Byondis BV

Byondis' antibody-drug conjugate treatment was assessed in a phase 3 trial dubbed TULIP. Byondis' efforts to get an antibody-drug conjugate (ADC) treatment for HER-2 positive metastatic breast cancer approved have been pruned by the FDA.  Last July, the federal agency accepted the Dutch company’s application for trastuzumab duocarmazine, also known as SYD985, an anti-HER2 ADC designed to treat HER2-positive unresectable locally advanced or metastatic breast cancer. The FDA set an expected decision date for May 12. Now, the agency has rejected the drug in a complete response letter, saying that further unspecified information is needed, according to the biotech's Monday release. Byondis said the request would require time and resources “that extend beyond the current evaluation period,” according to a company release. The biotech expressed disappointment but plans to continue seeking approval of the lead asset in the EU and the U.K.   "We continue to believe that SYD985 can present a meaningful treatment option for patients living with HER2-positive metastatic breast cancer," Byondis CEO Marco Timmers, Ph.D., said in a May 15 release. "We appreciate the FDA's guidance and support and will carefully evaluate the complete response letter and consider potential next steps." SYD985 was assessed in a multicenter, open-label, randomized phase 3 trial dubbed TULIP. The study showed a statistically significant improvement over a physician's choice of treatment among 436 patients with pretreated HER2-positive unresectable locally advanced or metastatic breast cancer, according to Byondis. The asset—which received fast-track designation from the FDA in 2018—contains the monoclonal antibody Herceptin and an investigational cleavable linker drug, which can help boost the success of ADC therapies by making tumor cells selectively release the toxin in the therapy.   Byondis is trying to enter a tight market dominated by Big Pharma. In the physicians' choice trial, SYD985 was evaluated against GSK’s Tykerb, Genentech’s Xeloda, Eisai’s Halaven, Roche’s Herceptin and the chemotherapy Navelbine.  The company is also testing out SYD985 in patients with endometrial cancer, efforts that are currently in phase 2 development.   

Dutch biopharma Byondis that the U.S. FDA issued a complete response letter for the company's lead asset, an anti-HER2 antibody-drug conjugate (ADC) for breast cancer treatment. With its BLA, Byondis sought approval for SYD985 in HER2-positive unresectable locally advanced or metastatic breast cancer — a disease with a high unmet medical need. According to Byondis, the agency requested additional information that "requires time and resources that extend beyond the current evaluation period." Byondis submitted its to the FDA back in July of last year, along with aMarketing Authorization Application to the . The EMA's decision is still pending, and is between April 2023 and October 2023. The BLA and MAA were supported by data from the phase 2 TULIP trial comparing SYD985 to physician’s choice (PC) treatment in patients with pre-treated HER2-positive unresectable breast cancer. The study met its primary endpoint of progression-free survival, demonstrating a statistically significant improvement of 2.1 months over PC. The trial also demonstrated supportive overall survival. Despite the CRL, Byondis remains optimistic about SYD985’s potential and is working with the FDA on next steps. “We continue to believe that SYD985 can present a meaningful treatment option for patients living with HER2-positive metastatic breast cancer,” said Byondis CEO Marco Timmers. HER2has become an increasingly popular target for drugmakers in the cancer space. Back in BioNTech signed a $1.5 billiondeal with China-based biotech DualityBio to co-develop and commercialize two cancer ADCs candidates, including DualityBio’s lead candidate, DB-1303, which is a topoisomerase-1 inhibitor-based ADC directed against HER2. Eisai and China-based Bliss Biopharmaceutical just a clinical trial collaboration agreement — with the option to license — for BlissBio's ADC candidate directed against HER2 for the treatment of cancers. SYD985 is also in for uterine cancer and solid tumors.

