The Antibody Society

the official website of the antibody society

The Antibody Society

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

Most read from mAbs, January 2019

by

The Antibody Society is pleased and proud to be affiliated with mAbs, a multi-disciplinary journal dedicated to advancing the art and science of antibody research and development. We hope you enjoy these summaries based on the abstracts of the most read papers published in a recent issue. All the articles are open access; PDFs can be freely downloaded by following the links below.

Issue 11.1 (January 2019)

Evolution of a comprehensive, orthogonal approach to sequence variant analysis for biotherapeutics.
As discussed by Lin et al., a cross-functional team of Pfizer colleagues from the Analytical and Bioprocess Development departments worked closely together for over 6 years to formulate and communicate a practical, reliable sequence variant (SV) testing strategy with state-of-the-art techniques that did not necessitate more resources or lengthen project timelines. The final SV screening strategy relies on next-generation sequencing and amino acid analysis as frontline techniques to identify mammalian cell clones with genetic mutations and recognize cell culture process media/feed conditions that induce misincorporations, respectively. Once an industry-wide challenge, sequence variation is now routinely monitored and controlled at Pfizer (and other biopharmaceutical companies) through increased awareness, dedicated cross-line efforts, smart comprehensive strategies, and advances in instrumentation/software, resulting in even higher product quality standards for biopharmaceutical products.

The first World Health Organization International Standard for infliximab products: A step towards maintaining harmonized biological activity.
In this Brief Report, Metcalfe et al. present a collaborative study designed to assess the suitability of the first international standard (IS) for infliximab to serve as an IS for the in vitro biological activity of infliximab. The IS was developed by the UK’s National Institute for Biological Standards and Control (NIBSC). The study involved participants using in vitro cell-based bioassays (TNF neutralization, antibody-dependent cell-mediated cytotoxicity and complement-dependent cytotoxicity) and binding assays. The results of this study showed that the candidate preparation, coded 16/170, is suitable as an IS for infliximab bioactivity. This infliximab IS from NIBSC, is intended to support in vitro bioassay calibration and validation by defining international units of bioactivity

Anti-PD1 ‘SHR-1210ʹ aberrantly targets pro-angiogenic receptors and this polyspecificity can be ablated by paratope refinement.
Finlay et al. report that the combination of receptor proteome screening and optimization of the antibody binding interface succeeded in generating novel, higher-potency, specificity-enhanced therapeutic IgGs from a single, clinically sub-optimal progenitor. They show that highly-specific off-target binding events might be an under-appreciated phenomenon in therapeutic antibody development, but that these unwanted properties can be fully ameliorated by paratope refinement.

Deamidation and isomerization liability analysis of 131 clinical-stage antibodies.
As discussed by Lu et al., knowledge of the chemical stability characteristics of clinical-stage therapeutic monoclonal antibodies (mAbs) is fragmented and lacks comprehensive comparative assessment. To address this knowledge gap, the authors produced 131 mAbs with amino acid sequences corresponding to the variable regions of clinical-stage mAbs, subjected these to low and high pH stresses and identified the resulting modifications at amino acid-level resolution via tryptic peptide mapping. Among this large set of mAbs, relatively high frequencies of asparagine deamidation events were observed in CDRs H2 and L1, while CDRs H3, H2 and L1 contained relatively high frequencies of instances of aspartate isomerization.

Like this post but not a member? Please join!
Members receive a discounted subscription rate ($84/yr online access) for mAbs.

First approval for romosozumab

by

Japan’s Ministry of Health, Labor and Welfare has granted a marketing authorization for romosozumab (EVENITY) for the treatment of osteoporosis in patients at high risk of fracture. Developed by Amgen and UCB, romosozumab is a humanized IgG2 monoclonal antibody that targets sclerostin. The approval in Japan is based on results from the Phase 3 FRAME and BRIDGE studies, which included 7,180 postmenopausal women with osteoporosis and 245 men with osteoporosis, respectively.

