The Antibody Society

the official website of the antibody society

An international non-profit supporting antibody-related research and development.

Emergency use authorization requests for anti-SARS-CoV-2 antibodies under FDA review

by

On October 7, 2020, Eli Lilly and Company and Regeneron announced that they have submitted requests to the  U.S. Food and Drug Administration (FDA) for emergency use authorizations (EUA) of their anti-SARS-CoV-2 monoclonal antibodies.

Lilly’s EUA request is for bamlanivimab (LY-CoV555) monotherapy in higher-risk patients who have been recently diagnosed with mild-to-moderate COVID-19. According to the company, up to 100,000 doses of 700 mg LY-CoV555 monotherapy may be available in October, and one million doses available in Q4 2020.

The combination of LY-CoV555 and LY-CoV016, which bind complementary regions of the SARS-CoV-2 spike protein, for the treatment of symptomatic COVID-19 in an outpatient setting is also being evaluated. Lilly anticipates submission of an EUA request for combination therapy in November, and may have data to support a biologics license application submission for combination therapy as early as Q2 2021.

Regeneron’s EUA request is for REGN-COV2, which is a combination of two anti-SARS-CoV-2 monoclonal antibodies (REGN10933 and REGN10987). Regeneron was granted a $450 million contract to manufacture and supply REGN-COV2 by the US government, which has committed to making the doses available to Americans for free. The agreement covers a fixed number of bulk lots that are intended to be completed in the fall of 2020, as well as fill/finish and storage activities. At the time of the EUA request, Regeneron had doses available for ~ 50,000 patients, and expects to have doses available for a total of 300,000 patients within several months.

The Antibody Society is tracking the progress of recombinant biologic COVID-19 interventions in preclinical and clinical studies. Summary data for all anti-SARS-CoV-2 antibodies in clinical studies can be found here.

Two new antibody therapeutics enter FDA review

by

The first biologics license applications (BLAs) for two antibody therapeutics, balstilimab (AGEN2034) and loncastuximab tesirine (ADCT-042), have recently been submitted to the US Food and Drug Administration, bringing the total number of antibody therapeutics undergoing a first review to 18 (see table here for details).

Balstilimab (Agenus Inc.)

Balstilimab (AGEN2034) is a human IgG4k antibody directed against PD-1, a negative regulator of immune activation expressed by T cells. Numerous antibodies that target PD-1 or its ligand PD-L1 (e.g., pembrolizumab, nivolumab, cemiplimab, avelumab, durvalumab) are marketed as treatments for solid tumors as well as lymphoma. Agenus’ clinical studies of balstilimab have focused on its use, either as monotherapy or in combination with anti-CTLA4 zalifrelimab (AGEN1884), as a treatment for cervical cancer.  FDA granted both balstilimab and the balstilimab/ zalifrelimab combination Fast Track designations for the treatment of cervical cancer. On September 18, 2020, Agenus Inc. announced that they had initiated a rolling BLA to FDA for balstilimab as monotherapy for the treatment of recurrent/metastatic cervical cancer. Agenus controls worldwide rights to balstilimab, except for certain South American rights, which are controlled by Recepta Biopharma, and Greater China rights, which are exclusively licensed to Betta Pharmaceuticals.

Data from a randomized, blinded, non-comparative, two-arm Phase 2 study (NCT03894215) supported the BLA submission. This study evaluated the efficacy and safety of balstilimab as monotherapy or in combination with zalifrelimab for treatment of patients with advanced cervical cancer who relapsed or progressed after receiving first-line platinum-based chemotherapy for a maximum of 24 months, or until disease progression or unacceptable toxicity. The goal of the study is to evaluate the efficacy of each arm against its relevant historical controls. The primary outcome measure is the objective response rate (ORR) to balstilimab administered with placebo (Treatment Arm 1 – monotherapy), or with zalifrelimab (Treatment Arm 2 – combination therapy). Data from the study were presented at the 2020 European Society for Medical Oncology Virtual Congress. Of 160 patients included in the balstilimab monotherapy arm, the ORRs in PD-L1-positive patients and all patients were 19% and 14%, respectively. Of 143 patients included in the balstilimab/ zalifrelimab combination arm, the ORRs in PD-L1-positive patients and all patients were 27% and 22%, respectively.

