Zymeworks' detailed understanding of protein dynamics helps the company's research scientists to profile protein hotspots and refine protein engineering approaches. Photo Courtesy Zymeworks.
Zymeworks' detailed understanding of protein dynamics helps the company's research scientists to profile protein hotspots and refine protein engineering approaches. Photo Courtesy Zymeworks.

Zymeworks, a clinical-stage biopharmaceutical company based in Vancouver, British Columbia, has won the 6th Annual World ADC Awards in the Best ADC Platform Technology Category for ZymeLink,™ a propitiatory ADC platform technology.

The company uses molecular modeling software for optimize protein structures to develops protein therapeutics, including bispecific antibodies and bispecific antibody-drug conjugates for the treatment of cancer. mandatory.

The awards ceremony took place on Thursday October 10, 2019 at the Manchester Grand Hyatt, San Diego, California during 10th annual World ADC 2019, a ‘must attend’ industry meeting for anyone involved in the development and manufacturing of ADCs, held October 8 – 11, 2019 in San Diego, CA.

Novel antibody-drug conjugate
ZW49, Zymeworks’ investigational antibody-drug conjugate or ADC, was created using the company’s proprietary Azymetric™ and ZymeLink™ technology platforms. The trial drug is an anti-HER2 biparatopic antibody designed to targets two distinct HER2 epitopes and binds to the same domains as trastuzumab and pertuzumab, conjugated to a cleavable linker and novel auristatin payload. [1]

Antibody-drug Conjugates or ADCs are highly targeted biopharmaceutical drugs that combine monoclonal antibodies specific to surface antigens present on particular tumor cells with highly potent anti-cancer agents linked via a chemical linker.

Advertisement #3

With five approved drugs on the market, ADCs have become a powerful class of therapeutic agents for the treatment of patients with cancer.

Zymeworks’ ADC, ZW49, is currently in a first-in-human, Phase I, multicenter, open-label, dose-escalation study (NCT03821233) to establish the maximum- tolerated dose (MTD) or recommended dosage (RD) to assess the safety and tolerability. The trial includes patients with locally advanced, unresectable or metastatic high and low HER2-expressing cancers and addresses unmet medical needs, including brain metastases.[1]

Interim trial data, reported during the 2018 San Antonio Breast Cancer Symposium (SABCS) held in December 4-8, 2018 in San Antonio, Texas, demonstrated that ZW49 was well-tolerated in preclinical studies, with efficacy competitive to ado trastuzumab emtansine (T-DM1; Kadcyla®, Genentech/Roche). The available toxicology data confirmed the safety of dosing above predicted efficacious level.[2]

Platform technologies
Zymeworks’ Azymetric™ platform includes a suite of proprietary, transferable, amino acid changes in the monoclonal antibody CH3 domain to facilitate interaction of two distinct heavy chains that can be introduced to generate bispecific IgG-like antibodies that bind two antigens.

These amino acid changes are also introduced at the heavy-light chain interfaces where they facilitate the correct pairing of the heavy chains with their respective cognate light chains.

The resulting Azymetric™ antibodies are compatible with glyco-engineering and other Fc modifications to enhance therapeutic activity.

The technology was developed to specifically target synergistic drug targets, while retaining the desirable features of typical monoclonal antibodies, such as standard manufacturing processes with comparable production yields, long serum half-life, the ability to mediate effector function and low immunogenicity risk.

One of the unique characteristics of the technology is that, in contrast to other bispecific platforms, Zymeworks’ Azymetric™ platform is compatible with alternative antigen binding formats, such as Fabs, scFvs, and VHHs) and cytotoxic conjugates.

In developing ZW49, scientists at Zymeworks used the company’s Azymetric™ platform in combination with ZymeLink™, a next-generation ADC platform technology which includes a suite of proprietary cytotoxins, stable linkers, and conjugation technologies compatible with traditional antibodies and proteins. This technology was created as a foundation for the development of multifunctional therapeutics designed to overcome the limitations of existing ADCs.

6th World ADC Awards
Each year the World ADC Awards recognizes innovation, leadership, and devotion in the development of antibody-drug conjugate research and development. The annual awards acknowledges anyone pushing the boundaries, dedicating their careers and companies to the pursuit of developing a novel way to fight cancer and hematological malignancies and showcases the extraordinary endeavors, teamwork and commercial acumen that has propelled the field to the forefront of cancer research today.

“The Finalists for 2019 reflects the exciting year we have seen for the ADC space with novel innovations and world class research truly accelerating the field,” noted Elayda Hearne, Program Director, World ADC.

“We are delighted to celebrate and highlight a spotlight on companies that demonstrate the dedication, leadership and innovation that exists in this crucial area of oncology therapeutics,” Hearne added.

