6 Upcoming Bispecific Antibodies Beyond Oncology

Imagine a world where treatment options are as precise as a scalpel and as adaptable as a chameleon. Bispecific antibodies are paving the way for this future, bringing revolutionary advancements not just in oncology but across various therapeutic fields. By harnessing the power of these dual-targeting agents, researchers are unlocking new possibilities in treating complex diseases with unprecedented specificity and efficacy. Beyond their groundbreaking work in cancer, bispecific antibodies are making waves in autoimmune disorders, infectious diseases, and even rare genetic conditions, offering hope where conventional therapies fall short. 

As we stand on the brink of this new frontier, bispecific antibodies promise to unlock unprecedented therapeutic possibilities, heralding a new era where treatment is not only more targeted but also more effective. With each new discovery and clinical trial, we’re inching closer to a new era of personalized medicine that promises not just to manage, but to potentially cure some of the most challenging health conditions. The horizon is bursting with potential—are we ready to embrace it?

6 Bispecific Antibodies on the Horizon Beyond Oncology

BsAbs have emerged as promising therapeutics against cancer indications. At present, cancer indications account for the majority of bispecific antibody development. The US FDA has approved bispecific antibodies for cancer indications in addition to hemophilia A, diabetic macular edema, and neovascular (wet) age-related macular degeneration (AMD). 

Most of the BsAbs are now being explored for cancer indications, although a limited number of BsAbs are also being developed for non-oncology indications. The key companies that are active in the non-oncology space include Provention Bio, Sanofi, AbbVie, AstraZeneca, MoonLake Immunotherapeutics, and IGM Biosciences. Here, have a look at the 6 promising bispecific antibodies in the pipeline by these leading companies.

MoonLake Immunotherapeutics’ Sonelokimab 

Sonelokimab (M1095) is an experimental humanized Nanobody weighing approximately 40 kDa, made up of three VHH domains connected by flexible glycine-serine linkers. It binds with high affinity to IL-17A and IL-17F through two of its domains, effectively blocking the formation of IL-17A/A, IL-17A/F, and IL-17F/F dimers.

The company has finished a Phase II trial for sonelokimab to treat moderate-to-severe hidradenitis suppurativa and is now assessing the drug in two Phase III hidradenitis suppurativa clinical trial studies. The 24-week topline results were shared at the AAD 2024 annual meeting. This Phase III program follows MoonLake’s announcement in February 2024 of a positive outcome from end-of-Phase II discussions with the US FDA and favorable feedback from the EMA, which endorsed MoonLake’s plan for advancing to Phase III. 

The Phase III VELA program will involve 800 patients across VELA-1 and VELA-2. This is the first Phase III study in hidradenitis suppurativa to use HiSCR75 as the primary endpoint. The company anticipates topline results for the primary endpoint of the Phase III VELA trial at Week 16, along with data on other endpoints, to be available by mid-2025.

In addition to this, IGM Biosciences is also conducting a Phase Ib clinical study to evaluate their bispecific antibody, Imvotamab for the treatment of Rheumatoid arthritis. The purpose of this study is to determine the safety and tolerability of imvotamab in adult participants with active Rheumatoid arthritis who are refractory or intolerant to 2 previous biologic disease-modifying anti-rheumatic drugs (bDMARD) or targeted synthetic disease-modifying anti-rheumatic drugs (tsDMARD) therapies.

AbbVie’s Lutikizumab

Lutikizumab (ABT-981) is an investigational hidradenitis suppurativa drug with dual-variable domains that targets interleukin (IL) 1α and 1β. It is currently being researched for use in various immune-mediated conditions, such as hidradenitis suppurativa and ulcerative colitis. Research indicates that IL 1α and 1β levels are increased in hidradenitis suppurativa lesions. However, Lutikizumab is still under investigation and has not yet received approval from regulatory agencies, so its safety and effectiveness have not been confirmed.

In January 2024, AbbVie announced Phase II results indicating that adults with moderate to severe hidradenitis suppurativa who had not responded to anti-TNF therapy showed better response rates when treated with lutikizumab (ABT-981) at doses of 300 mg every other week or 300 mg weekly, achieving 59.5 percent (nominal p=0.027) and 48.7 percent (nominal p=0.197) respectively, compared to 35.0 percent for placebo in the primary endpoint of achieving HS Clinical Response (HiSCR 50) at week 16. As a result, AbbVie moved lutikizumab into Phase III of its clinical development program for hidradenitis suppurativa.

