Allele awarded NIH grant to develop nanoantibody therapies for treatment of sepsis

News Medical Life Sciences: The National Institute of General Medical Sciences of NIH has awarded a Small Business Innovative Research grant to Allele Biotechnology and Pharmaceuticals to develop new single-domain nanoantibody (nAb) therapies for the treatment of sepsis. Sepsis and septic shock are among the leading causes of death in intensive care units (ICUs). The global incidence of sepsis has increased over the years, while the mortality rate, which can reach over 60% for septic shock, has been virtually unchanged for the past three decades due to lack of a cure or effective treatments.

Scientists at Allele have focused on how to intervene with so-called “cytokine storm,” an intense inflammatory response that occurs early in the pathogenesis of sepsis and causes vascular endothelial barrier dysfunction. Other companies have attempted to develop sepsis therapeutics using conventional monoclonal antibodies targeting similar upstream cytokines. However, monoclonal antibody drugs failed to meaningfully improve the mortality rate of sepsis in clinical trials, because the antibodies did not produce significant enough benefits to patients within the relevant time window.

Allele has engineered novel multi-valent and multi-specific nAbs, originally identified from an immunized llama, to combat cytokine storms. These nAbs have superior therapeutic efficacy over conventional antibody drugs in animal models of sepsis because of their unique structural and functional properties. nAbs, also known as VHH domains, are small fragments of antibodies (12-15 Kd) that are very stable and easy to produce. Allele’s research team has found that this class of antibodies possess an outstanding capacity to penetrate to tissues and tumors. Moreover, nAbs can bind epitopes that are difficult for conventional antibodies to access. The first ever approval of a nAb-based drug—caplacizumab, a von Willebrand factor (vWF) target— has been issued to a Belgian company, Ablynx, which has worked almost exclusively on nAbs for 17 years. Ablynx was recently acquired by Sanofi for $4.8 billion.

Allele’s involvement in the nAb field began in 2008. The biotech company has received continued NIH funding since 2011 and private investments since 2013. These funds strengthened Allele’s platform, allowing Allele to drastically enhance its capacity of internal research and outside collaboration. Allele now generates high quality nAbs targeting the most devastating diseases including cancers, inflammation, neurological and ophthalmological diseases, and possesses dozens of exciting nAb drug candidates in its pipeline. With the new funding support from NIH, Allele will aggressively move towards clinical stage in finding a much-needed medicine that reduces death from sepsis.

Source:
http://www.allelebiotech.com/

Tags: Ablynx, biologicals, bivalent, multivalent, nanobody, sepsis

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, jhigginbotham@allelebiotech.com; Dr. Nobuki Nakanishi, nnakanishi@allelebiotech.com

Tags: bivalent, llama antibody, mAb, multivalent, nAb, nanoantibodies, nanoantibody, nanobodies, nanobody, single domain antibody, VHH