The Antibody Society

the official website of the antibody society

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

A newly certified AIRR-compliant software tool: The Immcantation Framework

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The AIRR Community is excited to announce that the Immcantation Framework has been certified as compliant with the AIRR-C v1.0 standard for AIRR-Seq software tools.

In an effort to enable rigorous and reproducible immune repertoire research at the largest scale possible, the AIRR-C Software Working Group has established a standard to validate software tools using the AIRR-C Standards and meeting a series of interoperability and quality criteria. Developers interested in certifying their tools should complete the checklist and submit it to the AIRR-C Software Working Group for evaluation and ratification by its members.

More details can be found at the website AIRR Software WG – Guidance for AIRR Software Tools.

All compliant tools will be issued a badge and listed on the website AIRR Software WG – List of Tools Certified as Compliant.

Rare Disease Day, February 28, 2021

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On or about the last day of February each year, the rare disease community comes together to raise awareness of these conditions. In the US, any disease affecting fewer than 200,000 people (1 per ~1,650 people) is considered rare, while a disease is defined as rare in Europe when it affects fewer than 1 in 2,000 people. There are more than 7,000 rare diseases, and these collectively affect ~ 25-30 million Americans. Information about specific rare diseases can be found in the National Organization for Rare Disorders’ Rare Disorders Database and the National Institutes of Health’s Genetic and Rare Diseases Information Center.

In the US, the Orphan Drug Act passed by Congress in 1983 incentivizes the development of drugs to treat rare diseases. Similar programs in Europe, Japan, as well as other countries, also allow other regulatory agencies to grant ‘orphan drug’ designations.  Hundreds of drugs have been approved for the treatment of rare diseases, including numerous antibody therapeutics, although substantial medical need still remains. Antibody therapeutics recently approved for rare diseases include:

  • Caplacizumab (Cablivi), a treatment for acquired thrombotic thrombocytopenic purpura, which is a rare blood clotting disorder.
  • Crizanlizumab (Adakveo), indicated to reduce the frequency of vaso-occlusive crisis, which is a painful complication of sickle cell disease that occurs when blood circulation is obstructed by sickled red blood cells.
  • Teprotumumab (Tepezza), indicated for thyroid eye disease, which is associated with an outward bulging of the eye that can cause eye pain, double vision, light sensitivity or difficulty closing the eye.
  • Inebilizumab (Uplizna) and satralizumab (Enspryng), treatments for neuromyelitis optica spectrum disorder, which is a rare autoimmune disorder of the central nervous system that primarily damages the optic nerve(s) and spinal cord, causing blindness, muscle weakness and paralysis.
  • Evinacumab (Evkeeza), a treatment for homozygous familial hypercholesterolemia, which is a genetic condition that causes severely high cholesterol.
  • Ansuvimab (Ebanga) and the triple antibody cocktail of atoltivimab, maftivimab, and odesivimab (Inmazeb) for the treatment for Zaire ebolavirus (Ebolavirus) infection.
  • Naxitamab (DANYELZA®) for the treatment of relapsed or refractory high-risk neuroblastoma in the bone or bone marrow.

More information about these antibody therapeutics, including target, format and year of approval, can be found here.

Other antibody therapeutics for rare diseases are in late-stage clinical studies and may be approved soon, including:

  • Garetosmab, which is undergoing evaluation as a treatment for fibrodysplasia ossificans progressive (FOP), an ultra-rare genetic disorder characterized by the progressive replacement of soft tissue, such as muscles, tendons, and ligaments, by bone, a process known as heterotopic ossification. Regeneron plans regulatory submission(s) for garetosmab for FOP in 2021.
  • Mirvetuximab soravtansine, which is undergoing evaluation as a treatment for ovarian cancer. ImmunoGen anticipates the submission of a biologics license application for accelerated approval of mirvetuximab soravtansine for ovarian cancer during the second half of 2021.
  • KN046, which is undergoing evaluation as a treatment for thymic carcinoma. Alphamab Oncology has announced that the Phase 2 clinical trial (NCT04469725) of KN046 to treat thymic carcinoma will support their plan to submit marketing applications for KN046 to China’s National Medical Products Administration and the US Food and Drug Administration in 2021.

More information about antibody therapeutics in late-stage studies can be found in ‘Antibodies to Watch in 2021‘.

Keep up to date on US and EU approvals all year by visiting our website!

The Antibody Society maintains a comprehensive table of approved monoclonal antibody therapeutics and those in regulatory review in the EU or US. The table, which is located in the Web Resources section of the Society’s website, can be downloaded in Excel format.

FDA approves Evkeeza (evinacumab-dgnb) for homozygous familial hypercholesterolemia

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On February 11, 2021, the US Food and Drug Administration approved Evkeeza (evinacumab-dgnb) injection as an add-on treatment for patients aged 12 years and older with homozygous familial hypercholesterolemia (HoFH), a genetic condition that causes severely high cholesterol. Evkeeza received orphan drug and breakthrough therapy designations for this indication, and the biological license application received a priority review.

Evinacumab is a human IgG4k antibody targeting angiopoietin-like 3 (ANGPTL3), which regulates the metabolism of plasma lipids, including low-density lipoprotein (LDL) cholesterol, high-density lipoprotein cholesterol, and triglycerides. The antibody was derived from Regeneron’s Velocimmune® technology platform, and includes a stabilizing mutation in the hinge region to minimize half-antibody formation.