Byondis' Lead IO Therapy Scheduled to Enter Phase I Study This Year NIJMEGEN, Netherlands, April 17, 2023 /PRNewswire/ -- Byondis B.V., an independent, clinical-stage Dutch biopharmaceutical company creating precision medicines, today announced that the Journal for ImmunoTherapy of Cancer (the official journal of the Society for Immunotherapy of Cancer) has published encouraging preclinical data on its investigational monoclonal antibody (mAb) BYON4228. BYON4228 targets and blocks the Cluster of Differentiation 47-Signal Regulatory Protein alpha (CD47-SIRPα) interaction responsible for tumors' ability to escape recognition and destruction by the immune system. The Byondis paper, "BYON4228 is a pan-allelic antagonistic SIRPα antibody that potentiates destruction of antibody-opsonized tumor cells and lacks binding to SIRPγ on T cells," reports the findings of an extensive preclinical characterization of the novel SIRPα-directed antibody, including direct comparisons to previously reported anti-SIRPα antibodies. Side-by-side comparisons show that BYON4228 has a unique and favorable preclinical profile. The therapy is scheduled to enter First-in-Human (Phase I) study later this year. The Phase I clinical study (NCT05737628) is designed to evaluate BYON4228 alone and in combination with rituximab in patients with relapsed/refractory CD20-positive B-cell non-Hodgkin's lymphoma. Byondis Chief Scientific Officer Wim Dokter, Ph.D. explains: "BYON4228 is a pan-allelic antibody, meaning it recognizes the two major SIRPα variants in humans. In addition, because BYON4228 does not recognize SIRPγ, a related molecule on T cells, it should not compromise T cell activity." "This implies that the therapy could benefit all eligible patients. Used in combination, BYON4228 can potentially increase the efficacy of a wide range of therapeutic mAbs in different blood and solid cancers," Byondis Chief Executive Officer Marco Timmers, Ph.D. added. According to the published data, BYON4228 potentiates macrophage- and neutrophil-mediated killing of both hematologic and solid cancer cells in vitro in the presence of a variety of tumor-targeting antibodies, including trastuzumab, rituximab, daratumumab, panitumumab and cetuximab. In vivo, BYON4228 promotes the anti-tumor activity of such antibodies. Finally, BYON4228 shows a favorable preclinical safety profile. More About BYON4228 BYON4228 is a humanized therapeutic monoclonal antibody designed to stimulate the innate immune system. It binds to SIRPα expressed on innate immune cells, especially monocytes, macrophages and neutrophils. BYON4228 blocks binding of SIRPα to CD47 (a cell surface molecule often over-expressed on cancer cells), preventing signaling through the CD47-SIRPα axis. The CD47-SIRPα axis limits the antibody-mediated destruction of cancer cells by transducing a "don't eat me" signal to the immune system. By inhibiting the CD47-SIRPα axis, BYON4228 prevents the inhibitory "don't eat me" signal to be detected, thereby stimulating the immune cell to do what it is supposed to do: destroy the tumor cell. As a pan-allelic antagonistic SIRPα antibody that lacks binding to SIRPγ on T cells, BYON4228 has the potential to become best in class. It distinguishes itself from previously reported SIRPα antibodies that in all probability are representative of antibodies currently being tested in clinical trials. About Byondis Driven to improve patients' lives, Byondis is a privately held, Dutch clinical-stage biopharmaceutical research and development company creating precision medicines targeting intractable cancers and autoimmune diseases. Byondis' broad development portfolio comprises targeted and immuno-oncology (IO) therapies in preclinical, early- and late-stage clinical phases. These candidates combine Byondis' expertise in linker-drug (LD) technology, antibody-drug conjugation, targeted cytotoxic therapy, and monoclonal antibody (mAb) development. Byondis designs and produces next generation antibody-drug conjugates (ADCs), as well as mAbs and new chemical entities (NCEs) that can stand alone or be incorporated in its ADCs. Byondis has a dedicated team of more than 400 employees, including highly educated scientists and skilled technicians working in state-of-the-art R&D laboratories and Good Manufacturing Practice (GMP) production and conjugation facilities on its campus in Nijmegen, the Netherlands. The company collaborates with other global biotechnology and pharmaceutical companies and many leading academic research institutions. For more information, visit . Logo: SOURCE Byondis B.V.