The American Society of Hematology meeting closed yesterday and served to shine the light on the latest research and progress of new therapies targeting hematological malignancies as well as other serious blood disorders. Specifically, a great deal of attention was focused on the treatment of blood cancers and, judging by the increase in value of the BioWorld Cancer index, investors and analysts alike were impressed with what they heard. The index pushed 17.6% higher in November, and, by market close Tuesday, it was tracking up 4% in December, helped by the performance of those index members presenting at the ASH meeting. (See BioWorld Cancer index.) 

Leading gainer 

Menlo Park, Calif.-based Forty Seven Inc. moved the needle big time, with its shares (NASDAQ:FTSV) vaulting a whopping 174% in December following an impressive showing at the meeting. The company presented updated data from its phase Ib trial evaluating magrolimab, its monoclonal anti-CD47 antibody that is designed to interfere with recognition of CD47 by the SIRPα receptor on macrophages, thus blocking the "don't eat me" signal used by cancer cells to avoid being ingested by macrophages, combined with azacitidine to treat myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML).

The data showed the combination regimen is active and well-tolerated in patients with MDS and AML. The study is designed to evaluate magrolimab in combination with azacitidine in untreated patients with higher-risk MDS and untreated patients with AML, who are ineligible for induction chemotherapy. In higher-risk MDS, the overall response rate (ORR) was 92% as 12 patients achieved a complete response (CR), with 33% achieving a marrow CR and 8% achieving hematologic improvement.  

Industry watchers agreed that the data were compelling, including Mizuho Securities analyst Mara Goldstein, who wrote in a report, “We like shares of FTSV based on our view that magrolimab is an untapped immuno-oncology (I-O) opportunity, with a speed to market strategy. Updated dataset at ASH showed magrolimab in MDS to have the beginnings of a competitive profile based on updated efficacy results (ORR & CR).” 

Going forward, the company said it plans to continue enrolling patients in the ongoing phase Ib trial with an amended protocol, and to initiate a phase III study, ENHANCE, to evaluate the combination of magrolimab and azacitidine compared to azacitidine alone. It believes that this strategy provides “two distinct opportunities to achieve an accelerated approval, with a potential BLA filing expected in the fourth quarter of 2021.” 

Forty Seven’s shares were a hit in November, too, climbing 83%. In the period, the company announced it had signed a research collaboration with Cambridge, Mass.- based Bluebird Bio Inc. to undertake clinical proof-of-concept studies for its antibody-based conditioning regimen, FSI-174 (anti-cKIT antibody) plus magrolimab, with Bluebird's ex vivo lentiviral vector hematopoietic stem cell gene therapy platform. The deal will focus on a conditioning approach aimed to deliver reduced toxicity and will initially target diseases that have the potential to be corrected with transplantation of autologous gene-modified blood-forming stem cells. If successful, the new conditioning regimen could allow for more patients to undergo gene therapy, the companies noted. They expect to initiate a phase Ib trial next year. 

New York-based TG Therapeutics Inc. was another star performer at ASH. The company’s shares (NASDAQ:TGTX) have soared 15% this month (130% YTD) after it reported the first clinical data from its once-daily, oral, BTK inhibitor, TG-1701, as a single agent and as a triple therapy in combination with ublituximab (TG-1101), the firm’s glycoengineered anti-CD20 monoclonal antibody, and umbralisib (TGR-1202), its oral, dual inhibitor of PI3K delta and CK1 epsilon, in patients with relapsed/refractory non-Hodgkin’s lymphoma and chronic lymphocytic leukemia.  

The data showed TG-1701 is an active BTK inhibitor as a single agent and that the combination of U2 plus TG-1701 has been generally well-tolerated and active with six of seven patients responding to the triple therapy at 100 mg QD, the lowest dose of TG-1701 tested. All patients treated with the triple combination of TG-1701 plus U2 remain on study. 

Optimization of chemotherapy  

Index member Beyondspring Inc.’s shares (NASDAQ:BYSI) are trading 21% higher this month. It presented a poster at ASH on its lead asset, plinabulin, a marine-derived small molecule that sequesters tubulin heterodimers in a differentiated manner from other agents in that class. The phase III data provided a rationale for combining the compound with pegfilgrastim (Neulasta) due to their differing mechanisms of action for preventing chemotherapy-induced neutropenia (CIN). Previously, the company had reported positive phase II data, which demonstrated that plinabulin combined with Neulasta offered superior protection against CIN and significantly less bone pain for patients compared to Neulasta alone, with statistical significance.  

Other cancers 

Among those index members working on other cancers, Lexington, Mass.-based Agenus Inc., an immuno-oncology company with a pipeline of immune checkpoint antibodies, adoptive cell therapies and cancer vaccines, has enjoyed a credible market performance of late with its shares (NASDAQ:AGEN) trading up 62% in November. During the period, the company reported it received a $10 million up-front payment related to a license agreement with New York-based Urogen Pharma Ltd. Agenus is providing access to zalifrelimab (AGEN-1884, an anti-CTLA4 antibody) for use with Urogen's sustained-release technology for intravesical delivery in patients with urinary tract cancers. It will be eligible to receive up to $200 million in potential downstream development, regulatory and commercial milestones, as well as 14% to 20% royalties on net sales. 

It has been a great year for Vancouver, British Columbia-based Zymeworks Inc., with its shares (NASDAQ:ZYME) up 188% year-to-date and 26% in November alone. In its third-quarter financial results, it reported updated phase I data that continued to show that ZW-25, a bispecific antibody that can simultaneously bind two non-overlapping epitopes of HER2, known as biparatopic binding, monotherapy provides antitumor activity and durable disease control across multiple tumor types in heavily pretreated patients, including biliary tract cancer (BTC), colorectal cancer, gynecological cancers and gastroesophageal adenocarcinoma. The company said encouraging response rates in BTC support the initiation of a registration-enabling phase II trial evaluating single-agent ZW-25 as a second-line treatment for patients with HER2‑expressing BTC. 

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