Albumin binding Nanofitins, a new scaffold to extend half-life of biologics – a case study with Sanofi with their Exenatide peptide.
Affilogic published with Sanofi on using albumin binding Nanofitins as a half-life extension module with Exenatide biologically active.
Many small active biologics (smaller than 70kDa) face reduced half-life, less than an hour impairing their therapeutic activity. One way to solve these problems is to fuse the small biologic to a larger molecule that provides half-life extension. Some of them targets the albumin, a circulating protein of the blood, and the binding to this protein allows better half-life, mediated by FcRn-mediated reycling. However, half-life extension may reduce the therapeutic activity of the API. Here has been evaluated an albumin binding Nanofitin (ABNF) cross reacting with MSA and HSA, for half-life extension of the Exenatide, a GLP1R agonist indicated in the treatment of type 2 diabetes mellitus. Exenatide-ABNF fusion displays potent glycemic control and significantly prolonged duration of action (sustained activity for at least 3 days) compared to the parent peptide. It was found that the activity of Exenatide is fully maintained in the classical in vitro GLP1R cell based assay based on cAMP measurements, regardless of the linker length.
All that together show significant interest in using ABNF as half-life extension module for therapeutics that would need such a feature.
“Respitude” Affilogic’s project laureate of the AMI “Nouvelles Biothérapies & outils de production”.
The “Respitude project support the development of a candidate Nanofitin simultaneously targeting multiple epitopes of the SARS-Cov2 S surface protein, neutralizing its interaction with cells, and take it to phase I/IIa clinical stage.
Nanofitins being 20 times smaller than antibodies, highly soluble and extremely stable proteins, they can be easily nebulized. Affilogic already demonstrated bio-distribution of Nanofitins into different compartments of the lungs in animal models.
The #FranceRelance investment plan includes 800 Million Euros (from #PIA), to help biotherapies development, stimulate competitiveness and follow the development of the French industrial environment which is necessary in order to no longer depend 95% on foreign biotherapies.
Development of multispecific assemblies of Nanofitins® with anti-tumor activities @ PEGS Europe 2021
Ms. Perrine Jacquot, Ph.D. student working at Affilogic and at the Western Cancer Institute (Institut de Cancérologie de l’Ouest, Saint-Herblain, France) presented her latest results in November in Barcelona during PEGS Europe 2021.
Nanofitins® are small and robust affinity proteins considered as alternatives to antibodies. These proteins can easily be associated with each other in order to increase avidity or multi-specificity. In the development of anti-tumor strategies, the assembly of Nanofitins® with various activities (targeting of receptors / soluble factors, recruitment of immune cells, etc) allows the targeting of multiple pathways involved in cancer progression and aims at the development of an effective anti-tumor response with limited toxicities.
This project was partially sponsored from January 2018 to December 2020 by a grant from the European Regional Development Fund (ERDF / FEDER) via the Region Pays de Loire.
Nanofitins targeting heat shock protein 110: an innovative immunotherapeutic modality in cancer
Affilogic recently published with some partners an article on anti-HSP110 Nanofitins in cancer immunotherapy.
The presence of an inactivating HSP110 mutation in colorectal cancers has been correlated with an excellent prognosis and with the ability of HSP110 to favor the formation of tolerogenic (M2-like) macrophages. These clinical and experimental results suggest a potentially powerful new strategy against colorectal cancer: the inhibition of HSP110. As an alternative to neutralizing antibodies for cancer immunotherapy, we have selected Nanofitins targeting and inhibiting HSP110 chaperone activity. We have demonstrated that the anti-HSP110 Nanofitins tested accumulate within the tumor (PET/SCAN), the best candidate showing a subnanomolar affinity for HSP110. Such Nanofitin reduced tumor growth, and was associated with an increase in immune cells infiltrating the tumor and particularly cytotoxic macrophages in the CT26 colorectal cancer mice model. These results were confirmed in a chicken chorioallantoic membrane tumor model. Finally, we showed the complementarity between the anti-HSP110 Nanofitin and an anti-PD-L1 Nanofitin in the in vivo and in ovo tumor models. Altogether, Nanofitins appear to be promising new immunotherapeutic lead compounds.
This work was performed in collaboration with INSERM (UMR1231), University of Bourgogne Franche-Comté, Anticancer Center Georges François Leclerc and the company Inovotion.
