The Non-Hodgkin's Lymphoma (NHL) treatment landscape is poised for significant expansion, with over 220 pipeline therapies currently in development by more than 200 pharmaceutical companies, according to a comprehensive report by DelveInsight.
The "Non-Hodgkin Lymphoma Pipeline Insight 2025" report highlights the extensive research efforts aimed at addressing unmet needs in NHL treatment, particularly for patients with relapsed or refractory disease.
Key Pipeline Candidates Show Promise in Clinical Trials
Among the most advanced candidates, several therapies are demonstrating encouraging results in clinical trials:
Mosunetuzumab (Hoffmann-La Roche), a humanized T-cell bispecific antibody, represents an innovative approach to NHL treatment. The molecule simultaneously binds to CD3 epsilon on T-cells and CD20 on B-cells, effectively redirecting T-cell cytotoxic activity against malignant B-cells. Currently in Phase III trials, Mosunetuzumab is being evaluated in combination with Polatuzumab Vedotin against standard rituximab-based regimens in relapsed/refractory aggressive B-cell NHL.
Tisagenlecleucel (Novartis), a CD19-directed genetically modified autologous T-cell immunotherapy, has advanced to Phase III clinical trials. This CAR-T therapy uses a lentiviral vector to encode an anti-CD19 chimeric antigen receptor, incorporating both CD3 zeta and 4-1BB signaling domains to enhance T-cell expansion, activation, and persistence.
Capivasertib (AstraZeneca) takes a different approach by targeting AKT isoforms. By inhibiting AKT, the drug prevents phosphorylation of substrates that mediate cellular processes including cell division, apoptosis, and metabolism. This candidate is currently in Phase II evaluation.
BI-1206 (BioInvent) addresses a unique mechanism of treatment resistance. This high-affinity monoclonal antibody selectively binds to FcγRIIB (CD32B), the only inhibitory member of the FcγR family. Overexpression of FcγRIIB in NHL has been associated with poor prognosis. Early data from Phase I/IIa trials suggest BI-1206 can restore rituximab activity in relapsed NHL patients.
HMPL-760 (Hutchmed) represents the next generation of Bruton's tyrosine kinase (BTK) inhibitors. This highly selective, non-covalent, third-generation BTK inhibitor targets both wild-type and C481S mutant enzymes, potentially addressing resistance to first-generation BTK inhibitors.
Major Companies Leading NHL Research
The report identifies numerous pharmaceutical companies actively developing NHL therapies, including industry leaders and specialized biotech firms:
- Novartis
- AstraZeneca
- Genentech
- BioInvent
- Genmab
- Gilead Sciences
- Incyte Corporation
- Regeneron Pharmaceuticals
- IGM Biosciences
Additional companies with significant NHL pipeline assets include SystImmune, Nordic Nanovector, Pacylex Pharmaceuticals, Artiva Biotherapeutics, Chipscreen Biosciences, and dozens more.
Diverse Therapeutic Approaches
The NHL pipeline encompasses diverse therapeutic modalities and mechanisms of action:
- Monoclonal antibodies targeting various B-cell surface proteins
- Bispecific antibodies engaging T-cells against cancer cells
- CAR-T cell therapies with enhanced persistence and efficacy
- Small molecule inhibitors targeting signaling pathways
- Gene therapies with novel delivery mechanisms
Routes of administration vary widely, including oral, parenteral, intravenous, subcutaneous, and topical formulations, offering potential improvements in treatment convenience and adherence.
Clinical Trial Activity
Recent clinical trial activity highlights the momentum in NHL research. In March 2025, Hoffmann-La Roche initiated a Phase I/II study evaluating Glofitamab (RO7082859) as both monotherapy and in combination with Obinutuzumab in relapsed/refractory B-cell NHL patients.
Concurrently, Bristol-Myers Squibb launched a Phase 1/2 study investigating the safety and preliminary efficacy of Relatlimab plus Nivolumab in pediatric and young adult patients with recurrent or refractory classical Hodgkin Lymphoma and Non-Hodgkin Lymphoma.
Future Outlook
The robust NHL pipeline suggests significant potential for treatment advances in coming years. Novel mechanisms of action, combination approaches, and therapies targeting specific NHL subtypes may address current limitations in efficacy and tolerability.
As these therapies progress through clinical development, healthcare providers and patients can anticipate expanded treatment options, particularly for difficult-to-treat forms of NHL such as mantle cell lymphoma and other aggressive B-cell lymphomas.
The comprehensive nature of current research efforts—spanning multiple therapeutic modalities, targets, and mechanisms of action—underscores the pharmaceutical industry's commitment to improving outcomes for NHL patients worldwide.
