Shares of Adaptimmune Therapeutics plc (NASDAQ:ADAP) rocketed to $11.07 Friday, up $127% or $6.21, on updated data rolled out at the American Society of Clinical Oncology (ASCO) meeting, held virtually this year.
During an oral presentation, David Hong, of the MD Anderson Cancer Center, reported positive durability and efficacy findings in synovial sarcoma from the ADP-A2M4 phase I trial. Based on those data, Oxfordshire, U.K.-based Adaptimmune said the phase II SPEARHEAD-1 experiment in advanced synovial sarcoma or myxoid/round cell liposarcoma can back registration for the drug. The data also led to removal of the futility analysis from SPEARHEAD-1, with researchers dropping the sample size from 60 to 45 patients. CEO Adrian Rawcliffe said in a webcast that the company has had “productive interactions with regulatory authorities, and the totality of this progress supports our ambition to launch our first commercial product in sarcoma in the U.S. in 2022.” Chief Medical Officer Elliot Norry said he was “thrilled to report these data today, and even more excited for the next six to 12 months as we accumulate results” from more patients.
Adaptimmune is deploying its SPEAR (Specific Peptide Enhanced Affinity Receptor) T‑cell platform against MAGE-A4, expressed in 20% to 40% of various tumors and closer to 70% for sarcomas. Another target is AFP, a marker for liver cancer that's expressed in about a third of early stage hepatocellular carcinomas and increases as the tumor progresses. SPEAR uses affinity optimization to select T-cell receptors (TCRs) that bind tightly to specific peptides presented by human leukocyte antigen (HLA) on tumors.
The company also described a new response in a patient with lung cancer, and a response in a patient with head and neck cancer (first reported in January). Unveiled, too, were new responses in the Surpass phase I trial with second-generation product ADP-A2M4CD8 in HLA-A2-positive subjects with MAGE-A4-positive tumors, confirming the potential for SPEAR weaponry taking aim at MAGE-A4 to treat a broad range of cancers along with sarcoma. Results also bolster the rationale for two new phase II experiments, Adaptimmune said: SPEARHEAD-2 in head and neck cancer, which will begin later this year, and an effort in esophagogastric junction (EGJ) cancer planned for the first half of 2021. Also at ASCO, the company made known a design modification to Surpass that will move the study through dose escalation. Although the trial was originally designed with three cohorts (one giving 0.8-1.2 billion cells, another 1.2-3 billion cells, and the third 3-6 billion cells), Adaptimmune has decided to merge the second and third cohorts. The firm offered details of SPEARHEAD-2 as well, which will test ADP-A2M4 plus New York-based Bristol Myers Squibb Co.’s Keytruda (nivolumab) in first-line head and neck cancer.
SVB Leerink analyst Jonathan Chang liked the progress, with some caveats. “The new responses are highlighted by two new partial responses [PRs] (EGJ and head and neck, both unconfirmed)” from Surpass, he wrote in a report. “ADP-A2M4CD8 now has PRs in the first three of four patients treated in the dose-escalation study.” With first-generation product ADP-A2M4, Adaptimmune reported its first lung cancer PR and one more synovial sarcoma PR, which maintains the 50% overall response rate in the latter indication. The company said it will focus Surpass enrollment going forward on indications where work has found early signs of activity such as tumors of the lung, EGJ, head and neck, and bladder. “While more solid tumor responses have arrived, we believe it will still be important to demonstrate durability in these non-sarcoma indications,” Chang wrote in a report, hailing ADP-A2M4CD8’s “early but impressive activity at lower cell doses, reigniting excitement for broad tumor applicability.” Competition is “steadily increasing,” he acknowledged, but Adaptimmune “remains a leader in the potentially disruptive [TCR] field and we view continued execution on their MAGE-A4 targeted opportunity as key to the story.” Chang moved his price target from $4 to $11.
Adaptimmune has a phase I trial testing an AFP-targeting TCR product, ADP-A2AFP, in hepatocellular carcinoma (HCC), which has reached the expansion cohort. Following disclosure of a confirmed complete response (CR) for the first patient enrolled in the third cohort (5 billion cells), the next two patients in that cohort did not respond. At the request of investigators, the company opened a cohort for patients with non-HCC tumors that express AFP; one patient has been treated in that cohort but also hasn’t responded. Dose-escalation data will be disclosed at the virtual European Association for the Study of the Liver conference in August. “Although some patients have progressed, I remain encouraged by these early data, and we continue to recruit in the expansion phase,” Norry said.
CEO Rawcliffe pointed to the firm’s pipeline, with efforts in 10 solid tumor indications, including three ongoing or planned phase II trials. He reminded listeners how “markedly different this is from where we were, even a year ago. I don’t know of any other cell therapy company that has demonstrated such clear responses, including a CR, with T-cell monotherapy across a range of solid tumors in patients with late-stage cancer.” Preclinical research is ongoing, he said, adding that the first program has been established in the deal with Tokyo-based Astellas Pharma Inc.: an allogeneic HLA independent TCR therapy that Adaptimmune calls HiT. Signed in January, the Astellas pact is “indicative of the company we want to be, and the types of deals we want to do, going forward,” he said. Worth up to $897.5 million in all, the tie brought $50 million up front.