Provention Bio/Sanofi’s PRV-3279

PRV-3279 is an investigational humanized bispecific DART molecule that targets the B-cell surface proteins CD32B and CD79B. By simultaneously engaging these receptors, it inhibits B cell function and suppresses autoantibody production, effectively regulating B cells without causing their depletion. Provention Bio is initially developing PRV-3279 to intercept systemic lupus erythematosus (SLE), a chronic autoimmune disorder marked by abnormal B cell overactivation and the pathological production of autoantibodies. Additionally, PRV-3279 has the potential to prevent or reduce the immunogenicity of biotherapeutics, including gene therapy vectors and transgenes. Currently, Provention is evaluating PRV-3279 in the PREVAIL-2 study, focused on lupus.

The PREVAIL-2 study is a Phase IIa proof-of-concept (POC) trial focused on moderate-to-severe SLE patients who respond to a brief course of corticosteroids and are then monitored for relapse after being randomized to receive either PRV-3279 or a placebo. This study design allows for the withdrawal of most concurrent medications, facilitating a clear POC assessment. The trial will take place in the US and Hong Kong, with screening already underway in the US. 

The goal is to identify and enroll around 100 patients, who will receive six monthly infusions of either PRV-3279 or a placebo, with the primary efficacy outcome measured at 24 weeks. In previous studies, PRV-3279 was well-tolerated, with Phase I trials (including the PREVAIL-1 study) demonstrating long-lasting inhibition of B cell function, evidenced by a reduction in IgM levels 8 weeks after the final dose. These findings, along with data showing that CD32B genetic variants are linked to SLE and that PRV-3279 inhibits B cells from SLE patients, justify further evaluation of SLE.

AstraZeneca’s MEDI-7352

MEDI7352 is a bi-specific fusion protein that targets both nerve growth factor (NGF) and tumor necrosis factor receptor 2 (TNFR2). Increased NGF levels are associated with various painful conditions while inhibiting the TNF receptor has demonstrated pain reduction in inflammatory joint diseases during clinical trials. This drug candidate, a new molecular entity (NME), is administered via intravenous or subcutaneous injection. It is currently in phase II development for the treatment of painful osteoarthritis of the knee, painful diabetic neuropathy, and osteoarthritis-related pain.

IGM Biosciences’ Imvotamab

Imvotamab is a bispecific T cell-engaging IgM antibody designed to target both CD20 and CD3 proteins. It is believed that, with its 10 binding units for CD20, imvotamab may have a stronger ability to bind to CD20-expressing B cells compared to IgG bispecific antibodies, which have only one or two CD20 binding units.

Imvotamab could provide significant advantages over current B cell therapies. Preclinical research indicates that it can penetrate and deplete CD20-expressing cells in tissues such as the bone marrow, spleen, and lymph nodes. Furthermore, in vitro studies demonstrate that imvotamab is considerably more effective than rituximab in depleting cells with low CD20 expression. These findings suggest that imvotamab may enable a deeper depletion of B cells than currently available antibody therapies.

IGM Biosciences is testing imvotamab in B cell-mediated autoimmune diseases and is conducting Phase Ib clinical trials in patients with severe systemic lupus erythematosus (SLE), rheumatoid arthritis, and idiopathic inflammatory myopathies.

AstraZeneca’s AZD1163

AstraZeneca’s novel anti-PAD2/4 bispecific antibody, AZD1163, is being developed through phage display technology and shows a strong binding affinity for recombinant human PAD2 and PAD4. AZD1163 successfully inhibits endogenous PAD activity in the serum and synovial fluid of rheumatoid arthritis patients, without causing proinflammatory responses or disrupting normal neutrophil functions.

In studies with non-human primates, a single dose of 5 mg/kg of AZD1163 led to a prolonged reduction in PAD activity for eight weeks, even in samples with high PAD4 levels similar to those in some rheumatoid arthritis patients’ serum.

Currently, AstraZeneca is evaluating this bispecific antibody in a Phase I trial (NCT06103877; Recruiting), with initial data expected in 2025. The study aims to assess the safety and tolerability of AZD1163 when given intravenously and subcutaneously to healthy participants.

What Lies Ahed for Bispecific Antibodies Beyond Oncology 

As the spotlight on bispecific antibodies has traditionally shone brightly on oncology, the future promises an even more expansive horizon for these innovative therapeutics. With their unique ability to target two different antigens simultaneously, bispecific antibodies are poised to revolutionize treatment paradigms across a spectrum of diseases. Beyond cancer, these tailored therapies are making strides in autoimmune disorders, where they could potentially reprogram the immune system to halt destructive inflammation. Imagine a world where conditions like rheumatoid arthritis and multiple sclerosis are managed with precision therapies that address multiple disease mechanisms at once.

Additionally, bispecific antibodies hold the key to advancing treatments in infectious diseases, including chronic viral infections and emerging pathogens. By harnessing their dual-targeting capability, researchers are developing next-generation treatments that could neutralize complex viral infections more effectively than ever before. As we venture into this new era, the potential applications of bispecific antibodies could reshape the landscape of medicine, offering hope and innovative solutions for a range of unmet medical needs.