A biologics license application (BLA) for romosozumab as a treatment of osteoporosis in postmenopausal women at high risk for fracture was submitted to the U.S. Food and Drug Administration (FDA) in July 2016, but additional safety and efficacy data was requested in the FDA’s complete response letter, as announced by Amgen and UCB in July 2017. In July 2018, Amgen and UCB announced that the BLA had been resubmitted. In addition to data from early-stage clinical studies, the original BLA included data from the Phase 3 FRAME study. The resubmitted BLA includes results from the more recent Phase 3 ARCH study, an alendronate-active comparator trial including 4,093 postmenopausal women with osteoporosis who experienced a fracture, and the Phase 3 BRIDGE study. The FDA’s Bone, Reproductive and Urologic Drugs Advisory Committee is scheduled to review data supporting the BLA for romosozumab at a meeting on January 16, 2019.

The European Medicines Agency is also currently reviewing a marketing application for romosozumab.

Like this post but not a member? Please join!

The Antibody Society maintains a comprehensive table of approved antibody therapeutics and those in regulatory review in the EU or US. Please log in to access the table, which is located in the Members Only section and can be downloaded in Excel format.

“Antibodies to watch in 2019”

by

The latest “Antibodies to watch” article is now freely accessible at mAbs! 

For the past 10 years, the annual ‘Antibodies to watch’ articles have provided updates on key events in the late-stage development of antibody therapeutics, such as first regulatory review or approval, that occurred in the year before publication or were anticipated to occur during the year of publication. To commemorate the 10th anniversary of the article series and to celebrate the 2018 Nobel Prizes in Chemistry and in Physiology or Medicine, which were given for work that is highly relevant to antibody therapeutics research and development, the scope of the data presented was expanded to include an overview of all commercial clinical development of antibody therapeutics and approval success rates for this class of molecules. The data indicate that: 1) antibody therapeutics are entering clinical study, and being approved, in record numbers; 2) the commercial pipeline is robust, with over 570 antibody therapeutics at various clinical phases, including 62 in late-stage clinical studies; and 3) Phase 1 to approval success rates are favorable, ranging from 17–25%, depending on the therapeutic area (cancer vs. non-cancer).

As of November 2018, a record number of antibodies (erenumab (Aimovig), fremanezumab (Ajovy), galcanezumab (Emgality), burosumab (Crysvita), lanadelumab (Takhzyro), caplacizumab (Cablivi), mogamulizumab (Poteligeo), moxetumomab pasudodox (Lumoxiti), cemiplimab (Libtayo), ibalizumab (Trogarzo), tildrakizumab (Ilumetri, Ilumya), emapalumab (Gamifant)) that treat a wide variety of diseases were granted a first approval in either the European Union (EU) or United States (US). Also as of November 2018, 4 antibody therapeutics (sacituzumab govitecan, ravulizumab, risankizumab, romosozumab) were being considered for their first marketing approval in the EU or US, and an additional 3 antibody therapeutics developed by Chinese companies (tislelizumab, sintilimab, camrelizumab) were in regulatory review in China. In addition, the data show that 3 product candidates (leronlimab, brolucizumab, polatuzumab vedotin) may enter regulatory review by the end of 2018, and at least 12 (eptinezumab, teprotumumab, crizanlizumab, satralizumab, tanezumab, isatuximab, spartalizumab, MOR208, oportuzumab monatox, TSR-042, enfortumab vedotin, ublituximab) may enter regulatory review in 2019. Notably, approximately half (18 of 33) of the late-stage pipeline of antibody therapeutics for cancer are immune checkpoint modulators or antibody-drug conjugates. Of these, 7 (tremelimumab, spartalizumab, BCD-100, omburtamab, mirvetuximab soravtansine, trastuzumab duocarmazine, and depatuxizumab mafodotin) are being evaluated in clinical studies with primary completion dates in late 2018 and in 2019, and are thus ‘antibodies to watch’. The Antibody Society looks forward to documenting progress made with these and other ‘antibodies to watch’ in the next installment of this article series.

