BioPharma, Pharma

Gilead’s $285M Confidence Vote for Next-Gen Cancer Med & New Cell Therapy Tech

Gilead Sciences is increasing its stake in partner Arcellx and expanding the cell therapy alliance the companies started in 2022. The deal expands the lead partnered program to more cancers and gives Gilead a chance at another Arcellx cell therapy candidate made with different technology.

Gilead Sciences

When Gilead Sciences inked its partnership with Arcellx last year, the deal was a bet that the cell therapy developer’s lead multiple myeloma therapeutic candidate would offer advantages over rival products now on the market. Gilead is now deepening its ties to Arcellx by expanding the scope of the partnered program while also getting a shot at another therapeutic candidate that could bring further advantages to multiple myeloma treatment.

Financial terms of the new agreement announced Wednesday call for Gilead to make a $200 million equity investment in Arcellx. The Foster City, California-based drugmaker will also pay Arcellx $85 million up front.

Arcellx is among the companies developing next-generation CAR T-therapies for cancer. The lead program of the Gaithersburg, Maryland-based biotech is CART-ddBCMA, a cell therapy that targets the cancer protein BCMA in order to treat multiple myeloma.

BCMA is already treated by cell therapies. Bristol Myers Squibb and 2Seventy Bio brought Abecma to the market, and Johnson & Johnson and Legend Biotech have commercialized Carvykti. But Arcellx’s approach could offer better safety and efficacy. The company makes its multiple myeloma therapy with technology that engineers cells with binding domains that enhance specificity to the BCMA target, reducing the risk of off-target effects. A pivotal Phase 2 test of CART-ddBCMA recently resumed after the lifting of a clinical hold placed on the study in June following a patient death. Under the deal struck last year, Gilead subsidiary Kite and Arcellx will share in commercialization of this therapy, if it’s approved. Under the new agreement announced Wednesday, the scope of the alliance on this molecule is expanding to include lymphomas.

“We are pleased to see the momentum with the CART-ddBCMA multiple myeloma program, enabling Kite to enter an area of high unmet need and bring a new, potentially best-in-class cell therapy to patients,” Cindy Perettie, executive vice president of Kite, said in a prepared statement.

The agreement last year also gave Gilead the option to license programs developed with another Arcellx technology called ARC-SparX. This platform makes cell therapy modular and more controllable. The engineered T cells, which Arcellx calls ARC-T cells, are inactive in the body. Activation happens only in the presence of a separately dosed SparX protein that binds to an antigen on a cancer cell. This approach separates antigen recognition from tumor killing.

“By separating these functions, our approach renders the killing function of the ARC-T cell dependent on the antigen specificity and dose of the SparX protein rather than on uncontrolled CAR T proliferation as is the case with conventional CAR T-therapy,” the company explained in its annual report.

ARC-SparX enables dosing to be modified over the course of a patient’s treatment, Arcellx said. The technology also simplifies the complicated process of manufacturing cell therapies. Safety is another potential advantage. The killing effect of conventional cell therapies is unregulated, which can lead to toxic effects. Arcellx says ARC-SparX enables adjustment of the dose and the dosing schedule of the SparX protein. It also enables the ARC-T cells to rest, reducing the risk of T cell exhaustion. Arcellx said Gilead has exercised its option to negotiate a license for one ARC-SparX program, ACLX-001. This BCMA-targeting cell therapy is in Phase 1 testing in multiple myeloma.

In a note sent to investors, Leerink Partners analyst Daina Graybosch said the new partnership is a sign Gilead is confident in Arcellx’s lead cell therapy program and in the biotech’s ARC-SparX technology. ARC-SparX offers a simpler manufacturing process and tighter quality control, which lowers the cost of goods and improves both the consistency and quality of the end product.

“If successful, we believe such a ‘multi-line solution’ could disrupt the multiple myeloma CAR T-market and could give Arcellx/Kite a competitive advantage over Legend and [Johnson & Johnson],” Graybosch said.

Under the original agreement, Arcellx stood to earn up to $3.9 billion in milestone payments. The new agreement puts Arcellx in line for additional milestone payments, but the total amount was not disclosed. Gilead’s equity investment brings its stake in Arcellx to 13% and expands the biotech’s cash runway into 2027. More news is coming from Arcellx in the short-term. Phase 1 data for CART-ddBCMA are scheduled for presentation next month during the annual meeting of the American Society of Hematology in San Diego.

Photo: David Paul Morris/Bloomberg, via Getty Images