Affilogic to receive public funding for a new production unit as winner of the French industrial relocation plan
Affilogic is one of the first 31 winners of the industrial relocation plan recently unveiled by the Minister of the Economy, Bruno Le Maire. Within three years, it wants to create a production unit for the Nanofitins, synthetic proteins (…), which are designed to attach themselves to a chosen biological target to purify it, detect it, or block its action. These molecules are used in particular to inhibit pathological mechanisms. “The major pathologies targeted include Crohn’s disease, pancreatic cancer, brain and ophthalmic diseases,” explains Olivier Kitten, the CEO. “(…) Today, we want to create a 1,500 m² unit in the Nantes region to multiply our production capacity by a factor of 100. » With this €5 million investment, Affilogic is set to double its workforce (currently 25 people) in Nantes over three years.
Development of multispecific assemblies of Nanofitins with anti-tumor activities @ the 8th Antibody Industrial Symposium 2020
Digital, November 2020
Affilogic is developing a new anti-cancer therapeutic approach. Different multispecific assemblies of Nanofitins are developed with a variation of the modules that compose them. In order to potentiate the anti-tumor response, the choice of Nanofitin modules to assemble focuses on those with activities involved in cancer synergistic signaling pathways. In the development of multispecific anti-tumor proteins, Nanofitins provide several advantages. Indeed, thanks to their good tolerance to engineering modifications as well as the non-involvement of their N- and C-terminal ends in the binding, their multimerizations with other molecules / proteins / toxins / antibodies and Nanofitins are facilitated and used in order to do multi-targeting and/or increase avidity. Moreover the robustness of these proteins limits the possibilities of their deactivation in the presence of an aggressive tumor environment. In addition, the absence of cysteines and post-translational modifications allows the production in prokaryotic system of several Nanofitins grouped in a single molecule, which will bring an attractive cost in the multimers development. Finally, their low molecular weight promotes their diffusion within the tumor mass and gives them a short plasma half-life allowing the elimination in a few minutes of unbound proteins which is interesting for reducing side effects.
This project was partially sponsored from January 2018 to December 2020 by a grant from the European Regional Development Fund (ERDF / FEDER) via the Region Pays de Loire.
One molecule, several targets!
Multispecific Nanofitin assemblies for modulating the tumor microenvironment @ PEGS Europe 2020
Digital, November 2020
Many efforts have been devoted in recent years towards reconditioning the tumor microenvironment to mount an immune response against the tumor. While holding promises, our understanding of the manipulation of the immune system remains limited and has to be addressed with other technical challenges, such as tumor penetration, off-target systemic toxicity, and simultaneous co-engagement of several tumor progression pathways. We will be sharing our strategy to answer these different challenges using the Nanofitin scaffold, with examples of multispecific constructions directed against several tumor progression pathways (angiogenesis, T cell population, and macrophage differentiation).
My Thesis in 180 Seconds by Perrine Jacquot
The Affilogic Team is very proud to announce that one of its Ph.D. student, Ms. Perrine Jacquot, has participated to the international competition My Thesis in 180 Seconds. Since Summer 2019, Perrine has been working on the “Development of a multi-specific combination of nanofitins exhibiting anti-tumor activity” at Affilogic and at the Western Cancer Institute (Institut de Cancérologie de l’Ouest, Saint-Herblain, France). To relive her performance, please click below !
Affilogic’s intervention at PEGS Europe 2019
Lisbon, Portugal, November 2019
This year at the PEGS Europe 2019 congress, Dr. Mathieu Cinier has been co-presenting the short course entitled “Engineering of Bispecific Antibodies and Multi-Specific Non Antibody Scaffolds”.
Non-antibody scaffolds represent a new class of therapeutic molecules that fill a molecular weight gap between antibodies and peptides. While sharing the high specificity and potency of antibodies, their low molecular weight and simple structure make them amenable to peptide-like properties such as high tissue penetration. They are also easy to assemble, providing then a straightforward “plug and play” approach to combine active modules into a single molecule that displays the desired druglike properties. At the age of multi-functional therapeutic molecules, non-antibody scaffolds continue to rise up with an increasing number of ongoing clinical phases, making them valuable assets in the landscape of next generation biologics.
Diversity of folds and library designs
Affilogic at BIO 2019 : “Partnering is in our DNA”
Philadelphia, Pennsylvania, June 2019
Nanofitin-Antibody fusion as a novel multispecific platform: providing extra specificities while maintaining developability
Webinar Oxford Global, June 2019
Building on antibody expertise, many different bispecific formats have been engineered to allow the additional neutralization of an escaping pathway or the recruitment of effectors, but often at the expense of the overall physico-chemical properties of the biologic itself compared to the actual state of the art for monoclonal antibodies. Nanofitin-Antibody fusion is proposed as a novel multispecific platform, whereby additional targeting specificities are provided by the fusion of Nanofitins to existing antibodies without altering their initial physico-chemical properties.
