AbbVie will end its CD47 partnership, returning all rights for the drug, according to Shanghai’s I-Mab.

In 2020, AbbVie acquired ex-China rights to anti-CD47 monoclonal antibody lemzoparlimab (TJC4) in a deal worth up to $2 billion, including options on two other I-Mab candidates. I-Mab will keep $200 million in AbbVie upfront and milestone payments.

AbbVie said the breakup was a “strategic decision,” a description that was not explained, though the company has ended several partnerships recently. A year ago, AbbVie reduced the scope of the I-Med partnership, stopping two Phase Ib trials of lemzoparlimab, one in myelodysplastic syndrome (MDS) and the other in acute myeloid leukemia.

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I-Mab is not the only China company to find itself with global rights to a lead drug after signing a big-dollar out-licensing for the candidate. A week earlier, Novartis ended a $2.2 billion Global partnership with BeiGene for its PD-1 drug.

As a result, I-Mab will regain the global rights to develop and commercialize all CD47 compounds covered by the deal, including the only named candidate, lemzoparlimab. The company is currently conducting a China Phase III registrational study of lemzoparlimab in combination with azacitidine as a first-line therapy in patients with higher-risk myelodysplastic syndrome.

In 2022, I-Mab announced that lemzoparlimab showed encouraging results in a China Phase II trial for the MDS indication. Lemzoparlimab was administered in combination with azacytidine, an AbbVie approved drug. After six months of treatment with lemzoparlimab-azacytidine, the overall response rate (ORR) was 87% and complete response rate (CRR) was 40%

AbbVie and I-Mab announced their global agreement in September 2020. For an upfront payment of $180 million and the promise of up to $1.74 billion in success-based milestones, AbbVie earned exclusive rights (ex-China) to develop and commercialize lemzoparlimab. The deal also allowed for potential future targets using other I-Mab CD47 molecules.

In August 2022, AbbVie scaled the partnership back. Although the partners did not disclose the reason for ending the two trials, I-Mab said the decision was not triggered by “specific or unexpected safety concerns.” I-Mab said the partnership could still deliver up to $1.3 billion in development, regulatory and sales milestones.

If approved for China use, lemzoparlimab could become a first-in-class CD47 antibody for hematologic malignancies in China, according to I-Mab. Lemzoparlimab is a novel CD47 antibody designed to offer better drug safety without compromising efficacy. I-Mab is currently conducting a China Phase III registrational study of lemzoparlimab in combination with azacitidine (AZA) as a first-line treatment of patients with higher-risk myelodysplastic syndrome.

For AbbVie, renouncing the I-Mab partnership follows soon after it announced that it would not exercise its exclusive licensing option for Harpoon Therapeutics’ TriTAC candidate HPN217, which is in a Phase I trial for multiple myeloma. And, in August, AbbVie also ended development of two early-stage oncology candidates from its developmental pipeline: ABBV-011, an anti-SEZ6 antibody-drug conjugate in clinical trials for relapsed or refractory lung cancer; and ABBV-647, a Pfizer-partnered ADC targeting the PTK7 protein to treat solid tumors.

In an SEC filing, I-Mab said, “Lemzoparlimab has the potential to be the first-in-class CD47 antibody for hematologic malignancies in China, The company will continue to review follow-up data from the Phase II study of lemzoparlimab in HR-MDS, as well as all available and upcoming data from other investigational CD47 therapies, to explore future development opportunities with lemzoparlimab.”

I-Mab’s pipeline consists of more than 10 clinical and pre-clinical stage drug candidates driven by its Fast-to-Proof-of-Concept and Fast-to-Market development programs through internal R&D and global partnerships and commercial partnerships. I-Mab has established its global footprint in Shanghai, Hangzhou, Guangzhou and Hong Kong in China, and Maryland and San Diego in the US.

A version of this article was first published in ChinaBio Today on September 25, 2023