Data from the Phase 3 ELIPSE trial (NCT03399786) was used as the basis of regulatory submissions. In this study 65 patients were randomized to receive either IV administration of evinacumab 15 mg/kg every four weeks (n=43) or placebo (n=22), plus other lipid-lowering therapies. The primary endpoint was the percent change from baseline in the LDL cholesterol level at Week 24. At baseline, LDL cholesterol was 260 mg/dL in the evinacumab group and 247 mg/dL in the placebo group. The primary endpoint of the study was met. Relative to baseline, the LDL cholesterol level at Week 24 was reduced by 47.1% in the patients administered evinacumab, but increased 1.9% in the placebo group.

Keep up to date on US and EU approvals all year by visiting our website!

The Antibody Society maintains a comprehensive table of approved monoclonal antibody therapeutics and those in regulatory review in the EU or US. The table, which is located in the Web Resources section of the Society’s website, can be downloaded in Excel format.

Evinacumab is the first investigational (i.e., not previously approved for any indication) antibody therapeutic to be granted an approval in the EU or US in 2021. There are currently 17 investigational antibody therapeutics in regulatory review in the EU or US.

FDA issues Emergency Use Authorization for bamlanivimab/etesevimab combination

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On February 9, 2021, the U.S. Food and Drug Administration issued an emergency use authorization (EUA) for bamlanivimab and etesevimab administered together for the treatment of mild to moderate COVID-19 in adults and pediatric who test positive for SARS-CoV-2 and who are at high risk for progressing to severe COVID-19. Developed by Eli Lilly and Company, bamlanivimab and etesevimab are monoclonal antibodies (mAbs) that target overlapping regions of the SARS-CoV-2 spike protein.

The EUA was based on a randomized, double-blind, placebo-controlled clinical trial in 1,035 non-hospitalized adults with mild to moderate COVID-19 symptoms who were at high risk for progressing to severe COVID-19. Of these patients, 518 received a single infusion of bamlanivimab (2.8 g) and etesevimab (2.8 g) together, and 517 received placebo. The primary endpoint was COVID-19 related hospitalizations or death by any cause during 29 days of follow-up.  Hospitalization or death occurred in 11 (2%) patients treated the mAb combination vs. 36 (7%) patients who received placebo. All 10 deaths (2%) occurred in the placebo group.

The authorized dosage of 700 milligrams bamlanivimab and 1400 milligrams etesevimab administered together is based on analyses of available preclinical, clinical, and virologic data, as well as pharmacokinetic and pharmacodynamic modeling, which, in totality, support that the authorized dosage is expected to have a similar clinical and virologic effect to the dose evaluated in the clinical trial. Use of the mAb combination is not authorized for patients who are hospitalized due to COVID-19 or require oxygen therapy due to COVID-19.

In November 2020, FDA issued an EUA for a single infusion of 700 mg bamlanivimab for the treatment of mild-to-moderate COVID-19 in adult and certain pediatric patients. Since the monotherapy and the combination treatment are expected to benefit patients at high risk of disease progression, both 700 milligrams bamlanivimab alone and the combination of 700 milligrams bamlanivimab and 1,400 milligrams etesevimab administered together will be available under an EUA.

Call for Papers on Biopharmaceutical Informatics

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As evident from papers published in mAbs in recent years, computation is being increasingly used in the discovery and development of antibody-based biologic drugs. To celebrate the rise of biopharmaceutical informatics directed towards antibody R & D, we invite The Antibody Society members, mAbs readers and the broader scientific community to contribute review articles focused on highlighting how computation has enabled their investigations or led them to new ones. The reviews should narrate the state of the art and speculate on new vistas for computational applications in the field.

We are particularly interested in reviews in the following topics:

  • Analyses of immune repertoires and their role in target validation and drug discovery.
  • Analyses of antibody structure-function relationships with emphasis on therapeutic antibody-based biologics.
  • Structure-based design of antibody fragments (e.g., nanobodies) and antibody-based multi-specific molecular formats.
  • Design of antibody libraries for different display strategies and/or with improved developability.
  • Structure-based affinity maturation and optimization of biologic lead candidates.
  • Molecular simulations of antibodies to understand their solution behaviors, such as aggregation, viscosity and physicochemical degradation.
  • Consideration of developability in biologic drug discovery and design.
  • Developability assessments at early-stage development.
  • Specific and non-specific interactions formed by antibodies in vitro and in vivo.
  • Computation in antibody formulations – design of novel excipients.
  • Applications of artificial Intelligence and machine learning towards antibody discovery, development and manufacturing.
  • Progress and challenges in modeling antibodies and multi-specific formats.
  • Predicting chemical degradation in antibody-based biologic drugs.
  • Optimizing antigens for greater immunization success.

Although these topics are especially of interest, we welcome well-written reviews in related areas as well.

Publication charges will be waived for six of the best review articles selected from pre-submission inquiries, which should consist of the title, abstract and general outline of the intended review article.

The deadline for the pre-submission enquiries is February 15, 2021, and the deadline for submission of the completed review articles is June 30, 2021.

Please send pre-submission inquiries to Assistant Editor Dr. Sandeep Kumar (skumarmabs@gmail.com) and Editor-in-Chief Dr. Janice Reichert (reichert.biotechconsulting@gmail.com), and contact us if you have any questions.