Selection of winners
The finalists and winners were shortlisted from over 1,147 votes cast and scientific proposals from each submission were evaluated by our Judging panel.

In each of the 9 categories the top 5, judged by the greatest number of votes, were shortlisted. Each shortlisted entry was then invited to submit a short proposal explaining why they should win the award. With entrants details kept anonymous the award’s judges deliberated to determine a winner and honorable mention in each category.

The jury for 6th Annual World ADC Awards was made up of leading industry experts, including Chris Martin (Chief Executive Officer, ADC Therapeutics), David Thurston (Professor, Kings College, London, United Kingdom), Ian Schwartz (Technology Consultant Bioconjugation, Sartorius Stedim), Jagath Reddy Junutula (Vice President, Antibody Discovery & Development, Cellerent Therapeutics), John Lambert (Executive Vice President, Emeritus & Distinguished Fellow, ImmunoGen), Rakesh Dixit (President & Chieg Executive Officer, Bionavigen) and Scott Dylla (Independent Biotech Angel Investor, Advisor and Entrepreneur).

“The World ADC Awards brings to light the excellence within the ADC field,” observed Jagath Reddy Junutula, Vice President, Antibody Discovery & Development, Cellerent Therapeutics, one of the jurors.

“The World ADC Awards recognizes the innovation, leadership, and devotion on a global platform. I am truly honored to be part of the judging for World ADC Awards and I am delighted to see the growth in the ADC field and the continuing momentum and progress in the ADC field,” Junutula concluded.

Winner and Runner Up

CategoryWinner and Runner Up
Best ADC Platform TechnologyZymeworks (ZymeLink™) – Winner
LegoChem Bio (Scaffold Based Approach) – Runner Up
Best New Drug DeveloperADC Therapeutics – Winner
Zymeworks – Runner Up
Most Promising Clinical CandidateTrastuzumab Deruxtecan (DS-8201a) – Winner
Enfortumab Vedotin (Seattle Genetics/Astellas) – Runner Up
Best Contract Manufacturing (CMO) ProviderBSP Pharmaceuticals – Winner
Millipore Sigma – Runner Up
Best Contract Research (CRO) ProviderPPD – Winner
Abzena – Runner Up
Best Pre-Clinical PublicationChemically triggered drug release from an antibody-drug conjugate leads to potent antitumour activity in mice. Rossin R, Versteegen RM, Wu J, Khasanov A, Wessels HJ, Steenbergen EJ, Ten Hoeve W, Janssen HM, van Onzen AHAM, Hudson PJ, Robillard MS. Nat Commun. 2018 May 4;9(1):1484. – [Pubmed][Article] Winner
Chemically Defined Antibody- and Small Molecule-Drug Conjugates for in Vivo Tumor Targeting Applications: A Comparative Analysis. Cazzamalli S, Dal Corso A, Widmayer F, Neri D. J Am Chem Soc. 2018 Feb 7;140(5):1617-1621. [Pubmed][Article]- Runner Up
Best Clinical PublicationBrentuximab Vedotin with Chemotherapy for Stage III or IV Hodgkin’s Lymphoma. Connors JM, Jurczak W, Straus DJ, Ansell SM, Kim WS, Gallamini A, Younes A, Alekseev S, Illés Á, Picardi M, Lech-Maranda E, Oki Y, Feldman T, Smolewski P, Savage KJ, Bartlett NL, Walewski J, Chen R, Ramchandren R, Zinzani PL, Cunningham D, Rosta A, Josephson NC, Song E, Sachs J, Liu R, Jolin HA, Huebner D, Radford J; ECHELON-1 Study Group. N Engl J Med. 2018 Jan 25;378(4):331-344. doi: 10.1056/NEJMoa1708984. [Pubmed][Article] – Winner.
Individual Input to the Field 2018Dario Neri (ETH Zurich)
Long Standing Contribution to the FieldAlain Beck (Pierre Fabre)

Clinical Trials
[1] A Dose Finding Study of ZW49 in Patients With HER2-Positive Cancers – NCT03821233

[2] Hamblett KJ, Barnscher SD, Davies RH, Hammond PW, Hernandez A, Wickman GR, Fung VK, Ding T, Garnett G, Galey AS, Zwierzchowski P, Clavette BC, Winters GC, Rich JR, Rowse GJ, Babcook JS, Hausman D. ZW49, a HER2 targeted biparatopic antibody drug conjugate for the treatment of HER2 expressing cancers [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl): Abstract nr P6-17-13.

An edited version of this article was originally published in ADC Review | Journal of Antibody-drug Conjugates on October 11, 2019

Advertisement #5