by Manasi Vaidya in New York
Byondis is drafting plans to pursue commercialisation partners for when results from its Phase III breast cancer antibody-drug conjugate study are released in 2Q21, said CEO Marco Timmers, PhD. Byondis is working with the CRO Syneos Health to manage the Phase III SYD985 trial dubbed TULIP, he noted.
The Nijmegen, the Netherlands-based company, is also assessing SYD985 in other solid tumours trials. It has enrolled 35 of the targeted 60 Her2-expressing endometrial cancer patients in the Phase II study (NCT04205630), said Timmers. The Phase I study (NCT04235101) evaluating a SYD985 combination is recruiting the fifth dose-escalation cohort, he noted.
In breast cancer, Byondis plans to start a rolling BLA submission for SYD985 in January since SYD985 has a Fast Track designation from the FDA and will look for a commercial partner to sell the asset to on a more concerted level once data is available in 2Q, said Timmers. TULIP (NCT03262935) is evaluating the anti-Her2 ADC in metastatic breast cancer patients who have progressed on at least two Her2-targeting treatment regimens.
Byondis has had introductory conversations with global pharma players, he added. It plans to substantiate this partnership in 2H21 and expects it to take a year from that time for the drug to be launched, he added.
The company would prefer a global partner to ensure a faster and more efficient deal, said Timmers. The ideal partner would have a presence in oncology, especially solid tumors, with its own pipeline so it can bring combination strategies to the table, he noted. He pointed to the company’s ongoing efforts to combine SYD985 with GlaxoSmithKline’s PARP inhibitor Zejula (niraparib) as an example of a synergistic combination, while coupling with other drug classes like CDK4/6 inhibitors could also be trialed. Eli Lilly, Pfizer and Novartis have approved CDK 4/6 inhibitors in breast cancer.
Byondis manufactures SYD985 itself in a facility in the Netherlands at a scale suitable for the initial years of commercial launch and will provide the partner with the ADC, said Timmers.
SYD985 development plans
The company anticipates submitting TULIP data for presentation at the American Society of Clinical Oncology (ASCO) 2021 meeting, but it would depend on the recorded PFS in the trial, its primary endpoint, said Timmers. SYD985 has an improved toxicity profile compared to other ADCs like Roche’s Kadcyla (adotrastuzumab emtansine) and AstraZeneca’s /Daiichi Sankyo Enhertu (trastuzumab deruxtecan), according to the CEO. The level of circulating duocarmycin—SYD985’s cytotoxic payload—is 100–200-fold lower on a molar basis than the aforementioned ADCs, he said.
In addition to the TULIP trial in Her2+ metastatic breast cancer, the CEO also highlighted the drug’s potential in Her2-low expressing tumours, where it plans to continue clinical development or hand it over to a partner. The Phase II endometrial cancer data could be presented at the European Society of Medical Oncology meeting in September 2021, he noted. The trial has a primary completion date in April 2022. The design is based on clinical activity observed in heavily pretreated endometrial cancer patients, said Timmers, adding the Phase II is excluding those who have received more than two lines of therapy. Close to 40% of endometrial cancer patients express Her2, including the Her2-low expressors, he said.
As for Byondis’ 120-patient Phase I study evaluating the SYD985/Zejula combination in solid tumours, the trial has a traditional 3+3 dose-escalation design, he explained. Once a tolerable combination dose is identified, the company plans to expand the study in ovarian and breast cancer where Zejula is approved, he said. The study is testing varying dosing regimens of both SYD985 and Zejula to better understand how to overcome toxicity concerns with PARP inhibitor combinations, said Timmers. Zejula impairs tumour cells’ ability to repair DNA damage and SYD985’s payload duocarmycin is a DNA damaging agent, he explained. Preclinical data from patient-derived xenograft models has indicated the combination results in additive cell-killing activity, said Timmers on the rationale behind the strategy.
Byondis’ parent company Synthon Pharmaceuticals launched its biopharmaceutical business in 2007 which was branded as Byondis in April 2020. In 2019, private equity firm BC Partners acquired a majority stake in Synthon, and funds associated with that sale were invested in Byondis’ pipeline, making the company’s finances relatively secure with no immediate funding needs, said Timmers.
Manasi Vaidya is an Associate Editor for Pharmaceutical Technology parent company GlobalData’s investigative journalism team. A version of this article originally appeared on the Insights module of GlobalData’s Pharmaceutical Intelligence Center. To access more articles like this, visit GlobalData.