“KJ-103 has a distinct mechanism of action that could transform cancer treatment if its activity is confirmed in patients,” says Gordon. “LifeArc’s humanized antibody is right at the centre of that.”
Gordon Ngan, VP Business Development, KisoJi Biotechnology Inc.
The first unconjugated
TROP-2-targeted antibody, humanized for KisoJi Biotechnology Inc.
Working with KisoJi Biotechnology, we’ve humanized a first-in-class unconjugated antibody to target TROP-2, a highly promising cancer cell target. This is the first unconjugated anti-TROP-2 antibody to show strong efficacy in in vivo models.
Overview
We work with partners across industry, academia, charity and beyond to humanize antibodies with the potential to transform outcomes for patients.
Working closely with the biotechnology company KisoJi, we have humanized a novel unconjugated antibody against TROP-2.
This first-in-class anti-TROP-2 antibody achieves robust therapeutic activity without the need for a conjugated payload. Now partnered with Cancer Research UK for clinical testing, the antibody offers new hope for people with many forms of cancer.
We wanted to work with a reputable partner to humanize our highly potent unconjugated antibody against TROP-2 – the first of its kind, which we discovered in our KisoMouse platform. We chose LifeArc as a partner because of their history, expertise and reputation, with some serious blockbusters under their belt. We thought, “why not go to the best?”
Even though we’re in Canada and LifeArc is in the UK, working together was like working as one team. We were very impressed with LifeArc’s thoroughness, efficiency and comprehensive approach to antibody humanization.”
Gordon Ngan, VP Business Development, KisoJi Biotechnology Inc.
Pursuing TROP-2: an attractive cancer target
Overexpressed in most solid cancer cells but in very low levels in normal human tissues, TROP-2 represents an excellent target for a therapeutic antibody that can activate an anti-cancer immune response. But efforts to drug this target to date have proven challenging.
All validated anti-TROP-2 agents – including one FDA-approved drug for breast cancer, whose accelerated approval in advanced bladder cancer was recently withdrawn – are antibody-drug conjugates (ADCs). ADCs combine a target-seeking antibody with a toxic payload, ideally released at the site of the tumour. While potent, the payload isn’t tumour-specific, and healthy neighbouring cells can get caught in the crossfire. This limits the dosage that can be given and the breadth of the therapeutic window.
“TROP-2 is a fantastic target,” says Gordon Ngan, VP Business Development at KisoJi. “The problem has been finding a way to target TROP-2 on the cancer cell without damaging healthy cells along the way. We know that ADCs are associated with significant toxicity, yet the fact that nearly all competitive programmes in development that target TROP-2 are ADCs is disappointing.”
Using their unique multi-species transgenic mouse platform, KisoMouse, the KisoJi team discovered a number of single-domain antibodies against TROP-2. Many of them slowed or prevented tumour growth in mouse xenograft models without requiring a cytotoxic payload.
The KisoJi team approached us with a number of potential candidates to humanize.
“We had first-of-their-kind antibodies emerging from our platform. We wanted to give them the best chance of success,” says Gordon. “That’s why we decided to work with LifeArc.”
A new approach with a single-domain antibody
KisoJi’s antibodies fused a single antigen-binding heavy chain variable domain with a crystallisable fragment (Fc) that interacts with the immune system. The smaller binding domains may help to overcome challenges associated with previous anti-TROP-2 efforts, such as being able to reach otherwise inaccessible epitopes.
Keen to ensure the success of the project, we developed innovative methods to design stable molecules that maintained the binding affinity of KisoJi’s parent antibodies, with minimal immunogenicity in humans.
Our partnership blended KisoJi’s expert team of scientists with our deep experience in antibody humanization, producing lead antibodies with optimal expression levels and binding, stability and biophysical characteristics.
“After LifeArc generated around 30 variants across each candidate, we analysed the variants for functional activity at our labs in Canada, making sure they still behaved in the same way as the original molecules,” says Gordon. “Working together was very much like working as one united team, from shipping materials between continents to discussing data in project meetings.”
Most of the humanized antibodies showed potent efficacy – including shrinking tumours in preclinical human xenograft models – with similar binding affinity as the parent antibodies.
Properties of the anti-TROP2-antibody:
- Parent species: mouse with camelid VHH/VH genes
- Target: TROP-2
- Modality: single domain antibody with Fc
- Class of drug: unconjugated antibody
- Outcome: affinity, efficacy and stability to match parent antibody
Our humanized antibody enters drug development and manufacture
The humanized unconjugated anti-TROP-2 antibody, known as KJ-103, is now the subject of a clinical development partnership between KisoJi and Cancer Research UK, announced in October 2024.
The new partnership will test KJ-103 in a Phase 1/2a clinical trial, in selected TROP-2-expressing solid tumours.
If effective, our anti-TROP-2 antibody could provide a novel, robust treatment – potentially with minimal toxicity against healthy cells – for people with a broad range of cancer types. High levels of TROP-2 are found on many solid cancers, including hard-to-treat indications for which patients face poor prognoses, such as lung cancer, ovarian cancer and pancreatic cancer.
We’re proud to work with partners on complex, high-risk projects like this, fuelled by compelling evidence and a great potential for impact. We take on the financial risk so our partners don’t have to, helping promising molecules move one step closer to the clinic.
“KJ-103 has a distinct mechanism of action that could transform cancer treatment if its activity is confirmed in patients,” says Gordon. “LifeArc’s humanized antibody is right at the centre of that.”
Parnter with us to humanize your antibody
We have a breadth of experience in antibody humanization and consider any target, therapeutic indication or modality.
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