Nanofitin is a small (7 kDa) single chain, hyperstable, cysteine-free, and highly soluble alternative scaffold that can be custom-engineered for a defined targeting specificity. Nanofitins are easily assembled with each other or with third-party molecules such as antibodies by simple, rapid and proven methods to design an ideal targeted molecule. With the strong rational behind the targeting of multiple disease pathways, the trend is moving smoothly from the design of bispecific to multi-specific antibodies, which could be easily adapted with Nanofitins. Thanks to their small size, Nanofitins can be plugged on an antibody at different locations, either as a single module or as an assembly, while still providing a minimal hindrance on the antibody that retain its functionality. Resulting Nanofitin-Antibody fusions benefit from the high stability and solubility of the Nanofitin scaffold, providing to the Nanofitin-based multi-specific platform a developablility advantage.
Takeda opens a new research center in San Diego
San Diego, California, April 2019
On April 30th, 2019, Takeda opened a new research facility in San Diego, California. As a partner of choice of Takeda San Diego, Olivier Kitten, Affilogic’s CEO, had the chance to take part in this grand opening and present Affilogic’s recent advances in common areas of interest. This research center is home to four research platform groups: structural biology, early target discovery, computational biology and biologics, providing key capabilities to discover and advance promising molecules.
Takeda is a global, R&D-driven biopharmaceutical leader, focusing its R&D efforts on four therapeutic areas: Oncology, Gastroenterology, Neuroscience and Rare Diseases. Takeda collaborates with partners around the world to unlock innovation and deliver potentially transformative therapies to patients.
Since September 2016, Takeda and Affilogic are collaborating to use Affilogic’s proprietary Nanofitins® platform in therapies targeting the central nervous system. Takeda and Affilogic are leveraging their respective competencies to validate and optimize Nanofitins® that enable Takeda to deliver biotherapeutic candidates into the brain to address neurological disorders.
“Takeda has world class expertise in central nervous system drug discovery. We are very enthusiastic to work together to develop innovative biotherapeutics for the treatment of neurological diseases” said Olivier Kitten. “Takeda is a partner of choice for Affilogic to significantly expand the number of research programs relying on our Nanofitins® platform advancing into clinical trials. I was really honored to attend this new opening.”
Affilogic’s intervention at the Biologics Series UK 2019
London, UK, April 2019
Dr. Mathieu Cinier, Scientific Director at Affilogic, spoke at the 12th Annual antibodies Congress.
Dr. Mathieu Cinier, invited to speak on the theme of “Bioconjugates – ADC engineering”, gave a conference entitled “The Nanofitin® Technology As A Versatile Platform For Cancer Imaging and Drug Conjugates”.
Most of the antibody alternative scaffolds claim to benefit from their small size in term of tissue penetration. This comes at the expense of a short serum half-life, which keeps animating debates as regards the actual benefit of using alternative scaffolds to generate drug conjugates. In this presentation, Dr Mathieu Cinier shared our original approach to evaluate in vivo tumor penetration with side by side comparison of the Nanofitin® scaffold technology and a full size antibody to draw some conclusions on how size, and other parameters, do influence tumor penetration, providing then to the audience new insights and perspectives for drug conjugates optimization.
Affilogic and Samabriva entered into an Option and License Agreement to develop Nanofitin®-conjugated biotherapeutics to treat Lysosomal Storage Disorders
Nantes and Amiens, France, September 2018
Affilogic and Samabriva jointly announced that they recently entered into an Option and License Agreement to develop biotherapeutics for the treatment of patients with Lysosomal Storage Disorders. Samabriva will use Affilogic’s proprietary Nanofitins® technology to develop new therapies to address strong unmet needs in these patients such as the associated neurological damages.
In the framework of a research collaboration initiated in 2016, Samabriva will pursue the evaluation of Nanofitin® candidates selected by Affilogic from their proprietary libraries in combination with lysosomal enzymes. The partners will combine research efforts to optimize such Nanofitin®- conjugated biotherapeutics in order to satisfy unmet medical needs in the treatment of patients with Lysosomal Storage Disorders.
Affilogic’s involvement in the DiaSyn project
Madrid, Spain, May 2018
Dr. Mathieu Cinier, Scientific Director, made a presentation about Affilogic’s involvement in the DiaSyn project.
