Please login to the form below

Not currently logged in

Regeneron’s early stage bispecific shows promise

Bispecifics and antibody drug conjugates will challenge CAR-Ts


The potentially revolutionary nature of CAR-Ts has made them the hottest properties in haemato-oncology in recent years, but a wave of bispecific antibody therapies look set to challenge them.

Representing an evolution of the well-established monoclonal antibody platform, bispecifics can hit two or more cell surface targets. This approach could see them match the clinical performance of CAR-Ts, but with a far easier and lower cost manufacturing process, and without the risk of serious side effects including cytokine-release syndrome (CRS).

Regeneron is one many companies developing bispecifics, and on Saturday at the ASH 2018 congress in San Diego, unveiled phase 1 proof of concept data for its REGN1979 in relapsed or refractory (R/R) follicular lymphoma and diffuse large B-cell lymphoma (DLBCL), the two most common types of Non-Hodgkins Lymphoma (NHL).

The company says REGN1979 demonstrated an acceptable safety and tolerability profile with no observed dose-limiting toxicities (DLTs), and no clinically-significant neurotoxicities, including no occurence of seizures or encephalopathy.

The drug binds to CD3 on immune system T-cells and CD20 on B-cell malignancies.

The clinical response from patients was very encouraging: heavily pre-treated patients with R/R FL grades 1 to 3a who received REGN1979 doses of 5 mg to 40 mg, experienced a 100% overall response rate (ORR) (8 complete responses [CR] and 2 partial responses, with 90% of responders maintained a response during treatment.

Regeneron says it will now initiate in 2019 a phase 2 trial of the drug, which could be sufficient to file with regulators, and says it could be a future first line therapy.

"While a high response rate is frequently observed in the first-line treatment of follicular lymphoma, it is remarkable to see a 100% response rate in heavily pre-treated relapsed or refractory follicular lymphoma patients," said Israel Lowy, M.D., Ph.D., Head of Clinical and Translational Sciences, Oncology at Regeneron.

Dose escalation will continue in the more difficult-to-treat DLBCL setting to see if efficacy can be improved further in these patients.

REGN1979 is being investigated in combination with Regeneron’s newly FDA-approved checkpoint inhibitor Libtayo (cemiplimab-rwlc) in an ongoing phase 1 study.

While Libtayo is far behind the immunotherapy leaders of Merck & Co’s Keytruda and BMS’ Opdivo, the firm is hoping to gain an edge by testing a combination of the two therapies, making it the first to investigate the combination of  of a CD20xCD3 bispecific antibody with a PD-1 or PD-L1 inhibitor.

George Yancopoulos

Regeneron's George Yancopoulos

"There have been tremendous recent advances in the field of immuno-oncology, with new breakthrough therapies including checkpoint inhibitors and personalised cell-based therapies," said George D. Yancopoulos, M.D., Ph.D., President and Chief Scientific Officer at Regeneron.

Yancopoulos said its bispecific pipeline could offer off-the-shelf alternatives to cell-based therapies for both solid tumours and haematologic malignancies.

Its bispecific antibody pipeline includes REGN1979 and a MUC16xCD3 antibody for ovarian cancer in early development, with a BCMAxCD3 antibody for multiple myeloma expected to enter human studies before the end of this year.

“In 2019, we expect to start clinical trials of a new class of bispecific antibodies that engage cellular immunity in novel ways,” he added. “We believe that cancer treatment in the future will require precision medicine-based combinations of these and other approaches and that Regeneron is well positioned to be a future leader in this exciting area."

Also presenting bispecific antibodies at ASH are Amgen (AMG 420) and Pfizer (PF-06863135).

Another alternative platform is antibody-drug conjugates (ADCs). GlaxoSmithKline is presenting early data from its anti-BCMA GSK2857916 at the congress.

Article by
Andrew McConaghie

3rd December 2018

From: Research



Featured jobs

Subscribe to our email news alerts


Add my company
Anthill Agency

Digital communications agency empowering clients through their digital transformation journey. Whether through training, delivering solutions or devising digital strategies, we...

Latest intelligence

Article: Like, Like, Like: Harnessing the power of social media insights
Its Know Your Numbers week
Do you know yours?...
What is changing in mental health and dementia care?
Paul Midgley, of Wilmington Healthcare, takes a look at the NHS Long Term Plan's bid to transform mental health and dementia services...