SAN FRANCISCO – At the 43rd annual JP Morgan Healthcare Conference on Wednesday, iTeos outlined development plans for its anti-TIGIT antibody belrestotug, AbbVie provided updates on its cMET-targeting antibody-drug conjugate telisotuzumab vedotin, and Lexeo Therapeutics said it is looking for a partner to advance its APOE4-associated Alzheimer's drug LX1001. Meanwhile, Grail discussed the recent launch of a new version of Galleri, the firm's blood-based multi-cancer early detection test.
Below are short reports from presentations from these companies.
iTeos
iTeos Therapeutics anticipates this year an interim readout from its Phase III GALAXIES Lung-301 trial of its anti-TIGIT antibody belrestotug in combination with GlaxoSmithKline's anti-PD-1 monoclonal antibody Jemperli (dostarlimab) versus Merck's Keytruda (pembrolizumab) in PD-L1-high non-small cell lung cancer (NSCLC).
iTeos partnered in 2021 with GlaxoSmithKline to codevelop and commercialize belrestotug, which previously had been designated GSK4428859A and EOS884448.
In the Phase III trial, iTeos is enrolling about 1,000 patients with unresectable, locally advanced or metastatic PD-L1-high (50 percent or more) NSCLC who have not received prior treatment to receive belrestotug-Jemperli or Keytruda-placebo by intravenous infusion. Researchers are tracking progression-free survival and overall survival as the study's primary endpoints, and the study's secondary endpoints include overall response rate, molecular response rate, and duration of response. iTeos CEO Michel Detheux said the interim results are expected to include overall response rate and safety data from more than 150 patients.
The firm is also looking forward to top-line data from the Phase II GALAXIES Lung-201 trial in the second quarter of 2025, which is to include 12-month progression-free survival, overall response rate, safety, and circulating tumor DNA biomarker results from more than 240 patients. Trial investigators are evaluating belrestotug alone and in combination with Jemperli compared to Jemperli monotherapy in about 340 patients with PD-L1-high NSCLC.
iTeos presented interim data from GALAXIES Lung-201 in September 2024 that showed patients on the belrestotug regimen had overall response rates ranging from 63.3 percent to 76.7 percent, depending on the dose, compared to 37.5 percent for Jemperli alone. Of patients with evaluable ctDNA samples at baseline and at week seven, the median ctDNA reduction was 65 percent for Jemperli monotherapy and between 55 percent and 97 percent for belrestotug plus Jemperli, depending on the dose. Patients on the belrestotug combo, however, had an increase in immune-related adverse events.
iTeos Chief Medical Officer David Feltquate said during his presentation that the company hopes to see these promising overall response rates for belrestotug translate to favorable progression-free survival in the upcoming data readouts.
AbbVie
In 2025, AbbVie expects to continue advancing its antibody-drug conjugate (ADC) assets and net US approval for its cMET-targeting ADC telisotuzumab vedotin (Teliso-V) in non-small cell lung cancer.
The firm submitted a biologics license application to the US Food and Drug Administration in September seeking approval for Teliso-V in previously treated, locally advanced or metastatic EGFR wild-type, nonsquamous NSCLC patients with c-Met protein overexpression.
AbbVie CSO Roopal Thakkar said at the conference that the firm is quickly advancing a follow-on product to Teliso-V: ABBV-400 or telisotuzumab adizutecan, an ADC that targets c-MET and Topo-1.
ABBV-400 is currently being studied in several trials in non-small cell lung, colorectal, and gastroesophageal cancers. Thakkar added that AbbVie is looking to report data from a tumor-agnostic trial of ABBV-400 in MET-amplified tumors and expects to begin making plans for Phase III trials this year.
"We started to read out early data [for ABBV-400] similar to the Teliso-V population, [and] the efficacy is already substantially higher than what we've observed with Teliso-V," Thakkar said. "And we've seen almost a doubling of the patient population that we may be able to access [with ABBV-400]."
AbbVie is also advancing a candidate in the same setting as its approved ADC for ovarian cancer, Elahere (mirvetuximab soravtansine). Elahere is approved in the US and Europe for previously treated patients with folate receptor alpha (FRa)-positive, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer.
The follow-on candidate, IMGN-151, is a FRa-targeting ADC. Thakkar noted that the firm expects to report data from an ongoing trial of IMGN-151 in recurrent endometrial cancer or high-grade serous epithelial ovarian, fallopian tube, and primary peritoneal cancer.
AbbVie is also hoping to expand its treatable population for Elahere by showing activity in an ongoing trial involving FRa-positive, platinum sensitive epithelial ovarian, fallopian tube, or primary peritoneal cancer patients. If successful, this could mean a potential "doubling of the population" from the current platinum-resistant indication, Thakkar said.
"We'll start to get an idea of dose optimizing both [Elahere and IMGN-151] in combination with platinum-based chemo, bevacizumab, and PARP inhibitors, and be able to pick the best [combination] in that particular segment or [by] different FRa expression levels," he said.