The overall objective of the DiaSyn project is to develop a PET imaging tracer for highly specific and sensitive detection and quantification of αSynuclein in the brain. It is based on the combined use of nano-tools together with a bioorthogonal imaging approach. The project’s work, which has started in September 2016, shall be performed in 3 years by Affilogic and its partners, the University of Liège, the University of Artois, UCB Biopharma and the Cajal Institute.
Affilogic’s intervention at PEGS Boston
Boston, USA, May 2018
Dr. Mathieu Cinier, Scientific Director at Affilogic, spoke at the Essential Protein Engineering Summit.
Dr. Mathieu Cinier, invited to speak on the theme of “Innovating Therapeutic Fusion Protein”, gave a conference entitled “Nanofitin®-Antibody Fusion as a Novel Multispecific Platform”. Many different bispecific formats have been engineered to allow the additional neutralization of an escaping pathway or the recruitment of effectors, but often at the expense of the overall physicochemical properties of the biologic itself compared to the actual state of the art for monoclonal antibodies. Nanofitin®-Antibody fusion is proposed as a novel multispecific platform.
Additional targeting specificities are provided by the fusion of Nanofitins® to existing antibodies, without altering their initial physico-chemical properties. Affilogic thinks that the bispecific field might provide a new breakthrough for the management of complex diseases, but that keeping in mind molecules shall still be developable as therapeutics is paramount. As such, Affilogic is proposing a developability oriented novel multispecific platform. Thanks to their small size, Nanofitins® can be plugged on an antibody at different locations, either as a single module or as an assembly, while still providing a minimal hindrance on the antibody that retain its functionality. Moreover, Nanofitin®-Antibody fusions benefit from the high stability and solubility of the Nanofitin® scaffold, providing to the Nanofitin®-based multi-specific platform a developablility advantage.
Affilogic’s intervention at the 4th Biologics & Biosimilars Congress
Berlin, Germany, March 2018
Dr. Mathieu Cinier, Scientific Director at Affilogic, spoke at the 4th Biologics & Biosimilars Congress.
Dr. Mathieu Cinier, invited to speak on the theme of “Protein Biotherapeutics”, made a presentation entitled “Nanofitins® as a versatile platform for cancer imaging and drug conjugates”, exemplified by a case study concerning anti-EGFR Nanofitins® cross-reacting on both the human and murine EGFR.
Using the Nanofitin® technology as a vector for radioimaging displays many advantages, like the possibility to tailor the selection to obtain cross-reactive Nanofitin® (allowing a better significance of the preclinical studies in murine model in term of biodistribution) and their fast systemic clearance (meaning compatibility with fast decaying radio-isotope, simple radioactive waste handling, no accumulation in healthy organs, better patient compliance and higher production capacity). The high stability of the scaffold and the absence of cysteine allows easy regioselective conjugation.
Using the Nanofitin technology as a vector for drug conjugate also offers benefits. Their small scaffold enables a high tissue penetration, and their fast clearance can be tuned to allow longer resilience via Affilogic’s proprietary half-life extension technology. Nanofitins® can also be easily conjugated to nanoparticles and payloads, via chemical conjugation or genetic fusion.
Affilogic wins the award of the best pitch at the RIBs 2018
Paris, France, February 2018
Affilogic was part of the 14 startups selected by a jury of oncologists, investors and industrialists to attend the French “Rencontres Internationales de Biotechnologie”. Dr. Olivier Kitten, Founder and CEO at Affilogic, won the award of the best pitch.
The objective of the RIBs is to bring together international industrialists and selected startups on the basis of their research themes, the excellence of their project and their desire to forge alliances with pharmaceutical companies. The RIBs 2018 was on the theme of immuno-oncology. The overall strategy of Affilogic is to treat cancer via multiple pathways thanks to multi-functional Nanofitin®-based targeted drugs. Two partnering schemes are possible : Affilogic can partner with pharmaceutical companies on existing Nanofitin® modules currently developed in immuno-oncology that are not encumbered by any exclusivity rights given to a current partner, or can generate new Nanofitins® since it also has a platform-based business model.
Affilogic made a new presentation at the last World Vaccine Congress
Barcelona, Spain, October 2017
Dr. Anne Chevrel, R&D Project Manager at Affilogic, made a presentation at the last World Vaccines Congress in Barcelona, entitled “Innovative affinity chromatography platform for streamlined purification of vaccines at reduced costs and lower environmental footprint”.
This presentation showed the progresses of Affilogic and its Divine partners, Aquaporin, GenIbet, GSK, iBet and Merck, in the development of an affinity chromatography platform using specific Nanofitins® and Aquaporin membranes. This innovative affinitychromatography platform outperforms the current vaccines purification process by reducing the number of downstream operations and reducing product loss.
