HONG KONG Xian, China-based Yufan Biotechnologies Co. Ltd. has partnered with Pittsburgh-based Abound Bio Inc. to discover and develop antibodies directing CAR T cells against cancer targets.

The three-year partnership will see the two companies incorporate antibodies for novel cancer targets into the enhanced, HPK1 (hematopoietic progenitor kinase 1)-inhibited CAR T-cell platform, they said. The agreement covers 10 cancer targets, including difficult to treat solid tumors such as liver cancer, Abounds CEO John Mellors told BioWorld.

Although both companies declined to reveal financial details, Mellors said, I calculate that Yufans technology added to Abounds antibodies gives a value greater than two." Yufan declined to comment for the article, but CEO Yan Zhang said, "The partnership with Abound will improve CAR T-cell products for cancer therapy.

The two companies will also share expertise and any potential commercial upside, as well as inventorship and development rights. Yufan definitely benefits, both financially and non-financially, particularly via development rights in China, Mellors said.

The companies will conduct preclinical, then clinical testing of the new CAR T cells against solid tumors, with trials expected to start in the first or second quarter of 2021, Mellors said. They will target the greater China market initially, with the rest of the world to follow. No other firms have been targeted as future partners yet.

Academic roots

The partnership between Yufan and Abound started with an academic collaboration between the National Cancer Institute and Tsinghua University, based on the work led by the universitys professor of pharmaceutical science, Xuebin Liao, who co-founded Yufan along with Zhang. That work demonstrated that HPK1 promotes T-cell exhaustion through NFkB-Blimp1 activation, and that blocking HPK1, via either gene knockout or small-molecule inhibitors, improves CAR T-cell immunotherapy.

Yufan was founded in July 2016 as part of the Xi'an Hi-tech Industries Development Zone Central Organization Departments Thousand Talents program. It focuses on upstream technology development, services and antibody screening for immuno-oncology therapy. The company is developing CAR T cells with a deleted HKP1 gene to prevent cell exhaustion, with a first-in-human clinical study of the XYF-19 HPK1 knockout CD19 CAR T product currently underway in patients with relapsed or refractory CD19+ leukemia or lymphoma.

Other projects include CAR T-cell therapy, CAR T-cell GMP production, immune cell gene editing CRISPR/Cas9 technology, a phage antibody library, phage display technology, and the buildout of a human antibody screening platform. The company is currently collaborating with the Air Force Military Medical Universitys Xijing Hospital on an investigational CAR T-cell therapy.

Yufan plans to invest 100 million (US$14.72 million) to build manufacturing facilities for CAR T-cell therapies to treat refractory and relapsed leukemia and lymphoma and expects to generate annual sales of between 200 million to 400 million once those candidates reach market.

Across the Pacific, Abound is an early stage biotechnology company developing antibody-based biological therapeutics for cancer and infectious diseases.

One infectious disease that the company is concentrating on is COVID-19, with the number of global cases topping 35 million as of Oct. 5, according to Johns Hopkins University data. An Abound team led by Mellors and the companys chief scientific officer, Dimiter Dimitrov, discovered human monoclonal antibodies with neutralizing activity in the laboratory against SARS-CoV-2, the virus that causes COVID-19, from antibody libraries.

Although the antibodies have proved effective in low doses in mouse and hamsters, human trials have not yet started. However, the antibodies are ready for testing in CAR T cells in preclinical models, and we hope to rapidly progress to clinical studies, Mellors said.

The company is currently proceeding with production and clinical development for regulatory approval and commercialization in the MENA and ASEAN regions, clinching an agreement with Saudi-U.S. joint venture Saudivax earlier in the year.

The Yufan-Abound partnership also aims to tap the lucrative T-cell market, which was valued at $2.7 billion in 2017 and is expected to reach $8.21 billion in 2025, growing at a compounded annual growth rate (CAGR) of 14.9% between 2017 and 2025, according to Frost & Sullivans report Growth Opportunities in the Global Cell Therapy Market, Forecast to 2025.

Amendments in regulatory and reimbursement policies, as well as the implementation of conditional approval policies for regenerative medicine, will further drive the market by expediting product launches, Aarti Chitale, Frost & Sullivan senior research analyst for transformational health, wrote. Additionally, improvements in cell culturing techniques alongside the use of different stem cells such as adipose-derived stem cells, mesenchymal stem cells, and induced pluripotent stem cells will strengthen the market with superior treatment options for non-oncological conditions such as neurological, musculoskeletal, and dermatological conditions, she added.

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Yufan inks deal with Abound to develop antibodies directing CAR T cells against cancer targets - BioWorld Online