While the halls remained silent at McCormick Place in Chicago – the traditional meeting spot for thousands of delegates attending the American Society of Clinical Oncology (ASCO) meeting – the online version still managed to attract about 40,000 registrants, similar to years past. The abbreviated meeting concentrated on scientific presentations, with 250 oral presentations along with 2,500 posters.
Overall, data presented at the meeting over the weekend appear to have garnered investor approval, with the BioWorld Cancer index advancing 3%, by market close Monday, and a further 1.7% by the closing bell today. (See BioWorld Cancer index, below.)
Wall Street darling
Star of the show, in terms of stock price movement, was Adaptimmune Therapeutics plc, whose shares (NASDAQ:ADAP) soared 139%, increasing $6.78, on positive durability and efficacy findings in synovial sarcoma from the ADP-A2M4 phase I trial. Based on the data, the company said the phase II SPEARHEAD-1 study in advanced synovial sarcoma or myxoid/round cell liposarcoma can support 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. The company is using 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.
It also reported new responses in the SURPASS trial, confirming the potential for SPEAR T‑cell therapies targeting MAGE-A4 to treat a broad range of cancers in addition to sarcoma. Those data further support the rationale for two new phase II trials, it said. They will be SPEARHEAD-2 in head and neck cancer, which will begin later this year, and a second trial in esophagogastric junction (EGJ) cancer planned for the first half of next year.
In a research note last week, SVB Leerink analyst Jonathan Chang wrote, following a meeting with the company’s management team, “Overall, we believe the path forward in synovial sarcoma is a positive first step for ADAP's stated goal of launching the first TCR T-cell therapy in 2022.”
The company was quick to take advantage of its elevated share price, going to market with an underwritten public offering of 20.5 million of its American depositary shares (ADSs) priced at $11 per ADS. The underwriters have also been granted a 30-day option to purchase up to an additional 3.07 million ADSs at the public offering price. The company expects to gross $225.5 million, excluding any exercise of the underwriters’ option to purchase additional ADSs. The net proceeds will be used to support the development of Adaptimmune’s immunotherapies into and through clinical trials as well as for other general corporate purposes.
Positive early data
Lexington, Mass.-based Agenus Inc. saw its shares (NASDAQ:AGEN), jump 47% on positive data for AGEN-1181, a multifunctional Fc-engineered next-generation anti-CTLA4 antibody that is being tested in the clinic both as monotherapy and in combination with balstilimab (Agenus's anti-PD-1).
Both single and combo treatments saw encouraging preliminary efficacy, with objective responses (both complete and partial) as well as prolonged stable disease in a variety of advanced cancers progressing after standard therapies, explained presenter Steven O'Day, executive director of the John Wayne Cancer Institute and Cancer Clinic. “These early data, including responses in patients with CD16 polymorphisms, support the accelerated development of AGEN-1181 into multiple tumors, including PD-1-refractory melanoma, NSCLC and others."
South San Francisco-based Allogene Therapeutics Inc. (NASDAQ:ALLO), which is developing allogeneic CAR T (AlloCAR T) therapies for cancer, pushed 6% higher following its ASCO presentation to add to its already strong 61% increase in May.
At ASCO, the firm disclosed positive first results from the dose-escalation phase I Alpha study of ALLO-501, an anti-CD19 allogeneic CAR T therapy, in relapsed/refractory non-Hodgkin lymphoma. The study deploys ALLO-647, Allogene's anti-CD52 monoclonal antibody, as a part of its differentiated LD depletion regimen. Allogene is developing ALLO-501 with Les Laboratoires Servier SAS under an exclusive license granted by Paris-based Cellectis SA.
For the efficacy analysis, 19 out of 22 patients reached at least one-month assessment as of the May cutoff. Responses were observed across all cell doses and tumor histologies (diffuse large B-cell lymphoma and follicular lymphoma) with an overall response rate (ORR) of 63% and complete response (CR) rate of 37%.
The company also took the opportunity to price an underwritten public offering of 11.7 million shares priced at $47 per share for expected gross proceeds of approximately $550 million. In addition, the underwriters have been granted a 30-day option to purchase up to 1.75 million additional shares of its common stock at the public offering price.
Shares of Cambridge, Mass.-based Agios Pharmaceuticals Inc. (NASDAQ:AGIO) dipped about 2% during the period. The company reported updated data from an ongoing phase I study evaluating single-agent vorasidenib in isocitrate dehydrogenase (IDH)-mutant advanced solid tumors, including glioma. Vorasidenib is currently being evaluated in the registration-enabling phase III INDIGO study as a potential treatment for patients with residual or recurrent grade 2 non-enhancing glioma. The safety analysis conducted on the 22 patients with non-enhancing glioma as of the data cutoff demonstrated that vorasidenib has a favorable safety profile at dose levels below 100 mg once daily.
Canaccord Genuity analyst John Newman viewed the updated vorasidenib data positively, with ORR of 18.2% and a 55.4% 24-month PFS rate.
After pushing 68% higher in May, shares of New York-based TG Therapeutics Inc. (NASDAQ:TGTX) dropped back about 7%. The company reported the final results from the GENUINE phase III study evaluating the combination of ublituximab, a glycoengineered anti-CD20 monoclonal antibody, plus ibrutinib compared to ibrutinib alone in patients with previously treated high-risk chronic lymphocytic leukemia (CLL).
Michael S. Weiss, the company’s CEO, commented, “We believe these data support the potential of combination therapies to improve outcomes for patients with high-risk CLL, especially those with 17p deletion/TP53 mutation, who continue to progress more rapidly than those without high-risk cytogenetics.”
The presentation included data from 117 patients treated with either ublituximab plus ibrutinib (n=59) or ibrutinib alone (n=58). As of the cutoff date of Sept. 1, 2019, patients had a median follow-up time of 41.9 months. The addition of ublituximab to ibrutinib compared to ibrutinib monotherapy significantly improved ORR (93% compared to 78%; p=0.019). Median PFS was not reached in the ublituximab plus ibrutinib arm and was 35.9 months in the ibrutinib monotherapy arm (hazard ratio 0.46), with del17p/TP53mut patients seeing the greatest difference in PFS.