Antikor Biopharma is pioneering an innovative drug delivery technology called OptiLink, specifically-tailored for solid tumours. It is unique by utilising optimally-engineered, small-format, tumour-specific antibodies with appropriately-designed linkers to deliver therapeutic payloads deep into tumours. Unlike its competitors, who use full-size antibody-drug conjugates (ADCs), Antikor's technology enables much smaller fragment-drug conjugates (FDCs) to be developed. These have many advantages: FDC products potentially have a higher therapeutic index for cancer therapy as they are more potent, can be dosed more aggressively because they clear from normal tissues more quickly and penetrate rapidly and deeply into tumours enabling faster and more effective tumour destruction. FDC's properties may also have safety advantages for immunotherapy. Through previous Innovate-UK support, Antikor discovered its lead pre-clinical FDC candidate (ANT-045) aimed at gastric cancer which is now entering formal IND-enabling studies with expectations for a regulatory filing in 12 months. Antikor is now expanding its technology toolbox and pipeline to another difficult-to-treat solid tumour, ovarian cancer (OvCa). There are few well-characterised targets for OvCa and this disease is notoriously insensitive checkpoint inhibitor or other approved immunotherapy drugs. We have identified a suitable target for OvCa, well-matched to our technology and we need to innovate and develop our expertise around the emerging immune-stimulating payloads. This discovery and early development project aims to produce a panel of OvCa-specific antibody fragments and to synthesize immuno-stimulating linker-payload derivatives that are compatible with our smaller, more-penetrating format. We already have advanced data on antibody discovery and preliminary data on conjugating immuno-stimulating payloads to produce immune-stimulating FDCs (i-FDCs) and this project builds on this to refine the synthesis and discover some potentially novel and patentable i-FDC products. Using our established process, we will use our suite of biophysical analytical techniques and biological assays to fully-characterise candidate i-FDCs, aiming to generate early proof-of-concept in animal models. Success will be followed by further investment to develop leads in advanced models and ultimately fill Antikor's pipeline with further innovative and much-needed product for solid tumour immuno-therapy.

Antikor Biopharma is pioneering an innovative drug delivery platform called OptiLink, tailored for solid tumours. It is unique by utilising specially-engineered, small-format, tumour-specific antibodies with appropriately-designed linkers to specifically deliver potent cytotoxic payloads deep into tumours. Unlike its competitors, who use full-size antibody-drug conjugates (ADCs), Antikor's technology enables much smaller fragment-drug conjugates (FDCs) to be developed. These have many advantages: FDC products potentially have a higher therapeutic index for cancer therapy as they are more potent, can be dosed more aggressively because they clear from normal tissues more quickly and penetrate rapidly and deeply into tumours enabling faster and more effective tumour destruction. Through previous Innovate-UK support, Antikor expanded and refined its technology and discovered a strong pre-clinical FDC candidate (ANT-045) aimed at gastric cancer which is now entering formal IND-enabling studies with expectations for a regulatory filing in 18 months. Antikor is now expanding its pipeline to another difficult-to-treat solid tumour, colorectal cancer (CRC). Although gastrointestinal in nature, this has very different challenges to gastric. There are fewer well-characterised targets for CRC and this disease is notoriously insensitive or rapidly-develops resistance to microtubule inhibitor drugs. We have identified a suitable but emerging target for CRC, well- matched to our technology and we need to innovate and develop our expertise around DNA-damaging payloads. This discovery and early development project aims to discover a panel of antibody fragments (using our proprietary libraries optimised for FDCs) and to synthesize linker-payload derivatives that are compatible with our smaller, more penetrating format. We have already implemented the discovery strategy and have preliminary data on some promising candidates and we need to expand this to have a wider range to choose from. We also have preliminary chemistry data and this project builds on this to refine the synthesis and discover some potentially novel and patentable new linker-payloads New payloads will be conjugated to new antibody fragments to create novel and proprietary FDCs for CRC therapy. Using our established process, we will use our suite of biophysical analytical techniques and biological assays to fully-characterise candidate FDCs, aiming to generate early proof-of-concept in animal models. Success will be followed by further investment to develop leads in advanced models and ultimately fill Antikor's pipeline with a second innovate and much- needed product for solid tumour therapy.

Antikor Biopharma is pioneering an innovative drug delivery platform called OptiLink. It harnesses the immune system by using tumour-seeking antibodies to specifically deliver potent cytotoxic payloads to tumours. Unlike its competitors, who use full antibody-drug conjugates (ADCs), Antikor's technology enables much smaller fragment-drug conjugates (FDCs) to be developed. These have many advantages: FDC products potentially have a higher therapeutic index for cancer therapy as they are more potent, can be dosed more aggressively because they clear from normal tissues more quickly and penetrate rapidly and deeply into tumours, enabling faster tumour destruction. Antikor is developing an FDC for gastric cancer which promises to overcome the challenges in treating this disease. This project entails the advanced preclinical development and manufacturing process optimisation and CMO-technology transfer to support regulatory submissions for future clinical development.

