The cancer protein CD47 is a hot target for drug developers, but it’s not without issues. Antibody drugs that block this protein can also spark anemia. I-Mab designed its antibody to pose less of an anemia risk and AbbVie, seeing an opportunity to catch up to other CD47 contenders and potentially stand apart from them, has agreed to pay $200 million to secure rights to the compound.
The I-Mab (NASDAQ: IMAB) drug, lemzoparlimab, is currently in early clinical development. The $200 million that AbbVie (NASDAQ: ABBV) is paying Shangahi-based I-Mab (NASDAQ: IMAB) breaks down to $180 million up front plus a $20 million milestone payment for the positive Phase 1 results that were recently reported. AbbVie gets the right to develop and commercialize the drug globally, except for mainland China, Macau, and Hong Kong, where I-Mab retains rights.
I-Mab could earn up to $1.74 billion in milestones payments tied to the progress of the drug, plus royalties from sales if its North Chicago, IL-based partner is able to commercialize the drug outside of China. The alliance could expand to other drugs in their respective pipelines. In addition, the two companies plan to explore drug combinations, including a potential pairing of lemzoparlimab with AbbVie blood cancer drug venclexta.
The CD47 protein is one of the ways cancers avoid the immune system. Found in abundance on the surface of cancer cells, these proteins send out a signal that immune cells interpret as “don’t eat me.” Blocking CD47 is intended to allow a type of an immune cell called a macrophage to recognize cancer cells and then gobble them up. The approach is still experimental but Gilead Sciences (NASDAQ: GILD) liked the early results reported by Forty Seven so much that it agreed earlier this year to pay $4.9 billion to acquire that cancer immunotherapy developer and its lead CD47 inhibitor, magrolimab. The drug has been tested in patients with myelodysplastic syndromes and acute myeloid leukemia.
The problem with a drug that blocks CD47 on cancer cells is that it does the same on red blood cells. Immune cells then see the red blood cells as targets and they eat them, leading to anemia. Forty Seven tried to reduce the anemia risk by first administering a priming dose that gets rid of old red blood cells but spares the younger and healthier ones that don’t express the “eat me” signal. According to research published earlier this year in Frontiers in Oncology, the priming dose led to transient and mild anemia, followed by the generation of new red blood cells that don’t express the “eat me” signals, and are therefore unaffected by magrolimab.
I-Mab aims to reduce anemia risks without a priming dose. The company’s drug is designed to minimize its ability to bind to red blood cells while retaining anti-tumor capabilities. In preclinical tests, I-Mab has reported that the drug spared red blood cells. Last month, the company reported preliminary Phase 1 data showing that the drug was well tolerated without any dose-limiting toxicity or severe problems associated with blood. Speaking on a conference call Friday, I-Mab founder and honorary chairman Jingwu Zang said that the full Phase 1 data will be presented at the annual meeting of the Society for Immunotherapy of Cancer, which this year is scheduled to start on Nov. 10.
The AbbVie/I-Mab alliance could extend beyond lemzoparlimab. Jielun Zhu, I-Mab’s chief financial officer, said on the call that AbbVie also gains the right of first negotiation to license two CD47-targeting bispecific antibody programs that I-Mab currently has in preclinical development. The preliminary terms are $500 million in upfront and milestone payments for each of those programs.
In a Friday research note, SVB Leerink analyst Geoffrey Porges wrote that the Gilead drug remains the frontrunner in a CD47 chase that includes at least seven antibody candidates. But he added that I-Mab’s early Phase 1 results appear to confirm the company’s thesis that its drug does have a lower affinity for binding to red blood cells. The deal with I-Mab, he said, potentially extends and strengthens the AbbVie blood cancer franchise. It’s the second cancer immunotherapy alliance AbbVie has reached this summer. In June, the company paid Genmab (NASDAQ: GMAB) $750 million up front to kickstart a partnership on the Danish company’s bispecific antibody drugs.
Separately on Friday, I-Mab announced a $418 million private placement by a group of investors led by Hillhouse Capital. Those investors purchased 12.7 million American depositary shares at $33 apiece, a 2.9 percent premium to the volume-weighted average price of the stock for the past 30 days.
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