Neogene Co-Founder and CEO Carsten Linnemann, PhD,

AstraZeneca has agreed to acquire Neogene Therapeutics for up to $320 million cash, the companies said Tuesday, in a deal intended to bolster the buyer’s portfolio of cancer-fighting cell therapies.

Neogene specializes in discovering, developing, and manufacturing next-generation T-cell receptor therapies (TCR-Ts) to treat solid tumors. TCR-Ts are designed to recognize intracellular targets, including cancer-specific mutations, thus potentially unlocking targets previously inaccessible through cell therapies.

Neogene reasons that its TCR-T approach offers an advantage over most current cell therapy approaches in oncology, which have focused on modifying the immune system’s T cells to recognize proteins expressed on the surface of cancer cells.

“This acquisition represents a unique opportunity to bring innovative science and leading experts in T-cell receptor biology and cell therapy manufacturing together with our internal oncology cell therapy team, unlocking new ways to target cancer,” Susan Galbraith, executive vice president, oncology R&D, AstraZeneca, said in a statement. “Neogene’s leading TCR discovery capabilities and extensive manufacturing experience complement the cell therapy capability we have built over the last three years and allow us to accelerate the development of potentially curative cell therapies for the benefit of patients.”

AstraZeneca reasons that it can build upon its portfolio of chimeric antigen receptor T-cell (CAR-T) therapies for blood cancers by also developing CAR-T candidates that target solid tumors by overcoming the immune-suppressive tumor microenvironment. The pharma giant is developing next-generation cell therapies from which physicians could select off-the-shelf treatments using the cells of healthy donors.

Privately-held Neogene is advancing a pipeline of individualized TCR therapies as well as TCR therapies targeting shared neoantigens—including mutated KRAS (mKRAS) and mutated TP53 (mTP53).

That pipeline is led by the company’s only disclosed drug candidate NT-125, an autologous, fully-individualized, multi-specific TCR therapy targeting neoantigens, and being developed to treat advanced solid tumors. In May, Neogene received from Dutch regulators its first Clinical Trial Application (CTA) approval for a Phase I study of NT-125. The Phase I study is designed to enroll adult patients with various types of advanced solid tumors, in partnership with the Netherlands Cancer Institute (NKI).

NT-125 is designed to contain up to five distinct neoantigen-specific TCRs per patient in a single cell product of engineered T cells, allowing multiple neoantigens presented by HLA class I and HLA class II molecules to be targeted—which according to Neogene is intended to create a more impactful TCR therapy for more patients.

Preventing antigen escape

NT-125 aims to reduce the probability of antigen escape and potentially maximize the depth and durability of clinical responses in a patient population with difficult-to-treat tumors and high unmet need, according to the company.

Neogene will maintain its current bases of operations with a combined 120 employees in Santa Monica, CA, and Amsterdam, the Netherlands, and will operate as a wholly-owned subsidiary of AstraZeneca, the companies added.

AstraZeneca agreed to pay $200 million upfront for Neogene, plus up to $120 million in combined payments tied to achieving milestones and non-contingent consideration.

The acquisition is set to close in the first quarter of 2023, subject to customary closing conditions and regulatory clearances.

AstraZeneca said the Neogene acquisition will not affect previously-issued guidances to investors. In releasing third-quarter results on November 10, AstraZeneca raised its guidance on “core” earnings per share at constant exchange rates—to an increase by a high-20s to low-30s percentage, vs a mid-to-high twenties increase that was previously forecast. At actual exchange rates, AstraZeneca now expects its FY 2022 Core EPS growth to be reduced by a mid-to-high single-digit percentage due to currency fluctuations, versus previous guidance in the mid-single digits.

[“Core” results exclude costs related to the acquisition of Alexion, amortization of intangibles, impairments, restructuring charges, and the settlement of a patent dispute with Chugai Pharmaceutical that led AstraZeneca to pay Chugai $775 million in the second quarter.]

Neogene CEO Carsten Linnemann, PhD, co-founded the company in 2018 with Ton Schumacher, PhD, chairman of Neogene’s Scientific Advisory Board and principal investigator at the Netherlands Cancer Institute, Oncode Institute, in partnership with life sciences investment/incubation firm Two River, and cell therapy pioneer Arie Belldegrun, MD, the founder of Kite Pharma (acquired by Gilead Sciences for $11.9 billion in 2017), and a co-founder and executive chairman of Allogene Therapeutics.

Neogene has raised capital through investors that have included Vida Ventures, TPG, EcoR1 Capital, Jeito Capital, Syncona, Polaris Partners, and Pontifax.

“Our expertise, clinical portfolio, and platform technologies in this area combined with AstraZeneca’s leadership in oncology and global footprint means we are well-positioned to translate pioneering science into novel treatments for hard-to-treat cancers,” Linnemann stated.