Servier’s Frontline AML Win Puts Focus on Four Small Caps Ahead of ASH

Servier’s Tibsovo met its primary endpoint in a Phase 3 trial in newly diagnosed, chemotherapy-eligible acute myeloid leukemia, a setting where targeted drugs have played a limited role. In the HOVON 150 study, run by the nonprofit HOVON and the German academic network AMLSG, 487 patients with IDH1-mutant AML or high-risk myelodysplastic syndrome were randomized. The Tibsovo regimen achieved a 74% two-year event-free survival rate, compared with 35% for chemotherapy and placebo. Overall survival data are still pending. Tibsovo is currently approved for relapsed AML and for newly diagnosed patients who cannot tolerate intensive chemotherapy.

The result adds to a broader shift toward targeted therapy earlier in AML treatment. It also leaves a large group of patients with limited options. Many patients relapse after venetoclax-based regimens, which have become a standard backbone, and those with TP53 mutations face especially poor outcomes. Four small caps presenting at the American Society of Hematology annual meeting, December 12–15 in New Orleans, are targeting those gaps.

SELLAS targets venetoclax resistance

SELLAS Life Sciences (NASDAQ: SLS) will present Phase 2 data for SLS009 (tambiciclib), a CDK9 inhibitor, added to azacitidine and venetoclax in 62 patients whose AML relapsed after venetoclax-based treatment. At the selected dose, patients with monocytic AML had a 54% response rate and 5.8-month median overall survival, and patients with TP53-mutated AML had a 57% response rate and 8.8-month median survival. SELLAS compares those results with historical survival of about 2.5 months in these settings. An 80-patient study in newly diagnosed AML is enrolling, with early data expected in the fourth quarter. SELLAS also expects topline results soon from its Phase 3 REGAL study of galinpepimut-S.

Actinium brings targeted radiation to resistant disease

Actinium Pharmaceuticals (NYSE American: ATNM) is developing Actimab-A, an antibody that delivers a radioactive payload to CD33-positive leukemia cells. Its ASH abstract reports long-term safety follow-up from a Phase 1 study combining Actimab-A with CLAG-M salvage chemotherapy. Previously reported data from the study showed estimated one-year overall survival of 59% in patients previously treated with venetoclax and 51% in patients with TP53 mutations. Actinium is advancing Actimab-A toward a Phase 2/3 trial, with additional development through a collaboration with the National Cancer Institute.

Cullinan tests an immunotherapy approach

Cullinan Therapeutics (NASDAQ: CGEM) is developing CLN-049, a T cell engager that directs the immune system against FLT3-expressing leukemia cells, regardless of FLT3 mutation status. Cullinan will present updated Phase 1 data in relapsed or refractory AML and MDS, including activity at its selected Phase 2 doses, and has started a study combining CLN-049 with azacitidine and venetoclax in newly diagnosed patients. There are currently no approved immunotherapies for AML. CLN-049 has Orphan Drug and Fast Track designations from the FDA.

Rigel competes directly with Tibsovo

Rigel Pharmaceuticals (NASDAQ: RIGL) markets REZLIDHIA, an IDH1 inhibitor approved for relapsed or refractory IDH1-mutated AML, the same target as Tibsovo. REZLIDHIA sales grew 27% to $8.9 million in the second quarter. Rigel cites an analysis suggesting the two drugs produce similar response rates in relapsed disease, with potentially more durable responses for REZLIDHIA. Through a collaboration with MD Anderson, Rigel is also evaluating REZLIDHIA in newly diagnosed patients. Tibsovo’s frontline data raise the stakes for that work, since the IDH1 drug used first may shape treatment for the rest of the market.

What to watch

Rigel is the only one of the four with an approved AML drug, and it now faces a stronger Tibsovo in the IDH1 market. SELLAS, Actinium and Cullinan are earlier, testing whether their approaches can extend survival for patients current therapies don’t help. ASH in December will add data on all three, and SELLAS’s REGAL readout could arrive first.