Update: Data in “Antibodies to watch in 2019” is as of November 2018. As noted in the post below, risankizumab was approved by FDA on December 21, 2018, bringing the total number of antibody therapeutics approved in the EU or US during 2018 to 13.

First approval for ravulizumab

by

On December 21, 2018, the US Food and Drug Administration approved Ultomiris (ravulizumab) injection for the treatment of adult patients with paroxysmal nocturnal hemoglobinuria (PNH), a rare and life-threatening blood disease characterized by hemolysis of red blood cells mediated by the complement system. Developed by Alexion Pharmaceuticals, ravulizumab is a humanized mAb that inhibits complement component 5 (C5). The biologics license application for ravulizumab received a Priority Review designation. In a Phase 3 study, ravulizumab demonstrated non-inferiority to Soliris® (anti-C5 eculizumab) in complement-inhibitor treatment-naïve patients with PNH. Also developed by Alexion Pharmaceuticals, Soliris® was first approved for PNH in 2007. Ravulizumab is also undergoing regulatory review in the EU. It was granted Orphan Drug designation in both the US and EU for the treatment of patients with PNH.

Like this post but not a member? Please join!

The Antibody Society maintains a comprehensive table of approved mAb therapeutics and those in regulatory review in the EU or US. As of December 21, a total of 13 antibody therapeutics had been granted first approvals in either the US or EU in 2018, and marketing applications for another 3 that have not yet been approved in either the EU or US are undergoing review in these regions. Please log in to access the table in Excel format, located in the Members Only section.

Grad/PostDoc Poster Awards presented at Antibody Engineering &Therapeutics

by

Congratulations to our 2018 Graduate Student and Post-doctoral Poster Award winners! An award ceremony was held on December 12th at the Society’s annual meeting, Antibody Engineering &Therapeutics, to recognize the recipients. The winners were:

Junpeng Qi (Postdoctoral Associate, The Scripps Research Institute). Poster title: Potent and selective antitumor activity of a T cell-engaging bispecific antibody targeting a membrane-proximal epitope of ROR1.

Pietro Sormanni (Borysiewicz Biomedical Sciences Fellow (postdoctoral), University of Cambridge). Poster title: Third generation antibody discovery: In silico rational design.

Madeleine Jennewein (Ph.D. candidate, Harvard University). Poster title: Trans-placental antibody transfer selects for highly functional antibodies.


Junpeng Qi – Scripps Research Institute (The Rader Lab)

“I would to thank The Antibody Society for giving me this award. It is a great opportunity, especially for a young scientist, to get the latest progress in antibody engineering and therapeutics, and to be connected with the excellent scientists in the antibody field. From this impressive annual meeting I learned that we can do amazing science with antibodies and develop fantastic antibody therapeutics benefiting patients as well.”

Pietro Sormanni – University of Cambridge (The Vendruscolo Lab)

“I am immensely grateful to The Antibody Society for selecting my application, and even more for organizing this award. This award has given me the opportunity to attend this terrific meeting, to learn about world-class research in both industry and academia, and more importantly to share and discuss my own work with leading scientists from across the world. I would like to stress the importance of the existence of awards such as this, and I call for the Society and the sponsors of the meeting to make available more of these awards and travel grants to early career researchers. Because at the end of the day, the growing community of postdoctoral researchers and graduate students is the engine that powers biomedical research, certainly in academia, and increasingly also in industry. And these travel grants provide us with the unique opportunity to get out of the lab, come to these meetings and greatly expand our research horizons, and generate new ideas. So I hope to see a bit more space dedicated to early career researchers in future editions of this meeting, thank you all for your attention, and again to The Antibody Society for this award.”

Madeleine F Jennewein – Harvard University (The Alter Lab)

Madeleine Jennewein was unexpectedly unable to join us at the meeting in San Diego, but we thank her for her participation and wish her the best with her work.