Other ADCs that AbbVie expects to report data from in 2025 include ABBV-706 in SEZ6-expressing small cell lung cancer and neuroendocrine tumors along with pivekimab sunirine in CD123-positive hematologic malignancies, such as acute myeloid leukemia and blastic plasmacytoid dendritic cell neoplasm.
"These data will start to read out in a meaningful way with Phase III [results] in 2027, 2028, and 2029," Thakkar said.
Lexeo Therapeutics
Lexeo Therapeutics is no longer independently developing its gene therapy candidate for APOE4-associated Alzheimer's disease, despite promising early biomarker results, and is seeking a development partner.
LX1001 is designed as a treatment for Alzheimer's patients with two copies of the APOE4 allele, which is associated with a higher risk of developing the neurodegenerative disease. The investigational gene therapy delivers a copy of the APOE2 allele, which is thought to have a neuroprotective effect, lowering the risk of developing the disease and slowing disease progression in those who do develop it.
The Alzheimer's program will only progress with a partner, and Lexeo does not plan to deploy additional capital into it, Lexeo CEO Nolan Townsend said.
He said he hopes to have an update on advancing the LX1001 program later this year.
LX1001 is "something we think deserves further exposition," Townsend said, but "from the perspective of a small company, it's a challenge for us to take forward several cardiac programs and an Alzheimer's portfolio."
At the Clinical Trials on Alzheimer's Disease conference in Madrid in October, Lexeo reported positive interim results from a Phase I/II trial of LX1001, including dose-dependent increases in APOE2 protein expression, stable reductions in tau, and no reports of amyloid-related imaging abnormalities (ARIA), an adverse event seen in other Alzheimer's drugs that have recently been approved.
Lexeo at the time said it had engaged with the US Food and Drug Administration on these data and expected to provide a regulatory update in 2025.
Lexeo is now honing its focus on developing gene therapies for cardiac diseases and is preparing for a pivotal trial to evaluate a candidate in Friedreich's ataxia cardiomyopathy, LX2006.
Lexeo has reached alignment with the FDA on components that could underpin an accelerated approval, such as using left-ventricular mass index (LVMI) reduction and frataxin protein expression as surrogate endpoints that could be co-primary endpoints in a potential pivotal trial of the gene therapy.
Historically, the FDA has shied away from using surrogate endpoints and has required clinical outcomes to approve cardiovascular treatments, according to Townsend, which has made it challenging to develop precision medicines in this space. "But this has been changing over the past few years," he said.
Townsend said Lexeo could initiate a registrational trial for LX2006 by the end of 2025 or early 2026, in which it expects to enroll patients with abnormal LVMI, which wasn't a requirement of the Phase I/II trial. In the study, the company is proposing using at least a 10 percent reduction in LVMI and a threshold of 40 percent frataxin positive area as endpoints.
So far, 16 patients have received LX2006 within Lexeo's Phase I/II SUNRISE-FA trial and an investigator-initiated study at Weill Cornell Medicine, and based on interim Phase I/II results, most patients who had abnormal LVMI at baseline have achieved these outcomes. Lexeo expects to be able to share data from the highest-dose cohort of the clinical trial by mid-year.
Lexeo had about $157 million in cash and marketable securities as of Sept. 30, giving it a projected runway into 2027.
Grail
Grail CEO Bob Ragusa talked to investors about the recent launch of a new version of Galleri, the firm's blood-based multi-cancer early detection test, noting that it should reduce the costs of goods and services.
Introduced in December, the new assay is "both fully automated and integrated," he said. Grail has eliminated "numerous" manual steps, leading to greater efficiency and improved quality control. It has also reduced the methylation sequencing panel "to the most informative regions," allowing four times the number of samples to be run on a flow cell, leading to reduced sequencing costs. Grail has also updated the test report, revising how the cancer signal of origin is classified and simplifying the report to 18 regions "to provide more valuable information to physicians," he said.
"We are transitioning to that new version of the test today and anticipate realizing the benefit from this investment as volumes grow over time," he said. "The implementation of these updates has substantially expanded our capacity" and can support "several years of growth" with no additional capital expenditure.
In 2024, Grail ran 137,000 Galleri tests, bringing the cumulative number of tests sold to more than 290,000, as of Dec. 31. That led to revenues of $124 million to $126 million, up 34 percent from the prior year. US Galleri sales were between $107 million and $110 million, up 45 percent from the prior year.
Ragusa noted that 2024 was an eventful year for the firm. In June, it completed its separation from Illumina and underwent a restructuring in August, cutting 30 percent of its workforce.
Grail has approximately $767 million in cash, providing a runway into 2028. Its cash burn in 2024 was $579 million; however, it has reduced its burn rate "substantially" and expects to go through less than $320 million in 2025.
In 2025, Grail expects US Galleri sales to grow between 20 percent and 30 percent year over year. "This reflects the reduced investment that we're making in [our] commercial [team] as we work towards achieving commercial spend neutrality," Ragusa said.
The year should also see the early readout of the firm's Pathfinder 2 study on Galleri's performance, he said.
Grail intends to eventually submit a premarket approval application to the US Food and Drug Administration for Galleri and pursue broader payor reimbursement for the test.