Creating precision medicines for better care€¦ · Creating precision medicines for better care...
1
ADVERTISEMENT FEATURE ADVERTISER RETAINS SOLE RESPONSIBILITY FOR CONTENT Byondis B.V. www.byondis.com Creating precision medicines for better care Targeting oncology and autoimmune diseases, Byondis takes its pipeline of development programs to clinical proof-of-concept and then seeks partnerships for later-stage clinical development and commercialization. Despite the huge advances in drug development over the past few decades, there are still many areas of unmet medical need. Byondis, based in Nijmegen, the Netherlands, is developing a pipeline of preci- sion medicines targeting intractable cancers and autoimmune 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 sale of the generics business to a private equity firm in 2019, Synthon Biopharmaceuticals continued as a stand-alone company and rebranded in 2020 as Byondis. The business model today is to develop projects to clinical proof-of-concept and then seek partners for later-stage clinical development and commer- cialization. This relies on an up-to-date pipeline of new biological and chemical entities, as Marco Timmers, CEO, explained, “We review the literature for new mechanisms and new targets for monoclo- nal antibodies, ADCs [antibody–drug conjugates] and small molecule programs, in pathways that interest us. Our aim is to have a pipeline with a num- ber of programs at different development stages.” In addition to its therapeutic pipeline, Byondis also has a proprietary linker-drug technology with potential in oncology and autoimmune diseases, and is also seeking new combinations of linkers and payloads with different mechanisms of action. The company’s mission is supported by part- nerships with national and international research institutions, including the Sanquin Blood Supply Foundation in the Netherlands. Clinical pipeline development Byondis’ oncology pipeline has two ADCs in clinical trials, and two in early development. The lead pro- gram, [vic-]trastuzumab duocarmazine (SYD985), combines the anti-HER2 antibody trastuzumab with a 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 the chance of systemic toxicity, as circulating levels of the free payload are negligible, in contrast to other ADC platforms. As a DNA alkylator, rather than a tubulin-binding drug, it isn’t reliant on the tumor cells diving rapidly,” said Timmers. “Uptake of the activated payload by neighbouring tumor cells with lower HER2 expression may also improve the efficacy potential, the so-called bystander effect.” [vic-]trastuzumab duocarmazine is in a pivotal phase 3 clinical trial for metastatic breast cancer, and in phase 2 clinical trials for neoadjuvant use in early-stage breast cancer. “Our phase 1a and 1b clinical trials showed very low levels of systemic toxicity. This validated our approach, and allowed us to move into early stage disease before marketing approval of the first indi- cation. We are also carrying out a phase 2 trial in uterine serous carcinoma, a rare and aggressive form of endometrial cancer that has no approved HER2-targeted therapy,” said Timmers. The low toxicity of [vic-]trastuzumab duocarma- zine and its action as a drug that damages DNA gives it potential as part of a combination therapy, for example, with PARP inhibitors, which stop the cancer cells from repairing their damaged DNA. After preclinical studies suggested synergy between the two mechanisms of action, Byondis is now conducting a dose-escalation study of [vic-] trastuzumab duocarmazine combined with the PARP inhibitor niraparib in, for example, HER2-low breast cancer and ovarian cancer. “We hope that the combination will improve the therapeutic window, creating more opportunities for therapy,” said Timmers. Byondis is more than just an ADC company. The pipeline also includes an immuno-oncology monoclonal antibody (mAb), and a new chemical entity for autoimmune diseases in early develop- ment. The aim is to enter first-in-human studies with four additional development programs in the coming two years. Making partnering easy Timmers and his business development and licens- ing team aim to ensure that dealmaking discussions with pharma, biotech and research institutions move forward as smoothly as possible. “We pride ourselves on being open and flexible. We can work with potential partners to create an agreement that is adapted to their needs, from a straightforward licensing deal in return for a fee and 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 a worldwide licensing deal. In the license agreement, Byondis retained the ability to use trastuzumab- anns in the manufacture of [vic-]trastuzumab duocarmazine. Unlike many other mid-sized biotech companies, Byondis has in-house good manufacturing practice (GMP) manufacturing and conjugation facilities for both mAbs and ADCs. Byondis can support partners by manufacturing in quantities up to early commercial launch, either as part of a service for licensees that obtain Byondis’ linker-drug platform technology, or for partners that will commercialize the ADCs developed by Byondis. Proteolytic cleavage and subsequent release of payload in tumor microenvironment Diffusion of active payload to neighboring tumor cells (bystander effect) Uptake of ADC by internalization and intracellular release of payload Inactivated payload Activated payload (SYD986) b b a a c c Tumor cell Tumor cell Lysosome Target (HER2) Protease- cleavable linker Antibody (trastuzumab) Fig. 1 | The three-way mechanism of action of SYD985. Declan Nolan, Vice President Strategic Business Initiatives Byondis B.V. Nijmegen, the Netherlands Tel: +31 24 679 5100 Email: [email protected] CONTACT “ Byondis’ oncology pipeline has two ADCs in clinical trials, and two in early development www.nature.com/biopharmdeal | September 2020 | B11
Transcript of Creating precision medicines for better care€¦ · Creating precision medicines for better care...
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: [email protected]
CON
TACT
“Byondis’ oncologypipeline has two ADCs
in clinical trials, and two inearly development
www.nature.com/biopharmdeal | September 2020 | B11