The COVID-19 pandemic is the 3rd-known coronaviral-disease with an alarmingly-high transmission rate. These incidences will keep returning and we must be prepared with innovative technologies to combat future epidemics/pandemics. Vaccinations are the gold-standard but this may not always be successful and can have adverse effects and/or lead to incomplete protection. Antibody-Drug Conjugates (ADCs) are a form of targeted chemotherapy using immunoglobulins to deliver cytotoxic chemotherapy drugs (payloads) to tumours. Antikor are developing the next evolution of this concept using much smaller antibody-fragments that can penetrate tumours more effectively, clear from the body more rapidly whilst delivering more payload due to our proprietary high-loading technology. We propose to apply our FDC platform by harnessing these key features to develop a therapeutic drug that could rapidly reduce COVID-19 viral-load over a matter of hours thereby reducing disease severity, intensive-care-unit hospitalisation and death. Antikor has proprietary antibody-fragment libraries with the expertise to discover antibodies to practically any target, has identified suitable 'payloads' and has all the resources and experience to develop anti-viral FDCs. There is no precedent for this novel drug class but there is a strong case from the supporting data showing a correlation between viral load and disease severity. The technical approach (6-months) will be to use phage-display technology to discover antibody-fragments against COVID-19, with candidates emerging from Antikor's library already pre-designed to form stable, highly-loaded drug-conjugates. Leads will be candidates for more detailed biological studies including rodent models of coronaviral infection/clearance, which will be done in collaboration with identified respiratory virologists. This approach acts to reduce viral load more rapidly than drugs like hydroxychloroquine or replication inhibitors and could be more effective than conventional neutralising antibodies due to the clearance mechanisms harnessed and faster tissue perfusion into critical organs such as the lung and kidneys. If successful, Antikor has networks to commercialise this therapy which enables patient benefits to be realised sooner and add value to the Company through a broader technology proposition. EXTENSION FOR IMPACT We wish to change the scope to extend the project's impact by setting and completing further deliverables that will maximise the chances of Antikor's COVID-19 FDC becoming a viable and beneficial therapy. In the past 4 months, we have made excellent progress to discover many COVID-19 recognising antibodies and have started to make conjugates that will be tested as drug product candidates. We wish to conduct more development work to include manufacturing assessment so that viable candidates will make better commercial 'products' and importantly, we wish to conduct a commercial market assessment for COVID-19 therapies at all stages of development. All of these additional tasks will de-risk the project and increase the chances of developing a commercially-viable product to treat COVID-19 infected patients

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Antikor Biopharma is pioneering an innovative drug delivery platform called OptiLink. It harnesses the immune system by using miniaturised tumour-specific antibodies to specifically deliver high quantities of potent cytotoxic payloads to tumours. Unlike its competitors, who use full antibody-drug conjugates (ADCs), Antikor's technology enables much smaller fragment-drug conjugates (FDCs) to be developed. These have many advantages: FDC products potentially have a higher therapeutic index for cancer therapy as they are more potent, can be dosed more aggressively because they clear from normal tissues more quickly and penetrate rapidly and deeply into tumours enabling faster tumour destruction. Through previous Innovate-UK BMC support, Antikor expanded and refined its technology and discovered a very strong pre-clinical FDC candidate against a target found on around 50% of all gastric cancers, and on many more solid tumours. This candidate therapeutic, called 77F3 FDC has excellent 'developability' properties (high yielding production, high stability, strong potency) and was able to cure a heterogeneous-target expressing tumour xenograft model. This project entails further preclinical development in order to improve its manufacturing so that it is a more homogenous product. This will be by the application of strategies already shown to be successful for ADCs, but innovatively-applied to this novel format (peptide-mapping mass spectrometry). This will increase the chances that this will become a viable candidate, satisfying regulatory requirements, that can be taken into clinical development.

