruction.
   • Blocker: Recognizes antigens on normal cells, protecting them from harm.
2. Precision Targeting
   • Exploits specific genetic losses common in tumor cells but not in normal cells.
   • Example: The blocker targets HLA-A*02, often lost in tumor cells but present in normal cells.
   • Enables selective killing of tumor cells while sparing normal cells.
3. Modularity and Flexibility
   • Highly adaptable platform allowing creation of various therapy candidates.
   • Combines different activators and blockers to target specific cancer types.
   • Supports both autologous and allogeneic immune cell therapies.
   • Applicable to multiple types of immune cells and manufacturing platforms.
4. Safety Mechanism
   • Blocker technology acts as a self-actuated safety switch.
   • Protects normal cells from therapeutic effects intended for tumor cells.
   • Helps overcome toxicity barriers and expand the therapeutic window.
   • Allows for potentially safer and more effective treatment doses.

Clinical Applications

• A2 Biotherapeutics is advancing several programs using the Tmod™ platform:
  • A2B530 and A2B694 are in various stages of clinical development.
  • These therapies target different solid tumors including non-small cell lung cancer, colorectal cancer, pancreatic cancer, ovarian cancer, and mesothelioma. The Tmod™ platform represents a significant advancement in T cell therapies, offering a precise, personalized, and potentially safer approach to treating solid tumors. By leveraging the platform's unique dual-receptor design and modular nature, A2 Biotherapeutics aims to develop more effective cancer treatments while minimizing damage to healthy tissues.

Industry Peers

A2 Biotherapeutics operates within the biotechnology sector, specifically focusing on cell therapy treatments for solid tumors. The company's innovative approach places it among several notable peers and competitors in the field.

Direct Competitors in Cell Therapy

1. Triumvira: Develops T-cell therapies for cancer treatment.
2. Neogene: Focuses on personalized T-cell therapies for cancer.
3. NexImmune: Works on T-cell-based immunotherapies. These companies share A2 Biotherapeutics' focus on advancing cell therapies for cancer treatment, making them direct competitors in the field.

Broader Oncology and Biotechnology Peers

1. Clovis Oncology: Develops and commercializes cancer treatments.
2. Dermavant Sciences: Known for dermatology work but competes in the broader biotech space.
3. Metrum Research Group: Involved in biopharmaceutical research and development.
4. ArcherDX: Develops precision immunotherapies and genetic testing solutions.
5. Inscripta: Works on gene editing and synthetic biology.
6. Apellis Pharmaceuticals: Develops treatments for various diseases, including cancer and autoimmune disorders. These companies, while not direct competitors in cell therapy, operate within the broader oncology and biotechnology sectors, contributing to the overall competitive landscape.

Key Industry Characteristics

The biotechnology sector, particularly in cell therapy and cancer treatment, is characterized by:

• Innovation Focus: Companies invest heavily in research and development to create novel therapeutic approaches.
• Clinical-Stage Development: Many companies, including A2 Biotherapeutics, have therapies in various stages of clinical trials.
• Significant Funding: The sector attracts substantial investment due to the potential for groundbreaking treatments.
• Precision Medicine: There's a growing trend towards personalized treatments tailored to individual patients or specific cancer types.
• Collaborative Environment: Despite competition, companies often collaborate on research or licensing agreements to advance the field. A2 Biotherapeutics' position in this competitive landscape is defined by its unique Tmod™ platform, which offers a novel approach to addressing the challenges of solid tumor treatment. As the field of cell therapy continues to evolve, A2 Biotherapeutics and its peers are at the forefront of developing potentially life-changing treatments for cancer patients.