A D V E R T I S E M E N T F E A T U R E

A D V E R T I S E R R E TA I N S S O L E R E S P O N S I B I L I T Y F O R C O N T E N T

Byondis B.V.www.byondis.com

Creating precision medicines for better careTargeting oncology and autoimmune diseases, Byondis takes its pipeline of development programs to clinicalproof-of-concept and then seeks partnerships for later-stage clinical development and commercialization.

Despite the huge advances in drug developmentover the past few decades, there are still many areasof unmet medical need. Byondis, based in Nijmegen,the Netherlands, is developing a pipeline of preci-sion medicines targeting intractable cancers andautoimmune diseases.

Byondis began life as Synthon Biopharmaceuticals,an affiliate of generics company Synthon. The affili-ate initially focused on biosimilars and later on inno-vative biologics and small molecules. After the saleof the generics business to a private equity firm in2019, Synthon Biopharmaceuticals continued asa stand-alone company and rebranded in 2020as Byondis.

The business model today is to develop projectsto clinical proof-of-concept and then seek partnersfor later-stage clinical development and commer-cialization. This relies on an up-to-date pipelineof new biological and chemical entities, as MarcoTimmers, CEO, explained, “We review the literaturefor new mechanisms and new targets for monoclo-nal antibodies, ADCs [antibody–drug conjugates]and small molecule programs, in pathways thatinterest us. Our aim is to have a pipeline with a num-ber of programs at different development stages.”

In addition to its therapeutic pipeline, Byondisalso has a proprietary linker-drug technology withpotential in oncology and autoimmune diseases,and is also seeking new combinations of linkersand payloads with different mechanisms of action.

The company’s mission is supported by part-nerships with national and international researchinstitutions, including the Sanquin Blood SupplyFoundation in the Netherlands.

Clinical pipeline developmentByondis’ oncology pipeline has two ADCs in clinicaltrials, and two in early development. The lead pro-gram, [vic-]trastuzumab duocarmazine (SYD985),combines the anti-HER2 antibody trastuzumab witha synthetic duocarmycin prodrug (Fig. 1).

“The duocarmycin derivative is delivered as a pro-drug, activated only in the tumor, with a short half-life when it reaches the circulation. This reduces thechance of systemic toxicity, as circulating levels ofthe free payload are negligible, in contrast to otherADC platforms. As a DNA alkylator, rather than atubulin-binding drug, it isn’t reliant on the tumorcells diving rapidly,” said Timmers. “Uptake of theactivated payload by neighbouring tumor cellswith lower HER2 expression may also improve theefficacy potential, the so-called bystander effect.”

[vic-]trastuzumab duocarmazine is in a pivotalphase 3 clinical trial for metastatic breast cancer,and in phase 2 clinical trials for neoadjuvant use inearly-stage breast cancer.

“Our phase 1a and 1b clinical trials showed verylow levels of systemic toxicity. This validated ourapproach, and allowed us to move into early stagedisease before marketing approval of the first indi-cation. We are also carrying out a phase 2 trial inuterine serous carcinoma, a rare and aggressiveform of endometrial cancer that has no approvedHER2-targeted therapy,” said Timmers.

The low toxicity of [vic-]trastuzumab duocarma-zine and its action as a drug that damages DNAgives it potential as part of a combination therapy,for example, with PARP inhibitors, which stopthe cancer cells from repairing their damagedDNA. After preclinical studies suggested synergybetween the two mechanisms of action, Byondis isnow conducting a dose-escalation study of [vic-]trastuzumab duocarmazine combined with thePARP inhibitor niraparib in, for example, HER2-lowbreast cancer and ovarian cancer.

“We hope that the combination will improve thetherapeutic window, creating more opportunitiesfor therapy,” said Timmers.

Byondis is more than just an ADC company.The pipeline also includes an immuno-oncologymonoclonal antibody (mAb), and a new chemicalentity for autoimmune diseases in early develop-ment. The aim is to enter first-in-human studieswith four additional development programs in thecoming two years.

Making partnering easyTimmers and his business development and licens-ing team aim to ensure that dealmaking discussionswith pharma, biotech and research institutionsmove forward as smoothly as possible.

“We pride ourselves on being open and flexible.We can work with potential partners to create anagreement that is adapted to their needs, from astraightforward licensing deal in return for a feeand milestone payments, to a comprehensive pack-age that includes early and clinical development,manufacturing and supply, IP [intellectual property]and regulatory support,” said Timmers.

In 2012, Byondis, as Synthon Biopharmaceuticals,successfully licensed a trastuzumab biosimilar(trastuzumab-anns, Kanjinti) to Amgen in aworldwide licensing deal. In the license agreement,Byondis retained the ability to use trastuzumab-anns in the manufacture of [vic-]trastuzumabduocarmazine.

Unlike many other mid-sized biotech companies,Byondis has in-house good manufacturing practice(GMP) manufacturing and conjugation facilitiesfor both mAbs and ADCs. Byondis can supportpartners by manufacturing in quantities up to earlycommercial launch, either as part of a service forlicensees that obtain Byondis’ linker-drug platformtechnology, or for partners that will commercializethe ADCs developed by Byondis.

Proteolytic cleavageand subsequentrelease of payloadin tumormicroenvironment

Di�usion of activepayload toneighboringtumor cells(bystander e�ect)

Uptake of ADC byinternalization andintracellular releaseof payload

Inactivatedpayload

Activatedpayload(SYD986)

b

b

a

a

cc

Tumor cell

Tumor cell

Lysosome

Target (HER2)

Protease-cleavablelinker

Antibody(trastuzumab)

Fig. 1 | The three-way mechanism of action of SYD985.

Declan Nolan, Vice PresidentStrategic Business InitiativesByondis B.V.Nijmegen, the NetherlandsTel: +31 24 679 5100Email: bd@byondis.com

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“Byondis’ oncologypipeline has two ADCs

in clinical trials, and two inearly development

www.nature.com/biopharmdeal | September 2020 | B11