Nanoantibody Development Shows Momentum —Join the Dance Now Or Play Catch-up Forever

Oct 8, 2017, San Diego, CA: Last week, Belgian company Ablynx Inc. announced IPO plans based on robust results from a Phase III study with caplacizumab, the very first nanoantibody drug ready for market.

Caplacizumab targets von Willebrand factor (vWF), will benefit patients afflicted with acquired thrombotic thrombocytopenic purpura (aTTP), a life-threatening autoimmune blood clotting disorder.

The Phase III study (named as HERCULES) met the primary endpoint, namely a statistically significant reduction in time to platelet count response in patients, besides providing standard-of-care. Patients on caplacizumab were 1.5 times more likely to achieve platelet count response at any given time point, compared to placebo control. In addition, the study also met two key secondary endpoints, namely, a 74% reduction in the percentage of patients with recurrence of aTTP or related death, and absence of any major thromboembolic event during study. In addition, the proportion of patients with a recurrence of aTTP during the study period (including the 28 day follow-up period after discontinuation of the drug) was 67% lower in the caplacizumab arm compared to the placebo arm, demonstrating the sustained benefits from the treatment.

Ablynx immediately sought to capitalize the outstanding clinical benefits provided by caplacizumab. On the same day of publicizing their clinical trial results, Ablynx announced filing of a Registration Statement on Form F-1 with the U.S. Securities and Exchange Commission for a proposed stock offering (IPO in the US in the form of American Depositary Shares (“ADSs”) and private placement of ordinary shares in Europe). Ablynx plans to obtain $150 million to finance its commercialization of their new nanoantibody in the U.S. and Europe. With the new developments, the company also expects to accelerate the clinical development of other nanoantibodies, including ALX-0171 which targets respiratory syncytial virus (RSV) infection.

With these exciting news out on the market, now is a great time for the traditional players in the pharmaceutical industry to take a good look and seriously evaluate the possibility to add nanoantibody to their development portfolio. The time is now because success of the new Ablynx drug has minimized the investment risk by proving the feasibility, potential, and advantages of nanoantibodies. The time is now because the field of therapeutic nanoantibodies is still wide open, unlike other crowded, highly competitive arena of conventional antibodies. The time is now, also because with nanoantibodies just starting to get onto the map, an investment in nanoantibodies has the potential of delivering extraordinary returns.

Allele is actively involved in the preclinical development of therapeutic nanoantibody for the past several years, and has accumulated significant IP and technological know-how in this space, and a dozen or so programs ranging from oncology to inflammation. We have a high-speed new technology by which we can get dozens of new nanoantibodies per year, and a pipeline by which we routinely perform humanization, bi- or multi-valency, and expression optimization. We welcome inquiries into our development program, collaboration or joint development proposals, and in exploring investment opportunities with us.

Contact Alleleblog or the Allele nAb team: Dr. Jenny Higginbotham,; Dr. Nobuki Nakanishi,

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What Does It Take to Bring New Nano Antibodies (nAbs) to the Hands of Researchers?

Judging from the hundreds of papers published using camelid VHH antibodies as reagents, there are probably thousands of researchers who have experience with this type of antibodies by now. We like to call the ~15kD camelid VHH antibody nano antibody or nAbTM. Once someone experiences how well a nAb works for co-IP using a fluorescent protein as tag, they often wonder what it takes to bring nAbs to broader use.

The success of a nAb project starts with the antigen presentation. It is critical to build the capability to produce large quantities of recombinant antigen for immunization. At Allele, our scientists also established some unique presentation formats for traditionally difficult targets (e.g. large membrane proteins).

After llama immunization, the next step is screening. With the goal of creating large scale nano antibodies against diverse targets, we have developed multiple high throughput screening methods to cover very large, diverse libraries generated from immunized animals. The technologies will continue to evolve as the scale of nAb generation continues to expand. We have the ability to functionally screen for site-blocking antibodies and antibodies that only recognized natively folded targets, or targets in their naturally occurring presentations.

A nAb isolation project does not end with the obtaining of a cDNA clone. Or, if it does, the nAb is probably not as great as what Allele Biotech has been offering. In our hands, all nAbs go through an engineering step beginning with the generation of a 3D structural model of the isolated clone. We use structure-guided design to alter the protein, allowing us to improve its properties. This includes increasing affinity, solubility, or altering the protein to improve performance for specific applications. We also like to use known structures of traditional monoclonal antibodies to assist camelid VHH antibody engineering against specific targets.

With a finalized clone in hand, the next step is to establish protocols for commercial production. The Allele team spends a tremendous amount of effort aimed solely at high-yield, low-cost recombinant VHH antibody production in a variety of formats, so that the costs for other scientists to take advantage of these great reagents can be kept as low as possible.

Last but not the least, nAb labeling, including conjugating stable soluble VHH antibody to solid supports for immunoprecipitation or to fluorophores for detection, requires additional expertise and tight operation control. However, our vision is to have a modular system for antibody labeling that will enable the end user to select from a variety of fluorophores and other detection tags, which can be instantaneously and irreversibly coupled via simple mixing.

Note added: we work with commercial (diagnostic and clinical) partners from developing nAbs all the way to the market. We have expert scientists available to customers and licensees for consultation and troubleshooting antibody- and imaging-related questions and problems.

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