The first family of vaccines being the glycoconjugates vaccines, Nanofitins® directed against CRM197 (carrier protein for glycoconjugates vaccines) have been discovered, identified, characterized and successfully conjugated to resin. Dynamic binding experiments have been realized, and a pilot scale using Hollow Fiber Forward Osmosis showed a water recovery using forward osmosis of 90% in 30 minutes.
Affilogic presented orally deliverable anti-TNFalpha Nanofitins® at PEGS Europe
Lisbon, Portugal, November 2016
Mathieu Cinier, Scientific Director at Affilogic, presented the very significant progress made by SADEL consortium in developing an orally available anti-TNFalpha Nanofitin® to treat Inflammatory Bowel Diseases.
Despite a remarkable efficacy, treatment of inflammatory bowel diseases using systemic administration of anti-TNF-alpha antibodies remains associated with serious adverse effects. Extreme stability of the Nanofitins, a novel alternative scaffold, in gut environment allows development of orally available anti-TNF-alpha therapeutics by Affilogic and partners (SADEL FP7 European programme) to benefit from a better targeting to the inflammation site while decreasing systemic exposure and related side effects.
Affilogic presented a rational design approach to predict Nanofitins® targeting a defined epitope at PEGS Europe
Lisbon, Portugal, November 2016
Simon Huet shared the results of his Ph.D. thesis hosted in Affilogic R&D lab with a poster entitled “Full-computational design of anti-GFP Nanofitins binding a pre-selected interaction surface”
Besides druggability predictions, such as modeling the immunogenicity profiles of Nanofitins® confirming their promising safety profile, bioinformatics tools were assessed at Affilogic for the assistedgeneration of Nanofitins® through the computed design of their interaction surface. When the region to be targeted is already known, this approach could reduce the screening effort by framing the generation process to binders targeting only the desired epitope, therefore predicting their activity. This poster describes how two distinct regions of the GFP were targeted by in silico design of the Nanofitin® scaffold. At the bench level, one candidate was shown to successfully bind to the GFP at the pre-selected surface imposed by design, representing a specific hot-spot for subsequent affinity maturation.
Affilogic presented a Poster at the last World Vaccine Congress
Barcelona, Spain, October 2016
The DiViNe partners were happy to communicate the first results of the project at the last World Vaccines Congress in Barcelona with a poster entitled “Vaccines purification by affinity chromatography with Nanofitin ligands: demonstration with glycoconjugates”.
This poster explains why the DiViNe approach and the use of affinity chromatography with custom-designed specific Nanofitins will enable to improve the current vaccines purification process by reducing the number of downstream operations and reducing product loss.
The partners are developing a flexible Nanofitin-based platform for vaccines purification and it is illustrated on the poster with the first family of vaccines i.e. the glycoconjugate vaccines. We describe discovery and identification of Nanofitins directed against the CRM197 carrier protein, as well as their conjugation to resin.
Affilogic announces collaboration with Takeda
Nantes, France, September 2016
Affilogic and Takeda will validate and optimize Nanofitins® to deliver biotherapeutic candidates into the brain to address neurological disorders.
“Takeda is a partner of choice for Affilogic to significantly expand the number of research programs relying on our Nanofitins® platform advancing into clinical trials” said Olivier Kitten, Chief Executive Officer of Affilogic.”
Affilogic announces collaboration with Sanofi
Nantes, France, June 2016
Affilogic enters into a Research Collaboration and Licensing agreement with Sanofi on Nanofitin®-conjugated biotherapeutics.
“We’re very proud to announce this collaboration with Sanofi. This is an important step forward to demonstrate the potency of our Nanofitin® platform with a leading pharmaceutical company.” said Olivier KITTEN, Chief Executive Officer of Affilogic. “With Sanofi, Affilogic has found an ideal partner to raise value to our technology and generate Nanofitin®-conjugate drugs.”
Affilogic announces collaboration with BIND Therapeutics
Nantes, France, May 2016
Affilogic will provide BIND with access to Nanofitins® that are keys modulators of anti-tumor immunity.
“We are excited about our collaboration with BIND Therapeutics and believe our Nanofitin® targeting ligands can play an important role in BIND’s innovative medicine strategy,” said Olivier Kitten, chief executive officer, AFFILOGIC. “BIND’s ACCURINS® platform has proven very effective at encapsulating and controlling the release kinetics of a wide variety of therapeutic payloads. When combined with our ability to specifically tailor Nanofitins to target important immune-oncology checkpoints, we believe this collaboration could lead to the discovery and development of truly innovative therapeutics.”