Loncastuximab tesirine (ADC Therapeutics SA)

Loncastuximab tesirine (ADCT-042) is an ADC composed of an anti-CD19 humanized IgG1k antibody conjugated via a linker to pyrrolobenzodiazepine (PBD)-dimer toxin that induces the killing of CD19-expressing malignant B cells. The FDA granted Orphan Drug designation to ADCT-402 for the treatment of diffuse large B-cell lymphoma (DLBCL) and mantle cell lymphoma. On September 21, 2020, ADC Therapeutics SA announced the submission of a BLA to FDA for loncastuximab tesirine for the treatment of patients with relapsed or refractory DLBCL.

The BLA submission was supported by data from the open-label, single-arm Phase 2 LOTIS 2 study (NCT03589469), which evaluated the safety and efficacy of loncastuximab tesirine for the treatment of patients with relapsed or refractory DLBCL following ≥2 lines of prior systemic therapy. A total of 145 patients received loncastuximab tesirine as an IV infusion over 30 minutes on Day 1 of each cycle (every 3 weeks) at a dose of 150 μg/kg for 2 cycles, then 75 μg/kg for subsequent cycles for up to one year or until disease progression, unacceptable toxicity, or other discontinuation criteria. The primary outcome measure is the overall response rate (ORR). Positive initial data from LOTIS 2 were presented during the virtual 25th Annual Congress of the European Hematology Association. The ORR was 48.3% (70/145 patients), the complete response rate (CRR) was 24.1% (35/145 patients), and the median duration of response was 10.25 months. The toxicity profile was manageable and no new safety concerns were identified.

Antibody research reagents: Market survey data now available

by

The research reagent landscape is changing continuously and keeping up to date on all the significant occurrences takes time, connections, and objectivity. As such, for the past several years, Pivotal Scientific has observed, assessed and compiled an annual Antibody Market Report which gives new ideas and fresh insights about the market over the previous year and indicates how companies can grow in such a competitive market.

Within the report, the State of the Industry survey contains detailed information on the research reagent marketplace from the perspective of key distributors and manufacturers. This is Pivotal Scientific’s fourth yearly survey to better understand the research reagent industry. Once again, our respondents were separated into life science reagent manufacturers, and life science reagent distributors. Questions were focused on key areas of the reagent industry, sales & marketing, logistics, mergers & acquisitions, and product validation.

Key findings:

  • The majority of companies polled reported increasing sales during 2019. As a result, respondents were optimistic, predicting further sales increases and market growth in 2020. This confidence resulted in many distributors considering hiring more staff or opening more offices, although manufacturers displayed a little more caution by limiting expansion compared to previous years.
  • The Asian market continues to expand, with more products from China being distributed by respondents, and China and Japan becoming a bigger source of revenue for our manufacturers. Conversely, the UK appears to be a smaller source of revenue for our polled manufacturers in 2019. This could be due to worries over Brexit reducing science funding and/or spending. The US still dominates the market, being a major supplier of products to distributors and a major source of revenue to manufacturers. To take advantage of this large market, most manufacturers who responded are either based in the US or have a US office.
  • The consensus between distributors and manufacturers is that product quality matters most to their customers, while the main market opportunities are thought to be associated with antibodies and kits. The research area generating the most interest continues to be cancer, and their key competitors unsurprisingly are Abcam, Thermo Fisher Scientific, Bio-Techne and BD Biosciences.
  • The respondents acknowledged the industry could still be doing more to improve product validation. Whilst levels of validation vary between distributors, manufacturers appear to be making a concerted effort to increase validation standards.
  • We can expect further mergers and acquisitions to take place in 2020. Many companies have stated an interest in either buying or selling in 2020, especially amongst the polled distributors.

Need more details?

A more detailed analysis of the results of our survey and industry insights can be found in the Pivotal Scientific Antibody Market Report 2020.

First study results for anti-SARS-CoV-2 antibody LY-CoV555

by

On September 16, 2020, Eli Lilly and Company announced proof of concept data from an interim analysis of the Phase 2 BLAZE-1 clinical trial (NCT04427501) of LY-CoV555 (also known as LY3819253), an anti-SARS-CoV-2 IgG1 antibody. The randomized, double-blind, placebo-controlled study included 4 arms (placebo, 700 mg, 2800 mg, and 7000 mg administered intravenously (IV)), and enrolled mild-to-moderate recently diagnosed COVID-19 patients. Treatment is provided in an outpatient setting. The study was initiated on June 17, 2020 and has an estimated primary completion date of September 20, 2020.

