Byondis B.V. (formerly Synthon Biopharmaceuticals) announced that Quantum Leap Healthcare Collaborative (Quantum Leap) selected the company’s investigational antibody-drug conjugate (ADC) SYD985 ([vic-]trastuzumab duocarmazine) for a new investigational treatment arm in its ongoing I-SPY 2 TRIAL for neoadjuvant treatment of locally advanced breast cancer. This treatment arm will focus on treatment for HER2-low early-stage breast cancer.
The I-SPY 2 TRIAL (Investigation of Serial studies to Predict Your Therapeutic Response with Imaging And moLecular analysis) is a standing Phase II randomized, controlled, multicentre study aimed at rapidly screening and identifying promising treatments in specific subgroups of women with newly-diagnosed, high-risk, locally advanced breast cancer (Stage II/III). Quantum Leap, sponsor of the I-SPY 2 TRIAL, leads a pre-competitive consortium that includes the U.S. Food & Drug Administration (FDA), industry, patient advocates, philanthropic sponsors, and clinicians from 16 major U.S. cancer research centres.
The new I-SPY 2 treatment arm will evaluate SYD985 against standard of care therapy in Stage II/III early-stage, high-risk breast cancer patients, with a focus on tumours with heterogeneous and low HER2 expression. Byondis will supply the investigational drug and provide financial and regulatory support. Quantum Leap, as sponsor, will provide the clinical sites and clinical expertise.
SYD985 is Byondis’ most advanced ADC, targeting a range of HER2-positive cancers such as metastatic breast cancer (MBC) and endometrial cancer. The company is currently conducting a Phase III study of SYD985 (TULIP or SYD985.002) to compare its efficacy and safety to physician’s choice treatment in patients with HER2-positive unresectable locally advanced or metastatic breast cancer. Previously, the FDA granted fast track designation for SYD985 based on promising data from heavily pre-treated last-line HER2-positive MBC patients participating in a two-part Phase I clinical trial (SYD985.001).
SYD985 uses Byondis’ unique, proprietary linker-drug (LD) technology. Although marketed ADCs have improved therapeutic indices compared to classical non-targeted chemotherapeutic agents, there is still room for improvement.
SYD985 is comprised of the monoclonal antibody trastuzumab and a cleavable linker-drug called valine-citrulline-seco-DUocarmycin-hydroxyBenzamide-Azaindole (vc-seco-DUBA). The antibody part of SYD985 binds to HER2 on the surface of the cancer cell and the ADC is internalized by the cell. After proteolytic cleavage of the linker, the inactive cytotoxin is activated and DNA damage is induced, resulting in tumour cell death. SYD985 can be considered a form of targeted chemotherapy.

Start Codon, a new model of life science and healthcare business accelerator, has announced its first cohort of start-up companies. Start Codon aims to minimise risk and translate early stage research into successful start-ups, ready for funding and partnership. Start Codon has worked closely with four life science and healthcare companies that were enrolled into the programme in February this year.
They are:

1. Enhanc3D Genomics, a functional genomics spin-out of the Babraham Institute (Cambridge, UK) whose platform technology links non-coding sequence variants to their target genes in order to identify novel therapeutic targets
2. Drishti Discoveries, a start-up leveraging a proprietary gene silencing technology to develop therapies for rare inherited diseases
3. Spirea, a spin-out from the University of Cambridge, who is developing the next generation of antibody drug conjugate cancer therapeutics which carry more drug payload to tumour cells, resulting in greater efficacy, tolerability and the ability to treat more cancer patients
4. Semarion, a University of Cambridge spin-out, who is revolutionising cell-based assays for drug discovery and life science through its proprietary SemaCyte microcarrier platform, which leverages novel materials physics for assay miniaturisation, multiplexing, and automation

Start Codon plans to invest in and support up to 50 start-up companies over the next five years. The accelerator is now accepting applications for its second and third cohorts of companies. Early stage start-up companies in the life sciences and healthcare space are invited to apply via https://startcodon.co/application-form

Concarlo Holdings has received a US patent for IpY, a novel therapeutic peptide that addresses drug-resistant breast cancer by targeting a unique cellular pathway — p27Kip1. The patent is the latest step in Concarlo’s journey to commercialize revolutionary medicines for metastatic breast cancer.
Concarlo has also announced that a new provisional patent application has been filed for modified versions of the therapeutic peptide that are believed to exhibit enhanced bioavailability. Concarlo is a Brooklyn, New York-based biotechnology innovator dedicated to developing sophisticated, targeted therapies and diagnostics in the oncology space. The IpY technology is the first to address the high incidence of drug-refractory disease that develops with currently available CDK4 inhibitor (CDK4i) treatments. Such a solution has the potential to drastically increase overall survival of breast cancer patients.
The recent introduction of CDK4i drugs, a class of medicines that directly targets the CDK4/6 pathway implicated in many malignancies, has had a significant impact on the way in which metastatic breast cancer is managed. However, such therapeutics are associated with patients transitioning to a treatment-resistant form of the condition, despite initial extended periods of remission. Backed by more than 20 years of research and development expertise, Concarlo has developed IpY and a companion diagnostic, ApY, to effectively overcome the issue of CDK4i resistance and roll out a more targeted treatment approach for optimized patient outcomes.
“Despite the clinical efficacy of CDK4 inhibitors, we’re seeing that primary or secondary resistance to therapy is presenting a significant challenge to overall survival,” said Dr. Dominique Bridon, Chief Development Officer at Concarlo. “With the IpY technology and its unique mechanism of action, we’re effectively targeting CDK4 while simultaneously inhibiting another target — CDK2 — which has been found to be a key molecular player in the development of drug resistance. In doing so, we are the first company to successfully address the CDK4i resistance issue to provide long-term durable tumour arrest. Combined with its highly specific targeting and low toxicity profile, the positive impact of this drug on the breast cancer treatment landscape is hard to understate.”
Concarlo was formed in 2016 and is supported by a team of internationally renowned experts forming its Scientific Advisory Board. To date, the company has raised more than $3.1 million to support the development, improvement, and commercialization of its IpY and ApY technologies to bring a precision medicine approach to breast cancer management. The newly issued patent for IpY and the provisional patent application for modified versions of the peptide are the first key milestones in Concarlo’s plan to build an extensive patent estate to maintain market exclusivity for its clinically relevant therapeutics.