John Orwin, President, and CEO at Atreca Shares his Views on Developing Novel Therapies for Cancer

Shots:

John spoke about the development of a T cell engaging bispecific antibody directed against a novel solid tumor target under Atreca’s existing collaboration with Xencor
He also talked about how this joint program combines the Atreca-discovered antibody, APN-346958, with Xencor’s XmAb CD3 bispecific antibody platform
The interview gives an understanding of Atreca’s focus on developing novel therapeutics generated by its differentiated discovery platform

Smriti: Can you please give our readers a brief about your existing strategic collaboration with Xencor?

John Orwin: Our collaboration with Xencor, signed in 2020, is focused on researching, developing and commercializing T cell engaging bispecific antibodies as potential therapeutics in oncology. Under the terms of the agreement Atreca provides antibodies against novel tumor targets from which Xencor engineers XmAb bispecific antibodies that also bind to the CD3 receptor on T cells. Up to two joint programs can be mutually selected for further development and commercialization, with each partner sharing 50 percent of costs and profits. Each company will lead development, regulatory and commercialization activities for one of the joint programs. In addition, the agreement allows for each partner to pursue up to two programs independently.

Smriti: Discuss about the development of the T Cell Engaging Bispecific Antibody Directed program with Xencor? What are the various tumor types you are targeting under this?

John Orwin: We believe that Xencor’s approach to weaponization has the potential to complement our approach to discovery, which leverages the human system to identify novel antibodies against tumor selective targets. The program announced recently is the first joint program to emerge from the collaboration and combines Atreca-discovered antibody, APN-346958, with Xencor’s XmAb CD3 bispecific antibody platform. The target of ‘958 is a novel RNA-binding protein and is tumor-reactive in at least 50% of samples for six tumor types evaluated, including: colorectal, thyroid, head and neck, urothelial, melanoma and brain cancer.

Smriti: How will Xencor’s XmAb bispecific Fc and cytotoxic T-cell binding domain be advantageous to this joint program based on APN-346958?

John Orwin: Xencor has considerable expertise in generating CD3-binding bispecific T cell engagers, from initial antibody engineering and manufacturing through clinical development. In particular, Xencor has developed an advanced platform for rapidly building, evaluating, and developing CD3-binding T cell engagers that should enable the two parties to combine Atreca’s novel antibody-target pairs with varying levels of T cell activation and in a range of geometries that optimize therapeutic response.

Smriti: Tell us how you are planning to lay out this program and what outcomes are you expecting from this?

John Orwin: Preclinical development is ongoing and we expect to name a candidate from the program later this year. Once a candidate is chosen we will seek to validate it in a series of animal models while simultaneously developing a robust immunohistochemistry assay for patient selection, evaluating PK/tolerability in NHP, and finalizing CMC for the initial clinical studies.

Smriti: Shed some light on the key candidate from this program APN-346958? What are the plans to file the IND application for it?

John Orwin: APN-346958 is the Atreca-discovered antibody that the program is based upon. We expect to name a candidate later this year and are targeting an IND filing by early 2025. Atreca will lead clinical development of the program.

Smriti: Are you planning to develop any additional programs with Xencor in solid tumors through its CD3 bispecific engineering?

John Orwin: Early-stage research on additional programs is ongoing as part of the existing collaboration, which allows for one additional joint program and up to two independent programs for each partner.

Smriti: Please give an overview of Atreca’s oncology portfolio. What are the ongoing oncology programs?

John Orwin: Atreca’s oncology pipeline consists exclusively of tumor targeting antibodies discovered in-house. The pipeline is led by ATRC-101, which is currently being evaluated in a Phase 1b clinical trial both as monotherapy and in combination with pembrolizumab. ATRC-101 has been well tolerated in the trial and has generated promising early results, including a PR in lung cancer patients treated with monotherapy and a CR in melanoma patients treated with the combo therapy. In addition to ATRC-101 and APN-346958, Atreca is independently advancing a preclinical program based on APN-497444, which targets a novel tumor glycan present on a number of prevalent tumor types, in particular colorectal cancer.

Image Source: Canva

About the Author:

John Orwin is the President and CEO of Atreca. He is a dynamic leader with a passion for addressing critical unmet needs to improve the lives of patients. In his current role, he is helping lead the charge for Atreca’s revolutionary and proprietary approach to oncology treatment, which has the potential to change the lives of large groups of patients. Orwin brings over 25 years of diverse experience in the biotechnology and pharmaceutical industries, having held senior positions at leading pharmaceutical and biotechnology companies, including Johnson & Johnson, Affymax, Rhone-Poulenc Rorer, Genentech, and Relypsa