  • The prespecified primary endpoint, change from baseline in viral load at day 11, was met at the 2800 mg dose level, but not the others. Additional analyses of viral data demonstrated that LY-CoV555 improved viral clearance at an earlier time point (day 3) and reduced the proportion of patients with persistently high viral load at later time points. Most patients, including those receiving placebo, demonstrated near complete viral clearance by day 11.
  • Analysis of pooled data from all dose groups indicated the rate of hospitalizations and ER visits was 1.7% (5/302) for LY-CoV555 vs. 6% (9/150) for placebo. Across all treatment groups (including placebo), no patients progressed to mechanical ventilation or died.
  • Viral RNA sequencing revealed putative LY-CoV555-resistance variants in placebo and all treatment arms. The rate of resistance variants was numerically higher in treated patients (8 percent) versus placebo (6 percent).
  • LY-CoV555 was well-tolerated, with no drug-related serious adverse events reported. Treatment emergent adverse events were similar across all dose groups and comparable to placebo.

Details for the BLAZE-1 study were updated on August 21, 2020 to include an experimental treatment arm comprising LY3819253 + LY3832479 (also known as LY-CoV016) administered IV.  LY-CoV016 binds a different epitope in the SARS-CoV-2 spike region compared to LY-CoV555. Across all treatment arms, the trial will enroll an estimated 800 participants.

Summary data for all anti-SARS-CoV-2 antibodies in clinical studies can be found here.

Fighting the Forever-war Against Infectious Diseases

by

Author: Nick Hutchinson, Mammalian Cell Culture, Business Steering Group Lead, FUJIFILM Diosynth Biotechnologies (nick.hutchinson@fujifilm.com)

The COVID-19 crisis has had a devastating impact on populations across the world and caused the death of hundreds of thousands of people. The Antibody Society spoke to Dr. Jacob Glanville, CEO and President of Distributed Bio, Inc. to learn how his company has approached the development of new antibody therapeutics against the SARS-CoV-2 Coronavirus. He described how the crisis has stimulated innovation that may revolutionize the way we approach antibody discovery and development once the current pandemic is under control.

Dr Glanville explained, “The problem, when we think of every major outbreak, such as Ebola, SARS, MERS, Swine Flu, Avian Flu, is that the time it takes to develop a new drug is too long compared to the speed with which we need it. De novo discovery is too slow.”

To develop antibody therapeutics against COVID-19 as quickly as possible, Distributed Bio identified anti-SARS antibodies from almost 20 years ago that researchers had already shown would neutralize the SARS virus in vitro, protect mice from lethal challenge, and had known crystal structures. These antibodies have been studied extensively but were eventually too late to have an impact on the SARS crisis of 2003. It was Glanville’s idea to take advantage of the detailed functional research already performed on these antibodies and, try to retrofit them to bind to the new version of their original target the virus SARS-CoV-2. For this purpose, Distributed Bio applied their Tumbler technology, a computationally-guided antibody optimization method, capable of producing a library of billions of variants of individual antibodies exploring variations of all six complementarity-determining regions simultaneously.

“The novel coronavirus has around 74% homology in identity with the SARS receptor binding domain. I knew exactly how similar they were to the novel coronavirus as we had crystal structures of the SARS epitope. I believed that if we took five anti-SARS antibodies, there was going to be a pretty good chance that we would be able to adapt them to be a potent medicine against COVID-19,” said Glanville. “We already knew that they had the correct function, that they bound the right epitope in the right orientation with the right elbow angles. I believed that we could optimize them and enhance their affinity by making billions of versions of the antibodies within the library,” he continued.

According to Glanville, this is crucially important because historically, with outbreaks such as Ebola, the first antibodies launched were essentially prototypes with low potency or had inferior characteristics such as poor thermostability. It was the best-in-class not the first antibody that was successful, ultimately.

Distributed Bio were able to adapt all five antibodies in just nine weeks, a testament to the remarkable speed of these novel technologies. They sent a set of the most promising candidates to five laboratories which independently confirmed their ability to bind to the new SARS-CoV-2. The company then selected the two most potent antibodies for in-vivo testing, and two laboratories confirmed independently that both candidates protected healthy, as well as immuno-compromised animals using hamster models.

[Read more…]