"Antikor is developing a novel and disruptive platform for oncology drug delivery called **Fragment Drug Conjugates (FDC)**. Here, cytotoxic payloads are specifically delivered to solid tumours. Our platform differentiates from other similar Antibody Drug Conjugates (ADC) approaches in that our format can penetrate tumours faster and more effectively, deliver more payload and clear from normal tissues quicker, leading to better products for increased patient survival and quality of life. The current generation of linkers used to connect the payload to the antibody were designed for large antibodies. This project will develop shorter linkers that do not hinder antibody binding but can maintain FDC solubility and other beneficial features. This project will innovate around the design and chemical synthesis of novel linkers containing hydrophilic sugar units and short polyethylene glycol chains using three clinically-established cytotoxic payloads. These linker-payloads will be synthesised to laboratory scale (tens of milligrams) and then be used to make model FDCs to test in a range of biophysical (binding, aggregation and stability) and biological (cell-kill potency and plasma clearance) assays to identify novel, next-generation linkers that better-match our FDC technology. These linkers will be innovative by having novel structures and features that enhance FDCs, leading to improved future products for solid cancers."

Antikor Biopharma is pioneering an innovative drug delivery platform called OptiLink. It harnesses the immune system by using tumour-seeking antibodies to specifically deliver potent cytotoxic payloads to tumours. Unlike its competitors, who use full antibody-drug conjugates (ADCs), Antikor’s technology enables much smaller fragment-drug conjugates (FDCs) to be developed. These have many advantages: FDC products potentially have a higher therapeutic index for cancer therapy as they are more potent, can be dosed more aggressively because they clear from normal tissues more quickly and penetrate rapidly and deeply into tumours enabling faster tumour destruction. Antikor is developing an FDC for gastric cancer which promises to overcome the challenges in treating this disease. This project entails the discovery and manufacture of a number of candidates, based on existing, compelling proof-of-concept data, with in vitro and in vivo analyses in human tumour models of gastric cancer, to lead to a candidate that can be taken into clinical development.

Antibody drug conjugates (ADCs) are a new wave of targeted cancer therapies that promise dramatically increased survival with significantly lower side effects. Potent toxic “payloads” are attached to tumour-cell specific targeting vehicles called antibodies. This is an early technology with only 2 approved products. There is still a need to develop improved payloads, especially ones that do not succumb to drug resistance in patients and also ones that can potentially kill the dormant cancer stem cells that reside deep within tumours. PhotoBiotics has some experience working with a novel class of payloads that works by many different and independent cellular mechanisms, thereby reducing the likelihood that a cell can mutate and become resistant and increasing the chance of killing dormant cancer cells. In this application, PhotoBiotics will use state-of-the-art established as well as novel strategies to make and evaluate more potent payloads in a form that can be linked onto targeting antibodies to generate significantly better ADCs than are in the clinic today.

Gastric cancer is a major unmet clinical need and a significant business opportunity. Treatment options are few and endoscopic investigation and treatment need advances to improve success rates and patient survival. PhotoBiotics Ltd, University College London's (UCL)-Chemistry and UCL's-National Medical Laser Centre are strengthening their partnership with the help of TSB feasibility grant funding in Photonics-based theranostics to develop a novel "see and treat" approach for gastric cancers. Using the fragment of a clinically-approved antibody together with a fluorescent dye that absorbs and emits in the infra-red region of the light spectrum and Photobiotics' leading soluble photosensitiser, this team aims to generate some preliminary proof-of-concept data for the feasibility of a combined fluorescence diagnosis and photodynamic therapy agent. The team aims to investigate the technical issues in conjugating multiple, different small molecule entities to an antibody fragment whilst retaining full antibody function and no cross-over interference between the two optically-active small molecules. If successful, this data will be used for future fund-raising to develop the idea further into a possible product for all parties to co-develop, leading to better treatment options for patients with gastric cancer.

Oesophageal Cancer is rapidly rising and is the 4th largest cancer killer in men. This project supports combining PhotoBiotics' proprietary OptiLink technology and its own drugs with experts from Imperial College and University College London National Medical Laser Centre to develop a novel antibody-directed phototherapy (ADP) drug to treat cancer. These drugs have few side effects and tumours cannot develop drug resistance to them. We have identified a clinically-validated target and have preliminary data to show that we can tackle this for Oesophageal Cancer. Photobiotics will oversee the manufacture and testing of the drug, Imperial College will help to generate functional data and UCL will treat tumours using their established models. If successful, thus funding will lead to major interest from the pharmaceutical industry to take this into clinical trials.

PhotoBiotics is a biotechnology company established from Imperial College London to develop antibody drug conjugates (ADCs) to treat cancer and other associated diseases. Its patented OptiLink platform enables high drug loading of small antibody fragments leading to enhanced formulation, tumour specificity, reduced side effects and high potency. In this TSB co-funded project, PhotoBiotics is exploring how the OptiLink platform can be used to target and reformulate an existing poorly soluble cancer chemotherapy drug - doxorubicin. The resulting drugs could be safer and easier to administer, with higher levels of potency due to their tumour specificity.