Strategic Alliance Helps the Development Antibody Fragment-Drug Conjugates

In August 2019 Antikor Biopharma and Essex Bio-Technology confirmed that the companies had entered into an investment agreement for up to U.S. $ 3,100,000.

The investment from Essex Bio-Investment, a wholly-owned subsidiary of Essex Bio-Technology, allows Antikor to consolidate and expand its position as a leading innovator in smaller-format antibody-drug conjugate therapies for solid tumors.

Essex Bio-Technology develops, manufactures and commercializes genetically engineered therapeutic basic fibroblast growth factor (rb-bFGF, FGF-2), a survival factor for neural precursor cells, having five commercialized biologics marketed in China since 1998.

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Antibody fragment-drug conjugates
Similar to antibody-drug conjugates or ADCs, these therapies, called fragment-drug conjugates or FDCs combine the pharmacological potency of highly cytotoxic drugs with the high specificity of an antibody against tumor-associated targets.

However, in contrast to ADCs, FDCs comprise much smaller antibody fragments (single-chain scFvs) than ‘whole’ antibody drug conjugates (ADCs). As a result, they are relatively easy to discover and can be bioengineered for multiple drug-molecule conjugation, leading to higher loadings than has so far been achieved with whole monoclonal antibodies.

Fragment-drug conjugates demonstrate superior tumor penetration and rapid elimination (clearance) from normal tissues, resulting in less side effects. FDC’s can also be manufactured with high drug-to-antibody ratios (DAR) but without running the risk of problems with product manufacturing or stability.[1]

New data demonstrates that using a highly potent, clinically-validated cytotoxic payload, FDCs are better tolerated and less toxic than antibody-drug conjugates (ADCs) carrying the same quantity of payload.

“These pivotal data strengthen Antikor’s proposition that highly-loaded FDCs can be a superior approach to treating solid tumors, while further reducing the risk of liver, renal and hematological toxicities often associated with whole ADCs,” noted Gokhan Yahioglu, Ph.D, Director of Chemistry and Antikor’s co-founder.

“The major issue about applying ADCs successfully in oncology is getting a wide enough therapeutic window in patients. Our data suggest that our approach can open up this window whilst hitting solid tumours more effectively,” added Mahendra Deonarain, Ph.D, Antikor’s Chief Executive Officer and Scief Science Officer.

Antikor’s FDCs have been developed to have a much wider therapeutic index (TI) than current antibody-drug conjugates (ADCs), with consequent potential benefits for cancer patients.

The enhanced TI has been confirmed in 4 different animal tumor models, with tumor killing data showing that Antikor’s FDC platform is superior to ADCs in terms of efficacy, speed of regression, durability (longer lasting cures) and lower side effects (body weight).

“[Our] novel approach uses small antibody fragments, which incorporate its revolutionary OptiLinkTM technology platform, to yield products with uniquely high drug-to-antibody ratios (DAR of 6-10 cancer drugs). These high DAR FDCs have been shown to penetrate tumours more rapidly than conventional ADCs, enabling them to act faster and clear more rapidly from normal tissues. This reduces side-effects, achieves a wider TI and delivers a significantly superior therapeutic benefit,” Deonarain said.

Next generation therapy
As a next-generation cancer therapy that can overcome the many limitations of existing treatment options, FDCs have exciting market potential, with predicted sales of drug-conjugates of over U.S. $ 18 billion by 2022.

“We believe we have a platform that is tailored to make an impact in an area of major unmet medical need, and with EssexBio’s considerable commercial and clinical expertise, we now have the opportunity for translating the promised advantages of Antikor’s proprietary products into clinical benefit,” noted Mahendra Deonarain, Antikor’s Chief Executive Officer.

“We are excited to have established a strong alliance with Antikor”, said Malcolm Ngiam, President of Essex Bio-Investment.

“Fragment-drug conjugate is an innovative approach with the potential to overcome many of the challenges faced by current treatment methods. The research and commercial partnership with Antikor is an important step towards developing first-in-class treatment for cancer,” Ngiam added.

Anti-HER2 FDC
Antikor is developing ANT043, an anti-HER2 antibody fragment-drug conjugates for the treatment of multiple solid tumors. In preclinical studies the investigational drug has demonstrated more rapid and complete tumor regression compared with a trastuzumab-based ADC in human gastric cancer models. At the same time the trial drug seems to be better tolerated.

Furthermore, Antikor has proprietary single-chain Fv libraries optimised for FDC discovery, and linker-payload expertise enabling efficient and effective FDC discovery and development for oncology and beyond. Based in Stevenage Bioscience Catalyst Innovation Park, just north of London, UK, the company has received numerous Innovate-UK grant awards.

The company’s novel technology platform is expected to enrich Essex Bio-Technology’s research pipeline and is aligned with EssexBio’s long-term research and commercial strategy.

Antikor’s interest and expertise in the use of much smaller mAb fragments (eg, single-chain scFvs) to covalently attach anti-cancer drugs, began with PhotoBiotics in 2001.

As an Imperial College spin-out company, PhotoBiotics, today a wholly owned subsidiary of Antikor, developed a novel way of specifically targeting photosensitiser payloads to tumors to improve the success of photodynamic therapy.

Reference
[1] Deonarain MP, Yahioglu G, Stamati I, Marklew J. Emerging formats for next-generation antibody drug conjugates. Expert Opin Drug Discov. 2015 May;10(5):463-81. doi: 10.1517/17460441.2015.1025049. Epub 2015 Mar 23. [Pubmed][Article]